Human marginal zone B cell development from early T2 progenitors.

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health

HLA genotyping in the international Type 1 Diabetes Genetics Consortium

Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers

One year outcomes of a mentoring scheme for female academics: a pilot study at the Institute of Psychiatry, King's College London

<p>Abstract</p> <p>Background</p> <p>The professional development of under-represented faculty may be enhanced by mentorship, but we understand very little about the mechanisms by which mentoring brings about change. Our study posed the research question, what are the mechanisms by which mentoring may support professional development in under-represented groups?</p> <p>The study aims to: (i) to pilot a mentoring scheme for female academics; (ii) to compare various health-related and attitudinal measures in mentees at baseline, 6 months, and 1 year into the mentoring relationship and, (iii) to compare pre-mentoring expectations to outcomes at 6 months and 1 year follow-up for mentees and mentors.</p> <p>Methods</p> <p>Female academic mentees were matched 1:1 or 2:1 with more senior academic mentors. Online surveys were conducted to compare health-related and attitudinal measures and expectations of mentoring at baseline with outcomes at 6 months and 1 year using paired t-tests and McNemar's test for matched cohort data.</p> <p>Results</p> <p>N = 46 mentoring pairs, 44 (96%) mentees completed the pre-mentoring survey, 37 (80%) at 6 months and 30 (65%) at 1 year. Job-related well-being (anxiety-contentment), self-esteem and self-efficacy all improved significantly and work-family conflict diminished at 1 year. Highest expectations were career progression (39; 89%), increased confidence (38; 87%), development of networking skills (33; 75%), better time-management (29; 66%) and better work-life balance (28; 64%). For mentees, expectations at baseline were higher than perceived achievements at 6 months or 1 year follow-up.</p> <p>For mentors (N = 39), 36 (92%) completed the pre-mentoring survey, 32 (82%) at 6 months and 28 (72%) at 1 year. Mentors' highest expectations were of satisfaction in seeing people progress (26; 69%), seeing junior staff develop and grow (19; 53%), helping solve problems (18; 50%), helping women advance their careers (18; 50%) and helping remove career obstacles (13; 36%). Overall, gains at 6 months and 1 year exceeded pre-mentoring expectations.</p> <p>Conclusions</p> <p>This uncontrolled pilot study suggests that mentoring can improve aspects of job-related well-being, self-esteem and self-efficacy over 6 months, with further improvements seen after 1 year for female academics. Work-family conflict can also diminish. Despite these gains, mentees' prior expectations were shown to be unrealistically high, but mentors' expectations were exceeded.</p

Different expectations: a comparative history of structure, experience, and strategic alliances in the U.S. and U.K. poultry sectors, 1920-1990

This comparative historical analysis demonstrates how memory and reflexive interpretations of the past can shape entrepreneurial willingness to collaborate with larger firms in an industry. Emphasizing the importance of spatial metaphors and periodization for developing historical knowledge, the paper focuses on how the historical space of experience explains how entrepreneurs make strategic choices regarding collaboration under conditions of complexity and uncertainty. Comparing the U.S. and U.K. emerging poultry sectors offers a methodologically novel analysis of an important but little‐studied agribusiness sector, offering a dual reading that compares two versions of historical reasoning both theoretically and empirically

Shark personalities? Repeatability of social network traits in a widely distributed predatory fish

Interest in animal personalities has generated a burgeoning literature on repeatability in individual traits such as boldness or exploration through time or across different contexts. Yet, repeatability can be influenced by the interactive social strategies of individuals, for example, consistent inter-individual variation in aggression is well documented. Previous work has largely focused on the social aspects of repeatability in animal behaviour by testing individuals in dyadic pairings. Under natural conditions, individuals interact in a heterogeneous polyadic network. However, the extent to which there is repeatability of social traits at this higher order network level remains unknown. Here, we provide the first empirical evidence of consistent and repeatable animal social networks. Using a model species of shark, a taxonomic group in which repeatability in behaviour has yet to be described, we repeatedly quantified the social networks of ten independent shark groups across different habitats, testing repeatability in individual network position under changing environments. To understand better the mechanisms behind repeatable social behaviour, we also explored the coupling between individual preferences for specific group sizes and social network position. We quantify repeatability in sharks by demonstrating that despite changes in aggregation measured at the group level, the social network position of individuals is consistent across treatments. Group size preferences were found to influence the social network position of individuals in small groups but less so for larger groups suggesting network structure, and thus, repeatability was driven by social preference over aggregation tendency

Soluble CD23 Controls IgE Synthesis and Homeostasis in Human B Cells

CD23, the low affinity receptor for IgE, exists in membrane and soluble forms. Soluble CD23 fragments are released from membrane CD23 by the endogenous metalloprotease, ADAM10. When purified tonsil B cells are incubated with IL-4 and anti-CD40 to induce class switching to IgE in vitro, membrane CD23 is up-regulated and soluble CD23 accumulates in the medium prior to IgE synthesis. We have uncoupled the effects of membrane CD23 cleavage and accumulation of soluble CD23 on IgE synthesis in this system. We show that siRNA inhibition of CD23 synthesis or inhibition of membrane CD23 cleavage by an ADAM10 inhibitor, GI254023X, suppress IL-4 and anti-CD40-stimulated IgE synthesis. Addition of a recombinant trimeric soluble CD23, ‘triCD23’, enhances IgE synthesis in this system. This occurs even when endogenous membrane CD23 is protected from cleavage by GI254023X, indicating that IgE synthesis is positively controlled by soluble CD23. We show that triCD23 binds to cells co-expressing membrane IgE and membrane CD21 and caps these proteins on the B cell membrane. Up-regulation of IgE by soluble CD23 occurs after class switch recombination and its effects are isotype-specific. These results suggest that membrane IgE and membrane CD21 co-operate in the soluble CD23-mediated positive regulation of IgE synthesis on cells committed to IgE synthesis. Feedback regulation may occur when the concentration of secreted IgE becomes great enough to allow binding to membrane CD23, thus preventing further release of soluble CD23. We interpret these results with the aid of a model for the up-regulation of IgE by soluble CD23

Functional Reactive Polymer Electrospun Matrix

Synthetic multifunctional electrospun composites are a new class of hybrid materials with many potential applications. However, the lack of an efficient, reactive large-area substrate has been one of the major limitations in the development of these materials as advanced functional platforms. Herein, we demonstrate the utility of electrospun poly(glycidyl methacrylate) films as a highly versatile platform for the development of functional nanostructured materials anchored to a surface. The utility of this platform as a reactive substrate is demonstrated by grafting poly(N-isopropylacrylamide) to incorporate stimuli–responsive properties. Additionally, we demonstrate that functional nanocomposites can be fabricated using this platform with properties for sensing, fluorescence imaging, and magneto-responsiveness