Crosbydrachmann4134

[This corrects the article DOI 10.3389/fphys.2021.625044.].Previously, we reported that in airway smooth muscle (ASM), the cytosolic Ca2+ ([Ca2+] cyt ) and force response induced by acetyl choline (ACh) are increased by exposure to the pro-inflammatory cytokine tumor necrosis factor α (TNFα). The increase in ASM force induced by TNFα was not associated with an increase in regulatory myosin light chain (rMLC20) phosphorylation but was associated with an increase in contractile protein (actin and myosin) concentration and an enhancement of Ca2+ dependent actin polymerization. The sensitivity of ASM force generation to elevated [Ca2+] cyt (Ca2+ sensitivity) is dynamic involving both the shorter-term canonical calmodulin-myosin light chain kinase (MLCK) signaling cascade that regulates rMLC20 phosphorylation and cross-bridge recruitment as well as the longer-term regulation of actin polymerization that regulates contractile unit recruitment and actin tethering to the cortical cytoskeleton. In this study, we simultaneously measured [Ca2+] cyt and force responses to ACh and explored the impact of 24-h TNFα on the dynamic relationship between [Ca2+] cyt and force responses. The temporal delay between the onset of [Ca2+] cyt and force responses was not affected by TNFα. Similarly, the rates of rise of [Ca2+] cyt and force responses were not affected by TNFα. The absence of an impact of TNFα on the short delay relationships between [Ca2+] cyt and force was consistent with the absence of an effect of [Ca2+] cyt and force on rMLC20 phosphorylation. However, the integral of the phase-loop plot of [Ca2+] cyt and force increased with TNFα, consistent with an impact on actin polymerization and, contractile unit recruitment and actin tethering to the cortical cytoskeleton.The bile acid pool with its individual bile acids (BA) is modulated in the enterohepatic circulation by the liver as the primary site of synthesis, the motility of the gallbladder and of the intestinal tract, as well as by bacterial enzymes in the intestine. The nuclear receptor farnesoid X receptor (FXR) and Gpbar1 (TGR5) are important set screws in this process. Bile acids have a vasodilatory effect, at least according to in vitro studies. The present review examines the question of the extent to which the increase in bile acids in plasma could be responsible for the hyperdynamic circulatory disturbance of liver cirrhosis and whether modulation of the bile acid pool, for example, via administration of ursodeoxycholic acid (UDCA) or via modulation of the dysbiosis present in liver cirrhosis could influence the hemodynamic disorder of liver cirrhosis. According to our analysis, the evidence for this is limited. Long-term studies on this question are lacking.Advanced maternal age (≥35 years old) increases the risk of pregnancy complications such as preeclampsia and fetal growth restriction. We previously demonstrated vascular dysfunction and abnormal pregnancy outcomes in a rat model of advanced maternal age. However, vascular adaptations to pregnancy in aging were not studied. We hypothesize that advanced maternal age is associated with a more vasoconstrictive phenotype due to reduced nitric oxide (NO) and increased activity of matrix metalloproteinases (MMPs), contributing to impaired vascular adaptations to pregnancy. A rat model of advanced maternal age was used young (4 months) and aged (9.5 months; ∼35 years in humans) non-pregnant and pregnant rats. On gestational day 20 (term = 22 days; non-pregnant rats were aged-matched), blood pressure and heart rate were measured (tail cuff plethysmography) and vascular function was assessed in mesenteric arteries (wire myography). Endothelium-dependent relaxation to methylcholine (MCh) was assessed in the presence/abt rats (p less then 0.05). No significant changes in bigET-1 conversion occurred in the presence of MMP-inhibitor, whereas ECE-1 inhibition reduced bigET-1 constriction in aged rats (p less then 0.01). No differences in ET-1 sensitivity were observed. In conclusion, contrary to our hypothesis, reduced blood pressure, and an increased EDH-dependent contribution to vasodilation suggest a compensatory mechanism that may reflect beneficial adaptations in these aged rats that were able to maintain pregnancy. These data increase our understanding of how the vascular adaptive pathways in pregnancy compensate for advanced maternal age.Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In addition, PNNs in the terete hypothalamic nucleus display a sexual dimorphism with females higher than males, and high-fat diet feeding increases terete PNNs only in female mice but not in male mice. On the other hand, PNNs in other hypothalamic regions are not influenced by sex, gonadal hormones or dietary interventions. In summary, we demonstrated that hypothalamic PNNs are regulated in a region-specific manner and these results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones and diets.Background Human adaptive response to exercise interventions is often described as group average and SD to represent the typical response for most individuals, but studies reporting individual responses to exercise show a wide range of responses. Objective To characterize the physiological effects and inter-individual variability on fat mass and other health-related and physical performance outcomes after 12 weeks of high-intensity interval training (HIIT) and dietary energy restriction in overweight/obese adult women. Dabrafenib mouse Methods Thirty untrained adult overweight and obese women (age = 27.4 ± 7.9 years; BMI = 29.9 ± 3.3 kg/m2) successfully completed a 12-week supervised HIIT program and an individually prescribed home hypocaloric diet (75% of daily energy requirements) throughout the whole intervention. High and low responders to the intervention were those individuals who were able to lose ≥ 10 and less then 10% of initial absolute fat mass (i.e., kilograms), respectively. Results The prevalence for high and mass, blood pressure, and cardiorespiratory fitness (CRF). However, a wide range of inter-individual variability was observed in the adaptative response to the intervention. Furthermore, subjects classified as low responders for fat mass reduction could be high responders (HiRes) in many other health-related and physical performance outcomes. Thus, the beneficial effects of exercise in obese and overweight women go further beyond the adaptive response to a single outcome variable such as fat mass or total body mass reduction.Purpose Light affects a variety of non-image forming processes, such as circadian rhythm entrainment and the pupillary light reflex, which are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). The purpose of this study was to assess the effects of long- and short-wavelength ambient lighting on activity patterns and pupil responses in rhesus monkeys. Methods Infant rhesus monkeys were reared under either broadband "white" light (n = 14), long-wavelength "red" light (n = 20; 630 nm), or short-wavelength "blue" light (n = 21; 465 nm) on a 12-h light/dark cycle starting at 24.1 ± 2.6 days of age. Activity was measured for the first 4 months of the experimental period using a Fitbit activity tracking device and quantified as average step counts during the daytime (lights-on) and nighttime (lights-off) periods. Pupil responses to 1 s red (651 nm) and blue (456 nm) stimuli were measured after approximately 8 months. Pupil metrics included maximum constriction and the 6 s post-illumination pupil response (PIPR). Results Activity during the lights-on period increased with age during the first 10 weeks (p 0.05 for all). Conclusion Findings suggest that long-term exposure to 12-h narrowband blue light results in greater disruption in nighttime behavioral patterns compared to narrowband red light. Normal pupil responses measured later in the rearing period suggest that ipRGCs adapt after long-term exposure to narrowband lighting.Blood perfusion is an important index for the function of the cardiovascular system and it can be indicated by the blood flow distribution in the vascular tree. As the blood flow in a vascular tree varies in a large range of scales and fractal analysis owns the ability to describe multi-scale properties, it is reasonable to apply fractal analysis to depict the blood flow distribution. The objective of this study is to establish fractal methods for analyzing the blood flow distribution which can be applied to real vascular trees. For this purpose, the modified methods in fractal geometry were applied and a special strategy was raised to make sure that these methods are applicable to an arbitrary vascular tree. The validation of the proposed methods on real arterial trees verified the ability of the produced parameters (fractal dimension and multifractal spectrum) in distinguishing the blood flow distribution under different physiological states. Furthermore, the physiological significance of the fractal paramethods are capable of depicting the multi-scale features of the blood flow distribution in the vascular tree and further are potential for investigating vascular physiology.Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are the most prevalent metabolic liver diseases globally. Due to the complex pathogenic mechanisms of NAFLD and AFLD, no specific drugs were approved at present. Lipid accumulation, oxidative stress, insulin resistance, inflammation, and dietary habits are all closely related to the pathogenesis of NAFLD and AFLD. However, the mechanism that promotes disease progression has not been fully elucidated. Meanwhile, the gut microbiota and their metabolites also play an important role in the pathogenesis and development of NAFLD and AFLD. This article comparatively reviewed the shared and specific signaling pathways, clinical trials, and potential intervention effectors of NAFLD and AFLD, revealing their similarities and differences. By comparing the shared and specific molecular regulatory mechanisms, this paper provides mutual reference strategies for preventing and treating NAFLD, AFLD, and related metabolic diseases. Furthermore, it provides enlightenment for discovering novel therapies of safe and effective drugs targeting the metabolic liver disease.Rationale Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration. Methods Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants.