Neuromuscular fatigue induced by a 90-minute soccer game modeling

This study aimed to quantify neuromuscular fatigue induced by a soccer game. Eight amateur soccer players (age 20.4 ± 1.3 years, mass 70.4 ± 6.9 kg, and height 174.9 ± 5.2 cm) reproduced a 90-minute soccer game modeling composed of two 45-minute periods separated by a 15-minute rest. Torque of quadriceps and hamstring muscle groups associated with electromyography, sprint speed, and vertical jump height was assessed before, at halftime, and immediately after the modeling. Most physical qualities decreased throughout the game with greater decays at match end than at halftime. Contrarily to quadriceps muscles, hamstring torque impairments were not accompanied by electromyographic activity reductions. Squat jump height was reduced at halftime and game end without any change for countermovement jumps. The sprint speed decrease was associated with stride frequency impairments without any change in amplitude and contact time. We concluded on torque production capacity and specific performance impairments during and after soccer games. Neuromuscular fatigue appeared primarily centrally mediated as attested by the reduced quadriceps muscle activity.     

Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes

Gastrointestinal bypass surgeries restore metabolic homeostasis in patients with type 2 diabetes and obesity(1), but the underlying mechanisms remain elusive. Duodenal-jejunal bypass surgery (DJB), an experimental surgical technique that excludes the duodenum and proximal jejunum from nutrient transit(1,2), lowers glucose concentrations in nonobese type 2 diabetic rats(2–5). Given that DJB redirects and enhances nutrient flow into the jejunum and that jejunal nutrient sensing affects feeding(6,7), the repositioned jejunum after DJB represents a junction at which nutrients could regulate glucose homeostasis. Here we found that intrajejunal nutrient administration lowered endogenous glucose production in normal rats through a gut-brain-liver network in the presence of basal plasma insulin concentrations. Inhibition of jejunal glucose uptake or formation of long chain fatty acyl-coA negated the metabolic effects of glucose or lipid, respectively, in normal rats, and altered the rapid (2 d) glucose-lowering effect induced by DJB in streptozotocin (STZ)-induced uncontrolled diabetic rats during refeeding. Lastly, in insulin-deficient autoimmune type 1 diabetic rats and STZ-induced diabetic rats, DJB lowered glucose concentrations in 2 d independently of changes in plasma insulin concentrations, food intake and body weight. These data unveil a glucoregulatory role of jejunal nutrient sensing and its relevance in the early improvement of glycemic control after DJB in rat models of uncontrolled diabetes.     

Migratory constraints on yolk precursors limit yolk androgen deposition and underlie a brood reduction strategy in rockhopper penguins

Hormonally mediated maternal effects link maternal phenotype and environmental conditions to offspring phenotype. The production of lipid-rich maternal yolk precursors may provide a mechanism by which lipophilic steroid hormones can be transported to developing yolks, thus predicting a positive correlation between yolk precursors in mothers and androgen levels in eggs. Using rockhopper penguins (Eudyptes chrysocome), which produce a two-egg clutch characterized by extreme egg-size dimorphism, reversed hatching asynchrony and brood-reduction, we examined correlations between circulating concentrations of the primary yolk-precursor vitellogenin (VTG) and levels of yolk androgens. Previous work in Eudyptes penguins has shown that egg-size dimorphism is the product of migratory constraints on yolk precursor production. We predicted that if yolk precursors are constrained, androgen transport to developing yolks would be similarly constrained. We reveal positive linear relationships between maternal VTG and androgens in small A-eggs but not larger B-eggs, which is consistent with a migratory constraint operating on the A-egg. Results suggest that intra-clutch variation in total yolk androgen levels depends on the production and uptake of yolk precursors. The brood reduction strategy common to Eudyptes might thus be best described as the result of a migratory constraint.     

Novel, potent non-covalent thrombin inhibitors incorporating p(3)-lactam scaffolds

Evolution of P(1)-argininal inhibitor prototypes led to a series of non-covalent P(3)-7-membered lactam inhibitors 1a-w, featuring novel peptidomimetic units that probe each of the S(1), S(2), and S(3) specificity pockets of thrombin. Rigid P(1)-arginine surrogates possessing a wide range of basicity (calcd pK(a)'s approximately neutral-14) were surveyed. The design, synthesis, and biological activity of these targets are presented.     

Spatially Resolved Characterization of Biogenic Manganese Oxide Production within a Bacterial Biofilm

Pseudomonas putida strain MnB1, a biofilm-forming bacterial culture, was used as a model for the study of bacterial Mn oxidation in freshwater and soil environments. The oxidation of aqueous Mn⁺² [Mn⁺²_(aq)] by P. putida was characterized by spatially and temporally resolving the oxidation state of Mn in the presence of a bacterial biofilm, using scanning transmission X-ray microscopy (STXM) combined with near-edge X-ray absorption fine structure (NEXAFS) spectroscopy at the Mn L_2,3 absorption edges. Subsamples were collected from growth flasks containing 0.1 and 1 mM total Mn at 16, 24, 36, and 48 h after inoculation. Immediately after collection, the unprocessed hydrated subsamples were imaged at a 40-nm resolution. Manganese NEXAFS spectra were extracted from X-ray energy sequences of STXM images (stacks) and fit with linear combinations of well-characterized reference spectra to obtain quantitative relative abundances of Mn(II), Mn(III), and Mn(IV). Careful consideration was given to uncertainty in the normalization of the reference spectra, choice of reference compounds, and chemical changes due to radiation damage. The STXM results confirm that Mn⁺²_(aq) was removed from solution by P. putida and was concentrated as Mn(III) and Mn(IV) immediately adjacent to the bacterial cells. The Mn precipitates were completely enveloped by bacterial biofilm material. The distribution of Mn oxidation states was spatially heterogeneous within and between the clusters of bacterial cells. Scanning transmission X-ray microscopy is a promising tool for advancing the study of hydrated interfaces between minerals and bacteria, particularly in cases where the structure of bacterial biofilms needs to be maintained.     

Viral clearance using disposable systems in monoclonal antibody commercial downstream processing

Once highly selective protein A affinity is chosen for robust mAb downstream processing, the major role of polishing steps is to remove product related impurities, trace amounts of host cell proteins, DNA/RNA, and potential viral contaminants. Disposable systems can act as powerful options either to replace or in addition to polishing column chromatography to ensure product purity and excellent viral clearance power for patients' safety. In this presentation, the implementation of three disposable systems such as depth filtration, membrane chromatography, and nanometer filtration technology in a commercial process are introduced. The data set of viral clearance with these systems is presented. Application advantages and disadvantages including cost analysis are further discussed.     

Genotype-specific genomic markers associated with primary hepatomas, based on complete genomic sequencing of hepatitis B virus

We aimed to identify genomic markers in hepatitis B virus (HBV) that are associated with hepatocellular carcinoma (HCC) development by comparing the complete genomic sequences of HBVs among patients with HCC and those without. One hundred patients with HBV-related HCC and 100 age-matched HBV-infected non-HCC patients (controls) were studied. HBV DNA from serum was directly sequenced to study the whole viral genome. Data mining and rule learning were employed to develop diagnostic algorithms. An independent cohort of 132 cases (43 HCC and 89 non-HCC) was used to validate the accuracy of these algorithms. Among the 100 cases of HCC, 37 had genotype B (all subgenotype Ba) and 63 had genotype C (16 subgenotype Ce and 47 subgenotype Cs) HBV infection. In the control group, 51 had genotype B and 49 had genotype C (10 subgenotype Ce and 39 subgenotype Cs) HBV infection. Genomic algorithms associated with HCC were derived based on genotype/subgenotype-specific mutations. In genotype B HBV, mutations C1165T, A1762T and G1764A, T2712C/A/G, and A/T2525C were associated with HCC. HCC-related mutations T31C, T53C, and A1499G were associated with HBV subgenotype Ce, and mutations G1613A, G1899A, T2170C/G, and T2441C were associated with HBV subgenotype Cs. Amino acid changes caused by these mutations were found in the X, envelope, and precore/core regions in association with HBV genotype B, Ce, and Cs, respectively. In conclusion, infections with different genotypes of HBV (B, Ce, and Cs) carry different genomic markers for HCC at different parts of the HBV genome. Different HBV genotypes may have different virologic mechanisms of hepatocarcinogenesis.