Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus: sortase catalyzed in vitro transpeptidation reaction using LPXTG peptide and NH2-Gly3 substrates

Staphylococcus aureus sortase anchors surface proteins to the cell wall envelope by cleaving polypeptides at the LPXTG motif. Surface proteins are linked to the peptidoglycan by an amide bond between the C-terminal carboxyl and the amino group of the pentaglycine cross-bridge. We find that purified recombinant sortase hydrolyzed peptides bearing an LPXTG motif at the peptide bond between threonine and glycine. In the presence of NH2-Gly3, sortase catalyzed exclusively a transpeptidation reaction, linking the carboxyl group of threonine to the amino group of NH2-Gly3. In the presence of amino group donors the rate of sortase mediated cleavage at the LPXTG motif was increased. Hydrolysis and transpeptidation required the sulfhydryl of cysteine 184, suggesting that sortase catalyzed the transpeptidation reaction of surface protein anchoring via the formation of a thioester acyl-enzyme intermediate

Gut Microbes and the Brain: Paradigm Shift in Neuroscience

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject

Banach Analytic Sets and a Non-Linear Version of the Levi Extension Theorem

We prove a certain non-linear version of the Levi extension theorem for meromorphic functions. This means that the meromorphic function in question is supposed to be extendable along a sequence of complex curves, which are arbitrary, not necessarily straight lines. Moreover, these curves are not supposed to belong to any finite dimensional analytic family. The conclusion of our theorem is that nevertheless the function in question meromorphically extends along an (infinite dimensional) analytic family of complex curves and its domain of existence is a pinched domain filled in by this analytic family.Comment: 19 pages, This is the final version with significant corrections and improvements. To appear in Arkiv f\"or matemati

French translation and validation of the Jefferson Scale of Empathy - Health Professions Student version

Background: Background: Jefferson Scale of Empathy is one of the most widely used tools worldwide to assess empathy. The extended version for Health Professions Students (JSE HPS) has not yet been translated into French. Objective: The aim of our study was to translate the JSE HPS into French and assess the psychometric properties of this new version (JSE HPS Fr). Methods: The JSE HPS was translated according to international recommendations. The main psychometric qualities (test-retest reliability, internal consistency, floor and ceiling effects and construct validity) were studied in a sample of physiotherapy students. Participants provided general information (age, gender, year of study) and completed the JSE HPS Fr and the Questionnaire of Cognitive and Affective Empathy (QCAE). Participants were also asked to complete the JSE-HPS-Fr again one week later to assess its test-retest reliability. Results: 408 students (161 males and 247 females; mean age: 21.3 years) participated. The JSE HPS Fr demonstrated good test-retest reliability for the total score (ICC=0.81) and good internal consistency (α Cronbach: 0.79). The JSE HPS also showed good convergent validity with the QCAE questionnaire (r=0.41, p<0.05). No floor or ceiling effects were observed. Conclusions: The results indicate that the JSE HPS Fr is a valid and reliable tool to assess the level of empathy of French-speaking physiotherapy students

Angiogenesis and MMP-2expression in Oral Squamous Cell Carcinoma&Verrucous Carcinoma and its Correlation with Clinicopathological Parameters

Background: An important step of tumor progression in which Matrix metalloproteinase have been implicated is angiogenesis, because these enzymes degrade the extracellular matrix and provide a permissive microenvironment for the growth of new blood vessels. The present study conducted to evaluate the immunohistochemical expression ofMatrixmetalloproteinase -2(MMP-2) andangiogenic marker (CD34) in Oralsquamous cell carcinoma(SCC)versus verrucous carcinoma(VC) and to correlate their expressions with the clinicopathological parameters. Material & Methods: MMP-2 and CD34 expression was examined immunohistochemically in twenty four paraffin tissue blocks of squamous cell carcinoma and verrucous carcinoma (twelve cases of each).  Results: All cases of Oral SCC exhibited positive   immunostaining for MMP-2, while only one case of VC showed –ve expression. Interestingly all cases of VC showed –ve MMP-2 immunostaining of the basal cell layer. Generally lymphatic vessels were more than blood vessels in both VC&SCC cases. The mean MMP-2 immunoexpression was (59.00%) for both stage I &stage II, while the higher CD34 immuno expression was in stage I. The mean expression of MMP-2 was higher in well differentiated OSCCs, while for CD34 it was higher in poorly differentiated OSCCs followed by moderately differentiated, then well differentiated, however no statistically significant difference was found. Non- significant correlation was found concerning the expression of both markers for both lesions. Conclusion: No statistical correlation was found between MMP-2 expression and angiogenesis in OSCC and OVC

Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base

Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis

The gastrointestinal (GI) tract contains much of the body’s serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes

Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer.

To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%) patients displaying p53-positive phenotype, defined as > or = 25% of positive cells. Patients with two or more first-degree relatives with cancer had an odds ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with those without a family history of cancer (trend test, P = 0.11). A possible association between body weight and p53 overexpression was observed. The ORs were 1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest quartile in comparison with the lowest quartile (trend test, P = 0.06). No association between occupational physical activity, smoking, drinking, parity and p53 overexpression was identified. The results suggest that p53 overexpression may be related to genetic predisposition to colorectal cancer, and p53-positive and p53-negative colorectal cancers may be controlled by different aetiological pathways