The human gut microbiota is a complex system that is essential to the health of the host. Increasing evidence suggests that the gut microbiota may play an important role in the pathogenesis of colorectal cancer (CRC). In this study, we used pyrosequencing of the 16S rRNA gene V3 region to characterize the fecal microbiota of 19 patients with CRC and 20 healthy control subjects. The results revealed striking differences in fecal microbial population patterns between these two groups. Partial least-squares discriminant analysis showed that 17 phylotypes closely related to Bacteroides were enriched in the gut microbiota of CRC patients, whereas nine operational taxonomic units, represented by the butyrate-producing genera Faecalibacterium and Roseburia, were significantly less abundant. A positive correlation was observed between the abundance of Bacteroides species and CRC disease status (R = 0.462, P = 0.046 < 0.5). In addition, 16 genera were significantly more abundant in CRC samples than in controls, including potentially pathogenic Fusobacterium and Campylobacter species at genus level. The dysbiosis of fecal microbiota, characterized by the enrichment of potential pathogens and the decrease in butyrate-producing members, may therefore represent a specific microbial signature of CRC. A greater understanding of the dynamics of the fecal microbiota may assist in the development of novel fecal microbiome-related diagnostic tools for CRC.

This report provides a perspective on metabolic glycoengineering methodology developed over the past two decades that allows natural sialic acids to be replaced with chemical variants in living cells and animals. Examples are given demonstrating how this technology provides the glycoscientist with chemical tools that are beginning to reproduce Mother Nature's control over complex biological systems - such as the human brain - through subtle modifications in sialic acid chemistry. Several metabolic substrates (e.g., ManNAc, Neu5Ac, and CMP-Neu5Ac analogs) can be used to feed flux into the sialic acid biosynthetic pathway resulting in numerous - and sometime quite unexpected - biological repercussions upon nonnatural sialoside display in cellular glycans. Once on the cell surface, ketone-, azide-, thiol-, or alkyne-modified glycans can be transformed with numerous ligands via bioorthogonal chemoselective ligation reactions, greatly increasing the versatility and potential application of this technology. Recently, sialic acid glycoengineering methodology has been extended to other pathways with analog incorporation now possible in surface-displayed GalNAc and fucose residues as well as nucleocytoplasmic O-GlcNAc-modified proteins. Finally, recent efforts to increase the "druggability" of sugar analogs used in metabolic glycoengineering, which have resulted in unanticipated "scaffold-dependent" activities, are summarized.

BackgroundGuided self-help interventions for PTSD (post-traumatic stress disorder) are a promising tool for the dissemination of contemporary psychological treatment.ObjectiveThis study investigated the efficacy of the Chinese version of the My Trauma Recovery (CMTR) website.MethodsIn an urban context, 90 survivors of different trauma types were recruited via Internet advertisements and allocated to a randomized controlled trial (RCT) with a waiting list control condition. In addition, in a rural context, 93 survivors mainly of the 2008 Sichuan earthquake were recruited in-person for a parallel RCT in which the website intervention was conducted in a counseling center and guided by volunteers. Assessment was completed online on a professional Chinese survey website. The primary outcome measure was the Post-traumatic Diagnostic Scale (PDS); secondary outcome measures were Symptom Checklist 90-Depression (SCL-D), Trauma Coping Self-Efficacy Scale (CSE), Post-traumatic Cognitive Changes (PCC), and Social Functioning Impairment (SFI) questionnaires adopted from the My Trauma Recovery website.ResultsFor the urban sample, findings indicated a significant group×time interaction in post-traumatic symptom severity (F 1,88=7.65, P=.007). CMTR reduced post-traumatic symptoms significantly with high effect size after one month of treatment (F 1,45=15.13, Cohen’s d=0.81, P<.001) and the reduction was sustained over a 3-month follow-up (F 1,45=17.29, Cohen’s d=0.87, P<.001). In the rural sample, the group×time interaction was also significant in post-traumatic symptom severity (F 1,91=5.35, P=.02). Post-traumatic symptoms decreased significantly after treatment (F 1,48=43.97, Cohen’s d=1.34, P<.001) and during the follow-up period (F 1,48=24.22, Cohen’s d=0.99, P<.001). Additional outcome measures (post-traumatic cognitive changes, depression) indicated a range of positive effects, in particular in the urban sample (group×time interactions: F 1,88=5.32-8.37, all Ps<.03), contributing to the positive evidence for self-help interventions. Differences in the effects in the two RCTs are exploratorily explained by sociodemographic, motivational, and setting feature differences between the two samples.ConclusionsThese findings give support for the short-term efficacy of CMTR in the two Chinese populations and contribute to the literature that self-help Web-based programs can be used to provide mental health help for traumatized persons.Trial RegistrationAustralia New Zealand Clinical Trials Registry (ANZCTR): ACTRN12611000951954; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12611000951954 (Archived by WebCite at http://www.webcitation.org/6G7WyNODk).

Enterotoxigenic Escherichia coli (ETEC) cause secretory diarrhea in children and travelers to endemic areas. ETEC spreads through the fecal-oral route. After ingestion, ETEC passes through the stomach and duodenum before it colonizes the lower part of the small intestine, exposing bacteria to a wide range of pH and environmental conditions. This study aimed to determine the impact of external pH and activity of the Cyclic AMP receptor protein (CRP) on the regulation of production and secretion of heat labile (LT) enterotoxin. ETEC strain E2863wt and its isogenic mutant E2863ΔCRP were grown in LBK media buffered to pH 5, 7 and 9. GM1 ELISA, cDNA and cAMP analyses were carried out on bacterial pellet and supernatant samples derived from 3 and 5 hours growth and from overnight cultures. We confirm that CRP is a repressor of LT transcription and production as has been shown before but we show for the first time that CRP is a positive regulator of LT secretion both in vitro and in vivo. LT secretion increased at neutral to alkaline pH compared to acidic pH 5 where secretion was completely inhibited. At pH 9 secretion of LT was optimal resulting in 600 percent increase of secreted LT compared to unbuffered LBK media. This effect was not due to membrane leakage since the bacteria were viable at pH 9. The results indicate that the transition to the alkaline duodenum and/or exposure to high pH close to the epithelium as well as activation of the global transcription factor CRP are signals that induce secretion of the LT toxin in ETEC.