5,167 results match your criteria: "Gladstone|UCSF Center for Cell Circuitry[Affiliation]"

Article Synopsis
  • The study examines gene regulatory changes associated with cancer by analyzing chromatin accessibility across eight different tumor types, revealing the influence of copy number alterations on tumor characteristics.
  • Researchers found specific chromatin signatures in cancer that are closely related to healthy cell types, particularly noting similarities between basal-like breast cancer and secretory-type luminal epithelial cells.
  • Advanced neural network models highlighted the significance of noncoding mutations near cancer-associated genes, suggesting that widely dispersed mutations in cancer have important functional roles in gene regulation.
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Genomics methods have uncovered patterns in a range of biological systems, but obscure important aspects of cell behavior: the shapes, relative locations, movement, and interactions of cells in space. Spatial technologies that collect genomic or epigenomic data while preserving spatial information have begun to overcome these limitations. These new data promise a deeper understanding of the factors that affect cellular behavior, and in particular the ability to directly test existing theories about cell state and variation in the context of morphology, location, motility, and signaling that could not be tested before.

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Article Synopsis
  • HMGB1 is an important protein that increases the accessibility of DNA in nucleosomes and counteracts the effects of linker histone H1, even though it is less abundant and binds less strongly than H1.
  • Research shows that HMGB1 can mitigate H1's inhibiting effect on DNA accessibility without actually removing H1, highlighting how they can coexist on the same nucleosome.
  • The study reveals that HMGB1 binds at sites on the nucleosome that are distinct from where H1 binds, causing local DNA distortion and enabling a wider variety of chromatin states, which could also apply to other chromatin regulatory proteins.
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While often represented as static entities, gene networks are highly context-dependent. Here, we developed a multi-task learning strategy to yield context-specific representations of gene network dynamics. We assembled a corpus comprising ~103 million human single-cell transcriptomes from a broad range of tissues and diseases and performed a two stage pretraining, first with non-malignant cells to generate a foundational model and then with continual learning on cancer cells to tune the model to the cancer domain.

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Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis.

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Asundexian versus Apixaban in Patients with Atrial Fibrillation.

N Engl J Med

January 2025

From Duke Clinical Research Institute, Duke University School of Medicine (J.P.P., M.R.P., R.D.L., W.S.J., J. Harrington, S.J.E., F.W.R., J.H.A.), and Duke University Medical Center (J.P.P., M.R.P., R.D.L., W.S.J., J. Harrington, F.W.R., J.H.A.) - both in Durham, NC; Hirslanden Clinic Zurich, Zurich, Switzerland (J.S.); the School of Medicine, Tulane University, New Orleans (K.F.); the University Medical Center, University of Groningen, Groningen (I.C.V.G., M.R.), Radboud University Medical Center, Nijmegen (M.H.), Rijnstate Hospital, Arnhem (M.H.), and the Dutch Network for Cardiovascular Research, Utrecht (M.H.) - all in the Netherlands; Cooper Medical School of Rowan University, Camden (A.M.R.), and Bayer U.S., Whippany (R.C.) - both in New Jersey; the Cardiology Center of Beijing, Anzhen Hospital No. 2, Beijing (C.-S.M.); the Canadian VIGOUR Centre, University of Alberta, Edmonton, and St. Michael's Hospital, Unity Health Toronto, and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto - all in Canada (S.G.G.); the Uppsala Clinical Research Center and the Department of Medical Sciences, Uppsala University, Uppsala, Sweden (J.O.); the Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia (C.H.); the Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan (M.A.); the School of Cardiology, University of Pisa, and the Cardiology Division, Pisa University Hospital, Pisa (R.D.C.), and Santa Maria della Misericordia Hospital, University of Perugia, Perugia (V.C.) - all in Italy; the Department of Cardiology, University Heart and Vascular Center Hamburg, and the German Center for Cardiovascular Research, Hamburg (P.K.), and Bayer, Wuppertal (C.N., T.V., H.M.) - all in Germany; the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (P.K.), the Faculty of Medicine, National Heart and Lung Institute, Imperial College, London (D.A.G.), the Centre for Health Services and Clinical Research, Faculty of Life and Medical Sciences, University of Hertfordshire, Hatfield (D.A.G.), and the Liverpool Centre for Cardiovascular Science at University of Liverpool and John Moores University and Liverpool Heart and Chest Hospital, Liverpool (G.Y.H.L.) - all in the United Kingdom; the Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark (G.Y.H.L.); and Bayer, São Paulo (J. Hung).

Background: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.

Methods: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban.

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Article Synopsis
  • COVID-19 is linked to serious thrombotic events and neurological symptoms that can persist in long COVID patients, but the mechanisms behind these complications are not well understood and treatment options are limited.
  • *Fibrinogen, a key component of blood clots, is found in high amounts in the lungs and brains of COVID-19 patients, where it correlates with the severity of the disease and can predict cognitive issues afterward.
  • *Research shows that fibrin interacts with the SARS-CoV-2 spike protein, causing inflammatory blood clots that contribute to complications like inflammation and nerve damage, suggesting that therapies targeting fibrin may be beneficial for treating both acute and long COVID cases.*
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Animal and bacterial viruses share conserved mechanisms of immune evasion.

Cell

October 2024

Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address:

Animal and bacterial cells sense and defend against viral infections using evolutionarily conserved antiviral signaling pathways. Here, we show that viruses overcome host signaling using mechanisms of immune evasion that are directly shared across the eukaryotic and prokaryotic kingdoms of life. Structures of animal poxvirus proteins that inhibit host cGAS-STING signaling demonstrate architectural and catalytic active-site homology shared with bacteriophage Acb1 proteins, which inactivate CBASS anti-phage defense.

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Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions.

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A genome-wide CRISPR screen identifies BRD4 as a regulator of cardiomyocyte differentiation.

Nat Cardiovasc Res

March 2024

Cardiovascular Institute, Epigenetics Institute, and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Human induced pluripotent stem cell (hiPSC) to cardiomyocyte (CM) differentiation has reshaped approaches to studying cardiac development and disease. In this study, we employed a genome-wide CRISPR screen in a hiPSC to CM differentiation system and reveal here that BRD4, a member of the bromodomain and extraterminal (BET) family, regulates CM differentiation. Chemical inhibition of BET proteins in mouse embryonic stem cell (mESC)-derived or hiPSC-derived cardiac progenitor cells (CPCs) results in decreased CM differentiation and persistence of cells expressing progenitor markers.

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Neutralizing and binding antibody responses to SARS-CoV-2 with hybrid immunity in pregnancy.

NPJ Vaccines

August 2024

Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.

Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity.

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Objectives: Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus).

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The rapid evolution of viruses generates proteins that are essential for infectivity and replication but with unknown functions, due to extreme sequence divergence. Here, using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, we found that 62% of viral proteins are structurally distinct and lack homologues in the AlphaFold database. Among the remaining 38% of viral proteins, many have non-viral structural analogues that revealed surprising similarities between human pathogens and their eukaryotic hosts.

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Suppressed HIV antibody responses following exposure to antiretrovirals-evidence from PrEP randomized trials and early antiretroviral treatment initiation studies.

Int J Infect Dis

November 2024

Vitalant Research Institute, San Francisco, California, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA; Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening.

Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP).

Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users.

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Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses.

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Torsional Twist of the SARS-CoV and SARS-CoV-2 SUD-N and SUD-M domains.

bioRxiv

August 2024

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Coronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vacuole that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge.

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Maternal diabetes mellitus is among the most frequent environmental contributors to congenital birth defects, including heart defects and craniofacial anomalies, yet the cell types affected and mechanisms of disruption are largely unknown. Using multi-modal single cell analyses, here we show that maternal diabetes affects the epigenomic landscape of specific subsets of cardiac and craniofacial progenitors during embryogenesis. A previously unrecognized cardiac progenitor subpopulation expressing the homeodomain-containing protein ALX3 showed prominent chromatin accessibility changes and acquired a more posterior identity.

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Visual Dose Monitoring for Whole Breast Radiation Therapy Treatments via Combined Cherenkov Imaging and Scintillation Dosimetry.

Int J Radiat Oncol Biol Phys

February 2025

Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; The Department of Radiation Oncology and Applied Sciences, Dartmouth Cancer Center, Dartmouth Health, Lebanon, New Hampshire.

Article Synopsis
  • The study explores a new method for monitoring radiation doses during whole breast radiation therapy (WBRT) using scintillation dosimetry and Cherenkov imaging to improve accuracy and reduce secondary cancer risk.
  • Ten patients were monitored with small scintillator dosimeters compared to traditional optically stimulated luminescent dosimeters (OSLDs), showing a high accuracy in dose measurement with only a 2.8% discrepancy on average.
  • The findings suggest that this integrated approach allows for quicker and more effective verification of radiation doses in real-time, improving patient safety by ensuring precise dose delivery.
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Pan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020: a prospective cohort study.

Lancet Microbe

October 2024

Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway; Parasites and Microbes, Wellcome Sanger Institute, Cambridge, UK; Helsinki Institute for Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. Electronic address:

Article Synopsis
  • The study aimed to evaluate the risk and prevalence of hospital-acquired bacterial infections in intensive care units during the first wave of COVID-19 by using advanced deep-sequencing techniques.
  • Conducted in a hard-hit region in northern Italy, the research involved collecting and analyzing samples from patients in both regular wards and ICUs to identify specific bacterial pathogens.
  • The findings highlighted the effectiveness of this novel sequencing approach in tracking bacterial transmission and understanding antimicrobial resistance during a time of increased patient load.
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The envelope (E) protein of SARS-CoV-2 is the smallest of the three structural membrane proteins of the virus. E mediates budding of the progeny virus in the endoplasmic reticulum Golgi intermediate compartment of the cell. It also conducts ions, and this channel activity is associated with the pathogenicity of SARS-CoV-2.

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Article Synopsis
  • Enhancers are key regulatory elements in our DNA that can produce enhancer RNAs (eRNAs), and their malfunction can lead to diseases known as enhanceropathies, which need more research to understand specific mechanisms.
  • This study focuses on AANCR, a noncoding RNA related to the APOE gene in Alzheimer's Disease, showing that it plays a vital role in regulating APOE expression and influencing inflammation in brain cells called astrocytes.
  • By identifying how AANCR is activated and its effects, the research suggests it could be a valuable target for developing treatments for neurodegenerative diseases.
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SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral lifecycle by suppressing host innate immune responses.

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Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability. However, how best to quantify genome-wide noise, remains unclear. Here we utilize a small-molecule perturbation (IdU) to amplify noise and assess noise quantification from numerous scRNA-seq algorithms on human and mouse datasets, and then compare to noise quantification from single-molecule RNA FISH (smFISH) for a panel of representative genes.

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Current and future directions in network biology.

Bioinform Adv

August 2024

Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN 46556, United States.

Article Synopsis
  • Network biology is an interdisciplinary field that combines computational and biological sciences to improve understanding of cellular functions and diseases, though it is still a developing area after two decades.* -
  • The field faces challenges due to the increasing complexity and diversity of biological data, but active research areas include molecular networks, patient similarity networks, and machine learning applications.* -
  • The article provides an overview of recent advancements, highlights future directions, and emphasizes the need for diverse scientific communities and educational initiatives within network biology.*
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