Fecal Proteolytic Bacteria and Staphylococcal Superantigens Are Associated With Abdominal Pain Severity in Irritable Bowel Syndrome.

Introduction: Changes in the composition of the gut microbiota have been associated with the development of irritable bowel syndrome (IBS). However, to what extent specific bacterial species relate to clinical symptoms remains poorly characterized. We investigated the clinical relevance of bacterial species linked with increased proteolytic activity, histamine production, and superantigen (SAg) production in patients with IBS.

Human nuclear hormone receptor activity contributes to malaria parasite liver stage development.

Chemical genetic approaches have had a transformative impact on discovery of drug targets for malaria but have primarily been used for parasite targets. To identify human pathways required for intrahepatic development of parasite, we implemented multiplex cytological profiling of malaria infected hepatocytes treated with liver stage active compounds. Some compounds, including MMV1088447 and MMV1346624, exhibited profiles similar to cells treated with nuclear hormone receptor (NHR) agonist/antagonists.

Enhanced copper removal from contaminated kaolinite soil by electrokinetic process using compost reactive filter media.

Electrokinetic (EK) remediation is a promising technology for soil decontamination, although basic pH in the soil close to cathode has constrained EK effectiveness due to heavy metal precipitation. This study aimed to enhance copper removal from kaolinite soil by integrating EK with compost (C) as recyclable reactive filter media (RFM) for the first time. Compost placed near the cathode served as an adsorbent to bind copper ions while buffering the advancement of the alkaline front in soil.

Copper removal from contaminated soil through electrokinetic process with reactive filter media.

Electrokinetic (EK) remediation has been used in the removal of metal ions from contaminated soil. This study focused on integrating the EK technique with different reactive filter media (RFM) of activated carbon (AC) and biochar (BC) for the first time without adding chemicals to facilitate the removal of copper ions from the contaminated kaolinite soil. Tests based on EK, EK coupled with AC (EK-AC), and EK combined with BC (EK-BC) were performed under an electric potential of 10 V, and the overall removal efficiency of copper ions decreased as EK-BC > EK-AC > EK.

Predictability of European winter 2016/2017.

Winter 2016/2017 was one of the driest on record for central Europe and the United Kingdom. This was the result of blocked atmospheric circulation with high pressure centred over North-West Europe dominating the winter mean circulation pattern. Using large ensembles of simulated winters, we find that the observed winter 2016/2017 circulation was very similar in pattern and strength to the circulation associated with the top 10% of driest Central European winters.

Randomised clinical trial: Bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation.

Background: Constipation is a prevalent gastrointestinal disorder. Patient dissatisfaction with prescribed medications is common, and there is need for alternative management strategies. Evidence shows that Bifidobacterium species may be beneficial in constipation.

Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome.

Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR), which has been proposed to mediate pain in patients with irritable bowel syndrome (IBS).

Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission.

G protein-coupled receptors (GPCRs) are considered to function primarily at the plasma membrane, where they interact with extracellular ligands and couple to G proteins that transmit intracellular signals. Consequently, therapeutic drugs are designed to target GPCRs at the plasma membrane. Activated GPCRs undergo clathrin-dependent endocytosis.

Bridging the divide: illuminating the path of intercellular exchange through ring canals.

Ring canals are made from arrested cleavage furrows, and provide direct cytoplasmic connections among sibling cells. They are well documented for their participation in Drosophila oogenesis, but little is known about their role in several somatic tissues in which they are also found. Using a variety of genetic tools in live and fixed tissue, we recently demonstrated that rapid intercellular exchange occurs through somatic ring canals by diffusion, and presented evidence that ring canals permit equilibration of protein among transcriptionally mosaic cells.

Protein equilibration through somatic ring canals in Drosophila.

Although intercellular bridges resulting from incomplete cytokinesis were discovered in somatic Drosophila tissues decades ago, the impact of these structures on intercellular communication and tissue biology is largely unknown. In this work, we demonstrate that the ~250-nanometer-diameter somatic ring canals permit diffusion of cytoplasmic contents between connected cells and across mitotic clone boundaries and enable the equilibration of protein between transcriptionally mosaic follicle cells in the Drosophila ovary. We obtained similar, although more restricted, results in the larval imaginal discs.

Intercellular protein movement in syncytial Drosophila follicle cells.

Ring canals connecting Drosophila germline, follicle and imaginal disc cells provide direct contact of cytoplasm between cells. To date, little is known about the formation, structure, or function of the somatic ring canals present in follicle and imaginal disc cells. Here, we show by confocal and electron microscopy that Pavarotti kinesin-like protein and Visgun are stable components of somatic ring canals.

Mechanisms of symptom reduction in treatment for obsessions.

Objective: We explored the dynamic relationship between cognition and obsession severity during 2 different treatments for primary obsessions, examining evidence for the hypothesis that symptom reduction would be mediated by appraisals about the meaning of unwanted intrusive thoughts.

Method: Data from a recent randomized controlled trial were analyzed with traditional mediation analyses and latent difference scores. The trial had compared cognitive behavioral therapy and stress management training among 73 patients with primary obsessions.

Technical Advance: Function and efficacy of an {alpha}4-integrin antagonist using bioluminescence imaging to detect leukocyte trafficking in murine experimental colitis.

Leukocyte trafficking is a therapeutic target in IBD. The integrins α₄β and α₄β₁ regulate leukocyte migration into tissues and lymphoid organs. Current strategies rely on biologics, such as mAb, to inhibit leukocyte recruitment.

Characterization of a calcitonin gene-related peptide release assay in rat isolated distal colon.

The release of calcitonin gene-related peptide (CGRP) plays a key role gastrointestinal tract homeostasis. We aimed to investigate mechanisms that mediate CGRP release from the rat colon in vitro. Colon segments were stimulated and the amount of CGRP released was measured using an enzyme immunoassay.

Treatment of obsessions: a randomized controlled trial.

This study tested Rachman's cognitive behavioral method for treating obsessions not accompanied by prominent overt compulsions. The cognitive behavioral treatment was compared to waitlist control and an active and credible comparison of stress management training (SMT). Of the 73 adults who were randomized, 67 completed treatment, and 58 were available for one-year follow-up.

Targeting gut T cell Ca2+ release-activated Ca2+ channels inhibits T cell cytokine production and T-box transcription factor T-bet in inflammatory bowel disease.

Prolonged Ca(2+) entry through Ca(2+) release-activated Ca(2+) (CRAC) channels is crucial in activating the Ca(2+)-sensitive transcription factor NFAT, which is responsible for directing T cell proliferation and cytokine gene expression. To establish whether targeting CRAC might counteract intestinal inflammation, we evaluated the in vitro effect of a selective CRAC inhibitor on T cell cytokine production and T-bet expression by lamina propria mononuclear cells (LPMC) and biopsy specimens from inflammatory bowel disease (IBD) patients. The inhibitory activity of the CRAC blocker was investigated through patch-clamp experiments on rat basophilic leukemia cells and fluorometric imaging plate reader intracellular Ca(2+) assays using thapsigargin-stimulated Jurkat T cells and its detailed selectivity profile defined using a range of in vitro radioligand binding and functional assays.

Group and individual treatment of obsessive-compulsive disorder using cognitive therapy and exposure plus response prevention: a 2-year follow-up of two randomized trials.

Relatively little is known about the long-term durability of group treatments for obsessive-compulsive disorder (OCD) and contemporary cognitive treatments. The current study investigated the 2-year follow-up results for participants who completed randomized trials of group or individual treatment and received either cognitive therapy (CT) or exposure plus response prevention (ERP). Yale-Brown Obsessive Compulsive Scale (YBOCS) scores for individual ERP and CT were not significantly different over 2 years.

Validation of a conscious rat model for the discovery of novel agents that inhibit gastric acid secretion.

Identification of novel drug molecules requires the extensive evaluation in vitro and in vivo. Following in vitro evaluation it is necessary to efficiently screen numerous novel molecules in vivo using relatively simple methodology that requires small numbers of animals, is rapid to perform, and provides results that can definitely discriminate potential candidates for further investigation. Herein, we describe the results of three standard compounds (omeprazole, a proton pump inhibitor; cimetidine, an histamine H(2) receptor antagonist; and AR-H047108, a potassium competitive acid blocker) in the rat aspiration model (under both basal and stimulated conditions), and compared the effects with those in the pyloric ligation model with a view to comparing the results in terms of sensitivity, robustness and simplicity of the methodology.

Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats.

Visceral hypersensitivity has been implicated as an important pathophysiological mechanism in functional gastrointestinal disorders. In this study, we investigated whether the sustained visceral hyperalgesia induced by repeated psychological stress in rats involves the activation of CRF(1) signaling system using two different antagonists. Male Wistar rats were exposed to 10 consecutive days of water avoidance stress (WAS) or sham stress for 1 h/day, and the visceromotor response to phasic colorectal distension (CRD) was assessed before and after the stress period.

Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis.

Modulation of adhesion molecule expression or function is regarded as a promising therapy for inflammatory conditions. This study evaluates the effects of an inhibitor of adhesion molecule expression (GI270384X) in two experimental models of colitis. Colitis of different severity was induced in C57BL/6J mice by administering 1, 2, or 3% dextran sulfate sodium (DSS).

Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia.

Despite its beneficial effect in IBS patients, the mechanism of action of the 5-HT3 receptor (5-HT3R) antagonist alosetron is still incompletely understood. We aimed to characterize the effect and site(s) of action in a model of stress-induced sensitization of visceral nociception in rats. Adult male Wistar rats were equipped for recording of visceromotor response (VMR) to phasic colorectal distension (CRD; 10-60 mmHg).

5-HT in the enteric nervous system: gut function and neuropharmacology.

In recent times, the perception of functional gastrointestinal disorders such as irritable bowel syndrome (IBS) has shifted fundamentally. Such disorders are now thought of as serious diseases characterized by perturbations in the neuronal regulation of gastrointestinal function. The concept of visceral hypersensitivity, the characterization of neuronal networks in the 'brain-gut axis' and the identification of several novel 5-HT-mediated mechanisms have contributed to this shift.