Digital Commons Network^™

Antibodies Targeting Epitopes On The Cell-Surface Form Of Ns1 Protect Against Zika Virus Infection During Pregnancy, Alex W. Wessel, Nurgun Kose, Robin G. Bombardi, Vicky Roy, Warangkana Chantima, Juthathip Mongkolsapaya, Melissa A. Edeling, Christopher A. Nelson, Irene Bosch, Galit Alter, Gavin R. Screaton, David H. Fremont, James E. Crowe Jr, Michael S. Diamond

Open Access Publications

No abstract provided.

Chemical Inhibition Of Papd5/7 Rescues Telomerase Function And Hematopoiesis In Dyskeratosis Congenita, Siddharth Shukla, Ho-Chang Jeong, Christopher M. Sturgeon, Roy Parker, Luis Francisco Zirnberger Batista

Open Access Publications

No abstract provided.

Primary Cilia Control Glucose Homeostasis Via Islet Paracrine Interactions, Jing W. Hughes, Jung Hoon Cho, Hannah E. Conway, Michael R. Digruccio, Xue Wen Ng, Henry F. Roseman, Damien Abreu, Fumihiko Urano, David W. Piston

Open Access Publications

No abstract provided.

Motile Onchocerca Volvulus Microfilariae In The Anterior Chamber Of The Eye, Michael E Gyasi, Augustine R Hong, Gary J Weil

Open Access Publications

No abstract provided.

A Systematic Review Examining Associations Between Cardiovascular Conditions And Driving Outcomes Among Older Drivers, Ganesh M Babulal, Ramana Kolady, Sarah H Stout, Catherine M Roe

Open Access Publications

There is a vast literature on stroke as a cardiovascular disease and driving outcomes, however little is known about other cardiovascular conditions and driving. The purpose of this review is to examine the literature for studies assessing the effect of non-stroke, vascular conditions on daily driving, reported crash risk and driving decline in older adult drivers as captured by naturalistic methodologies. A systematic review of Embase, Ovid and Scopus Plus examined articles on driving and vascular conditions among older adults. A search yielded 443 articles and, following two screenings, no articles remained that focused on non-stroke, vascular conditions and naturalistic …

Alterations In Plasma Triglycerides And Ceramides: Links With Cardiac Function In Humans With Type 2 Diabetes, Linda R. Peterson, Xuntian Jiang, Ling Chen, Anne C. Goldberg, Marsha S. Farmer, Daniel S. Ory, Jean E. Schaffer

Open Access Publications

No abstract provided.

Gene Therapy For Follistatin Mitigates Systemic Metabolic Inflammation And Post-Traumatic Arthritis In High-Fat Diet-Induced Obesity, Ruhang Tang, Natalia S Harasymowicz, Chia-Lung Wu, Kelsey H Collins, Yun-Rak Choi, Sara J Oswald, Farshid Guilak

Open Access Publications

Obesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Follistatin (FST), a protein that binds myostatin and activin, may have the potential to enhance muscle formation while inhibiting inflammation. Here, we hypothesized that adeno-associated virus 9 (AAV9) delivery of FST enhances muscle formation and mitigates metabolic inflammation and knee OA caused by a high-fat diet in mice. AAV-mediated FST delivery exhibited decreased obesity-induced inflammatory adipokines and cytokines systemically and in the joint synovial fluid. …

A Role For Malignant Brain Tumor Domain-Containing Protein 1 In Human Endometrial Stromal Cell Decidualization, Sangappa B Chadchan, Vineet K Maurya, Gwendalyn L Krekeler, Emily S Jungheim, Ramakrishna Kommagani

Open Access Publications

Up to 30% of women experience early miscarriage due to impaired decidualization. For implantation to occur, the uterine endometrial stromal fibroblast-like cells must differentiate into decidual cells, but the genes required for decidualization have not been fully defined. Here, we show that Malignant Brain Tumor Domain-containing Protein 1 (MBTD1), a member of the polycomb group protein family, is critical for human endometrial stromal cell (HESC) decidualization. MBTD1 predominantly localized to HESCs during the secretory phase and the levels were significantly elevated during

The Tethering Function Of Mitofusin2 Controls Osteoclast Differentiation By Modulating The Ca2+–Nfatc1 Axis, Anna Ballard, Rong Zeng, Allahdad Zarei, Christine Shao, Linda Cox, Hui Yan, Antonietta Franco, Gerald W. Dorn Ii, Roberta Faccio, Deborah J. Veis

Open Access Publications

No abstract provided.

Photoreceptor Responses To Light In The Pathogenesis Of Diabetic Retinopathy, Shahriyar P Majidi, Rithwick Rajagopal

Open Access Publications

Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of …

Bet Bromodomain Inhibition Attenuates Cardiac Phenotype In Myocyte-Specific Lamin A/C-Deficient Mice, Gaelle Auguste, Leila Rouhi, Scot J Matkovich, Cristian Coarfa, Matthew J Robertson, Grazyna Czernuszewicz, Priyatansh Gurha, Ali J Marian

Open Access Publications

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. …

Effects Of Hypoxic And Ischemic Clinical Conditions On The Outcomes Of Acute Ischemic Stroke Patients, Umeshkumar Athiraman, Rene Tempelhoff, Menelaos Karanikolas

Open Access Publications

No abstract provided.

Deficiency Of Peroxiredoxin 2 Exacerbates Angiotensin Ii-Induced Abdominal Aortic Aneurysm, Se-Jin Jeong, Min Ji Cho, Na Young Ko, Sinai Kim, In-Hyuk Jung, Jeong-Ki Min, Sang Hak Lee, Jong-Gil Park, Goo Taeg Oh

Open Access Publications

No abstract provided.

Neutrophil Swarming Delays The Growth Of Clusters Of Pathogenic Fungi, Alex Hopke, Allison Scherer, Samantha Kreuzburg, Michael S. Abers, Christa S. Zerbe, Mary C. Dinauer, Michael K. Mansour, Daniel Irimia

Open Access Publications

No abstract provided.

Maternal Race/Ethnicity And Postpartum Diabetes Screening: A Systematic Review And Meta-Analysis, Cynthia J. Herrick, Ritika Puri, Rana Rahaman, Angela Hardi, Karyn Stewart, Graham A. Colditz

Open Access Publications

No abstract provided.

Peptidoglycan Editing Provides Immunity To Acinetobacter Baumannii During Bacterial Warfare, Nguyen-Hung Le, Gisela Di Venanzio, Juvenal Lopez, Seth W Hennon, Mario F Feldman, Et Al

Open Access Publications

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium

Early Diagnosis And Intervention In Cystic Fibrosis: Imagining The Unimaginable, Andrea M Coverstone, Thomas W Ferkol

Open Access Publications

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of …

Direct Neuronal Reprogramming Of Common Marmoset Fibroblasts By Ascl1, Microrna-9/9*, And Microrna-124 Overexpression, Akisa Nemoto, Reona Kobayashi, Sho Yoshimatsu, Yuta Sato, Takahiro Kondo, Andrew S Yoo, Seiji Shiozawa, Hideyuki Okano

Open Access Publications

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Relationships Between Big-Five Personality Factors And Alzheimer's Disease Pathology In Autosomal Dominant Alzheimer's Disease, Andrew J Aschenbrenner, Jennifer Petros, Eric Mcdade, Guoqiao Wang, David A Balota, Tammie Ls Benzinger, Carlos Cruchaga, Chengjie Xiong, Richard Perrin, Anne M Fagan, John C Morris, Randall Bateman, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD.

Methods: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to …

Dopamine D3 Receptor: A Neglected Participant In Parkinson Disease Pathogenesis And Treatment?, Pengfei Yang, Joel S Perlmutter, Tammie L S Benzinger, John C Morris, Jinbin Xu

Open Access Publications

Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms which relentlessly and progressively lead to substantial disability and economic burden. Pathologically, these symptoms follow the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) associated with abnormal α-synuclein (α-Syn) deposition as cytoplasmic inclusions called Lewy bodies in pigmented brainstem nuclei, and in dystrophic neurons in striatal and cortical regions (Lewy neurites). Pharmacotherapy for PD focuses on improving quality of life and primarily targets dopaminergic pathways. Dopamine acts through two families of receptors, dopamine D1-like and dopamine D2-like; dopamine D3 receptors (D3R) belong to dopamine …

Therapeutic Enhancement Of Blood-Brain And Blood-Tumor Barriers Permeability By Laser Interstitial Thermal Therapy, Afshin Salehi, Mounica R Paturu, Bhuvic Patel, Matthew D Cain, Tatenda Mahlokozera, Alicia B Yang, Tsen-Hsuan Lin, Eric C Leuthardt, Hiroko Yano, Sheng-Kwei Song, Robyn S Klein, Robert Schmidt, Albert H Kim

Open Access Publications

BACKGROUND: The blood-brain and blood-tumor barriers (BBB and BTB), which restrict the entry of most drugs into the brain and tumor, respectively, are a significant challenge in the treatment of glioblastoma. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique increasingly used clinically for tumor cell ablation. Recent evidence suggests that LITT might locally disrupt BBB integrity, creating a potential therapeutic window of opportunity to deliver otherwise brain-impermeant agents.

METHODS: We established a LITT mouse model to test if laser therapy can increase BBB/BTB permeability in vivo. Mice underwent orthotopic glioblastoma tumor implantation followed by LITT in combination …

Antipsychotic Effects On Cortical Morphology In Schizophrenia And Bipolar Disorders, Ruiqi Feng, Fay Y Womer, Et Al

Open Access Publications

No abstract provided.

Glibenclamide Reverses Cardiovascular Abnormalities Of Cantu Syndrome Driven By Katp Channel Overactivity, Conor Mcclenaghan, Yan Huang, Zihan Yan, Theresa M Harter, Carmen M Halabi, Rod Chalk, Attila Kovacs, Gijs Van Haaften, Maria S Remedi, Colin G Nichols

Open Access Publications

Cantu syndrome (CS) is a complex disorder caused by gain-of-function (GoF) mutations in ABCC9 and KCNJ8, which encode the SUR2 and Kir6.1 subunits, respectively, of vascular smooth muscle (VSM) KATP channels. CS includes dilated vasculature, marked cardiac hypertrophy, and other cardiovascular abnormalities. There is currently no targeted therapy, and it is unknown whether cardiovascular features can be reversed once manifest. Using combined transgenic and pharmacological approaches in a knockin mouse model of CS, we have shown that reversal of vascular and cardiac phenotypes can be achieved by genetic downregulation of KATP channel activity specifically in VSM, and by chronic administration …

Macrophage Lc3-Associated Phagocytosis Is An Immune Defense Against Streptococcus Pneumoniae That Diminishes With Host Aging, Megumi Inomata, Shuying Xu, Pallavi Chandra, Simin N. Meydani, Genzou Takemura, Jennifer A. Philips, John M. Leong

Open Access Publications

No abstract provided.

Induction Of Wnt16 Via Peptide-Mrna Nanoparticle-Based Delivery Maintains Cartilage Homeostasis, Huimin Yan, Ying Hu, Antonina Akk, Muhammad Farooq Rai, Hua Pan, Samuel A Wickline, Christine T N Pham

Open Access Publications

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants …

Electrical Impedance Myography For Reducing Sample Size In Duchenne Muscular Dystrophy Trials, Melanie L Leitner, Kush Kapur, Basil T Darras, Michele Yang, Brenda Wong, Laura Dalle Pazze, Julaine Florence, Martin Buck, Laura Freedman, Jose Bohorquez, Seward Rutkove, Craig Zaidman

Open Access Publications

OBJECTIVE: To evaluate the sensitivity of electrical impedance myography (EIM) to disease progression in both ambulatory and non-ambulatory boys with DMD.

METHODS AND PARTICIPANTS: A non-blinded, longitudinal cohort study of 29 ambulatory and 15 non-ambulatory boys with DMD and age-similar healthy boys. Subjects were followed for up to 1 year and assessed using the Myolex

RESULTS: In the ambulatory group, EIM 100 kHz resistance values showed significant change compared to the healthy boys. For example, in lower extremity muscles, the average change in EIM 100 kHz resistance values over 12 months led to an estimated effect size of 1.58. Based …

5-Fluorocytosine Resistance Is Associated With Hypermutation And Alterations In Capsule Biosynthesis In Cryptococcus, R. Blake Billmyre, Shelly Applen Clancey, Lucy X. Li, Tamara L. Doering, Joseph Heitman

Open Access Publications

No abstract provided.

Dill Extract Induces Elastic Fiber Neosynthesis And Functional Improvement In The Ascending Aorta Of Aged Mice With Reversal Of Age-Dependent Cardiac Hypertrophy And Involvement Of Lysyl Oxidase-Like-1, Wassim Fhayli, Quentin Boëté, Nadjib Kihal, Valérie Cenizo, Pascal Sommer, Walter A Boyle, Marie-Paule Jacob, Gilles Faury

Open Access Publications

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin …

Innate Immune Receptor Nod2 Mediates Lgr5+ Intestinal Stem Cell Protection Against Ros Cytotoxicity Via Mitophagy Stimulation, Antonin Levy, Aline Stedman, Eric Deutsch, Françoise Donnadieu, Herbert W. Virgin, Philippe J. Sansonetti, Giulia Nigro

Open Access Publications

No abstract provided.

L-Plastin Deficiency Produces Increased Trabecular Bone Due To Attenuation Of Sealing Ring Formation And Osteoclast Dysfunction, Meenakshi A. Chellaiah, Megan C. Moorer, Sunipa Majumdar, Hanan Aljohani, Sharon C. Morley, Vanessa Yingling, Joseph P. Stains

Open Access Publications

No abstract provided.