40 results match your criteria: "BioMed X Institute[Affiliation]"

Interleukin-2-secreting T helper cells promote extra-follicular B cell maturation via intrinsic regulation of a B cell mTOR-AKT-Blimp-1 axis.

Immunity

December 2024

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address:

During antigen-driven responses, B cells can differentiate at extra-follicular (EF) sites or initiate germinal centers (GCs) in processes that involve interactions with T cells. Here, we examined the roles of interleukin (IL)-2 secreted by T helper (Th) cells during cognate interactions with activated B cells. IL-2 boosted the expansion of EF plasma cells and the secretion of low-mutated immunoglobulin G (IgG).

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Article Synopsis
  • The study investigates how the surrounding DNA sequence affects the repair of double-stranded breaks caused by CRISPR/Cas9, using various genetically modified mouse embryonic stem cell lines.
  • Researchers analyzed over 236,000 mutation outcomes from 2800 synthetic DNA sequences, discovering specific roles of DNA repair proteins like Prkdc and Polm in generating small insertions and deletions.
  • They developed predictive models for these mutational outcomes based on their findings, enhancing the understanding of DNA repair mechanisms and enabling more accurate control of CRISPR-induced mutations.
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Real-time monitoring of therapeutic drugs is crucial for treatment management and pharmacokinetic studies. We present the optimization and affinity tuning of split-aptamer sandwich assay for real-time monitoring of the narrow therapeutic window drug vancomycin, using surface plasmon resonance (SPR). To achieve reversible, label-free sensing of small molecules by SPR, we adapted a vancomycin binding aptamer in a sandwich assay format through the split-aptamer approach.

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Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine.

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BPP: a platform for automatic biochemical pathway prediction.

Brief Bioinform

July 2024

School of Computing Science, University of Glasgow, 18 Lilybank Gardens, Glasgow G12 8RZ, United Kingdom.

A biochemical pathway consists of a series of interconnected biochemical reactions to accomplish specific life activities. The participating reactants and resultant products of a pathway, including gene fragments, proteins, and small molecules, coalesce to form a complex reaction network. Biochemical pathways play a critical role in the biochemical domain as they can reveal the flow of biochemical reactions in living organisms, making them essential for understanding life processes.

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Motivation: INCA is a powerful tool for metabolic flux analysis, however, import and export of data and results can be tedious and limit the use of INCA in automated workflows.

Results: The INCAWrapper enables the use of INCA purely through Python, which allows the use of INCA in common data science workflows.

Availability And Implementation: The INCAWrapper is implemented in Python and can be found at https://github.

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In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells from 25 synovial tissues affected by inflammatory arthritis, including 16 structural, 11 lymphoid, and 15 myeloid cell clusters.

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Organ-on-chip technology is a powerful tool for in vitro modeling. Combining it with organoids overcomes lumen inaccessibility while preserving cellular diversity and function of the intestinal epithelium. Here, we present a protocol for generating and analyzing organ-on-chips using human and mouse intestinal organoids.

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Human intestinal epithelial cells are the interface between luminal content and basally residing immune cells. They form a tight monolayer that constantly secretes mucus creating a multilayered protective barrier. Alterations in this barrier can lead to increased permeability which is common in systemic lupus erythematosus (SLE) patients.

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Joint-level responses to tofacitinib and methotrexate: a post hoc analysis of data from ORAL Start.

Arthritis Res Ther

September 2023

Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.

Background: Rheumatoid arthritis (RA) has a variable impact on different synovial joints, with inflammation being more commonly observed in some joints than others. Emerging evidence suggests that the anatomical variation in pathophysiology could result in differential responses to treatments across the joints, both within and between modes of action. This analysis aimed to characterize joint-specific responses to tofacitinib and methotrexate monotherapy in patients with RA.

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In Search of Disentanglement in Tandem Mass Spectrometry Datasets.

Biomolecules

September 2023

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark.

Generative modeling and representation learning of tandem mass spectrometry data aim to learn an interpretable and instrument-agnostic digital representation of metabolites directly from MS/MS spectra. Interpretable and instrument-agnostic digital representations would facilitate comparisons of MS/MS spectra between instrument vendors and enable better and more accurate queries of large MS/MS spectra databases for metabolite identification. In this study, we apply generative modeling and representation learning using variational autoencoders to understand the extent to which tandem mass spectra can be disentangled into their factors of generation (e.

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Liposomal aggregates sustain the release of rapamycin and protect cartilage from friction.

J Colloid Interface Sci

November 2023

Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland. Electronic address:

Liposomes show promise as biolubricants for damaged cartilage, but their small size results in low joint and cartilage retention. We developed a zinc ion-based liposomal drug delivery system for local osteoarthritis therapy, focusing on sustained release and tribological protection from phospholipid lubrication properties. Our strategy involved inducing aggregation of negatively charged liposomes with zinc ions to extend rapamycin (RAPA) release and improve cartilage lubrication.

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Mutagenic outcomes of CRISPR/Cas9-generated double-stranded breaks depend on both the sequence flanking the cut and cellular DNA damage repair. The interaction of these features has been largely unexplored, limiting our ability to understand and manipulate the outcomes. Here, we measured how the absence of 18 repair genes changed frequencies of 83,680 unique mutational outcomes generated by Cas9 double-stranded breaks at 2,838 synthetic target sequences in mouse embryonic stem cells.

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Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages.

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Dual truncation of tau by caspase-2 accelerates its CHIP-mediated degradation.

Neurobiol Dis

June 2023

BioMed X Institute, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany; AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen am Rhein, Germany. Electronic address:

Intraneuronal aggregates of the microtubule binding protein Tau are a hallmark of different neurodegenerative diseases including Alzheimer's disease (AD). In these aggregates, Tau is modified by posttranslational modifications such as phosphorylation as well as by proteolytic cleavage. Here we identify a novel Tau cleavage site at aspartate 65 (D65) that is specific for caspase-2.

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Developing an in vitro platform to study neuron-oligodendrocyte interaction, particularly myelination, is essential to understand aberrant myelination in neuropsychiatric and neurodegenerative diseases. Here, we provide a controlled, direct co-culture protocol for human induced-pluripotent-stem-cell (hiPSC)-derived neurons and oligodendrocytes on three-dimensional (3D) nanomatrix plates. We describe steps to differentiate hiPSCs into cortical neurons and oligodendrocyte lineage cells on 3D nanofibers.

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Talin-1 is the core mechanosensitive adapter protein linking integrins to the cytoskeleton. The TLN1 gene is comprised of 57 exons that encode the 2,541 amino acid TLN1 protein. TLN1 was previously considered to be expressed as a single isoform.

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Hotspot mutations in the NRAS gene are causative genetic events associated with the development of melanoma. Currently, there are no FDA-approved drugs directly targeting NRAS mutations. Previously, we showed that p38 acts as a tumor suppressor in vitro and in vivo with respect to NRAS-mutant melanoma.

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RNA-seq analysis of alternative pre-mRNA splicing has facilitated an unprecedented understanding of transcriptome complexity in health and disease. However, despite the availability of countless bioinformatic pipelines for transcriptome-wide splicing analysis, the use of these tools is often limited to expert bioinformaticians. The need for high computational power, combined with computational outputs that are complicated to visualize and interpret present obstacles to the broader research community.

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Mitochondrial reactive oxygen is critical for IL-12/IL-18-induced IFN-γ production by CD4 T cells and is regulated by Fas/FasL signaling.

Cell Death Dis

June 2022

Department of Immunology and Oncology, Centro Nacional de Biotecnología- Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.

Mitochondrial activation and the production of mitochondrial reactive oxygen species (mROS) are crucial for CD4 T cell responses and have a role in naïve cell signaling after TCR activation. However, little is known about mROS role in TCR-independent signaling and in recall responses. Here, we found that mROS are required for IL-12 plus IL-18-driven production of IFN-γ, an essential cytokine for inflammatory and autoimmune disease development.

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An Optimized Tissue Dissociation Protocol for Single-Cell RNA Sequencing Analysis of Fresh and Cultured Human Skin Biopsies.

Front Cell Dev Biol

April 2022

Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

We present an optimized dissociation protocol for preparing high-quality skin cell suspensions for in-depth single-cell RNA-sequencing (scRNA-seq) analysis of fresh and cultured human skin. Our protocol enabled the isolation of a consistently high number of highly viable skin cells from small freshly dissociated punch skin biopsies, which we use for scRNA-seq studies. We recapitulated not only the main cell populations of existing single-cell skin atlases, but also identified rare cell populations, such as mast cells.

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