B Cell Memory, CD23, and Lipid Metabolism: A Preliminary Study

We each receive vaccinations throughout our lives, which protect us from many pathogens and gives long-term protection through generating a subset of memory lymphocytes. This study explores whether CD23 (Fcε receptor) and high fat diet have roles in regulating memory B cells. CD23 in B cells was examined using CD23 transgenic mice. My data show that, after antigenic stimulation, CD23 co-aggregates with the BCR. The percentages of isotype switched B cells as well as other peripheral B cell subsets in the spleen are not altered in unimmunized CD23 transgenic mice, implicating that CD23 does not have any significant role in the generation of memory B cells. High fat diet with and without high cholesterol led to increased numbers of mature follicular B cells and decreases in transitional B cells in a NPC1L1 independent manner.The marginal zone B cells numbers are increased in the mice fed high fat/high cholesterol diets. This suggests a possible role of high fat/high cholesterol diet in regulating the peripheral development of B cells

Macrophage CGI-58 Deficiency Activates ROS-Inflammasome Pathway to Promote Insulin Resistance in Mice

SummaryOvernutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated in high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific CGI-58 knockout (MaKO) in mice aggravates HFD-induced glucose intolerance and IR, which is associated with augmented systemic/tissue inflammation and proinflammatory activation of adipose tissue macrophages. CGI-58-deficient macrophages exhibit mitochondrial dysfunction due to defective peroxisome proliferator-activated receptor (PPAR)γ signaling. Consequently, they overproduce reactive oxygen species (ROS) to potentiate secretion of proinflammatory cytokines by activating NLRP3 inflammasome. Anti-ROS treatment or NLRP3 silencing prevents CGI-58-deficient macrophages from oversecreting proinflammatory cytokines and from inducing proinflammatory signaling and IR in the cocultured fat slices. Anti-ROS treatment also prevents exacerbation of inflammation and IR in HFD-fed MaKO mice. Our data thus establish CGI-58 as a suppressor of overnutrition-induced NLRP3 inflammasome activation in macrophages

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Proceedings of the OHBM Brainhack 2021

The global pandemic presented new challenges and op-portunities for organizing conferences, and OHBM 2021was no exception. The OHBM Brainhack is an event thatoccurs just prior to the OHBM meeting, typically in-per-son, where scientists of all levels of expertise and interestgather to work and learn together for a few days in a col-laborative hacking-style environment on projects of com-mon interest (1). Building off the success of the OHBM2020 Hackathon (2), the 2021 Open Science SpecialInterest Group came together online to organize a largecoordinated Brainhack event that would take place overthe course of 4 days. The OHBM 2021 Brainhack eventwas organized along two guiding principles, providinga highly inclusive collaborative environment for inter-action between scientists across disciplines and levelsof expertise to push forward important projects thatneed support, also known as the “Hack-Track” of theBrainhack. The second aim of the OHBM Brainhack is toempower scientists to improve the quality of their sci-entific endeavors by providing high-quality hands-ontraining on best practices in open-science approaches.This is best exemplified by the training events providedby the “Train-Track” at the OHBM 2021 Brainhack. Here,we briefly explain both of these elements of the OHBM2021 Brainhack, before continuing on to the Brainhackproceedings