Manganese SOD Mimics Are Effective Against Heat Stress in a Mutant Fission Yeast Deficient in Mitochondrial Superoxide Dismutase

Previous studies revealed a close connection between heat shock and manganese-dependent superoxide dismutase (SOD2) in eukaryotes. This paper shows that SOD mimics based on manganese complexes caused an increase in thermotolerance for a mutant fission yeast deficient in mitochondrial superoxide dismutase. Manganese compounds used for tests are SOD mimics, from two different classes: salen manganese (EUK-8) and Mn porphyrin (Mn(III)TE-2-PyP(5+)). The tests were conducted using a Schizosaccharomyces pombe model, comparing the viability of two strains at chronic heat stress (37°C)--a wild type versus a strain with the mitochondrial superoxide dismutase gene deleted [SOD2(-)]. The presence of massive free radical species in S. pombe SOD2(-) was demonstrated using a luminol-enhanced chemiluminescence test derived from a menadione-mediated survival protocol. Conclusions: Survival tests revealed that the SOD2-deleted S. pombe is about 100 times more sensitive to heat stress than the wild-type strain. This survival deficit can be corrected by EUK-8 and Mn(III)TE-2-PyP(5+) to almost the same degree but not by manganese chloride II (MnCl(2)). Using a simple spot assay for viability testing, this new model proved to be an easy alternative for the initial estimation of manganese SOD mimics efficiency.     

4-D blood flow in the human right ventricle

Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 ± 0.3 mJ) than the other flow components (P < 0.001 and P < 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P < 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.     

Temporal graphical models for cross-species gene regulatory network discovery

Many genes and biological processes function in similar ways across different species. Cross-species gene expression analysis, as a powerful tool to characterize the dynamical properties of the cell, has found a number of applications, such as identifying a conserved core set of cell cycle genes. However, to the best of our knowledge, there is limited effort on developing appropriate techniques to capture the causality relations between genes from time-series microarray data across species. In this paper, we present hidden Markov random field regression with L(1) penalty to uncover the regulatory network structure for different species. The algorithm provides a framework for sharing information across species via hidden component graphs and is able to incorporate domain knowledge across species easily. We demonstrate our method on two synthetic datasets and apply it to discover causal graphs from innate immune response data.     

Structural basis for cell surface patterning through NetrinG-NGL interactions

Brain wiring depends on cells making highly localized and selective connections through surface protein-protein interactions, including those between NetrinGs and NetrinG ligands (NGLs). The NetrinGs are members of the structurally uncharacterized netrin family. We present a comprehensive crystallographic analysis comprising NetrinG1-NGL1 and NetrinG2-NGL2 complexes, unliganded NetrinG2 and NGL3. Cognate NetrinG-NGL interactions depend on three specificity-conferring NetrinG loops, clasped tightly by matching NGL surfaces. We engineered these NGL surfaces to implant custom-made affinities for NetrinG1 and NetrinG2. In a cellular patterning assay, we demonstrate that NetrinG-binding selectivity can direct the sorting of a mixed population of NGLs into discrete cell surface subdomains. These results provide a molecular model for selectivity-based patterning in a neuronal recognition system, dysregulation of which is associated with severe neuropsychological disorders.     

Training sessions with tackles impair upper-limb neuromuscular function in elite rugby union

The aim of this study was to investigate the response to non-tackle and tackle field-based training on upper- and lower-limb neuromuscular function in elite rugby union players. Nine elite senior elite rugby union players (mean age = 21 ± 2 years; height = 184 ± 7 cm; body mass 91.0 ± 9 kg) were evaluated before and immediately following 17 training sessions. A total of 306 assessments were performed. Data on neuromuscular function of plyometric push-up and countermovement jump were calculated from force signals using inverse dynamics. The change from pre- to post-session was investigated across non-tackle and tackle training using a linear mixed model. Considering upper-limb neuromuscular function, peak concentric power [P = 0.024; ES = 0.33 95%CI (0.04, 0.62)] was significantly lower after tackle compared to non-tackle training. In addition, peak countermovement jump eccentric power was significantly lower after non-tackle compared to tackle training [P = 0.044; ES = -0.4 95%CI (-0.69, -0.1)] in lower-limb neuromuscular function. Overall, the results indicated that the type of training influences upper- and lower-limb neuromuscular function differently immediately after training. Indeed, due to physical contact, the upper-body neuromuscular function increased during tackle training. In contrast, lower-body neuromuscular function emerged only in non-tackle training, due to the greater distance covered during this type of training session. Coaches and practitioners should plan adequate weekly training sessions according to this information.     

Triglycerides in the Human Kidney Cortex: Relationship with Body Size

Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.     

Romanian experience in child celiac disease diagnosis

Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensitivity and specificity tests", but in line with changing clinical features of celiac disease, its diagnosis has undergone significant changes in recent years. These changes in the diagnosis of celiac disease, we have decided to analyze them.     

Identification of General Patterns of Nutrient and Labile Carbon Control on Soil Carbon Dynamics Across a Successional Gradient

Carbon (C) inputs and nutrient availability are known to affect soil organic carbon (SOC) stocks. However, general rules regarding the operation of these factors across a range of soil nutrient availabilities and substrate qualities are unidentified. “Priming” (stimulated decomposition by labile C inputs) and ‘preferential substrate utilization’ (retarded decomposition due to shifts in community composition towards microbes that do not mineralize SOC) are two hypotheses to explain effects of labile C additions on SOC dynamics. For effects of nutrient additions (nitrogen and phosphorus) on SOC dynamics, the stoichiometric (faster decomposition of materials of low carbon-to-nutrient ratios) and ‘microbial mining’ (that is, reduced breakdown of recalcitrant C forms for nutrients under fertile conditions) hypotheses have been proposed. Using the natural gradient of soil nutrient availability and substrate quality of a chronosequence, combined with labile C and nutrient amendments, we explored the support for these contrasting hypotheses. Additions of labile C, nitrogen (N), phosphorus (P), and combinations of C and N and C and P were applied to three sites: 2-year fallow grassland, mature grassland and forest, and the effects of site and nutrient additions on litter decomposition and soil C dynamics were assessed. The response to C addition supported the preferential substrate hypothesis for easily degradable litter C and the priming hypothesis for SOC, but only in nitrogen-enriched soils of the forest site. Responses to N addition supported the microbial mining hypothesis irrespective of C substrate (litter or SOC), but only in the forest site. Further, P addition effects on SOC support the stoichiometric hypothesis; P availability appeared key to soil C release (priming) in the forest site if labile C and N is available. These results clearly link previously contrasting hypotheses of the factors controlling SOC with the natural gradient in litter quality and nutrient availability that exists in ecosystems at different successional stages. A holistic theory that incorporates this variability of responses, due to different mechanisms, depending on nutrient availability and substrate quality is essential for devising management strategies to safeguard soil C stocks.     

Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. a simulation Study

Background

The aim of the study was to find a simple intravenous glucose tolerance test (IVGTT) that can be used to estimate insulin sensitivity.

Methods

In 20 healthy volunteers aged between 18 and 51 years (mean, 28) comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the M_bw (glucose uptake) obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (V _d) and the clearance (CL) of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUC_ins). Uptake of glucose during the clamp was corrected for body weight (M_bw).

Results

There was a 7-fold variation in M_bw. Algorithms based on the slope of the glucose-elimination curve (CL/V _d) in combination with AUC_ins obtained during the IVGTT showed statistically significant correlations with M_bw, the linearity being r² = 0.63-0.83. The best algorithms were associated with a 25-75^th prediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision.

Conclusion

Simple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.