DOCSLIB.ORG

An Assessment of the Effect of X-Ray Radiation on DNA Marker Profiles Obtained from Human Teeth

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Assessment of the Effect of X-Ray Radiation on DNA Marker Profiles Obtained from Human Teeth University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Masters Theses Graduate School 8-2013 An Assessment of the Effect of X-ray Radiation on DNA Marker Profiles Obtained from Human Teeth Erin Lynn Knapp [email protected] Follow this and additional works at: https://trace.tennessee.edu/utk_gradthes Part of the Biological and Physical Anthropology Commons Recommended Citation Knapp, Erin Lynn, "An Assessment of the Effect of X-ray Radiation on DNA Marker Profiles Obtained from Human Teeth. " Master's Thesis, University of Tennessee, 2013. https://trace.tennessee.edu/utk_gradthes/2444 This Thesis is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Masters Theses by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a thesis written by Erin Lynn Knapp entitled "An Assessment of the Effect of X-ray Radiation on DNA Marker Profiles Obtained from Human Teeth." I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Master of Arts, with a major in Anthropology. Graciela Cabana, Major Professor We have read this thesis and recommend its acceptance: Benjamin M. Auerbach, Lee M. Jantz Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) An Assessment of the Effect of X-ray Radiation on DNA Marker Profiles Obtained from Human Teeth A Thesis Presented for the Master of Arts Degree The University of Tennessee, Knoxville Erin Lynn Knapp August 2013 ii Acknowledgements First, I would like to thank my advisor, Dr. Graciela Cabana, for her support, ideas, and editing prowess. I also am thankful for the help and support from my committee members, Dr. Benjamin Auerbach and Dr. Lee Jantz. I would also like to thank everyone who attended the lab meetings at the Molecular Anthropology Lab over the last few semesters. You have all been great sounding boards. I also need to thank Dr. Michael Keene and my writing coach Ellen Rideout for helping me revise and revise again. I thank the Forensic Anthropology Center and the William M. Bass Endowment for the funding, materials, and ability to perform this thesis research. I thank Dr. Randall Pearce, DDS for providing the tooth samples to the University of Tennessee Department of Anthropology. I also thank the Molecular Anthropology Labs and Molecular Biology Resource Facility for allowing me the use of the facilities to process and analyze my samples. Many thanks to Joseph A. May and Veronica Brown for help analyzing my samples and learning how the fragment analyzer machine and software work. Thanks to Cathy Graves, R.T. at the UT Student Health Center for helping me X-ray my samples. Finally, thanks to my friends and family for encouraging me in every way to pursue my graduate education. iii Abstract X-ray radiation is known to destroy cells and damage DNA, yet human remains from forensic anthropology cases are routinely exposed to X-ray radiation as part of the documentation and evidence collection process. If X-ray radiation significantly impacts the quality of DNA extracted from human remains in forensic cases, then the validity of a resulting genetic profile is called into question. To better understand how X-ray radiation affects DNA profiles, specifically profiles consisting of short tandem repeat (STR) markers, this study followed standard forensic X-ray and genetic profiling protocols to obtain DNA profiles on individual molar teeth, before and after they were exposed to a single X-ray dosage event. The results of the study demonstrate that X-ray radiation did indeed affect DNA profiles, in two ways. First, the total number of DNA markers recovered pre-and post-X-ray radiation decreased significantly between the pre- (control) and post-(experimental) irradiation. Second, the overall amount of DNA per genetic marker recovered was significantly reduced, as measured by Relative Fluorescence Units (RFUs). Interestingly, contrary to expectations, the DNA markers recovered did not exhibit significant shortened fragments lengths post- irradiation, otherwise known as “allelic stutter.” Thus, it seems that X-ray exposure tended to damage DNA marker variants to such an extent that DNA markers were completely unrecoverable post- irradiation, rather than simply damaged to a point of producing allelic stutter. Importantly, X-ray radiation altered DNA marker profiles of individual cases before and after X-ray radiation. The post-radiation sample exhibited a significant amount of “allelic dropout,” leading to a condition known as “false homozygosity,” when one only DNA variant for a given locus is represented in a genetic profile instead of the two different variants that may actually be found in the sample. These results indicate further research is required to understand iv the stochastic effects of X-ray irradiation on DNA, and suggest that forensic samples undergo DNA analysis prior to exposure to X-ray radiation. v Table of Contents Introduction ..................................................................................................................................... 1 Chapter 1: Background ................................................................................................................... 7 DNA Structure............................................................................................................................. 8 Normal Degradation and Decay of DNA .................................................................................. 12 Short Tandem Repeats (STRs) .................................................................................................. 16 CODIS Markers ..................................................................................................................... 21 STR Genotyping: Relevant Issues............................................................................................. 23 PCR – Polymerase Chain Reaction ....................................................................................... 24 Allelic Stutter ......................................................................................................................... 25 Non-Template Addition ......................................................................................................... 29 Allele Dropout and Null Alleles ............................................................................................ 30 Microvariants and Off-Ladder Alleles .................................................................................. 31 Low Template DNA (LT DNA)................................................................................................ 32 Analytical Methods................................................................................................................ 34 X-rays ........................................................................................................................................ 37 DNA Damage from X-Ray ....................................................................................................... 38 Single Strand Breaks (SSBs) ................................................................................................. 39 Double Strand Breaks (DSBs) ............................................................................................... 40 Damaged Bases...................................................................................................................... 42 Forensic X-Ray Protocols ......................................................................................................... 43 Chapter 2: Research Questions, Study Design, and Methods ....................................................... 46 Research Questions ................................................................................................................... 46 Research Study Design.............................................................................................................. 47 Samples .................................................................................................................................. 47 Study Workflow .................................................................................................................... 48 Experimental Methods .............................................................................................................. 50 Contamination Controls ......................................................................................................... 51 Extraction Protocols .............................................................................................................. 53 PCR Set-Up and Amplification ............................................................................................. 55 DNA Visualization ................................................................................................................ 56 vi Experimental Sample Treatment: X-ray radiation................................................................. 57 Fragment Analysis ................................................................................................................. 58 Statistical Design & Methods ...................................................................................................
Load more

Recommended publications
  • Annotation-1 Annotation-1
    Annotation-1 Baseline Resuscitation Normal Saline Resuscitation PFP Shock Annotation-1 Aminoacids Arginine and proline metabolism Carnitine and fatty acid metabolsim Glutamate metabolism Glycerophospholipid biosynthesis Glycolysis and sugars GSH homeostasis GSH homeostasis/Glyoxlate Hexosamine Indole and Tryptophan Nucleotides Other Panthothenate metabolism Pentose Phosphate Pathway Serine biosynthesis and one-carbon metabolism Signaling Sulfur metabolism TCA cycle urea cycle relative row min row max Baseline_14 Baseline_16 Baseline_13 Baseline_15 Baseline_22 Baseline_2 Baseline_12 Baseline_3 Baseline_4 Baseline_9 Baseline_7 Baseline_8 Shock_13 Shock_12 Shock_15 Shock_22 Shock_14 Shock_16 Shock_2 Shock_3 Shock_7 Shock_4 Shock_8 Shock_9 Res_NS_14 Res_NS_13 Res_NS_16 Res_NS_12 Res_NS_22 Res_NS_15 Res_PFP_2 Res_PFP_3 Res_PFP_7 Res_PFP_4 Res_PFP_8 Res_PFP_9 Annotation-1 Annotation-1 Annotation Annotation-1 L-Arginine Aminoacids L-Isoleucine Aminoacids Leucine Aminoacids L-Cysteine Aminoacids L-Alanine Aminoacids L-Aspartate Aminoacids L-Glutamate Aminoacids L-Glutamine Aminoacids L-Histidine Aminoacids L-Lysine Aminoacids L-Methionine Aminoacids L-Tyrosine Aminoacids L-Asparagine Aminoacids L-Threonine Aminoacids L-Cystine Aminoacids L-Serine Aminoacids L-Proline Aminoacids L-Valine Aminoacids L-Tryptophan Aminoacids Glycine Aminoacids L-Kynurenine Aminoacids L-Phenylalanine Aminoacids CMP Nucleotides 6-Hydroxynicotinate Nucleotides 5-6-Dihydrouracil Nucleotides AMP Nucleotides dAMP Nucleotides GMP Nucleotides Guanine Nucleotides 2-5-Dihydroxypyridine
    [Show full text]
  • 35 Disorders of Purine and Pyrimidine Metabolism
    35 Disorders of Purine and Pyrimidine Metabolism Georges van den Berghe, M.- Françoise Vincent, Sandrine Marie 35.1 Inborn Errors of Purine Metabolism – 435 35.1.1 Phosphoribosyl Pyrophosphate Synthetase Superactivity – 435 35.1.2 Adenylosuccinase Deficiency – 436 35.1.3 AICA-Ribosiduria – 437 35.1.4 Muscle AMP Deaminase Deficiency – 437 35.1.5 Adenosine Deaminase Deficiency – 438 35.1.6 Adenosine Deaminase Superactivity – 439 35.1.7 Purine Nucleoside Phosphorylase Deficiency – 440 35.1.8 Xanthine Oxidase Deficiency – 440 35.1.9 Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency – 441 35.1.10 Adenine Phosphoribosyltransferase Deficiency – 442 35.1.11 Deoxyguanosine Kinase Deficiency – 442 35.2 Inborn Errors of Pyrimidine Metabolism – 445 35.2.1 UMP Synthase Deficiency (Hereditary Orotic Aciduria) – 445 35.2.2 Dihydropyrimidine Dehydrogenase Deficiency – 445 35.2.3 Dihydropyrimidinase Deficiency – 446 35.2.4 Ureidopropionase Deficiency – 446 35.2.5 Pyrimidine 5’-Nucleotidase Deficiency – 446 35.2.6 Cytosolic 5’-Nucleotidase Superactivity – 447 35.2.7 Thymidine Phosphorylase Deficiency – 447 35.2.8 Thymidine Kinase Deficiency – 447 References – 447 434 Chapter 35 · Disorders of Purine and Pyrimidine Metabolism Purine Metabolism Purine nucleotides are essential cellular constituents 4 The catabolic pathway starts from GMP, IMP and which intervene in energy transfer, metabolic regula- AMP, and produces uric acid, a poorly soluble tion, and synthesis of DNA and RNA. Purine metabo- compound, which tends to crystallize once its lism can be divided into three pathways: plasma concentration surpasses 6.5–7 mg/dl (0.38– 4 The biosynthetic pathway, often termed de novo, 0.47 mmol/l). starts with the formation of phosphoribosyl pyro- 4 The salvage pathway utilizes the purine bases, gua- phosphate (PRPP) and leads to the synthesis of nine, hypoxanthine and adenine, which are pro- inosine monophosphate (IMP).
    [Show full text]
  • Clinical Symptoms of Defects in Pyrimidine Metabolism
    ClinicalClinical symptomssymptoms ofof DefectsDefects inin pyrimidinepyrimidine metabolismmetabolism Birgit Assmann Department of General Pediatrics Universtiy Children‘s Hospital Düsseldorf, Germany Overview • Biosynthesis: UMP Synthase • Degradation: –– PyrimidinePyrimidine 55‘‘--Nucleotidase(UMPNucleotidase(UMP--Hydrolase)Hydrolase) – [Thymidine-Phosphorylase, mitochondrial] –– DihydropyrimidineDihydropyrimidine DehydrogenaseDehydrogenase –– DihydropyrimidinaseDihydropyrimidinase –– UreidopropionaseUreidopropionase HCO3+gluNH2 carbamoyl-P orotic acid OMP OPRT UMP OD UMPS UMPSUMPS == uridinemonophosphateuridinemonophosphate synthasesynthase Bifunctional enzyme (one gene): a) Orotate phosphoribosyl transferase (OPRT) b) Orotidine decarboxylase (OD) UMPS deficiency • = Hereditary orotic aciduria Hallmarks:Hallmarks: - MegaloblasticMegaloblastic anemiaanemia inin infantsinfants >> IfIf untreateduntreated:: FailureFailure toto thrivethrive PsychomotorPsychomotor retardationretardation • Therapy: uridine (≥100-150 mg/kg/d) Defects of pyrimidine degradation • Pyrimidine 5‘-Nucleotidase deficiency - chronic hemolytic anemia + basophilic stippling of erythrocytes • Thymidine phosphorylase deficiency = MNGIE=Mitoch. NeuroGastroIntestinal Encephalomyopathy Mitochondrial disorder with elevatedelevated urinaryurinary thymidinethymidine excretionexcretion HCO3+gluNH2 carbamoyl-P orotic acid OMP TMP UMP UMPS thymidine cytosolic 5‘- uridine Thym. Nucleotidase phosphor ylase thymine uracil Pyrimidine 5‘-Nucleotidase- SuperactivitySuperactivity • Existence
    [Show full text]
  • Experimental Investigations of Blunt Force Trauma in the Human Skeleton
    EXPERIMENTAL INVESTIGATIONS OF BLUNT FORCE TRAUMA IN THE HUMAN SKELETON By Mariyam I. Isa A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Anthropology—Doctor of Philosophy 2020 ABSTRACT EXPERIMENTAL INVESTIGATIONS OF BLUNT FORCE TRAUMA IN THE HUMAN SKELETON By Mariyam I. Isa In forensic anthropology, skeletal trauma is a growing area of analysis that can contribute important evidence about the circumstances of an individual’s death. In bioarchaeology, patterns of skeletal trauma are situated within a cultural context to explore human behaviors across time and space. Trauma analysis involves transforming observations of fracture patterns in the human skeleton into inferences about the circumstances involved in their production. This analysis is based on the foundational assumption that fracture behavior is the nonrandom result of interactions between extrinsic factors influencing the stresses placed on bone and intrinsic factors affecting bone’s ability to withstand these stresses. Biomechanical principles provide the theoretical foundation for generating hypotheses about how various extrinsic and intrinsic factors affect the formation of fracture patterns, and about how these factors can be read from fracture patterns. However, research is necessary to test and refine these hypotheses and, on a more basic level, to document the relationships between “input” variables of interest and fracture “outputs.” One research approach involves the use of forensic and/or clinical case samples. Case- based approaches are important because they provide data from real scenarios and contexts that may be similar to those encountered in unknown cases. However, a limitation is that input variables are not directly measured or controlled and therefore cannot be precisely known.
    [Show full text]
  • Lc and Lc-Free Mass Spectrometry Applications in Non-Targeted Metabolomics for Disease Detection and Early Prediction
    LC AND LC-FREE MASS SPECTROMETRY APPLICATIONS IN NON-TARGETED METABOLOMICS FOR DISEASE DETECTION AND EARLY PREDICTION A Dissertation Presented to The Academic Faculty by Xiaoling Zang In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Chemistry and Biochemistry Georgia Institute of Technology August 2018 COPYRIGHT © 2018 BY XIAOLING ZANG LC AND LC-FREE MASS SPECTROMETRY APPLICATIONS IN NON-TARGETED METABOLOMICS FOR DISEASE DETECTION AND EARLY PREDICTION Approved by: Dr. Facundo M. Fernández, Advisor Dr. Ronghu Wu School of Chemistry and Biochemistry School of Chemistry and Biochemistry Georgia Institute of Technology Georgia Institute of Technology Dr. María E. Monge, Co-advisor Dr. Matthew Torres Centro de Investigaciones en School of Biology Bionanociencias (CIBION) Georgia Institute of Technology Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Dr. Julia Kubanek Dr. Mark Styczynski School of Chemistry and Biochemistry School of Chemical and Biomolecular Georgia Institute of Technology Engineering Georgia Institute of Technology Date Approved: July 23, 2018 Never give up on what you really want to do. The person with big dreams is more powerful than one with all the facts. -Albert Einstein, The World as I See It1 ACKNOWLEDGEMENTS There are many people who have helped and supported me a lot during my 6-year Ph.D. life at Georgia Tech. First of all, I want to express my deepest gratitude to my advisor, Dr. Facundo M. Fernández, for his guidance, support, patience and encouragement during my whole Ph.D. study. Under his mentorship over the last 6 years, I have gained so much knowledge and experience in mass spectrometry and have grown to become more independent and capable in handling the research projects.
    [Show full text]
  • Behavior of Activities of Thymidine Metabolizing Enzymes in Human Leukemia-Lymphoma Cells1
    [CANCER RESEARCH 49. 1090-1094. March I, 1989] Behavior of Activities of Thymidine Metabolizing Enzymes in Human Leukemia-Lymphoma Cells1 Taiichi Shiotani, Yasuko Hashimoto, Terukazu Tanaka, and Shozo Irino First Department of Internal Medicine, Kagawa Medical School, Ikenobe, Miki, Kagawa, 761-07, Japan ABSTRACT 7). These observations indicate the importance of this catabolic enzyme for dThd utilization. Thymidylate, an important pre The behavior of the activities of thymidine metabolizing enzymes, cursor of DNA synthesis, also may be produced by the de novo dihydrothymine dehydrogenase (EC 1.3.1.2) and thymidine phosphoryl- pathway through dTMP synthase. The correlation between cell ase (EC 2.4.2.4) for thymidine degradation, thymidine kinase (EC proliferation and dThd kinase (3, 4, 6, 8, 9) or dTMP synthase 2.7.1.75) and thymidylate synthase (EC 2.1.1.45) for DNA synthesis, was elucidated in cytosolic extracts from normal human lymphocytes and (8, 10, 11) has been demonstrated. The enhanced capacity for 13 human leukemia-lymphoma cell lines. In the normal human lympho the salvage pathway in leukemia (12, 13) appears to limit the cytes, the activities of dihydrothymine dehydrogenase, thymidine phos- antitumor effectiveness of antimetabolites of de novo pyrimidine phorylase, thymidine kinase, and thymidylate synthase were 6.88, 796, biosynthesis. The enzymic capacities of the de novo and salvage 0.30, and 0.29 nmol/h/mg protein, respectively. In leukemia-lymphoma pathways and dThd catabolism have not been determined si cell lines, the activities of synthetic enzymes, thymidine kinase, and multaneously in human leukemia-lymphoma cells. Therefore, thymidylate synthase, increased two- to 79-fold and 22- to 407-fold of the elucidation of the behavior of the enzymic capacities in the the normal lymphocyte values.
    [Show full text]
  • 73Rd Aafs Annual Scientific Meeting
    AMERICAN ACADEMY OF FORENSIC SCIENCES 73RD AAFS ANNUAL SCIENTIFIC MEETING PROGRAM • FEBRUARY 2021 WELCOME MESSAGE Welcome to the 73rd American Academy of Forensic Sciences Annual Scientific Meeting. We are 100% virtual this year and it is my pleasure and excitement to greet each and every one of you. While we could not be in Houston, we have planned a jammed packed week of science, collegial interactions, collaborations, learning, social networking, and just plain fun! The Academy has nearly 6,500 members representing 70 countries. We usually meet annually in the U.S., but this year we are meeting virtually and worldwide for the first time. I cannot wait to see how many locations across the globe will be represented by our attendees. Jeri D. Ropero-Miller, PhD 2020-21 AAFS President Our meeting theme this year, One Academy Pursuing Justice through Truth and Evidence, has fueled the culture of the Academy since its inception. It has also encouraged more than 1,000 presentations for this week with over 560 oral, more that 380 posters, and countless presenters in the 18 workshops, and special sessions. The Exhibit Hall will be accessible to attendees the entire week. Don’t miss out on all the latest products and technology available to the forensic science industry. You also will want to participate in the Gamification activity by going on a virtual scavenger hunt to earn points towards winning some fun prizes. Don’t forget to visit the online AAFS store between sessions for your chance to purchase meeting apparel. I cannot thank everyone enough for all the effort, dedication, and support for making this virtual event memorable for all.
    [Show full text]
  • Possible Prediction of Adverse Reactions to Pyrimidine Chemotherapy from Urinary Pyrimidine Levels and a Case of Asymptomatic Adult Dihydropyrimidinuria1
    Vol. 2, 1937-1 941, December 1996 Clinical Cancer Research 1937 Possible Prediction of Adverse Reactions to Pyrimidine Chemotherapy from Urinary Pyrimidine Levels and a Case of Asymptomatic Adult Dihydropyrimidinuria1 Katsuo Hayashi,2 Kiyoshi Kidouchi, INTRODUCTION Satoshi Sumi, Masashi Mizokami, Etsuro Onto, Pyrimidine chemotherapy agents such as 5-FU3 are used widely but can occasionally cause serious adverse reactions. In Kazunoni Kumada, Ryuzo Ueda, and pyrimidine metabolism, uracil and thymine are first converted to Yoshino Wada dihydropyrimidines (dihydrouracil and dihydrothymine) by Departments of Medicine [K. H., K. Ku.] and Pediatrics [K. Ki.], DPD and then are metabolized to 3-ureidopropionic acid and Nagoya City Higashi General Hospital, 2-23 Wakamizu 1-chome, 3-ureidoisobutyric acid, respectively, by dihydropyrimidinase. Chikusa-ku, Nagoya 464, Japan, and Department of Pediatrics [S. S., These compounds are converted subsequently into 3-alanine Y. W.] and Second Department of Medicine [M. M., E. 0., R. U.], Nagoya City University Medical School. Nagoya, Japan and -arninoisobutyric acid, respectively ( 1). Because about 80% of an administered dose of 5-FU is degraded by this pathway, there is a possibility of adverse reactions occurring as ABSTRACT a result of DPD or dihydrophrimidinase deficiency. The value of Deficiency of dihydropyrimidine dehydrogenase or di- measuring peripheral blood monocyte DPD activity before ad- hydropyrimidinase, enzymes that catalyze the breakdown of ministering 5-FU has been suggested in Western countries (2- pyrimidine chemotherapy agents such as 5-fluorouracil, 6), but DPD deficiency has not been reported in Japan. may cause serious adverse reactions to these agents. We Using a method that permits analysis of dihydrouracil and attempted to establish the reference range for urinary pyri- uracil in small volumes of urine, we previously screened Japa- midines in adults to detect individuals with abnormal py- nese infants for abnormalities of pyrimidine metabolism and rimidine metabolism.
    [Show full text]
  • Purine Metabolism Regulates DNA Repair and Therapy Resistance in Glioblastoma
    ARTICLE https://doi.org/10.1038/s41467-020-17512-x OPEN Purine metabolism regulates DNA repair and therapy resistance in glioblastoma Weihua Zhou1,14, Yangyang Yao1,2,14, Andrew J. Scott1,3,14, Kari Wilder-Romans1, Joseph J. Dresser1, Christian K. Werner 1, Hanshi Sun1, Drew Pratt4, Peter Sajjakulnukit 5, Shuang G. Zhao1, Mary Davis1, Barbara S. Nelson5, Christopher J. Halbrook5, Li Zhang5, Francesco Gatto 6, Yoshie Umemura3,7, Angela K. Walker8, Maureen Kachman 8, Jann N. Sarkaria 9, Jianping Xiong2, Meredith A. Morgan1,3, Alnawaz Rehemtualla1,3, Maria G. Castro 3,10,11, Pedro Lowenstein 3,10,11, Sriram Chandrasekaran 3,12, ✉ Theodore S. Lawrence1,3, Costas A. Lyssiotis 3,5,13 & Daniel R. Wahl 1,3 1234567890():,; Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guany- lates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, adminis- tration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.
    [Show full text]
  • ABSTRACT the Journal of Forensic Radiology and Imaging Was
    ABSTRACT The Journal of Forensic Radiology and Imaging was launched in 2013 with the aim to collate the literature and demonstrate high-quality case studies on image-based modalities across the forensic sciences. Largely, the focus of this journal has been on the transmissive aspect of forensic imaging, and therefore a significant number of high-quality case studies have been published focusing on computed tomography and magnetic resonance imaging. As a result, the ‘and imaging’ aspect is often neglected. Since 2013, technology has fundamentally evolved, and a number of new techniques have become accessible or have been demonstrated as particularly useful within many sub-disciplines of forensic science. These include active and passive surface scanning techniques, and the availability of three-dimensional printing. Therefore, this article discusses non-contact techniques, their applications, advantages, and considerations on the current state of play of imaging in forensic science. HIGHLIGHTS • We discuss the application of 3D imaging within the context of forensic science. • We highlight the available documentation techniques assessing their advantages and disadvantages. • This article provides several recommendations for future best practice. 1. Introduction In 2013, the Journal of Forensic Radiology and Imaging (JOFRI) was launched to help collate the literature on imaging-based modalities across the forensic sciences. This was achieved by presenting high-quality case studies and specialist reviews with the underlying theme of non- invasive documentation techniques. Arguably, the use of imaging techniques within this discipline and the development of this journal was instigated by the large amount of research undertaken on virtual autopsies. However, now five years on, the use of imaging has rapidly developed across many sub-disciplines within the forensic sciences.
    [Show full text]
  • British Journal of Nutrition (2015), 113, 560–573 Doi:10.1017/S0007114514004000 Q the Authors 2015
    Downloaded from British Journal of Nutrition (2015), 113, 560–573 doi:10.1017/S0007114514004000 q The Authors 2015 https://www.cambridge.org/core Absorption and intermediary metabolism of purines and pyrimidines in lactating dairy cows Charlotte Stentoft1*, Betina Amdisen Røjen2, Søren Krogh Jensen1, Niels B. Kristensen2, . IP address: Mogens Vestergaard1 and Mogens Larsen1 1Department of Animal Science, Aarhus University, Foulum, Blichers Alle´ 20, DK-8830 Tjele, Denmark 170.106.35.229 2Knowledge Centre for Agriculture, DK-8200 Aarhus N, Denmark (Submitted 23 June 2014 – Final revision received 27 October 2014 – Accepted 9 November 2014 – First published online 26 January 2015) , on 30 Sep 2021 at 08:56:31 Abstract About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic metabolism were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was sampled simul- taneously from four veins with eight hourly samples from four multi-catheterised Holstein cows. Quantification of twenty purines and pyrimidines was performed with HPLC–MS/MS, and net fluxes were estimated across the PDV, hepatic tissue and total splanchnic , subject to the Cambridge Core terms of use, available at tissue (TSP). Concentration differences between veins of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation products (DP) were different from zero (P#0·05), resulting in the net PDV releases of purine NS (0·33–1·3 mmol/h), purine BS (0·0023–0·018 mmol/h), purine DP (7·0–7·8 mmol/h), pyrimidine NS (0·30–2·8 mmol/h) and pyrimidine DP (0·047–0·77 mmol/h).
    [Show full text]
  • 3Rd Congress of the ISFRI: Abstracts
    Journal of Forensic Radiology and Imaging 2 (2014) 95–107 Contents lists available at ScienceDirect Journal of Forensic Radiology and Imaging journal homepage: www.elsevier.com/locate/jofri 3rd Congress of the ISFRI: Abstracts Session 1 – Ballistics and miscellaneous 1.1. MSCT and micro-CT analysis in a case of 1.2. A novel approach to automated bloodstain pattern “dyadic-death”. Homicide-suicide or analysis using an active bloodstain shape model suicide-homicide? P. Joris a, W. Develter b, E. Jenar b, D. Vandermeulen a, W. Coudyzer c, A. Viero a, G. Cecchetto a, C. Muscovich b, C. Giraudo b, G. Viel a J. Wuestenbergs a, B. De Dobbelaer a, W. Van de Voorde b, E. Geusens c, P. Claes a a Institute of Legal Medicine, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Falloppio 50, 35121 a University of Leuven (KUL), Department of Electrical Engineering, Padova, Italy ESAT/PSI Medical Image Computing & UZ Leuven, Medical Imaging b Radiology Section, Department of Medicine, University of Padova, Research Center & iMinds, Future Health Department, Belgium Via Giustiniani 3, 35121 Padova, Italy b University Hospitals Leuven (UZ), Department of Forensic Medicine, Belgium c University Hospitals Leuven (UZ), Department of Radiology, Belgium Objectives: The application of post-mortem multislice computed tomography (MSCT) and micro-CT analysis to the reconstruction of a Objectives: Conventional blood pattern analysis is a tedious and singular case of “dyadic death”, where a single gunshot was fired. time- consuming process due to the many actions that must be performed Materials and methods: Crime scene investigation and crimina- by the pattern analyst.
    [Show full text]