Mitochondrial proteomics: analysis of a whole mitochondrial extract with two-dimensional electrophoresis

Mitochondria are complex organelles, and their proteomics analysis requires a combination of techniques. The emphasis in this chapter is made first on mitochondria preparation from cultured mammalian cells, then on the separation of the mitochondrial proteins with two-dimensional electrophoresis (2DE), showing some adjustment over the classical techniques to improve resolution of the mitochondrial proteins. This covers both the protein solubilization, the electrophoretic part per se, and the protein detection on the gels, which makes the interface with the protein identification part relying on mass spectrometry

Effects of copper on the early development of Xenopus laevis: the case of CuSO4 and Bordeaux mixture solutions

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Square root and division elimination in PVS

International audienceIn this paper we present a new strategy for PVS that imple- ments a square root and division elimination in order to use automatic arithmetic strategies that were not able to deal with these operations in the ﰁrst place. This strategy relies on a PVS formalization of the square root and division elimination and deep embedding of PVS expressions inside PVS. Therefore using computational reﰂection and symbolic com- putation we are able to automatically transform expressions into division and square root free ones before using these decision procedures

Efficient Certified Resolution Proof Checking

We present a novel propositional proof tracing format that eliminates complex processing, thus enabling efficient (formal) proof checking. The benefits of this format are demonstrated by implementing a proof checker in C, which outperforms a state-of-the-art checker by two orders of magnitude. We then formalize the theory underlying propositional proof checking in Coq, and extract a correct-by-construction proof checker for our format from the formalization. An empirical evaluation using 280 unsatisfiable instances from the 2015 and 2016 SAT competitions shows that this certified checker usually performs comparably to a state-of-the-art non-certified proof checker. Using this format, we formally verify the recent 200 TB proof of the Boolean Pythagorean Triples conjecture

Effects of sports drinks on the maintenance of physical performance during 3 tennis matches: A randomized controlled study

Background: Tennis tournaments often involve playing several consecutive matches interspersed with short periods of recovery. Objective: The objective of this study was firstly to assess the impact of several successive tennis matches on the physical performance of competitive players and secondly to evaluate the potential of sports drinks to minimize the fatigue induced by repeated matches. Methods: This was a crossover, randomized controlled study. Eight male regionally-ranked tennis players participated in this study. Players underwent a series of physical tests to assess their strength, speed, power and endurance following the completion of three tennis matches each of two hours duration played over three consecutive half-days (1.5 day period for each condition). In the first condition the players consumed a sports drink before, during and after each match; in the second, they drank an identical volume of placebo water. The results obtained were compared with the third 'rest' condition in which the subjects did not play any tennis. Main outcomes measured were maximal isometric strength and fatigability of knee and elbow extensors, 20-m sprint speed, jumping height, specific repeated sprint ability test and hand grip strength. Results: The physical test results for the lower limbs showed no significant differences between the three conditions. Conversely, on the upper limbs the EMG data showed greater fatigue of the triceps brachii in the placebo condition compared to the rest condition, while the ingestion of sports drinks attenuated this fatigue. Conclusions: This study has demonstrated for the first time that, when tennis players are adequately hydrated and ingest balanced meals between matches, then no large drop in physical performance is observed even during consecutive competitive matches

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Steering Away from Current Amoxicillin Dose Reductions in Hospitalized Patients with Impaired Kidney Function to Avoid Subtherapeutic Drug Exposure.

Current dose reductions recommended for amoxicillin in patients with impaired kidney function could lead to suboptimal treatments. In a prospective, observational study in hospitalized adults with varying kidney function treated with an IV or oral dose of amoxicillin, amoxicillin concentrations were measured in 1-2 samples on the second day of treatment. Pharmacometric modelling and simulations were performed to evaluate the probability of target attainment (PTA) for 40% of the time above MIC following standard (1000 mg q6h), reduced or increased IV dosing strategies. A total of 210 amoxicillin samples was collected from 155 patients with kidney function based on a CKD-EPI of between 12 and 165 mL/min/1.73 m2. Amoxicillin clearance could be well predicted with body weight and CKD-EPI. Recommended dose adjustments resulted in a clinically relevant reduction in the PTA for the nonspecies-related PK/PD breakpoint MIC of 8 mg/L (92%, 62% and 38% with a CKD-EPI of 10, 20 and 30 mL/min/1.73 m2, respectively, versus 100% for the standard dose). For MICs ≤ 2 mg/L, PTA > 90% was reached in these patients following both reduced and standard dose regimens. Our study showed that for amoxicillin, recommended dose reductions with impaired kidney function could lead to subtherapeutic amoxicillin concentrations in hospitalized patients, especially when targeting less susceptible pathogens