Oral Branched-Chain Amino Acid Supplements That Reduce Brain Serotonin During Exercise in Rats Also Lower Brain Catecholamines

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge

An accurate model for genetic hitch-hiking

We suggest a simple deterministic approximation for the growth of the favoured-allele frequency during a selective sweep. Using this approximation we introduce an accurate model for genetic hitch-hiking. Only when Ns < 10 (N is the population size and s denotes the selection coefficient), are discrepancies between our approximation and direct numerical simulations of a Moran model noticeable. Our model describes the gene genealogies of a contiguous segment of neutral loci close to the selected one, and it does not assume that the selective sweep happens instantaneously. This enables us to compute SNP distributions on the neutral segment without bias.Comment: 12 pages, 10 figure

A Factory-based Approach to Support E-commerce Agent Fabrication

With the development of Internet computing and software agent technologies, agent-based e-commerce is emerging. How to create agents for e-commerce applications has become an important issue along the way to success. We propose a factory-based approach to support agent fabrication in e-commerce and elaborate a design based on the SAFER (Secure Agent Fabrication, Evolution & Roaming) framework. The details of agent fabrication, modular agent structure, agent life cycle, as well as advantages of agent fabrication are presented. Product-brokering agent is employed as a practical agent type to demonstrate our design and Java-based implementation

Entometabolomics: applications of modern analytical techniques to insect studies

Metabolomic analyses can reveal associations between an organism's metabolome and further aspects of its phenotypic state, an attractive prospect for many life-sciences researchers. The metabolomic approach has been employed in some, but not many, insect study systems, starting in 1990 with the evaluation of the metabolic effects of parasitism on moth larvae. Metabolomics has now been applied to a variety of aspects of insect biology, including behaviour, infection, temperature stress responses, CO2 sedation, and bacteria–insect symbiosis. From a technical and reporting standpoint, these studies have adopted a range of approaches utilising established experimental methodologies. Here, we review current literature and evaluate the metabolomic approaches typically utilised by entomologists. We suggest that improvements can be made in several areas, including sampling procedures, the reduction in sampling and equipment variation, the use of sample extracts, statistical analyses, confirmation, and metabolite identification. Overall, it is clear that metabolomics can identify correlations between phenotypic states and underlying cellular metabolism that previous, more targeted, approaches are incapable of measuring. The unique combination of untargeted global analyses with high-resolution quantitative analyses results in a tool with great potential for future entomological investigations

Global Dynamic Characterization and Load Rating of Bridge Structures Utilizing Economical Dynamic Excitation Devices

Experimental modal analysis (EMA) of bridges and other civil structures can be used to acquire quantitative data describing their condition, and enhance opportunities for structural health monitoring and related fields. The use of EMA on civil structures has been limited by the high cost of the excitation devices that are required for the best data quality. The objective of the research reported herein is to evaluate a low-cost excitation system for multiple-input, multiple-output (MIMO) EMA, enabling the production of accurate estimates of the global behavior of in-service bridges. The prototype excitation system is composed of consumer entertainment devices, namely tactile transducers and subwoofer amplifiers, which are capable of providing excitation in the range of 5 Hz to 200 Hz. The use of these devices in vibration testing is unprecedented, and their low cost allows approximately 30 structural degrees-of-freedom to be excited for the price of a single purpose-built laboratory shaker device. Methods are developed to systematically characterize the operational performance of the devices. Research and testing are also performed to optimize the techniques by which the system can be used for MIMO EMA of bridges. The excitation system is then validated for MIMO EMA by dynamically characterizing a large-scale laboratory structure and comparing the results to those from traditional excitation methods. The system is then deployed on an in-service highway bridge, representing the first time that more than two shakers have been used in MIMO EMA testing of a bridge. The identification results using MIMO EMA are shown to be superior to those found using traditional excitation methods. Finally, the identified modal parameters of the in-service bridge are used in load rating. Direct use of the modal properties of a bridge for load rating is unprecedented, and a relatively simple method to use measured modal flexibility to help determine live load demand is developed herein. The bridge load ratings calculated from the new method are compared to traditional methods. In summary, a low-cost excitation system is optimized and systematically evaluated for MIMO EMA testing of civil structures, and the use of the system is validated in the laboratory and in the field. A new method to improve bridge rating reliability is then developed using the high quality modal parameters found via the optimized testing process

Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA-induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.This study was supported by Ministerio de Economía y Competitividad (MINECO SAF2016‐80305‐P), Instituto de Salud Carlos III (ISCIII) Fondo Europeo de Desarrollo Regional (FEDER) a way to build Europe (PI14/00386, PI14/0041, PIE13/00051, PI13/01488; PI17‐01495, CiberCV, CiberDEM), FP7 grant e‐PREDICE, by the Fundación Renal Iñigo Álvarez de Toledo (FRIAT)/Instituto Reina Sofía de Investigación Nefrológica and from Roche‐IdiPa

Ureteroscopy-assisted percutaneous kidney access made easy: first clinical experience with a novel navigation system using electromagnetic guidance (IDEAL Stage 1)

Background: Puncture of the renal collecting system represents a challenging step in percutaneous nephrolithotomy (PCNL). Limitations related to the use of standard fluoroscopic-based and ultrasound-based maneuvers have been recognized. Objectives: To describe the technique and early clinical outcomes of a novel navigation system for percutaneous kidney access. Design, setting, and participants: This was a proof-of-concept study (IDEAL phase 1) conducted at a single academic center. Ten PCNL procedures were performed for patients with kidney stones. Surgical procedure: Flexible ureterorenoscopy was performed to determine the optimal renal calyx for access. An electromagnetic sensor was inserted through the working channel. Then the selected calyx was punctured with a needle with a sensor on the tip guided by real-time three-dimensional images observed on the monitor. Outcome measurements and statistical analysis: The primary endpoints were the accuracy and clinical applicability of the system in clinical use. Secondary endpoints were the time to successful puncture, the number of attempts for successful puncture, and complications. Results and limitations: Ten patients were enrolled in the study. The median age was 47.1 yr (30-63), median body mass index was 22.85 kg/m(2) (19-28.3), and median stone size was 2.13 cm (1.5-2.5 cm). All stones were in the renal pelvis. The Guy's stone score was 1 in nine cases and 2 in one case. All 10 punctures of the collecting system were successfully completed at the first attempt without X-ray exposure. The median time to successful puncture starting from insertion of the needle was 20 s (range 15-35). No complications occurred. Conclusions: We describe the first clinical application of a novel navigation system using real-time electromagnetic sensors for percutaneous kidney access. This new technology overcomes the intrinsic limitations of traditional methods of kidney access, allowing safe, precise, fast, and effective puncture of the renal collecting system. Patient summary: We describe a new technology allowing safe and easy puncture of the kidney without radiation exposure. This could significantly facilitate one of the most challenging steps in percutaneous removal of kidney stones.info:eu-repo/semantics/publishedVersio

Prolonged constant load cycling exercise is associated with reduced gross efficiency and increased muscle oxygen uptake

This study investigated the effects of prolonged constant load cycling exercise on cycling efficiency and local muscle oxygen uptake responses. Fourteen well-trained cyclists each completed a 2-h steady-state cycling bout at 60% of their maximal minute power output to assess changes in gross cycling efficiency (GE) and muscle oxygen uptake (mVO2) at time points 5, 30, 60, 90, and 120 min. Near-infrared spatially resolved spectroscopy (NIRS) was used to continually monitor tissue oxygenation of the Vastus Lateralis muscle, with arterial occlusions (OCC) applied to assess mVO2 . The half-recovery time of oxygenated hemoglobin (HbO2 ) was also assessed pre and post the 2-h cycling exercise by measuring the hyperemic response following a 5-min OCC. GE significantly declined during the 2-h cycling bout (18.4 ± 1.6 to 17.4 ± 1.4%; P < 0.01). Conversely, mVO2 increased, being significantly higher after 90 and 120 min than at min 5 (+0.04 mlO2 /min/100 g; P = 0.03). The half-recovery time for HbO2 was increased comparing pre and post the 2-h cycling exercise (+7.1 ± 19s), albeit not significantly (d: 0.48; P = 0.27). This study demonstrates that GE decreases during prolonged constant load cycling exercise and provides evidence of an increased mVO2 , suggestive of progressive mitochondrial or contractile inefficiency

Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity

textabstractBackground: To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum. Methods: In this prospective cohort study, 77 patients admitted with an acute hip fracture to Oslo University Hospital, Norway, were studied. The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography. The patients were assessed daily for delirium by the Confusion Assessment Method (pre-operatively and post-operative day 1-5 (all) or until discharge (delirious patients)). Pre-fracture dementia status was decided by an expert panel. Serum was collected pre-operatively and CSF immediately before spinal anesthesia. Results: Fifty-three (71 %) hip fracture patients developed delirium. In hip fracture patients without dementia (n = 39), those with delirium had significantly higher CSF levels of tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those without delirium. The same amino acids were also higher in CSF in delirious patients with dementia (n = 38). The correlations between serum and CSF amino acid levels were poor. Conclusion: Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group