Digital Commons Network^™

Identification And Characterization Of Novel Trpm1 Autoantibodies From Serum Of Patients With Melanoma-Associated Retinopathy, Juliette Varin, Margaret M. Reynolds, Nassima Bouzidi, Sarah Tick, Juliette Wohlschlegel, Ondine Becquart, Christelle Michiels, Olivier Dereure, Robert M. Duvoisin, Catherine W. Morgans, José-Alain Sahel, Quentin Samaran, Bernard Guillot, José S. Pulido, Isabelle Audo, Christina Zeitz

Open Access Publications

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti-TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding …

Come Together: Protein Assemblies, Aggregates And The Sarcostat At The Heart Of Cardiac Myocyte Homeostasis, Moydul Islam, Abhinav Diwan, Kartik Mani

Open Access Publications

Homeostasis in vertebrate systems is contingent on normal cardiac function. This, in turn, depends on intricate protein-based cellular machinery, both for contractile function, as well as, durability of cardiac myocytes. The cardiac small heat shock protein (csHsp) chaperone system, highlighted by αB-crystallin (CRYAB), a small heat shock protein (sHsp) that forms ∼3-5% of total cardiac mass, plays critical roles in maintaining proteostatic function via formation of self-assembled multimeric chaperones. In this work, we review these ancient proteins, from the evolutionarily preserved role of homologs in protists, fungi and invertebrate systems, as well as, the role of sHsps and chaperones in …

Subsequent Neoplasms And Late Mortality In Children Undergoing Allogeneic Transplantation For Nonmalignant Diseases, Justine M. Kahn, Robert J. Hayashi, Et Al.

Open Access Publications

No abstract provided.

Improving Hba1c With Glucose Self-Monitoring In Diabetic Patients With Epxdiabetes, A Phone Call And Text Message-Based Telemedicine Platform: A Randomized Controlled Trial, Ran Xu, Maggie Xing, Kavon Javaherian, Robert Peters, Will Ross, Carlos Bernal-Mizrachi

Open Access Publications

No abstract provided.

Case Report: Dsm-5 Misses An Edge Case In Tic Disorders Nosology, Kevin J. Black

Open Access Publications

A boy with multiple phonic tics, one lifetime motor tic, and no impairment or marked distress does not meet criteria for any DSM-5 tic disorder diagnosis. The next version of the Diagnostic and Statistical Manual should adjust the criteria for Tourette's Disorder and/or for "other specified tic disorder" and "unspecified tic disorder."

Targeting Histone Deacetylases To Modulate Graft-Versus-Host Disease And Graft-Versus-Leukemia, Sena Kim, Srikanth Santhanam, Sora Lim, Jaebok Choi

Open Access Publications

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main therapeutic strategy for patients with both malignant and nonmalignant disorders. The therapeutic benefits of allo-HSCT in malignant disorders are primarily derived from the graft-versus-leukemia (GvL) effect, in which T cells in the donor graft recognize and eradicate residual malignant cells. However, the same donor T cells can also recognize normal host tissues as foreign, leading to the development of graft-versus-host disease (GvHD), which is difficult to separate from GvL and is the most frequent and serious complication following allo-HSCT. Inhibition of donor T cell toxicity helps in reducing GvHD but also …

Harnessing Activin A Adjuvanticity To Promote Antibody Responses To Bg505 Hiv Envelope Trimers, Diane G Carnathan, Kirti Kaushik, Ali H Ellebedy, Chiamaka A Enemuo, Etse H Gebru, Pallavi Dhadvai, Mohammed Ata Ur Rasheed, Matthias G Pauthner, Gabriel Ozorowski, Rafi Ahmed, Dennis R Burton, Andrew B Ward, Guido Silvestri, Shane Crotty, Michela Locci

Open Access Publications

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Expanding The Genetic Architecture Of Nicotine Dependence And Its Shared Genetics With Multiple Traits, Bryan C. Quach, Michael J. Bray, Pamela Madden, Laura J. Bierut, Nancy L. Saccone, Et Al.

Open Access Publications

No abstract provided.

Work-Related And Personal Factors Associated With Mental Well-Being During The Covid-19 Response: Survey Of Health Care And Other Workers, Bradley A Evanoff, Jaime R Strickland, Ann Marie Dale, Lisa Hayibor, Emily Page, Jennifer G Duncan, Thomas Kannampallil, Diana L Gray

Open Access Publications

BACKGROUND: The response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented disruption in work conditions. This study describes the mental health and well-being of workers both with and without clinical exposure to patients with coronavirus disease (COVID-19).

OBJECTIVE: The aim of this study is to measure the prevalence of stress, anxiety, depression, work exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic and describe work-related and personal factors associated with their mental health and well-being.

METHODS: All faculty, staff, and postdoctoral fellows of …

Converging On Bladder Health Through Design Thinking: From An Ecology Of Influence To A Focused Set Of Research Questions, Jessica B Lewis, Sonya S Brady, Siobhan Sutcliffe, Ariana L Smith, Elizabeth R Mueller, Kyle Rudser, Alayne D Markland, Ann Stapleton, Sheila Gahagan, Shayna D Cunningham, Prevention Of Lower Urinary Tract Symptoms Plus Research Consortium

Open Access Publications

Lower urinary tract symptoms affect a substantial number of women in the United States (U.S.) and globally. In 2015, the Prevention of Lower Urinary tract Symptoms in women (PLUS) Research Consortium was funded to establish the scientific basis for prevention efforts by (1) understanding healthy bladder function and (2) identifying risk and protective factors for bladder health in women across the lifecourse. This transdisciplinary consortium generated a list of over 600 candidate risk and protective factors for bladder health in women and girls and refined and prioritized these into 29 focused research questions to inform a national longitudinal observational study …

Tictimer Web: Software For Measuring Tic Suppression Remotely, Jonathan K Black, Jonathan M Koller, Kevin J. Black

Open Access Publications

Woods and Himle developed a standardized tic suppression paradigm (TSP) for the experimental setting, to quantify the effects of intentional tic suppression in Tourette syndrome. We previously provided a computer program to facilitate recording tic occurrence and to automate reward delivery during the several experimental conditions of the TSP. The present article describes a web-based program that performs the same functions. Implementing this program on the web allows research sessions to be performed remotely, in tandem with a video calling program. Relevant data for each session, such as the timing of tics and dispensed rewards, are stored in plain text …

Tourette Syndrome Research Highlights From 2019, Andreas Hartmann, Yulia Worbe, Kevin J Black

Open Access Publications

This is the sixth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2019 relevant to Tourette syndrome and other tic disorders. The highlights from 2020 is being drafted on the Authorea online authoring platform; readers are encouraged to add references or give feedback on our selections comments feature on this page. After the calendar year ends, this article is submitted as the annual update for the Tics collection F1000Research.

Revisiting The Spectrum Of Bladder Health: Relationships Between Lower Urinary Tract Symptoms And Multiple Measures Of Well-Being, Siobhan Sutcliffe, Charles Cain, Tamara Bavendam, C. Neill Epperson, Colleen M. Fitzgerald, Sheila Gahagan, Alayne D. Markland, David A. Shoham, Ariana L. Smith, Kyle Rudser, Prevention Of Lower Urinary Tract Symptoms Research Consortium

Open Access Publications

No abstract provided.

Evolution And Structure Of Clinically Relevant Gene Fusions In Multiple Myeloma, Steven M. Foltz, Qingsong Gao, Christopher J. Yoon, Hua Sun, Lijun Yao, Yize Li, Reyka G. Jayasinghe, Song Cao, Justin King, Daniel R. Kohnen, Mark A. Fiala, Li Ding, Ravi Vij

Open Access Publications

No abstract provided.

Therapies For Tuberculosis And Aids: Myeloid-Derived Suppressor Cells In Focus, Anca Dorhoi, Shabaana A Khader, Et Al

Open Access Publications

The critical role of suppressive myeloid cells in immune regulation has come to the forefront in cancer research, with myeloid-derived suppressor cells (MDSCs) as a main oncology immunotherapeutic target. Recent improvement and standardization of criteria classifying tumor-induced MDSCs have led to unified descriptions and also promoted MDSC research in tuberculosis (TB) and AIDS. Despite convincing evidence on the induction of MDSCs by pathogen-derived molecules and inflammatory mediators in TB and AIDS, very little attention has been given to their therapeutic modulation or roles in vaccination in these diseases. Clinical manifestations in TB are consequences of complex host-pathogen interactions and are …

Site-1 Protease Ablation In The Osterix-Lineage In Mice Results In Bone Marrow Neutrophilia And Hematopoietic Stem Cell Alterations, Debabrata Patra, Joongho Kim, Qiang Zhang, Eric Tycksen, Linda J Sandell

Open Access Publications

Site-1 protease (S1P) ablation in the osterix-lineage in mice drastically reduces bone development and downregulates bone marrow-derived skeletal stem cells. Here we show that these mice also suffer from spina bifida occulta with a characteristic lack of bone fusion in the posterior neural arches. Molecular analysis of bone marrow-derived non-red blood cell cells, via single-cell RNA-Seq and protein mass spectrometry, demonstrate that these mice have a much-altered bone marrow with a significant increase in neutrophils and

The Relation Between Personality And Biomarkers In Sensitivity And Conversion To Alzheimer-Type Dementia, Janet M Duchek, Andrew J Aschenbrenner, Anne M Fagan, Tammie L S Benzinger, John C Morris, David A Balota

Open Access Publications

OBJECTIVES: The present study explored relationships among personality, Alzheimer's disease (AD) biomarkers, and dementia by addressing the following questions: (1) Does personality discriminate healthy aging and earliest detectable stage of AD? (2) Does personality predict conversion from healthy aging to early-stage AD? (3) Do AD biomarkers mediate any observed relationships between personality and dementia status/conversion?

METHODS: Both self- and informant ratings of personality were obtained in a large well-characterized longitudinal sample of cognitively normal older adults (N = 436) and individuals with early-stage dementia (N = 74). Biomarkers included amyloid imaging, hippocampal volume, cerebral spinal fluid (CSF) Aβ42, and CSF …

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.

Microglia Implicated In Tauopathy In The Striatum Of Neurodegenerative Disease Patients From Genotype To Phenotype, Huifangjie Li, William C Knight, Pengfei Yang, Yingqiu Guo, Joel S Perlmutter, John C Morris, Randall J Bateman, Tammie L S Benzinger, Jinbin Xu

Open Access Publications

We found interactions between dopamine and oxidative damage in the striatum involved in advanced neurodegeneration, which probably change the microglial phenotype. We observed possible microglia dystrophy in the striatum of neurodegenerative brains. To investigate the interactions between oxidative damage and microglial phenotype, we quantified myeloperoxidase (MPO), poly (ADP-Ribose) (PAR), and triggering receptors expressed on myeloid cell 2 (TREM2) using enzyme-linked immunosorbent assay (ELISA). To test the correlations of microglia dystrophy and tauopathy, we quantified translocator protein (TSPO) and tau fibrils using autoradiography. We chose the caudate and putamen of Lewy body diseases (LBDs) (Parkinson's disease, Parkinson's disease dementia, and Dementia …

Natural Bladder Flling Alters Resting Brain Function At Multiple Spatial Scales: A Proof‑Of‑Concept Mapp Network Neuroimaging Study, Ishtiaq Mawla, Henry Lai, Gerald Andriole, Et Al.

Open Access Publications

No abstract provided.

Social Jetlag And Prostate Cancer Incidence In Alberta's Tomorrow Project: A Prospective Cohort Study, Liang Hu, Andrew Harper, Emily Heer, Jessica Mcneil, Chao Cao, Yikyung Park, Kevin Martell, Geoffrey Gotto, Grace Shen-Tu, Cheryl Peters, Darren Brenner, Lin Yang

Open Access Publications

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta's Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-<1 h (from 0 to anything smaller than 1), 1-<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (

Proteomic Resistance Biomarkers For Pi3k Inhibitor In Triple Negative Breast Cancer Patient-Derived Xenograft Models, Zhanfang Guo, Tina Primeau, Jingqin Luo, Cynthia Zhang, Hua Sun, Jeremy Hoog, Feng Gao, Shixia Huang, Dean P Edwards, Sherri R Davies, Rebecca Aft, Li Ding, Matthew J Ellis, Shunqiang Li, Cynthia X Ma

Open Access Publications

PI3K pathway activation is frequently observed in triple negative breast cancer (TNBC). However, single agent PI3K inhibitors have shown limited anti-tumor activity. To investigate biomarkers of response and resistance mechanisms, we tested 17 TNBC patient-derived xenograft (PDX) models representing diverse genomic backgrounds and varying degrees of PI3K pathway signaling activities for their tumor growth response to the pan-PI3K inhibitor, BKM120. Baseline and post-treatment PDX tumors were subjected to reverse phase protein array (RPPA) to identify protein markers associated with tumor growth response. While BKM120 consistently reduced PI3K pathway activity, as demonstrated by reduced levels of phosphorylated AKT, percentage tumor growth …

Dissemination And Implementation Research In Sports And Exercise Medicine And Sports Physical Therapy: Translating Evidence To Practice And Policy, Oluwatoyosi B A Owoeye, Rachel S Rauvola, Ross C Brownson

Open Access Publications

Knowledge from research evidence is wasted unless it is applied. While the scientific evidence base for many sports and exercise medicine and sports physical therapy interventions is robust, real-world implementation and evolution to scale remains an ongoing challenge. Dissemination and implementation research is important to generate evidence-informed, cost-effective and context-specific strategies for implementation partners and stakeholders to effectively apply and sustain the best research evidence in public health and clinical practice. However, this field of inquiry remains underexplored in sports and exercise medicine and sports physical therapy. Most intervention studies in sports and exercise medicine and sports physical therapy are …

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.

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 …

Postural Directionality And Head Tremor In Cervical Dystonia, Qiyu Chen, Jeanne P Vu, Elizabeth Cisneros, Casey N Benadof, Zheng Zhang, Richard L Barbano, Christopher G Goetz, Joseph Jankovic, Hyder A Jinnah, Joel S Perlmutter, Mark I Appelbaum, Glenn T Stebbins, Cynthia L Comella, David A Peterson

Open Access Publications

Background: Although abnormal head and neck postures are defining features of cervical dystonia (CD), head tremor (HT) is also common. However, little is known about the relationship between abnormal postures and HT in CD.

Methods: We analyzed clinical data and video recordings from 185 patients enrolled by the Dystonia Coalition. We calculated the likelihood of their HT and HT type ("regular" vs. "jerky") given directionality of abnormal head postures, disease duration, sex, and age.

Results: Patients with retrocollis were more likely to have HT than patients with anterocollis (X

Discussion: We found that HT is more likely for CD patients …

Utilization Of The Sharing Antimicrobial Reports For Pediatric Stewardship (Sharps) Collaborative Electronic Mailing List (Listserv) By Healthcare Professionals, Christopher C Mcpherson, Zachary A Vesoulis, Talene A Metjian, Mirela Grabic, Summer Reyes, Sydney Reyes, Christina Krucylak, Cindy Terrill, Jason G Newland

Open Access Publications

Optimizing pediatric antimicrobial stewardship is challenging. In this retrospective study, we evaluated 515 original e-mails to 482 members of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative electronic mailing list ([email protected]). The plurality of threads discussed clinical practice guidelines, and pharmacists were most likely to initiate and respond. Representation was geographically diverse within and outside the United States.

Termini Restraining Of Small Membrane Proteins Enables Structure Determination At Near-Atomic Resolution, Shixuan Liu, Shuang Li, Yihu Yang, Weikai Li

Open Access Publications

Small membrane proteins are difficult targets for structural characterization. Here, we stabilize their folding by restraining their amino and carboxyl termini with associable protein entities, exemplified by the two halves of a superfolder GFP. The termini-restrained proteins are functional and show improved stability during overexpression and purification. The reassembled GFP provides a versatile scaffold for membrane protein crystallization, enables diffraction to atomic resolution, and facilitates crystal identification, phase determination, and density modification. This strategy gives rise to 14 new structures of five vertebrate proteins from distinct functional families, bringing a substantial expansion to the structural database of small membrane proteins. …

Fenofibrate Reduces The Severity Of Neuroretinopathy In A Type 2 Model Of Diabetes Without Inducing Peroxisome Proliferator-Activated Receptor Alpha-Dependent Retinal Gene Expression, Jennifer M Enright, Sheng Zhang, Christina Thebeau, Emily Siebert, Alexander Jin, Veda Gadiraju, Xiaodong Zhang, Shiming Chen, Clay F Semenkovich, Rithwick Rajagopal

Open Access Publications

Fenofibrate slows the progression of clinical diabetic retinopathy (DR), but its mechanism of action in the retina remains unclear. Fenofibrate is a known agonist of peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor critical for regulating metabolism, inflammation and oxidative stress. Using a DR mouse model,

Cholesterol 25-Hydroxylase Suppresses Sars-Cov-2 Replication By Blocking Membrane Fusion, Ruochen Zang, James Brett Case, Xiucui Ma, Maria Florencia Gomez Castro, Zhuoming Liu, Qiru Zeng, Haiyan Zhao, Juhee Son, Paul W. Rothlauf, Gaopeng Hou, Michael D. Vahey, Kartik Mani, Daved H. Fremont, Abhinav Diwan, Michael S. Diamond, Sean P.J. Whelan, Siyuan Ding, Et Al.

Open Access Publications

No abstract provided.