Rotary motors of bacterial flagella are driven by ions that move across the cytoplasmic membrane down an electrochemical gradient. For Escherichia coli, the ions are protons, and the maximum work per unit charge that they can do is the protonmotive force. To test whether motor efficiency is limited by proton leakage or mechanical nonlinearities, we measured torque as a function of protonmotive force. Filamentous cells were drawn into micropipettes and energized with an external voltage source. Torque was proportional to protonmotive force up to -150 mV, twice the span accessible by earlier techniques. This is consistent with a mechanism in which a fixed number of protons, working at unit efficiency, carry the motor through each revolution. We also found that individual torque-generating elements inactivate at low potentials or potentials of reverse sign. When normal potentials are restored, they reactivate sequentially.

Background— Although resveratrol has multiple beneficial cardiovascular effects, whether resveratrol can be used for the treatment and management of heart failure (HF) remains unclear. In the current study, we determined whether resveratrol treatment of mice with established HF could lessen the detrimental phenotype associated with pressure-overload–induced HF and identified physiological and molecular mechanisms contributing to this. Methods and Results— C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks post surgery, a cohort of mice with established HF (% ejection fraction <45) was administered resveratrol (≈320 mg/kg per day). Despite a lack of improvement in ejection fraction, resveratrol treatment significantly increased median survival of mice with HF, lessened cardiac fibrosis, reduced gene expression of several disease markers for hypertrophy and extracellular matrix remodeling that were upregulated in HF, promoted beneficial remodeling, and improved diastolic function. Resveratrol treatment of mice with established HF also restored the levels of mitochondrial oxidative phosphorylation complexes, restored cardiac AMP-activated protein kinase activation, and improved myocardial insulin sensitivity to promote glucose metabolism and significantly improved myocardial energetic status. Finally, noncardiac symptoms of HF, such as peripheral insulin sensitivity, vascular function, and physical activity, were improved with resveratrol treatment. Conclusions— Resveratrol treatment of mice with established HF lessens the severity of the HF phenotype by lessening cardiac fibrosis, improving molecular and structural remodeling of the heart, and enhancing diastolic function, vascular function, and energy metabolism.

Key pointsr Prenatal hypoxia, a common outcome of many pregnancy complications, predisposes offspring to chronic diseases in later life.r We investigated the effect of prenatal hypoxia, on a background of a high-fat diet, on metabolic and cardiac function in adult male and female rat offspring. We also examined the therapeutic role of resveratrol supplementation in preventing metabolic and cardiac dysfunction.r Prenatal hypoxia impaired both metabolic and cardiac function in male and only cardiac function in female rat offspring. We also observed that male rat offspring were more susceptible to metabolic and cardiac dysfunction as compared with their female counterparts; this provides evidence of sexual dichotomy in the fetal programming of diseases due to prenatal hypoxia.r Resveratrol supplementation in the diet improved metabolic and cardiac function independent of sex; this provides evidence of a possible therapeutic role of resveratrol in susceptible male and female rat offspring exposed to prenatal hypoxia.Abstract Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.

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Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response.

A mobile exposure and air pollution measurement system was developed and used for on-freeway ultrafine particle health effects studies. A nine-passenger van was modified with a high-efficiency particulate air (HEPA) filtration system that can deliver filtered or unfiltered air to an exposure chamber inside the van. State-of-the-art instruments were used to measure concentration and size distribution of fine and ultrafine particles and the concentration of carbon monoxide (CO), black carbon (BC), particle-bound polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5) mass, and oxides of nitrogen (NOx) inside the exposure chamber. This paper presents the construction and technical details of the van and air pollutant concentrations collected in 32 2-hr runs on two major Los Angeles freeways, Interstate 405 (1-405; mostly gasoline traffic) and Interstate 710 (1-710; large proportion of heavy-duty diesel traffic). More than 97% of particles were removed when the flow through the filter box was switched from bypass mode to filter mode while the vehicle was driving on both freeways. The filtration system thus provides a great particulate matter exposure contrast while keeping gas-phase pollutant concentrations the same. Under bypass mode, average total particle number concentration observed inside the exposure chamber was around 8.4 x 10(4) and 1.3 x 10(5) particles cm(-3) on the I-405 and the I-710 freeways, respectively. Bimodal size distributions were consistent and similar for both freeways with the first mode around 16-20 nm and the second mode around 50-55 nm. BC and particle-bound PAH concentrations were more than two times greater on the I-710 than on the I-405 freeway. Very weak correlations were observed between total particle number concentrations and other vehicular pollutants on the freeways.

β1β2M-KO mice display evidence of dilated cardiomyopathy. This is the first mouse model of AMPK deficiency that demonstrates cardiac dysfunction in the absence of pathological stress and provides insights into the role of AMPK in regulating myocardial function, metabolism, hypertrophy, and the progression to heart failure.

No abstract