Cell-wall polysaccharides play an important role in decay resistance of Sphagnum and actively depressed decomposition in vitro

Sphagnum-dominated peatlands head the list of ecosystems with the largest known reservoirs of organic carbon (C). The bulk of this C is stored in decomposition-resistant litter of one bryophyte genus: Sphagnum. Understanding how Sphagnum litter chemistry controls C mineralization is essential for understanding potential interactions between environmental changes and C mineralization in peatlands. We aimed to separate the effects of phenolics from structural polysaccharides on decay of Sphagnum. We measured aerobic microbial respiration of different moss litter types in a lab. We used chemical treatments to step-wise remove the chemical compounds thought to be important in decay-resistance in three taxonomically distant moss genera. We also focused on the effect of Sphagnum-specific cell-wall pectin-like polysaccharides (sphagnan) on C and N mineralization. Removing polymeric lignin-like phenolics had only negligible effects on C mineralization of Sphagnum litter, but increased mineralization of two other bryophyte genera, suggesting a minor role of these phenolics in decay resistance of Sphagnum but a major role of cell-wall polysaccharides. Carboxyl groups of pectin-like polysaccharides represented a C-source in non-Sphagnum litters but resisted decay in Sphagnum. Finally, isolated sphagnan did not serve as C-source but inhibited C and N mineralization instead, reminiscent of the effects reported for phenolics in other ecosystems. Our results emphasize the role of polysaccharides in resistance to, and active inhibition of, microbial mineralization in Sphagnum-dominated litter. As the polysaccharides displayed decay-inhibiting properties hitherto associated with phenolics (lignin, polyphenols), it raises the question if polysaccharide-dominated litter also shares similar environmental controls on decomposition, such as temperature or nutrient and water availability.     

Gender difference in antidiuretic response to desmopressin

Increased age and female gender are well-known risk factors for the development of desmopressin-induced hyponatremia. However, little focus has been on exploring gender differences in the antidiuretic response to desmopressin. Based on an exploratory analysis from three clinical trials, we report a significant gender difference in the effects of desmopressin on nocturnal urine volume that could not be explained by pharmacokinetic differences. Mean desmopressin concentration profiles were tested for covariates, and age and gender were not statistically significant and only weight was significant for log(C(max)) (P = 0.0183) and borderline significant for log(AUC) (P = 0.0571). The decrease in nocturnal urine volume in nocturia patients treated with desmopressin over 28 days was significantly larger for women at the lower desmopressin melt doses of 10 and 25 μg than for men. The ED(50) for men was modeled to be 43.2 μg and 16.1 μg for women, with the ED(50) men/women estimated to be 2.7 (1.3-8.1 95% CI), corresponding to significantly higher sensitivity to desmopressin in women. An increasing incidence of hyponatremia with increasing dose was found, and at the highest dose level of 100 μg decreases in serum sodium were approximately twofold greater in women over 50 yr of age than in men. A new dose recommendation stratified by gender is suggested in the treatment of nocturia: for men, 50- to 100-μg melt is an efficacious and safe dose, while for women a dose of 25 μg melt is recommended as efficacious with no observed incidences of hyponatremia. Areas for further research are proposed to uncover pathophysiological mechanism(s) behind these gender differences.     

Variation in NOD2 augments Th2- and Th17 responses to myelin basic protein in multiple sclerosis

Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p<0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p<0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p<0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism influences T helper (Th) cell 2- and Th17 cell responses in MNC from MS patients.     

The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as “variants of uncertain significance”, being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.     

Effects of carbohydrate supplementation on performance and carbohydrate oxidation after intensified cycling training.

To study the effects of carbohydrate (CHO) supplementation on performance changes and symptoms of overreaching, six male endurance cyclists completed 1 wk of normal (N), 8 days of intensified (ITP), and 2 wk of recovery training (R) on two occasions in a randomized crossover design. Subjects completed one trial with a 6% CHO solution provided before and during training and a 20% solution in the 1 h postexercise (H-CHO trial). On the other occasion, subjects consumed a 2% CHO solution at the same time points (L-CHO). A significant decline in time to fatigue at approximately 63% maximal power output (H-CHO: 17 +/- 3%; L-CHO: 26 +/- 7%) and a significant increase in mood disturbance occurred in both trials after ITP. The decline in performance was significantly greater in the L-CHO trial. After ITP, a significant decrease in estimated muscle glycogen oxidation (H-CHO: N 49.3 +/- 2.9 kcal/30 min, ITP 32.6 +/- 3.4 kcal/30 min; L-CHO: N 49.1 +/- 30 kcal/30 min, ITP 39.0 +/- 5.6 kcal/30 min) and increase in fat oxidation (H-CHO: N 16.3 +/- 2.4 kcal/30 min, ITP 27.8 +/- 2.3 kcal/30 min; L-CHO: N 16.9 +/- 2.6 kcal/30 min, ITP: 25.4 +/- 3.5 kcal/30 min) occurred alongside significant increases in glycerol and free fatty acids and decreases in free triglycerides in both trials. An interaction effect was observed for submaximal plasma concentrations of cortisol and epinephrine, with significantly greater reductions in these stress hormones in L-CHO compared with H-CHO after ITP. These findings suggest that CHO supplementation can reduce the symptoms of overreaching but cannot prevent its development. Decreased endocrine responsiveness to exercise may be implicated in the decreased performance and increased mood disturbance characteristic of overreaching.     

Cholic Acid Induces a Cftr Dependent Biliary Secretion and Liver Growth Response in Mice

The cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr^-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous) or chronic (three weeks via the diet). In Cftr^-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr^-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr^-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr^-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr^-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr^-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr^-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.     

The l-α-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in l-arginine-induced insulin release

GPRC6A is a seven-transmembrane receptor activated by a wide range of l-α-amino acids, most potently by l-arginine and other basic amino acids. The receptor is broadly expressed, but its exact physiological role remains to be elucidated. It is well established that l-arginine stimulates insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism. In this study, we demonstrate that GPRC6A is expressed in islets of Langerhans, but activation of the receptor by l-arginine did not stimulate insulin secretion. We also investigated central metabolic parameters in GPRC6A knockout mice compared with wildtype littermates and found no difference in glucose metabolism or body fat percentage when mice were administered a standard chow diet. In conclusion, our data do not support a role for GPRC6A in l-arginine-induced insulin release and glucose metabolism under normal physiological conditions.