ObjectiveTo investigate the functional effects of probiotic treatment on the gut microbiota, as well as liver and adipose gene expression in diet-induced obese mice.DesignMale C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce obesity, and then randomized to receive HFD+probiotic (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, n = 9) or HFD+placebo (n = 9) for another 10 weeks. Normal diet (ND) fed mice (n = 9) served as non-obese controls.ResultsDiet-induced obese mice treated with probiotics showed reduced body weight gain and fat accumulation as well as lowered plasma insulin, leptin, total-cholesterol and liver toxicity biomarkers. A total of 151,061 pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564, 5,274 and 4,464 reads for the ND, HFD+placebo and HFD+probiotic groups, respectively. Gut microbiota species were shared among the experimental groups despite the different diets and treatments. The diversity of the gut microbiota and its composition were significantly altered in the diet-induced obese mice and after probiotic treatment. We observed concurrent transcriptional changes in adipose tissue and the liver. In adipose tissue, pro-inflammatory genes (TNFα, IL6, IL1β and MCP1) were down-regulated in mice receiving probiotic treatment. In the liver, fatty acid oxidation-related genes (PGC1α, CPT1, CPT2 and ACOX1) were up-regulated in mice receiving probiotic treatment.ConclusionsThe gut microbiota of diet-induced obese mice appears to be modulated in mice receiving probiotic treatment. Probiotic treatment might reduce diet-induced obesity and modulate genes associated with metabolism and inflammation in the liver and adipose tissue.

Highlights d RIPLET, not TRIM25, is the obligatory ubiquitin E3 ligase for RIG-I d RIPLET recognizes pre-assembled RIG-I oligomers on dsRNA and ubiquitinates RIG-I d RIPLET can cross-bridge RIG-I filaments formed on longer dsRNA d The two binding modes synergize for length dependent dsRNA discrimination by RIG-I

Cationic silane complexes of general structure (POCOP)Ir(H)(HSiR(3)) {POCOP = 2,6-[OP(tBu)(2)](2)C(6)H(3)} catalyze hydrosilylations of CO(2). Using bulky silanes results in formation of bis(silyl)acetals and methyl silyl ethers as well as siloxanes and CH(4). Using less bulky silanes such as Me(2)EtSiH or Me(2)PhSiH results in rapid formation of CH(4) and siloxane with no detection of bis(silyl)acetal and methyl silyl ether intermediates. The catalyst system is long-lived, and 8300 turnovers can be achieved using Me(2)PhSiH with a 0.0077 mol % loading of iridium. The proposed mechanism for the conversion of CO(2) to CH(4) involves initial formation of the unobserved HCOOSiR(3). This formate ester is then reduced sequentially to R(3)SiOCH(2)OSiR(3), then R(3)SiOCH(3), and finally to R(3)SiOSiR(3) and CH(4).

Emerging evidence has revealed an endocrine function for skeletal muscle; in fact, certain anti-inflammatory cytokines are secreted only from contractile skeletal muscle. However, the skeletal muscle secretome as a whole is poorly characterized, as is how it changes in response to extracellular stimuli. Herein, we sought to identify and characterize the members of the skeletal muscle secretome, and to determine which protein secretion levels were modulated in response to insulin stimulation. To conduct these studies, we treated differentiated L6 rat skeletal muscle cells with insulin or left them untreated, and we comparatively analyzed the proteins secreted into the media. We fractionated this conditioned media using offline RP HPLC, digested the fractionated proteins, and analyzed the resulting peptides with LC-ESI-MS/MS. We identified a total of 254 proteins, and by using three different filtering methods, we identified 153 of these as secretory proteins. Fourteen proteins were secreted at higher levels under insulin stimulation, including several proteins known to be highly secreted in metabolic diseases; 19 proteins were secreted at lower levels under insulin stimulation. These result not only pinpointed several previously unknown, insulin induced, secretory proteins of skeletal muscle, it also described a novel approach for conditioned secretome analysis.

A four segment trial-repeat model is developed to model sales of a frequently purchased product in the early stage of the product's life cycle. The model can be calibrated using aggregate data alone. Two versions of the model, one emphasizing the competitive aspect of marketing communications and another emphasizing the informative aspect, are estimated from data on 21 newly launched pharmaceutical products. The model provides valuable diagnostics such as an early estimate of the long-run market share of the new product, a decomposition of total sales (into trial sales due to marketing activities, trial sales due to word-of-mouth, and repeat sales), the changing composition of the trial market and repeat market over time, and the time when the trial market is expected to be saturated. In addition, the effectiveness of the entrant's marketing efforts, word-of-mouth communication, and buyers' trial experience are analyzed with the model. A cross-sectional analysis based on the empirical estimation results of our model reveals interesting insights into product introduction strategies. We find that: 1) the effectiveness of the firms' communication activities on trial is related mainly to product quality attributes and market growth whereas that of word-of-mouth is associated with product class characteristics and market competitiveness, and 2) the effect of product trial on repeat purchases is related mainly to product quality attributes and various market characteristics such as size, growth, competitiveness, and familiarity.diffusion, new product research

In this study we found that CXCL12 is an adipocyte-derived chemotactic factor that recruits macrophages, and that it is a required factor for the establishment of obesity-induced adipose tissue inflammation and systemic insulin resistance.

Hydrosilation of a variety of ketones and aldehydes using the cationic iridium catalyst, (POCOP)Ir(H)(acetone)+, 1, (POCOP = 2,6-bis(di-tert-butyl phosphinito)phenyl) is reported. With triethyl silane, all but exceptionally bulky ketones undergo quantitative reactions employing 0.5 mol% catalyst in 20-30 min at 25 °C. Hydrosilation of esters and amides results in over-reduction and cleavage of C-O and C-N bonds, respectively. The diastereoselectivity of hydrosilation of 4-tert-butyl cyclohexanone has been examined using numerous silanes and is highly temperature dependent. Using EtMe2SiH, analysis of the ratio of cis:trans hydrosilation products as a function of temperature yields values for ΔΔH‡ (ΔH‡ (trans) - ΔH‡ (cis)) and ΔΔS‡ (ΔS‡ (trans) - ΔS‡(cis)) of -2.5 kcal/mol and -6.9 e.u., respectively. Mechanistic studies show that the ketone complex, (POCOP)Ir(H)(ketone)+, is the catalyst resting state and is in equilibrium with low concentration of the silane complex, (POCOP)Ir(H)(HSiR3)+. The silane complex transfers R3Si+ to ketone forming the oxocarbenium ion, R3SiOCR’2+, which is reduced by the resulting neutral dihydride 3, (POCOP)Ir(H)2, to yield product R3SiOCHR’2 and (POCOP)IrH+ which closes the catalytic cycle.

Implementation of the AKI alert system was associated with beneficial effects in terms of an improved rate of recovery from AKI. Therefore, widespread adoption of such systems could be considered in general hospitals.