Digital Commons Network^™

Altered Outer Hair Cell Mitochondrial And Subsurface Cisternae Connectomics Are Candidate Mechanisms For Hearing Loss In Mice, Guy Perkins, Jeong Han Lee, Seojin Park, Mincheol Kang, Maria C. Perez-Flores, Saeyeon Ju, Grady Phillips, Anna Lysakowski, Michael Anne Gratton, Ebenezer N. Yamoah

Open Access Publications

Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, ER, and plasma membrane promote regulation of multiple functions, which include intracellular Ca

Satellite Glial Cells Promote Regenerative Growth In Sensory Neurons, Oshri Avraham, Pan-Yue Deng, Sara Jones, Rejji Kuruvilla, Clay F. Semenkovich, Vitaly A. Klyachko, Valeria Cavalli

Open Access Publications

No abstract provided.

Large-Scale Targeted Sequencing Identifies Risk Genes For Neurodevelopmental Disorders, Tianyun Wang, Tychele N. Turner, Et Al.

Open Access Publications

No abstract provided.

Apoptotic Stress Induces Bax-Dependent, Caspase-Independent Redistribution Of Linc Complex Nesprins, Liora Lindenboim, Dan Grozki, Ayelet R. Amsalem-Zafran, Aida Peña-Blanco, Gregg G. Gundersen, Christoph Borner, Didier Hodzic, Ana J. Garcia-Sáez, Howard J. Worman, Reuven Stein

Open Access Publications

No abstract provided.

Braf Alteration In Central And Peripheral Nervous System Tumors, Komal Srinivasa, Kevin A Cross, Sonika Dahiya

Open Access Publications

No abstract provided.

Targeted Muscle Reinnervation For The Management Of Pain In The Setting Of Major Limb Amputation, Blair R Peters, Stephanie A Russo, Julie M West, Amy M Moore, Steven A Schulz

Open Access Publications

The life altering nature of major limb amputations may be further complicated by neuroma formation in up to 60% of the estimated 2 million major limb amputees in the United States. This can be a source of pain and functional limitation of the residual limb. Pain associated with neuromas may limit prosthetic limb use, require reoperation, lead to opioid dependence, and dramatically reduce quality of life. A number of management options have been described including excision alone, excision with repair, excision with transposition, and targeted muscle reinnervation. Targeted muscle reinnervation has been shown to reduce phantom limb and neuroma pain …

Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation And Immunity, Min Xu, Wei Yang, Xuanchuan Wang, Deepak Kumar Nayak

Open Access Publications

Alveolar macrophage (AM) is a mononuclear phagocyte key to the defense against respiratory infections. To understand AM's role in airway disease development, we examined the influence of Secretoglobin family 1a member 1 (SCGB1A1), a pulmonary surfactant protein, on AM development and function. In a murine model, high-throughput RNA-sequencing and gene expression analyses were performed on purified AMs isolated from mice lacking in

A Novel Method For High-Dimensional Anatomical Mapping Of Extra-Axial Cerebrospinal Fluid: Application To The Infant Brain, Mahmoud Mostapha, Sun Hyung Kim, Alan C Evans, Stephen R Dager, Annette M Estes, Robert C Mckinstry, Kelly N Botteron, Guido Gerig, Stephen M Pizer, Robert T Schultz, Heather C Hazlett, Joseph Piven, Jessica B Girault, Mark D Shen, Martin A Styner

Open Access Publications

Cerebrospinal fluid (CSF) plays an essential role in early postnatal brain development. Extra-axial CSF (EA-CSF) volume, which is characterized by CSF in the subarachnoid space surrounding the brain, is a promising marker in the early detection of young children at risk for neurodevelopmental disorders. Previous studies have focused on global EA-CSF volume across the entire dorsal extent of the brain, and not regionally-specific EA-CSF measurements, because no tools were previously available for extracting local EA-CSF measures suitable for localized cortical surface analysis. In this paper, we propose a novel framework for the localized, cortical surface-based analysis of EA-CSF. The proposed …

Deconstructing Tumor Heterogeneity: The Stromal Perspective, Renee E. Vickman, Douglas V. Faget, Sheila A. Stewart, Et Al

Open Access Publications

Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive

Orsay Virus Cp-Δ Adopts A Novel Β-Bracelet Structural Fold And Incorporates Into Virions As A Head Fiber, Yusong R. Guo, Yanlin Fan, Ying Zhou, Miao Jin, Jim L. Zhang, Hongbing Jiang, Matthew V. Holt, Tao Wang, Nicolas L. Young, David Wang, Weiwei Zhong, Yizhi J. Tao

Open Access Publications

Fiber proteins are commonly found in eukaryotic and prokaryotic viruses, where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via noncovalent interactions. Orsay virus, a small RNA virus which specifically infects the laboratory model nematode

Isg15 Fast-Tracks Dna Replication, Alice Meroni, Alessandro Vindigni

Open Access Publications

In this issue, Raso et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.202002175) uncover a novel replication fork speed regulatory network controlled by the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), which plays a central role in the innate immune response and regulates tumorigenesis as well as chemotherapy response.

Sex Differences In Population Dynamics During Formation Of Kidney Bacterial Communities By Uropathogenic Escherichia Coli, Lisa K. Mclellan, Allyssa L. Daugherty, David A. Hunstad

Open Access Publications

No abstract provided.

Depressogenic Self-Schemas Are Associated With Smaller Regional Grey Matter Volume In Never-Depressed Preadolescents, Pan Liu, Matthew R J Vandemeer, Marc F Joanisse, Deanna M Barch, David J A Dozois, Elizabeth P Hayden

Open Access Publications

Self-referential processing (i.e., self-schemas that guide processing of self-descriptive information) emerges early in youth, with deeper encoding of negative self-descriptors and/or shallower encoding of positive self-descriptors causally linked to depression. However, the relationship between depressogenic self-schemas and brain structure is unclear. We investigated associations between self-schemas and regional grey matter volume (GMV) in 84 never-depressed preadolescents oversampled for depression risk based on maternal depression history. Self-schemas were assessed using a Self-Referent Encoding Task (SRET) and regional GMV was indexed via voxel-based morphometry analysis of structural magnetic resonance imaging data. Youths' positive self-schemas were associated with greater regional GMV within the …

Atacgraph: Profiling Genome-Wide Chromatin Accessibility From Atac-Seq, Rita Jui-Hsien Lu, Yen-Ting Liu, Chih Wei Huang, Ming-Ren Yen, Chung-Yen Lin, Pao-Yang Chen

Open Access Publications

Assay for transposase-accessible chromatin using sequencing data (ATAC-seq) is an efficient and precise method for revealing chromatin accessibility across the genome. Most of the current ATAC-seq tools follow chromatin immunoprecipitation sequencing (ChIP-seq) strategies that do not consider ATAC-seq-specific properties. To incorporate specific ATAC-seq quality control and the underlying biology of chromatin accessibility, we developed a bioinformatics software named ATACgraph for analyzing and visualizing ATAC-seq data. ATACgraph profiles accessible chromatin regions and provides ATAC-seq-specific information including definitions of nucleosome-free regions (NFRs) and nucleosome-occupied regions. ATACgraph also allows identification of differentially accessible regions between two ATAC-seq datasets. ATACgraph incorporates the docker image …

Campylobacter Colonization, Environmental Enteric Dysfunction, Stunting, And Associated Risk Factors Among Young Children In Rural Ethiopia: A Cross-Sectional Study From The Campylobacter Genomics And Environmental Enteric Dysfunction (Caged) Project, Dehao Chen, Mark J Manary, Et Al

Open Access Publications

Livestock farming provides a possible mechanism by which smallholder farmers can meet their household need for animal source foods (ASF), which may reduce the risk of stunting. However, direct/indirect contacts with domestic animals may increase colonization by

Cd4 Inhibits Helper T Cell Activation At Lower Affinity Threshold For Full-Length T Cell Receptors Than Single Chain Signaling Constructs, Deborah K Johnson, Wyatt Magoffin, Sheldon J Myers, Jordan G Finnell, John C Hancock, Taylor S Orton, Stephen P Persaud, Kenneth A Christensen, K Scott Weber

Open Access Publications

CD4

Insights From Genetic Studies Of Cerebral Palsy, Sara A Lewis, Sheetal Shetty, Bryce A Wilson, Aris J Huang, Sheng Chih Jin, Hayley Smithers-Sheedy, Michael C Fahey, Michael C Kruer

Open Access Publications

Cohort-based whole exome and whole genome sequencing and copy number variant (CNV) studies have identified genetic etiologies for a sizable proportion of patients with cerebral palsy (CP). These findings indicate that genetic mutations collectively comprise an important cause of CP. We review findings in CP genomics and propose criteria for CP-associated genes at the level of gene discovery, research study, and clinical application. We review the published literature and report 18 genes and 5 CNVs from genomics studies with strong evidence of for the pathophysiology of CP. CP-associated genes often disrupt early brain developmental programming or predispose individuals to known …

Assessment Of Potential Risk Factors For The Development Of Persistent Postural-Perceptual Dizziness: A Case-Control Pilot Study, Aaron Trinidade, Paula Harman, Jon Stone, Jeffrey P Staab, Joel A Goebel

Open Access Publications

No abstract provided.

Nonmicrobial Activation Of Tlrs Controls Intestinal Growth, Wound Repair, And Radioprotection, William F Stenson, Matthew A Ciorba

Open Access Publications

TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE

Mental Distress And Human Rights Violations During Covid-19: A Rapid Review Of The Evidence Informing Rights, Mental Health Needs, And Public Policy Around Vulnerable Populations, Muhammad Rahman, Rabab Ahmed, Ross Brownson, Mary Mckay, Et Al

Open Access Publications

No abstract provided.

Anti-Cd20 B Cell Treatment For Relapsing Multiple Sclerosis, Charles A Roach, Anne H Cross

Open Access Publications

Several clinical trials have demonstrated the efficacy of lytic therapies targeting B cells in the treatment of relapsing multiple sclerosis (MS). More modest efficacy has been noted in the primary progressive subtype of MS. Clinical success has increased interest in the role of B cells in the pathogenesis of MS and in ways to potentially improve upon current B cell therapies. In this mini review, we will critically review previous and ongoing clinical trials of anti-CD20 monoclonal antibodies in MS, including rituximab, ocrelizumab, ofatumumab, and ublituximab. Side effects and adverse event profiles will be discussed. Studies examining the proposed mechanisms …

Apurinic/Apyrimidinic Endonuclease 1 Restricts The Internalization Of Bacteria Into Human Intestinal Epithelial Cells Through The Inhibition Of Rac1, Gerco Den Hartog, Lindsay D Butcher, Amber L Ablack, Laura A Pace, Jailal N G Ablack, Richard Xiong, Soumita Das, Thaddeus S Stappenbeck, Lars Eckmann, Peter B Ernst, Sheila E Crowe

Open Access Publications

Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected with

Regulatory T Cells Developing Peri-Weaning Are Continually Required To Restrain Th2 Systemic Responses Later In Life, Kathryn A. Knoop, Keely G Mcdonald, Chyi-Song Hsieh, Phillip I Tarr, Rodney D Newberry

Open Access Publications

Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development …

Rna Based Approaches To Profile Oncogenic Pathways From Low Quantity Samples To Drive Precision Oncology Strategies, Anja Van De Stolpe, Wim Verhaegh, Jean-Yves Blay, Cynthia X Ma, Patrick Pauwels, Mark Pegram, Hans Prenen, Dirk De Ruysscher, Nabil F Saba, Susan F Slovin, Karen Willard-Gallo, Hatim Husain

Open Access Publications

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples. In contrast, the transcriptome contains information on signaling pathway activity and can complement genomic analyses. Here we present the validation and clinical application of a new knowledge-based mRNA-based diagnostic assay platform (OncoSignal) for measuring activity of relevant signaling …

Advances In Modeling The Immune Microenvironment Of Colorectal Cancer, Paul Sukwoo Yoon, Nuala Del Piccolo, Venktesh S Shirure, Yushuan Peng, Amanda Kirane, Robert J Canter, Ryan C Fields, Steven C George, Sepideh Gholami

Open Access Publications

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are …

Ige And T Cell Reactivity To A Comprehensive Panel Of Cockroach Allergens In Relation To Disease, Anna Pomés, Véronique Schulten, Jill Glesner, Ricardo Da Silva Antunes, Aaron Sutherland, Leonard B Bacharier, Avraham Beigelman, Paula Busse, April Frazier, Alessandro Sette

Open Access Publications

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort.

Nab-Paclitaxel Plus Durvalumab In Patients With Previously Treated Advanced Stage Non-Small Cell Lung Cancer (Abound.2l+), Daniel Morgensztern, Manuel Cobo Dols, Santiago Ponce Aix, Pieter E Postmus, Jaafar Bennouna, Jürgen R Fischer, Oscar Juan-Vidal, David J Stewart, Andrea Ardizzoni, Rafia Bhore, Marianne Wolfsteiner, Martin Reck, Denis Talbot, Ramaswamy Govindan, Teng Jin Ong

Open Access Publications

No abstract provided.

Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological And Immunohistochemical Analysis Of 94 Cases, Qingfu Zhang, Yunan Han, Yao Zhang, Dan Liu, Jian Ming, Bo Huang, Xueshan Qiu

Open Access Publications

Purpose: This study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).

Materials and Methods: We collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate

Results: Among the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 …

Toxic Effects Of Endoplasmic Reticulum Stress Transducer Bbf2h7-Derived Small Peptide Fragments On Neuronal Cells, Koji Matsuhisa, Longjie Cai, Atsushi Saito, Fumika Sakaue, Yasunao Kamikawa, Sachiko Fujiwara, Rie Asada, Yukitsuka Kudo, Kazunori Imaizumi

Open Access Publications

No abstract provided.

Randomized Controlled Crossover Trials Of The Pharmacokinetics Of Prc-063, A Novel Multilayer Extended-Release Formulation Of Methylphenidate, In Healthy Adults, Martin A. Katzman, Greg Mattingly, Larry J. Klassen, Marc J. Cataldo, Graeme A. E. Donnelly

Open Access Publications

No abstract provided.