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OBJECTIVES - To evaluate the effect of a single dose of pimobendan on left atrial (LA) function in healthy cats. ANIMALS - Eleven client owned healthy cats. MATERIAL AND METHODS - Standardized and repeated echocardiographic examinations were performed on healthy and conscious cats before and after a single dose of orally administered pimobendan (1.25 mg/cat). Left atrial systolic functional parameters were assessed. RESULTS - Some of the tested parameters of LA function showed significant improvement after pimobendan administration, whereas no significant effect on left ventricular function was observed. In particular, LA minimal diameters obtained from M-mode images in short (p=0.018) and long (p=0.009) axis reduced after pimobendan administration, whereas LA fractional shortening from short (p=0.027) and long (p=0.042) axis and LA appendage emptying velocity (p less then 0.001) significantly increased. A mild increase in heart rate (p=0.001), and a transient increase on the peak systolic wave pulmonary vein velocity (p=0.008) were also recorded as a possible effect. CONCLUSIONS - A single dose of pimobendan appears to impact LA function in healthy cats. However, because of the small number of cats included, and the absence of a placebo group, these results cannot be definitively separated from the effect of time. Additional studies are needed to understand if similar effects are observed in cats with cardiomyopathy and LA dilatation. V.The Ataxia-telangiectasia mutated (ATM) kinase responds to DNA double-strand breaks and other forms of cellular stress, including reactive oxygen species (ROS). Recent work in the field has uncovered links between mitochondrial ROS and ATM activation, suggesting that ATM acts as a sensor for mitochondrial derived ROS and regulates ROS accumulation in cells through this pathway. In addition, characterization of cells from Ataxia-telangiectasia patients as well as ATM-deficient mice and cell models suggest a role for ATM in modulating mitochondrial gene expression and function. Here we review ROS responses related to ATM function, recent evidence for ATM roles in mitochondrial maintenance and turnover, and the relationship between ATM and regulation of protein homeostasis. Proteasome inhibitors have great success for their therapeutic potential against hematologic malignancies. First generation proteasome inhibitor bortezomib induced peripheral neuropathy is considered as a limiting factor in chemotherapy and its second-generation counterpart carfilzomib is associated with lower rates of neurotoxicity. The mitochondrial toxicity (mitotoxicity) hypothesis arises from studies with animal models of bortezomib induced peripheral neuropathy. However, molecular mechanisms are not fully elucidated and the role of mitotoxicity in bortezomib and carfilzomib induced neurotoxicity has not been investigated comparatively. Herein, we characterized the neurotoxic effects of bortezomib and carfilzomib at the molecular level in human neuronal cells using LC-MS/MS analysis, flow cytometry, RT-qPCR, confocal microscopy and western blotting. We showed that bortezomib and carfilzomib affected the human neuronal proteome differently, and bortezomib caused higher proteotoxic stress via protein oxidation, protein K48-ubiquitination, heat shock protein expression upregulation and reduction of mitochondria membrane potential. Bortezomib and carfilzomib did not affect the gene expression levels related to mitochondrial dynamics (optic atrophy 1; OPA1, mitofusin 1; MFN1, mitofusin 2; MFN2, fission 1; FIS1, dynamin-related protein 1; DRP1) and overall mitophagy rate whereas, PINK1/Parkin mediated mitophagy gene expressions were altered with both drugs. Bortezomib and carfilzomib caused downregulation of the contents of mitochondrial oxidative phosphorylation complexes, voltage-dependent anion channel 1 (VDAC1) and uncoupling protein 2 (UCP2) similarly. Our findings suggest that, both drugs induce mitotoxicity besides proteotoxic stress in human neuronal cells and the higher incidence of neurotoxicity with bortezomib than carfilzomib is not directly related to mitochondrial pathways. An overarching theme of cellular regulation in bacteria arises from the trade-off between growth and stress resilience. In addition, the formation of biofilms contributes to stress survival, since these dense multicellular aggregates, in which cells are embedded in an extracellular matrix of self-produced polymers, represent a self-constructed protective and homeostatic 'niche'. As shown here for the model bacterium Escherichia coli, the inverse coordination of bacterial growth with survival and the transition to multicellularity is achieved by a highly integrated regulatory network with several sigma subunits of RNA polymerase and a small number of transcriptional hubs as central players. By conveying information about the actual (micro)environments, nucleotide second messengers such as cAMP, (p)ppGpp, and in particular c-di-GMP are the key triggers and drivers that promote either growth or stress resistance and organized multicellularity in a world of limited resources. Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI) is an important diagnostic technique that can quantify the structure and function of microvasculature processes, using T1 relaxation times and tracer kinetic maps. However, a series of methodological limitations affect both the accuracy and standardisation of the quantified maps, and consequently their diagnostic ability. The main methodological challenge in the quantification of tracer kinetics is a multi-parameter optimization, with correlated parameters that have different scales, which results in local minima particularly when measurements are highly undersampled. [https://www.selleckchem.com/products/resatorvid.html Resatorvid solubility dmso] This work suggests a novel data driven optimization scheme, based on a variation of the Stochastic Gradient Langevin dynamics (SGLD) Markov chain Monte Carlo algorithm, which combines stochastic gradient descent and Langevin dynamics. The proposed SGDL algorithm avoided local minima and accurately quantified proton density, T1 relaxation times and tracer kinetics. Joint direct parameterization significantly benefited the quantification of proton density, T1 relaxation times, and the selection of a suitable tracer kinetic model per tissue type.