Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling

Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer's patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood. In mice infected with Yersinia pseudotuberculosis, we found that PP barrier dysfunction is dependent on the Yersinia virulence plasmid and the expression of TLR-2 by hematopoietic cells, but not by intestinal epithelial cells. Upon TLR-2 stimulation, Y. pseudotuberculosis-infected monocytes activated caspase-1 and produced IL-1β. In turn, IL-1β increased NF-κB and myosin light chain kinase activation in intestinal epithelial cells, thus disrupting the intestinal barrier by opening the tight junctions. Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection.     

Spatial Distribution and Burden of Emerging Arboviruses in French Guiana

Despite the health, social and economic impact of arboviruses in French Guiana, very little is known about the extent to which infection burden is shared between individuals. We conducted a large multiplexed serological survey among 2697 individuals from June to October 2017. All serum samples were tested for IgG antibodies against DENV, CHIKV, ZIKV and MAYV using a recombinant antigen-based microsphere immunoassay with a subset further evaluated through anti-ZIKV microneutralization tests. The overall DENV seroprevalence was estimated at 73.1% (70.6–75.4) in the whole territory with estimations by serotype at 68.9% for DENV-1, 38.8% for DENV-2, 42.3% for DENV-3, and 56.1% for DENV-4. The overall seroprevalence of CHIKV, ZIKV and MAYV antibodies was 20.3% (17.7–23.1), 23.3% (20.9–25.9) and 3.3% (2.7–4.1), respectively. We provide a consistent overview of the burden of emerging arboviruses in French Guiana, with useful findings for risk mapping, future prevention and control programs. The majority of the population remains susceptible to CHIKV and ZIKV, which could potentially facilitate the risk of further re-emergences. Our results underscore the need to strengthen MAYV surveillance in order to rapidly detect any substantial changes in MAYV circulation patterns.     

XPS analysis of poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] film surfaces exposed to an allylamine low-pressure plasma

Homogeneous and stable layers were deposited through allylamine plasma polymerization (75 W, 100 Pa, 15 min) onto poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] (91 : 9 wt.-%) (P(HB-co-9%HV)) film surfaces, XPS analysis using take-off angles of 20° and 70° and performed 10 days and 20 days after plasma treatment gives information on the composition (in atom%) of the modified surface: C, 62.74; N, 19.60; O, 17.65. The unexpected oxygen percentage is weaker if argon plasma pretreatment (25 W, 40 Pa, 5 min) is applied. Then, a succinct mechanism is proposed. The study of changes in element ratios and binding energy values shows that the majority of incorporated functional groups seem to be amide and imine groups.     

Molecular characterization by array comparative genomic hybridization and DNA sequencing of 194 desmoid tumors

Desmoid tumors are fibroblastic/myofibroblastic proliferations. Previous studies reported that CTNNB1 mutations were detected in 84% and that mutations of the APC gene were found in several cases of sporadic desmoid tumors lacking CTNNB1 mutations. Forty tumors were analyzed by comparative genomic hybridization (CGH). Karyotype and fluorescence in situ hybridization revealed a nonrandom occurrence of trisomy 8 associated with an increased risk of recurrence. We report the first molecular characterization including a large series of patients. We performed array CGH on frozen samples of 194 tumors, and we screened for APC mutations in patients without CNNTB1 mutation. A high frequency of genomically normal tumors was observed. Four relevant and recurrent alterations (loss of 6q, loss of 5q, gain of 20q, and gain of Chromosome 8) were found in 40 out of 46 tumors with chromosomal changes. Gain of Chromosomes 8 and 20 was not associated with an increased risk of recurrence. Cases with loss of 5q had a minimal common region in 5q22.5 including the APC locus. Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome. A better understanding of the pathogenetic pathways in the initiation and progression of desmoid tumors requires studies of 8q and 20q gains, as well as of 6q and 5q losses, and study of the Wnt/β‐catenin pathway. © 2010 Wiley‐Liss, Inc.     

Recurrent 16p11.2 microdeletions in autism

Autism is a childhood neurodevelopmental disorder with a strong genetic component, yet the identification of autism susceptibility loci remains elusive. We investigated 180 autism probands and 372 control subjects by array comparative genomic hybridization (aCGH) using a 19K whole-genome tiling path bacterial artificial chromosome microarray to identify submicroscopic chromosomal rearrangements specific to autism. We discovered a recurrent 16p11.2 microdeletion in two probands with autism and none in controls. The deletion spans approximately 500-kb and is flanked by approximately 147-kb segmental duplications (SDs) that are >99% identical, a common characteristic of genomic disorders. We assessed the frequency of this new autism genomic disorder by screening an additional 532 probands and 465 controls by quantitative PCR and identified two more patients but no controls with the microdeletion, indicating a combined frequency of 0.6% (4/712 autism versus 0/837 controls; Fisher exact test P = 0.044). We confirmed all 16p11.2 deletions using fluorescence in situ hybridization, microsatellite analyses and aCGH, and mapped the approximate deletion breakpoints to the edges of the flanking SDs using a custom-designed high-density oligonucleotide microarray. Bioinformatic analysis localized 12 of the 25 genes within the microdeletion to nodes in one interaction network. We performed phenotype analyses and found no striking features that distinguish patients with the 16p11.2 microdeletion as a distinct autism subtype. Our work reports the first frequency, breakpoint, bioinformatic and phenotypic analyses of a de novo 16p11.2 microdeletion that represents one of the most common recurrent genomic disorders associated with autism to date.     

Apoptotic cell capture by DCs induces unexpectedly robust autologous CD4+ T‐cell responses

Apoptotic cells represent an important source of self‐antigens and their engulfment by dendritic cells (DCs) is usually considered to be related to tolerance induction. We report here an unexpectedly high level of human CD4⁺ T‐cell proliferation induced by autologous DCs loaded with autologous apoptotic cells, due to the activation of more than 10% of naive CD4⁺ T cells. This proliferation is not due to an increase in the costimulatory capacity of DCs, but is dependent on apoptotic cell‐associated material processed through an endo‐lysosomal pathway and presented on DC MHC class II molecules. Autologous CD4⁺ T cells stimulated with apoptotic cell‐loaded DCs exhibit suppressive capacities. However, in the presence of bacterial lipopolysaccharide, apoptotic cell‐loaded DCs induce the generation of IL‐17‐producing cells. Thus, apoptotic cell engulfment by DCs may lead to increased autologous responses, initially generating CD4⁺ T cells with suppressive capacities able to differentiate into Th17 cells in the presence of a bacterial danger signal such as LPS.     

A predictive model of vitamin D insufficiency in older community people: From the São Paulo Aging & Health Study (SPAH)

Objective

To evaluate the prevalence of 25-hydroxyvitamin D insufficiency (25OHD < 20 ng/mL) and to develop a predictive model for this status.

Methods

This is a cross-sectional study including 908 community-dwelling older subjects, 18% (158) of which were randomly selected to be a “test” sample, with the remaining (750) composing a “development” sample. A radioimmunoassay technique was used to measure 25OHD levels. Anthropometrical data, information about lifestyle habits and co-morbidities were obtained. Multiple logistic regression models were created. An Index Risk of Vitamin D Insufficiency (IRVDI) was designed and subsequently validated. The performance of this tool was assessed through ROC analysis.

Results

The prevalence of 25OHD < 20 ng/mL was of 58.0% (CI 95% 51.6–64.6). The clinical independent factors for 25OHD < 20 ng/mL were female gender (OR = 2.16; 95%CI 1.13–4.13; p = 0.020), diabetes (OR = 1.84; 95%CI 1.23–2.74; p = 0.003) and season (winter/spring) (OR = 3.63, 95%CI 2.62–4.88; p < 0.001). After statistical adjustments, the IRVDI was able to identify older people at risk for vitamin D insufficiency with a sensitivity of 55.9%, specificity 72.3% and ROC area of 0.685 (p < 0.001).

Conclusions

Our results suggest that vitamin D insufficiency is common among Brazilian community-dwelling elderly. Female gender, diabetes and the season (winter/spring) were the important parameters that predicted this status. The clinical use of these parameters can be help to design and target appropriate public health interventions. The IRVDI is a convenient tool for the selection of older people at risk for vitamin D insufficiency.