MS4a4B, a CD20 Homologue in T Cells, Inhibits T Cell Propagation by Modulation of Cell Cycle

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK) and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cell

In Vivo, Multimodal Imaging of B Cell Distribution and Response to Antibody Immunotherapy in Mice

BACKGROUND: B cell depletion immunotherapy has been successfully employed to treat non-Hodgkin's lymphoma. In recent years, increasing attention has been directed towards also using B-cell depletion therapy as a treatment option in autoimmune disorders. However, it appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells, but it is not apparent that this measurement accurately reflects systemic B cell dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Cellular imaging of the targeted population in vivo may provide significant insight towards effective therapy and a greater understanding of underlying disease mechanics. Superparamagnetic iron oxide (SPIO) nanoparticles in concert with near infrared (NIR) fluorescent dyes were used to label and track primary C57BL/6 B cells. Following antibody mediated B cell depletion (anti-CD79), NIR-only labeled cells were expeditiously cleared from the circulation and spleen. Interestingly, B cells labeled with both SPIO and NIR were not depleted in the spleen. CONCLUSIONS/SIGNIFICANCE: Whole body fluorescent tracking of B cells enabled noninvasive, longitudinal imaging of both the distribution and subsequent depletion of B lymphocytes in the spleen. Quantification of depletion revealed a greater than 40% decrease in splenic fluorescent signal-to-background ratio in antibody treated versus control mice. These data suggest that in vivo imaging can be used to follow B cell dynamics, but that the labeling method will need to be carefully chosen. SPIO labeling for tracking purposes, generally thought to be benign, appears to interfere with B cell functions and requires further examination

Mental health and burnout syndrome among postgraduate students in medical and multidisciplinary residencies during the COVID-19 pandemic in Brazil : protocol for a prospective cohort study

Background: The COVID-19 pandemic has led to high levels of physical, psychological, and social stress among health care professionals, including postgraduate students in medical and multidisciplinary residencies. This stress is associated with the intense fear of occupational exposure to SARS-CoV-2, the virus known to cause COVID-19. These professionals are at risk of developing physical and mental illnesses not only due to the infection but also due to prolonged exposure to multidimensional stress and continued work overload. Objective: This study aims to evaluate the prevalence of symptoms suggestive of mental disorders and burnout syndrome and determine the risk factors for burnout among postgraduate students in medical and multidisciplinary residencies in Brazil during the COVID-19 pandemic. Methods: For this prospective cohort study with parallel groups, participants were recruited between July and September 2020 to achieve a sample size of at least 1144 participants. Research instruments such as Depression, Anxiety, and Stress Scale; Patient Health Questionnaire; Brief Resilient Coping Scale; and Oldenburg Burnout Inventory will be used to collect data. Data will be collected in 2 waves: the first wave will include data related to sample characterization and psychosocial evaluation, and the second wave will be launched 12 weeks later and will include an evaluation of the incidence of burnout as well as correlations with the potential predictive factors collected in the first wave. Additionally, we will collect data regarding participants’ withdrawal from work. Results: The recruitment took place from July 29 to September 5, 2020. Data analyses for this phase is already in progress. The second phase of the study is also in progress. The final data collection began on December 1, 2020, and it will be completed by December 31, 2020. Conclusions: We believe the findings of this study will help evaluate the impact of the COVID-19 pandemic on the mental health conditions of health professionals in Brazil as well as contribute to the planning and implementation of appropriate measures that can alleviate these mental health challenges. International Registered Report Identifier (IRRID): DERR1-10.2196/2429

Effects of fermentation on the phytochemical composition and antioxidant properties of soy germ

Soy germ is a remarkable source of bioactive phytochemicals offering an interesting alternative as starting ingredient for fermented food. This work aimed to determine whether lactic acid bacteria fermentation of soy germ induces changes on its phytochemical composition. The antioxidant properties of fermented soy germ samples periodically taken during the fermentation process were evaluated and correlated with the concentration and structural modifications of isoflavones, saponins, phytosterols and tocopherols. Fermented soy germ extracts exhibited a higher inhibition effect against the superoxide anion radical, and lesser but significant ferric-reducing and DPPH radical scavenging effects compared with raw soy germ. By comparison to the traditional whole seed-based products, soy germ exhibits higher levels of isoflavones, saponins, phytosterols and tocopherols. All these phytochemicals contributed to the antioxidant capacity of soy germ and were conserved under lactic acid bacteria fermentation

Gadolinium oxide hybrid nanoparticles: combining imagery and therapy

International audienc