Properties of myenteric neurones and mucosal functions in the distal colon of diet-induced obese mice.

Colonic transit and mucosal integrity are believed to be impaired in obesity. However, a comprehensive assessment of altered colonic functions, inflammatory changes and neuronal signalling of obese animals is missing. In mice, we studied the impact of diet-induced obesity (DIO) on: (i) in vivo colonic transit; (ii) signalling in the myenteric plexus by recording responses to nicotine and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), together with the expression of tryptophan hydroxylase (TPH) 1 and 2, serotonin reuptake transporter, choline acetyltransferase and the paired box gene 4; and (iii) expression of proinflammatory cytokines, epithelial permeability and density of macrophages, mast cells and enterochromaffin cells.

University and student segmentation: multilevel latent-class analysis of students' attitudes towards research methods and statistics.

Background: It is often claimed that psychology students' attitudes towards research methods and statistics affect course enrollment, persistence, achievement, and course climate. However, the inter-institutional variability has been widely neglected in the research on students' attitudes towards research methods and statistics, but it is important for didactic purposes (heterogeneity of the student population).

Aims: The paper presents a scale based on findings of the social psychology of attitudes (polar and emotion-based concept) in conjunction with a method for capturing beginning university students' attitudes towards research methods and statistics and identifying the proportion of students having positive attitudes at the institutional level.

Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation.

Hanseniaspora opuntiae, Saccharomyces cerevisiae, Lactobacillus fermentum, and Acetobacter pasteurianus predominate during well-performed Malaysian cocoa bean box fermentations, underlining the importance of these microbial species for a successful cocoa bean fermentation process.

Two spontaneous Malaysian cocoa bean box fermentations (one farm, two plantation plots) were investigated. Physical parameters, microbial community dynamics, yeast and bacterial species diversity [mainly lactic acid bacteria (LAB) and acetic acid bacteria (AAB)], and metabolite kinetics were monitored, and chocolates were produced from the respective fermented dry cocoa beans. Similar microbial growth and metabolite profiles were obtained for the two fermentations.

The peptide transporter PEPT1 is expressed in distal colon in rodents and humans and contributes to water absorption.

The peptide transporter PEPT1, expressed in the brush border membrane of enterocytes, mediates the uptake of di- and tripeptides from luminal protein digestion in the small intestine. PEPT1 was proposed not to be expressed in normal colonic mucosa but may become detectable in inflammatory states such as Crohn's disease or ulcerative colitis. We reassessed colonic expression of PEPT1 by performing a systematic analysis of PEPT1 mRNA and protein levels in healthy colonic tissues in mice, rats, and humans.

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses.

Protein cold adaptation strategy via a unique seven-amino acid domain in the icefish (Chionodraco hamatus) PEPT1 transporter.

Adaptation of organisms to extreme environments requires proteins to work at thermodynamically unfavorable conditions. To adapt to subzero temperatures, proteins increase the flexibility of parts of, or even the whole, 3D structure to compensate for the lower thermal kinetic energy available at low temperatures. This may be achieved through single-site amino acid substitutions in regions of the protein that undergo large movements during the catalytic cycle, such as in enzymes or transporter proteins.

Mice lacking the intestinal peptide transporter display reduced energy intake and a subtle maldigestion/malabsorption that protects them from diet-induced obesity.

The intestinal transporter PEPT1 mediates the absorption of di- and tripeptides originating from breakdown of dietary proteins. Whereas mice lacking PEPT1 did not display any obvious changes in phenotype on a high-carbohydrate control diet (HCD), Pept1(-/-) mice fed a high-fat diet (HFD) showed a markedly reduced weight gain and reduced body fat stores. They were additionally protected from hyperglycemia and hyperinsulinemia.

Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice.

In studies emphasizing antiobesogenic and anti-inflammatory effects of long-chain n-3 polyunsaturated fatty acids (LC-n-3 PUFA), diets with very high fat content, not well-defined fat quality, and extreme n-6/n-3 PUFA ratios have been applied frequently. Additionally, comparative analyses of visceral adipose tissues (VAT) were neglected. Considering the link of visceral obesity to insulin resistance or inflammatory bowel diseases, we hypothesized that VAT, especially mesenteric adipose tissue (MAT), may exhibit differential responsiveness to diets through modulation of metabolic and inflammatory processes.

Hepatic methionine homeostasis is conserved in C57BL/6N mice on high-fat diet despite major changes in hepatic one-carbon metabolism.

Obesity is an underlying risk factor in the development of cardiovascular disease, dyslipidemia and non-alcoholic fatty liver disease (NAFLD). Increased hepatic lipid accumulation is a hallmark in the progression of NAFLD and impairments in liver phosphatidylcholine (PC) metabolism may be central to the pathogenesis. Hepatic PC biosynthesis, which is linked to the one-carbon (C1) metabolism by phosphatidylethanolamine N-methyltransferase, is known to be important for hepatic lipid export by VLDL particles.

Heterogeneity of inter-rater reliabilities of grant peer reviews and its determinants: a general estimating equations approach.

Background: One of the most important weaknesses of the peer review process is that different reviewers' ratings of the same grant proposal typically differ. Studies on the inter-rater reliability of peer reviews mostly report only average values across all submitted proposals. But inter-rater reliabilities can vary depending on the scientific discipline or the requested grant sum, for instance.

Formation of phosphoglycosides in Caenorhabditis elegans: a novel biotransformation pathway.

Background: Caenorhabditis elegans (C. elegans) has become a widely used model to explore the effect of food constituents on health as well as on life-span extension. The results imply that besides essential nutrients several flavonoids are able to impact the aging process.

Dynamic changes of the Caenorhabditis elegans proteome during ontogenesis assessed by quantitative analysis with 15N metabolic labeling.

The development of the nematode Caenorhabditis elegans is a highly dynamic process. Although various studies have assessed global transcriptome changes, information on the dynamics of the proteome during ontogenesis is not available. We metabolically labeled C.

Diet-induced obesity in ad libitum-fed mice: food texture overrides the effect of macronutrient composition.

Diet-induced obesity in mice can be achieved through the use of diets with different macronutrient compositions and textures. We aimed at determining the contribution of macronutrient composition to obesity development and associated pathophysiological changes in mice. C57BL/6N mice were offered a control, a high-fat or a Western-style diet, either as pellet (H for hard) or with identical composition in powder form (S for soft), resulting in C-S, C-H, HF-H, HF-S, W-H and W-S groups, respectively.

Knowledge and attitudes about tetanus and rabies: a population-based survey from Karachi, Pakistan.

Objective: To evaluate public knowledge regarding predisposing factors, fatality and prevention of Tetanus and Rabies and attitudes toward vaccination and post-exposure prophylaxis.

Methods: A population-based, cross-sectional survey was conducted in all the 18 towns of Karachi, the largest metropolitan city of Pakistan, from December 2007 to January 2008. Men and women of more than 18 years of age were included in the study which used a self-reporting questionarre as its tool.

Acetatifactor muris gen. nov., sp. nov., a novel bacterium isolated from the intestine of an obese mouse.

We used selective agar media for culturing bacteria from the caecum of mice fed a high calorie diet. In addition to the isolation of Enterobacteriaceae growing on a medium containing cholesterol and bile salts, we focused on the characterization of strain CT-m2(T), which, based on 16S rDNA analysis, did not appear to correspond to any currently described organisms. The isolate belongs to the Clostridium cluster XIV and is most closely related to members of the Lachnospiraceae, including the genera Anaerostipes, Blautia, Butyrivibrio, Clostridium, Coprococcus, Eubacterium, Robinsoniella, Roseburia, Ruminococcus and Syntrophococcus (≤90 % similarity).

A new signalling pathway for parallel fibre presynaptic type 4 metabotropic glutamate receptors (mGluR4) in the rat cerebellar cortex.

In the rodent cerebellum, pharmacological activation of mGluR4 acutely depresses excitatory synaptic transmission at parallel fibre–Purkinje cell synapses. This depression involves the inhibition of presynaptic calcium (Ca2+) influx that ultimately controls glutamate release. In this study, we investigate the molecular basis of mGluR4-mediated inhibition of presynaptic Ca2+ transients.

A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies.

Background: Efatutazone (CS-7017), a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist, exerts anticancer activity in preclinical models. The authors conducted a phase 1 study to determine the recommended phase 2 dose, safety, tolerability, and pharmacokinetics of efatutazone.

Methods: Patients with advanced solid malignancies and no curative therapeutic options were enrolled to receive a given dose of efatutazone, administered orally (PO) twice daily for 6 weeks, in a 3 + 3 intercohort dose-escalation trial.

Native presynaptic metabotropic glutamate receptor 4 (mGluR4) interacts with exocytosis proteins in rat cerebellum.

The eight pre- or/and post-synaptic metabotropic glutamatergic receptors (mGluRs) modulate rapid excitatory transmission sustained by ionotropic receptors. They are classified in three families according to their percentage of sequence identity and their pharmacological properties. mGluR4 belongs to group III and is mainly localized presynaptically.

The dynamic range of the human metabolome revealed by challenges.

Metabolic challenge protocols, such as the oral glucose tolerance test, can uncover early alterations in metabolism preceding chronic diseases. Nevertheless, most metabolomics data accessible today reflect the fasting state. To analyze the dynamics of the human metabolome in response to environmental stimuli, we submitted 15 young healthy male volunteers to a highly controlled 4 d challenge protocol, including 36 h fasting, oral glucose and lipid tests, liquid test meals, physical exercise, and cold stress.

C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia.

Background: Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined.

Methods: We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w) cholesterol.

A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential.

Metabotropic glutamate (mGlu) receptors are promising targets to treat numerous brain disorders. So far, allosteric modulators are the only subtype selective ligands, but pure agonists still have strong therapeutic potential. Here, we aimed at investigating the possibility of developing subtype-selective agonists by extending the glutamate-like structure to hit a nonconsensus binding area.