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Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.

Researchers at the Precision Immunology Institute at the Icahn School of Medicine (PrIISM), New York, describe their contribution to the global research effort against COVID-19 by trying to separate signal from noise in the preprint arena.This Comment article from the Precision Immunology Institute at the Icahn School of Medicine (PrIISM), New York, describes their efforts to provide critical reviews of COVID-19 articles posted daily on the preprint servers bioRxiv and medRxiv.

Objectives/Goals: To determine the heterogeneity in CD4:CD8 ratio in a well-characterized cohort of PWH and to investigate the predictors of intestinal CD4:CD8 ratio reconstitution (CD4:CD8>1) and its impact on systemic inflammation. Methods/Study Population: We enrolled 52 PWH on ART and with peripheral HIV-RNA Results/Anticipated Results: PWH had a lower CD4:CD8 ratio both in the peripheral blood [p1. This subset of PWH was more likely female (62% vs. 38%, p = 0.0158), diagnosed with HIV for a longer time [p = 0.0347] have longer duration of most recent viral suppression [p = 0.0365] higher CD4+ T cells at enrollment [p =  0.0262] and higher CD4+ T cell nadir. Multiple logistic regression showed that duration of HIV infection [OR 1.13 (95% C.I. 1.02–1.3)] and CD4 =  T cell nadir[OR 1.01 (95% C.I. 1.001–1.016)] were associated with colonic CD4:CD8 >1. Colonic CD4:CD8 ratio partially correlated with the peripheral blood CD4:CD8 ratio (r = 0.274, p = 0.068) and with the pro-inflammatory cytokines IL-20 (r =  -0.413, p = 0.036) and SLAMF-1 (r =  -0.329, p = 0.074). Discussion/Significance of Impact: In PWH, CD4:CD8 ratio

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models 1 , 2 . Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence. In a cohort of 87 individuals with COVID-19, the memory B cell response at 6.2 months after the onset of disease evolves in a manner that is consistent with the persistence of SARS-CoV-2 antigen.

B cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n  = 145; validation cohort 1, n  = 664; and validation cohort 2, n  = 143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammation. Using single-cell RNA sequencing, single-cell IgH gene sequencing and protein-level validation, we mapped the compositional, transcriptional and clonotypic landscape of mucosal and circulating B cells. We found major perturbations within the mucosal B cell compartment, including an expansion of naive B cells and IgG + plasma cells with curtailed diversity and maturation. Furthermore, we isolated an auto-reactive plasma cell clone targeting integrin αvβ6 from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing TFH-like T peripheral helper cells that were associated with the pathogenic B cell response. Finally, across all three cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that correlates with disease activity and predicts disease complications. Our data demonstrate a highly dysregulated B cell response in UC and highlight a potential role of B cells in disease pathogenesis. Multi-modal profiling reveals major alterations in colonic B cells in patients with ulcerative colitis, including reduced clonal diversity of plasma cells, and suggests that circulating gut-homing plasmablasts could serve as a biomarker for disease activity.

Infectious diseases are globally associated with high mortality in spite of the availability of therapeutic agents against most pathogenic microorganisms. This is due to the emergence of new infectious diseases and novel pathogen strategies to evade host defenses. There is thus a need to develop potent therapeutics and techniques for effective delivery of vaccines and drugs. Particles based on poly(lactic acid) and poly(lactic-co-glycolic acid) polymer-based particles are suitable delivery systems due to their biodegradable and biocompatible nature. They can be tailored to display various properties such as sustained release, dose sparing, bioactivity maintenance and targeted delivery. This review focuses on polymeric particle-based delivery systems to develop novel vaccines or drugs. Cellular interactions of particulate systems and the mechanism of action in animal models are also discussed.

Background Formation of inclusion bodies poses a major hurdle in recovery of bioactive recombinant protein from Escherichia coli . Urea and guanidine hydrochloride have routinely been used to solubilize inclusion body proteins, but many times result in poor recovery of bioactive protein. High pH buffers, detergents and organic solvents like n -propanol have been successfully used as mild solubilization agents for high throughput recovery of bioactive protein from bacterial inclusion bodies. These mild solubilization agents preserve native-like secondary structures of proteins in inclusion body aggregates and result in improved recovery of bioactive protein as compared to conventional solubilization agents. Here we demonstrate solubilization of human growth hormone inclusion body aggregates using 30 % trifluoroethanol in presence of 3 M urea and its refolding into bioactive form. Results Human growth hormone was expressed in E. coli M15 (pREP) cells in the form of inclusion bodies. Different concentrations of trifluoroethanol with or without addition of low concentration (3 M) of urea were used for solubilization of inclusion body aggregates. Thirty percent trifluoroethanol in combination with 3 M urea was found to be suitable for efficient solubilization of human growth hormone inclusion bodies. Solubilized protein was refolded by dilution and purified by anion exchange and size exclusion chromatography. Purified protein was analyzed for secondary and tertiary structure using different spectroscopic tools and was found to be bioactive by cell proliferation assay. To understand the mechanism of action of trifluoroethanol, secondary and tertiary structure of human growth hormone in trifluoroethanol was compared to that in presence of other denaturants like urea and guanidine hydrochloride. Trifluoroethanol was found to be stabilizing the secondary structure and destabilizing the tertiary structure of protein. Finally, it was observed that trifluoroethanol can be used to solubilize inclusion bodies of a number of proteins. Conclusions Trifluoroethanol was found to be a suitable mild solubilization agent for bacterial inclusion bodies. Fully functional, bioactive human growth hormone was recovered in high yield from inclusion bodies using trifluoroethanol based solubilization buffer. It was also observed that trifluoroethanol has potential to solubilize inclusion bodies of different proteins.

This thesis presents a comparative exploration of the role perceptions and journalistic practices of war reporters working in India and the UK – covering wars between 1998 and 2003. Adopting field theory and boundary maintenance as analytical tools, it explores how reporters in Indian and the UK enforce their self-perceived identity criteria and occupational practices within the field of war reporting. The thesis traces their normative ideas, cognitive orientations, professional practices and narrated performances. The theoretical framework is developed around concepts of role perception, journalistic neutrality, the social construction of reality and models of news media performance.

Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. IgA PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia. Intestinal germinal center B cell reduction in HIV-1 infection linked to reduced IgA plasma cells and systemic inflammation.