Digital Commons Network^™

Live Neuron High-Content Screening Reveals Synaptotoxic Activity In Alzheimer Mouse Model Homogenates, Hao Jiang, Thomas J. Esparza, Terrance T. Kummer, Haining Zhong, Jens Rettig, David L. Brody

Open Access Publications

No abstract provided.

Remethylation Of Dnmt3a−/− Hematopoietic Cells Is Associated With Partial Correction Of Gene Dysregulation And Reduced Myeloid Skewing, Shamika Ketkar, Angela M. Verdoni, Amanda M. Smith, Celia V. Bangert, Elizabeth R. Leight, David Y. Chen, Meryl K. Brune, Nichole M. Helton, Mieke Hoock, Daniel R. George, Catrina Fronick, Robert S. Fulton, Sai Mukund Ramakrishnan, Gue Su Chang, Allegra A. Petti, David H. Spencer, Christopher A. Miller, Timothy J. Ley

Open Access Publications

No abstract provided.

Exercise Training Results In Lower Amyloid Plaque Load And Greater Cognitive Function In An Intensity Dependent Manner In The Tg2576 Mouse Model Of Alzheimer's Disease, Riya Thomas, Scott D Zimmerman, Kayla M Yuede, John R Cirrito, Leon M Tai, Benjamin F Timson, Carla M Yuede

Open Access Publications

Three months of exercise training (ET) decreases soluble Aβ

Sensitivity Analysis Of Monte Carlo Model Of A Gantry-Mounted Passively Scattered Proton System, Milad Baradaran-Ghahfarokhi, Francisco Reynoso, Michael T Prusator, Baozhou Sun, Tianyu Zhao

Open Access Publications

PURPOSE: This study aimed to present guidance on the correlation between treatment nozzle and proton source parameters, and dose distribution of a passive double scattering compact proton therapy unit, known as Mevion S250.

METHODS: All 24 beam options were modeled using the MCNPX MC code. The calculated physical dose for pristine peak, profiles, and spread out Bragg peak (SOBP) were benchmarked with the measured data. Track-averaged LET (LET

RESULTS: For the physical dose distribution, the MCNPX MC model matched measurements data for all the options to within 2 mm and 2% criterion. The Mevion S250 was found to have a …

Human Plasmacytoid Dendritic Cells And Cutaneous Melanoma, Matilde Monti, Francesca Consoli, Raffaella Vescovi, Mattia Bugatti, William Vermi

Open Access Publications

The prognosis of metastatic melanoma (MM) patients has remained poor for a long time. However, the recent introduction of effective target therapies (BRAF and MEK inhibitors for BRAFV600-mutated MM) and immunotherapies (anti-CTLA-4 and anti-PD-1) has significantly improved the survival of MM patients. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells (pDCs) exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. A distinctive feature of pDCs is the production of high …

A Single-Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor Alters The Development Of Host Immunity, Munir Akkaya, Patrick W Sheehan, Et Al

Open Access Publications

The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host's ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite

Mirna-Based Rapid Differentiation Of Purified Neurons From Hpscs Advancestowards Quick Screening For Neuronal Disease Phenotypes In Vitro, Mitsuru Ishikawa, Takeshi Aoyama, Shoichiro Shibata, Takefumi Sone, Hiroyuki Miyoshi, Hirotaka Watanabe, Mari Nakamura, Saori Morota, Hiroyuki Uchino, Andrew S Yoo, Hideyuki Okano

Open Access Publications

Obtaining differentiated cells with high physiological functions by an efficient, but simple and rapid differentiation method is crucial for modeling neuronal diseases in vitro using human pluripotent stem cells (hPSCs). Currently, methods involving the transient expression of one or a couple of transcription factors have been established as techniques for inducing neuronal differentiation in a rapid, single step. It has also been reported that microRNAs can function as reprogramming effectors for directly reprogramming human dermal fibroblasts to neurons. In this study, we tested the effect of adding neuronal microRNAs, miRNA-9/9*, and miR-124 (miR-9/9*-124), for the neuronal induction method of hPSCs …

Radiation And Checkpoint Inhibitor Immunotherapy Lead To Long Term Disease Control In A Metastatic Rcc Patient With Brain Metastases, Maria Levitin, Joel Ofori, Woo Jae Shin, Jiayi Huang, Mackenzie Daly, Dengfeng Cao, Russell Pachynski

Open Access Publications

Renal cell carcinoma (RCC) comprises 4.2% of all new cancer cases in the United States and 30% of cases are metastatic (mRCC) at diagnosis. Brain metastatic RCC historically has poor prognosis, but the development of immune checkpoint inhibitors has revolutionized their care and may be successfully combined with SBRT to improve prognosis. Here, we present a case of a patient with mRCC who had brain metastases treated with concurrent immune checkpoint inhibitors and SBRT. He continues to survive with good functional status years following his initial diagnosis. We discuss the relevant history regarding treatment approach in patients with brain metastatic …

When Sting Meets Viruses: Sensing, Trafficking And Response, Zhaohe Li, Siqi Cai, Yutong Sun, Li Li, Siyuan Ding, Xin Wang

Open Access Publications

To effectively defend against microbial pathogens, the host cells mount antiviral innate immune responses by producing interferons (IFNs), and hundreds of IFN-stimulated genes (ISGs). Upon recognition of cytoplasmic viral or bacterial DNAs and abnormal endogenous DNAs, the DNA sensor cGAS synthesizes 2',3'-cGAMP that induces STING (stimulator of interferon genes) undergoing conformational changes, cellular trafficking, and the activation of downstream factors. Therefore, STING plays a pivotal role in preventing microbial pathogen infection by sensing DNAs during pathogen invasion. This review is dedicated to the recent advances in the dynamic regulations of STING activation, intracellular trafficking, and post-translational modifications (PTMs) by the …

A Spinal Neural Circuitry For Converting Touch To Itch Sensation, Sihan Chen, Xiao-Fei Gao, Yuxi Zhou, Ben-Long Liu, Xian-Yu Liu, Yufen Zhang, Devin M. Barry, Kun Liu, Yingfu Jiao, Rita Bardoni, Weifeng Yu, Zhou-Feng Chen

Open Access Publications

No abstract provided.

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.

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.

Site-Specific Effects Of Neurosteroids On Gaba(A) Receptor Activation And Desensitization, Yusuke Sugasawa, Wayland W.L. Cheng, John R. Bracamontes, Zi-Wei Chen, Lei Wang, Allison L. Germann, Spencer R. Pierce, Thomas C. Senneff, Kathiresan Krishnan, David E. Reichert, Douglas F. Covey, Gustav Akk, Alex S. Evers

Open Access Publications

This study examines how site-specific binding to three identified neurosteroid-binding sites in the α

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

Open Access Publications

No abstract provided.

Viral-Immune Cell Interactions At The Maternal-Fetal Interface In Human Pregnancy, Elaine L Parker, Rachel B Silverstein, Sonam Verma, Indira U Mysorekar

Open Access Publications

The human decidua and placenta form a distinct environment distinguished for its promotion of immunotolerance to infiltrating semiallogeneic trophoblast cells to enable successful pregnancy. The maternal-fetal interface also successfully precludes transmission of most pathogens. This barrier function occurs in conjunction with a diverse influx of decidual immune cells including natural killer cells, macrophages and T cells. However, several viruses, among other microorganisms, manage to escape destruction by the host adaptive and innate immune system, leading to congenital infection and adverse pregnancy outcomes. In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika …

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 …

Characterization Of The Complete Mitochondrial Genomes Of Two Sibling Species Of Parasitic Roundworms, Haemonchus Contortus And Teladorsagia Circumcincta, Nikola Palevich, Paul H Maclean, Young-Jun Choi, Makedonka Mitreva

Open Access Publications

No abstract provided.

Phase I Study Of Vemurafenib In Children With Recurrent Or Progressive Brafv600e Mutant Brain Tumors: Pacific Pediatric Neuro-Oncology Consortium Study (Pnoc-002), Theodore Nicolaides, Karen Gauvain, Et Al

Open Access Publications

No abstract provided.

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.

Cadmium Activates Ampa And Nmda Receptors With M3 Helix Cysteine Substitutions, Timothy J. Wilding, James E. Huettner

Open Access Publications

AMPA and NMDA receptors are ligand-gated ion channels that depolarize postsynaptic neurons when activated by the neurotransmitter L-glutamate. Changes in the distribution and activity of these receptors underlie learning and memory, but excessive change is associated with an array of neurological disorders, including cognitive impairment, developmental delay, and epilepsy. All of the ionotropic glutamate receptors (iGluRs) exhibit similar tetrameric architecture, transmembrane topology, and basic framework for activation; conformational changes induced by extracellular agonist binding deform and splay open the inner helix bundle crossing that occludes ion flux through the channel. NMDA receptors require agonist binding to all four subunits, whereas …

Identification Of New Helicobacter Pylori Subpopulations In Native Americans And Mestizos From Peru, Andrés Julián Gutiérrez-Escobar, Douglas E Berg, Et Al

Open Access Publications

Region-specific

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 …

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