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Background Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. Methods To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk ( N  = 66), sesame ( N  = 38), peanut ( N  = 71), and tree nuts ( N  = 58), and non-allergic controls ( N  = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy ( N  = 84) and controls ( N  = 31). Results The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri ( P. copri ) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. Conclusions Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.

BackgroundFamilial Steroid-sensitive Nephrotic Syndrome (SSNS) is rare, complicating the identification of candidate genes. A recent population-based approach study of SSNS identified HLA-DQA1 and Phospholipase C-Gamma 2 (PLCG2) missense coding variants as candidate loci. PLCG2 is a signaling molecule regulated by phosphorylation and is critical for Ca2+ flux in cells of the immune system.MethodsIn order to detect a candidate gene for familial SSNS, we conducted an whole-exome sequencing in a pedigree consisting of two healthy parents, two non-identical twin brothers with SSNS, and a healthy young sibling. Flow cytometric assays were conducted to investigate the effects of the identified PLCG2 rare variants on B cell receptor-mediated PLCG2 tyrosine 759 phosphorylation, as well as on Ca2+ flux.ResultsTwo missense rare variants in the PLCG2 gene were detected in the affected twins. An increase in tyrosine phosphorylation of PLCG2 as well as more rapid Ca2+ flux were noted in response to stimulation in the affected twins compared to their parents.ConclusionsRare variants in PLCG2 segregated with disease in familial SSNS. Functional studies suggest the combined rare variants result in a gain of function in PLCG2 activity. Taken together, these results support PLCG2 as a possible candidate locus for familial SSNS.

The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological memory and cancer therapies. This approach is limited, however, by the failure to efficiently engraft human B lymphocytes in immunodeficient mice. We hypothesized that this deficiency was due to the failure of the murine microenvironment to support human B cell survival. We report that while the human B lymphocyte survival factor, B lymphocyte stimulator (BLyS/BAFF) enhances the survival of human B cells ex vivo, murine BLyS has no such protective effect. Although human B cells bound both human and murine BLyS, nuclear accumulation of NF-kappaB p52, an indication of the induction of a protective anti-apoptotic response, following stimulation with human BLyS was more robust than that induced with murine BLyS suggesting a fundamental disparity in BLyS receptor signaling. Efficient engraftment of both human B and T lymphocytes in NOD rag1(-/-) Prf1(-/-) immunodeficient mice treated with recombinant human BLyS is observed after adoptive transfer of human PBL relative to PBS treated controls. Human BLyS treated recipients had on average 40-fold higher levels of serum Ig than controls and mounted a de novo antibody response to the thymus-independent antigens in pneumovax vaccine. The data indicate that production of fully immunologically competent humanized mice from PBL can be markedly facilitated by providing human BLyS.

An interview with Michael Appel, a board-certified anesthesiologist and chief patient safety officer for Northeast Georgia Health System Inc in Gainesville, GA, is presented. Appel talks about, among other things, accident analysis and remediation process, and the one lesson from the aeronautical industry that healthcare could adopt.

Evaluation of: Othman A, Abd Rahman N, Yusof R. Induction of MHC class I HLA-A2 promoter by dengue virus occurs at the NFκB binding domains of the class I regulatory complex. Virus Res. 163(1), 238-245 (2011). Unlike many other viruses that downregulate MHC class I expression on infected cell membranes, flaviviruses were reported to upregulate the MHC class I expression. Dengue virus was shown to induce HLA class I expression; however, the precise transcriptional mechanism that is used by the virus remains unclear. This article assessed the findings of a recently published report describing the mechanism used by dengue virus to induce HLA-A2 expression and characterizing the transcription factors that are involved. The study showed that p50/p65 and p65/65 NF-κB dimers bind to the class I regulatory complex within the HLA-A2 promoter. This finding and its significance for the design of possible antiviral therapeutic agents are discussed in this article.

Combined treatment with allogeneic small lymphocytes or T-depleted small lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitted indefinite pancreatic islet allograft survival in 37 of 40 recipients that differed from islet donors at major and minor histocompatibility loci. The effect of the allogeneic small lymphocytes was donor antigen-specific. Neither treatment alone was as effective as combined treatment, although anti-CD40L by itself allowed indefinite islet allograft survival in 40% of recipients. Our interpretation is that small lymphocytes expressing donor antigens in the absence of appropriate costimulatory signals are tolerogenic for alloreactive host cells. Anti-CD40L antibody may prevent host T cells from inducing costimulatory signals in donor lymphocytes or islet grafts.

This collection of papers gives an insight into the inter-disciplinary debate from the \"Interuniversitäres Netzwerk Biographie und Lebensweltforschung\" (INBL) (Inter-University Network of Biographical and Lebenswelt Research), which is comprised of investigative groups from the Universities of Bremen, Göttingen and Bielefeld. The articles argue mostly about method and methodological aspects of qualitative research. These are reflections on methods and results of qualitative research projects as seen through the various disciplines of Sociology, Educational and Cultural Sciences, Psychology and Ethnology. They are viewed through a range of action fields such as theoretical and applied research and teaching and professional practice--simultaneously a strength and weakness of the book. In spite of an introductory chapter, the connections between the articles are often not explicit. Nevertheless, the book gives interesting suggestions for rumination about real and relevant questions in all aspects of the ongoing development of qualitative research. URN: urn:nbn:de:0114-fqs050311

Semi-permanent capillary coatings are an effective tool in capillary electrophoresis (CE), allowing an analyst to control the conditions inside the capillary such as the electroosmotic flow (EOF) for the purposes of separating analytes. However, they pose a dilemma in CE due to their ability to be easily degraded through the separation process if not constantly being refreshed. Phospholipid bilayers, a type of semi-permanent coating, are diverse option for an assortment of separations but prove difficult in maintaining a consistent EOF and are easily removed by mechanical means over consecutive rinses. This work looks to utilize two unsaturated phospholipid bilayers, DPPC and DOPC, and cross-link their individual monomers with the binding agent osmium tetroxide. To determine the efficacy of this coating, the integrity of the coating and the consistency of the EOF over consecutive runs were observed after various modifications to the phospholipid preparation process were made. Both DPPC and DOPC showed significant masking of the capillary’s negative charge as indicated by a decreased EOF magnitude, but still showed signs of gradually increasing over time as portions of the coating were rinsed away. Charged proteins often provide a challenge in CE due to their tendency to adsorb to the capillary surface and was a way to further test the coatings’ integrity. While some proteins did experience band broadening issues, the cross-linked coating maintained its integrity through multiple runs with anionic proteins, indicating how effective the coating became when cross-linked. Finally, crosslinking the phospholipids made a more robust coating which showed a lowered EOF magnitude when left exposed to the air and when rinsed with the organic solvent methanol (MeOH). This work provides a greater insight into the efficacy of cross-linking phospholipid bilayers as a capillary coating in CE, which are less expensive than permanent coatings and respect projects that are time sensitive.