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Sacubitril/valsartan (Sac/Val), a combined angiotensin-II receptor blocker (Val) and neprilysin inhibitor (Sac) in a 11 molar ratio, was shown to decrease the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and reduced left ventricular (LV) ejection fraction. This study examined the effects of Sac/Val on LV structure, function, and bioenergetics, and on biomarkers of kidney injury and kidney function in dogs with experimental cardiorenal syndrome.

Fourteen dogs with cardiorenal syndrome (coronary microembolization-induced HF and renal dysfunction) were randomized to 3 months Sac/Val therapy (100 mg once daily, n = 7) or no therapy (control, n = 7). LV ejection fraction and troponin-I, as well as biomarkers of kidney injury/function including serum creatinine and urinary kidney injury molecule-1 were measured before and at end of therapy and the change (treatment effect change) calculated. Mitochondrial function measures, including the maximum rate of adenosine tripho decreases biomarkers of heart and kidney injury. The results offer mechanistic insights into the benefits of Sac/Val in HF with compromised renal function.The function of the gonadotropin-releasing hormone (GnRH) neuron is critical to maintain reproductive function and a significant decrease in GnRH can lead to disorders affecting fertility, including hypogonadotropic hypogonadism. Spexin (SPX) is a novel hypothalamic neuropeptide that exerts inhibitory effects on reproduction and feeding by acting through galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3). Fatty acids can act as nutritional signals that regulate the hypothalamic-pituitary-gonadal (HPG) axis, and elevated levels of circulating saturated fatty acids associated with high fat diet (HFD)-feeding have been shown to induce neuroinflammation, endoplasmic reticulum stress and hormonal resistance in the hypothalamus, as well as alter neuropeptide expression. We previously demonstrated that palmitate, the most common saturated fatty acid in a HFD, elevates the expression of Spx, Galr2 and Galr3 mRNA in a model of appetite-regulating neuropeptide Y hypothalamic neurons. Here, we found that Spx, Galr2 and Galr3 mRNA were also significantly induced by palmitate in a model of reproductive GnRH neurons, mHypoA-GnRH/GFP. As a follow-up to our previous report, we examined the molecular pathways by which Spx and galanin receptor mRNA was regulated in this cell line. Furthermore, we performed inhibitor studies, which revealed that the effect of palmitate on Spx and Galr3 mRNA involved activation of the innate immune receptor TLR4, and we detected differential regulation of the three genes by the protein kinases PKC, JNK, ERK, and p38. However, the intracellular metabolism of palmitate to ceramide did not appear to be involved in the palmitate-mediated gene regulation. Overall, this suggests that SPX may play a role in reproduction at the level of the hypothalamus and the pathways by which Spx, Galr2 and Galr3 are altered by fatty acids could provide insight into the mechanisms underlying reproductive dysfunction in obesity.The hypothalamic-pituitary axis (HP axis) plays a critical and integrative role in the endocrine system control to maintain homeostasis. The HP axis is responsible for the hormonal events necessary to regulate the thyroid, adrenal glands, gonads, somatic growth, among other functions. 10058-F4 molecular weight Endocrine-disrupting chemicals (EDCs) are a worldwide public health concern. There is growing evidence that exposure to EDCs such as bisphenol A (BPA), some phthalates, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and biphenyls (PBBs), dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and atrazine (ATR), is associated with HP axis abnormalities. EDCs act on hormone receptors and their downstream signaling pathways and can interfere with hormone synthesis, metabolism, and actions. Because the HP axis function is particularly sensitive to endogenous hormonal changes, disruptions by EDCs can alter HP axis proper function, leading to important endocrine irregularities. Here, we review the evidence that EDCs could directly affect the mammalian HP axis function.Wheat aphids are major wheat sap sucking pests found throughout the world. The analysis of wheat aphid population dynamics to develop aphid control strategies is therefore important. Even if all factors that control the size of aphid populations are known, several mathematical tools are needed to help us understand their combined effect. Based on the knowledge of population ecology and catastrophe theory, we proposed a generalized population dynamics model to describe variation of wheat aphid populations and obtained a dynamic threshold function for aphid control. Field survey data from 1997 to 2002 were used to validate this model. The results indicated the model could predict the results of practical measures against a pest if the factors of their immediate effects are known or could be estimated. By explaining and forecasting the size of an aphid outbreak and its probability of occurrence, this catastrophe model can provide a scientific basis for wheat aphid control.A new nonlinear phenomenon has been studied theoretically on one of the main cytoskeletal element of eukaryotic cells, namely chaos in microtubules vibrations. The general model of microtubules is used to draw phase portraits and Lyapunov spectra. The examination of numerical results reveals that the velocity of the chaotic wave could be the physical parameter that governs chaos. The energy released after the hydrolysation of guanosine triphosphate is converted to active turbulence leading to chaos. The high values of the Lyapunov exponents give hints that there are strong dissipations yielding in the lessening of the velocity of chaotic wave propagation in the microtubules. Moreover, the role of chaos in information processing has been established in microtubules. The energy coming from hydrolysis of guanosine triphosphate stimulates the tubulin leading it to probe its environment and collect information. The net sum of Lyapunov exponents is found to be positive in this stage of the process. Also, the collected information is compressed with a negative sum of Lyapunov exponents.

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