62 research outputs found

    Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells

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    Germinal centers (GCs) are the sites where B cells undergo affinity maturation. The regulation of cellular output from the GC is not well understood. Here, we show that from the earliest stages of the GC response, plasmablasts emerge at the GC-T zone interface (GTI). We define two main factors that regulate this process: Tfh-derived IL-21, which supports production of plasmablasts from the GC, and TNFSF13 (APRIL), which is produced by a population of podoplanin+CD157highfibroblastic reticular cells located in the GTI that are also rich in message for IL-6 and chemokines CXCL12, CCL19, and CCL21. Plasmablasts in the GTI express the APRIL receptor TNFRSF13B (TACI), and blocking TACI interactions specifically reduces the numbers of plasmablasts appearing in the GTI. Plasma cells generated in the GTI may provide an early source of affinity-matured antibodies that may neutralize pathogens or provide feedback regulating GC B cell selection

    Plasma membrane Ca 2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca 2+ homeostasis in mice

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    The amplitude and duration of Ca2+ signaling is crucial for B‐cell development and self‐tolerance; however, the mechanisms for terminating Ca2+ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca2+ from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B‐cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B‐1a cells. Mouse and naïve human B cells showed only PMCA1 expression and no PMCA4 by western blot, in contrast to T cells, which did express PMCA4. Calcium handling was normal in Pmca4−/− B cells, but Pmca1 KO B cells had elevated basal levels of Ca2+, elevated levels in ER stores, and reduced Ca2+ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B‐cell Ca2+ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca2+ in B cells

    Factors Surrounding Child Seat Usage in Rideshare Services [Supporting Dataset]

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    69A3551747115/Project 01-005National Transportation Library (NTL) Curation Note: As this dataset is preserved in a repository outside U.S. DOT control, as allowed by the U.S. DOT's Public Access Plan (https://doi.org/10.21949/1503647) Section 7.4.2 Data, the NTL staff has performed NO additional curation actions on this dataset. The current level of dataset documentation is the responsibility of the dataset creator. NTL staff last accessed this dataset at its repository URL on 2022-11-11. If, in the future, you have trouble accessing this dataset at the host repository, please email [email protected] describing your problem. NTL staff will do its best to assist you at that time.This project represents a collaborative, multimodal effort to understand the current state of child passenger safety with respect to rideshare vehicles, with the aim of using this information to develop an effective set of outreach tools. The project team included faculty and student members from the Virginia Tech and Texas A&M Transportation Institutes. Project phases included an in-depth review of the child passenger safety regulatory literature across the United States, a series of focus groups with rideshare riders and drivers, a nationwide internet survey of riders\u2019 and drivers\u2019 knowledge and attitudes toward child passenger safety, and the development of an informational website with a corresponding media outreach campaign. Researchers found that there is a general lack of knowledge of and awareness about the issues surrounding transporting children in this new transportation paradigm, and efforts must continue from both educational and regulatory perspectives to clarify in what ways parents and rideshare drivers can and must safely transport children. The total size of the described zip file is 1.0 MB. Docx files are document files created in Microsoft Word. These files can be opened using Microsoft Word or with an open source text viewer such as Apache OpenOffice. PDFs are used to display text and images and can be opened with any PDF reader or editor. Text files can be view in notepad or any document reading software. Files with the .xlsx extension are Microsoft Excel spreadsheet files. These can be opened in Excel or open-source spreadsheet programs

    The influencing machine

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    Reader published to accompany the group exhibition The Influencing Machine, held at nGbK, Berlin, Germany from December 2018 to January 2019 (see http://insight.cumbria.ac.uk/id/eprint/4291/). This publication addresses the exhibition's various questions, extending its focus to historical continuities and social contexts, with contributions by Geoffrey C. Bowker and Susan Leigh Star, Simone Brown, Wendy Hui Kyong Chun, Kashmir Hill, Lilly Irani, Lee Mackinnon, Tahani Nadim, Lucy Suchman, Cher Tan, and Neli Wagner
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