Centrin 2 Is Required for Mouse Olfactory Ciliary Trafficking and Development of Ependymal Cilia Planar Polarity
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Old Data and Friends Improve with Age: Advancements with the Updated Tools of Genenetwork
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.24.445383; this version posted May 25, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Old data and friends improve with age: Advancements with the updated tools of GeneNetwork Alisha Chunduri1, David G. Ashbrook2 1Department of Biotechnology, Chaitanya Bharathi Institute of Technology, Hyderabad 500075, India 2Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA Abstract Understanding gene-by-environment interactions is important across biology, particularly behaviour. Families of isogenic strains are excellently placed, as the same genome can be tested in multiple environments. The BXD’s recent expansion to 140 strains makes them the largest family of murine isogenic genomes, and therefore give great power to detect QTL. Indefinite reproducible genometypes can be leveraged; old data can be reanalysed with emerging tools to produce novel biological insights. To highlight the importance of reanalyses, we obtained drug- and behavioural-phenotypes from Philip et al. 2010, and reanalysed their data with new genotypes from sequencing, and new models (GEMMA and R/qtl2). We discover QTL on chromosomes 3, 5, 9, 11, and 14, not found in the original study. We narrowed down the candidate genes based on their ability to alter gene expression and/or protein function, using cis-eQTL analysis, and variants predicted to be deleterious. Co-expression analysis (‘gene friends’) and human PheWAS were used to further narrow candidates. -
Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation 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 Doctoral Dissertations 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 dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R. -
The Basal Bodies of Chlamydomonas Reinhardtii Susan K
Dutcher and O’Toole Cilia (2016) 5:18 DOI 10.1186/s13630-016-0039-z Cilia REVIEW Open Access The basal bodies of Chlamydomonas reinhardtii Susan K. Dutcher1* and Eileen T. O’Toole2 Abstract The unicellular green alga, Chlamydomonas reinhardtii, is a biflagellated cell that can swim or glide. C. reinhardtii cells are amenable to genetic, biochemical, proteomic, and microscopic analysis of its basal bodies. The basal bodies contain triplet microtubules and a well-ordered transition zone. Both the mother and daughter basal bodies assemble flagella. Many of the proteins found in other basal body-containing organisms are present in the Chlamydomonas genome, and mutants in these genes affect the assembly of basal bodies. Electron microscopic analysis shows that basal body duplication is site-specific and this may be important for the proper duplication and spatial organization of these organelles. Chlamydomonas is an excellent model for the study of basal bodies as well as the transition zone. Keywords: Site-specific basal body duplication, Cartwheel, Transition zone, Centrin fibers Phylogeny and conservation of proteins Centrin, SPD2/CEP192, Asterless/CEP152; CEP70, The green lineage or Viridiplantae consists of the green delta-tubulin, and epsilon-tubulin. Chlamydomonas has algae, which include Chlamydomonas, the angiosperms homologs of all of these based on sequence conservation (the land plants), and the gymnosperms (conifers, cycads, except PLK4, CEP152, and CEP192. Several lines of evi- ginkgos). They are grouped together because they have dence suggests that CEP152, CEP192, and PLK4 interact chlorophyll a and b and lack phycobiliproteins. The green [20, 52] and their concomitant absence in several organ- algae together with the cycads and ginkgos have basal isms suggests that other mechanisms exist that allow for bodies and cilia, while the angiosperms and conifers have control of duplication [4]. -
Treating Dysosmia, from Saline to Surgery
日鼻誌47!:51~52,2008 特別講演2 TREATING DYSOSMIA, FROM SALINE TO SURGERY Donald A. Leopold, MD, FACS University of Nebraska Medical Center, Omaha, Nebraska, United States of America The sense of smell begins with airflow through the nose. The exact path of this airflow has only recently been investigated. Some of this data comes from models, both life size and enlarged models using measurements of airflow. Additional information comes from computerized airflow models of the nasal cavities. The neural pathways of olfaction begin with the olfactory receptors high in the nasal cavity. After transduction from the chemical to the electrical information, this information is transferred through the olfactory bulb and into the central brain. Patients typically present with one of three different types of dysosmia. The first is simply a decreased ability to perceive smells(hyposmia and anosmia). The two remaining types of dysosmia relate to distortions of perceived smells. One of these(parosmia)is a distortion of smell odorants that are actually in the environment. The third type is theperceptionofanodorwhenthereisnoodorantintheenvironment(phantosmia or hallucination). The clinical task of the physician seeing these patients is to decide on the etiology of the problem and to recom- mend therapy if possible. The clinical history is one of the best tools the clinician has, but the physical examination, sensory testing and imaging can also be helpful. Diagnostic categories for these patients are many, but the most com- mon include nasal inflammatory disease for about a third of these patients, the losses that occur after an upper respira- tory infection in about 25 percent of the patients and head trauma in about 15 percent of patients. -
Par6c Is at the Mother Centriole and Controls Centrosomal Protein
860 Research Article Par6c is at the mother centriole and controls centrosomal protein composition through a Par6a-dependent pathway Vale´rian Dormoy, Kati Tormanen and Christine Su¨ tterlin* Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697-2300, USA *Author for correspondence ([email protected]) Accepted 3 December 2012 Journal of Cell Science 126, 860–870 ß 2013. Published by The Company of Biologists Ltd doi: 10.1242/jcs.121186 Summary The centrosome contains two centrioles that differ in age, protein composition and function. This non-membrane bound organelle is known to regulate microtubule organization in dividing cells and ciliogenesis in quiescent cells. These specific roles depend on protein appendages at the older, or mother, centriole. In this study, we identified the polarity protein partitioning defective 6 homolog gamma (Par6c) as a novel component of the mother centriole. This specific localization required the Par6c C-terminus, but was independent of intact microtubules, the dynein/dynactin complex and the components of the PAR polarity complex. Par6c depletion resulted in altered centrosomal protein composition, with the loss of a large number of proteins, including Par6a and p150Glued, from the centrosome. As a consequence, there were defects in ciliogenesis, microtubule organization and centrosome reorientation during migration. Par6c interacted with Par3 and aPKC, but these proteins were not required for the regulation of centrosomal protein composition. Par6c also associated with Par6a, which controls protein recruitment to the centrosome through p150Glued. Our study is the first to identify Par6c as a component of the mother centriole and to report a role of a mother centriole protein in the regulation of centrosomal protein composition. -
Cep57, a NEDD1-Binding Pericentriolar Material Component, Is Essential for Spindle Pole Integrity
Cell Research (2012) :1-12. © 2012 IBCB, SIBS, CAS All rights reserved 1001-0602/12 $ 32.00 npg ORIGINAL ARTICLE www.nature.com/cr Cep57, a NEDD1-binding pericentriolar material component, is essential for spindle pole integrity Qixi Wu1, *, Runsheng He1, *, Haining Zhou1, Albert CH Yu2, Bo Zhang1, Junlin Teng1, Jianguo Chen1, 3 1The State Key Laboratory of Biomembrane and Membrane Bioengineering and The Key Laboratory of Cell Proliferation and Dif- ferentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China; 2Department of Neurobi- ology, Neuroscience Research Institute, School of Basic Medical Sciences, Peking University, Beijing 100191, China; 3The Center for Theoretical Biology, Peking University, Beijing 100871, China Formation of a bipolar spindle is indispensable for faithful chromosome segregation and cell division. Spindle in- tegrity is largely dependent on the centrosome and the microtubule network. Centrosome protein Cep57 can bundle microtubules in mammalian cells. Its related protein (Cep57R) in Xenopus was characterized as a stabilization factor for microtubule-kinetochore attachment. Here we show that Cep57 is a pericentriolar material (PCM) component. Its interaction with NEDD1 is necessary for the centrosome localization of Cep57. Depletion of Cep57 leads to unaligned chromosomes and a multipolar spindle, which is induced by PCM fragmentation. In the absence of Cep57, cen- trosome microtubule array assembly activity is weakened, and the spindle length and microtubule density decrease. As a spindle microtubule-binding protein, Cep57 is also responsible for the proper organization of the spindle micro- tubule and localization of spindle pole focusing proteins. Collectively, these results suggest that Cep57, as a NEDD1- binding centrosome component, could function as a spindle pole- and microtubule-stabilizing factor for establishing robust spindle architecture. -
Taste and Smell Disorders in Clinical Neurology
TASTE AND SMELL DISORDERS IN CLINICAL NEUROLOGY OUTLINE A. Anatomy and Physiology of the Taste and Smell System B. Quantifying Chemosensory Disturbances C. Common Neurological and Medical Disorders causing Primary Smell Impairment with Secondary Loss of Food Flavors a. Post Traumatic Anosmia b. Medications (prescribed & over the counter) c. Alcohol Abuse d. Neurodegenerative Disorders e. Multiple Sclerosis f. Migraine g. Chronic Medical Disorders (liver and kidney disease, thyroid deficiency, Diabetes). D. Common Neurological and Medical Disorders Causing a Primary Taste disorder with usually Normal Olfactory Function. a. Medications (prescribed and over the counter), b. Toxins (smoking and Radiation Treatments) c. Chronic medical Disorders ( Liver and Kidney Disease, Hypothyroidism, GERD, Diabetes,) d. Neurological Disorders( Bell’s Palsy, Stroke, MS,) e. Intubation during an emergency or for general anesthesia. E. Abnormal Smells and Tastes (Dysosmia and Dysgeusia): Diagnosis and Treatment F. Morbidity of Smell and Taste Impairment. G. Treatment of Smell and Taste Impairment (Education, Counseling ,Changes in Food Preparation) H. Role of Smell Testing in the Diagnosis of Neurodegenerative Disorders 1 BACKGROUND Disorders of taste and smell play a very important role in many neurological conditions such as; head trauma, facial and trigeminal nerve impairment, and many neurodegenerative disorders such as Alzheimer’s, Parkinson Disorders, Lewy Body Disease and Frontal Temporal Dementia. Impaired smell and taste impairs quality of life such as loss of food enjoyment, weight loss or weight gain, decreased appetite and safety concerns such as inability to smell smoke, gas, spoiled food and one’s body odor. Dysosmia and Dysgeusia are very unpleasant disorders that often accompany smell and taste impairments. -
Paroxysmal Bilateral Dysosmia Treated by Resection of the Olfactory Bulbs
160 Surg Neurol 1993 ;40:160-3 Paroxysmal Bilateral Dysosmia Treated by Resection of the Olfactory Bulbs J.M. Markert, M.D., D.O. Hartshorn, M.D., and S.M. Farhat, M.D. Department of Surgery, Section of Neurosurgery and Department of Otolaryngology, Head and Neck Surgery, University of Michigan Medical Center, and Catherine McAuley Health Center, Ann Arbor, Michigan Markert JM, Hartshorn DO, Farhat SM. Paroxysmal bilateral Case Report dysosmia treated by resection of the olfactory bulbs. Surg Neurol 1993;40:160-3. P.G., a 37-year-old woman, was seen in November 1988. She reported a 17 year history of dysosmia with paroxysms of peculiar sensations of smell. These sensa- Dysosmia, or the distortion of olfaction, is most commonly tions were usually brought on by inhalation of other preceded by viral illness or head trauma, but has a variety strong odors, such as cigars, perfume, or onions; how- of etiologies. The precise nature of the disease process remains obscure. Medical management is largely empiric, ever, they also could be triggered by sudden turning of and has been aimed at treating underlying illnesses, re- the head, a big sniff, or emotional and physical stress. stricting triggering medications, as well as various phar- The common cold or flu would also exacerbate the sensa- macologic interventions. Successful eradication of a severe tion. Dysosmia paroxysms were described as unlike any case of persistent unilateral paroxysmal dysosmia with other odor, and always the same: of a hot, foul and resection of the ipsilateral olfactory bulb has been re- smoky nature on the right, and a sickeningly sweet, ported. -
Supplemental Information
Supplemental information Dissection of the genomic structure of the miR-183/96/182 gene. Previously, we showed that the miR-183/96/182 cluster is an intergenic miRNA cluster, located in a ~60-kb interval between the genes encoding nuclear respiratory factor-1 (Nrf1) and ubiquitin-conjugating enzyme E2H (Ube2h) on mouse chr6qA3.3 (1). To start to uncover the genomic structure of the miR- 183/96/182 gene, we first studied genomic features around miR-183/96/182 in the UCSC genome browser (http://genome.UCSC.edu/), and identified two CpG islands 3.4-6.5 kb 5’ of pre-miR-183, the most 5’ miRNA of the cluster (Fig. 1A; Fig. S1 and Seq. S1). A cDNA clone, AK044220, located at 3.2-4.6 kb 5’ to pre-miR-183, encompasses the second CpG island (Fig. 1A; Fig. S1). We hypothesized that this cDNA clone was derived from 5’ exon(s) of the primary transcript of the miR-183/96/182 gene, as CpG islands are often associated with promoters (2). Supporting this hypothesis, multiple expressed sequences detected by gene-trap clones, including clone D016D06 (3, 4), were co-localized with the cDNA clone AK044220 (Fig. 1A; Fig. S1). Clone D016D06, deposited by the German GeneTrap Consortium (GGTC) (http://tikus.gsf.de) (3, 4), was derived from insertion of a retroviral construct, rFlpROSAβgeo in 129S2 ES cells (Fig. 1A and C). The rFlpROSAβgeo construct carries a promoterless reporter gene, the β−geo cassette - an in-frame fusion of the β-galactosidase and neomycin resistance (Neor) gene (5), with a splicing acceptor (SA) immediately upstream, and a polyA signal downstream of the β−geo cassette (Fig. -
Coordination of Centrosome Homeostasis and DNA Repair Is Intact in MCF-7 and Disrupted in MDA-MB 231 Breast Cancer Cells
Published OnlineFirst April 13, 2010; DOI: 10.1158/0008-5472.CAN-09-3800 Tumor and Stem Cell Biology Cancer Research Coordination of Centrosome Homeostasis and DNA Repair Is Intact in MCF-7 and Disrupted in MDA-MB 231 Breast Cancer Cells Ilie D. Acu1, Tieju Liu1,3, Kelly Suino-Powell1,4, Steven M. Mooney1, Antonino B. D'Assoro1, Nicholas Rowland1, Alysson R. Muotri5, Ricardo G. Correa6, Yun Niu3, Rajiv Kumar1,2, and Jeffrey L. Salisbury1 Abstract When cells encounter substantial DNA damage, critical cell cycle events are halted while DNA repair mechanisms are activated to restore genome integrity. Genomic integrity also depends on proper assembly and function of the bipolar mitotic spindle, which is required for equal chromosome segregation. Failure to execute either of these processes leads to genomic instability, aging, and cancer. Here, we show that following DNA damage in the breast cancer cell line MCF-7, the centrosome protein centrin2 moves from the cytoplasm and accumulates in the nucleus in a xeroderma pigmentosum complementation group C protein (XPC)– dependent manner, reducing the available cytoplasmic pool of this key centriole protein and preventing cen- trosome amplification. MDA-MB 231 cells do not express XPC and fail to move centrin into the nucleus following DNA damage. Reintroduction of XPC expression in MDA-MB 231 cells rescues nuclear centrin2 sequestration and reestablishes control against centrosome amplification, regardless of mutant p53 status. Importantly, the capacity to repair DNA damage was also dependent on the availability of centrin2 in the nucleus. These observations show that centrin and XPC cooperate in a reciprocal mechanism to coordinate centrosome homeostasis and DNA repair and suggest that this process may provide a tractable target to develop treatments to slow progression of cancer and aging. -
Critical Illness and Changes in Sensory Perception
Proceedings of the Nutrition Society (2007), 66, 331–345 DOI:10.1017/S0029665107005599 g The Author 2007 Critical illness and changes in sensory perception Susan S. Schiffman Department of Psychiatry, 54212 Woodhall Building, Duke University Medical Center, Durham, NC 27710–3259, USA Impairments of sensory perception that occur during a period of critical care can seriously impact on health and nutritional status, activities of daily living, independence, quality of life and the possibility of recovery. It is emphasized from the outset that sensory losses in critically- ill patients may or may not be related to their current medical condition. The present paper provides an overview of all five senses (vision, hearing, taste, smell and touch) and describes the factors that contribute to sensory losses in critically-ill patients, including medications, medical conditions and treatments and the process of aging itself. Cancer and stroke are two critical illnesses in which profound sensory decrements often occur. Many sensory complaints in patients with cancer are related to alteration in sensory signals caused by damage to the sensory receptors. However, some complaints, such as taste aversions in patients with cancer, are not related to altered sensory physiology per se but to learned aversions that arise during the noxious effects of radiotherapy and chemotherapy. The paper also reviews a study in which the sensory performance (of all five senses) was compared in three groups of elderly subjects: (1) patients who had undergone coronary artery bypass surgery; (2) patients with cardio- vascular conditions but with no history of surgery; (3) healthy non-medicated age-matched controls. -
Clinical Diagnosis and Treatment of Olfactory Dysfunction
Clinical Diagnosis and Treatment of Olfactory Dysfunction Seok Hyun Cho Hanyang Med Rev 2014;34:107-115 http://dx.doi.org/10.7599/hmr.2014.34.3.107 Department of Otorhinolaryngology-Head and Neck Surgery, Hanyang University College of Medicine, Seoul, Korea pISSN 1738-429X eISSN 2234-4446 Olfactory dysfunction is a relatively common disorder that is often under-recognized by Correspondence to: Seok Hyun Cho Department of Otorhinolaryngology-Head both patients and clinicians. It occurs more frequently in older ages and men, and decreases and Neck Surgery, Hanyang University patients’ quality of life, as olfactory dysfunction may affect the emotion and memory func- Hospital, 222 Wangsimni-ro, Seongdong-gu, tions. Three main causes of olfactory dysfunction are sinonasal diseases, upper respiratory Seoul 133-792, Korea Tel: +82-2-2290-8583 viral infection, and head trauma. Olfactory dysfunction is classified quantitatively (hypos- Fax: +82-2-2293-3335 mia and anosmia) and qualitatively (parosmia and phantosmia). From a pathophysiologi- E-mail: [email protected] cal perspective, olfactory dysfunction is also classified by conductive or sensorineural types. All patients with olfactory dysfunction will need a complete history and physical examina- Received 17 April 2014 Revised 23 June 2014 tion to identify any possible or underlying causes and psychophysical olfactory tests are Accepted 3 July 2014 essential to estimate the residual olfactory function, which is the most important prognos- This is an Open Access article distributed under tic factor. CT or MRI may be adjunctively used in some indicated cases such as head trauma the terms of the Creative Commons Attribution and neurodegenerative disorders.