Digital Commons Network^™

Disease-Associated Mutations In Niemann-Pick Type C1 Alter Er Calcium Signaling And Neuronal Plasticity, Scott A. Tiscione, Oscar Vivas, Kenneth S. Ginsburg, Donald M. Bers, Daniel S. Ory, Luis F. Santana, Rose E. Dixon, Eamonn J. Dickson

Open Access Publications

Niemann-Pick type C1 (NPC1) protein is essential for the transport of externally derived cholesterol from lysosomes to other organelles. Deficiency of NPC1 underlies the progressive NPC1 neurodegenerative disorder. Currently, there are no curative therapies for this fatal disease. Given the Ca

Association Of Longitudinal Changes In Cerebrospinal Fluid Total Tau And Phosphorylated Tau 181 And Brain Atrophy With Disease Progression In Patients With Alzheimer Disease, Jorge J. Llibre-Guerra, Yan Li, Suzanne E. Schindler, Brian A. Gordon, Anne M. Fagan, John C. Morris, Tammie L.S. Benzinger, Jason Hassenstab, Sarah B. Berman, David M. Holtzman, Chengjie Xiong, Randall J. Bateman, Eric Mcdade

Open Access Publications

Importance: The amyloid/tau/neurodegeneration (A/T/N) framework uses cerebrospinal fluid (CSF) levels of total tau (tTau) as a marker of neurodegeneration and CSF levels of phosphorylated tau 181 (pTau181) as a marker of tau tangles. However, it is unclear whether CSF levels of tTau and pTau181 have similar or different trajectories over the course of Alzheimer disease.

Objectives: To examine the rates of change in CSF levels of tTau and pTau181 across the Alzheimer disease course and how the rates of change are associated with brain atrophy as measured by magnetic resonance imaging.

Design, Setting, and Participants: This cohort study was set …

Tricarboxylic Acid Cycle Enzyme Activities In A Mouse Model Of Methylmalonic Aciduria, Parith Wongkittichote, Gary Cunningham, Marshall L Summar, Elena Pumbo, Patrick Forny, Matthias R Baumgartner, Kimberly A Chapman

Open Access Publications

Methylmalonic acidemia (MMA) is a propionate pathway disorder caused by dysfunction of the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). MMUT catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA, an anaplerotic reaction which feeds into the tricarboxylic acid (TCA) cycle. As part of the pathological mechanisms of MMA, previous studies have suggested there is decreased TCA activity due to a "toxic inhibition" of TCA cycle enzymes by MMA related metabolites, in addition to reduced anaplerosis. Here, we have utilized mitochondria isolated from livers of a mouse model of MMA (Mut-ko/ki) and their littermate controls (Ki/wt) to examine the amounts and enzyme functions of …

Phenotypic And Genotypic Characterization Of Linezolid-Resistant Enterococcus Faecium From The Usa And Pakistan, Kate E Wardenburg, Robert F Potter, Alaric W D'Souza, Tahir Hussain, Meghan A Wallace, Saadia Andleeb, Carey-Ann D Burnham, Gautam Dantas

2010-2019 OA Pubs

OBJECTIVES: Linezolid is an important therapeutic option for the treatment of infections caused by VRE. Linezolid is a synthetic antimicrobial and resistance to this antimicrobial agent remains relatively rare. As a result, data on the comparative genomics of linezolid resistance determinants in Enterococcus faecium are relatively sparse.

METHODS: To address this knowledge gap in E. faecium, we deployed phenotypic antibiotic susceptibility testing and Illumina WGS on hospital surface (environmental) and clinical isolates from the USA and Pakistan.

RESULTS: We found complete concordance between isolate source country and mechanism of linezolid resistance, with all the US isolates possessing a 23S rRNA …

Reproducibility Of Cognitive Endpoints In Clinical Trials: Lessons From Neurofibromatosis Type 1, Jonathan M Payne, David H Gutmann, Et Al

Open Access Publications

OBJECTIVE: Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism-based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test-retest reliability of the measures and the application of data reduction techniques to improve reproducibility.

METHODS: Data were analyzed from the STARS clinical trial (n = 146), a multi-center double-blind placebo-controlled phase II trial of lovastatin, …

Online And Clicker Quizzing On Jargon Terms Enhances Definition-Focused But Not Conceptually Focused Biology Exam Performance, Steven C. Pan, James Cooke, Jeri L. Little, Mark A. Mcdaniel, Erin R. Foster, Lisa Tabor Connor, Timothy C. Rickard

Open Access Publications

Mastery of jargon terms is an important part of student learning in biology and other science, technology, engineering, and mathematics domains. In two experiments, we investigated whether prelecture quizzes enhance memory for jargon terms, and whether that enhanced familiarity can facilitate learning of related concepts that are encountered during subsequent lectures and readings. Undergraduate students enrolled in neuroanatomy and physiology courses completed 10-minute low-stakes quizzes with feedback on jargon terms either online (experiment 1) or using in-class clickers (experiment 2). Quizzes occurred before conventional course instruction in which the terms were used. On exams occurring up to 12 weeks later, …

Linking The Effects Of Helminth Infection, Diet And The Gut Microbiota With Human Whole-Blood Signatures, Soo Ching Lee, Mei San Tang, Alice V. Easton, Joseph Cooper Devlin, Ling Ling Chua, Ilseung Cho, Foong Ming Moy, Tsung Fei Khang, Yvonne A. L. Lim, P'Ng Loke

Open Access Publications

Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc …

Standard Operating Procedure For Curation And Clinical Interpretation Of Variants In Cancer, Arpad M Danos, Kilannin Krysiak, Erica K Barnell, Adam C Coffman, Joshua F Mcmichael, Susanna Kiwala, Nicholas C Spies, Lana M Sheta, Shahil P Pema, Lynzey Kujan, Kaitlin A Clark, Amber Z Wollam, Alex H Wagner, Malachi Griffith, Obi L Griffith, Et Al

Open Access Publications

Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their level of public accessibility, and the complexity of the models used to capture clinical knowledge. CIViC (Clinical Interpretation of Variants in Cancer - www.civicdb.org) is a fully open, free-to-use cancer variant interpretation knowledgebase that incorporates highly detailed curation of evidence obtained from peer-reviewed publications and meeting abstracts, and currently holds over 6300 Evidence Items for over 2300 variants derived from over 400 genes. CIViC has seen increased adoption by, and also undertaken collaboration …

Mutations In Lamb2 Are Associated With Albuminuria And Optic Nerve Hypoplasia With Hypopituitarism, Mona Tahoun, Jennifer C Chandler, Emma Ashton, Scott Haston, Athia Hannan, Ji Soo Kim, Felipe D'Arco, D Bockenhauer, G Anderson, Meei-Hua Lin, Salah Marzouk, Marwa H Saied, Jeffrey H Miner, Mehul T Dattani, Aoife M Waters

Open Access Publications

CONTEXT: Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome).

CASE DESCRIPTION: This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel …

Entry By Multiple Picornaviruses Is Dependent On A Pathway That Includes Tnk2, Wasl, And Nck1, Hongbing Jiang, Christian Leung, Stephen Tahan, David Wang

Open Access Publications

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes,

Three Genetic-Environmental Networks For Human Personality, Igor Zwir, Coral Del-Val, Dragan M Svrakic, Nigel Lester, Sandor Rozsa, Maribel Martinez, Daniel Mamah, C Charles Gu, C Robert Cloninger, Et Al

Open Access Publications

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are …

Metabolism Of Non-Enzymatically Derived Oxysterols: Clues From Sterol Metabolic Disorders, William J Griffiths, Eylan Yutuc, Jonas Abdel-Khalik, Peter J Crick, Thomas Hearn, Alison Dickson, Brian W Bigger, Teresa Hoi-Yee Wu, Anu Goenka, Arunabha Ghosh, Simon A. Jones, Douglas F Covey, Daniel S Ory, Yuqin Wang

Open Access Publications

Cholestane-3β,5α,6β-triol (3β,5α,6β-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7β-hydroxycholesterol (7β-HC) can also be formed by free radical oxidation of cholesterol. Here we investigate how 3β,5α,6β-triol, 7-OC and 7β-HC are metabolised to bile acids. We show, by monitoring oxysterol metabolites in plasma samples rich in 3β,5α,6β-triol, 7-OC and 7β-HC, that these three oxysterols fall into novel branches of the acidic pathway of bile acid biosynthesis becoming (25R)26-hydroxylated then carboxylated, 24-hydroxylated and side-chain shortened to give the final products 3β,5α,6β-trihydroxycholanoic, 3β-hydroxy-7-oxochol-5-enoic and …

The Impact Of Systemic Precision Medicine And Immunotherapy Treatments On Brain Metastases, Rowland H. Han, Gavin P. Dunn, Milan G. Chheda, Albert H. Kim

Open Access Publications

Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell lung cancer (NSCLC), numerous clinical trials have demonstrated intracranial activity for inhibitors of EGFR and ALK. Patients with melanoma brain metastases may benefit from systemic therapy using BRAF-inhibitors with and without trametinib. Several targeted options are available for breast cancer brain metastases that overexpress HER2, although agents with intracranial activity …

Gut Microbiota: From The Forgotten Organ To A Potential Key Player In The Pathology Of Alzheimer's Disease, Dong-Oh Seo, David M Holtzman

Open Access Publications

More than 300 years ago, Antony van Leewenhoeck first described observing single-celled microorganisms, which he termed "animalcules," examining his saliva under a microscope. Although the idea of the coexistence of microorganisms in our body is not new, we have only recently been able to investigate their ecological relationship to our body, with the development of high-throughput molecular techniques. The diverse microorganism communities residing in our guts are established and maintained by complex interactions among microorganisms and their host. Notably, their alteration has been implicated in influencing various diseases including neurological diseases. Alzheimer's disease (AD) is the most common cause of …

The Community Structure Of Functional Brain Networks Exhibits Scale-Specific Patterns Of Inter- And Intra-Subject Variability, Richard F Betzel, Maxwell A Bertolero, Evan M Gordon, Caterina Gratton, Nico U F Dosenbach, Danielle S Bassett

2010-2019 OA Pubs

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain's modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time …

Associations Of Race And Ethnicity With Risk Of Developing Invasive Breast Cancer After Lobular Carcinoma In Situ, Vanessa Dania, Ying Liu, Foluso Ademuyiwa, Jason D Weber, Graham A Colditz

Open Access Publications

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS.

METHODS: We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015. Cox proportional hazards regression was used to estimate race/ethnicity-associated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of subsequent invasive breast cancer.

RESULTS: During a median follow-up of 90 months, 1567 patients developed invasive breast cancer. The 10-year incidence was 7.9% for Asians, …

Direct Binding Of Phosphatidylglycerol At Specific Sites Modulates Desensitization Of A Ligand-Gated Ion Channel, Ailing Tong, John T. Petroff Ii, Fong-Fu Hsu, Philipp A.M. Schmidpeter, Crina M. Nimigean, Liam Sharp, Grace Brannigan, Wayland W.L. Cheng

Open Access Publications

Pentameric ligand-gated ion channels (pLGICs) are essential determinants of synaptic transmission, and are modulated by specific lipids including anionic phospholipids. The exact modulatory effect of anionic phospholipids in pLGICs and the mechanism of this effect are not well understood. Using native mass spectrometry, coarse-grained molecular dynamics simulations and functional assays, we show that the anionic phospholipid, 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), preferentially binds to and stabilizes the pLGIC, Erwinia ligand-gated ion channel (ELIC), and decreases ELIC desensitization. Mutations of five arginines located in the interfacial regions of the transmembrane domain (TMD) reduce POPG binding, and a subset of these mutations increase ELIC …

Molecular Game Theory For A Toxin-Dominant Food Chain Model, Bowen Li, Jonathan R Silva, Jianmin Cui, Et Al.

2010-2019 OA Pubs

Animal toxins that are used to subdue prey and deter predators act as the key drivers in natural food chains and ecosystems. However, the predators of venomous animals may exploit feeding adaptation strategies to overcome toxins their prey produce. Much remains unknown about the genetic and molecular game process in the toxin-dominant food chain model. Here, we show an evolutionary strategy in different trophic levels of scorpion-eating amphibians, scorpions and insects, representing each predation relationship in habitats dominated by the paralytic toxins of scorpions. For scorpions preying on insects, we found that the scorpion α-toxins irreversibly activate the skeletal muscle …

Svtools: Population-Scale Analysis Of Structural Variation, David E Larson, Haley J Abel, Colby Chiang, Abhijit Badve, Indraniel Das, James M Eldred, Ryan M Layer, Ira M Hall

Open Access Publications

SUMMARY: Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps-including deletions, duplications, mobile element insertions, inversions and other rearrangements-in many thousands of human genomes. We show that this pipeline …

Defining Components Of Early Functional Rehabilitation For Acute Achilles Tendon Rupture: A Systematic Review, Jennifer A Zellers, Marianne Christensen, Inge Lunding Kjær, Michael Skovdal Rathleff, Karin Grävare Silbernagel

Open Access Publications

Background: Early functional rehabilitation is frequently discussed in treating Achilles tendon rupture. A consistent definition of what constitutes early functional rehabilitation has not been established across the literature, despite studies supporting its efficacy. A standardized definition would be helpful to pool data across studies, allow for between-study comparisons, and ultimately work toward developing clinical guidelines.

Purpose: To define early functional rehabilitation (including when it is initiated and what it entails) when used to treat Achilles tendon rupture and to identify outcome measures for evaluating the effect of treatment.

Study Design: Systematic review; Level of evidence, 4.

Methods: Ovid MEDLINE, EMBASE, …

Pharmacokinetics Of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules In De Novo Liver Transplant, Derek A Dubay, Lewis Teperman, Kimi Ueda, Andrew Silverman, William Chapman, Angel E Alsina, Carmelina Tyler, Daniel R Stevens

2010-2019 OA Pubs

The pharmacokinetics of once-daily extended-release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open-label study, de novo liver transplant recipients were randomized to LCPT 0.07-0.13 mg/kg/day (taken once daily; n = 29) or twice-daily immediate-release tacrolimus capsules (IR-Tac) at 0.10-0.15 mg/kg/day (divided twice daily; n = 29). Subsequent doses of both drugs were adjusted to maintain tacrolimus trough concentrations of 5 to 20 ng/mL through day 90, and 5-15 ng/mL thereafter. Twenty-four-hour pharmacokinetic profiles were obtained on days 1, 7, and 14, with trough concentration and efficacy/safety monitoring through year …

Noda-Like Rna Viruses Infecting Caenorhabditis Nematodes: Sympatry, Diversity, And Reassortment, Lise Frézal, Hyeim Jung, Stephen Tahan, David Wang, Marie-Anne Félix

Open Access Publications

Three RNA viruses related to nodaviruses were previously described to naturally infect the nematode

Maternal Fluoxetine Exposure Alters Cortical Hemodynamic And Calcium Response Of Offspring To Somatosensory Stimuli, Rachel M Rahn, Susan E Maloney, Lindsey M Brier, Joseph D Dougherty, Joseph P Culver

Open Access Publications

Epidemiological studies have found an increased incidence of neurodevelopmental disorders in populations prenatally exposed to selective serotonin reuptake inhibitors (SSRIs). Optical imaging provides a minimally invasive way to determine if perinatal SSRI exposure has long-term effects on cortical function. Herein we probed the functional neuroimaging effects of perinatal SSRI exposure in a fluoxetine (FLX)-exposed mouse model. While resting-state homotopic contralateral functional connectivity was unperturbed, the evoked cortical response to forepaw stimulation was altered in FLX mice. The stimulated cortex showed decreased activity for FLX versus controls, by both hemodynamic responses [oxyhemoglobin (HbO

Human Monoclonal Antibodies Against Chikungunya Virus Target Multiple Distinct Epitopes In The E1 And E2 Glycoproteins, Jose A. Quiroz, Ryan J. Malonis, Larissa B. Thackray, Courtney A. Cohen, Jesper Pallesen, Rohit K. Jangra, Rebecca S. Brown, Daniel Hofmann, Frederick W. Holtsberg, Sergey Shulenin, Elisabeth K. Nyakatura, Lorellin A. Durnell, Vinayak Rayannavar, Johanna P. Daily, Andrew B. Ward, M. Javad Aman, John M. Dye, Kartik Chandran, Michael S. Diamond, Margaret Kielian, Jonathan R. Lai

Open Access Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two …

Dc-Script Deficiency Delays Mouse Mammary Gland Development And Branching Morphogenesis, Chunling Tang, Renske J E Van Den Bijgaart, Maaike W G Looman, Nina Tel-Karthaus, Annemarie M A De Graaf, Susan Gilfillan, Marco Colonna, Marleen Ansems, Gosse J Adema

Open Access Publications

Mammary glands are unique organs in which major adaptive changes occur in morphogenesis and development after birth. Breast cancer is the most common cancer and a major cause of mortality in females worldwide. We have previously identified the loss of expression of the transcription regulator DC-SCRIPT (Zfp366) as a prominent prognostic event in estrogen receptor positive breast cancer patients. DC-SCRIPT affects multiple transcriptional events in breast cancer cells, including estrogen and progesterone receptor-mediated transcription, and promotes CDKN2B-related cell cycle arrest. As loss of DC-SCRIPT expression appears an early event in breast cancer development, we here investigated the role of DC-SCRIPT …

Vav1 Inhibits Rankl-Induced Osteoclast Differentiation And Bone Resorption., Jin Sun Jang, In Soon Kang, Young-Nam Cha, Zang Hee Lee, Mary C Dinauer, Young-June Kim, Chaekyun Kim

Open Access Publications

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1-/-) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a …

Association Of Intestinal Alkaline Phosphatase With Necrotizing Enterocolitis Among Premature Infants, Maya Heath, Rebecca Buckley, Zeromeh Gerber, Porcha Davis, Laura Linneman, Qingqing Gong, Brian Barkemeyer, Zhide Fang, Misty Good, Duna Penn, Sunyoung Kim

Open Access Publications

Importance: Necrotizing enterocolitis (NEC) in preterm infants is an often-fatal gastrointestinal tract emergency. A robust NEC biomarker that is not confounded by sepsis could improve bedside management, lead to lower morbidity and mortality, and permit patient selection in randomized clinical trials of possible therapeutic approaches.

Objective: To evaluate whether aberrant intestinal alkaline phosphatase (IAP) biochemistry in infant stool is a molecular biomarker for NEC and not associated with sepsis.

Design, Setting, and Participants: This multicenter diagnostic study enrolled 136 premature infants (gestational age, <37 weeks) in 2 hospitals in Louisiana and 1 hospital in Missouri. Data were collected and analyzed from May 2015 to November 2018.

Exposures: Infant stool samples were collected between 24 and 40 or more weeks postconceptual age. Enrolled infants …

Burden Of Cause-Specific Mortality Associated With Pm2.5 Air Pollution In The United States, Benjamin Bowe, Yan Xie, Yan Yan, Ziyad Al-Aly

Open Access Publications

Importance: Ambient fine particulate matter (PM2.5) air pollution is associated with increased risk of several causes of death. However, epidemiologic evidence suggests that current knowledge does not comprehensively capture all causes of death associated with PM2.5 exposure.

Objective: To systematically identify causes of death associated with PM2.5 pollution and estimate the burden of death for each cause in the United States.

Design, Setting, and Participants: In a cohort study of US veterans followed up between 2006 and 2016, ensemble modeling was used to identify and characterize morphology of the association between PM2.5 and causes of death. Burden of death associated …

Cis-Regulatory Basis Of Sister Cell Type Divergence In The Vertebrate Retina, Daniel P Murphy, Andrew Eo Hughes, Karen A Lawrence, Connie A Myers, Joseph C Corbo

2010-2019 OA Pubs

Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types, but the mechanisms underlying sister cell type divergence are not well understood. Here, we study a canonical pair of sister cell types, retinal photoreceptors and bipolar cells, to identify the key

Redefining Noradrenergic Neuromodulation Of Behavior: Impacts Of A Modular Locus Coeruleus Architecture, Dan J. Chandler, Patricia Jensen, Jordan G. Mccall, Anthony E. Pickering, Lindsay A. Schwarz, Nelson K. Totah

Open Access Publications

The locus coeruleus (LC) is a seemingly singular and compact neuromodulatory nucleus that is a prominent component of disparate theories of brain function due to its broad noradrenergic projections throughout the CNS. As a diffuse neuromodulatory system, noradrenaline affects learning and decision making, control of sleep and wakefulness, sensory salience including pain, and the physiology of correlated forebrain activity (ensembles and networks) and brain hemodynamic responses. However, our understanding of the LC is undergoing a dramatic shift due to the application of state-of-the-art methods that reveal a nucleus of many modules that provide targeted neuromodulation. Here, we review the evidence …