Medicine and Health Sciences Commons^™

Connectivity Differences Between Gulf War Illness (Gwi) Phenotypes During A Test Of Attention, Tomas Clarke, Jessie Jamieson, Patrick Malone, Rakib U. Rayhan, Stuart Washington, John W. Vanmeter, James N. Baraniuk

Department of Mathematics: Faculty Publications

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention …

Resistance To Ectromelia Virus Infection Requires Cgas In Bone Marrow-Derived Cells Which Can Be Bypassed With Cgamp Therapy., Eric B. Wong, Brian Montoya, Maria Ferez, Colby Stotesbury, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Cells sensing infection produce Type I interferons (IFN-I) to stimulate Interferon Stimulated Genes (ISGs) that confer resistance to viruses. During lympho-hematogenous spread of the mouse pathogen ectromelia virus (ECTV), the adaptor STING and the transcription factor IRF7 are required for IFN-I and ISG induction and resistance to ECTV. However, it is unknown which cells sense ECTV and which pathogen recognition receptor (PRR) upstream of STING is required for IFN-I and ISG induction. We found that cyclic-GMP-AMP (cGAMP) synthase (cGAS), a DNA-sensing PRR, is required in bone marrow-derived (BMD) but not in other cells for IFN-I and ISG induction and for …

Chloroviruses, James L. Van Etten, Irina V. Agarkova, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large dsDNA, plaque-forming viruses that infect certain chlorella-like green algae; the algae are normally mutualistic endosymbionts of protists and metazoans and are often referred to as zoochlorellae. The viruses are ubiquitous in inland aqueous environments throughout the world and occasionally single types reach titers of thousands of plaque-forming units per ml of native water. The viruses are icosahedral in shape with a spike structure located at one of the vertices. They contain an internal membrane that is required for infectivity. The viral genomes are 290 to 370 kb in size, which encode up to 16 tRNAs and 330 …

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as why …

A "Choose-Your-Own" Classroom-Based Activity That Promotes Scientific Inquiry About Rna Interference, Jeremy L. Hsu

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

RNA interference (RNAi), the process that results in the degradation of a target gene’s mRNA, is a fundamental part of eukaryotic gene regulation and is also an important molecular technique that allows for experimental manipulation of gene expression without altering DNA sequences. Despite the importance of RNAi, there have been relatively few lecture-based activities designed to teach about the consequences of this process and counter common misconceptions. I present here an inquiry-based activity that is centered around a “choose your own experiment” design where students generate hypotheses and critically evaluate their ideas by choosing several simulated experiments. The activity presents …

An Analysis Of Abdominal Stability Following Hyperthermic Exercise In Euhydrated And Dehydrated Conditions, Carli Ceckanowicz

Honors Scholar Theses

Core stability is essential for maintaining safety and optimizing performance during exercise and sport. The purpose of this study is to analyze how heat and hydration status (euhydrated USG<1.025 or dehydrated USG>1.025) can impair trunk stability in males and females (in both follicular and luteal phases) using the Trunk Stability Test (TST). Participants complete three blocks of 30 minutes of hyperthermic (35±1.299 ^oC and 49.418±5.0329% relative humidity) treadmill exercise. Exercise intensity is equivalent to 15 minutes at either 11W/kg or 7W/kg and the following 15 minutes at either 7W/kg or 4W/kg, respectively, based on individual heat production data. TST data will …

Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …

The Use Of Probiotics To Prevent Ventilator-Associated Pneumonia In Adults, Michael Roper, Paige Douthett

Physician Assistant Capstones, 2016 to 2019

Objective: To assess the efficacy and safety of preventing the acquisition of ventilator- associated pneumonia with the use of probiotic supplementation, as compared to a placebo, among hospitalized adult men and women receiving more than 24 hours of mechanical ventilation. Design: Systematic Literature Review. Methods: Systematic searches were conducted through PubMed and Scopus using the search terms “ventilator”, “probiotics”, and “prevention”. Records were excluded from the analysis if they were published before 2015, full text was not available, studies other than randomized control trial or cohort studies, and if the study population was less than 18 years old. Results: Of …

Subanesthetic Iv Ketamine Reduces Acute Suicidal Ideation In Patients With Mood Disorders, Kimberly Jenko, Jack Anzilotti

Physician Assistant Capstones, 2016 to 2019

Background. Depression and suicide are common in the United States and present a significant problem in the healthcare landscape. Currently, there are few options that can rapidly reduce suicidal ideation in patients with depression. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to reduce acute suicidality in patients with depression. Previous studies have a reduction of suicidal ideation compared to saline placebo, but few studies have shown a significant effect compared to a similar psychoactive drug such as midazolam.

Method. A search of PubMed and PsychNET was performed in September 2018 using the terms “ketamine,” “suicide,” …

Reattachment Of The Multifidus Tendon In Lumbar Surgery To Decrease Postoperative Back Pain: A Technical Note., Neil Klinger, Emre Yilmaz, Dia R Halalmeh, R Shane Tubbs, Marc D Moisi

Articles, Abstracts, and Reports

The posterior midline approach to the lumbar spine requires significant manipulation of the paraspinal muscles. Muscle detachment and retraction results in iatrogenic damage such as crush injury, devascularization, and denervation, all of which have been associated with postoperative pain. The muscle most directly affected by the posterior approach is the lumbar multifidus (LM), the largest and most medial of the deep lumbar paraspinal muscles. The effects of the posterior approach on the integrity of the LM is concerning, as multiple studies have demonstrated that intraoperative injuries sustained by the LM lead to postoperative muscle atrophy and potentially worsening low back …

Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

Langerhans Cells Orchestrate The Protective Antiviral Innate Immune Response In The Lymph Node., Eric B. Wong, Brian Montoya, Colby Stotesbury, Maria Ferez, Ren-Huan Xu, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

During disseminating viral infections, a swift innate immune response (IIR) in the draining lymph node (dLN) that restricts systemic viral spread is critical for optimal resistance to disease. However, it is unclear how this IIR is orchestrated. We show that after footpad infection of mice with ectromelia virus, dendritic cells (DCs) highly expressing major histocompatibility complex class II (MHC class II^hi DCs), including CD207⁺ epidermal Langerhans cells (LCs), CD103⁺CD207⁺ double-positive dermal DCs (DP-DCs), and CD103⁻CD207⁻ double-negative dermal DCs (DN-DCs) migrate to the dLN from the skin carrying virus. MHC class II^{hi …}

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Effectiveness Of Individual Nutrition Education Compared To Group Education, In Improving Anthropometric And Biochemical Indices Among Hypertensive Adults With Excessive Body Weight: A Randomized Controlled Trial, Danuta Gajewska, Alicja Kucharska, Marcin Kozak, Shahla M. Wunderlich, Joanna Niegowska

Department of Nutrition and Food Studies Scholarship and Creative Works

Objective: The study aims to compare the effectiveness of individual and group nutrition education methods in improving key anthropometric and biochemical markers in drug-treated, overweight-obese hypertensive adults. Methods: The randomized trial included 170 patients with pharmacologically well-controlled primary hypertension and body mass index (BMI) ≥ 25 kg/m². For six months, the patients received six sessions, either one-to-one individual nutrition education (IE, n = 89) or group education (GE, n= 81), developed by dietitians. Anthropometric measurements, body composition, and fasting measures of biochemical parameters were obtained at baseline and after six months of intervention. Results: 150 patients completed the …

Allele-Specific Rna Interference Prevents Neuropathy In Charcot-Marie-Tooth Disease Type 2d Mouse Models., Kathryn H Morelli, Laurie B Griffin, Nettie K Pyne, Lindsay M Wallace, Allison M Fowler, Stephanie N Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O Kitzman, Samuel G Kocen, Timothy J Hines, Emily L Spaulding, James R Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q Harper, Robert W Burgess

Department of Biochemistry and Molecular Biology Faculty Papers

Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases - where treatment may require reduction in the expression of a toxic mutant protein resulting from a gain-of-function allele - is unclear. Here we show the efficacy of allele-specific RNAi as a potential therapy for Charcot-Marie-Tooth disease type 2D (CMT2D), caused by dominant mutations in glycyl-tRNA synthetase (GARS). A de novo mutation in GARS was identified in a patient with a severe peripheral neuropathy, and a mouse model precisely recreating the mutation …

A Macaque Connectome For Large-Scale Network Simulations In Thevirtualbrain, Kelly Shen, Gleb Bezgin, Michael Schirner, Petra Ritter, Stefan Everling, Anthony R. Mcintosh

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. Connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. Here we describe the construction of a macaque (Macaca mulatta and Macaca fascicularis) connectome for whole-cortex simulations in TheVirtualBrain, an open-source simulation platform. We take advantage of available axonal tract-tracing datasets and enhance the existing …

Predator-Induced Fear Causes Ptsd-Like Changes In The Brains And Behaviour Of Wild Animals, Liana Y. Zanette, Emma C. Hobbs, Lauren E. Witterick, Scott A. Macdougall-Shackleton, Michael Clinchy

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Predator-induced fear is both, one of the most common stressors employed in animal model studies of post-traumatic stress disorder (PTSD), and a major focus of research in ecology. There has been a growing discourse between these disciplines but no direct empirical linkage. We endeavoured to provide this empirical linkage by conducting experiments drawing upon the strengths of both disciplines. Exposure to a natural cue of predator danger (predator vocalizations), had enduring effects of at least 7 days duration involving both, a heightened sensitivity to predator danger (indicative of an enduring memory of fear), and elevated neuronal …

Consciousness-Specific Dynamic Interactions Of Brain Integration And Functional Diversity, Andrea I. Luppi, Michael M. Craig, Ioannis Pappas, Paola Finoia, Guy B. Williams, Judith Allanson, John D. Pickard, Adrian M. Owen, Lorina Naci, David K. Menon, Emmanuel A. Stamatakis

Brain and Mind Institute Researchers' Publications

Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain’s default mode …

Sighting Acute Myocardial Infarction Through Platelet Gene Expression., Giuliana Gobbi, Cecilia Carubbi, Guidantonio Malagoli Tagliazucchi, Elena Masselli, Prisco Mirandola, Filippo Pigazzani, Antonio Crocamo, Maria Francesca Notarangelo, Sergio Suma, Elvezia Paraboschi, Giuseppe Maglietta, Srikanth Nagalla, Giulia Pozzi, Daniela Galli, Mauro Vaccarezza, Paolo Fortina, Sankar Addya, Adam Ertel, Paul Bray, Stefano Duga, Carlo Berzuini, Marco Vitale, Diego Ardissino

Department of Cancer Biology Faculty Papers

Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression …

Altered Motor, Anxiety-Related And Attentional Task Performance At Baseline Associate With Multiple Gene Copies Of The Vesicular Acetylcholine Transporter And Related Protein Overexpression In Chat::Cre+ Rats, Craig P. Mantanona, Johan Alsiö, Joanna L. Elson, Beth M. Fisher, Jeffrey W. Dalley, Timothy Bussey, Ilse S. Pienaar

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Transgenic rodents expressing Cre recombinase cell specifically are used for exploring mechanisms regulating behavior, including those mediated by cholinergic signaling. However, it was recently reported that transgenic mice overexpressing a bacterial artificial chromosome containing choline acetyltransferase (ChAT) gene, for synthesizing the neurotransmitter acetylcholine, present with multiple vesicular acetylcholine transporter (VAChT) gene copies, resulting in altered cholinergic tone and accompanying behavioral abnormalities. Since ChAT::Cre+ rats, used increasingly for understanding the biological basis of CNS disorders, utilize the mouse ChAT promotor to control Cre recombinase expression, we assessed for similar genotypical and phenotypical differences in such rats compared …

Are Specific Learning Disorders Truly Specific, And Are They Disorders?, Lien Peters, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors Specific learning disorders, such as dyslexia and dyscalculia, are frequently studied to inform our understanding of cognitive development, genetic mechanisms and brain function. In this Opinion Paper, we discuss limitations of this research approach, including the use of arbitrary criteria to select groups of children, heterogeneity within groups and overlap between domains of learning. By drawing on evidence from cognitive science, neuroscience and genetics, we propose an alternative, dimensional framework. We argue that we need to overcome the problems associated with a categorical approach by taking into account interacting factors at multiple levels of analysis that …

Msto1 Mutations Cause Mtdna Depletion, Manifesting As Muscular Dystrophy With Cerebellar Involvement., S Donkervoort, R Sabouny, P Yun, L Gauquelin, K R Chao, Y Hu, I Al Khatib, A Töpf, P Mohassel, B B Cummings, R Kaur, D Saade, S A Moore, L B Waddell, M A Farrar, J K Goodrich, P Uapinyoying, S H S Chan, A Javed, M E Leach, P Karachunski, J Dalton, L Medne, A Harper, C Thompson, Isabelle Thiffault, S Specht, R E Lamont, Carol J. Saunders, H Racher, F P Bernier, D Mowat, N Witting, J Vissing, R Hanson, Keith A. Coffman, Meagan K. Hainlen, J S Parboosingh, A Carnevale, G Yoon, R E Schnur, Care4rare Canada Consortium, K M Boycott, J K Mah, V Straub, A Reghan Foley, A M Innes, C G Bönnemann, T E Shutt

Manuscripts, Articles, Book Chapters and Other Papers

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA …

The Dynamic Impacts Of Online Healthcare Community On Physician Altruism: A Hidden Markov Model, Kai Luo, Qiu-Hong Wang, Hock Hai Teo

Research Collection School Of Computing and Information Systems

Physician altruism is not only a key foundation of modern medical professionalism, but also a critical component in the theoretical health economics study. There is considerable interest in understanding the impacts of contemporary healthcare technology on physician altruism. In this paper, we investigate the dynamic influence of multiple incentive mechanisms developed by an online healthcare community (OHC) on physician altruism. We model physician altruism as the degree of tendency to benefit the patients at the cost of oneself and focus on the incentive mechanisms that give physicians social and economic returns. The dynamics of physician altruism is characterized via a …

Examining The Theoretical Mechanisms Underlying Health Information Exchange Impact On Healthcare Outcomes: A Physician Agency Perspective, Fang Zhou, Qiu-Hong Wang, Hock Hai Teo

Research Collection School Of Computing and Information Systems

Health information exchange (HIE) is presumed to reduce medical costs by facilitating information sharing across healthcare providers. Existing studies focused on different medical costs or one set of costs, and resulted in mixed findings. We examine the effects of patient access to HIE on two of the most important medical costs of a hospitalization episode - test costs and medication costs - through a natural experiment and the discharge data of a hospital. Besides the negative direct effect of access to HIT on tests costs, we also find its positive spillover effect on medication costs, such that more patients having …

Genome-Wide Association Analysis Of Hippocampal Volume Identifies Enrichment Of Neurogenesis-Related Pathways, Emrin Horgusluoglu-Moloch, Shannon L. Risacher, Paul K. Crane, Derrek Hibar, Paul M. Thompson, Andrew J. Saykin, Kwangsik Nho, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher

Medical Biophysics Publications

© 2019, The Author(s). Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer’s Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.

Multimodal Hippocampal Subfield Grading For Alzheimer’S Disease Classification, Kilian Hett, Vinh Thong Ta, Gwenaëlle Catheline, Thomas Tourdias, José V. Manjón, Pierrick Coupé, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine

Medical Biophysics Publications

© 2019, The Author(s). Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity …

Mousebytes, An Open-Access High-Throughput Pipeline And Database For Rodent Touchscreen-Based Cognitive Assessment, Flavio H. Beraldo, Daniel Palmer, Sara Memar, David I. Wasserman, Wai Jane V. Lee, Shuai Liang, Samantha D. Creighton, Benjamin Kolisnyk, Matthew F. Cowan, Justin Mels, Talal S. Masood, Chris Fodor, Mohammed A. Al-Onaizi, Robert Bartha, Tom Gee, Lisa M. Saksida, Timothy J. Bussey, Stephen S. Strother, Vania F. Prado, Boyer D. Winters, Marco A.M. Prado

Medical Biophysics Publications

© 2019, eLife Sciences Publications Ltd. All rights reserved. Open Science has changed research by making data accessible and shareable, contributing to replicability to accelerate and disseminate knowledge. However, for rodent cognitive studies the availability of tools to share and disseminate data is scarce. Automated touchscreen-based tests enable systematic cognitive assessment with easily standardised outputs that can facilitate data dissemination. Here we present an integration of touchscreen cognitive testing with an open-access database public repository (mousebytes.ca), as well as a Web platform for knowledge dissemination (https://touchscreencognition.org). We complement these resources with the largest dataset of age-dependent high-level cognitive assessment of …

3d Vessel-Wall Virtual Histology Of Whole-Body Perfused Mice Using A Novel Heavy Element Stain, P. Joy Dunmore-Buyze, Charmainne Cruje, Zengxuan Nong, Jason J. Lee, John A. Kiernan, J. Geoffrey Pickering, Maria Drangova

Medical Biophysics Publications

Virtual histology – utilizing high-resolution three-dimensional imaging – is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain – derived from an established histology stain (Verhoeff’s) – is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute …