Hendrick Hudson High School
Science May 2017
Research
Sponsored by the Hendrick Hudson Community Educational Foundation (HHCEF)
“ You are limited only by your imagination”
1 2 Hendrick Hudson High School
May 2017 Science Research
The Hendrick Hudson Science Research program had a very successful year. Jona- than Chung has been named a finalist in the Regeneron Science Talent Search, the nation’s oldest and most prestigious science and math competition for high school seniors. He also received science report and student initiative badges for his paper submission. Melanie Porras has been named a scholar (semi-finalist) for her project on artificial photosynthesis. 300 semi-finalists and 40 finalists are selected from a pool of over 1700 applicants. The Regeneron Science Talent Search, a program of Society for Science & the Public, focuses on identifying the next generation of scientists and engineers who will provide critical leadership in solving some of the world’s most pressing challenges while shaping the future of research and development for our na- tion and the world. Jonathan Chung presented his project in Washington, D.C., where he also had the opportunity to meet with national leaders and share their projects with the public at the National Geographic Society. Matthew Gofman received science report and student initiative badges for his submis- sion to the STS competition and placed third at the Tri-County Science Fair. Melanie Porras placed First in the plant sciences category at the Westchester Science and Engi- neering Fair (WESEF). Isabella Brizzi received the Stockholm Water Prize at WESEF as well. Melody Munitz competed as a junior at WESEF and got third place in the Behavior category. Deepa Mistry placed second at the Tri-County Science Fair.
3 Interaction of Circulating Gut Microbiota-generat- ed Metabolites with the Function and Expression of SLC6A3, the Dopamine Transporter, by Jona- than Chung (STS FINALIST, paper excerpt) (Se- nior) substrate and the 4 me- ment and function of tabolites at 100 µM and the brain through the 500 µM revealed that gut-brain axis, a bidirec- through Probiotics at 100 µM, propionic tional means of communica- acid, hippuric acid, and tion between the central and Many studies have used indoxyl sulfate reduced the enteric nervous systems probiotics, live bacteria or 14C-dopamine uptake. (Carabotti et al., 2015; Col- bacterial products, to alter Meanwhile, p-cresol lins et al., 2012; Dinan and the brain and behavior (Liu did not significantly af- Cryan 2013). In support et al., 2016). For example, fect uptake at 100 µM. of the gut-brain axis, many the probiotic Lactobacillus All four metabolites neurological diseases such rhamnosus decreased anxi- had little effect on 14C- as Autism, Rett syndrome, ety and despair-like behavior dopamine uptake at 500 Cerebral Palsy, Schizophre- and reduced stress-induced µM. To test expression, nia, and major depression increase of plasma corticos- HEK cells were exposed report gastrointestinal issues terone levels in mice (Cryan to the metabolites for as a prevalent comorbidity & Dinan 2012). Meanwhile, 24 hours at 250 nM. A (Heijtz et al., 2011). For ex- Bifidobacteria treatment - re bicinchoninic acid assay, ample, a study that included duced levels of 5-hydroxy- western blot, and uptake over 14,000 individuals with indoleacetic acid (5-HIAA) assay revealed that expo- Autism Spectrum Disorder in the frontal cortex and sure to p-cresol and pro- (ASD) found a higher preva- decreased levels of 3,4-di- Abstract pionic acid increased the lence of inflammatory bowel hydroxyphenylacetic acid Many mental conditions expression of DAT, while disease (IBD) and other GI (DOPAC) in the amygdaloid show comorbidity with gas- exposure to indoxyl sulfate disorders in ASD patients cortex (Desbonnet et al., trointestinal disorders. Cir- and hippuric acid reduced it. compared to controls (Ko- 2010). Another study dem- culating metabolites from Altered DAT expression in hane et al., 2012). Studies onstrated that chronic L. microorganisms in the gut the brain translates to an al- have also reported that gas- helveticus NS8 supplemen- have been documented to be tered synapse clearance rate trointestinal disorders corre- tation can counteract, with involved in communication of dopamine and altered do- late with symptom severity the efficacy of the selective between the gut and brain. paminergic signaling, both in ASD (Coury et al., 2012; serotonin reuptake inhibitor This study tests the effects of which have relevance to Buie et al., 2010). While the citalopram, chronic stress- of four representative me- many diseases implicated in causes of such disorders are induced behavioral, cogni- tabolites (propionic acid, in- gut-brain communication, insufficiently understood, tive, and biochemical aber- doxyl sulfate, hippuric acid, such as autism and schizo- they may be linked, directly rations (Liang et al., 2015). and p-cresol) on the activity phrenia. It was concluded or indirectly, to gut bacteria Live Lactobacillus plan- of one key target involved in that circulating metabolites as ASD individuals exhibit tarum PS128 treatment also neurotransmission, the dop- play important roles in the an altered composition of affected biochemical aberra- amine transporter (DAT). It gut-brain axis. the intestinal microbiota was hypothesized that these Introduction (Kang et al., 2013; Fine- four metabolites would af- gold et al., 2010; Gonda- The Gut-Microbiota-Brain fect the function and/or ex- lia et al., 2012; Finegold Axis pression of DAT. Using et al., 2002). However, a plasmid that carries the The gut microbiota com- a definitive answer as to recombinant DAT gene, a prises trillions of microbes how the gut and brain recombinant bacmid was that influence gastrointesti- communicate, whether created to infect attached nal physiology as well as the through neural, endo- HEK293-EM4 cells to as- function of distant organs crine, metabolic or im- sess the transport activity and susceptibility of the host mune pathways, is un- and expression of DAT in re- to disease (Evrenel and Cey- clear (Zhang and Davies, sponse to exposure to these lan, 2015). The brain is one 2016). metabolites. Uptake as- such organ as the gut micro- biota regulates the develop- Modulation of the says with 14C-dopamine as Brain and Behavior 4 tions, significantly increas- levels in serum. Notably, ing the levels of dopamine the commensal bacteria and serotonin in the brain. modulated, if not directly The enhancement in striatal produced, both indolepyru- dopamine neurotransmis- vate and 4-ethylphenylsul- sion following probiotic fate. Given its potential treatment may have caused role in behaviors relevant the enhanced locomotor to ASD, 4-EPS was tested activity observed (Liang et separately on naive mice. al., 2015). These successes Mice treated with 4EPS with probiotics support the potassium salt from 3 existence of the gut-brain weeks of age to 6 weeks of axis. But more important- age displayed anxiety-like ly, the ability of probiotics behavior similar to that ob- to alter monoamine levels served in MIA offspring. in the brain and normalize This outcome suggests that both the gut microbiota and specific symptoms relevant behavior reveal the poten- to ASD and other neu- tial role of bacteria in regu- rodevelopmental disorders disruptions in the seroton- mitochondrial function, lating gut-brain communi- may be connected to specific ergic system in the absence immune modulation, gap cation. metabolites. Combinations of a normal gut microbiota junction gating, and behav- Bacterial Metabolites as of metabolites may control (Clarke et al., 2013). Other ior (DeCastro et al., 2005; Messengers in the Gut- more complex behaviors metabolites such as 3-(3- Maurer et al., 2004). The in- Brain Axis (Hsiao et al., 2013). In the hydroxyphenyl)-3-hydroxy- creased intracellular neuronal gut, metabolites can influence One method of communi- propionic acid (HPHPA), a and glial acidification and neurotransmitter production. cation between the gut and Clostridia metabolite, inhibit calcium proportions altered Metabolites upregulated by the brain is through bacte- dopamine beta hydroxy- neurotransmitter release, spore forming bacteria, such rial metabolites, which are lase (Shaw, 2010). HPHPA which included glutamate, as α-tocopherol, tyramine, the intermediates and end among others were found at dopamine, norepinephrine, and 4-aminobenzoic acid points of biological pro- significantly higher concen- and serotonin (El-Ensary et (PABA), have been shown to cesses (Hsiao et al., 2013). trations in the urine samples al., 2012). These observa- promote 5-hydroxytryptam- Different bacteria produce of children with autism and tions following propionic ine (5-HT, serotonin) bio- different metabolites mean- in schizophrenia. The in- acid infusions demonstrate synthesis both in vivo, ing that an altered gut mi- hibition of dopamine beta the ability of metabolites to through injecting short chain crobiota creates a differ- hydroxylase, which is re- affect neurotransmitter sig- fatty acids in GF mice, and ent circulating metabolite quired for the conversion of naling. As part of investi- in vitro, through testing short profile (Dinan et al., 2015). dopamine to norepinephrine, gating the effects of antibi- chain fatty acids on chroma- The Maternal Immune may account for the excess otic treatment on cognitive ffin cell cultures (Yano et al., Activation (MIA) model dopamine implicated in the impairment, a recent study 2015; Nozawa et al., 2009). yields mice that exhibit etiology of psychotic behav- recorded differences in the These metabolites increased core behavioral symptoms ior and schizophrenia (Shaw, expression of neural signal- tryptophan hydroxylase 1 of ASD, a common autism 2010). ing-related molecules in the (TPH1) expression, suggest- neuropathology, increased Metabolites on Brain Neu- brain (Frohlich et al., 2016). ing that colonic enterochro- gut permeability, tight junc- rotransmission Circulating metabolite lev- maffin cells receive signals tion defects, and dysbiosis, els were also examined after from these particular me- Metabolites affect the brain an impaired microbiota. In antibiotic treatment. Many tabolites to enhance 5-HT directly. Propionic acid, an these mice, eight percent metabolites, including p- biosynthesis. In germ-free enteric bacterial metabolite, of all serum metabolites cresyl sulfate, propionate, mice, the elevated luminal reaches the brain by cross- were significantly altered. deoxycholic acid, and trim- concentrations of particular ing the gut-blood and blood- The metabolite 4-ethylphe- ethylamine-N-oxide, had microbial metabolites in- brain barrier passively and nylsulfate (4EPS) was of markedly different levels creased colonic and blood actively via high affinity particular interest due to a following antibiotic treat- 5-HT levels. The increased transporters (Thomas et al., staggering 46-fold increase ment. The serotonin trans- 5-HT levels increased 5-HT 2012; Conn et al., 1983). in serum levels of MIA off- porter, SLC6A4, was among uptake by circulating plate- Concentrating intracellularly spring that was completely the tested neural signaling- lets. The indigenous micro- in the brain, propionic acid restored by probiotic B. fra- related molecules in the biota, which produces many deleteriously affects various gilis treatment. Indolepyru- brain. After antibiotic treat- of these metabolites, can neurophysiological process- vate, a key molecule of the ment and when compared even modulate hippocampal es, including neurotransmit- tryptophan metabolism to the vehicle-treated mice, levels of 5-HT, indicated by ter release, gene expression, pathway, also had elevated SLC6A4 mRNA expres- 5 have been im- and expression, plicated in the uptake of 14C- gut brain com- dopamine and m u n i c a t i o n DAT expres- by probiotics sion in attached altering levels HEK293-EM4 of dopamine cells were both and serotonin performed in in the brain the presence and producing or absence of similar effects these metabo- to the selec- lites. As an tive serotonin independent re- reuptake inhib- search project, itor citalopram. the study was Additionally, conceived by antibiotic-in- me, the student, duced cogni- and was not tive impair- part of ongoing uptake did not dramatically ment altered work in my mentor’s lab. change when the concentra- the levels of (...) tion of the metabolites was sion was slightly reduced in many circulat- increased to 500 µM. This Results the hypothalamus and hip- ing metabolites, which led disproved the hypothesis pocampus, while mRNA ex- to alterations in the levels of Fig. 2 confirms the success- that these metabolites may pression was increased in the expression of the serotonin ful expression and function directly interact with the medial prefrontal cortex and transporter. However, to my of DAT in the HEK cells us- function of DAT by inhib- significantly increased in the knowledge (after intensive ing the recombinant bacmid iting uptake or some other amygdala. It was speculated literature research and con- virus. The 14C –dopamine mechanism. that the circulating metabo- sultation with my mentor) uptake curve from 0 to 90 The uptake assay performed lites might be responsible no study has tested the ef- minutes was used to choose with the cells exposed to the for gut-brain axis communi- fects of metabolites on DAT the 5-minute time point for metabolites at 250 nM for cation. at the molecular level. Giv- uptake in the presence of the 24 hours reflected greater Statement of Purpose en the identification of sev- metabolites. Fig. 3 shows variations in the uptake of that overall uptake of 14C Previous studies have shown eral circulating metabolites 14C-dopamine. Fig. 4 indi- that had significantly altered -dopamine was not signifi- cates that the uptake for the that circulating bacterial me- cantly affected regardless tabolites may have an inte- levels in a variety of mental p-cresol group was roughly conditions, it was hypoth- of whether the assay was at 20 percent greater than that gral role in communication metabolite concentrations between the gut and brain esized that these metabolites of the control. The propi- could interact with the func- of 100 nM or 500 nM. At onic acid group also showed because of the markedly the 5-minute time point for altered metabolite profiles tion and expression of DAT. about a 15 percent increase Four metabolites, propionic both concentrations, the in uptake compared to the recorded in mental illnesses uptake, measured in pico- and dysfunction. Separately, acid, p-cresol, hippuric acid, control. The increased up- and indoxyl sulfate, were moles, remained between 15 take indicates that more DAT metabolites have been shown and 20 picomoles. Uptake to affect neurotransmission chosen for the study. To test was expressed and thus more these metabolites on a mo- was slightly reduced in the was present to uptake 14C and behavior. Monoam- presence of propionic acid ines and their transporters lecular level with function -dopamine. The observable (PA) at 100 µM and in- changes in expression in doxyl sulfate (IS) at this uptake assay align with 100 µM. Uptake in the the fold changes in SLC6A4 presence of DMSO was mRNA expression observed also slightly reduced, in mice with antibiotic-in- which may account duced dysbiosis compared for the lower uptake in to vehicle-treated groups the presence of hippu- (Frohlich et al., 2016). In ric acid (HA), the only that study, the fold changes metabolite dissolved in expression of SLC6A4 in in DMSO, at 100 µM. the medial prefrontal cortex, Although uptake was hippocampus, amygdala, slightly reduced for sev- and hypothalamus never eral groups at 100 µM, left the range of 0.5 to 1.5.
6 hippuric acid reflected the The decreased extracellular decreased expression. The concentrations of dopamine altered expression levels of may be related to the eti- DAT support the hypothesis ologies of ASD, depression, that these metabolites could anxiety, and other mental alter the expression of DAT. disorders relevant to the Discussion gut-brain axis. This altered dopaminergic signaling has This was the first study to implications to schizophre- test the effects of circulat- nia, which has been found ing bacterial metabolites on to reduce DAT expression the dopamine transporter at a in the amygdala (Markota et molecular level. In a previ- al., 2014). Hippuric acid and ous study, antibiotic-induced indoxyl sulfate could be rel- gut dysbiosis changed the evant to this observation as profile of circulating metab- these metabolites decreased olites, including propionate DAT expression in this study. and p-cresyl sulfate (Frohlich The amygdala was also the et al., 2016). These metabo- However, the percent change bands indicate that more brain region that showed the lites are similar to propionic in uptake for the IS and HA DAT is present, which means most noticeable differences acid and p-cresol, metabo- groups were less more DAT was expressed. in expression of SLC6A4 lites used in this study. The Fig. 5 shows that the 4 me- There are two bands for after antibiotic treatment results matched the conclu- tabolites were not toxic to each group because of the (Frohlich et al., 2016). The sions of this previous study, the cells and did not affect presence of both immature commonality elucidates a which concluded that cogni- cell growth. Cell counting and mature proteins. The role for circulating metabo- tive impairment by antibi- revealed cell concentrations immature proteins, repre- lites to cause mental condi- otic-induced gut dysbiosis from ~3.75 to 4 million cells/ sented by the lower bands, tions such as cognitive im- caused changes in the ex- ml for all groups. This indi- are smaller than the mature pairment or schizophrenia pression of SLC6A4, the se- cated that any changes in the proteins and thus traveled by altering the expression of rotonin transporter (Frohlich amount of DAT expressed farther. The amount of im- monoamine transporters. mature and mature proteins et al., 2016). However, this would be attributable to a My study identifies specific had a positive correlation in study tested the effects on direct effect on expression metabolites that significantly all groups. Both the upper the function and levels of ex- rather than on cell growth. influence neurotransmission and lower bands for DAT pression of DAT in response The results of the bichin- by altering the expression of in the presence of p-cresol to these metabolites and is choninic acid assay (BCA) neural-signalling molecules. were much darker than the unprecedented in the lit- assay showed significant dif- Identification of these- me control group, indicating in- erature. The altered uptake ferences in protein concen- tabolites reveals more effi- creased expression of DAT. after 24 hours of exposure trations for the different me- cient probiotic and antibiotic The increased expression at 250 nM, altered protein tabolites after exposure for treatments. The use of prop- was consistent with the ele- concentrations, and differ- 24 hours. Compared to the er probiotics and antibiotics vated protein concentrations ences in band darkness in the control group that received can change the gut microbi- obtained from the BCA as- western blot can be attrib- only sodium butyrate and ota composition towards one say. For propionic acid, the uted to expression because the virus, protein concentra- that does not produce bacte- upper and lower bands were cell growth was confirmed tions were elevated for the rial metabolites harmful to also darker than the control, to be unaffected by the me- groups cultured in propionic the brain. Specifically, my but not as pronounced as tabolites. Similarly to how acid, indoxyl sulfate, and p- research suggests that the those of p-cresol. As with SLC6A4 may be involved in cresol. The propionic acid use of probiotics to normal- p-cresol, the increased ex- the cognitive deficits in pre- and p-cresol groups in par- ize the amount of bacteria pression matched the higher vious studies, altered expres- ticular displayed large differ- that produce propionic acid protein concentrations ob- sion of DAT has implications ences in protein concentra- and p-cresol would normal- tained from the BCA assay. in many mental illnesses re- tion. Meanwhile, the protein ize monoaminergic signal- Like the BCA, expression lated to the gut-brain axis. concentration of the cells ling in the brain. cultured with hippuric acid of DAT seemed to be higher The significant increased ex- was only slightly reduced in p-cresol than in propionic pression of DAT by p-cresol These results expand upon compared to the control. acid. On the other hand, and propionic acid indicates the work of previous studies the cells exposed to indoxyl that more DAT would be that show that propionic acid A western blot was per- present in the brain. This affects neuronal communi- formed to test specifically sulfate and hippuric acid ex- hibited decreased expression means that there would be cation, behavior, and neu- for the expression of DAT. an increased synapse clear- rotransmitter levels, includ- Fig. 7 reaffirms the results of of DAT. The lighter bands for both indoxyl sulfate and ance rate of dopamine by the ing dopamine and serotonin the BCA assay. The darker re-uptake of the transporter. (El-Ansary et al., 2012). 7 Altered expression of DAT nal and not part of ongoing of the metabolites and SERT by circulating work in the mentor’s lab. In that were readily metabolites could be respon- this study, the four selected available from com- Mentor: sible for the altered levels of circulating metabolites, pro- mercial sources on dopamine and serotonin af- pionic acid, indoxyl sulfate, expression and func- Dr. Matthias Quick, ter propionic acid injections. hippuric acid, and p-cresol, tion individually. In While these metabolites did did not affect DAT function, the body, these me- Ph.D. not directly affect the func- as shown by no substantial tabolites would in- tion of DAT, propionic acid effect on uptake at 5 minutes teract with the brain may affect the function of at both 100 µM and 500 µM. simultaneously and DAT indirectly by altering However, the four metabo- under more com- brain phospholipid molecu- lites, when added at 250 nM plex conditions. In lar species (Thomas et al., to cells expressing DAT, did the future, I would 2012). Specifically, propi- influence DAT expression, like to replicate the onic acid increased the ac- as evidenced by the BCA results of this study cumulation of molecular assay, western blot, and up- and look further into species with arachidonic take assay. Propionic acid the expression by ex- acid and decreased the pro- and p-cresol increased DAT amining the mRNA portions of molecular spe- expression while hippuric of DAT. I would cies with docosahexaenoic acid and indoxyl sulfate re- like to look into the ASSISTANT PROFES- acid (Thomas et al., 2012). duced expression. From cell mRNA transcription SOR of Clinical Neuro- Arachidonic acid has been counting it was determined factors involved in biology, Department of found to inhibit dopamine that the difference in expres- the transcription of Psychiatry and Center uptake by DAT (Chen et al., sion was not due to metabo- DAT mRNA and 2003). The other 3 metabo- lite cell toxicity or effects on other mechanisms for Molecular Recogni- lites may function in a simi- cell growth. These results that may have altered tion, lar fashion by altering phos- warrant a future study with a the expression of pholipid molecular species, larger sample size, allowing DAT. Future studies Columbia University and which may in turn influence for a more thorough analy- could test these me- College of Physicians DAT function and uptake. sis of the effect of the repre- tabolites with other A potential implication of sentative compounds in this implicated neural- and Surgeons. dopamine reuptake in gut study. The altered levels of signaling molecules dysbiosis-mediated altera- expression corroborate re- such as the serotonin We are very grateful for tions in brain function can cent findings that circulating transporter, nor- the dedication and help be assumed from the altered metabolites may be involved epinephrine trans- of Dr. Quick. expression of DAT by the 4 in altering the expression porter, brain-derived metabolites. Propionic acid of SLC6A4, the serotonin neurotrophic factor Bibliography has been used to create ani- transporter, in various brain (BDNF), and the N-methyl- mal mouse models of autism regions, most notably the D-aspartate receptor subunit Buie T, Campbell DB, Fuchs GJ, 3rd, (Shultz et al., 2008). Given amygdala (Frohlich et al., GRIN2B. These findings Furuta GT, Levy J, Vandewater J, Whi- the altered dopamine signal- 2016). They also corrobo- contribute to the under- taker AH, Atkins D, Bauman ML, Beau- ing in autism, the effects of rate other studies that refer- standing of the microbiota- det AL, et al. Evaluation, diagnosis, and propionic acid on the expres- ence changes in monoamine gut-brain axis and explore treatment of gastrointestinal disorders sion of DAT may be related levels and neurotransmitter causality in the interaction in individuals with ASDs: a consen- to the etiology of autism. signaling in the brain (Liu between the gut microbiota sus report. Pediatrics. 2010;125(Suppl Taking into account all the et al., 2016). These results and brain. By understand- 1):S1–18. data with circulating metab- at the molecular level also ing the effects of circulat- Carabotti, M., Scirocco, A., Maselli, M. olites, it is evident that gut confirm the hypothesis that ing enteric-derived bacte- A., & Severi, C. (2015). The gut-brain dysbiosis-related changes in profound alterations in the rial metabolites on the brain, axis: interactions between enteric mi- the concentrations of circu- circulating metabolite profile more can be revealed about crobiota, central and enteric nervous lating molecules may be a may be relevant to the com- the mechanism of commu- systems. Annals of Gastroenterology : means to signal to the brain munication between the gut nication of the gut-brain Quarterly Publication of the Hellenic and modify its function. and brain. However, as the axis. These findings about Society of Gastroenterology,28(2), Conclusions and Future circulating metabolite pro- the effects of metabolites on 203–209. Work file is much more complex monoamine transporters pro- Chen N, Appell M, Berfield JL, Reith than 4 metabolites, the sys- vide insight into how circu- MEA. Inhibition by arachidonic acid This was the first study of temic effects of metabolites lating metabolites influence and other fatty acids of dopamine up- this kind on DAT. Devel- on monoamine transporters mental illnesses, cognitive take at the human dopamine transport- oped and conducted by me, are difficult to quantify. This function, and behavior at the er. Eur J Pharmacol. 2003;478:89–95. the student, this independent study only tested the effects molecular level. doi: 10.1016/j.ejphar.2003.08.045. project was entirely origi- 8 Clarke G, Grenham S, Scully P, Fitzger- macology and Neuroscience, 13(3), Bickel J, Wattanasin N, Spence S, behavior in the rat: implications for an ald P, Moloney RD, Shanahan F, Dinan 239–244. http://doi.org/10.9758/ Murphy S, et al. The co-morbidity bur- animal model of autism. Neuropharma- TG, Cryan JF. The microbiome- cpn.2015.13.3.239 den of children and young adults with cology 2008, 54:901. gut-brain axis during early life regu- Finegold SM, Dowd SE, Gontcharova autism spectrum disorders. PLoS One. Thomas RH, Meeking MM, Mepham lates the hippocampal serotonergic V, Liu C, Henley KE, Wolcott RD, 2012;7:e33224. JR, Tichenoff L, Possmayer F, Liu S, system in a sex-dependent manner. Mol Youn E, Summanen PH, Granpeesheh Liang S., Wang T., Hu X., Luo J., Li W., MacFabe DF: The enteric bacterial me- Psychiatry. 2013;18:666–673. D, Dixon D, et al. Pyrosequencing study Wu X., et al. (2015) Administration of tabolite propionic acid alters brain and Collins SM, Surette M, Bercik P. The of fecal microflora of autistic and con- Lactobacillus helveticus ns8 improves plasma phospholipid molecular spe- interplay between the intestinal micro- trol children. Anaerobe. 2010;16:444– behavioral, cognitive, and biochemical cies: further development of a rodent biota and the brain. Nat Rev Microbiol 453. aberrations caused by chronic restraint model of autism spectrum disorders. 2012; 10: 735–742. Finegold S.M., Molitoris D., Song Y., stress. Neuroscience 310: 561–577. J Neuroinflammation. 2012, 9: 153- Conn AR, Fell DI, Steele RD: Charac- Liu C., Vaisanen M.L., Bolte E., Mcte- Liu W.-H., Chuang H.-L., Huang Y.-T., 10.1186/1742-2094-9 153. terization of alpha-keto acid transport ague M., Sandler R., Wexler H., Mar- et al. Alteration of behavior and mono- Yano JM, Yu K, Donaldson GP, et al. across blood brain barrier in rats. Am J lowe E.M., Collins M.D., Lawson P.A., amine levels attributable to Lactoba- : Indigenous bacteria from the gut mi- Physiol 1983, 245:E253-E260. Summanen P., Baysallar M., Tomzynski cillus plantarum PS128 in germ-free crobiota regulate host serotonin biosyn- Coury DL, Ashwood P, Fasano A, Fuchs T.J., Read E., Johnson E., Rolfe R., Na- mice. Behavioural Brain Research. thesis. Cell. 2015;161(2):264–76. G, Geraghty M, Kaul A, Mawe G, Pat- sir P., Shah H., Haake D.A., Manning 2016;298:202–209. doi: 10.1016/j. 10.1016/j.cell.2015.02.047. terson P, Jones NE. Gastrointestinal P., Kaul A. Gastrointestinal microflora bbr.2015.10.046. Zhang LS, Davies SS. Microbial me- conditions in children with autism spec- studies in late-onset autism. Clin. In- Liu X., Cao S., Zhang X. Modulation tabolism of dietary components to bio- trum disorder: developing a research fect. Dis. 2002;35:S6–S16. of gut microbiota–brain axis by probi- active metabolites: opportunities for agenda. Pediatrics. 2012;130(Suppl Frohlich EE, Farzi A, Mayerhofer R, otics, prebiotics, and diet. J Agric Food new therapeutic interventions. Genome 2):S160–168. Reichmann F, Jacan A, Wagner B, et Chem. 2015;63:7885–7895. Med. 2016. doi: 10.1186/s13073-016- Cryan JF, Dinan TG (2012) Mind-alter- al. Cognitive impairment by antibiotic- Markota M, Sin J, Pantazopoulos H, 0296-x. ing microorganisms: the impact of the induced gut dysbiosis: analysis of gut Jonilionis R, Berretta S. Reduced Do- gut microbiota on brain and behaviour. microbiota-brain communication. Brain pamine Transporter expression in the Nat Rev Neurosci 13:701–712. Behav Immun. 2016. doi:10.1016/j. amygdala of subjects diagnosed with bbi.2016.02.020. DeCastro M, Nankova BB, Shah P, Pa- schizophrenia. Schizophrenia Bulletin. tel P, Mally PV, Mishra R, La Gamma Gondalia SV, Palombo EA, Knowles 2014;40(5):984-991. doi:10.1093/sch- EF: Short chain fatty acids regulate SR, Cox SB, Meyer D, Austin DW. bul/sbu084. tyrosine hydroxylase gene expression Molecular characterisation of gastro- Maurer MH, Canis M, Kuschinsky W, through a cAMP dependent signaling intestinal microbiota of children with Duelli R: Correlation between local pathway. Brain Res Mol Brain Res autism (with and without gastrointesti- monocarboxylate transporter 1 (MCT1) 2005, 142:28–38. nal dysfunction) and their neurotypical and glucose transporter 1 (GLUT1) siblings. Autism Res. 2012;5:419–427. Desbonnet L., Garrett L., Clarke G., densities in the adult rat brain. Neurosci Kiely B., Cryan J.F., Dinan T.G. Effects Heijtz, R. D., Wang, S., Anuar, F., Qian, Lett 2004, 355:105–108. of the probiotic Bifidobacterium Y., Björkholm, B., Samuelsson, A., Pet- Nozawa, K., Kawabata-Shoda, E., infantis in the maternal separation tersson, S. (2011). Normal gut micro- Doihara, H., Kojima, R., Okada, H., model of depression. Neuroscience. biota modulates brain development and Mochizuki, S., Ito, H. (2009). TRPA1 2010;170:1179–1188. doi: 10.1016/j. behavior. Proceedings of the National regulates gastrointestinal motility neuroscience.2010.08.005. Academy of Sciences of the United through serotonin release from entero- States of America, 108(7), Dinan, T. G. and Cryan, J. F. (2013), chromaffin cells. Proceedings of the 3047–3052. http://doi.org/10.1073/ Melancholic microbes: a link between National Academy of Sciences of the pnas.1010529108. gut microbiota and depression?. Neuro- United States of America, 106(9), gastroenterol. Motil., 25: 713–719. Hsiao EY, McBride SW, Hsien S, Sha- 3408–3413. http://doi.org/10.1073/ doi:10.1111/nmo.12198. ron G, Hyde ER, McCue T, Mazmanian pnas.0805323106 SK. Microbiota modulate behavioral Dinan TG, Stilling RM, Stanton C, Shaw W. Increased urinary excretion and physiological abnormalities associ- Cryan JF.. Collective unconscious: of a 3-(3-hydroxyphenyl)-3-hydroxy- ated with neurodevelopmental disor- how gut microbes shape human be- propionic acid (HPHPA), an abnormal ders. Cell. 2013;155(7):1451–63. doi: havior. J Psychiatr Res (2015) 63:1 phenylalanine metabolite of Clostridia 10.1016/j.cell.2013.11.024. 9.10.1016/j.jpsychires.2015.02.021. spp. in the gastrointestinal tract, in urine Kang DW, Park JG, Ilhan ZE, Wallstrom samples from patients with autism and El-Ansary, A.K.; Ben Bacha, A.; Kotb, G, Labaer J, Adams JB, Krajmalnik- schizophrenia. Nutr Neurosci. 2010 M. Etiology of autistic features: The Brown R. Reduced Incidence of and Jun;13(3):135-43. persisting neurotoxic effects of propi- Other Fermenters in Intestinal Micro- onic acid. J. Neuroinflamm. 2012, 9, Shultz SR, MacFabe DF, Ossenkopp flora of Autistic Children. PLoS One. 74. KP, Scratch S, Whelan J, Taylor R, Cain 2013;8:e68322. DP: Intracerebroventricular injection Evrensel, A., & Ceylan, M. E. (2015). Kohane IS, McMurry A, Weber G, of propionic acid, an enteric bacterial The Gut-Brain Axis: The Missing Link MacFadden D, Rappaport L, Kunkel L, metabolic end-product, impairs social in Depression. Clinical Psychophar- 9 Analyzing the Role of Chlorophyll a, b, and d in Oxygenic Pho- tosynthesis, by Melanie Porras (STS Scholar, Paper excerpt) (Senior) Though higher and function affected by its of people. plant species use chemical composition but by Scientists are chlorophyll a and also by the position of each now look- chlorophyll b in element. ing at natures oxygenic pho- Introduction solar cells for inspiration tosynthesis, dis- taking note of the structural A persistent problem human- coveries of a new and mechanistic properties kind faces is the quest for a chlorophyll have that allow cyanobacteria and renewable energy source. In been made: chloro- plants flourish, even in low previous centuries, civiliza- phyll d. This study light conditions. tions have relied heavily on analyzes different fossil fuels but the burning Plants have created a highly chlorophyll pig- of fossil fuels is detrimental efficient solar cell, with- ef ments in the intent to both local and global en- ficiencies ~ 3x greater than to discover why vironments resulting in re- commercialized solar cells. plants evolved to searchers searching for new This process, known as pho- use certain pig- and renewable energy sourc- tosynthesis, uses sunlight ments. The meth- es. Nuclear, wind, and solar to oxidize water yielding ods used during energy harvesting technolo- molecular oxygen and pri- this experiment gies have been developed marily carbohydrates. More- was the use of den- Abstract but each has its own draw- over, this is accomplished sity functional theory (DFT) back. One of the most prom- with abundant, non-toxic, Oxygenic photosynthesis, and analyzing spectral prop- ising is solar energy because biodegradable components. the process of splitting water erties from absorption spec- the sun produces significant Photosynthesis captures the to synthesize carbon dioxide tra taken. Through further amounts of energy provid- sunlight reaching the surface into glucose and produce ox- comprehension of the vari- ing a promising renewable and provides much of the en- ygen, is effortlessly used by ous cofactors in photosyn- energy source for the future. ergy and all the oxygen the an abundance of plants ev- thesis we are continuing to Modern solar technologies remaining creatures need to ery day. However, scientists develop our understanding have low absorbencies, are survive. Billions of years of have not yet been able to of how to replicate a pho- too expensive, or have yet to evolution culminated into understand exactly how this tosynthetic process. The be commercialized, meaning the success of photosynthe- process works. Many cofac- results of this study deter- they can produce electricity sis leading scientists to try tors participate in the pro- mined that not only is chlo- suitable for now but cannot and recreate photosynthesis cess of photosynthesis, one rophyll’s spectral properties of them being chlorophyll. sustain the needs of billions in the lab. Moreover, since photosynthesis in the lab is customi- zable, solar xida- tion of water can be used to yield mo- lecular hydrogen, or conduct CO2 reduction to simple organic compounds like formaldehyde or even methanol. Chlorophyll (Chl) is a tetrapyrrolic molecular pigment that participates in many types of elec-
10 neighboring his- ure 2). P700 like P680, has a tidine residue. By special set of chlorophyll a losing a proton molecules, however it con- and an electron sists of Chl a and Chl a’, the concurrently, the 132-epimer of Chl a (Figure activation barrier 3). A more distinctive char- is reduced and the acteristic of PSI compared intermediate is to PSII is that the terminal an excitation of the mo- stabilized, allow- electron acceptor is a redox 1,6 lecular wave function. ing YZ to be reduced by the active Fe4S4 cluster. En- Depending on the organ- oxygen evolving complex ergy absorption and electron
ism, the LHC II can con- (OEC), specifically a Mn4Ca transfer in PSI commences tron transfer, making photo- tain various oxo cluster. The OEC under- at LHC I. Through similar 1 synthesis operate. Chl is a Chls like Chl a, Chl b, or Chl goes successive oxidations exciton transfer, energy is storing four oxidizing equiv- funneled to P creating the magnesium chlorin which is d, as well as other pigments 700 alents and as two water mol- excited state P * (Figure 2). capable of excited state ener- like carotenoids, to maximize 700 gy transfer, oxidation and re- photosynthetic capacity of ecules are oxidized; yielding The special pair transfers an duction, all of which enables 4 protons, 4 electrons, and electron to the primary elec- PSII.1 This antenna collects 5 photosynthetic reaction cen- light energy and funnels it to molecular oxygen. Here tron acceptor A0, a chloro- ters, or photosystems (PS) the OEC reaches its fully phyll molecule creating the the RC of •+ to conduct the oxidation of reduced state (S0), resulting charge separated pair P700 PSII through exciton trans- •- water releasing four protons in a recovered state for the A . The charge separated fer. In the RC, a group of 0 and four electrons. These complex. pair is stabilized by further Chl a molecules, called P , protons create a potential 680 electron transfer to A , a sec- known as a “special pair,” After the initial electron 1 gradient which produces the ond chlorophyll molecule, accepts the excitation energy transfers in PSII, many ubiquitous energy molecule and subsequently transferred creating the excited state, P more electron transfers are of life, ATP, while the elec- 3,4 performed with other mem- through FX, FB, and FA, a * (Figure 1). The num- •+ trons are used to store energy 680 series of Fe S clusters. P ber included in the name of brane bound protein com- 4 4 700 in the form of carbohydrates. is then re-reduced by plasto- a “special pair” describes plexes, like cytochrome b6f, The entire process of photo- cyanin, a reductant produced the certain wavelength it ab- and photosystem I (PSI) all synthesis requires numerous by cyt b6f, which converts sorbs. the while facilitating proton protein complexes which are transfer from the stroma to electrons from PSII to plas- P * subsequently transfers both cytoplasmic and trans- 680 the lumen membrane and for purposes an electron to, PheoD1, de- creating a of replication, photosystem noted by the red arrow in proton gra- II (PSII) is of primary focus Figure 1. This transfer results dient gener- because it conducts water in the charge separated state, •+ •- ating ATP. P Pheo which is further 1 oxidation. 680 Similar to stabilized by electron trans- The Chls of PSII are packed PSII, the ferred from Pheo•- to QA, the into proteins and utilized as composi- primary quinone acceptor. antenna in the light harvest- tion of the The electron is further trans- ing complex (LHCII), and PSI complex ferred from Qa•- to QB, the chlorophyll proteins (CP) as has an an- secondary plastoquinone and well as and charge transfer tenna com- terminal electron acceptor cofactors in reaction center plex, light creating the highly separated (RC).2 Photosystem II (PSII) harvesting electron hole pair P •+ QB•- is located in the thylakoid 680 complex I .3 The highly oxidizing P •+ membrane of chloroplast or- 680 (LHC I) and must be reduced in order to ganelles which contains both a RC which prevent damage to the pro- LHC II and CPs to maximize contains a tein complex. This reduction light absorption. Initially, group of occurs via the redox active Chl molecules in the LHC chlorophylls tyrosine residue, YZ, which II absorb photons of specific referred to undergoes proton-coupled wavelengths which promote as P (Fig- electron transfer with a 700 11 sists of primarily pigments. The structures density functional theory Chl d and roughly of these three pigments are (DFT) to analyze the effects 5% of Chl a.8 In similar in their modifications of substitution on the partial this unique cy- yet vary in their spectral and charge distributions and spin anobacteria, Chl d chemical properties. All spe- density distributions of the not only serves as cies are chlorins, which are highest occupied molecular a light harvester 17-18 dihydro porphyrins. Chl orbitals (HOMO) and lowest
of in LHCs but a has a vinyl group at R1 on unoccupied molecular orbit- also as the main the macrocycle and a methyl als (LUMO). We also sup-
reaction center, group at R2 (Figure 3). The port experimental findings believed to be an vinyl and methyl groups with theoretical methods similar set of spe- acts as weak electron donors to understand substitution
cial Chls, P740, in while the vinyl group ex- and structural effects on the PSI.7 Contrary to pands the π-system along the spectral and electrochemical higher plants and y-direction. Chl b is identi- properties of tocyanin while also contrib- other cyanobacte- cal to Chl a except in the re- Chl a, Chl b, and Chl d, to uting the proton gradient, ria which contain a Chl a/a’ placement of the R2 methyl better understand their prop- subsequently helping drive heterodimer in PSI, P740 in A. group with an aldehyde. This erties and to elucidate why the synthesis of ATP. marina contains a Chl d/d’ effect is important in that nature has evolved to use 6,7 The electrons generated from heterodimer. However, the a weak electron donor has these pigments. primary electron acceptor is been replaced with a strong water splitting are trans- (...) ferred from PSII and con- still a chlorophyll a; similar electron withdrawer as well Results tinue throughout the elec- to PSI in higher order plants as π-system alteration along tron transport chain and PSI and cyanobacteria. Although the x-direction. Chl d varies Quantum Mechanical Cal- to finally reduce ferredoxin much is known about PSI of in structure compared to Chl culations and the ferredoxin-NADP+ A. marina, the composition a in that the vinyl group in VASP DFT computations reductase, a flavoprotein; of the special pair in PSII is R1 has been replaced with were completed and ana- resulting in the production still a controversy. The pos- an aldehyde group, which lyzed to construct partial of NADPH. Once ATP and sibilities consist of a Chl d retains π-system conjuga- charge and spin density maps NADPH have been acquired dimer, 8 a Chl a dimer, 9 or a tion, but replaces an elec- for each molecules HOMO 10 the plant can start the chemi- Chl a/d heterodimer. tron donor with an electron and oxidized state. cal process of converting Statement of Purpose withdrawer. Although the Partial Charge Density two vary in structure their carbon dioxide into carbo- In the present study, we function is very similar. An The electron density maps hydrates. analyze the structural dif- explanation for this could be show an approximation of In recent years it has been ferences of chlorophyll pig- answered by the theory that charge distributions for mo- discovered that Chl d exist ments, specifically Chl a, states that Chl d may have lecular orbital. The calcu- as a dominant chlorophyll in Chl b, and Chl d, to better been synthesized from Chl a lated HOMO charge densi- the red algae, Acaryochloris understand how their chemi- ties for chlorophyll a, b, and 7 due to a presence of a certain marina. While most oxygen- cal substitution changes, enzyme, specifically cyto- d are depicted in Figure 5. ic photosynthetic systems their spectral, and electrical chrome P450 oxygenate.11 The density appears constant have mainly Chl a and low properties elucidate as to Here in this study we use ab- with density existing on N1- amounts of other accessory why phototrophic organisms sorbance spectroscopy and N3 but not on N4, the satu- chlorophylls, A. marina con- evolved to utilize different rated ring. Charge density is also observed across the Cα-Cβ bonds of rings 1-3 with some on the bridging carbons. Chl d was the only Chl to yield charge density on the nitrogen of ring 4. This density is due to the extensive conjugation expe- rienced by planar π-systems. In addition, density can be seen hyper-conjugating with
12 the substituents of C2, C7, cial and C8, C12, C17 and C18. This superfa- is partially why these groups cial, the are the electron donors. Con- Chl d di- jugation is also observed mer pair to extend to the π-system exhibited of substituents were differ- a bit of ences in electron densities electron are readily observed. Ac- d e n s i t y cording to our calculations, on the the aldehyde of Chl b has Chl with greater electron density than less den- the aldehyde located on Chl sity in the d. This change in electron HOMO. density at the aldehyde also S p i n affects nearby substituents Density as the C2 methyl group has The spin a greater electron density d e n s i t y compared to Chl a. Simi- distribu- larly, the aldehyde located tions por- in Chl b yielded an increase tra where in electron density of nearby spin can substituents. be found The special set of Chls ob- in the served in organisms are re- spin up more greatly studied. When and the effect of a HOMO-1 ferred to as such because (yellow) or spin down (cyan) analyzing the oxygen atom to HOMO for the anion, dif- of their cooperative work. state. In these calculations, in an aldehyde of cationic ferences were also observed. Therefore, it was expected the spin referred to is that of Chl b and Chl d, the un- Overall chlorophyll b experi- that the calculated HOMO an unpaired electron. Since paired electrons surrounding enced a decrease in electron of the Chl dimers had elec- spin density represents the Chl b had a net spin of spin density around the oxygen tron density distributed over net spin of an entire molecu- up, meanwhile Chl d had a atom in an aldehyde, while both pigments. Each Chl of lar wave function, and in the net spin of spin down (See chlorophyll d experienced the dimer has charge density case of monomeric Chl can Figure 7). However, when an increase. matching the distribution be an anion or cation, anion- looking at the anions of each The spin density values for of the monomeric models ic and cationic models of Chl chlorophyll it was the op- the Chl a and Chl d dimer shown in Figure 5. The main a, b, and d were calculated. posite, Chl b had a net spin pairs were also calculated differences observed is that In nature when Chlz, acces- of spin down and Chl d had and recorded. Overall the the Chl a dimer has a much sory chlorophyll in the PSII a net spin of spin up. When Chl d dimer pair (antarafa- more uniform charge distri- RC, gets photo-oxidized it analyzing the presence of an cial) has a greater spin den- bution over the two com- becomes a cation, positively aldehyde and its effect on the sity than the Chl a pair (See pared to the Chl d dimer, charged, thus in this study HOMO to LUMO of a neu- Figure 8). Specifically, the both antarafacial and supra- the cationic species was tral and cationic chlorophyll, Chl d dimer pair had a great facial (See Figure 6). In addition, the Chl d dimer exhib- ited charge density on the ligating his- tidine nitrogen to the Chl with more density. Calcula- tions of the LUMO of each dimer pair were yielded, for both the antarafa-
13 and the identified, and the HOMO- c a t i o n LUMO gap, measured in pair oc- electronvolts (eV), can be curs due calculated (See Table 1). to the Molecules that contains absence small HOMO-LUMO gaps of an are typically more reactive electron than molecules with larger in the gaps. 19 Gaps between MOs cationic can be used to identify mol- pair. ecules because in a UV-Vis Eigen- absorption spectra the Soret values band represents the HOMO to LUMO+1 gap and the Q T h e band shows the HOMO to eigen- LUMO gap. With the single v a l u e s chlorophylls the order of of each energy levels for both the molecule HOMO to LUMO+1 gap and were cal- the HOMO to LUMO gap c u l a t e d went as follows from great- as well; est to smallest: the neutral showing chlorophyll, the chlorophyll spin down density (seen in was slightly shifted towards the oc- anion, and then the chlo- blue) than Chl a. Interesting- the other chlorophyll. When cupancy and energy of spin rophyll cation. Since small ly noted, Chl d’s aldehyde looking at the cation species up and spin down electrons HOMO-LUMO gaps are (circled in red) experience a of the Chl d dimer pairs, the in each molecular orbital normally more reactive, it smaller electron density than LUMO of the Chl d dimer (MO). From here the can be concluded that overall Chl a’s methyl group (circled pairs contained similar elec- Highest Occupied Molecu- a chlorophyll anion is more in blue). However, when tron density on both chloro- lar Orbital (HOMO) and the reactive than the neutral and direction is taken into con- phylls. This difference be- Lowest Unoccupied Molec- cationic species. sideration, Chl d’s aldehyde tween the Chl d neutral pair ular Orbital (LUMO) can be More specifically it was the Chl b anion that proved to be the most reactive, with an HOMOLUMO gap of 0.2482 eV, out of all mole- cules tested. Overall the Chl a and Chl d HOMOLUMO gap values were close in range, about 0.06 eV at most in difference. In terms of the chlorophyll dimer pairs in all HOMO-LUMO+1 and HOMO-LUMO gap (for all dimer pair species) there was roughly a .05 eV dif- ference calculated. UV-Vis Spectroscopy of Pigment Extraction A UV-Vis spec- troscopy of the all pigments and each band was done. Graph 1 shows the absor- bance spectra of the pigment extract and each green band.
14 From here the absorption its environment but rather future studies to spectra of the green bands to certain elements. When try and synthesize was compared to the absorp- looking at the electron den- Chl d from the Mentor: tion spectra of known chlo- sity of the pigments and the Chl a we obtained. Dr. K. V. Lakshmi, rophyll dissolved in metha- effects of an aldehyde it was Past research has nol from Kobayashi’s paper concluded that Chl b expe- not yet defined an Ph.D. “Physicochemical properties rienced a slightly greater exact answer to of chlorophylls in oxygenic electron density around its replicate this pro- ASSOCIATE PROFESSOR photosynthesis – succession oxygen atom as opposed to cess, thus it would Chemistry and Chemical of co-factors from anoxy- Chl d. Yet when looking at be my goal to dis- Biology. genic to oxygenic photosyn- the effect of aldehydes on cover the possible thesis.” The green bands the HOMO and LUMO of enzyme that com- were then identified as chlo- these pigments, Chl d ex- mences the syn- SCIENTIFIC DIRECTOR of rophyll a for they had a simi- perienced an increase in thesis of Chl a into the Baruch ’60 Center for lar absorption peaks to ones the electron density around d and see if this Biochemical Solar Energy measured: 432.5 nm and the oxygen atom while Chl can occur/has oc- Research 665.8 nm.6 b experienced a decrease. curred in nature. Discussion/Conclusion This tells us that Chl d takes Once we discover Rensselaer Polytechnic In- a greater part when an elec- In this experiment we ana- why photo-oxi- stitute. tron is obtained than Chl b. lyzed the structural differ- dizing organisms When looking at the HOMO ences of Chl a, Chl b, and evolved the way We are grateful to Dr. Lak- and LUMO of a neutral Chl Chl d, to help us under- they did (for sur- shmi and Dr. G. Theophall d dimer pair (antara) certain stand why certain organisms vival or due to for their dedication and characteristics were seen. In evolved to use different pig- location; just to this case one of the chloro- help. ments. Though the structure name a few) then phylls of the pair experi- of these pigments contain a system that ful- R. A.; enced a greater electron den- similar variations, the effect ly enhances the potential of Korol’kova, D. V.; Tomo, T; Shen, J.-R. sity over the other in both the Chlorophylls d and f and their role in of elements in certain posi- photosynthesis is one step HOMO and LUMO. But, the primary photosynthetic processes of tions is critical. closer to being created. Sci- cyanobacteria. Biochemistry (Moscow) cationic species didn’t expe- entists need to understand 2016, 81–201. While the vinyl and methyl rience such a drastic differ- why the variations of chlo- 5. Velthuys, B.; Kok, B. Photosynthetic groups acts as weak electron ence between the two chlo- rophyll occur before they oxygen evolution from hydrogen per- donors the aldehyde acts as a oxide. Bioenergetics 1978, 221–221. rophylls in both the HOMO can choose a single chloro- strong electron withdrawer. 6. Kobayashi, M.; Akutsu, S.; Fuji- and LUMO; very similar to phyll pigment when creat- numa, D.; Furukawa, H.; Komatsu, Although the aldehyde in Chl the results found with the ing a solar cell. Once this H.; Hotota, Y.; Kato, Y.; Kuroiwa, Y.; b alters the π-system along Watanabe, T.; Ohnishi-Kameyama, M.; Chl a dimer pair. This tells us obstacle has been overcome the x-direction, Chl d’s al- Ono, H.; Ohkubo, S.; Miyashita, H. that while the Chl d species then commence the process dehyde retains the π-system Physicochemical properties of chlo- is cationic, which occurs in of replicating artificial pho- rophylls in oxygenic photosynthesis – conjugation. nature due the “special pair” tosynthesis on a solar panel succession of cofactors from anoxygen- From quantum mechanical ic to oxygenic photosynthesis. In Zvy being oxidized in photosyn- and implementing it into the Dubinsky, Photosynthesis 2013, 47–90. calculation, specifically cal- thesis, it has similar proper- real world. 7. Kobayashi, M.; Ohashi, S.; Iwamoto, culating the Eigen values, ties to a Chl a dimer pair and References K.; Shiraiwa, Y.; Kato, Y.; Watanabe, T. Redox potential of chlorophyll d in it can be concluded Chl d’s can possibly similar func- 1. Senge, M.O.; Ryan, A.A.; Letchford, vitro. Elsevier 2007, 596–602 R1 aldehyde position makes tions. Giving us a further K.A.; MacGowan, S.A.; Mielke, T.. Chlorophylls, 8. Nieuwenburg, P,; Clarke, R.J.; Cai, the molecule less reactive information on the possibili- Z.L.; Chen, M.; Larkum, A.W.D.; Symmetry, Chirality, and Photosynthe- Cabral, N.M.; Ghiggino, K.P.; Reimers, as opposed to Chl b. Chl ties of the “special pair” in sis. Symmetry 2014, 6, 781–843. d’s HOMO-LUMO gap be- J.R. Examination of the photophysical Acaryochloris marina’s PSII. 2. McConnell, I.; Li, G.; Brudvig, G. W. processes of chlorophyll d leading to ing similar in energy level Further investigation would Energy Conversion in Natural and Ar- a clarification of proposed uphill- en to Chl a tells us that these need to be gone to officially tificial Photosynthesis. Chemistry and ergy transfer processes in cells of Ac- Biology 2010, 17, 434–447. two pigments have similar aryochloris marina, Photochem. Photo- determine if A. marina PSI’s 3. Lakshmi, K.V.; Coates, C.S.; Smith, biol. 2003, 77, 628–637. properties and functions. A Chl d/d’ heterodimer evolved S., Chatterjee; R. The Radical Interme- 9. M. Mimuro; S. Akimoto; T. Gotoh; molecule’s reactivity is cru- from a Chl a dimer pair. diates of Photosystem II. The Biophys- M. Yokono; M. Akiyama; T. Tsuchiya; cial in photosynthesis as it ics of Photosynthesis, Biophysics for H. Miyashita; M. Kobayashi; I. Yamaza- Since Chl d is difficult to ob- the Life Sciences 2014, 299–320. ki, Identification of the primary electron cannot be easily disposed tain it would be part of my 4. Allakhverdiev, S. I.; Kreslavski, V. donor in PS II of the Chl d dominated to reacting with everything D.; Zharmukhamedov, S. K.; Voloshin, cyanobacterium Acaryo-chloris marina, 15 FEBS Lett. 2004, 556, 95–98. Biochemistry 2016, 201–2012 J.R.; & Kaiya, N. Crystal structure of optical and thermal infrared regions, 10. Kobayashi, M.; Watanabe, S.; Go- 12. Hoffmann, R.; Woodward, R. B. J. oxygen-evolving photosystem II at a 1990, 5, 207–213. toh, T,; Koizumi, H.; Itoh, Y.; Akiya- Cycloaddition Reactions. Am. Chem. resolution of 1.9 Å. Nature 2011, 473, 18. Kresse, G.; Furthmüller, J.; Effi- ma, M.; Shiraiwa, Y.; Soc. 1965, 87(9), 2046-2048 55–60 cient Iterative Schemes for Ab-Initio Tsuchiya, T.; Miyashita, H.; Mimuro, 13. Kresse, G.; Furthmüller, J.; Effi- 16. Hanwell, M.D.; Curtis, D.E.; Lo- Total-Energy Calculations Using a M.; Yamashita, T.; Watanabe, T. Minor cient Iterative Schemes for Ab-Initio nie, D.C.; Vandermeersch, T; Zurek, Plane-Wave Basis Set. Physical Review but key chlorophylls in photosystem II, Total-Energy Calculations Using a E; Hutchison, G.R. “Avogadro: An B. 1996, 54, 169–186. Photosynth. Res. 2005, 84, 201–207. Plane-Wave Basis Set. Physical Re- Advanced Semantic Chemical Editor, 19. Zhang, G.; Musgrave, C.B. Com- Visualization, and Analysis Platform.” 11. Allakhverdiev, S.I.; Kreslavski, view B. 1996, 54, 169–186. parison of DFT Methods for Molecu- Journal of Cheminformatics 2012, lar Orbital Eigenvalue Calculations. J. V.D.; Zharmukhamedov, S.K.; Vo- 14. Perdew, J.P.; Burke, K.; Ernzerhof, 4–17. loshin, R.A.; Korol’kova, D.V.; Tomo, M.; Generalized Gradient Approxima- Phys. Chem. A 2007, 111, 1554–1561 T.; and Shen, J.R. Chlorophylls d and tion Made Simple.Physical Review 17. Plata, J. Leaf chlorophyll content. f and Their Role in Primary Photo- Letters 1996, 77, 3865–3868. Instrumentation for studying veg- etation canopies for remote sensing in synthetic Processes of Cyanobacteria. 15. Umea, Y.; Kawakami, K,; Shen, Testing For Dispersant Effectiveness to Remediate Oil Spills Using a Baffled Flask Test With The Use of The Dispersant Corexit 9500 by Isabella Brizzi (STS paper excerpt) (Senior)
dispersed. Our Oils spills have been a prev- In consequence, such disas- initial hypothesis alent issue in society since ters may cause a significant (at higher RPM The Deepwater Oil Spill in decrease in a species popu- speeds and in April of 2010. Oil spills like lation (7). The Deepwater the presence of a the Deepwater Horizon Oil Horizon Oil Spill caused dispersant, more spill, often are responsible thousands of gallons of oil oil would be dis- for causing a population of to be leaked into the Gulf persed) was not species to become drasti- of Mexico, which affected supported in the cally affected, resulting in many aquatic species of preliminary ex- death within the population. wildlife (1). An example of periments: More Figure 1: (a) Standard Stock Calibration Curve data with the use of a dispersant (Part One). Graph displays Area vs the Concentration of oil in grams per liter. (b) oil was dispersed Standard Stock Calibration Curve data without the use of a dispersant (Part One). at lower RPM Graph displays Area vs the Concentration of the oil in grams per liter. The dashed speeds with the line represents the line of best fit. presence of a dis- persant. Based on these results, we modified the procedure; and all groups were tested with and without the use Abstract: of a dispersant, Corexit9500, a dispersant at 200 RPM for 10 minutes, for accidental oceanic oil allowing for less oil sticking spills, was studied to de- to the baffled flask. This new termine the most efficient data set showed that more oil parameters for its use while was dispersed in the presence reducing environmental im- of Corexit9500, even though pact. In our initial study, a some of the data showed that baffled flask test performed oil was still lost to the walls at 125 RPM and 250 RPM, of the baffled flask. More with and without dispersant studies have to be conducted for two hours to mimic wave to confirm that this effect is patterns (7). Liquid- liquid consistent and replicable, extracts were then measured thus the need for more trials in a UV spectrophotometer to be completed. to determine the percent oil Introduction: 16 out causing any unnecessary oil would be dispersed as harm to the environment. compared to without the use To do so, we would test for of dispersant.The purpose of the best possible conditions Part Two of this experiment for the dispersant, Corexit would be to follow the EPA’s 9500, working with a baffled protocol to collect data on flask at various RPMs. At dispersant effectiveness at RPM speeds with the use of 200 RPM for 10 minutes, to a dispersant, more oil would see how well the dispersant, be dispersed, facilitating its Corexit 9500 works more ef- removal. The different RPM ficiently without causing any speed would be used to stim- unnecessary harm to the en- ulate different wave patterns, vironment. It was originally Figure 5: (a) Standard Stock Calibration Curve data with the use of a dispersant (Part Two Graph displays Area vs the Concentration of oil in grams per liter. (b) creating an ocean like situa- hypothesized that at higher Standard Stock Calibration Curve data without the use of a dispersant (Part Two). tion. It is expected to find a RPM speeds, with the use of Graph displays Area vs the Concentration of the oil in grams per liter. The dashed line represents the line of best fit. significantly higher percent- a dispersant, more oil would age of the oil dispersed with be dispersed. (...) a similar situation would particles to be able to break the use of this dispersant in be the increase of deaths down further and be con- Results: the best possible conditions. in the Dolphin species fol- sumed by microorganisms Below are the equations nec- Without the use of a disper- lowing Hurricane Sandy. (3).Exposure to deadly tox- essary to determine the total sant, there would not be a Many of the dolphins who ins or chemicals can weaken amount of oil dispersed. percentage of oil dispersed washed up on beaches after an organism’s immune sys- at the RPMs tested. Area: Based on absorbance Hurricane Sandy were seen tem and make that organism at 340,370, and 400 nm from Part Two: to have died of the Dol- more susceptible to various the UV spectrometer mea- phin Morbillivirus, a virus diseases (1). Although many Based on the results of Part surements One, our hypothesis was belonging to the measles of the effects of dispersants (((Abs 340+Abs 370) X 30) modified: at 200 RPM with family (9). Recently in the are still unknown, modern /2 ) + (((Abs 370 + Abs 400) the use of a dispersant, more spring of 2015, another oil day dispersants are less toxic X 30) / 2) spill occurred off the coast than those previously used Figure 3: Bar graph compares data from Total Oil Dispersed and Percentage of Oil Dispersed of California releasing an (6). If the correct dispersant at 125 RPM and 250 RPM with and without the use of a dispersant, Corexit 9500. Bar graph estimated 105,000 gal- is used at the found optimal shows data from 2 hours. lons of oil released, due to condition, it can be expected ! a pipeline rupture (2). In that the effect on both the order to attempt to remedi- environment and the wild- ate the damage caused by life can be less severe. these disasters, the use of a Goals and Hypothesis dispersant is needed. A dis- Part One: persant is a liquid or gas that is commonly used to help The purpose of Part One of clean up oil spills. Disper- the experiment would be to sants can break down larger find the most effective con- particles of oil into smaller dition for a dispersant to particles. This allows the work most efficiently with- 17 that at higher Calibration Curves RPM speeds The table from Figure 6, and with the use shows four different tests of a dispersant, from Part Two, with and more oil would without dispersant at 200 be dispersed. My RPM for 10 minutes each. data showed that For each of these tests, the at lower RPM raw data from the total oil speeds with the dispersed, as well as the use of a disper- percentage of oil dispersed sant, more oil was (dispersant effectiveness) dispersed. The is shown on the table. This reason for this is data was calculated using because at high the slope from the calibra- Figure 4: LISSTX100 graph displays data from Part one, comparing the Volume Fraction to the RPM speeds, Oil Droplet Diameter Distribution in micrometers. tion curve slopes in Figure 5. such as 250 RPM, The raw data from the table The Area formula was used ure 1 and Figure 5) obtained a majority of the shows that with the use of to find the amount of total for Part One and Part Two, oil was lost to the walls of the dispersant, the percent- oil that would be dispersed are necessary for determin- the baffled flask. age of oil dispersed was sig- as well as its percentage (5). ing the Total Oil Dispersed The oil- water samples from nificantly higher than -with Total Oil Dispersed (calibra- in each Baffled Flask. The Part One were placed into out the use of a dispersant. tion curve slopes, obtained slope of the line of best fit a LISSTX100 machine to As seen in Figure 7, the raw from Figure 1 and Figure from each of the standard test for the volume fraction data from the table in Figure 5): stock curves is used with as well as the oil droplet 6 was taken and put into a their corresponding sample diameter distribution in mi- V DCM is the volume of the statistical data analysis pro- to determine the Total Oil crometers. As seen in Figure Dichloromethane. gram. The chart in Figure 7 Dispersed in each Baffled 4, the oil droplet size in mi- shows the averages of the per- V tw is the total volume of Flask. For example, a baf- crometers was much larger centage of oil dispersed with seawater that is used in the fled flask test at 200 RPM in particles that were not in dispersant and the percentage baffled flask. without dispersant, would contact with the dispersant, of oil dispersed without dis- V ew is the total volume of use the slope from the Part 2 Corexit 9500. A larger drop- persant. The average without seawater that is extracted Standard Stock Calibration let size, also correlated to dispersant is 2.765 %, which from the flask. curve without dispersant larger volume fraction. In is considerably lower than (Figure 5(b)). The standard Part Two of the experiment, the average with dispersant the procedures were altered Dispersant Effectiveness stock Calibration Curves which is 40.485 %. This to follow the EPA’s protocol (Percentage of Oil Dis- have much less room for er- data shows that in the pres- in order to receive the most persed) ror because they are not con- ence of Corexit 9500, more ducted within a baffled flask, accuracy. The data showed oil is dispersed than without Poil is the density of the par- and thus there is no oil to be that within the presence of the addition of a dispersant. ticular oil being tested. lost to the walls of the flask Corexit 9500, the oil drop- This result is highly signifi- Voil is the volume of the oil during its shaking period. lets size was successfully cant, as assessed with a t-test which is put into the flask- The table results from Fig- reduced, allowing for the and confirms the preliminary ure 2 are from Part One of oil droplets to be remedi- results as seen in part 1, the the experiment. The results ated more efficiently. Even use of dispersant is critical in were taken from a two hour though the results from Part increasing the percentage of sample. Part One’s results One of the experiment were oil dispersed. different from what was showed that more oil was dis- Discussion: Part 1: originally hypothesized, the persed at lower RPM speeds In both Part One and Part Calibration Curves which was unexpected. It data from the LISSTX100 machine shows that no mat- Two of the experiment it was The standard curves (Fig- was originally hypothesized ter the condition, Corexit seen that oil-water samples successfully reduces the oil with the dispersant, Corexit droplets size. 9500, had a higher percent- age of oil dispersed than Part 2: compared to the samples that 18 Mentor: Dr. Zhong Pan, Ph.D.
Post Doctoral Research As- sociate.
Center for Natural Resources Development and Protection, New Jersey Institute of Technology
We are very grateful to Dr. Pan for his dedication and help.
Figure 6: Table displays Part Two’s raw data from 4 identical tests, tested at 200 RPM, with and without the use of a dispersant. Each sample was tested at a time of 10 minutes, following the EPA’s part two of the use of Corexit 9500 in other protocol for accuracy experiment, bodies of water like rivers, each sample which have fewer waves, were tested without disper- Part One and Part Two of was shaken thus correlating to very low sant. Corexit 9500, a disper- the experiment to see how it for a time for 10 minutes at RPM speeds. sant with amphipathic prop- affects the percentage of oil 200 RPM and it was seen Conclusion: erties, has been used to clean dispersed by Corexit 9500 that there was much less oil Oil Spills have become an oil spills in environmental in each sample. If higher residue left the walls of the increasingly popular issue disasters (11). This data percentages of oil dispersed baffled flask, giving more within today’s modern so- shows that Corexit 9500, are seen, and Sylon CT is conclusive data. More stud- ciety. As the environment is effectively disperses the oil deemed environmentally ies need to be completed to constantly changing due to droplets allowing them to safe, it may be used in ad- confirm this data to test and global warming and the ris- become smaller particles. dition to Corexit 9500 in optimize other conditions for ing of sea levels, the world As the oil particles become future oil spill remediation. its use. In the future it would has become more suscepti- smaller, they can then be con- Part One’s be interesting to consider the sumed by microorganisms, prelimi- such as bacteria (3). The loss nary data of of oil in Part One of the ex- the experi- periment due to the walls of ment was the baffled flask made for a c o n d u c t e d larger margin of error and at a time of confused the results. The two hours at original variation, observed RPM speeds in the Part One experiments, of 125 and in the future could be fixed 250 RPM. by testing it again in future It was seen studies with the addition of that at higher Sylon CT. When the walls RPM speeds, of the baffled flask are lined a significant with Sylon CT, a majority of amount of Figure 7: Chart displays the statistical averages for Part Two’s data at 200 RPM for 10 minutes, with the oil is stopped from stick- the oil was and without dispersant. The average for the percentage of oil dispersed without the dispersant Corexit ing the walls of the baffled lost to the 9500 is 2.765 %, while the average for the percentage of oil dispersed with the dispersant Corexit 9500 flask (11). It may be benefi- baffled flask is 40.485 %. The averages for both the with and without dispersant within Figure 7 have error bars which represent the standard error of the mean. n=4, ** indicate p<0.001 in unpaired t-test cial to test Sylon CT in both itself. In
19 ble to natural disasters such that is both successful and repeatability.” Spill Science & Tech- BMC Microbiology BMC Microbiol, nology Bulletin 7.5 (2002): 299-308 13(1), 9. doi:10.1186/1471-2180-13-9 as oil spills. Oil dispersants efficient, allowing for the Venosa, Albert D, and Edith L Holder. Venn-Watson, S., Garrison, L., Litz, are likely to be used very least damage to be brought “Determining the dispersibility of J., Fougeres, E., Mase, B., Rappucci, often, as more of these di- to the environment as pos- South Louisiana crude oil by eight oil G., Rowles, T. (2015). Demographic sasters may occur. They do sible. dispersant products listed on the NCP Clusters Identified within the Northern Product Schedule.” Marine pollution Gulf of Mexico Common Bottlenose have detrimental effects on References bulletin 66.1 (2013): 73-77. Dolphin (Tursiops truncates) Unusual the immune system of ma- Barron, Mace G. “Ecological impacts US Environmental Protection Agency. Mortality Event: January 2010 - June rine mammals and thus it is of the deepwater horizon oil spill: (2014, December 31). COREXIT® 2013. PLOS ONE PLoS ONE, 10(2). implications for immunotoxicity.” EC9500A.Retrieved November 02, doi:10.1371/journal.pone.0117248 imperative to optimize the Toxicologic pathology 40.2 (2012): 2016, from https://www.epa.gov/emer- Kaku, V. J., Boufadel, M. C., Venosa, A. methodology for their use, 315-320. gency-response/corexitr-ec9500a D., & Weaver, J. (2006). Flow Dynam- such as lowering concen- “California oil spill: Up to 105,000 Zhao, L., Wang, B., Armenante, P. ics in Eccentrically Rotating Flasks gallons lost - CNN.com.” 2015. Used for Dispersant Effectiveness Test- trations based on wave pat- M., Conmy, R., & Boufadel, M. C. 24 Nov. 2015
Detecting Antecedents of Boredom in Students Using Intelligent Tutoring Systems by Matthew Gofman (STS paper excerpt) (Senior) point. We use accurately predict the onset data from the of boredom within students i n t e l l i g e n t and to reveal specific stu- mathematics dent actions which act as an tutoring sys- boredom antecedents. Un- epidemic of contemporary tem ASSIST- derstanding cues which pre- society as one of the most ments. With- cede boredom would enable widespread affects (Spacks, in this study, researchers to better under- 1995). However, boredom we attempt stand the causes of boredom receives significantly less to create a and allow educators to more research than alternate emo- model that effectively diminish the ad- tions (Pekrun, Goetz, Dan- best predicts verse impacts boredom has iels, Stupnisky, & Perry, boredom in on students by intervening 2010). It is often assumed students uti- when the antecedents are de- that this lack of research is lizing intelli- tected. While our model did a result of boredom being gent tutoring not reveal to be very predic- an unassuming and often systems by tive of boredom, out model taciturn affect, as opposed to using a com- did point out specific student other emotions such as ap- p u t a t i o n a l actions which can, with a prehension or anger (Pekrun, detector of level of statistical signifi- Goetz, Daniels, Stupnisky, Abstract boredom as cance higher than others, be & Perry, 2010). While seem- ingly discreet, the impacts Boredom is rampant through- the label. In order to develop used as antecedents of bore- of boredom are just as det- out students participating in the model, we had to engi- dom, providing a significant rimental (Pekrun, Goetz, online education and it is im- neer seventeen additional framework for future re- Daniels, Stupnisky, & Perry, perative to be able to predict features through distillation search 2010). Boredom is a par- which students will become of the data set given to us by Introduction ASSISTments. Our goal is lous emotion that has been bored before they reach that Boredom is considered to be for the model to be able to shown to be detrimental to 20 the learning process (Pekrun, ship between the student’s Purpose of Study Goetz, Daniels, Stupnisky, & recognition of boredom and The purpose of this Perry, 2010). the educator’s perception of study is to develop Dr. Ryan Baker, Ph.D. Boredom is associated with the antecedents (Daschmann, a model that is able irregular conduct (Wasson, Götz, & Stupnisky, 2014). to detect student 1981), absences (Wasson, Theoretical Antecedents of actions within in- 1981), and dropping out of Boredom telligent tutoring school (Bearden, Spencer, & Theoretical viewpoints on systems that are Moracco, 1989). antecedents of boredom ex- predictive of bore- Despite its profound impact ist (Goetz & Frenzel, 2006). dom. To our knowl- on the educational process, Pekrun’s control-value theo- edge, researchers antecedents of boredom are ry is often used a theoretical have yet to attempt seemingly neglected in re- model for predicting bore- to discover bore- dom antecedents on search (Daschmann, Götz, dom (Pekrun, Goetz, Daniels, ASSOCIATE PROFESSOR of the clip-level, such & Stupnisky, 2014). Being Stupnisky, & Perry, 2010). Cognitive Studies in Educa- able to discover antecedents This model pronounces en- as specific student tion is integral to being able to vironmental and subjective actions that could create boredom intervention causes. The subjective, or in- predict boredom. programs in educational set- dividual, antecedents are due Our goal is for this Teachers College, tings (Daschmann, Götz, & to the student’s perception model to be able Columbia University, NY Stupnisky, 2014). It is only over control over their spe- to predict, with a after educators understand cific situation and their as- level of statistical antecedents of boredom that sessment of worth (Pekrun, significance, which by around 40,000 middle they can alter their teaching Goetz, Daniels, Stupnisky, non-bored students will be- school students (Hawkins, system to alleviate boredom & Perry, 2010). Boredom come bored in the future, Heffernan, & Baker, 2013). within students (Daschmann, may occur if the student using certain cues that act ASSISTments evaluates the Götz, & Stupnisky, 2014). believes that they lack con- as boredom antecedents. students as they are work- Having knowledge of what Previous research projects trol or have too much of it ing, and sends the data to precedes boredom would be have discovered personal (Pekrun, Frenzel, Goetz, & the teacher (Hawkins, Hef- invaluable to educators and factors as antecedents of Perry 2007). The theory also fernan, & Baker, 2013). The developers of intelligent tu- boredom (Niculescua, Tem- describes that students may students are also provided toring systems. Understand- pelaara, Dailey-Hebertb, become bored if they believe with support in answering the ing certain actions that pre- Segersa, & Gijselaersa, that there is little value in questions, receiving either cede boredom would allow 2015; Daschmann, Götz, & what they are doing (Pekrun, hints, feedback, or scaffold- educators to intervene when Stupnisky, 2014) and have Goetz, Daniels, Stupnisky, ing (Hawkins, Heffernan, & such actions are detected, shown that the variance in & Perry, 2010). The envi- Baker, 2013). Hints come thus potentially preventing the individual problems is ronment around the student, in various levels, proceed- the onset of boredom. De- more predictive of boredom such as the teaching caliber, ing from high-level hints to velopers of online tutoring than the variance in the stu- can also dictate the emotions hints that provide the an- platforms could program the dents (Hawkins, Heffernan, of the students (Goetz, Fren- swer (Hawkins, Heffernan, platform to change the learn- & Baker, 2013). One of the zel, Stoeger & Hall, 2010). & Baker, 2013). Feedback is ing direction when the ante- most accepted sources from Another possible explanation provided if the student pro- cedents are detected. Thus, which researchers have dis- is that the principle anteced- vides erroneous responses discovering antecedents of covered antecedents of bore- ent of boredom is monotony (Hawkins, Heffernan, & boredom would lead to a dom in the past is from the (Hill & Perkins, 1985). If a Baker, 2013). Scaffolding decrease of boredom within personal perceptions of the student believes that a situa- splits the problem into nu- students in educational set- students (Kunter & Baumert, tion is repetitive, the student merous smaller problems in tings and lead to increase in 2006). According to this is likely to become bored order to assist the student in learning. approach, students under- (Hill & Perkins, 1985). Hill the process (Hawkins, Hef- stand when they are bored and Perkins specify that the Methodology fernan, & Baker, 2013). For and why they became bored task, the situation, and the We used data from AS- this study, we used data that (Daschmann, Götz, & Stup- person themselves all influ- SISTments, an online intel- had formerly been gathered nisky, 2014). Research has ence boredom development ligent mathematics tutoring from ASSISTments. The data also revealed the relation- (Hill & Perkins, 1985). system that is used weekly includes around 6,000,000
21 & Gowda, 2009). This Methodology acted as the detector’s The only data utilized within projected likelihood the model were the actions that the student was that fell within the anteced- bored when they made ent period of the detector’s a specific action (Hawk- prediction of boredom. Our ins, Heffernan, & Bak- initial study attempted to er, 2013). The detector develop a model containing was created by merging features that aggregated all ASSISTments log files values within the problem with thousands of bore- into the average, max, min, dom field observations and standard deviation of the (Hawkins, Heffernan, & values. For example, one col- Baker, 2013). umn would contain the aver- In order to determine the age of all the values within best predictive model a specific feature during of boredom, we had to the problem, while another perform additional data would contain the max, min, distillation on the AS- and standard deviation of the SISTments data set. By values within that feature. creating additional fea- These aggregated features tures, we were able to were developed for all of the create a more accurate variables that were includ- and predictive model ed in the data set and those than by simply using which we had developed. the data given. Through In order to determine the modifying an existing most predictive model of Figure 1: ASSISTments Example (Gowda, Baker, Pardos, & Heffernan, 2011 software base (Gold- boredom, we fit REPTree re- stein), we engineered gression models to the data in student actions gathered boredom was existent dur- seventeen additional order to predict the boredom from 2012-2013. ASSIST- ing that action as a number features that could be used detector confidence. REP- ments provides de-identified between 0 and 1, with num- to develop a more predictive Tree utilizes regression tree and publicly available data bers closer to 1 indicating a model of boredom (Table 2). logic, developing numerous for researchers. Included in higher probability that bore- Statistical Analysis and trees in a multitude of itera- the data set is an affect de- dom was present (Pardos, Results for Aggregated tions, ultimately revealing tector, in addition to infor- Baker, San Pedro, Gowda, Features the most predictive tree (Ka- mation regarding the start time of the problem, the end time of the problem, nature of the first attempt (correct or incorrect/hint), whether the student asked for all available hints, the total number of hints asked for, the total number of at- tempts on the problem, the time it took for the student to make their first action, among other variables (Ta- ble 1) (Pardos, Baker, San Pedro, Gowda, & Gowda, 2009). Every action includes a real-value confidence that
22 lmegh, 2015). To evaluate followed by “TotalTimeOn- cating the student was either ous 10 “TimeSinceSkill” the models, we used Spear- Skill,” “TotalSkillOpportuni- incorrect on the first attempt, values on that problem. We man’s rho measures. Spear- ties,” “ResponoseIsChosen,” or asked for help (Hawkins, took the 5-back, 10-back, man’s rho is a nonparametric “Correct,” and “TimeSinc- Heffernan, & Baker, 2013). 15-back, and 20-back values correlation coefficient that eSkill”. “Hint” provides a “TimeSinceSkill” provides for every variable we had. measures to what extent two value of 0 or 1, indicating a value in seconds which re- Results variables are related based whether or not a student veals the amount of time it The ‘n-back’ feature REP- on the monotonic relation- asked for a hint during that has been since the last time Tree analysis with 10 pa- ship (Laerd). The closer the action. “TotalTimeOnSkill” a problem of the same skill rameters resulted in a better Spearman’s rho value is to determines the total time the type had been seen by the spearman’s rho of 0.241, ±1, the stronger the relation- student has spent on the skill. student. indicating a stronger mono- ship is (Weir). “TotalSkillOpportunities” Statistical Analysis and Re- tonic relationship. While this provides the total amount of Results sults for ‘n-back’ Features monotonic relationship is unique problems that student Our initial REPTree analysis Methodology still ‘weak’ per se, the large has attempted on the skill with 10 parameters resulted increase in the spearman’s they are currently working Aggregating the values of the in a Spearman’s rho of 0.136. rho value after performing on. “ResponseIsChosen” re- data for each feature did not Values within the range of additional feature engineer- veals if the response type is result in a model that could .00-.19 are considered to ing is promising. This indi- a “choose one” question in act as a statistically signifi- have a very weak monotonic cates that aggregating data which the student has to pick cant predictor of boredom. In relationship (Weir). While distorts it in a way that makes the answer after being given place of aggregated features, our initial model was a rather it less predictive. multiple possible answers. we engineered ‘n-back’ fea- poor predictor of boredom, it In these questions, the stu- tures, which created a more The REPTree analysis re- did provide a framework for dent has a larger chance of predictive model. ‘N-back’ vealed that in general, the the development of a better picking the correct choice features refer to features ‘5-back’ variables were the model. While overall not through guessing. A value which take the summation of most predictive, revealing very predictive, the regres- of 0 or 1 is given in “Cor- all values a certain number, that student actions become sion tree revealed which rect,” with a 1 indicating that or n, actions back. For ex- more predictive of boredom features are the most predic- the student was correct on ample, a 10-back “TimeSin- the closer the student is to tive of boredom. “Hint” was the first attempt, and 0 indi- ceSkill” feature, would take becoming bored. Using the the most predictive feature, the summation of the previ- ‘n-back’ features as opposed 23 to the aggregates also re- improvements in the model, analyses, in hope of develop- Kunter, M., & Baumert, J. (2006). Who is the expert? Construct and criteria sulted in differing results, leading to .105 increase in ing a more predictive model validity of student and teacher ratings with “Past8BottomOut,” the Spearman’s rho value. of boredom. This research of instruction. Learning Environments “TotalSkillOpportunities,” While the Spearman’s rho has shown that the engineer- Research, 9(3), 231-251. “TotalPercentPastWrong,” still indicates a rather weak ing of more variables will Laerd (2016). Spearman’s Rank-Order Correlation. Spearman’s Rank-Order “AttemptCount,” “Correct,” monotonic relationship, our lead to a more predictive Correlation. Laerd Statistics. and “BottomHint” being initial results are still sig- model. Niculescua, A., Tempelaara, D., Dailey- the most predictive features. nificant. While the overall References Hebertb, A., Segersa, M., Gijselaersa, W. (2015). Exploring the antecedents Bearden, L., Spencer, W., & Moracco, “TotalSkillOpportunities” model may not be a strong of learning-related emotions and their J. (1989). A study of high school drop- relations with achievement outcomes. and “Correct” were also near predictor of model, the mod- outs. School Counselor, 37, 113–120. the top of the most predic- el did reveal which specific Frontline Learning Research, 3 (1), Daschmann, E., Götz, T., & Stupnisky, 1-17. tive features in our previous variables are predictive of R. (2013). Exploring the antecedents of Pardos, Z.A., Baker, R.S.J.d., San Pe- boredom: do teachers know why stu- study. “Past8BottomOut” boredom. Additionally, our dro, M.O.C.Z., Gowda, S.M., Gowda, dents are bored? Teaching and Teacher S.M. (2013) Affective states and state tallies the number of the research shows that actions Education, 39, 22-30. tests: Investigating how affect through- eight past problems that end- become more predictive of Goetz, T., & Frenzel, A. C. (2006). out the school year predicts end of year ed using a bottom out hint, boredom the closer the stu- Phänomenologie schulischer Lange- learning outcomes. Proceedings of the or the last hint in a sequence. dent is to becoming bored. weile [Phenomenology of boredom at 3rd International Conference on Learn- school]. Zeitschrift für Entwicklung- ing Analytics and Knowledge, 117- “TotalPercentPastWrong” These variables can, with spsychologie und Pädagogische Psy- 124. chologie, 38(4), 149-153. provides the summation a level of statistical signifi- Pekrun, R., Frenzel, A. C., Goetz, T., & of the percent of times that cance higher than others, be Goetz, T., Frenzel, A. C., Stoeger, H., Perry, R. P. (2007). The control-value & Hall, N. C. (2010). Antecedents of theory of achievement emotions: an the user has provided an in- used to predict which stu- everyday positive emotions: an experi- integrative approach to emotions in correct answer on the first dents that are not currently ence sampling analysis. Motivation and education. In P. A. Schutz, & R. Pekrun attempt while attempting bored will become bored in Emotion, 34(1), 49-6. (Eds.), Emotion in education (pp. 13- Goldstein, A.B. FeatureDistiller2null 36). San Diego, CA US: Elsevier Aca- problems of the same skill the future. Educators can [Computer Program]. demic Press. in the past. “AttemptCount” utilize such features to no- Gowda, S., Baker, R.S.J.d., Pardos, Z., Pekrun, Reinhard; Goetz, Thomas; gives the number of times tice specific values that are Heffernan, N. (2011). The Sum is Great- Daniels, Lia M.; Stupnisky, Robert H.; the student has attempted significant within the -vari er than the Parts: Ensembling Student Perry, Raymond P. Knowledge Models in ASSISTments. (2010). Boredom in achievement set- an answer on the problem able, and intervene in order Proceedings of the KDD 2011 Work- tings: Exploring control–value anteced- (Pardos, Baker, San Pedro, to possibly prevent the stu- shop on KDD in Educational Data. ents and performance outcomes of a ne- Gowda, & Gowda, 2009). dent from becoming bored Hawkins, W., Heffernan, N., Baker, glected emotion. Journal of Educational Psychology, Vol 102(3), 531-549. “BotomHint” gives a 0 or 1 in the future. Programmers R.S.J.d. (2013) Which is more respon- sible for boredom in intelligent tutoring Spacks, P. M. (1995). Boredom: The value indicating whether the of online tutoring systems systems: students (trait) or problems literary history of a state of mind. Chi- students asked for all of the can also code the platform to (state)? Proceedings of the 5th biannual cago, IL: University of Chicago Press. Conference on Affective Computing Wasson, A. S. (1981). Susceptibil- hints or not (Pardos, Baker, change the learning process and Intelligent Interaction. ity to boredom and deviant behavior San Pedro, Gowda, & Gow- when significant values are Hill, A. B., & Perkins, R. E. (1985). at school. Psychological Reports, 48, da, 2009). detected within the features Towards a model of boredom. British 901–902. Journal of Psychology, 76(2), 235-240. Conclusion, Implications that are considered anteced- Weir, Iain. Spearman’s Rank Correla- ents of boredom. The goal Kalmegh, Sushilkumar. (2015). Analy- tion - Introduction. StatsTutor. Stat- & Further Research sis of WEKA Data Mining Algorithm sTutor. of my future research is to REPTree, Simple Cart and RandomTree Additional feature engineer- engineer even more features, for Classification of Indian News. Inter- ing through the ‘n-back’ national Journal of Innovative Science, and perform more statistical features led to significant Engineering & Technology, 2(2).
Synergy of T Helper Cells TH 22 and TH 17 with TH 2 as possible factors in the onset and development of Atopic Dermatitis by Deepa Mistry (STS paper excerpt) (Senior) Abstract known and many studies TH22, TH1, and TH17 cy- regulated when targeted by Atopic dermatitis is an in- have been completed to tokines. The results are pre- different cytokines, and the flammatory skin disorder determine which genes and liminary but show that the genes INV, FLG, and LOR in which there are immune cytokines cause the disease. genes CCL20, LCN2, PI3, were downregulated. Of all and barrier abnormalities This experiment tests differ- DEFB4B, S100A7, CXCL1, of these genes, CXCL1 has in the skin. The root cause ent genes for their expres- IL19, CCL26, CXCL10, and the most synergistic proper- of Atopic Dermatitis is un- sion after being exposed to CAMP were generally up- ties with the combinations of different combinations of cytokines presented. Though 24 C u r r e n t to help manage atopic der- treatments that block the treat- matitis. Some symptom re- TH2 axis can help atopic ments of ducing treatments include dermatitis patients because a t o p i c antihistamines and antibiot- it reduces the severity of derma- ics [23]. With the highly in- the disease [18]. Since it titis are flamed skin, antihistamines does not completely treat h i g h l y work to reduce the irritation ineffec- and reduce swelling [23]. atopic dermatitis, it sug- tive [23]. The antibiotics are effective gests however, there may To p i c a l in cases where infections be other cytokines in- steroids have developed on the irri- volved [18]. are some- tated lesions [23]. There has also been re- t i m e s Literature Review search that shows TH22, p a i r e d TH1, and TH17 cytokines with NB- The root of the immune like IL-22, IL-17, are also U V B pathways in atopic der- photo- matitis lies in the T Helper involved in immune acti- t h e r a p y cells which are cells that vation in atopic dermatitis treatment help to activate cytotoxic [12]. The inflammatory b e c a u s e T cells to terminate abnor- mediator genes used are both act mal cells or foreign bodies CCL26, CXCL10, as im- [12]. IL-19, CXCL1, CAMP, muno- some of the results were in- suppressants which would The current model for this S100A7, LCN2, PI3, significant, the preliminary reduce the inflammatory re- pathway shows that the DEFB4B, and CXCL20 in results can lead to a more action associated with atopic hallmark of T helper cells addition to the keratino- in depth study on the root dermatitis [23]. In addition, in atopic dermatitis is the causes of Atopic Dermatitis. cyte differentiation genes cyclosporine, a common T H 2 cell [12]. Keratino- LOR, FLG, and INV. Introduction: immunosuppressant is also cytes work to form a barri- The LOR gene codes for Atopic Dermatitis is the a popular treatment for this er against foreign invaders Loricrin, a protein in the most common inflammatory disease [23]. However, due of the skin. Inatopic der- cornified cell envelope, a skin disease in which 10% of to toxicity issues from the matitis, the epidermal bar- children and 5% of adults are structure that serves as a oral steroids and other im- rier formed by keratino- affected [12]. It is an inflam- munosuppressants, there are protective barrier for the cytes is disrupted, forming matory skin disorder that is limitations for long term use skin against the environ- more colloquially known as [23]. Phototherapy is given lesions of eczema [32]. ment [21] . It is formed eczema [12]. There are two with a 308 nm excimer la- Research has shown that in fat cells underneath the important stages in atopic ser at a derma- dermatitis that show the pro- tologist’s office gression of the disease. The and is usually acute stage is the initial ir- administered ritation of the skin where it 2-3 times a looks bright red, “wet”, and week with a 48 flat [12]. The chronic stage is hour break in the dull, red, dry, and thick between treat- aftermath from the acute ments, making stage [12]. This skin disorder phototherapy a is known to be closely linked highly inconve- to both immune and barrier nient method of abnormalities [12]. About treatment [23]. 85% of cases begin in child- While treat- hood where early onset is ments may be common and there are more i n e f f e c t i v e , pediatric cases of atopic der- there are ways matitis than adult cases [23]. 25 Filaggrin, bonded component in the a pro- keratinocyte crosslinked tein that envelope [17]. It is found binds to in the cytoplasm that by the main transglutaminase is cross- structural linked to the membrane compo- proteins [17] . Involcrin is nent of important to Atopic Der- hairs in matitis because of its in- epithe- volvement in the cornified lial cells cell envelope in stratified [11] . A squamous epithelia [17]. mutation These epithelial cells are in this flattened and layers on a gene ag- basal membrane, protect- gravates ing the tissue underneath the kera- [17] . tin inter- In Atopic Dermatitis, the m e d i a t e cell’s membranes are af- filaments fected and there is poor in the protection of the tissue un- plasma membrane called [21]. The impacted bar- epidermis derneath the basal mem- terminally differenti- rier because of the defect [11] . It is also more likely brane [17]. The CCL26 ated stratified squamous on the LOR gene enables to make Atopic Dermatitis gene is one of the two CC epithelium, or epidermal abnormal processes of the more severe in adulthood (Cys-Cys) genes [5]. They cells [21]. When a muta- barrier and congenital dis- [11] . are involved in inflam- tion occurs in LOR gene orders of the skin such as The INV gene codes for matory processes and im- the protein malfunctions a Atopic Dermatitis [21]. Involcrin, a covalently munoregulatory processes barrier function of the skin The FLG gene codes for
26 which display chemotac- blood cells tic activity, the movement [16]. It in response to chemical codes for stimulus [5]. Since it is an inflam- produced by inflamma- m a t o r y tory cells and expressed in cytokine, endothelial cells, the mu- maintain- tation in this gene disrupts ing inflam- the inflammatory process- m a t i o n es and therefore enabling in Atopic Atopic Dermatitis to ap- Dermatitis pear on the skin [5]. [16]. The CXCL10 gene is an The CX- antimicrobial gene [6]. It CL1 gene codes for a chemokine, a is a protein signaling protein, of the c o d i n g CXC subfamily and the gene that receptor CXCR3 ligand codes for a [6]. This gene is part of chemokine protein is produced in the tion as well as control- the inflammatory cascade in the CXC subfam- skin and plays an impor- ling the inflammation in in Atopic Dermatitis and it ily, a signaling protein tant role in inflammation Atopic Dermatitis [3]. also acts as a natural killed secreted by cells [7]. The as it is related to the TH17 The S100A7 gene is a and T-cell migration. It chemokine plays a role inflammatory response protein coding gene that is secreted by interferon in inflammation and has [7]. codes for a member of gamma [6]. increased chemotactic ac- The CAMP gene is a pro- the S100 protein family The IL19 gene is a protein tivity [7]. It is a secreted tein coding gene that codes [26]. It is involved in the coding gene that codes growth factor that stimu- for a member a the antimi- regulation of cellular pro- for a cytokine in the IL19 lates cell growth, survival, crobial peptide family [3]. cesses, cell cycle progres- subfamily [16]. It is ex- differentiation, tissue re- It has antibacterial, anti- sion, and cell differentia- pressed in monocytes, pair, and most relevant, fungal, and antiviral activ- tion [26]. Overexpression large phagocytic white inflammation [7]. This ities as well as a role in cell of this protein can cause chemot- hyperproliferative skin axis, im- diseases and antibacte- m u n e rial activity that induces mediator immunomodulatory ac- induction, tivities [26]. Secreted and the by epithelial cells, the regulation protein acts as a defense of inflam- mechanism and is over- m a t o r y expressed in Atopic Der- responses matitis [26]. [3]. It is The LCN2 gene is a pro- a p r o t e i n tein coding gene that that pro- codes for a protein in the tects the lipocalin family [19]. It skin from plays a role in innate im- bacteria, munity by preventing bac- f u n g u s , terial growth [19]. This v i r u s e s , protein is involved in cel- and infec- lular processes, maintain- 27 ing skin homeostasis, and [9]. It comes from a fam- chemokine (CCL26), a ed all synergistic effects is has decreased levels in ily that kills microbes and Th1 chemokine (CX- when the mRNA expres- Atopic Dermatitis [19]. is deficient in Atopic Der- CL10), and Th17 markers sion was tested for each The PI3 gene codes for a matitis [9]. (IL-19, CXCL1, CAMP, cytokine as presented in elastase-specific inhibitor The CCL20 gene is an an- S100A7, LCN2, PI3, figure 5. It is a generally [25]. It acts as an antimi- timicrobial gene from the DEFB4B, and CXCL20). upregulated gene with two crobial peptide against small cytokine CC genes We are investigating the values in which the effect both gram positive and subfamily [4]. They are expression of these genes of IL-4, IL-13 and IL-22 gram negative bacteria involved in immunomod- to determine how the cells on the gene CXCL1 did not and fungal pathogens ulatory and inflammatory are responding to various have a significant p value, [25]. It is upregulated by processes [4]. Specifically, combinations of cytok- making them insignificant lipopolysaccharides and this gene works to attract ines. The results will help results as presented in fig- cytokines. In Atopic Der- inflammatory cells and us further understand the ure 3. The synergy may matitis, these pathways chemicals to the site of in- complex skin barrier path- mean that the combina- are over engaged [25]. flammation [4]. In Atopic ways of Atopic Dermati- tions of cytokines (I L-4, The DEFB4B gene is a Dermatitis, the gene is tis. IL-13 on IL-17; I L-4, IL- defensin coding gene that overexpressed and there is (...) 13 on IL-22; I L-4, IL-13 on IL-17 on IL-22; I L-4, codes for members of too much attraction of in- Results the defensin family [9]. flammatory mediators to IL-13 on IL-17 on IL-22, sites of inflammation [4]. While the genes LOR, INFg) are making the The defensins are small FLG, INV, CCL26, CX- Goals of Study/Hypoth- CXCL1 gene have higher cysteine-rich cationic pro- CL10, CAMP, S100A7, teins that are microbicidal, esis mRNA expression levels LCN2, PI3, DEFB4B, in Atopic Dermatitis than an agent that is destructive In this project we tested and CCL20 did not show to microorganisms, and in in normal skin as pre- the mRNA expression of any synergistic effects sented in figure 5. cytotoxic [9]. This gene inflammatory mediators in the mRNA expression The gene IL19 indicated codes beta 4, a defensin of each immune pathway in response to the com- antibiotic protein that is produced by keratinocytes synergistic effects when binations of TH22 and the mRNA expression was regulated by inflammation with stimulation of differ- TH17 cytokines, they ent combi- tested for oe combination still showed additive and of cytokines as presented nations of antagonistic effects. The cytokines. in figure 4. The gene IL19 Mentor: gene IL19 showed syn- has synergistic effects with Dr. Emma Guttman , Specifi- ergistic effects in mRNA cally we IL-4, IL-13 on IL-22 and expression in response to the p value, when IL-4, Ph.D. tested ter- IL-4, IL-13 on IL-22. The minal dif- IL-13 & IL-22 was tested gene CXCL1 showed the on the gene IL19, pre- ferentia- greatest synergistic effects tion genes sented a significant pvalue with all four combinations less than or equal to 0.005 ( L O R , of cytokines. These results F L G , as presented in figure 3. show how certain inflam- IL-4, IL-13 & IL-22 also I N V ) , matory mediators may a Th2 showed to be upregulat- play a role in the skin bar- ed by approximately .75 rier pathways of Atopic units as presented in figure PROFESSOR Dermatology; AS- Dermatitis. 3. The synergy may mean SOCIATE PROFESSOR Medicine, Discussion that the cytokines (I L-4, Clinical Immunology. Though these results are IL-13 on IL-17) are mak- preliminary, they indicate ing the IL19 gene have Mount Sinai Medical School, promising results for the higher mRNA expression ICahn Medical Institute. continuation of this study. levels in Atopic Dermati- The gene CXCL1 indicat- tis than in in normal skin. 28 The results for the other The hypothesis was sup- to the TH17 inflammatory like to further analyze the genes did not have any ported in this study be- pathways and possibly be results of the microarray synergistic effects but had cause CXCL1 and IL19 a direct cause of Atopic to see which other genes additive and antagonistic did show synergistic ef- Dermatitis. show synergistic effects effects. Though CXCL1 fects from the mRNA ex- The synergy may mean in mRNA expression from and IL19 have promis- pression for the different that the cytokines (I L-4, the combinations. ing preliminary results, combinations of TH22 IL-13 on IL-17) are mak- Investigating the expres- more test must be done and TH17 cytokines. The ing the IL19 gene have sion of these genes to to further show the effect synergy may mean that the higher mRNA expression determine how the cells of these genes on Atopic combinations of cytokines levels in Atopic Dermati- are responding to various Dermatitis. The synergis- (I L-4, IL-13 on IL-17; tis than in in normal skin. combinations of cytok- tic effects tells us that the I L-4, IL-13 on IL-22; I The IL19 gene codes for ines will help us further cytokines may have an L-4, IL-13 on IL-17 on a cytokine in the IL19 understand the complex affect on the genes that IL-22; I L-4, IL-13 on IL- subfamily, inflammatory skin barrier pathways of regulate inflammatory 17 on IL-22, INFg) are cytokine, maintaining Atopic Dermatitis and processes. The antagonis- making the CXCL1 gene inflammation in Atopic may help us provide ways tic effects that are shown have higher mRNA ex- Dermatitis [16]. This may to treat it. in the mRNA expression pression levels in Atopic mean that the gene IL19 Bibliography of certain combinations of Dermatitis than in normal has a direct linkage to the 1. Asahina, R., & Maeda, S. (2016, May). A review of the roles of kerati- cytokines will need to be skin. The CXCL1 gene inflammatory cytokine nocyte-derived cytokines and chemok- examined further to deter- codes for a chemokine in pathways and possibly be ines in the pathogenesis of atopic der- matitis in humans and dogs. Retrieved mine their roles in the skin the CXC subfamily, a sig- a direct cause of Atopic from https://www.ncbi.nlm.nih.gov/ barrier pathways. Due to naling protein secreted by Dermatitis. Due to limita- pubmed/27426268 the limitation of time, the 2. Belgrave, D. C.M., Simpson, A., cells and it plays a role in tions on time, this study’s Buchan, I. E., & Custovic, A. (2015, microarray results have inflammation and has- in results are purely prelimi- September). Atopic Dermatitis and Re- not yet been processed but spiratory Allergy: What is the Link. Re- creased chemotactic activ- nary and once the microar- trieved from https://www.ncbi.nlm.nih. once they are, we will be ity [7]. ray is completed, there will gov/pubmed/26566461 able to see thousands of This protein is produced be even more genes that 3. CAMP Gene(Protein Coding). (n.d.). genes’ synergistic, antago- Retrieved November 6, 2016, from in the skin and plays an are tested for synergistic, http://www.genecards.org/cgi-bin/card- nistic, and additive effects important role in inflam- additive, and antagonistic disp.pl?gene=CAMP in Atopic Dermatitis to 4. CCL20 Gene(Protein Coding). (n.d.). mation as it is related to effects. This notion will Retrieved November 6, 2016, from see what other inflamma- the TH17 inflammatory help further understand http://www.genecards.org/cgi-bin/card- tory genes play a role in disp.pl?gene=CCL20 response [7]. This may the complex immune sta- this disease. 5. CCL26 Gene (Protein Coding). mean that the gene CX- tus of Atopic Dermatitis. (n.d.). Retrieved November 6, 2016, Conclusion CL1 has a direct linkage In future studies we would from http://www.genecards.org/cgi-bin/ 29 carddisp.pl?gene=CCL26 14. Hamilton, J. D., Suarez-Farinas, E. (n.d.). New pathogenic and thera- TSLP expression induced via Toll-like 6. CXCL10 Gene (Protein Coding). M., Dhingra, N., Cardinale, I., Li, X., peutic paradigms in atopic dermatitis. receptor pathways in human keratino- (n.d.). Retrieved November 6, 2016, Kostic, A., .Guttman-Yassky, E. (2014). Retrieved from https://www.ncbi.nlm. cytes. Retrieved from https://www.ncbi. from http://www.genecards.org/cgi- Dupilumab improves the molecular nih.gov/pubmed/25542094 nlm.nih.gov/pubmed/24377934 bin/carddisp.pl?gene=CXCL10 signature in skin of patients with mod- 23. Noda, S., Krueger, J. G., & Gutt- 30. Tanaka, R. J., Ono, M., & Har- erate-to-severe atopic dermatitis. Re- 7. CXCL1 Gene(Protein Coding). man-Yassky, E. (2014). The transla- rington, H. A. (2011, May). Skin Bar- trieved from https://www.ncbi.nlm.nih. tional revolution and use of biologics rier Homeostasis in Atopic Dermatitis: (n.d.). Retrieved November 6, 2016, gov/pubmed/25482871 from http://www.genecards.org/cgi- in patients with inflammatory skin dis- Feedback Regulation of Kallikrein Ac- bin/carddisp.pl?gene=CXCL1 15. Ibrahim, Z. A., Ghaly, N. R., El-Tat- eases. American Academy of Allergy, tivity. Retrieved from http://journals. away, R. A., Khalil, S. M., & El-Batch, Asthma & Immunology. http://dx.doi. plos.org/plosone/article?id=10.1371/ 8. Darlenski, R., Kazandjieva, J., M. M. (2014). A proliferation-inducing org/10.1016/j.jaci.2014.11.015 journal.pone.0019895 Hristakieva, E., & Fluhr, J. W. (2014). ligand in atopic dermatitis and vitiligo. Atopic dermatitis as a systemic disease. 24. Ong, P. Y., & Leung, D. Y.M. (2016, 31. Tien, K.-J., Chou, C.-W., Lee, Retrieved from http://onlinelibrary.wi- July). Bacterial and Viral Infections in S.-Y., Yeh, N.-C., Yang, C.-Y., Yen, Retrieved from https://www.ncbi.nlm. ley.com/doi/10.1111/ijd.12176/full nih.gov/pubmed/24767188 Atopic Dermatitis: a Comprehensive F.-C., . . . Weng, S.-F. (2014, Febru- 16. IL19 Gene(Protein Coding). (n.d.). Review. Retrieved from https://www. ary). Obstructive Sleep Apnea and the 9. DEFB4B Gene(Protein Coding). Retrieved November 6, 2016, from ncbi.nlm.nih.gov/pubmed/27377298 Risk of Atopic Dermatitis: A Popula- (n.d.). Retrieved November 6, 2016, http://www.genecards.org/cgi-bin/card- 25. PI3 Gene(Protein Coding). (n.d.). tion-Based Case Control Study. Re- from http://www.genecards.org/cgi- disp.pl?gene=IL19 trieved from http://journals.plos.org/ bin/carddisp.pl?gene=DEFB4B Retrieved November 6, 2016, from 17. IVL Gene (Protein Coding). (n.d.). http://www.genecards.org/cgi-bin/card- plosone/article?id=10.1371/journal. 10. Du, H.-Y., Fu, H.-Y., Li, D.-N., Qiao, Retrieved November 6, 2016, from disp.pl?gene=PI3 pone.0089656 Y., Wang, Q.-W., & Liu, W. (2016). http://www.genecards.org/cgi-bin/card- 26. S100A7 Gene(Protein Coding). 32. Werfel, T. (2009, April). The The Expression and Regulation of In- disp.pl?gene=IVL Role of Leukocytes, Keratinocytes, terleukin-33 in Human Epidermal Ke- (n.d.). Retrieved November 6, 2016, 18. Janeway, C., Jr., Travers, P., & Wal- from http://www.genecards.org/cgi- and Allergen-kSpecific IgE in p> the ratinocytes: A New Mediator of Atopic Development of Atopic Dermatitis. Dermatitis and Its Possible Signaling port, M. (2001). Immunobiology: The bin/carddisp.pl?gene=S100A7 Immune System in p>Health and Dis- Journal of InvestigativeDermatology. Pathway. Retrieved from https://www. 27. Saluja, R., Khan, M., Church, M. http://dx.doi.org/10.1038/jid.2009.71 ncbi.nlm.nih.gov/pubmed/27348082 ease (5th ed.). Retrieved from K., & Maurer, M. (2015). The role of 11. FLG Gene (Protein Coding). (n.d.). http://www.ncbi.nlm.nih.gov/books/ IL-33 and mast cells in allergy and in- Retrieved November 6, 2016, from NBK27101/ flammation. Retrieved from http://www.genecards.org/cgi-bin/ 19. LCN2 Gene(Protein Coding). (n.d.). https://ctajournal.biomedcentral.com/ carddisp. cytokines and selective epi- Retrieved November 6, 2016, from articles/10.1186/s13601-015-0076-5 dermal proteins characterizes acute and http://www.genecards.org/cgi-bin/card- 28. Suarez-Farinas, M., Tintle, S., Sh- chronic atopic dermatitis. American disp.pl?gene=LCN2 emer, A., Chiricozzi, A., Nograles, Academy of Allergy, Asthma & Im- 20. Leung, D. Y.M. (2016, August). K.E., Cardinale, I., Guttman-Yassky, E. munology. http://dx.doi.org/10.1016/j. Clinical implications of new mechanis- (2011, April). Nonlesional atopic der- jaci.2012.07.012 tic insights into atopic dermatitis. Re- matitis skin is characterized by broad 13. Hamilton, J., Suarez-Farinas, M., trieved from https://www.ncbi.nlm.nih. terminal differentiation defects and Dhingra, N., Cardinale, I., Li, X., Ko- gov/pubmed/27191525 variable immune abnormalities. Re- stic, A., . . . p> Guttman-Yassky, E. 21. LOR Gene (Protein Coding). (n.d.). trieved from https://www.ncbi.nlm.nih. (2014, December). Dupilumab im- Retrieved November 6, 2016, from gov/pubmed/21388663 proves the molecular signature in skin http://www.genecards.org/cgi-bin/card- 29. Takai, T., Chen, X., Xie, Y., Vu, A. of patients with moderate-to-severe disp.pl?gene=LOR T., Le, T. A., Kinoshita, H., . . . Oku- atopic dermatitis. Elsevier Inc. http:// 22. Malajian, D., & Guttman-Yassky, mura, K. (2014). dx.doi.org/10.1016/j.jaci.2014.10.013 An Epidemiological Study of Aphantasia by Melody Munitz (WESEF paper excerpt) (Junior) Abstract tion, and calls for further research with an fMRI. Aphantasia is a newly recognized condition characterized by the lack of visual imagery. There has been little research con- Introduction ducted on it. We conducted a survey over social media di- One great human ability is that of visualisation, or being able rected to groups of Aphantasiacs, and received 312 respons- to conceive an image in one’s mind’s eye. Believed to be es. This epidemiological study of Aphantasia is the first of the product of fronto-parietal and posterior brain processes its kind, providing important information about the nature of (Bartolomeo, 2008), this skill has numerous practical impli- the condition and its effects on those who have it. The results cations, such as its assistance in learning, the formation of from this study do not suggest a genetic cause. The results relationships, and creativity, as well as mental state and other do prove that Aphantasiacs find mental workarounds to com- psychological processes. The formation of mental imagery pensate for their lack of visualization skills. One of the most is also linked to memory, as supported by Marks’ 1973 ex- prominent results relates to the majority of Aphantasiacs’ periment in which male and female subjects who claimed ability to dream visually, suggesting a different neurological to have varying visual imagery capabilities were shown an mechanism of recall in Aphantasia. Another important result image and then asked to recall it. The results showed that the lies in the fact that most Aphantasiacs experience diminished subjects who claimed to have higher visual imagery capa- imagery of their other senses, not simply visual; i.e., they bilities were more accurate in their recall of the images they have difficulty conjuring auditory or gustatory imagery. This had seen, allowing for the conclusion that “images have an also points to different activated brain regions in this condi- important role in memory” (Marks, 1973). In another experi- 30 ment relating to the correlation between eye movements and additional etiologi- visualization, there was “no evidence that vivid visualizers cal statistics of the showed more scanning activity than a group of Ss [patients] condition, includ- operationally defined to be poor at visualizing”, proving that ing age of onset, visual imagery is more than simply eye movements (Marks, how it is presented D.F., 1973) in both genders, Some of the first documented research regarding visual and progression, as imagery was conducted in England in 1880 by Sir Francis well as demograph- Galton, and was geared towards determining how different ics of the condition people’s visual imagery skills compare. In order to assess such as any poten- where each patient lay on the scale of visualization, Galton tial environmental developed the Vividness of Visual Imagery Questionnaire, risk factors, socio- which has since become a standard of scientifically quantify- economic factors, ing visualization skills. This survey describes several situ- or cultural corre- ations and then asks the participant to rate the vividness of lations. Addition- their mental imagery on a scale of 1-5. Through the use of ally, the study will the VVIQ and other similar tools and questionnaires, Galton consider the ef- found that not everyone is equipped with comparable visual fects of aphantasia imagery capabilities. While most people fall somewhere on on learning ability/ the high end of the spectrum, having good or even superb vi- disability, personal- sual imagery skills, there is a small percentage of people that ity, creativity, and chosen career path, as well as hypothesized possess very poor visualization abilities (Galton, 1880). In comorbidity between aphantasia and other conditions. This similar research conducted by Faw in 2009, assessing such data will facilitate an improved understanding of Aphantasia capabilities of 2,500 participants, it was found that 2.1-2.7% within the scientific community, and depending on the results of them fell in this small group, claiming extremely poor or of this study, further studies can be carried out in the hopes of absent visual imagination (Faw, 2009) understanding the cause of Aphantasia and possible preven- Until recently, aside from Faw’s limited work, this phenom- tative and therapeutic measures. enon has not received much scientific exploitation. Just re- Goal Of Study/Hypothesis cently, however, Professor Adam Zeman at the University Develop a survey to be administered to self-proclaimed of Exeter has begun conducting research on this topic. Since Aphantasia patients in order to verify their condition, as well named ‘aphantasia’ (Zeman, 2015), this condition is believed as gage additional statistics about Aphantasia that will facili- to be the result of two different types of neurogenic visual im- tate further scientific investigations. agery impairments: i) visual memory disorders, and ii) ‘im- This will serve as the first epidemiological study of this con- agery generation’ deprivation (Farah, 1984). To explore fur- dition, providing useful information regarding: ther features of Aphantasia, Zeman and his team distributed Age a shortened version of the aforementioned VVIQ as well as Gender a supplemental questionnaire addressing additional personal Evolution information to 21 participants who suspected that they had Social and economic correlations the condition, 19 of whom were male. This testing generated Cultural correlations various statistics; 5/21 reported having relatives who experi- Comorbidity ence similar symptoms, “10/21 claimed that all modalities of Effects of the Condition imagery [hearing, touch, smell, sight, taste] were affected”, People with Aphantasia will experience several common and that most participants claimed having realized their vi- traits, especially in regards to the effects of their lack of vi- sualizing deficit during their teens or early twenties through sualization. (...) conversation with ‘normal’ visualizers. Interestingly, despite Results the 21 participants’ VVIQ scores being tremendously lower Result 1: Screening for Aphantasia than those of the 121 control patients, the majority of sub- For each item on this questionnaire, try to form a visual im- jects claimed involuntary imagery, 10/21 during wakefulness age, and consider your experience carefully. For any image and 17/21 while dreaming. These statistics have helped to that you do experience, rate how vivid it is using the five- begin to quantify the condition of aphantasia, and are a good point scale described below. If you do not have a visual im- basis for further research, such as that I am planning to con- age, rate vividness as ‘1’. Only use ‘5’ for images that are duct (Zeman, 2015). truly as lively and vivid as real seeing. For both Result 1a and A questionnaire will be created and distributed via the in- Result 1b, the vast majority of participants scored their image ternet to self-proclaimed aphantasia patients whose answers, as a “1”, meaning they had no image at all. These results ver- upon undergoing statistical analysis, will aid in determining ify that this questionnaire was taken by people with Aphanta- 31 fessor Adam Zeman, is in the UK, and his research has re- sounded especially in his region. Result 3: Aphantasia in Blood Line These results do not seem to indicate any any familial trait of Aphantasia. This may mean that Aphantasia is not hereditary or based on a genetic trait. Since relatives are not available for testing, this result has to be taken with caution. Result 4: Academic Achievement among Aphantasiacs
Legend: Question: “Think of the front of a shop which you often go to. Consider the pic- ture that comes before your mind’s eye.” a: “The overall appearance of the shop from the opposite side of the road.” b: “A window display including colors, shapes and details of individual items for sale.” c: “You are near the entrance. The color, shape and details of the door.” d: “You enter the shop and go to the counter. You hand the clerk your money, and they give you back change.”
5 - Perfectly clear and vivid as real seeing 4 - Clear and reasonably vivid 3 - Moderately clear and lively 2 - Vague and dim 1 - No image at all, you only “know” that you are thinking of the object
Most subjects were in the top 10% of their class in high school. Most subjects graduated from college. These subjects with Aphantasia do not seem to be low performing academically, in fact, they seem to be very intelligent and academically successful. Some, if not many, people would day they were better students than they may have actually been. Therefore, the bias associated with this question must be taken into con- sideration. Additionally, this study is a bit biased toward a group of Aphantasiacs that is inherently more educated and aware, as they recognize their condition, and have found and sia, as they reported to very low visual imagery capabilities. joined a social media group for Aphantasia. This is a subjective question, and especially people with a Result 5: Impact of Aphantasia limited understanding of or limited experience with visual Question: “Please rate the effects of your diminished mind’s imagery may have a difficult time assessing their visual im- eye on these various elements. agery skills. Result 2: Age, Gender and Location of Subjects Result 2a: There was a fair representation of age amongst study participants, with most of the participants being in the range of 25-44 years. This study was conducted with partici- pants between a vast age range, and most ages were fairly represented. Result 2b: There was a fairly even 55% to 45% ratio of fe- male to male. This study did not have a bias toward one gen- der. Result 2c: Question: In what country do you currently re- side? Result 6: Creativity Among Aphantasiacs There was 40% to 60% distribution of participants residing The subjects reported Aphantasia having a moderate effect in the United States versus other countries. It can be assumed on their creativity and learning ability, and a stronger effect that a large majority of the 60% in other countries are from on their memory, glancing ability, and ability to recall faces. the United Kingdom, as the sole Aphantasia researcher, Pro- Aphantasiacs seem to compensate for their lack of visual 32 memory below average. This result suggests that a lack of vi- sual imagery has a negative effect on the strength of memory. We are planning on assessing the strength of memory of non- Aphantasiacs to see if this percentage constitutes a deficit of memory in relation to Aphantasia. Result 8: Learning Style of Aphantasiacs
Most subjects reported being either “kinesthetic” or “read- write” learners, with very few reporting to being visual learn- ers. Considering that the deficit of Aphantasia is centered around visual imagery, it makes sense that Aphantasiacs would not likely learn visually. If Aphantasia is as common imagery and most don’t see much of a deficit on their cre- as Faw proposed (2.1-2.7%) (Faw, 2009), schools should be ativity or learning ability. They do however, see Aphantasia aware of it, and implement various learning techniques to affecting their memory, glancing ability, and ability to recall benefit students of all types. faces. It is more difficult to see a means of compensation at Result 9: Glancing Ability in Aphantasiacs work here among Aphantasiacs considering these are visual- dependent tasks. When assessing the inconclusive results for creativity, in which 25% of the subjects reported a “1”, meaning Aphantasia had a very low effect on their creativity, and 23% reported a “5”, meaning a very high effect on their creativity, the varying definition of ‘creativity’ must be taken into consideration; these results may either speak to artistic creativity, or to being a creative thinker (i.e. thinking in a creative manner). The latter may be more prominent among These results show that approximately the same number of Aphantasiacs, as their possible compensation for their lack subjects reported average glancing ability as reported very of visual imagery and ability to think or learn in that manner poor glancing ability. Very few reported having excellent may mean they rely on other, ‘creative’, methods of think- glancing ability. These results allow for the conclusion to ing. Therefore, we deemed it important to have Aphantasi- be drawn that Aphantasia typically has a negative effect on acs describe their level of creativity. The varying definition glancing ability. of ‘creativity’ must again be taken into consideration; these Result 10: Effect of Aphantasia on All Sense Imagery results may either speak to artistic creativity, or to being a creative thinker (i.e. thinking in a creative manner). This re- sult of majority above-average creativity may speak to either interpretation of creativity, or more likely, a mix of both. Result 7: Strength of Memory in Aphantasiacs
Result 10a: The vast majority of subjects reported that they indeed have other types of decreased sense imagery. This question is aimed at determining if Aphantasia affects other types of sense imagery. These results seem to support this concept, hinting that Aphantasia may have effects beyond visual im- agery. Result 10b: Strength of Each Sense Imagery among Aphan- Most subjects reported that their memory is on the weaker end tasiacs of the spectrum, most reporting either average, mildly below Olfactory: Average score, 1.54, Score of 1: 71% average, or very poor memory. 47% reported a strength of Gustatory: Average score, 1.66, Score of 1: 66% 33 30% report them being extremely vivid, while only 12% re- port them being vague or lifeless. This is a very fascinat- ing result because it shows that though Aphantasia affects visualization while awake, many Aphantasiacs seem to be having very vivid visualizations while dreaming on a regular basis. This result also calls for further research that could explain what brain function allows for visualization while asleep, but prohibits it during wakefulness. It must be recog- nized that for people without any visual imagery on a regu- lar basis, even dim visual dreams may register as extremely Touch: Average score, 1.87%, Score of 1: 59% vivid. Therefore, the results about the strength of such visual Though this study asked about the strength of all types of im- dreams must be considered in the context of the study. agery in Aphantasiacs, not all of the results were especially Result 14: Face Recognition in Aphantasiacs telling. Because other sense imagery (auditory, gustatory, ol- factory) tends to be relatively weak in the general population, it is difficult to discern if the weakness identified by the stud- ied Aphantasiacs is the result of their condition, or is based on the fact that most people are not very strong in this regard to begin with. However, since most people have relatively strong auditory imagery, and Aphantasiacs reported relative- This result supports a possible link between Aphantasia and ly weak auditory imagery, this is the most telling result. This Prosopagnosia (the inability to recall or recognize faces), result for auditory imagery suggests that Aphantasia might hinting that Aphantasia could be the result of a malfunction affect imagery of other senses beyond visual. This is a very in the fusiform area, the region responsible for Prosopagno- interesting result that calls for additional research to be able sia. to compare it to a normal population of visualizers. Result 12: Flashes of Imagery Discussion Results: The majority of the subjects, 56%, report to having This questionnaire yielded many fascinating results. Re- flashes of imagery. 60% percent of these 56% reported visual sult 3 seems to weigh out the possibility of Aphantasia be- imagery flashes while asleep, 56% reported this occurrence ing a genetic condition, meaning further research should be on the verge of sleep, 22% experience this during wakeful- conducted to understand its cause. Results 4, 5 and 6 show ness, and 18% say they experience these visual imagery that Aphantasia does not seem to act as a major deficit to flashes both while awake and while asleep. A bit over half the success or function of those who have it, but rather just of the subjects report to having ‘flashes’ of imagery, mostly calls for mental and lifestyle adjustments to compensate for while asleep or on the verge of sleep. This is a very interest- its effects. This claim is further supported by Result 8 that ing set of data that requires further research to understand the shows that most people with Aphantasia learn in a non-visu- brain function that allows these flashes of imagery to occur, al manner. Results 7 and 9 show that Aphantasia does have and why specifically they are more commonly while the per- some negative effects, namely that Aphantasiacs may have son is asleep. For people with a limited understanding of, or a weaker memory and glancing ability. Result 10 provides limited experience with, visual imagery, it may be difficult especially fascinating results: that the vast majority of people to recognize and categorize these ‘flashes’. Therefore, these with decreased visual imagery also have weakened imagery results must be considered with an understanding of the sub- of their other senses. This is also connected to Result 14 that jects whom they are gathered from. suggests comorbidity between Aphantasia and Prosopagno- Result 13: Dreaming in Aphantasiacs sia. Result 12 yielded the intriguing result that most Aphan- tasiacs sometimes experience ‘flashes of imagery’, primar- ily while asleep or on the verge of sleep. Result 13 adds to this concept, showing that the vast majority of Aphantasi- acs have visual dreams, and in fact very vivid ones. This result definitely calls for further research to explain what brain mechanism allows for involuntary visualization while asleep, but not voluntary imagery while awake. In providing lots of unique and interesting results, this survey supported The vast majority of subjects, 82%, reported experienc- the hypothesis and served as the first epidemiological study ing visual dreams. Of these 82%, 39% always have visual of Aphantasia. Though this survey should not be considered dreams, 33% rarely have visual dreams and 28% frequently sole proof for any of the drawn conclusions, it has helped to have visual dreams. When the subjects have visual dreams, highlight what aspects of Aphantasia are in the greatest need 34 for further research. lives. Conclusion References: Bartolomeo, P. (2008). This study was very successful, in that it received many The neural correlates of Dr. Adam Zeman, MD responses and yielded many unprecedented results. Since visual mental imagery: an ongoing Aphantasia is such a newly recognized condition, lots of re- debate. Cortex, 44, 107- search is needed to understand its mechanisms and effects. 108. This survey, the only one of its kind, served as a strong ba- Farah, M.J. (1984). The neurological basis of sis for which to develop further research, highlighting the mental imagery: a com- specific aspects of the condition that require additional ex- ponential analysis. Cog- ploration. In terms of future research, I intend to strengthen nition, 18, 245-272. Faw, B. (2009). Con- the credibility of this data set by including a control group flicting intuitions may comprised of normal visualizers, as well as delving deeper be based on differing abilities - evidence from into some of the most interesting results this study yielded, mental imaging research. hopefully gathering fMRI data from Aphantasiacs to gain Journal of Conscious- a better understanding of their brain function. Considering ness Studies, 16, 45-68. Galton, Francis (1880). PROFESSOR of Cognitive Faw’s proposal that 2.1-2.7% of a population are likely to Statistics of mental im- have extremely diminished or entirely nonexistent visual agery. Mind, 5, 301-318. and Behavioral Neurology imagery capabilities (Faw, 2009), and recognizing the high Marks, David F. (1973) “Visual imagery differ- number of responses this study received in a very short pe- ences and eye move- University of Exeter, riod, it seems that Aphantasia is a relatively widespread and ments in the recall of Medical School, Exeter, pictures.” Perception & condition. Due to its nature, the condition undoubtedly has a Psychophysics 14.3 UK. huge affect on the lives of those who have it, and therefore, it is very important to understand it scientifically. By explor- Marks, D.F. (1973). Vi- sual imagery differences We are very grateful to Dr. ing Aphantasia, and learning more about it, Aphantasiacs in the recall of pictures. Zeman for his dedication will receive more answers about the bewildering and thus far British Journal of Psy- unexplained condition that has such a vast impact on their chology, 64: 17–24. and help Zeman, A., Dewar, M., & Della Sala, S. (2015). Lives without imagery: Congenital aphantasia. Cortex, 73, 378-380.
The Neuroprotective Effects of Ischemic Preconditioning in an In Vitro Stroke Model, by Quinn Gruber (Junior)
Ischemic strokes, which and cost the United States 33 After an ischemic insult, the emia. Lee et al. found that make up the majority of billion dollars in 2011; thus, brain lacks necessary anti- IPC increased levels of heme- strokes that occur, happen the search for a way to limit oxidant defenses to protect oxygenase 1, an antioxidant when blood flow to the brain stroke damage is essential neurons against free radical and antiapoptotic protein, is blocked (American Stroke (American Heart and Stroke excitotoxicity, the overex- and decreased levels of neu- Association, 2016). Strokes Associations, 2016). citation of glutamate amino ronal death (Lee, 2015). IPC can cause cognitive and Ischemic strokes cause dam- acid receptors such as the N- has also been found to both physical disabilities, and are age in two stages: the stroke, methyl-D-aspartate (NMDA) increase antioxidant enzyme the most prevalent cause of which prevents blood reach- receptor. Due to this antioxi- activity and decrease the size disability in the United States ing the brain, and during the dant deficiency, free radicals of cerebral infarcts from I/R (Mozaffarian, 2016). Al- reperfusion period, which is activate apoptosis and subse- (Saad, 2015). though the effects of a stroke when blood flow is restored. quently cause neuronal death Purpose of study: We will vary depending on which re- Causes of ischemia reperfu- (Dugan, 1999). determine the effectiveness of gion of the brain experienc- sion (I/R) damage are not One method of addressing IPre and IPost as treatments es the stroke, impacts may entirely known. I/R damage the lack of neuronal defenses for ischemic neuronal dam- include paralysis, declined has been linked to oxida- against stroke is the imple- age, and underlying receptor memory, speech, and cogni- tive stress and accumulation mentation of ischemic pre- mechanisms tion, and behavioral changes of free radicals, ions which conditioning (IPC), which Hypothesis: IPre and IPost (Johns Hopkins University, have a single unpaired elec- exposes neurons to a shorter treatments on hippocampal 2017). Strokes cause many tron, in turn causing inflam- and sublethal ischemia insult slice cultures protect neurons instances of death each year mation and cell apoptosis. before a more severe isch- from ischemia-induced death 35 propidium iodide ing cannot be ruled out as a duced damage, and improving (PI), a fluorescent possible treatment of isch- the slice culture model so that stain which perme- emia-induced injury. Since ischemic injury is more accu- ates damaged cell multiple studies have found rately represented. membranes and positive neuroprotective ef- References American Heart Association, & Ameri- binds itself with fects stemming from isch- can Stroke Association. (2016). Isch- DNA, indicating emic preconditioning, more emic Strokes (Clots). Retrieved January 3, 2017, from http://www.strokeasso- cell death. The experiments are required to ciation.org/STROKEORG/AboutStroke/ CA1, CA2, and determine the effectiveness TypesofStroke/IschemicClots/Ischemic- dentate gyrus (DG) of IPC in an in vitro stroke Strokes-Clots_UCM_310939_Article. jsp#.WGv0HFMrKYk were photographed model. Furthermore, one Mozaffarian, D., Benjamin, E. J., Go, under fluorescence must acknowledge the un- A. S., Arnett, D. K., Blaha, M. J., Cush- and under normal wieldiness of IPC regarding man, M.,Stroke Statistics Subcommit- tee. (2016). Heart Disease and Stroke light. Fluorescence its use as a stroke treatment. Statistics—2016 Update. Circulation, was measured in Since one cannot predict 133(4), e38–e360. http://doi.org/10.1161/ CIR.0000000000000350 arbitrary units, with exactly when a stroke will Johns Hopkins University. (2016). Ef- the average values occur, IPC is not necessar- fects of Stroke | Johns Hopkins Medicine and reduce brain damage of experimental ily a convenient method for Health Library. Retrieved January 9, from oxygen-glucose depri- 2017, from http://www.hopkinsmedicine. group fluorescence levels treating stroke damage. [add org/healthlibrary/conditions/nervous_ vation. normalized [unsure of how information about CAGB system_disorders/effects_of_stroke_ Materials and Methods: exactly the math works] with and how IPC can help with brain_attack_85,P00777/ American Heart and Stroke Associa- Researcher-performed pro- the average fluorescence of any possible damage from tions. (2016). Heart Disease and Stroke cedures: Mice were anesthe- control slices. restriction of blood flow dur- Statistics--2016 Update. Retrieved Janu- tized and sacrificed by - de ary 4, 2017, from http://www.heart.org/ Results: ing surgery] HEARTORG/General/Heart-and-Stroke- capitation. Hippocampi were There was no marked dif- Conclusion: Association-Statistics_UCM_319064_ retrieved from mice and ference between the con- Multiple studies have found SubHomePage.jsp sliced to a thickness of 400 Dugan LL, Choi DW. Free Radicals in trol, OGD, or IPC groups in ischemic preconditioning Hypoxia-Ischemia. In: Siegel GJ, Agra- μm using a vibratome before fluorescence photos. Slices as an effective method of noff BW, Albers RW, et al., editors. Basic distribution in plates. Slices showed little levels of fluo- reducing damage from isch- Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadel- were submerged in 1 mL rescence across all groups, emic insult. The mechanisms phia: Lippincott-Raven; 1999. Available culture media for one week indicating an error in experi- of IPC are still not clear but from: https://www.ncbi.nlm.nih.gov/ and placed in an incubator at mental procedure occurred, are theorized to involve books/NBK28241/ 5.0 % CO2 and 35 ℃ before resulting in flawed results. anti-inflammatory and experiments. Plates were Due to the lack of distin- antioxidant mecha- Mentor: distributed between multiple guishable trends in neuron nisms which allow the members of the lab for use in death, the experiments are brain to prepare for a Dr. Patric K. Stanton, separate experiments. inconclusive. more severe ischemic Ph.D. Student-performed proce- Discussion: insult. Our experiments dures: Ischemic precondi- Many past studies use an did not reflect the find- tioning and ischemic insults in vivo model to simulate ings of other scientists were simulated via oxygen- ischemia, inducing ischemic which support IPC as glucose deprivation (OGD). insult by bilateral carotid oc- a method of reducing Ischemic preconditioning clusion, clamping the arter- damage from ischemic (IPC) was performed by ies shut to induce ischemia. insult, but, due to the placing slices in oxygen and The in vitro model used inconclusive nature glucose deficient media and may not reflect an accurate of the results, further a hypoxygenic incubator. model of I/R, as the culture experimentation is re- Control slices remained in media does not necessarily quired to determine PROFESSOR of Cell Biology culture media and normal model blood flow in vivo. the impact of IPC on and Anatomy incubator. After OGD, slices The experiments do not pro- ischemic injury. Future New York Medical College, were returned to culture me- vide evidence to support the experiments will focus Valhalla, NY dia and incubator and given effectiveness of ischemic upon isolating specific a 24 hour reperfusion period. preconditioning; however, neural mechanisms We are grateful to Dr. Stan- After this reperfusion period, as the results are unreli- which may protect the ton for his help. slices were dyed with 10 mL able, ischemic precondition- brain from ischemia-in- 36 Using Bioinformatics to Interpret Epigenetic Research Data, by Peter Manthey (Junior)
Bioinformatics is an emerg- from more than 100,000 network and genetic cel- ing discipline that uses com- distinct organisms.” 1 As a lular mechanisms. This puter technology, statistics, result, there has been an in- new technology for mathematics, and engineer- crease in the application of modeling morphogen- ing to analyze and translate bioinformatics tools to help esis could help us to bet- biological and genetic data, medical researchers not ter understand defects as well as healthcare infor- only analyze larger quanti- that occur during limb mation. Although bioinfor- ties of data in shorter period development.2 In 2005 matics has been around since of time, but to also become additional research was the 1960s, it is now being more precise in diagnosis performed presenting widely used. In the simplest and determining treatments. CompuCell3D, a three- form, bioinformatics is data One breakthrough is using dimensional, cell-cen- that is collected from spe- DNA sequencing to break tered, multiscale frame- cific sources, run through apart a DNA strand which is work.3 unique code and organized made up of four nucleotide Today CompuCell3D is by the associated biological bases. By doing this scien- being used to in an open macromolecules. tists can determine variations source environment that The amount of data being for genetic diseases. Col- allows for “virtual tissue protein classifications and se- collected today throughout lecting all of this data and simulations of development, quence information to be used the world is enormous. One using bioinformatics will homeostasis, toxicity and to determine potential risk of of the largest databases being now allow doctors to break disease in tissues, organs and allergenic cross-reactivity. used for bioinformatics is the down a person’s entire hu- organisms, covering subcel- Over 55% of the US popula- GenBank, which is part of man genome in one day and lular, multi-cell and continu- tion has tested positive for the International Nucleotide provide personalized treat- um tissue scales.”4 some type of allergy. 8 Aller- Sequence Database Col- ment and medication. One In October of 2015, a group gies are caused by a person’s laboration. As of December bioinformatics software tool of scientists in Italy de- immune system which mis- 2015 this database contained currently being tested, will veloped a bioinformatics takes an allergen, a foreign over 203 billion nucleotide automate the interpretation program that is capable of body, as a threat and launches bases in more than 189 mil- of the genome data by ac- identifying potential bio- and attacks to neutralize it. lion sequences, collected cessing any medical journal, markers for diseases and dis- The researchers used bioin- from daily exchanges of data research and articles applica- orders know was SANIST. formatics to predict which with the DNA DataBank of ble to the data and allow the In this study, researchers proteins in parasitic worms Japan (DDBJ), the European treating doctor to reference used SANIST to identify a would cause a reaction similar Molecular Biology Labora- those sources for potential biomarker for prostate can- to an allergic reaction in hu- tory (EMBL), and GenBank treatment. cer known as carnitine, an mans. They were able to iso- at NCBI. In 2003, researchers from ammonium compound in- late in a parasitic worm one of “This database is produced several esteemed universities volved in fatty acid metabo- the most common proteins in and maintained by the Na- in the United States leveraged lism. The research found pollen. This protein was sim- tional Center for Biotech- CompuCell, a multi-model that canitine was expressed ilar to a protein only known nology Information (NCBI) framework for the simulation at lower levels in the plasma previously in the genomes as part of the International of morphogenesis, to simu- of prostate cancer patients of plants. Pollen is one of Nucleotide Sequence Da- late the formation of limbs in and concluded that SANIST the most prevalent allergens. tabase Collaboration (IN- multicellular organisms dur- was able to accurately iden- This bioinformatics tool will SDC). The National Center ing their embryonic stages of tify and separate individuals allow scientists to predict pro- for Biotechnology Informa- development. The program with prostate cancer from teins that cause allergies, and tion is a part of the National was designed to help re- those with benign conditions to design protein molecules 9 Institutes of Health in the searchers better understand at a rapid rate.7 for treating them. United States. GenBank and the processes of morphogen- In late October of 2015 sev- Right now research is occur- its collaborators receive se- esis. The program simula- eral databases have were ring to find a more accurate quences produced in labora- tion models the interactions created to provide doctors detection for ovarian cancer tories throughout the world between the gene regulatory with access to allergen lists, in women. Currently fifty 37 percent of women who have date agents for NSC 319726. matics to prove it is possible gins of animal development been diagnosed with ovarian This is because NSC 319726 to model cells with multiple lay in the effects of external cancer do not survive more has been found to reduce lev- age dependent parameters forces on how these animals than 5 years. The reason this els of RPS6KA6, a chemical in the CompuCell3D pro- develop. Dr. Stuart Newman cancer is so deadly is because that is found to be overex- gram by using local cell in- believes “that the origins of ovarian cancer is very hard to pressed in patients with can- teractions versus an external animal development lay in the detect, with signs only pre- cer due to it influencing the segmentation clock. The re- mobilization of physical orga- senting themselves normally growth of cancer cells.10 search concludes that somites nizational effects that resulted during later stages of devel- One of the most important are self-organizing structures when certain gene products of opment. In 2012, there were tools in the CompuCell3D whose size and shape is con- single-celled ancestors came over 200,000 documented program is the chemical field trolled by local cell-cell in- to operate on the spatial scale cases and 125,000 deaths tool. This tools allows re- teractions. of multicellular aggregates”. worldwide. Researchers have searchers to simulate the Over the last 10 years there Researchers compared the found that NSC 319726, a morphogenesis of multicellu- has also been significant embryological processes that small-molecule anticancer, lar organisms. The “French progress in the field of us- shapes the limb bud, teeth could be used to effectively flag” model displayed how ing bioinformatics for epi- and beaks to current theory treat ovarian cancer. This cells placed into varying po- genetic research. In 2010, of bone and cartilage devel- study used bioinformatics to sitions on the chemical field Bare Bones Pattern Forma- opment. Bioinformatics was analyze and map the interac- changed their parameters in- tion: A Core Regulatory Net- used to determine that the tions between differentially cluding target volume, shape, work in Varying Geometries current theory only applies expressed genes across a net- orientation and diffusion due Reproduces Major Features to limb development. This work. This allows research- to the surrounding environ- of Vertebrate Limb Devel- research has been the founda- ers to find potential targets ment. One prominent theory opment and Evolution used tion for a new therapy regard- for NSC 319726. The result surrounding the development bioinformatics to “simulat- ing the process of evolution in suggested that these genes of a curved bird beak is that ed the behavior of the core which an organism’s genetic and pathways may be candi- at a certain point in the beaks chondrogenic mechanism of expression or phenotype, will development, the developing limb in the often change before there is the cartilage bar presence of an FGF gradient an actual change in the organ- will pass through using a novel computational ism’s genetic code of geno- Mentor: a chemical field environment that permits type. This theory has more Dr. Stuart A. Newman, that weakens the simulation of LALI systems recently been used to examine Ph.D. strength of the in domains of varying shape the evolutionary changes that bar. This chemi- and size.” This research con- were first observed by Darwin cal field is stron- cluded when a gradient is during his finch study in the ger though at the present the limb it affects the Galapagos Islands. Research- bottom of the behavior of the mesenchyme ers were able to find that by bird’s beak than and can form limb-like skel- introducing different external it is on the top of etal structures. Bioinformat- factors into the environments the beak causing ics was applied to simulate of a developing bird embryo, it to develop a in vitro and in vivo limb de- all beak shapes described by hooked shape. velopment. This will allow Darwin in his studies could be Recent research doctors to better understand achieved. on the formation limb development and any Currently, cancer is the lead- of body seg- complications that may oc- ing cause of death worldwide, ments (somites) cur in utero. with 1.65 million cases di- in vertebrate In 2012 in the Physico-Ge- agnosed and 600,000 deaths PROFESSOR of Cell Biology embryos also netic Determinants in the caused by the disease in and Anatomy utilizes cell Evolution of Development United States alone. By us- growth with scientists found embryos ing information base off of New York Medical College, multiple param- exhibit an assortment of ste- the Glazier-Granier-Hogeweg Valhalla, NY. eters dependent reotypes and patterns dur- (GGH)-based model, which is of the age of the ing development that have used to explain how different We are grateful to Dr. New- developing cells. been present for millions cells locally interact with each man for his help This research of years. This has lead re- other in an organism, research used bioinfor- searchers to believe the ori- have been able to discover a 38 method for identifying cells determined if the simulation papers published using the autism-database.html. 7 Albini, A., Briga, D., Conti, M., that are either cancerous, or produces gaps or margins of CompuCell3D program such Bruno, A., Farioli, D., Canali, S., et al. are at risk of becoming can- error in the output graphics as “Searching a multicellular (2015). SANIST: a rapid mass spec- cerous based upon how they that parallel those observed model to tame tumor-induced trometric SACI/ESI data acquisition and elaboration platform for verifying interact with other surround- during original study. angiogenesis” to aid in the potential candidate biomarkers. Rapid ing cells in the organism. Methodology creation of the CompuCell3D Communications in Mass Spectrom- etry, 29(19), 1703-1710. It is evident that bioinfor- Celldraw.bat is used to create simulations. 8 (2010). Allergy Statistics and Allergy matics is a powerful tool in the initial cell layout. Facts - WebMD. Retrieved January 10, the evolution of predicting Twedit++ is used to define References 2016, from http://www.webmd.com/al- 1 GenBank Home. Retrieved January 10, lergies/allergy-statistics. and treating diseases. In this the cell properties and behav- 2016, from http://www.ncbi.nlm.nih.gov/ 9 Tyagi, N., Farnell, E. J., Fitzsimmons, research we will focus on us- iors, and edit the code. genbank/. C. M., Ryan, S., Tukahebwa, E., Mai- ing bioinformatics and the IDLE (Python GUI) is used 2 Izaguirre, J. A., Chaturvedi, R., Huang, zels, R. M., et al. (2015). Comparisons C., Cickovski, T., Coffland, J., Thomas, of Allergenic and Metazoan Parasite CompuCell3D simulation to write scripts for more ad- G., et al. (2004). CompuCell, a multi- Proteins: Allergy the Price of Immunity. software to more accurately vanced cellular functions model framework for simulation of PLoS Comput Biol, 11(10), e1004546. morphogenesis. Bioinformatics, 20(7), 10 Xue, J., Yang, G., Ding, H., Wang, P., model bird beak develop- CompuCell3D is used to run 1129-1137. & Wang, C. (2015). Role of NSC319726 ment during early stages of the simulation and produces 3 Cickovski, T. M., Huang, C., Chaturve- in ovarian cancer based on the bioin- fetal development. We will output graphics di, R., Glimm, T., Hentschel, H. G. E., formatics analyses. OncoTargets and Alber, M. S., et al. (2005). A framework therapy, 8, 3757. present results from numeri- Windows Movie Maker is for three-dimensional simulation of mor- Zhu, J., Zhang, Y., Alber, M. S., & New- cal biologically plausible used to edit the output still phogenesis. Computational Biology and man, S. A. (2010). Bare bones pattern simulations that demonstrate graphics into an animated Bioinformatics, IEEE/ACM Transactions formation: a core regulatory network in on, 2(4), 273-288. varying geometries reproduces major that the development of the simulation. 4 (2015). Compucell3d.org - Userexp.io. features of vertebrate limb develop- upper and lower beak grow The primary step is to estab- Retrieved January 24, 2016, from http:// ment and evolution. PLoS One, 5(5), userexp.io/compucell3d.org.html. e10892. independent of each other. lish a baseline by creating a 5 Home - Autism Society. Retrieved Jan- Newman, S. A. (2012). Physico-genetic This will be done by demon- simulation that modeled the uary 10, 2016, from http://www.autism- determinants in the evolution of devel- strating the significant shape development of the control society.org/. opment. Science, 338(6104), 217-219. 6 (2015). $9 million grant to establish *Linde-Medina, M., & Newman, S. A. differences between control specimen in the Limb Tooth open-access autism database ... Retrieved 2014). Limb, tooth, beak: Three modes and VPA-treated embryos at Beak Research. Also col- January 10, 2016, from https://med. of development and evolutionary inno- each stage. Success will be lected algorithms from other stanford.edu/news/all-news/2015/06/9- vation of form. Journal of biosciences, million-grant-to-establish-open-access- 39(2), 211-223
Epigenetics predicting our Future, by Kimberly McKoy (Sophomore)
Epigenetics are heritable cess, which is triggered by portance of methylation of changes in a gene sequence certain environmental con- how expressed genes in the (Simmons, 2008). Epige- ditions and lies between the generation of grandparents netics withholds a person’s genotype and the phenotype can be silenced in the next future as it has the power (Deichmann, 2016). The generation. to switch genes on or off genotype are all the genes in The mother’s environment (Simmons, 2008). Methyla- a patient. The phenotype is can cause trauma to her off- tion is the function of methyl the expression of genes that spring, this development is groups being added to DNA expresses a person’s height, based on the nurturing of the at the CpG sites. Methyla- weight and skin color, this is parents (Turcot, 2017) . With tion can turn off the protec- important as it develops who the lack of nurturing, the tive suppressor genes (Sim- we are as people. In addition, offsprings genes can be al- mons, 2008). These genes biochemical pathways of the tered by epigenetics and can are extremely important as cell are determined by the change many of the brain’s they protect the cell from presence of activated genes and body’s function, causing developing tumors. The tu- (Deichmann, 2016). The a mood disorder in the off- mor suppressor genes can be methylation patterns, which spring (Turcot, 2017). The silenced when the DNA is may silence certain genes, depression in the mother can 2017). Stress can create future methylated. In a patient, this are passed from the parent to transform into adult depres- diseases such as neurological can cause cancer (Simmons, the offspring. (Deichmann, sion and stress management diseases, by modifying gene 2008). Epigenetics is a pro- 2016). This shows us the im- for her offspring (Turcot, expression of the serotonin 39 transporter (5-HTT) influ- . As early trauma impacts the 2014). Abuse affects the egies (Kim, 2016). Extreme encing depressive responses response to stress, it affects organs of the body such as stress during childhood can in patients (Szyf, 2015 A). the digestive systems and the hypothalamus, pituitary lead to PTSD, this is formed The genetic variation, poly- other systems in the body, glands and adrenal glands by the excessive amount of morphism, is associated with causing an abnormal metab- (Yong, 2009). All three of cortisol, and many bodily the deficits in neurobehavior- olism in a patient (Machado, these organs create hor- functions not being able con- al functioning during infancy 2015). This is even more mones that control reactions trol it forming the symptoms (Szyf, 2015 A). There are pronounced in victims that to stressful situations and of PTSD (Zhao, 2013). This many epigenetic signatures have already been exposed trigger psychological chang- leaves epigenetic marks that of child abuse that could be to child abuse. es (Yong, 2009). The NR3C1 controls DNA methylation easily identified by looking at The hypothalamic-pituitary produces a protein called that can change the gene ex- gene expression. Genes that adrenal axis (HPAA) has a the glucocorticoid receptor, pression of the patient (Zhao, are silenced by methylation function to send messages which causes a reaction that 2013). 98% of genetic chang- caused by physical abuse from the adrenals, the pitu- deactivates the HPAA (Yong, es in childhood abuse are the can affect bodily functions itary and other organs. De- 2009). A deactivation of the same changes in gene expres- (Cecil, 2016). This includes pression is linked to the dys- HPAA causes a continuation sion in PTSD patients (Zhao, the important functions that regulation of the HPAA and of stress response which can 2013). our body brings such as car- this is because too much cor- cause someone to have high PTSD affects the gene expres- diovascular function, fear tisol can create an imbalance blood pressure and other nu- sion and brain function during response, and wound healing in the axis causing the dys- trition problems. the development in the cen- (Cecil, 2016). As a result, regulation (Farrell, 2016). There is a decreased hip- tral nervous system (Zannas, there is a risk of heart disease Early exposure to stress links pocampal hGR1f (Hip- 2015) . PTSD is linked with among individuals who were to the dysregulation in the al- pocampal Glucocorticoid immune function, trauma ex- physically abused as chil- tered levels of the glucocor- Receptor ) expression, and posure which may bring dis- dren (Cecil, 2016). Maltreat- ticoid receptor and can cause the human homologue in turbance to the HPAA; since ment has been consistently depression (Farrell, 2016). abused suicide victims com- it sends important messages associated with these dis- Cortisol and the glucocorti- pared to nonabused suicide to the brain (Zannas, 2015). eases and there is a reduced coids are attached onto the victims (Labonte, 2012) . Immune dysregulation in the volume of the corpus callo- glucocorticoid receptor. Glu- The decrease in the hGR1 periphery can contribute to sum in the prefrontal cortex cocorticoids are hormones expression associates with the development of PTSD and hippocampus (Cecil, that are involved in the me- the reduced HGR messenger in brain function (Zannas, 2016). This corpus callosum tabolism of carbohydrates, RNA with a promoter hyper- 2015). Immune dysregulation is responsible for joining two proteins and fats. Depressive methylation (Labonte, 2012). is the weakness in a patient’s parts of the brain together disorder and the hyperactiv- Hypermethylation is the in- immune function and immune with fibers. If methylation ity of the HPAA are linked creasing in methylation of system. PTSD causes the al- can silence some genes pre- to the modification of (NG- DNA which promotes exces- teration in the nuclear fac- venting functions, What else FI-A), proteins that are in the sive stress levels. The HGR tor Kappa B, and this factor can it change? nucleus (Farrell, 2016). This and its noncoding exon 1B, regulates inflammatory gene Modifications of the sero- protein activates the EGR 1C and 1H is decreased in networks (Guardado, 2016). tonin transporter (5-HTT) (early growth response) in the hippocampus of abused As a result, there is a decrease can change the behavioral adolescents. suicide victims (Labonte, in methylation of genes in im- responses in children. Such Child abuse is not just about 2012). mune and inflammatory func- modifications can happen the physical damage that is Childhood trauma affects tion in PTSD patients (Guar- in the womb of their moth- affected. Genes are affected many bodily functions and dado, 2016). Inflammatory ers and are influenced by as well, just like NR3C1 as an adolescent trauma can function is the function of the environmental circumstanc- gene, which codes for the turn into something more like body repairing cells and de- es. Early trauma can cause stress receptor called corti- PTSD. Childhood trauma is veloping tissue repair. PTSD changes in the precursor of sol (Eleanor, 2014). Corti- determinant of psychiatric increases the nuclear factor thyroid-hormone T4 and T3 sol is a stress hormone that disorders and in PTSD pa- kappa B which causes stress- (Machado, 2015) . Thyroid helps you respond to threat tients, which makes the brain induced inflammation and glands take the iodine that and danger (Eleanor, 2014). more vulnerable to trauma cognitive impairments which is in food and convert it into Children that deal with abuse (Kim, 2016). Understanding gives PTSD the symptoms thyroid hormones. Changes develop high levels of corti- how Epigenetic influences that it has (Guardado, 2016). in thyroid hormones can sol and develop low thresh- psychiatric illness can im- Ancestral experiences are cause changes in metabolism old stress levels (Eleanor, prove many therapeutic strat- copied in the epigenome for 40 human behavior in health netic signatures of childhood abuse and ness in psychiatric disorders. Prog- Neuropsychopharmacology (2015) 25, neglect: Implications for Psychiatric ress in Neuro-Psychopharmacology 682-702 http://dx.doi.org/10.1016/j. and diseases (Szyf, 2015 vulnerability. Journal of Psychiatric Re- & Biological Psychiatry 70 (2016) euroneuro.2014.01.00 B) . Nongenetic transmis- search 83 (2016) 184-194 http://dx.doi. 162-169 http://dx.doi.org/10.1016/j. (B) Szyf, Moshe. “Nongenetic inheri- sions could be triggered in org/10.1016/j.jpsychires.2016.09.010 pnpbp.2016.01.013 tance and transgenerational epigenetics.” Farrell, Chloe. Veronica O’Keane. Epi- Labonte, Benoit, Volodymyr (2015) responses to environmental genetics and the glucocorticoid receptor: Yerko,Jeffrey Gross, Naguib Mecha- Turcot ,Andree-Anne Bouvette-. Unter- exposure due to epigenetics A review of the implications in depres- war, Michael J. Meaney, Moshe Szyf, naehrer, Eva. Gaudreau, Helene. Lydon, sion. Psychiatry Research 242 (2016) and Gustavo Turecki. “ Differential John E. Steiner, Meir. Meaney,Michael. (Szyf, 2015 B). When the 349-356http://dx.doi.org/10.1016/j. Glucocorticoid Receptor Econ 1B,1C The Joint contribution of maternal his- phenotypic response to the psychres.2016.06.022 and 1H tory of early adversity and adulthood ancestral parental experience Guardado, Pedro. Anlys Olivera, Heath- Expression and Methylation in Suicide depression to socioeconomic status and er L. Rusch, Michael Roy, Christina Completers with a History of Child- potential relevance for offspring devel- creates generations of physi- Martin. Natasha Lejman, Hwyunhwa hood Abuse”(2012) opment. Journal of Affective Disorders cal environments that were Lee, Jessica M. Gill .Altered gene ex- Machado, T.D . G.A Salem, V.L. Boss, 207 (2017) 26-31 triggered by a multigenera- pression of the innate immune, neu- M.Z. Gold and, M.J. Meaney, M. Ar- Ute Deichmann. Epigenetics: The ori- roendocrine, and nuclear factor-kappa B ganonik, G.G Manfro, P.P. Silveira. Ear- gins and evolution of a fashionable top- tional transmission (Szyf, (NF-κB) systems is associated with ly Trauma is associated with decreased ic. Developmental Biology 416 (2016) 2015 B). Epigenetics pre- posttraumatic stress disorder in mili- peripheral levels of thyroid-hormone 249-254. http://dx.doi.org/10.1016/j. tary personnel.Journal of Anxiety Dis- T3 in adolescents. Int. J. Devl Neurosci- ydbio.2016.06.005 dicts our future by our genes orders 38 (2016) 9-20 http://dx.doi. ence 47 (2015) 304-308 http://dx.doi. Zannas S., Anthony, Nadine Provencal, affecting many functions by org/10.1016/j.janxdis.2015.12.004 org/10.1016/j.ijdevneu.2015.10.005 and Elisabeth B. Binder. “ Epigenetics the unexpected silencing of Hafner, Sophia J. Lund, Anders H.Great Nelsen, Eleanor. 30 July 2014.Abuse of Posttraumatic Stress Disorder: Current expectations – Epigenetics and the me- Casts a Long Shadow by Changing Evidence, Challenges,and Future Direc- methylation that each of us andering path from bench to bedside. Children’s Genes tions”. (2015) have to deal with. Biomedical Journal 39 (2016) 166- 176 Simmons, D. (2008) Epigenetic influ- Zhao,Roseanne.“Child abuse leave Epi- http://dx.doi.org/10.1016/j. ence and disease. Nature Education genetic marks” (2013) References bj.2016.01.008 1(1):6 Yong, Ed. February 22 2009.“Child Cecil, Charlotte A.M. , Rebecca G. Kim, Ji Sun. Lee, Seung-Hwan. Influ- (A)Szyf, Moshe. Epigenetics, a key for Abuse permanently modified stress genes Smith, Esther Walton, Jonathan Mill, ence of interactions between genes unlocking complex CNS disorders? in brains of suicide victims” Eamon J. McCrory, Essi Viding. Epige- and childhood trauma on refractori- Therapeutic Implications. European
The analysis of visual elements required for reading improvement for dyslexics by Hailey Kissner (Sophomore)
The formal definition of Dys- with math, reading and writ- omy. The process of early lexia is: “a specific learning ing and its psychological diagnosis with this disorder disability that is neurological impact on an individual. For is key, the earlier the bet- in origin. It is characterized example, dyslexics struggle ter because with time they by difficulties with accurate with issues of self-esteem, can learn how to cope with and/or fluent word recogni- depression, and social in- dyslexia and how it impacts tion and by poor spelling and securities. “A good way to daily life. Although, dyslexia decoding abilities. These dif- understand dyslexia is to es- cannot be outgrown or cured ficulties typically result from tablish what it is not. It’s not many teaching strategies us- a deficit in the phonologi- a sign of low intelligence or ing a multisensory approach cal component of language laziness. It’s also not due to and various other tools can that is often unexpected in poor vision. It’s a common improve life for a dyslexic. relation to other cognitive condition that affects the Individuals with dyslexia ex- abilities and the provision of way the brain processes writ- perience an immense amount effective classroom instruc- ten and spoken language” of hardship because their tion. Secondary consequenc- (Lapkin, n.d.). Dyslexia is problem with reading causes es may include problems in a learning disability charac- low self-esteem and frustra- Despite adversity, many cre- reading comprehension and terized with having issues tion. Therefore, dyslexics are ative minds with dyslexia reduced reading experience in speech, writing, reading, forced to identify what dif- have become famous such as that can impede the growth of and spelling. Often it takes ferent tools and techniques Tim Tebow, a football star and vocabulary and background dyslexics more time to un- aid their learning process. Dav Pilkey, the author and il- knowledge” (The Interna- derstand complicated topics Also, dyslexics have diffi- lustrator of the “The Adven- tional Dyslexia Association, and information may need culty articulating what they tures of Captain Underpants” 2013). to be processed differently. want to say, challenges with series (Lapkin, n.d.). The article by Lapkin, et al. This condition is claimed to memory, maintaining focus, More than 100 years ago dur- describes the symptoms of be caused by hereditary traits and difficulty with organiza- ing the November of 1896 in dyslexia including issues and differences in brain anat- tion and time management. Sussex England, Dr.W. Prin- 41 gle Morgan published the spoken language is involun- uses a functional MRI to that allograph representa- first description of dyslexia tary because reading can be learn about the double defi- tions are specific, in other a “Percy F., . . . aged 14,... learned at a conscious level. cit hypothesis. The group words,they are located at has always been a bright and Gregory struggling to read of poor readers and normal the beginning and end of the intelligent boy,” wrote W. long words and novel terms readers in the study, uses word ignoring how long it is. Pringle Morgan in the Brit- relates to the phonological tests such as phonological This provides an explanation ish Medical Journal, “quick deficit in dyslexia. A study awareness and rapid au- for the patient’s continuous at games, and in no way infe- done in the 1980’s showed tomatized naming while a errors because when reading, rior to others of his age. His that a preschoolers phono- preforming a with a fMRI. the allographs remained in great difficulty has been--and logical ability predicts later Knowing that the group of their positions and mistaken is now--his inability to learn skills at reading. Addition- individuals “showed dis- for a word later on . From this to read” (Shaywitz,1996). ally, the finding showed that sociation between brain re- study scientists also learned From 1896 to 1996 dyslexia remedial training interven- gions that were sensitive to that the beginning and the was believed to be a substi- tion correlated with phono- phonological awareness (left end of the word are related tute for intelligence because logical awareness improved inferior frontal and inferior to standard word orientation “only smart people could the children’s ability to read parietal regions) and rapid compared to spatial proper- read”(Shaywitz,1996). Dur- (Shaywitz,1996). naming (right cerebellar lob- ties like up and down (Johns ing the 1920’s scientists ule VI)”(Norton, 2014). Ac- Hopkins University, 2010). thought that dyslexics had a Scientists believe children cording to behavioral mea- A study from the Massachu- combination of issues with with developmental dyslexia sures it is displayed that the setts Institute of Technology the body’s visual system and are made up of three sub- double deficit group scored uncovered that dyslexics have a reading disorder, often eye types, rapid automatic nam- based upon their the lowest problems with voice recogni- training was recommended ing (RAN), phonological and on reading ability, the sys- tion. In the trial, individuals to help the alleged visual double deficit consisting of tem in which the tasks were with and without dyslexia deficits. Later on, the visual both RAN and phonological. scored was based on the indi- identified cartoon character issues in dyslexia were dis- In order to prove the double vidual’s performance. There voices in English and Man- proved and we now know deficit hypothesis various was little difference between darin with a computer screen that this condition is corre- research projects have been the reading ability according displaying multiple cartoon lated to the language system. conducted. For instance, re- to the testing of the double characters and had to match Shaywitz gives an example of searchers have ested adoles- deficit and single phonologi- the voices to the avatars on the the struggles of med student, cents in areas relating to the cal deficit (Norton, 2014). screen. The research showed Gregory, who was diagnosed specified subtypes through Unlike developmental dys- that the individuals with- with developmental dyslex- color naming, timed reading lexia which is obtained early out dyslexia could correctly ia in elementary school. As and math expression prob- in life, acquired dyslexia match the cartoons voices in a result, he received support lems etc. During the memory could form at any time be- English to the avatars on the and excelled in a program tasks, there was no major cause it is caused by damage computer screen 70 percent for gifted students. Later on difference between dyslexics to the brain. A study done by of the time and 50 percent of in his life, Gregory attended and the control who did not researchers at John Hopkins the time they could properly an Ivy League college where have have a learning disabil- University found possible match the Mandarin speak- he worked tirelessly in order ity. Children presumed with theories relating to reading ing cartoons with their ava- to get into medical school. the double deficit hypothesis in acquired dyslexics. A 69 tar. However, dyslexics were There Gregory struggled scored significantly lower year old patient with a rup- correct at matching the voices learning long words and in the reading and word de- tured cerebral aneurysm re- with the cartoon character in novel terms like labels re- coding tasks. Additionally, sulting in damage to the left both languages only 50 per- lated to the structure of the dyslexics completed less hemisphere of her brain, has cent of the time. Further prov- human body. A new model of math problems during the slow and inaccurate read- ing the theory that dyslexics dyslexia was created based math fluency and calcula- ing after her incident (Johns have difficulties with identi- off phonological processing, tion tasks. Finally dyslexics Hopkins University, 2010). fying voices (Belluck, 2016). that supports both neurologi- had a slower performance in By testing the patient, sci- According to a study done by cal and clinical symptoms of the color naming and digit entists found more support a professor at Harvard Uni- his reading disorder. In lan- matching tasks (Träff, 2016). for allographs, two or more versity, dyslexia is presumed guage processing, the words The study, “Functional neu- different forms of a letter or to be correlated with the struc- are decoded in the phono- roanatomical evidence for patterns of letters forming a ture of white and grey matter logical area of brain before the double-deficit hypothesis sound in a word during pre- in the brain. When an individ- being read. This system of of developmental dyslexia”. lexical reading which claim ual is reading a book the eye 42 takes in information which is pect that it is associated with where they never had activ- related with a improper func- then transported to the brain, issues with reading and spell- ity before. Meanwhile, non- tion of the human body’s neu- there the regions of the brain ing. The article references dyslexics had little brain robiological system (Hayashi, process what is being read.. a similar study which com- function in those areas . With 2014). White matter, contains ax- pared right handed dyslexics vital remedial training dys- Current research using neu- ons, long fibers, connecting and right handed non dyslex- lexics can further improve roplasticity, the process in neurons whose cell bodies ics (control group) brain ac- their reading skills and ex- which neurons establish new are located in grey matter, al- tivity during reading tasks. perience more activation in attachments between each lowing the essential process The results demonstrated the their brain (Segelken, 2006). other shows importance to the of connecting graphemes control group had more brain For years Haskins Labora- learning process in dyslexia. and phonemes. Additionally, stimulation while perform- tories, a nonprofit institution By conducting a functional white matter is responsible ing these tasks. This research working with Yale, has re- MRI or fMRI, a scan of the for reading development in also found that individuals searched dyslexia and other human brain which shows a the brain (WETA, 2015). who were skilled at decod- reading disorders. A more flow of blood to activated re- A phoneme is a sound of a ing during reading had more recent study, found differ- gions of the brain while the word which makes up graph- activation in the left side of ences in the brain between patient is performing certain emes, the written representa- the brain and right handed dyslexic children and normal tasks. Through the study of tion of a word. In language dyslexics had greater activ- readers while completing fMRI scans of dyslexics and processing, the words are ity in their frontal lobe when tasks relating to visuospatial non-dyslexics before and af- decoded in the phonologi- performing tasks (WETA, processing. The study par- ter remedial reading train- cal area of brain before be- 2015). ticipants were hooked up to ing scientists found that even ing read when reading aloud Ihe article “Further adven- a fMRI to track their speed after a year post training the (Shaywitz,1996). However, tures of the incredible plas- and precision and had to activation in dyslexics their in dyslexia, parts of the brain tic brain”, FMRI scans were carry out tasks such as read- brain continued to the point responsible for reading are taken before and after reme- ing in print and processing that there were normal levels not properly connected re- dial training in 7 to 12 year figures. From the results, in the left parietal lobe. These sulting in issues with reading olds with and without de- scientists learned that more results prove neuroplastic- fluency (Nasr, 2007). velopmental dyslexia. This brain stimulation occurred ity of the brain. Not only did In the article “Dyslexia and training taught them to cor- in the basal ganglia, an area the remedial training increase the Brain: What Does Cur- relate consonants and vowels of the brain responsible for brain activity, but it strength- rent Research Tell Us?” the to sounds. As a result of the learning, in non-dyslexic ened the brain’s connections authors describe dyslex- training, the children expe- brains when processing the further improving the dys- ics have less brain matter rienced more brain activa- figure tasks than reading in lexic children’s ability to in their left parietotemporal tion and had an easier time print when compared to ado- read. Nadine Gaab, conducted area, which is responsible for performing language and lescents with dyslexia who fMRI scans on 45 children, 22 verbal memory by allowing reading tasks. For instance, experienced more activation of which had developmental the brain to remember num- the scans of dyslexic chil- in their brains when process- dyslexia and 23 did not, all bers. The authors suggest dren showed stimulation on ing reading print. When con- of these kids were 10 years that a lack of brain matter the left side of the brain in ducting the specified tasks, old. Along with Gaab, col- can cause issues with phono- the left parietal cortex and average readers had greater leagues at the Massachusetts logical awareness and audi- left inferior frontal gyrus. activation in the left side of Institute of Technology aided tory processing. Addition- In comparison, non-dyslexic the brain while the dyslexics this investigation of dyslexia, ally, dyslexics usually have a children had less stimulation “lack the specialization for the results showed that when lack of white matter causing in those specific areas in the language processing in their the kids heard speech sounds different regions of the brain brain. Finally, the post reme- left hemispheres [and] have the non-dyslexics experienced to have difficulty communi- dial training FMRI scans in less hemispherically differ- brain activity in their left fron- cating with each other. Also, dyslexics showed that they entiated activity”(Hayashi, tal lobe while dyslexics did according to brain imaging had activation in the right- 2014). This backs the idea of not. Gaab’s data backs those studies, right handed indi- hemisphere frontal an area the hemispheric tradeoff hy- of Paula Tallal from over 30 viduals with dyslexia have of the brain responsible for pothesis in which when per- years ago when dyslexia was a bigger left hemisphere of nonverbal tasks, temporal forming one task the brain correlated to issues with pro- their brain than right in non- regions, responsible for ver- has limited room to multi- cessing speech sounds. In dyslexics. This symmetrical bal tasks and anterior cin- task. Through this important similar research conducted difference is being studied gulate gyrus , playing a role research was able to disprove the Yale Center for the Study currently; researchers sus- in cognition and emotions, theory that dyslexia was cor- of Learning and Attention, 43 Sally Shaywitz the director for dyslexics (Hall, 2016). ing to go out of their way to student interviews. Based on took fMRI scans of dyslexic With the aid of information enhance a student’s learning previous research, adult dys- and average readers while and communications tech- experience. In addition, the lexics were able to cope with reading nonsense words. nologies (ICT), dyslexics teacher should provide alter- their reading issues by using According to the data, the can improve their education native exams with a multi- context clues and background study found increased brain and learning skills. Recent sensory approach or exempt knowledge. Although, adults stimulation located in the research done by scientists the student from these activi- with dyslexia may read at av- left hemisphere of the brain in Greece conducted a study ties. Teachers should try new erage level “had verba devel- in the parieto-temporal re- to identify whether adoles- and innovative techniques, oped a qualitatively different gion. Clearly, dyslexia does cents with dyslexics test as these are usually most ef- word decoding ability with not cover just one area of better on paper or digitally. fective and creativity will a less specific orthographic the brain, but instead im- The specified experiment be appreciated (The British knowledge and show diffi- pacts many. Now with ex- used 20 students, 10 dyslexic Dyslexia Association, 2016). culties in lower level decod- tensive research done in and 10 non-dyslexic (control Through the use of an inno- ing and spelling” (Olofsson, the field of dyslexia, hope- group), every child took both vative Android multimedia 2012). When testing the 95 fully new interventions and the computer and paper test app, special education pre- participants, each individual treatments will be available on solving math problems. service teachers can learn session ranged from 1 hour 1.5 (Valeo,2008). To avoid inconsistencies of specific techniques in- or hours. The findings expressed In consonance with profes- accuracy the students were der to help teach dyslexics that the students had low per- sionals working alongside scrutinized by teachers while how to further improve their formance reading skills when school age children who have taking the computer based reading skills. The app uses using precision and timing. dyslexia, sports can have an exam (Anestis, 2015). The background information to According to the participant immense impact on the lives data showed that all students explain the teaching strate- questionnaire, most dyslexics of dyslexics. The article, had improved scores on the gies and includes a videos of struggled with note taking and “Sports: Strengthening Their digital test compared to the specialized dyslexic teachers reading in both Swedish and Self Confidence and School paper one. However, the in- demonstrating each learning English. In addition, the par- Skills” suggests that children dividuals with dyslexia had tool. It is greatly effective ticipant interview gave verbal should “guide the choice … a 18 percent improvement for teaching children with answers allowing for a more but parents should help them on the electronic exam com- dyslexia because it includes kinesthetic view of interven- to figure out what they’re pared with the control who a multisensory approach. A tions and tools that helped good at and what they enjoy. only had a small improve- pilot study was conducted dyslexics such as using audio- (Hall, 2016)” Evidently, kids ment of 9 percent (Anestis, with 30 university students books, working collaborative- should participate in sports 2015). As you can see, the receiving a degree in spe- ly, taking notes, reducing or that they find fun. From their use of ICT with adolescents cial education, all university shortening the text for reading experiences in playing sports with dyslexia is a better test students took the same intro and looking for summaries to these children will learn taking method than the tra- course, a assessment was article in order to read a short important lessons of accep- ditional paper test (Anestis, given both before and after amount while still processing tance, teamwork, concentra- 2015). the utilization of the app. the most important informa- tion, and confidence. One Dyslexia can affect an in- Although, there were slight tion (Olofsson, 2012). dyslexic correlated rowing dividual’s musical abilities. issues with the software, the Dyslexics often struggle with to writing a paper because For instance, people with pilot study showed that the reading fluency, reverse letters, “both require planning ahead this neurological disorder pre-special education teach- and omit words. Additionally, and making sure you have may struggle with sight ers had more knowledge af- they have issues tracking the all your equipment before reading, remembering in- ter trying out the app. Not words on the page while read- a competition is like mak- structions, understanding only improving the teacher’s ing. As a result, many studies ing sure you have all your terms and have difficulty skills, the technology helped based off the visual elements research outlined before with organization.. How- them better understand dys- of reading have been conduct- you start writing” the stu- ever, many interventions can lexics on an emotional level ed on dyslexics. For instance, dent derived that sports and be utilized to help improve (Osman, 2015). research based on font color academics both require time the areas dyslexics struggle A Swedish study of dys- while reading on a computer management and extensive with. Always, it is important lexia in university students determined that text that is in focus. Clearly, physical ac- to have a teacher who under- assessed dyslexic adults, in dark letters on a light back- tivity is a useful intervention stands the condition not only more than 8 different tests in- ground is most readable for not only for your average in music, but in all classes cluding RAN, reading com- dyslexics. Specifically, this child; it is far more effective and teachers should be will- prehension, a teacher and study showed that text is most 44 readable when the computer read in natural environments display is at a high bright- (“What is eye tracking and ness (Pijpker). Additionally, how does it work?”, 2016). other studies found that sim- The eye tracker device will pler backgrounds are easier measure the following: to read (LDAU). Therefore, Gaze points and fixations: combinations of darker text Definitely the most promi- and a light backgrounds will nent metrics in eye tracking speed up the rate at which the literature. Gaze points con- text is read (Pijpker). How- stitute the basic unit of mea- ever, less research has been sure – one gaze point equals conducted relating to various one raw sample captured by font colors, backgrounds, the the eye tracker. Gaze points use of the finger for tracking, can be aggregated into fixa- spacing, and tracking with a tions, a period in which our note card on printed paper eyes are locked toward a spe- with tests of eye tracking cific object. and reading fluency (Blood- Areas of interest (AOI) and sworth, 1992). heat maps: To concentrate Goal of Study the analysis on specific -re The specified study will aim gions on the stimulus, areas to analyze the implementa- of interest (AOI) can be de- tion of specific visual ele- fined. Heatmaps visualize ments for dyslexics while fixation positions and - tem reading aloud. The research poral changes of fixations will determine if these ad- as an overlay on a specific aptations will improve their stimulus across different re- short paragraph aloud with Hypothesis B, Text back- fluency, assuage the - fre spondents. a printed paper. During the ground: The normal white quency of skipping of lines Fixation sequences and fur- midpoint of the full exersise background with black font and omitting words and will ther metrics: There are sev- aa 15 minute break will be will the most effective for track eye movements. eral ways to analyze gaze administered. dyslexics because lighter Materials and Methods positions and fixations, for Expected Results backgrounds and darker fonts The following study will use example you can analyze the Hypothesis A, Spacing: The are easier to read. 40 children, 20 dyslexic (10 fixation sequences and the spacing of 3.5 will be most Hypothesis C, Font color:The M, 10 F) and 20 “normal” performance of different re- effective in reducing errors blue or red font will most ef- readers as the control group gions in an image or a video because the further apart the fective for dyslexics while (10 M, 10 F), all participants with respect to the time of text is from each other and reading aloud. were included if they were first fixation (TTFF) or the therefore it is assumed that it Hypothesis D, Finger Track- 12-18 years of age. number of respondents look- will be harder to skip lines. ing: Finger tracking will help Participants were excluded ing toward a specified region if they presented with with (respondent count). specific neurological issues (“What is eye tracking and such as Autism, Aspergers, how does it work?”, 2016) Downs Syndrome and visual After each section, the eye issues. tracker must be recalibrated The mobile glasses light-pu- to ensure complete accuracy. pil eye-tracker device (GET) Also, following each ses- manufactured by Tobii will sion, the amount of time it be used to both record au- takes the kids to read will be dio and video in order help recorded for fluency. In addi- analyze the pupils data when tion, common reading errors reading aloud with different made by dyslexics will be visual elements. A mobile eye recorded (see chart 1). For tracker will be used to allow each visual implementation subjects to move freely and the partipants will read one 45 dyslexics read and reduce January 2017, from http://www. slow-reading-in-dyslexia-tied-to- 905. doi:10.1002/9781118432501. the frequency of skipping bdadyslexia.org.uk/educator/mu- disorganized-brain-tracts/ index sic-and-dyslexia Norton, E., Black, J., Stanley, L., Norton, E. S., Black, J. M., Stan- lines and losing track of their Dyslexia and the Brain: What Does Tanaka, H., Gabrieli, J., Sawyer, ley, L. M., Tanaka, H., Gabrieli, J. place. Current Research Tell Us?. (2015). C., & Hoeft, F. (2014). Functional D., Sawyer, C., & Hoeft, F. (2014). Hypothesis E, Notecard Ldonline.org. Retrieved 12 Decem- neuroanatomical evidence for the Functional neuroanatomical evi- Tracking:Note tracking will ber 2016, from http://www.ldon- double-deficit hypothesis of devel- dence for the double-deficit hy- aid dyslexics while reading line.org/article/14907 opmental dyslexia. Neuropsycho- pothesis of developmental dyslexia. Early Levels of Representation in logia, 61, 235–246. http://dx.doi. Neuropsychologia,61, 235-246.Op- aloud and reduce the fre- Reading , Johns Hopkins Univer- org/10.1016/j timal Colors to Improve Readability for quency of skipping lines and sity. (2016). Sites.krieger.jhu.edu. Behe, B. K., Fernandez, T., Hud- People with Dyslexia. (n.d.). Retrieved Retrieved 13 December 2016, from dleston, P. T., Minahan, S., Getter, K. May 23, 2017, from https://www.w3.org/ losing track of there place. WAI/RD/2012/text-customization/r11 http://sites.krieger.jhu.edu/mcclos- L., Sage, L., & Jones, A. M. (n.d.). References Pijpker, C. (n.d.). Reading Performance Anestis, E. (2015). The Effects key-lab/current-projects/early-lev- Practical Field Use of Eye-tracking Of Dyslexics With A Special Font And of Using Information and Com- els-of-representation-in-reading/ Devices for Consumer ... Retrieved A Colored Background - University Of munication Technologies Instead Hall, N. (2016). Sports: Strength- May 23, 2017, from http://www.hrt. Twente Student Theses. Retrieved May of Traditional Paper Based Test, ening Their Self Confidence and msu.edu/uploads/535/78629/ETT- 23, 2017, from http://essay.utwente. During the Examination Process, School Skills. Dyslexia.yale.edu. Methods-Horttech.pd nl/63321/ on Students with Dyslexia. Pro- Retrieved 5 December 2016, from Bloodsworth, J. G. (1992, Novem- Tips to Make Your Text Easier to Read. (n.d.). Retrieved May 23, 2017, from cedia Computer Science, 65, 168- http://dyslexia.yale.edu/article_ ber 30). Legibility of Print. Re- http://www.ldau.org/ld-facts/guidelines- print.php?a=PAR_SportsDyslexia trieved May 23, 2017, from https:// 175. http://dx.doi.org/10.1016/j. for-font-size-color/ procs.2015.09.105 Hayashi, Y. (2014). Uncharted eric.ed.gov/?id=ED355497 Träff, U., Desoete, A., & Passolunghi, M. Belluck, P. (2016). Study Says Dys- Waters in Dyslexia Research. Yale Desroches, A. S., Joanisse, M. F., C. (2016). Symbolic and non-symbolic lexia May Affect Listening Compre- Scientific Magazine. Retrieved 13 & Robertson, E. K. (2006). Spe- number processing in children with de- hension. Nytimes.com. Retrieved 7 December 2016, from http://www. cific phonological impairments in velopmental dyslexia. Learning and December 2016, from http://www. yalescientific.org/2014/12/unchart- dyslexia revealed by eyetracking. Individual Differences. doi:10.1016/j. nytimes.com/2011/08/02/health/ ed-waters-in-dyslexia-research/ Cognition,100(3). doi:10.1016/j. lindif.2016.10.010 What is eye tracking and how does research/02dyslexia.html Nasr, Susan. “Slow Reading In Dys- cognition.2005.09.001 it work? (2016, October 28). Re- lexia Tied To Disorganized Brain Diagnostic and statistical manual of British Dyslexia Association,. trieved May 23, 2017, from https:// (2017). Music and Dyslexia. Tracts”. Harvard Gazette. Nap. mental disorders: DSM-IV. (2000). imotions.com/blog/eye-tracking-work/ Bdadyslexia.org.uk. Retrieved 9 2007. Web. 8 Dec. 2016 http://news. Index. (2012). The Handbook of the harvard.edu/gazette/story/2007/12/ Neuropsychology of Language, 904-
Colony Collapse Disorder in Apiology, by Thea Barbelet (Sophomore)
the Natural Resources Con- factors of CCD also include all samples taken from wheat servation Service (Marks et the mite Varroa destructor, fields and about 47% of sam- al., 2005). “Colony Collapse the single-celled gut parasite ples taken from grasslands at Disorder”, a focus of many Nosema apis, and the para- the same time (Hladik et al., studies in the United States site Nosema ceranae (Pettis 2016). Bifenthrin was detect- and Europe, has been treated et al., 2013). ed in about 46% of all wheat as the main factor of these Professional and public ap- field samples from 2014, and losses (Dainat et al., 2009). plication of pesticides causes 30% of grassland samples Characteristics of Colony them to spread throughout (Hladik et al., 2016). Bees Collapse Disorder, or CCD, an entire ecosystem, affect- kept in apiaries show even include the departure of most ing surface water, ground- more detections of residue. worker bees in a hive, but water, soil, turf, and the air A combination of fluvali- not the queen or brood. This (Aktar et al., 2009). Thiame- nate, which may cause birth eventually results in failure thoxam, a likely human car- defects, and coumaphos was of the hive, as it cannot be cinogen used to coat seeds, detected in 83.1% of samples Honey bee, Apis mellifera, maintained (Cresswell et al., and bifenthrin, a possible from a North American study populations around the world 2011). The widespread use human carcinogen applied in (Mullin et al., 2010). Some have been steadily decreas- of pesticides, which include aerosol or granule form, are pesticides containing cou- ing, triggering public atten- neonicotinoids, a new type the most commonly detected maphos are restricted by the tion yet no solution (Dainat of nicotine-mimicking insec- in captured wild bees from US Environmental Protection et al., 2009). In the United ticide, fungicides, and her- both grasslands and wheat Agency due to its high fatality States, honey bees are consid- bicides are being researched fields in Colorado (Hladik et risk in humans While there ered to be one of the most im- as stressors of CCD (Hladik al., 2016). In 2014, thiame- are discrepancies, such as us- portant native pollinators by et al., 2016). Contributing thoxam was found in half of age of different pesticides and 46 different methods of applica- devastating viruses, includ- actly how much insecticides evaluation by Hill’s epidemiological cri- teria. Pest Management Science, 68(6). tion, between bees in an agri- ing acute bee paralysis vi- bees may bring back into the https://doi.org/10.1002/ps.3290 cultural setting compared to rus, Israeli paralysis virus, hive (du Rand et al., 2015). Dainat, B., Evans, J. D., Chen, Y. P., Gau- bees in a more urban setting, Kashmir bee virus, and de- If this research becomes thier, L., & Neumann, P. (2012). Dead or alive: deformed wing virus and Varroa hives feel the effects every- formed wing virus. Diseases available, solutions may destructor reduce the life span of winter where. are easily spread through- come with it. Since strictly honeybees. Applied and Environmental Microbiology, 78(4), 981–7. https://doi. Bees inadvertently bring out a weakened colony, and outlawing all pesticides may org/10.1128/AEM.06537-11 these insecticides back into can even affect nearby hives never happen, researchers Dave Goulson, Elizabeth Nicholls, Cris- the hive, which then con- (Sánchez-Bayo et al., 2016). should work to strengthen the tina Botías, E. L. R. (2015). Bee declines driven by combined stress from parasites taminates pollen, nectar, bee Therefore, a colony some- bees themselves. Decreased pesticides and lack of flowers. Sciencex- bread, jelly, and honey. Bees how isolated from human susceptibility to pesticides press. do have a detoxification chemicals can still be bur- would be a direct result of in- Du Rand, E. E., Smit, S., Beukes, M., Apostolides, Z., Pirk, C. W. W., & Nicol- system that can effectively dened by them. creased bee immunity. Modi- son, S. W. (2015). Detoxification mecha- modify dietary nicotine into Past studies are not without fying a bee’s detoxification nisms of honey bees (Apis mellifera) resulting in tolerance of dietary nicotine. harmless metabolites, but flaw. For example, Hladik system could also allow it to Nature Publishing Group. https://doi. when placed under exces- reported that more in-depth metabolize more neonicoti- org/10.1038/srep11779 sive stress, a loss of vitality studies are required to bet- noids, making their applica- Habitat, W., & Leaflet, M. (2005). Native Pollinators, (34), 1–10. occurs. Since there are bees ter explain the correlation tion harmless. From a dif- Hladik, M. L., Vandever, M., & Smalling, of different ages and of dif- between native bees and ferent standpoint, protecting K. L. (2016). Exposure of native bees for- ferent job classes, a correla- their behavior as well as a hive from foreign bodies aging in an agricultural landscape to cur- rent-use pesticides. Science of the Total tion between the amount of their biology compared to would limit only the work- Environment. https://doi.org/10.1016/j. labor and required energy to pathogens. In the future, me- ers who foraged to pesticide scitotenv.2015.10.077 Pettis, J. S., Lichtenberg, E. M., Andree, function arises. For example, tabolism rates and foraging exposure. Nectar, honey, M., Stitzinger, J., Rose, R., vanEngels- foragers are more exposed to distances of specific species pollen, and the worker bees dorp, D., … Pham-Delegue, M. (2013). pesticides because they leave need to be examined, since themselves would all have to Crop Pollination Exposes Honey Bees to Pesticides Which Alters Their Suscepti- the hive, but have a diet far bees may forage outside of be sanitized. Miticides that bility to the Gut Pathogen Nosema cera- higher in protein than work- their immediate area and kill only pathogens could nae. PLoS ONE, 8(7), e70182. https:// ers, and therefore can metab- become exposed to differ- be made, but may not be the doi.org/10.1371/journal.pone.0070182 Sánchez-Bayo, F., Goulson, D., Pennac- olize nicotine with less stress ent pesticides than those best approach. Beekeepers chio, F., Nazzi, F., Goka, K., & Desneux, (du Rand et al., 2005). found near the hive. Fungi- such as Randy Oliver con- N. (2016). Are bee diseases linked to pesticides? - A brief review. Environment Besides this limited detoxifi- cides and herbicides are not sider it best to wean colonies International. https://doi.org/10.1016/j. cation system, bees have no as lethal but may have other off of chemicals altogether, envint.2016.01.009 natural resistance to insec- side effects, which should be even organic or natural ones, ticides nor pathogens they evaluated. Since only live and once genetic changes have previously not encoun- specimens were taken, sub- occur, in terms of immunity tered (Goulson et al., 2015). lethal amounts of pesticides or strength, they can protect Pesticide exposure leaves were accounted for, not how themselves. bees more susceptible to much it actually takes to kill parasites such as Varroa de- a bee (Hladik et al., 2016). References structor, Nosema apis, and No studies have found the Cresswell, J. E., Desneux, N., & vanEn- gelsdorp, D. (2012). Dietary traces of Nosema ceranae which can tolerance capacity regarding neonicotinoid pesticides as a cause of then cause a multitude of pesticides in a hive, or ex- population declines in honey bees: An A Study on Single-domain Antibodies by Buu-Hac Nguyen (Sopho- more)
Single-domain Antibodies tibodies are comprised of nanobody, has a greater ten- et al., 2010). Although these (sdAb), also known as nano- a heavy chain homodimer dency to interact with parts nanobodies are free from light bodies, are antibody frag- rather than of light chains of the target that are not eas- chains, the nanobodies remain ments that are derived from (Saerens et al., 2010). Stud- ily recognized by conven- fully functional (Cortez-Reta- camelids (Cortez-Retamozo ies have shown the antigen- tional antibodies because of mozo et al., 2004). They are et al., 2004). Single-domain binding portion of the heavy- their smaller size, which al- stable, highly soluble, dis- antibodies are used from chain antibodies, which lows access to hard-to-reach tinctly specific and have high camelids because the an- constitutes the complete areas of the target (Saerens affinity (Cortez-Retamozo et 47 main antibodies onto bio- pamine transporter without antibodies in the dopamine sensor surfaces with the becoming impaired. transporter (DAT) (Ciliax use of multiple immobi- In addition, nanobodies have et al., 1995). The antibod- lization strategies (Pia et the ability to treat diseases, ies were used for immuno- al., 2015). The character- such as cancer, by attaching localization of transporter ization of the interaction to the tumor site and killing protein in rat brain (Ciliax et with the single-domain cancer cells (McMurphy et al., 1995). This study showed antibodies’ specific target al., 2014). Previous studies how the antibodies target- was done by Surface Plas- have shown that nanobodies ing the N-terminus and the mon Resonance (SPR) specific to carcinoembryon- C-terminus were specific to biosensors, which are ic antigen (CEA), a protein the expressed cloned DAT, used to monitor biomo- which appears in the blood recognized the transporter lecular interactions due of cancer patients, targeted protein and were sensitive to to their high sensitivity a distinct non-overlapping the excess homologous fusion and reproducibility (Pia epitope on the CEA mol- protein (Ciliax et al., 1995). et al., 2015). Through the ecule (Cortez-Retamozo et The results of this study prove immobilization methods, al., 2004). An experiment how the generation of specific scientists determined the revealed how the nano- DAT antibodies will allow al., 2004). kinetic binding constants body conjugate stopped the further characterization of the Through these favorable of the immobilized nanobod- growth of the tumor xeno- cellular as well as subcellular characteristics and their mi- ies for their antigens on the graft that was placed in nude localization of DAT protein nuscule size, scientists are different surfaces. This data mice (Cortez-Retamozo et (Ciliax et al., 1995). examining the potential uses was compared to traditional al., 2004). These re- of single-domain antibodies monoclonal antibodies with sults show that the in biosensing applications their kinetic binding con- minuscule size of Mentor: as well as treating diseases stants and showed that the single-domain an- through isolating, cloning, immobilized nanobodies tibodies alters their Dr. Matthias Quick, and selecting nanobodies were the most successful in biodistribution and Ph.D. with specificity to the desired capturing molecules (Pia et distinctly improves antigens (Cortez-Retamozo al., 2015). Furthermore, the access to epitopes et al., 2004). The results of results of this study also re- (Cortez-Retamozo these studies exhibit the pos- vealed immobilized nano- et al., 2004). The sible use of nanobodies in bodies with high affinities to improved access to the dopamine transporter, a their antigens and high resis- epitopes further illus- protein that forces the neu- tance to numerous denaturing trates the likelihood rotransmitter dopamine into agents, such as temperature. of using nanobod- presynaptic neurons. These characteristics portray ies in the dopamine To determine the potential the possibility of using nano- transporter because use of nanobodies in biosens- bodies in the dopamine trans- of their smaller size, ASSISTANT PROFES- ing and diagnostic assays, porter because the nanobody as compared to whole SOR of Clinical Neuro- is likely to identify the do- antibodies, which has scientists secured single-do- biology, Department of better ac- cess to the Psychiatry and Center dopamine for Molecular Recogni- transport- tion, er. Fur- Columbia University and thermore, College of Physicians a previ- and Surgeons. ous study shows the We are very grateful for applica- the dedication and help tion of of Dr. Quick. s p e c i f i c w h o l e 48 Compared to whole antibod- bodies portray potential use gle Domain Antibodies as a Powerful regulation in normal and disease states. Tool for High Quality Surface Plasmon Trends in Pharmacological Sciences, ies, nanobodies are signifi- on the dopamine transporter. Resonance Studies. 34(9) cantly smaller, which alters The use of nanobodies on the McMurphy et al, (2014), PLOS ONE, Ciliax et al, (1995), The Journal of the biodistribution of the sin- dopamine transporter exhibit 9, n.a., 1-8. The Anti-Tumor Activity Neuroscience, 75(3): 1714-1723. The of a Neutralizing Nanobody Targeting Dopamine Transporter: Immunochemi- gle-domain antibodies and promising advancements in Leptin Receptor in a Mouse Model of cal Characterization and Localization in improves access to the target. immunotherapy. Melanoma. Brain. Saerens, D., (2010), World journal of Ablynx’s Nanobody [Digital image]. References Nanobodies also show high biological chemistry, 1, n.a., 235-238. (2015, August 11). Retrieved Dec. & Cortez-Retamozo et al, (2004), Cancer affinities for their target and Isolation and optimization of camelid jan., 16, from http://seekingalpha.com/ Research, 4, n.a., 2853–2857, Efficient single-domain antibodies: Dirk Saerens’ article/3429536-ablynx-unlike-any-oth- remain stable under denatur- Cancer Therapy with a Nanobody- work on Nanobodies. er-biotech-company Based Conjugate. ing agents; with these supe- Vaughan, R. A., & Foster, J. D. (2013). Della Pia, E. A. & Martinez, K. L., Mechanisms of dopamine transporter rior characteristics, nano- (2015), PLOS ONE, 10, n.a., 1-17. Sin-
Developmental Dyslexia by Jason Uyaguari (Sophomore)
The study of dyslexia is very interactive specialization. origin and that it is primarily important to a lot of people. Where through repeated caused by the phonological Developmental dyslexia is phonological exercises they problems in the brain. The affecting about seven per- form reciprocal pathways in Alternate theory is about the cent of school age children the brain. There are many motor and auditory deficits (Peterson,2012). So advance- studies that link phonology that lead to phonological ments in the understanding as a factor if not a main cause deficits and then the rest is of dyslexia, Would benefit a of dyslexia.Through correla- very similar in both theories. lot of people.There are many tions and other data their re- ( Ramus, 2003). questions still at hand when lationship becomes more and Also found in a foundation- it comes to dyslexia. I want more clear. ally unique study. Subjects to answer a couple of those Children with dyslexia have from three different cultures key questions. Is there a cor- a different neuroanatomi- were taken for this study on relation between a poor un- cal makeup in their brains dyslexia. When given differ- derstanding of your own lan- compared to people without ent reading tasks and under a guages phonology and more it.Which basically means PET scan they show reduced severe effects of dyslexia? the structure in their brain activation in parts of the If so how can we use this to is different than a control’s brain that deal with reading With four different subgroups help people with Dyslexia? brain. In this study they took (left temporal and occipital (DYS older) (DYS younger), Phonology is described as a control group of people lobes). They show this as a (TD younger)and (TD older). the relationship between cer- and looked at their MRI’s result of different amounts As expected the results dif- tain speech sounds that make and and looked at their right of concentration of grey and fered but the similarity be- up important parts of a lan- hemisphere. You can see dif- white matter. This supports tween The (DYS older) and guage. ferences in concentration of the theory that dyslexia is (TD younger) was unusual. In many studies the phono- white and grey matter in dif- connected to the phonologi- They also had different con- logical factor usually has a ferent parts of it such as the cal and other reading parts of centrations of white and grey significant impact on -over corpus gyrus.The difference the brain. Explicitly demon- matter in their brains ,with all ability in the tests. If you in anatomy is shown to be strating that the anatomical the (DYS younger) and )DYS look at the neuropsychologia significant. (Cutini,2016). makeup, In someone with older) (Hoeft, 2010). (Hoeft,2010) research paper. New research has led scien- developmental dyslexia (Si- Scientists Agree there’s a pho- Then you will see how the tists believe that a new side lani, 2005). nological factor to dyslexia, subject’s scores in the pho- effect of dyslexia is sensory People with dyslexia devel- and they want to compare nology tests correlate with and motor deficits called sen- op differently than people in people with dyslexia to their their other ones. Also in the sorimotor syndrome. This has a large study was conducted age matched controls in a the remediations paper and led to two theories in the re- with children with develop- series of tests from counting implications with dyslexia search of dyslexia . One that mental dyslexia in a number syllables to rhyming words. (kershner,2012). They speak the the reading impairment is of tests with phonological It’s determined that they have of a remediation plan called rooted in the left peri-sylvian tests and and reading tests. 49 deficits in performing tasks If someone gave me a chance cessing deficit linked to dyslexia (Farmer, M.E. & Klein, R.M. Psychon like this . With the phonol- to research developmen- Bull Rev (1995) 2: 460. doi:10.3758/ ogy of their languages. Also tal dyslexia With funding.I BF03210983) found is that training the would try to determine the phonological aspect of it im- extent of the phonoligical proves visual dyslexia and factor in dyslexia.How much helps with their reading and does it effect the reading and writing scores in their tasks writing? How does their ana- (Colling 2016). tomical makeup differ from Dyslexic readers react dif- people in the way that, people ferently to different number use the parts of the brain dif- of oscillations (Hz) ex: there ferently than variables? And is a negative correlation in most importantly How much phonological skills when can be remediated through alpha oscillations are used Phonological treatment such contrastingly there is a posi- as interactive specialisation. tive correlation when beta But there is still a lot more oscillations are used. This is work to be done on research one of the more clearer ex- in dyslexia . amples of the effects phonol- ogy has on this condition.( References De vos,2016) De vos, Atypical neural synchronization to speech envelope modulations in dys- But there’s also been another lexia ,(2017), Brain and language, 164, more overlooked aspect of 106-117, http://dx.doi.org/10.1016/j. bandl.2016.10.002) dyslexia, which is juggling Cutini, S., Szűcs, D., Mead, N., Huss, multitasking in the brain. In a M., & Goswami, U. (2016, December). study 23 teens ( age 13) were Atypical right hemisphere response to slow temporal modulations in children taken with their age matched with developmental dyslexia. Retrieved controls were asked to per- April 25, 2017, from https://www.ncbi. form single tasks like count- nlm.nih.gov/pubmed/27520749 4 Neural encoding of the speech en- ing backwards. But when velope by children with develop- asked to do a dual task para- mental dyslexia ( power, Brain and Language,2016 Centre for Neurosci- digm (simultaneously doing ence in Education,http://www.sci- tasks). 19 of the 23 dyslexic encedirect.com/science/article/pii/ kids showed a lot of impair- S0093934X15301681) 5 Shared temporoparietal dysfunction ment doing the tasks.This in dyslexia and typical readers with exposes the intricacy of dys- discrepancy in High IQ (Hoeft ,trends lexia and how it makes even in neuroscience,2016 volume 5 issue 4 http://www.sciencedirect.com/science/ how we foundationally think article/pii/S2211949316300503) different (Fawcett ,1990). 6 .Review and implications for reme- diation( Walker,The Neurophysiology However There has been of Dyslexia,2004,pages 45-55 http:// research in methods to help www.tandfonline.com/doi/abs/10.1300/ with the deficits of dyslexia. J184v10n01_04) 7 Automaticity a new framework for there appear to be some frac- dyslexia research (Cognition.Faw- tional ways to help dyslexic cett.1990.volume 35 issue 2 http:// people. This paper offers a www.sciencedirect.com/science/article/ pii/001002779090013A) phonological approach to it 8 Developmental dyslexia specific pho- called interactive specialisa- nological deficit or general sensorimo- tor dysfunctio(Ramus,Neurobiology,20 tion. Under the system they 03, volume8 https://www.ncbi.nlm.nih. try to make new pathways gov/pubmed/12744976) of reciprocal competitive ar- 9 .Brain abnormalities underlying al- tered activation in dyslexia: a voxel eas. This has been proved to based morphometry study ( Silani, help dyslexic readers with VBM study,2005 volume 10,https://ac- core problems in testing ademic.oup.com/brain/article-lookup/ doi/10.1093/brain/awh 579) (Kershner, 2016). 10 The evidence for a temporal pro- 50 Acknowledgments and help. their time to ensure that the University at Albany. This program would not • Dr. Emma Guttman, students get the best possible be possible without: Ph.D. Mount Sinai Medi- experience when they work Members of the School In- cal School, ICahn Medi- on site, in labs and during the stitutional Review Board: Mentors and Scientists. cal Institute. Professor school year. Dermatology; Assoicate Thank you for taking the Thank you to all of the sci- Professor Medicine, Administrators, Teachers time to review the work of entists who have taken our Clinical Immunology. and Staff. students’ projects througout high school students under Mount Sinai Medical the year. their wings and given them School, ICahn Medical • Mr. Joseph Hochreiter, unprecedented possibilities Institute. We are grateful Superintendent • Mr. James Mackin, to access genuine scientific to Dr. Guttman for her • Dr. Margaret Ruller, Principal. research, to act as profes- • Dr. Adam Zeman, MD, Executive Director of • Mrs. Tina Wilson, As- sionals and to express their Professor of Cognitive Curriculum and Instruc- sistant Principal talents and creativity in their andBehavioral Neurol- tion. • Mrs. Ann-Marie Gal- projects. ogy. University of Exeter, • Mr. Enrique Catalan, lagher, Science Teacher. Medical School, Exeter, Assistant Superintendent • Mrs. Eileen Cancro, • Dr. Matthias Quick, UK.We are very grate- for Business. Science Teacher Ph.D. Assistant Professor, ful to Dr. Zeman for his • Mr. James Mackin • Mrs. Kathryn Frost, Department of Psychiatry dedication and help Principal. Nurse. and Center for Molecular • Dr. Stuart A. Newman, • Mrs. Tina Wilson, As- • Dr. Matthias Quick, Recognition, Columbia Ph.D. Professor of Cell sistant Principal. Assistant Professor of University, College of Biology and Anatomy. • Mrs. Laura Neier, As- Clinical Neurobiology Physicians and Surgeons. New York Medical Col- sistant Principal. Dr. Quick served on our lege, Valhalla, NY. We • Dr. Mathew Swerdloff, Institutional Review are grateful to Dr. New- Executive Director of Board and guided other man for his help Educational Support science research students • Dr. Patric K. Stanton, Services. through their projects Ph.D. Professor of Cell • Ms. Beth Gruber, HH- throughout the years. Dr. Biology and Anatomy, CEF. Quick served a judge in New York Medical Col- • Ms. Laurie Small and all the major competi- lege, Valhalla, NY. We Ms. Jill Wheeler for tions of the tri-county are grateful to Dr. Stanton their sustaining support. area, hereby gaining for his help. • Ms. Clare Carey for important knowledge of • Dr. Ryan Baker, Ph.D., catering services the competition proces. Associate Professor of • The custodial staff. • Dr. Zhong Pan, Ph.D. Cognitive Studies in Edu- Post Doctoral Associate, cation. Teachers College, Science Research Col- New Jersey Institute of Columbia University, NY leagues: Technology, for welcom- ing Isabella Brizzi in his Sponsors: • Mr. Michael Blueglass, lab. We want to thank the Hen- Yorktown High School • Dr. K.V. Lakshmi, Ph.D. drick Hudson Community • Mr. Angelo Piccirillo, Associate Professor Educational Foundation (HH- Ossining High School Chemistry and Chemical CEF) for its on-going fund- • Mrs.Valerie Holmes, Biology. Scientific Direc- ing of the science research Ossining High School. tor of the Baruch ’60 program. • Mrs. Donna Light Center for Biochemical Donovan, Croton-on- Solar Energy Research . Parents Hudson. Rensselaer Polytechnic This program would not be • Mr. Leonard Behr Institute. Troy, NY. We successful without the sup- and Dr. Daniel Wulff, are grateful to Dr. Lak- port of the students’ families, Science Research in the shmi for her dedication who sacrifice so much of High School Program, 51 52 For more information on the Science Research Program, Contact Dr. Christine Rogers, Ph.D. [email protected]