Digital Commons Network^™

The Sport Publication Observational Research Tool (Sport): An Objective Tool To Score The Methodological Quality Of Observational Clinical Sports Medicine Research, Andrew W Kuhn, Paul M Inclan, Ameer A Haider, Michele N Christy, Robert Brophy, Matthew Smith, Matthew J Matava, Et Al.

2020-Current year OA Pubs

BACKGROUND: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases.

PURPOSE: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research.

STUDY DESIGN: Consensus statement.

METHODS: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the …

Blood Dna Methylation-Predicted Plasma Protein Levels And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Esther Jean-Baptiste, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.

METHODS: We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with …

Neural Cells Are Susceptible To Historic And Recently Emerged Oropouche Virus Strains, Kaleigh A. Connors, Maris R. Pedlow, Zachary D. Frey, Marjorie Cornejo Pontelli, Sean P. J. Whelan, W. Paul Duprex, Leonardo D'Aiuto, Zachary P. Wills, Amy L. Hartman

2020-Current year OA Pubs

Oropouche fever is a re-emerging global viral threat caused by infection with Oropouche virus (OROV). While disease is generally self-limiting, historical and recent reports of neurologic involvement highlight the importance of understanding the neuropathogenesis of OROV. In this study, we characterize viral replication kinetics in neurons, microglia, and astrocytes derived from immortalized, primary, and induced pluripotent stem cell-derived cells, which are all permissive to infection with the prototypic OROV BeAn19991. We demonstrate cell-type dependent replication kinetics with both historic and recently emerged viral strains. Further, we show that ex vivo rat brain slice cultures can be infected by all OROV …

Serine/Threonine Protein Kinase Phosphorylation Of Dosr Alters Target Gene Transcription Mechanics And Regulates Mycobacterium Tuberculosis Response To Nitric Oxide Stress, Natalie R. Sontag, Ana Ruiz Manzano, Alwyn M. V. Ecker, Eric A. Galburt, Shumin Tan

2020-Current year OA Pubs

Successful host colonization by bacterial pathogens requires appropriate response and adaptation to environmental signals encountered during infection, with two-component systems (TCSs) and serine/threonine protein kinases (STPKs) being two important signal transduction mechanisms. Mycobacterium tuberculosis (Mtb) possesses similar numbers of STPKs (11) and TCSs (12), but if and how these two regulatory systems coordinate to enable Mtb adaptation in response to key environmental cues remains poorly understood. Here, we identify extensive interactions between STPKs and TCSs, with a subset of STPKs demonstrating interactions with multiple TCS response regulators. STPK phosphorylation of purified DosR, the response regulator of the key nitric oxide …

Multi-Modal Pediatric Critical Care Datamart For Extracorporeal Support Prediction And Decision Support, Miranda Edmunds, Aditi Gupta, Inez Oh, Levi Kaster, Jonathan Sagel, Andrew Michelson, Yuyao Zhuge, Philip Payne, Ahmed Said

2020-Current year OA Pubs

OBJECTIVES: To develop a multimodal pediatric critical care datamart supporting predictive modeling and decision support tool development, integrating high-resolution physiologic and clinical data and future clinical deployment.

MATERIALS AND METHODS: We developed a continuously expanding datamart integrating electronic health record data, high-resolution telemetry, and extracorporeal membrane oxygenation (ECMO)-domain datasets. The platform links static and longitudinal time-series variables with expert-curated neurologic outcomes for both ECMO and non-ECMO patients, enabling trajectory-based analyses.

RESULTS: The datamart currently includes 25 762 pediatric patients, of whom 395 received ECMO support. The datamart captures granular longitudinal physiologic, laboratory, medication, and telemetry data suitable for dynamic predictive …

Clinical Presentation, Risk Factors And Outcome Of Non-Tuberculous Mycobacteria Infection In Hematopoietic Stem-Cell Transplantation: A Multinational Case-Control Study, Mario Fernández-Ruiz, Sasinuch Rutjanawech, Carlos Mejía-Chew, Et Al.

2020-Current year OA Pubs

BACKGROUND: The clinical and microbiological features of infection due to non-tuberculous mycobacteria (NTM) after hematopoietic stem-cell transplantation (HSCT) remain poorly understood.

METHODS: We performed a retrospective, multinational case-control study that included HSCT recipients (≥12 years) diagnosed with NTM disease between January 2008 and December 2018. Controls were HSCT recipients with no evidence of NTM disease, matched (1:2 ratio) by participating center and post-transplant survival. Logistic regression on matched pairs was used to investigate risk factors for NTM disease.

RESULTS: We included 25 cases of NTM disease. The most common HSCT type was allogeneic from unrelated donor (72.0%) after myeloablative conditioning …

Objective Selection Of Bone Mimetic Materials Using Impact Microindentation, Lucas R Budd, Rachana S Vaidya, Babak Jahani, Saideep Nakka, Alexander Proctor, Peter T Burks, Blake K Montgomery, Simon Y Tang

2020-Current year OA Pubs

BACKGROUND: Research and development for orthopedic medical devices, implants, surgical technique, and surgical education all require the appropriate selection of bone mimetic materials to align with the physiologic conditions. There is a critical need for an objective measure of material strength that can be collected, practically, on both bone mimetic materials and living human bone to improve mimetic material selection.

METHODS: This study stratifies commonly used synthetic materials in orthopedic research, as well as animal and human bone, using impact microindentation. The impact microindentation is performed with the OsteoProbe, an FDA-approved handheld medical device that can quantify material strength via …

Risk Factors For Complication And Reoperation In The Treatment Of Discoid Lateral Meniscus In Children And Adolescents: A Multicenter Study, Suzanna Ohlsen, Jeffrey J Nepple, Et Al.

2020-Current year OA Pubs

BACKGROUND: The discoid lateral meniscus (DLM) is a common congenital abnormality of the meniscus. Tears are common, and initial treatment is often not definitive, leading to a spectrum of complications, including persistent symptoms, meniscal insufficiency, osteochondral defects, and recurrent tears potentially requiring reoperation.

PURPOSE: To determine demographic, injury, and perioperative risk factors that increase the likelihood of complications and reoperation after treatment in patients with DLM.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Patients surgically treated for DLM from 9 institutions between 2000 and 2020 were reviewed. Data on demographics, presenting symptoms and signs, surgical findings and treatments, …

Sequence And Chemical Specificity Define The Functional Landscape Of Intrinsically Disordered Regions, Iris Langstein-Skora, Ryan J Emenecker, Alex S Holehouse, Et Al.

2020-Current year OA Pubs

Intrinsically disordered regions (IDRs) pervasively engage in essential molecular functions, yet they are often poorly conserved as assessed by sequence alignment. To explore the seeming paradox of how sequence variability is compatible with persistent function, we examined the functional determinants for a poorly conserved but essential IDR. We show that IDR function depends on two distinct but related properties: sequence and chemical specificity. Whereas sequence specificity operates via binding motifs and depends on the precise order and identity of residues, chemical specificity reflects the sequence-encoded chemistry of multivalent interactions across an IDR and depends on local and global chemical properties. …

Computational Single-Neuron Mechanisms Of Visual Object Coding In The Human Temporal Lobe, Runnan Cao, Jie Zhang, Jie Zheng, Yue Wang, Peter Brunner, Jon T Willie, Shuo Wang

2020-Current year OA Pubs

Understanding how the human brain encodes visual objects involves deciphering the neural computations and circuits in the temporal lobe. Here, we recorded intracranial EEG from the human ventral temporal cortex (VTC) and medial temporal lobe (MTL), as well as single-neuron activity in the MTL, to investigate the computational mechanisms of neural object coding. The VTC exhibited axis-based feature coding, and a neural feature space could be constructed using VTC neural axes, within which visual objects clustered according to high-level categorical relationships. Importantly, MTL neurons encoded receptive fields within this VTC neural feature space, exhibiting selective responses to objects that shared …

A Systemic Selective Modified Mrna Delivery Platform For Preventing Chemotherapy-Induced Cardiotoxicity, Jimeen Yoo, Mengcheng Shen, Et Al.

2020-Current year OA Pubs

Doxorubicin (Dox) is a widely employed chemotherapeutic agent, but its use is clinically limited by dose-accumulative cardiotoxicity. More specifically, Dox induces oxidative stress and causes pro-apoptotic ceramide accumulation in cardiomyocytes (CMs). Acid ceramidase (AC) modified mRNA (modRNA) has been shown to reduce ceramide levels and protect the heart following ischemic injury; however, therapeutic modRNA applications have been hindered by the need for invasive delivery. Here, we present a platform for minimally intrusive transmission of modRNA to the heart. This CM-selective modRNA translational system (cmSMRTs) is encapsulated in lipid nanoparticles for intravenous (IV) delivery to enable systemic administration with high cardiac …

Prediabetes Associates With Musculoskeletal Alterations Independent Of Total Body Adiposity, Alan Fappi, Clifton J Holmes, Chao Cao, Vasavi Shabrish, Aman P Aher, Karen Shen, Paul K Commean, Dwight A Towler, Dominic N Reeds, Gretchen A Meyer, Bettina Mittendorfer

2020-Current year OA Pubs

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown.

METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

Leveraging The Pedsnet Clinical Research Network And Electronic Health Record Data To Enhance Efficiency Of Trial Enrollment For A Rare Pediatric Rheumatic Disease, Pamela F Weiss, Levon Utidjian, Mitchell Maltenfort, Hanieh Razzaghi, Timothy G Brandon, Cassandra Muir, Cora Sears, Edward J Oberle, Jennifer Cooper, Kevin Baszis, Mary B Toth, Esi M Morgan, Christopher B Forrest

2020-Current year OA Pubs

BACKGROUND: We evaluated the PEDSnet clinical research network for study enrollment of juvenile spondyloarthritis, a rare rheumatic disease that includes enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA). METHODS: An electronic health record (EHR)-based typology was developed by an interdisciplinary team to query EHR data for a spectrum of pediatric rheumatic diseases (2009–2023) from 8 PEDSnet centers. The prevalence, characteristics and drug exposures for juvenile spondyloarthritis was explored to gauge feasibility of leveraging the network for study enrollment. Next, the typology was adapted to identify subjects for a clinical trial; the efficiency of EHR typology query was compared to standard screening …

Human Chorionic Gonadotropin Decreases Cerebral Cystic Encephalomalacia And Parvalbumin Interneuron Degeneration In A Pro-Inflammatory Model Of Mouse Neonatal Hypoxia-Ischemia, Benjamin Miller, Alexander Crider, Bhooma Aravamuthan, Rafael Galindo

2020-Current year OA Pubs

Human chorionic gonadotropin (hCG) is an immunoregulatory and neurotrophic glycoprotein of potential clinical utility in the neonate at risk for cerebral injury. However, hCG has not been demonstrated to affect the pro-degenerative actions of inflammation in neonatal brain injury. Here we utilize a neonatal mouse model of mild hypoxia-ischemia (HI) combined with intraperitoneal administration of lipopolysaccharide (LPS) to evaluate the neuroprotective actions of hCG in the setting of systemic inflammation. Intraperitoneal treatment with hCG significantly decreased tissue loss and cystic degeneration in the hippocampus and cerebral cortex of term-equivalent neonatal mice exposed to LPS and HI. Noting that parvalbumin immunoreactive …

Sequential Platinum And Parp Inhibition Enhances Pd1 Immunotherapy Efficacy In Murine Brca2 Mutated Pancreatic Cancer, John C Mcvey, Max M Wattenberg, Heather Coho, Kayjana Infante, Kelly Markowitz, Devora Delman, Cynthia Clendenin, Emma E Furth, Rashmi Tondon, Ben Z Stanger, Robert H Vonderheide, Kim A Reiss, Gregory L Beatty

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, …

A Heterogeneous Population Code At The First Synapse Of Vision, Tessa Herzog, Takeshi Yoshimatsu, Jose Moya-Diaz, Ben James, Leon Lagnado, Tom Baden

2020-Current year OA Pubs

Vision begins when photoreceptors convert fluctuations in light intensity into temporal patterns of glutamate release that drive the retinal network. The input-output relation at this first stage has not been studied in vivo so it is not known how it operates across a photoreceptor population. Using glutamate imaging in zebrafish, we find that individual type 1 cones (PR1; ancestral red cones), which dominate daylight vision in non-avian vertebrates, encode visual stimuli with high reliability and time-precision but routinely vary in sensitivity to luminance, contrast and frequency across the population. Variations in input-output relations are generated by feedback from the horizontal …

Olutasidenib In Recurrent/Relapsed Locally Advanced Or Metastatic Idh1-Mutated Chondrosarcoma: Phase 1b/2 Trial, Robin L Jones, Roman Groisberg, Jean-Yves Blay, Howard Colman, Macarena De La Fuente, Patricia Roxburgh, Mwe Mwe Chao, Hua Tian, Florence Duffaud, Rastislav Bahleda, Brian A Van Tine

2020-Current year OA Pubs

Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efficacy of olutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identifier: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive …

Establishing T1 And Ecv Mapping Based Nomogram Differentiate Acute Ischemic And Nonischemic Myocardial Injury: A Proof-Of-Concept Study, Yanping Su, Kan Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To develop and validate a nomogram based on T1 and extracellular volume fraction (ECV) mapping derived from cardiovascular magnetic resonance (CMR) for differentiating ischemic from nonischemic cardiomyopathies during the acute phase.

METHODS: This retrospective study included patients who underwent CMR at the Fifth Affiliated Hospital of Wenzhou Medical University (internal dataset) and the Fifth Affiliated Hospital of Sun Yat-sen University (external dataset). Patients were assigned to a training set (n = 73), a test set (n = 30), an internal validation set (n = 28), and an external validation set (n = 16). Six multivariable logistic regression models were …

The Effects Of Ovine-Derived Reinforced Tissue Matrix Surrounding Silicone-Based Implants In A Rat Prepectoral Reconstruction Model, Sai L Pinni, Cameron Martin, Nicholas Fadell, Xiaochao Xia, Evan Marsh, Lauren Schellhardt, Xiaowei Li, Matthew D Wood, Justin M Sacks

2020-Current year OA Pubs

Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, prepectoral rat model. We used this model to evaluate the response to an extracellular matrix-based product: ovine-derived reinforced tissue matrix (RTM). Two-piece negative molds were developed through computer-aided design and 3D-printed. The molds were filled with various polydimethylsiloxane mixtures and dip-coated to fabricate implants. Implant material characterization revealed that the implants retained the original 3D-printed mold shape …

Mast Cells Promote Pathology And Susceptibility In Tuberculosis, Ananya Gupta, Vibha Taneja, Javier Rangel-Moreno, Nilofer Naqvi, Abhimanyu, Yun Tao, Mushtaq Ahmed, Kuldeep Singh Chauhan, Daniela Trejo-Ponce De Leon, Gustavo Ramírez-Martínez, Luis Jiménez-Alvarez, Cesar Luna-Rivero, Joaquin Zuniga, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the bacterium

Defining The Heterogeneous Molecular Landscape Of Lung Cancer Cell Responses To Epigenetic Inhibition, Chuwei Lin, Catherine M Sniezek, Christopher D Mcgann, Rashmi Karki, Ross M Giglio, Benjamin A Garcia, José L Mcfaline-Figueroa, Devin K Schweppe

2020-Current year OA Pubs

Epigenetic inhibitors exhibit powerful antiproliferative and anticancer activities. However, cellular responses to small-molecule epigenetic inhibition are heterogeneous and dependent on factors such as the genetic background and metabolic state of cells, as well as on-/off-target engagement of individual small-molecule compounds. The molecular study of the extent of this heterogeneity often measures changes in a single cell line. To more comprehensively profile the effects of small-molecule perturbations and their influence on heterogeneous cellular responses, we present a molecular resource based on the quantification of chromatin, proteome, and transcriptome remodeling due to histone deacetylase inhibitors (HDACi) in non-isogenic cell lines. Through quantitative …

Ablation Of Cd38 In Multiple Myeloma Cells Leads To An Aggressive Phenotype In A Mouse Xenograft Model, Michael R Dyer, Alex Zheleznyak, Erin N Teubner, Julie L Prior, Brad Manion, Zhenghan Jing, Amit K Sharma, Junwei Du, Rui Tang, Mark A Fiala, John F Dipersio, Deborah Veis, Julie O'Neal, Mikhail Y Berezin, Monica Shokeen

2020-Current year OA Pubs

Multiple myeloma (MM) is a plasma cell malignancy characterized by bone pain and end-organ failure. A major challenge in treating MM is therapeutic resistance. CD38-targeted immunotherapies, such as daratumumab, have significantly improved outcomes; however, variable responses, resistance, and relapse remain vital challenges. We hypothesized that loss of CD38 drives a more aggressive phenotype and resistance to therapy. To test this, we developed a CD38 knockout (KO) clone of a human MM cell line and evaluated it in immunodeficient mice. Mice with CD38 KO tumors exhibited an increased tumor burden and reduced survival compared with those with CD38 wild-type (WT) tumors. …

Biomarkers Of Response To Neoadjuvant Palbociclib Plus Anastrozole In Endocrine-Resistant Estrogen Receptor-Positive/Her2-Negative Breast Cancer: A Phase 2 Trial, Tim Kong, Alex Mabry, Maureen Highkin, Jeremy Hoog, Zhanfang Guo, Adrian Gonzales-Gonzales, Shana Thomas, Yingduo Song, Feng Gao, Mateusz Opyrchal, Lindsay Peterson, Foluso Ademuyiwa, Julie Margenthaler, Rebecca Aft, Katherine Glover-Collins, Leslie Nehring, Yu Tao, Souzan Sanati, Ian S Hagemann, Fouad Boulos, Li Ding, Stephen T Oh, Ron Bose, Jason D Weber, Jingqin Luo, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774). Thirty-four patients with clinical stage II/III ER + /HER2- BCs resistant to standard neoadjuvant endocrine therapy (on-treatment Ki67 > 10%) received neoadjuvant ANA/PAL, with serial biopsies analyzed. The primary endpoint, complete cell cycle arrest (CCCA; Ki67

Redefining The Role Of Chaperones For Dot/Icm T4bss-Mediated Substrate Translocation By Legionella Pneumophila, Sukhithasri Vijayrajratnam, Ahmet Hasanovic, Joseph P Vogel

2020-Current year OA Pubs

Legionella pneumophila, the etiological agent of legionnaires' disease, establishes its intracellular niche through the Dot/Icm type IVB secretion system, which translocates ∼300 effector proteins into host cells. Efficient secretion of many effectors requires the IcmS and IcmW chaperones, which interact with both substrates and the type IV coupling protein DotL. A prior model proposed that IcmSW are released from substrates during translocation by transfer to the C terminus of DotL and then recycled to the cytoplasm. This model predicts an excess cytoplasmic pool of IcmSW and their dissociation from DotL. We tested these predictions using quantitative stoichiometric analysis of Dot/Icm …

Dual Roles Of Trpv2 In The Innate Immune Response To Cytosolic Dna: Arresting Dormant And Boosting Activated Sting, Chen Cheng, Hsiang-Ting Lu, Shan Li, Zhongsheng You

2020-Current year OA Pubs

The cGAS/STING-dependent innate immune pathway is central in the cellular response to cytosolic DNA derived from viral infections, genotoxic stress, or mitochondrial defects. While efficient activation of the pathway is crucial for defending against pathogens and cancer, maintaining its dormancy without stimuli is equally important to avoid autoimmunity. However, the precise control of the cGAS/STING pathway remains poorly understood. Here, we report that the ion channel TRPV2 regulates both the dormancy and activation of STING. TRPV2 associates with STING and suppresses spontaneous STING activation in the absence of cytoDNA but dissociates from STING and promotes its activation by releasing Ca

Distinct Contributions Of Etv2+ And Flk1+ Progenitors To Endothelial, Hematopoietic, And Cardiac Lineages, Dereck Alleyne, Minseo Kim, Jun Wu, Yoojung Kwon, Ye-Ram Kim, Ashraf Ul Kabir, Matthew Ishahak, Jeffrey R Millman, Changxu Fan, Hyung Joo Lee, Karen Krchma, Xiaoyun Xing, Kory Lavine, Ting Wang, Kyunghee Choi

2020-Current year OA Pubs

The ETS family transcription factor ETV2, VEGFA, and its receptor FLK1 are essential for hematopoietic, vascular, and cardiac development. Here, we combine dual Etv2 and Flk1 lineage tracing with molecular profiling to define how mesoderm progenitors are allocated to hematopoietic, endothelial, cardiomyocyte, and smooth muscle lineages. We demonstrate that hematopoietic, endothelial, and cardiac valves arise from dual Etv2

Myd88 Signaling In Myeloid Cells Induces Gastrointestinal Tract Injury And Systemic Inflammation After West Nile Virus Infection, Shih-Ching Lin, Fang R Zhao, Matthias Mack, Gabriel Mbalaviele, Michael S Diamond

2020-Current year OA Pubs

Humans with autoantibodies to type I interferons (IFNs) are at higher risk for neurological disease after West Nile virus (WNV) infection. IFN signaling deficient WNV-infected mice develop greater inflammation in the brain, which correlates with loss of gut barrier integrity. Here, we investigate the immune pathways that mediate this virus-gut-brain axis of inflammation. Myd88

Inducible Deletion Of Dgat1 And 2 From Microglia Exacerbates Neurodegeneration And Endolysosomal Lipid Accumulation In Male Ps19 Mice, G Travis Tabor, Alexandra Litvinchuk, Yun Chen, Austin Allison, Carisa Zeng, Hao Hu, Peter B Lin, Prabal Sharma, Samira Parhizkar, Sihui Song, Xin Bao, Abhirami K Iyer, Shih Feng You, Javier Remolina Serrano, Melissa Manis, Emily Franke, Anil G Cashikar, Carla M Yuede, Celeste M Karch, Eric J Huang, Maxim Artyomov, Jason D Ulrich, David M Holtzman, Et Al.

2020-Current year OA Pubs

Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipids are often assumed to be contained in lipid droplets (LDs). While studies have been performed in cell culture and Drosophila models to characterize glial LDs, the roles of microglial LD biogenesis in mammalian tauopathy are unclear. To address this issue, we induced the deletion of diacylglycerol acyltransferases (DGATs) 1 and 2, enzymes critical for LD formation, from microglia in the PS19 mouse model of tauopathy. Microglial DGAT double knockout (KO) exacerbated neurodegeneration and increased the abundance of brain cholesteryl esters in male PS19 …

Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang

2020-Current year OA Pubs

BACKGROUND: Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored. RESULTS: In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific …