Dowdschmitt3726

Plasma cell longevity is dependent on their accessing and residing in so-called survival niches that are predominantly located in the bone marrow. It is proposed that by some process a small fraction of the plasma cells generated in response to new antigen challenges can enter into the long-lived repertoire by displacing existing plasma cells. Several lines of research show that this process is not stochastic as not all resident, long-lived plasma cells appear equally likely to be displaced. The basis of these differences might reside in the niches, the plasma cells or a combination of both that intersect to create a distribution of susceptibility to replacement and lifespans. In this review, I consider factors that might vary in plasma cells and thus influence their access to niches and the ability of newly generated plasma cells to survive over the long-term. This article is protected by copyright. All rights reserved.Numerous bacterial toxins exert their activity by inactivating or modulating a specific intracellular host target. For this purpose, these toxins have developed efficient strategies to overcome the different host cell defenses including specific binding to cell surface, internalization, passage through the endosome or plasma membrane, exploiting intracellular trafficking and addressing to intracellular targets. Several intracellularly active toxins deliver an active domain into the cytosol that interacts with a target localized to the inner face of the plasma membrane. Thus, the large clostridial glucosylating toxins (LCGTs) target Rho/Ras-GTPases, certain virulence factors of Gram negative bacteria, Rho-GTPases, while Pasteurella multocida toxin (PMT) targets trimeric G-proteins. Others such as botulinum neurotoxins and tetanus neurotoxin have their substrate on synaptic vesicle membrane. LCGTs, PMT, and certain virulence factors from Vibrio sp. show a particular structure constituted of a 4 α-helices bundle (4HBM) protruding from the catalytic site that specifically binds to the membrane phospholipids and then trap the catalytic domain at the proximity of the membrane anchored substrate. Structural and functional analysis indicate that the 4HBM tip of the Clostridium sordellii lethal toxin (TcsL) from the LCGT family contain two loops forming a cavity that mediates the binding to phospholipids and more specifically to phosphatidylserine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Differences in core or tissue-specific ribosomal protein (Rp) composition within ribosomes contribute to ribosome heterogeneity and functional variability. Yet, the degree to which ribosome heterogeneity modulates development is unknown. The Drosophila melanogaster eRpL22 family contains structurally diverse paralogues, eRpL22 and eRpL22-like. Unlike ubiquitously expressed eRpL22, eRpL22-like expression is tissue-specific, notably within the male germline and the eye. We investigated expression within the developing eye to uncover tissue/cell types where specific paralogue roles might be defined. RESULTS Immunohistochemistry analysis confirms ubiquitous eRpL22 expression throughout eye development. In larvae, eRpL22-like is ubiquitously expressed, but highly enriched in the peripodial epithelium (PE). In early pupae, eRpL22-like is broadly distributed in multiple cell types, but later, is primarily enriched in interommatidial hair cells (IoHC). Adult patterns include the ring of accessory cells around ommatidia. Adult retinae IoHC patterning phenotypes (shown by scanning electron microscopy) may be linked to RNAi-mediated eRpL22-like depletion within larval PE. Immunoblots and polysome profile analyses show multiple variants of eRpL22-like across development, with the variant at the expected molecular mass co-sedimenting with active ribosomes. CONCLUSION Our data reveal differential patterns of eRpL22-like expression relative to eRpL22 and suggest a specific role for eRpL22-like in developmental patterning of the eye. This article is protected by copyright. All rights reserved. © 2020 Wiley Periodicals, Inc.OBJECTIVE To study time to pregnancy (TTP) and factors associated with TTP in women with axial spondyloarthritis (axSpA), compared to women with rheumatoid arthritis (RA). METHODS We included 274 women with axSpA and 317 women with RA from the Norwegian nationwide registry RevNatus. For all the women, we had retrospectively collected data on TTP, and a subgroup also had prospectively collected data. We compared TTP in women with axSpA to women with RA using Kaplan-Meier plots and log-rank test. To identify factors associated with TTP, we used Cox proportional hazard regression. RESULTS TTP exceeded 12 months in 21% of women with axSpA. In the subgroup followed prospectively, 32% had TTP which exceeded 12 months. check details Longer TTP was associated with older age, nulliparity, and longer disease duration, with hazard ratios of 0.97 (95% CI 0.94 to 1.00), 0.66 (95% CI 0.50 to 0.88), and 0.94 (95% CI 0.91 to 0.98) respectively. Disease activity, medication, and self-reported health-related quality of life were not associated with TTP. We found no statistically significant differences between axSpA and RA in regard to TTP. CONCLUSION In women with axSpA, longer TTP was associated with older age, nulliparity, and longer disease duration. © 2020, The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.OBJECTIVE To compare the severity of psychological distress between epilepsy patients and healthy controls during the COVID-19 outbreak in southwest China, as well as identify potential risk factors of severe psychological distress among epilepsy patients. METHODS This cross-sectional case control study examined a consecutive sample of patients older than 15 years treated at the epilepsy center of West China Hospital between 01 and 29 February 2020. As controls, sex- and age-matched healthy visitors of inpatients (unrelated to the patients) were also enrolled during the same period. Data on demographics and attention paid to COVID-19 were collected by online questionnaire, data on epilepsy features were collected from electronic medical records, and psychological distress was evaluated using the Kessler 6-item (K-6) psychological distress scale. Potential risk factors of severe psychological distress were identified using multivariate logistic regression. RESULTS The 252 patients and 252 controls in this study were similar along all demographic variables except family income.