Apolipoprotein C-II deficiency: detection of immunoreactive apolipoprotein C-II in the intestinal mucosa of two patients

Recent data suggest that mutant immunoreactive forms of apolipoprotein C-II (apoC-II) can be detected in the plasma of patients with the apoC-II deficiency syndrome. We studied the possible presence of apoC-II mutants in the plasma of two patients with apoC-II deficiency by immunological means. The patients were hypertriglyceridemic, and apoC-II was undetectable in plasma as determined by radial immunodiffusion, electroimmunoassay, and immunonephelometry. Furthermore, apoC-II was undetectable either by electrophoresis or by immunoblotting in the plasma of the probands, while apoC-II was present in the plasma of their parents, although at less than half-normal concentration. Immunochemical localization of apoC-II, however, showed that the apoprotein could be detected within the enterocytes obtained from the intestinal mucosa of the patients. From these data we conclude that the patients synthesize apoC-II, at least in the intestine

Bacterial DNAemia is associated with serum zonulin levels in older subjects

The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. In this context, we performed the quantification and the taxonomic profiling of the bacterial DNA in blood samples collected from forty-three older subjects enrolled in a nursing home. Quantitative PCR targeting the 16S rRNA gene revealed that all samples contained detectable amounts of bacterial DNA with a concentration that varied considerably between subjects. Correlation analyses revealed that the bacterial DNAemia (expressed as concentration of 16S rRNA gene copies in blood) significantly associated with the serum levels of zonulin, a marker of intestinal permeability. This result was confirmed by the analysis of a second set of blood samples collected from the same subjects. 16S rRNA gene profiling revealed that most of the bacterial DNA detected in blood was ascribable to the phylum Proteobacteria with a predominance of the genus Pseudomonas. Several control samples were also analyzed to assess the influence of contaminant bacterial DNA potentially originating from reagents and materials. The data reported here suggest that para-cellular permeability of epithelial (and, potentially, endothelial) cell layers may play an important role in bacterial migration into the bloodstream. Bacterial DNAemia is likely to impact on several aspects of host physiology and could underpin the development and prognosis of various diseases in older subjects

191pd_pr9 weeks versus 1 year adjuvant trastuzumab for her2 early breast cancer subgroup analysis of the shorther trial allows to identify patients for whom a shorter trastuzumab administration may have a favourable risk benefit ratio

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Identidad y Memoria: Los Adultos Mayores cuentan la historia del ex Mercado Abasto de Avellaneda

El proyecto tiene como objetivo generar un aporte comunicacional y social con doble sentido: por un lado lograr la recuperación histórica del Ex Mercado de Abasto de la Ciudad de Avellaneda y su posterior desarrollo como Universidad Nacional, y por otro lado, revalorizar la voz de los adultos mayores y su rol activo en la sociedad actual. A través de los testimonios de estos actores sociales, fieles protagonistas del funcionamiento de aquel antiguo centro comercial, se pretende lograr un registro de historias de vida en formato escrito, fotográfico y audiovisual, que den cuentan de la reconstrucción histórica del lugar. A su vez, el trabajo se plantea como una herramienta de generación/fortalecimiento de lazos sociales comunitarios, vínculos que se entretejen sobre la base de identidades, pertenencias y memoria. El proceso de trabajo se basa en el trabajo  conjunto adultos mayores – jóvenes, fundado en un aprendizaje mutuo e intercambio intergeneracional. De esta manera, no sólo se logra revalorizar un lugar histórico, sino que también se realiza un aporte favorable para retraer la distancia generacional existente en el país entre dichos actores sociales. El presente proyecto se encuentra todavía en proceso y tiene lugar en la Universidad Nacional de Avellaneda a través de encuentros de reflexión-memoria bajo la modalidad de taller, donde los estudiantes empiezan a delinear sus  primeras prácticas pre profesionales y los adultos mayores son participantes activos de las mismas. Las producciones finales relatarán cómo se vivía cuando el predio pertenecía al Mercado de Abasto y empezarán, además, a contar la historia de la naciente Universidad Nacional de Avellaneda

RESEARCHERS' PYRAMID. A NEW OPPORTUNITY FOR ITALIAN ONCOLOGY RESEARCH INFRASTRUCTURE?

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Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers

Myeloid cell expressed proprotein convertase FURIN attenuates inflammation

The proprotein convertase enzyme FURIN processes immature pro-proteins into functional end- products. FURIN is upregulated in activated immune cells and it regulates T-cell dependent peripheral tolerance and the Th1/Th2 balance. FURIN also promotes the infectivity of pathogens by activating bacterial toxins and by processing viral proteins. Here, we evaluated the role of FURIN in LysM+ myeloid cells in vivo. Mice with a conditional deletion of FURIN in their myeloid cells (LysMCre-fur(fl/fl)) were healthy and showed unchanged proportions of neutrophils and macrophages. Instead, LysMCre-fur(fl/fl) mice had elevated serum IL-1\u3b2 levels and reduced numbers of splenocytes. An LPS injection resulted in accelerated mortality, elevated serum proinflammatory cytokines and upregulated numbers of pro-inflammatory macrophages. A genome-wide gene expression analysis revealed the overexpression of several pro-inflammatory genes in resting FURIN-deficient macrophages. Moreover, FURIN inhibited Nos2 and promoted the expression of Arg1, which implies that FURIN regulates the M1/M2-type macrophage balance. FURIN was required for the normal production of the bioactive TGF-\u3b21 cytokine, but it inhibited the maturation of the inflammation-provoking TACE and Caspase-1 enzymes. In conclusion, FURIN has an anti-inflammatory function in LysM+ myeloid cells in vivo

Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome

Background: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). Objective: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. Methods: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. Results: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad TH1/TH2/TH17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by TH1 effector T cells. Conclusions: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS

Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity

TgaA, a VirB1-like component belonging to a putative type IV secretion system of Bifidobacterium bifidum MIMBb75

Bifidobacterium bifidum MIMBb75 is a human intestinal isolate demonstrated to be interactive with the host and efficacious as a probiotic. However, the molecular biology of this microorganism is yet largely unknown. For this reason, we undertook wholegenome sequencing of B. bifidum MIMBb75 to identify potential genetic factors that would explain the metabolic and probiotic attributes of this bacterium. Comparative genomic analysis revealed a 45-kb chromosomal region that comprises 19 putative genes coding for a potential type IV secretion system (T4SS). Thus, we undertook the initial characterization of this genetic region by studying the putative virB1-like gene, named tgaA. Gene tgaA encodes a peptidoglycan lytic enzyme containing two active domains: lytic murein transglycosylase (LT, cd00254.3) and cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP, pfam05257.4). By means of several in vitro assays, we experimentally confirmed that protein TgaA, consistent with its computationally assigned role, has peptidoglycan lytic activity, which is principally associated to the LT domain. Furthermore, immunofluorescence and immunogold labeling showed that the protein TgaA is abundantly expressed on the cell surface of B. bifidum MIMBb75. According to the literature, the T4SSs, which have not been characterized before in bifidobacteria, can have important implications for bacterial cell-to-cell communication as well as cross talk with host cells, justifying the interest for further studies aimed at the investigation of this genetic region