Digital Commons Network^™

Levels And Patterns Of Self-Reported And Objectively-Measured Free-Living Physical Activity Among Prostate Cancer Survivors: A Prospective Cohort Study, Lee Smith, Jung Ae Lee, Junbae Mun, Ratna Pakpahan, Kellie R Imm, Sonya Izadi, Adam S Kibel, Graham A Colditz, Robert L Grubb Iii, Kathleen Y Wolin, Siobhan Sutcliffe, Lin Yang

Open Access Publications

BACKGROUND: No prior study has measured or compared self-reported and objectively measured physical activity trajectories in prostate cancer survivors before and after treatment.

METHODS: Clinically localized prostate cancer patients treated with radical prostatectomy were recruited between 2011 and 2014. Of the 350 participants enrolled at the main site, 310 provided self-reported physical activity at baseline before radical prostatectomy, and 5 weeks, 6 months, and 12 months after radical prostatectomy. A subset of participants (n = 81) provided objectively measured physical activity at all study time points by wearing an accelerometer for 7 days each. Changes in activity over time were …

Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon

Open Access Publications

No abstract provided.

Plaidoh: A Novel Method For Functional Prediction Of Long Non-Coding Rnas Identifies Cancer-Specific Lncrna Activities, Sarah C Pyfrom, Hong Luo, Jacqueline E Payton

Open Access Publications

BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.

RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, …

Comprehensive Gene Expression Meta-Analysis Identifies Signature Genes That Distinguish Microglia From Peripheral Monocytes/Macrophages In Health And Glioma, Verena Haage, Marcus Semtner, Ramon Oliveira Vidal, Daniel Perez Hernandez, Winnie W Pong, Zhihong Chen, Dolores Hambardzumyan, Vincent Magrini, Amy Ly, Jason Walker, Elaine Mardis, Philipp Mertins, Sascha Sauer, Helmut Kettenmann, David H Gutmann

Open Access Publications

Monocytes/macrophages have begun to emerge as key cellular modulators of brain homeostasis and central nervous system (CNS) disease. In the healthy brain, resident microglia are the predominant macrophage cell population; however, under conditions of blood-brain barrier leakage, peripheral monocytes/macrophages can infiltrate the brain and participate in CNS disease pathogenesis. Distinguishing these two populations is often challenging, owing to a paucity of universally accepted and reliable markers. To identify discriminatory marker sets for microglia and peripheral monocytes/macrophages, we employed a large meta-analytic approach using five published murine transcriptional datasets. Following hierarchical clustering, we filtered the top differentially expressed genes (DEGs) through …

Ilc2s Are The Predominant Source Of Intestinal Ilc-Derived Il-10, Jennifer K Bando, Susan Gilfillan, Blanda Di Luccia, José L Fachi, Cristiane Sécca, Marina Cella, Marco Colonna

Open Access Publications

Although innate lymphoid cells (ILCs) functionally analogous to T helper type 1 (Th1), Th2, and Th17 cells are well characterized, an ILC subset strictly equivalent to IL-10-secreting regulatory T cells has only recently been proposed. Here, we report the absence of an intestinal regulatory ILC population distinct from group 1 ILCs (ILC1s), ILC2s, and ILC3s in (1) mice bred in our animal facility; (2) mice from The Jackson Laboratory, Taconic Biosciences, and Charles River Laboratories; and (3) mice subjected to intestinal inflammation. Instead, a low percentage of intestinal ILC2s produced IL-10 at steady state. A screen for putative IL-10 elicitors …

Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt

Open Access Publications

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons …

Lats1/2 Kinases Trigger Self-Renewal Of Cancer Stem Cells In Aggressive Oral Cancer, Masami Nozaki, Norikazu Yabuta, Moe Fukuzawa, Satomi Mukai, Ayumi Okamoto, Towa Sasakura, Kohshiro Fukushima, Yoko Naito, Gregory D. Longmore, Hiroshi Nojima

Open Access Publications

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed …

Outcomes And Toxicity Following Yttrium-90 Radioembolization For Hepatic Metastases From Neuroendocrine Tumors-A Single-Institution Experience, Darryl A. Zuckerman, Richard F. Kennard, Amit Roy, Parag J. Parikh, Ashley A. Weiner

Open Access Publications

Background: The prognosis of patients with hepatic metastases from neuroendocrine tumors (NET) is generally good, and radioembolization with Yttrium-90 microspheres is a locoregional therapy that is used in efforts to improve hepatic disease control and survival. This study aims to describe the survival outcomes and toxicities associated with radioembolization for hepatic-predominant metastatic NET in a large single-institution cohort.

Methods: A total of 59 patients underwent radioembolization for metastatic NET with hepatic predominant disease at a single academic center. Patient outcomes were analyzed by Kaplan-Meier survival analysis and toxicities were detailed and described. Ten patients within the cohort underwent post-treatment dosimetric …

Mitochondrial Fusion Supports Increased Oxidative Phosphorylation During Cell Proliferation, Cong-Hui Yao, Rencheng Wang, Yahui Wang, Che-Pei Kung, Jason D. Weber, Gary J. Patti

Open Access Publications

Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion. Impairing mitochondrial fusion by knocking down mitofusion-2 (Mfn2) was sufficient to attenuate proliferation, while overexpressing Mfn2 increased proliferation. Interestingly, impairing mitochondrial fusion decreased OXPHOS but did not deplete ATP levels. Instead, inhibition caused cells to transition from excreting …

Multiancestry Genome-Wide Association Study Of Lipid Levels Incorporating Gene-Alcohol Interactions, Paul S. De Vries, Yun J. Sung, Karen Schwander, Aldi T. Kraja, Mary F. Feitosa, Lisa De Las Fuentes, Renee De Mutsert, C Charles Gu, Yize Li, Treva K. Rice, Lihua Wang, Christine Williams, Mary K. Wojczynski, Michael A. Province, Dabeeru C. Rao, Et Al

Open Access Publications

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test …

Meta-Analysis Of Up To 622,409 Individuals Identifies 40 Novel Smoking Behaviour Associated Genetic Loci, A Mesut Erzurumluoglu, Mengzhen Liu, Victoria E. Jackson, Arpana Agrawal, Laura Bierut, Yi-Ling Chou, Andrew Heath, Pamela A F Madden, John Rice, Et Al

Open Access Publications

No abstract provided.

The Transcriptional Regulator Snon Promotes The Proliferation Of Cerebellar Granule Neuron Precursors In The Postnatal Mouse Brain, Xiaoying Chen, Ayan Chanda, Yoshiho Ikeuchi, Xiaoqing Zhang, Jared V. Goodman, Naveen C. Reddy, Shahriyar P. Majidi, Dennis Y. Wu, Sarah E. Smith, Abigail Godec, Anna Oldenborg, Harrison W. Gabel, Guoyan Zhao, Shirin Bonni, Azad Bonni

Open Access Publications

Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional KO of the transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal male and female mouse brain. In laser capture microdissection …

Voltage-Independent Sk-Channel Dysfunction Causes Neuronal Hyperexcitability In The Hippocampus Of Fmr1 Knock-Out Mice, Pan-Yue Deng, Dan Carlin, Young Mi Oh, Leila K. Myrick, Stephen T. Warren, Valeria Cavalli, Vitaly A. Klyachko

Open Access Publications

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (K

A Hox-Tale Regulatory Circuit For Neural Crest Patterning Is Conserved Across Vertebrates, Hugo J. Parker, Bony De Kumar, Stephen A. Green, Karin D. Prummel, Christopher Hess, Charles K. Kaufman, Christian Mosimann, Leanne M. Wiedemann, Marianne E. Bronner, Robb Krumlauf

Open Access Publications

No abstract provided.

Clinical Characterization Of Host Response To Simian Hemorrhagic Fever Virus Infection In Permissive And Refractory Hosts: A Model For Determining Mechanisms Of Vhf Pathogenesis, Adam L. Bailey, Et Al

Open Access Publications

No abstract provided.

Aav-Mediated Taz Gene Replacement Restores Mitochondrial And Cardioskeletal Function In Barth Syndrome, Silveli Suzuki-Hatano, Madhurima Saha, Skylar A. Rizzo, Rachael L. Witko, Bennett J. Gosiker, Manashwi Ramanathan, Meghan S. Soustek, Michael D. Jones, Peter B. Kang, Barry J. Byrne, W. Todd Cade, Christina A. Pacak

Open Access Publications

No abstract provided.

Clinical Trials In Multiple Sclerosis: Potential Future Trial Designs, Navid Manouchehri, Yinan Zhang, Amber Salter, Rehana Z Hussain, Hans-Peter Hartung, Bernhard Hemmer, Ralf Linker, Benjamin M Segal, Gary Cutter, Olaf Stüve

Open Access Publications

Clinical trials of new treatments in multiple sclerosis (MS) currently require large sample sizes and long durations in order to yield reliable results. The differential responses of an already heterogeneous population of MS patients to individual disease-modifying therapies (DMTs) will further complicate future trials. MS trials with smaller samples and faster outcomes are conceivable through the substitution of current clinical and MRI outcomes with objectively measureable genomic and proteomic biomarkers. Currently, biomarkers that could be utilized for diagnosis and monitoring of MS disease activity are in the early validation phase. The power of single biomarkers or multiple correlated biomarkers to …

Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part I: Biological Diagnostics, Michael S. Diamond, Et Al

Open Access Publications

No abstract provided.

Phosphatidylcholine Synthesis Through Cholinephosphate Cytidylyltransferase Is Dispensable In Leishmania Major, Samrat Moitra, Mattie C. Pawlowic, Fong-Fu Hsu, Kai Zhang

Open Access Publications

No abstract provided.

Association Of High Birth Weight With Incident Heart Failure In The Aric Study, Abdirahim Rashid, Anandita Agarwala, Eric Novak, David L. Brown

Open Access Publications

No abstract provided.

Estimates Of The 2016 Global Burden Of Kidney Disease Attributable To Ambient Fine Particulate Matter Air Pollution, Benjamin Bowe, Yan Xie, Tingting Li, Yan Yan, Hong Xian, Ziyad Al-Aly

Open Access Publications

No abstract provided.

Mild Chronic Perturbation Of Inhibition Severely Alters Hippocampal Function, Min-Yu Sun, Luke Ziolkowski, Peter Lambert, Hong-Jin Shu, Micah Keiser, Nicholas Rensing, Natasha Warikoo, Monika Martinek, Carson Platnick, Ann Benz, John Bracamontes, Gustav Akk, Joe Henry Steinbach, Charles F. Zorumski, Michael Wong, Steven Mennerick

Open Access Publications

No abstract provided.

A Short Translational Ramp Determines The Efficiency Of Protein Synthesis, Manasvi Verma, Junhong Choi, Kyle A. Cottrell, Zeno Lavagnino, Erica N. Thomas, Slavica Pavlovic-Djuranovic, Pawel Szczesny, David W. Piston, Hani S. Zaher, Joseph D. Puglisi, Sergej Djuranovic

Open Access Publications

No abstract provided.

The Single-Cell Transcriptomic Landscape Of Early Human Diabetic Nephropathy, Parker C. Wilson, Haojia Wu, Yuhei Kirita, Kohei Uchimura, Nicolas Ledru, Helmut G. Rennke, Paul A. Welling, Sushrut S. Waikar, Benjamin D. Humphreys

Open Access Publications

No abstract provided.

Deficiency Of Dietary Fiber In Slc5a8-Null Mice Promotes Bacterial Dysbiosis And Alters Colonic Epithelial Transcriptome Towards Proinflammatory Milieu, Sathish Sivaprakasam, Pramodh K. Ganapathy, Mohd Omar Faruk Sikder, Moamen Elmassry, Sabarish Ramachandran, Kameswara Rao Kottapalli, Vadivel Ganapathy

Open Access Publications

No abstract provided.

Reduction Of Leukocyte Microvascular Adherence And Preservation Of Blood-Brain Barrier Function By Superoxide-Lowering Therapies In A Piglet Model Of Neonatal Asphyxia, Jacob B. Ruden, Kevin L. Quick, Ernesto R. Gonzales, Aarti R. Shah, T. S. Park, Nan Kennedy, Laura L. Dugan, Jeffrey M. Gidday

Open Access Publications

No abstract provided.

Tau Phosphorylation Rates Measured By Mass Spectrometry Differ In The Intracellular Brain Vs. Extracellular Cerebrospinal Fluid Compartments And Are Differentially Affected By Alzheimer’S Disease, Nicolas R. Barthelemy, Nipun Mallipeddi, Paul Moiseyev, Chihiro Sato, Randall J. Bateman

Open Access Publications

No abstract provided.

Cellular And Molecular Characterization Of Multiplex Autism In Human Induced Pluripotent Stem Cell-Derived Neurons, Emily M A Lewis, Kesavan Meganathan, Dustin Baldridge, Paul Gontarz, Bo Zhang, Azad Bonni, John N Constantino, Kristen L Kroll

Open Access Publications

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk.

Methods: Here, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a …

Crispr/Cas9 Mediated Generation Of An Ovine Model For Infantile Neuronal Ceroid Lipofuscinosis (Cln1 Disease), S. L. Eaton, C. Proudfoot, S. G. Lillico, P. Skehel, R. A. Kline, K. Hamer, N. M. Rzechorzek, E. Clutton, R. Gregson, T. King, C. A. O'Neill, J. D. Cooper, G. Thompson, C. B. Whitelaw, T. M. Wishart

Open Access Publications

No abstract provided.

Increased Mtdna Abundance And Improved Function In Human Barth Syndrome Patient Fibroblasts Following Aav-Taz Gene Delivery, Silveli Suzuki-Hatano, Mughil Sriramvenugopal, Manash Ramanathan, Meghan Soustek, Barry J. Byrne, W. T. Cade, Peter B. Kang, Christina A. Pacak

Open Access Publications

No abstract provided.