Testosterone and resistance training effects on muscle nitric oxide synthase isoforms in COPD men

SummaryBackgroundSkeletal muscle dysfunction contributes to exercise limitation in COPD. The role of the nitric oxide synthase (NOS) system in muscle dysfunction is ill defined. Reduced levels of endothelial NOS (eNOS) and elevated levels of inducible NOS (iNOS) in the skeletal muscle of COPD patients have been recently reported. We hypothesized that resistance exercise training (R) and/or testosterone supplementation (T) would alter the transcription and expression of the NOS isoenzymes in COPD skeletal muscle.MethodsVastus lateralis biopsies were obtained before and after a 10-week intervention in 40 men with severe COPD(age 67.7 ± 8.3, FEV1 41.4 ± 12.6% predicted): placebo + no training (P) (n = 11), placebo + resistance training (PR) (n = 8), testosterone + no training (T) (n = 11) and testosterone + resistance training (TR) (n = 10) groups. eNOS, nNOS and iNOS mRNA and protein levels were measured in each sample. mRNA and protein levels were measured using real-time PCR and enzyme-linked immunosorbant assay, respectively.ResultseNOS mRNA increased in the TR group compared to P and T groups (P < 0.001). eNOS protein was increased in TR and T groups after intervention (P < 0.05) but not in the PR group. nNOS protein increased in the PR, T, and TR groups (P < 0.05). iNOS protein decreased only in the TR group (P = 0.01).ConclusionResistance training and testosterone supplementation increased eNOS and nNOS proteins and decreased iNOS protein in the skeletal muscles of men with COPD. These changes in NO system might explain some of the favorable effects of these therapies

Modernizing and Harmonizing Regulatory Data Requirements for Genetically Modified Crops-Perspectives From a Workshop

Genetically modified (GM) crops that have been engineered to express transgenes have been in commercial use since 1995 and are annually grown on 200 million hectares globally. These crops have provided documented benefits to food security, rural economies, and the environment, with no substantiated case of food, feed, or environmental harm attributable to cultivation or consumption. Despite this extensive history of advantages and safety, the level of regulatory scrutiny has continually increased, placing undue burdens on regulators, developers, and society, while reinforcing consumer distrust of the technology. CropLife International held a workshop at the 16th International Society of Biosafety Research (ISBR) Symposium to examine the scientific basis for modernizing global regulatory frameworks for GM crops. Participants represented a spectrum of global stakeholders, including academic researchers, GM crop developers, regulatory consultants, and regulators. Concurrently examining the considerations of food and feed safety, along with environmental safety, for GM crops, the workshop presented recommendations for a core set of data that should always be considered, and supplementary (i.e., conditional) data that would be warranted only on a case-by-case basis to address specific plausible hypotheses of harm. Then, using a case-study involving a hypothetical GM maize event expressing two familiar traits (insect protection and herbicide tolerance), participants were asked to consider these recommendations and discuss if any additional data might be warranted to support a science-based risk assessment or for regulatory decision-making. The discussions during the workshop highlighted that the set of data to address the food, feed, and environmental safety of the hypothetical GM maize, in relation to a conventional comparator, could be modernized compared to current global regulatory requirements. If these scientific approaches to modernize data packages for GM crop regulation were adopted globally, GM crops could be commercialized in a more timely manner, thereby enabling development of more diverse GM traits to benefit growers, consumers, and the environment

Hydrogen-Helium Mixtures at High Pressure

The properties of hydrogen-helium mixtures at high pressure are crucial to address important questions about the interior of Giant planets e.g. whether Jupiter has a rocky core and did it emerge via core accretion? Using path integral Monte Carlo simulations, we study the properties of these mixtures as a function of temperature, density and composition. The equation of state is calculated and compared to chemical models. We probe the accuracy of the ideal mixing approximation commonly used in such models. Finally, we discuss the structure of the liquid in terms of pair correlation functions.Comment: Proceedings article of the 5th Conference on Cryocrystals and Quantum Crystals in Wroclaw, Poland, submitted to J. Low. Temp. Phys. (2004

Role of dispersal in resistance evolution and spread

Gene flow via immigration affects rate of evolution of resistance to a pest management tactic, while emigration from a resistant population can spread resistance alleles spatially. Whether resistance detected across the landscape reflects ongoing de novo evolution in different hotspots or spread from a single focal population can determine the most effective mitigation strategy. Pest dispersal dynamics determine the spatio-temporal scale at which mitigation tactics must be applied to contain or reverse resistance in an area. Independent evolution of resistance in different populations appears common but not universal. Conversely, spatial spread appears to be almost inevitable. However, rate and scale of spread depends largely on dispersal dynamics and interplay with factors such as fitness costs, spatially variable selection pressure and whether resistance alleles are spreading through an established population or being carried by populations colonizing new territory

Plant Trait Diversity Buffers Variability in Denitrification Potential over Changes in Season and Soil Conditions

BACKGROUND: Denitrification is an important ecosystem service that removes nitrogen (N) from N-polluted watersheds, buffering soil, stream, and river water quality from excess N by returning N to the atmosphere before it reaches lakes or oceans and leads to eutrophication. The denitrification enzyme activity (DEA) assay is widely used for measuring denitrification potential. Because DEA is a function of enzyme levels in soils, most ecologists studying denitrification have assumed that DEA is less sensitive to ambient levels of nitrate (NO(3)(-)) and soil carbon and thus, less variable over time than field measurements. In addition, plant diversity has been shown to have strong effects on microbial communities and belowground processes and could potentially alter the functional capacity of denitrifiers. Here, we examined three questions: (1) Does DEA vary through the growing season? (2) If so, can we predict DEA variability with environmental variables? (3) Does plant functional diversity affect DEA variability? METHODOLOGY/PRINCIPAL FINDINGS: The study site is a restored wetland in North Carolina, US with native wetland herbs planted in monocultures or mixes of four or eight species. We found that denitrification potentials for soils collected in July 2006 were significantly greater than for soils collected in May and late August 2006 (p<0.0001). Similarly, microbial biomass standardized DEA rates were significantly greater in July than May and August (p<0.0001). Of the soil variables measured--soil moisture, organic matter, total inorganic nitrogen, and microbial biomass--none consistently explained the pattern observed in DEA through time. There was no significant relationship between DEA and plant species richness or functional diversity. However, the seasonal variance in microbial biomass standardized DEA rates was significantly inversely related to plant species functional diversity (p<0.01). CONCLUSIONS/SIGNIFICANCE: These findings suggest that higher plant functional diversity may support a more constant level of DEA through time, buffering the ecosystem from changes in season and soil conditions

Model Convolution: A Computational Approach to Digital Image Interpretation

Digital fluorescence microscopy is commonly used to track individual proteins and their dynamics in living cells. However, extracting molecule-specific information from fluorescence images is often limited by the noise and blur intrinsic to the cell and the imaging system. Here we discuss a method called “model-convolution,” which uses experimentally measured noise and blur to simulate the process of imaging fluorescent proteins whose spatial distribution cannot be resolved. We then compare model-convolution to the more standard approach of experimental deconvolution. In some circumstances, standard experimental deconvolution approaches fail to yield the correct underlying fluorophore distribution. In these situations, model-convolution removes the uncertainty associated with deconvolution and therefore allows direct statistical comparison of experimental and theoretical data. Thus, if there are structural constraints on molecular organization, the model-convolution method better utilizes information gathered via fluorescence microscopy, and naturally integrates experiment and theory

Triptans attenuate capsaicin-induced CREB phosphorylation within the trigeminal nucleus caudalis: a mechanism to prevent central sensitization?

The c-AMP-responsive element binding protein (CREB) and its phosphorylated product (P-CREB) are nuclear proteins expressed after stimulation of pain-producing areas of the spinal cord. There is evidence indicating that central sensitization within dorsal horn neurons is dependent on P-CREB transcriptional regulation. The objectives of the study were to investigate the expression of P-CREB in cells in rat trigeminal nucleus caudalis after noxious stimulation and to determine whether pre-treatment with specific anti-migraine agents modulate this expression. CREB and P-CREB labelling was investigated within the trigeminal caudalis by immunohistochemistry after capsaicin stimulation. Subsequently, the effect of i.v. pre-treatment with either sumatriptan (n = 5), or naratriptan (n = 7) on P-CREB expression was studied. Five animals pre-treated with i.v. normal saline were served as controls. CREB and P-CREB labelling was robust in all animal groups within Sp5C. Both naratriptan and sumatriptan decreased P-CREB expression (p = 0.0003 and 0.0013) within the Sp5C. Triptans attenuate activation of CREB within the central parts of the trigeminal system, thereby leading to potential inhibition of central sensitization. P-CREB may serve as a new marker for post-synaptic neuronal activation within Sp5C in animal models relevant to migraine

The effect of a comprehensive lifestyle intervention on cardiovascular risk factors in pharmacologically treated patients with stable cardiovascular disease compared to usual care: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established.</p> <p>The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD) compared with usual care.</p> <p>Methods</p> <p>A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71) or control group (n = 75) using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication.</p> <p>Results</p> <p>The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference). In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor.</p> <p>Conclusions</p> <p>Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive lifestyle intervention had a beneficial effect on some cardiovascular risk factors. In the present era of cardiovascular therapy and with the increasing numbers of overweight and physically inactive patients, this study confirms the importance of risk factor control through lifestyle modification as a supplement to more intensified drug treatment in patients with CVD.</p> <p>Trial registration</p> <p>ISRCTN69776211 at <url>http://www.controlled-trials.com</url></p

MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

This article shows a novel function for the MAP1B protein, related to the control of actin dynamics through interaction with Tiam1