Tensin1 expression and function in chronic obstructive pulmonary disease

open access articleChronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs

Optimal monetary policy rules in a rational expectations model of the Phillips curve

In this paper we construct a rational expectations model based on a Phillips curve that embodies persistence in inflation. As we assume that the central bank targets the natural rate of output, there is no inflation bias. We derive optimal monetary policy rules that are state-contingent and shock-dependent both in the case where the central bank follows a commitment strategy and where it pursues a discretionary procedure. Numerical solutions show that in the state-contingent part there always exists a tradeoff between these two optimal rules in that the commitment rule involves smaller expected deviations of inflation from its target but larger expected deviations of output from its target; in the shock-dependent part there can be situations in which the discretionary rule is more effective in reducing the impact of the random shock on inflation and less effective in reducing the random shock on output. Only in the latter case it is possible that one rule is superior; otherwise it is generally the case that a tradeoff exists between these two rules

Noise Impacts from Professional Dog Grooming Forced-Air Dryers

This study was designed to measure the sound output of four commonly used brands of forced-air dryers used by dog groomers in the United States. Many dog groomers have questions about the effect of this exposure on their hearing, as well as on the hearing of the dogs that are being groomed. Readings taken from each dryer at 1 meter (the likely distance of the dryer from the groomer and the dog) showed average levels ranging from 105.5 to 108.3 dB SPL or 94.8 to 108.0 dBA. Using the 90 dBA criterion required by the US Occupational Safety and Health Administration, dog groomers/bathers are at risk if exposure to the lowest intensity dryer (94.8 dBA) exceeds 4 hours per day. If the more stringent 85 dBA criterion and 3 dB tradeoff is applied, less than one hour of exposure is permissible in an 8 hour day. Cautions are recommended for any persons exposed to noise from forced-air dryers

Tumor Growth Increases Neuroinflammation, Fatigue and Depressive-like Behavior Prior to Alterations in Muscle Function

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth

Aboveground Total and Green Biomass of Dryland Shrub Derived from Terrestrial Laser Scanning

Sagebrush (Artemisia tridentata), a dominant shrub species in the sagebrush-steppe ecosystem of the western US, is declining from its historical distribution due to feedbacks between climate and land use change, fire, and invasive species. Quantifying aboveground biomass of sagebrush is important for assessing carbon storage and monitoring the presence and distribution of this rapidly changing dryland ecosystem. Models of shrub canopy volume, derived from terrestrial laser scanning (TLS) point clouds, were used to accurately estimate aboveground sagebrush biomass. Ninety-one sagebrush plants were scanned and sampled across three study sites in the Great Basin, USA. Half of the plants were scanned and destructively sampled in the spring (n = 46), while the other half were scanned again in the fall before destructive sampling (n = 45). The latter set of sagebrush plants was scanned during both spring and fall to further test the ability of the TLS to quantify seasonal changes in green biomass. Sagebrush biomass was estimated using both a voxel and a 3-D convex hull approach applied to TLS point cloud data. The 3-D convex hull model estimated total and green biomass more accurately (R2 = 0.92 and R2 = 0.83, respectively) than the voxel-based method (R2 = 0.86 and R2 = 0.73, respectively). Seasonal differences in TLS-predicted green biomass were detected at two of the sites (p \u3c 0.001 and p = 0.029), elucidating the amount of ephemeral leaf loss in the face of summer drought. The methods presented herein are directly transferable to other dryland shrubs, and implementation of the convex hull model with similar sagebrush species is straightforward

Losartan Treatment Attenuates Tumor-induced Myocardial Dysfunction

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin–angiotensin–aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation