Hoffmanadkins5755

Obscurin is a giant cytoskeletal protein with structural and regulatory roles encoded by the OBSCN gene. Recently, mutations in OBSCN were associated with the development of different forms of cardiomyopathies, including hypertrophic cardiomyopathy (HCM). We previously reported that homozygous mice carrying the HCM-linked R4344Q obscurin mutation develop arrhythmia by 1-year of age under sedentary conditions characterized by increased heart rate, frequent incidents of premature ventricular contractions, and episodes of spontaneous ventricular tachycardia. In an effort to delineate the molecular mechanisms that contribute to the observed arrhythmic phenotype, we subjected protein lysates prepared from left ventricles of 1-year old R4344Q and wild-type mice to comparative proteomics analysis using tandem mass spectrometry; raw data are available via ProteomeXchange with identifier PXD017314. We found that the expression levels of proteins involved in cardiac function and disease, cytoskeletal organization, electropotential regulation, molecular transport and metabolism were significantly altered. Moreover, phospho-proteomic evaluation revealed changes in the phosphorylation profile of Ca2+ cycling proteins, including sAnk1.5, a major binding partner of obscurin localized in the sarcoplasmic reticulum; notably, this is the first report indicating that sAnk1 undergoes phosphorylation. Taken together, our findings implicate obscurin in diverse cellular processes within the myocardium, which is consistent with its multiple binding partners, localization in different subcellular compartments, and disease association.Oviposition is an important reproductive behavior that is triggered by mating in insects, and biogenic amines might be involved in its regulation. The effects of biogenic amines on oviposition have only been studied in a few insect species, and the findings to date have not been conclusive. In addition, there are few studies on the effects of biogenic amines on oviposition of the diamondback moth, Plutella xylostella L. Here, we tested how mating and biogenic amines regulate oviposition of P. xylostella by injecting amines and amine receptor antagonists into virgin and mated females and counting the number of eggs laid afterward. Biogenic amines of octopamine and tyramine could induce virgin adults of P. xylostella to lay eggs, while dopamine and serotonin had no such effect on oviposition. Furthermore, the octopamine antagonists mianserin, epinastine, and phentolamine inhibited oviposition by mated females. The tyramine antagonist yohimbine, dopamine antagonist SCH23390, and serotonin antagonist ketanserin did not block oviposition by mated females, and octopamine and tyramine-inducing oviposition by virgin females could be inhibited by the octopamine antagonists mianserin and epinastine instead of the tyramine antagonist yohimbine. We conclude that octopamine and its receptors are involved in mating-triggered oviposition in P. xylostella, while tyramine acts as a subsidiary. Further, the inducing effect of tyramine on oviposition is achieved via octopamine receptors instead of tyramine receptors. This experiment is helpful to further understand the role of biogenic amines in mating regulation and to provide a new strategy for controlling P. xylostella.Skeletal muscle disuse rapidly decreases muscle mass. Resistance training (RT) is believed as the most effective way to gain muscle mass via an increase in mTORC1 activity and muscle protein synthesis (MPS). However, it remains unclear whether muscle atrophy by disuse alters the mTORC1 activation and MPS response to an acute resistance exercise (RE) and chronic RT-mediated skeletal muscle hypertrophy. This study investigated the influence of disuse muscle atrophy on the response of mTORC1 activation and MPS to an acute RE. We also evaluated whether disuse muscle atrophy affects the response of RT-induced muscle mass gain. Thirty male Sprague-Dawley rats were randomly divided into control (CON) or hindlimb suspension (HS) groups. A 14-day HS via the tail was used as the model for gastrocnemius muscle disuse in the HS group. Unilateral lower limb muscle contraction using by percutaneous electrical stimulation was used to mimic the stimuli of RE. Ten bouts of RE were performed in 3-week as chronic RT. Our results showed that MPS and mTORC1 activity was unchanged after HS at basal state. However, the ribosomal RNA (rRNA) level was reduced in HS rats compared to that in CON rats at basal state. MPS and rRNA increased in both HS and CON rats in response to acute RE to the same extent. However, the level of mTORC1 activation in response to an acute RE was significantly higher in HS than that in the CON group at 12 h after exercise, even though no difference was observed at 3 h after exercise. The 10-bout RT significantly increased gastrocnemius muscle mass in both CON and HS rats. The response of muscle hypertrophy did not differ between the groups. Therefore, MPS in response to acute RE and muscle hypertrophy in response to chronic RT were unaltered after disuse muscle atrophy.Introduction Cough is a major symptom frequently experienced during exercise, mainly in asthmatic patients. Inhaled glucocorticoids represent the keystone treatment in the management of asthma, but little is known about interactions between cough and exercise, especially in controlled patients. During exercise, cough reflex (CR) appears downregulated in healthy animal models whereas a lack of desensitization of CR has been shown in ovalbumin-sensitized animal models, mimicking asthmatic disease. Aims and objectives The goal of our study was to clarify the potential modulation of the CR induced by inhaled corticosteroids (CS) in ovalbumin (OVA) sensitized rabbits during artificial limb exercise. Materials and methods Seventeen OVA sensitized rabbits were studied. Among them, 9 were treated with CS delivered intravenously (OVA-Corticoids). The ventilatory response to direct tracheal stimulation, performed at rest and during exercise, was determined to assess the incidence and the sensitivity of the CR. Broncho-alveolar lavage (BAL) and cell counts were performed to determine the level of airway inflammation. Exercise was mimicked by electrically induced hindlimb muscular contractions (EMC). Results Compared to rest values, EMC increased minute ventilation by 28% without any decrease in respiratory resistance (Rsr). Among 322 tracheal stimulations, 172 (53%) were performed at rest and 150 (47%) during exercise. The sensitivity of CR decreased during artificial limb exercise compared to baseline in OVA-Corticoids rabbits (p = 0.0313) while it remained unchanged in OVA rabbits (p = NS). Conclusion Corticosteroids appear to restore the desensitization of the CR in OVA sensitized rabbits during artificial limb exercise, suggesting the potential role of airway inflammation in the pathophysiology of cough during exercise in asthmatics.Optical mapping is a high-resolution fluorescence imaging technique, that uses voltage- or calcium-sensitive dyes to visualize electrical excitation waves on the heart surface. However, optical mapping is very susceptible to the motion of cardiac tissue, which results in so-called motion artifacts in the fluorescence signal. To avoid motion artifacts, contractions of the heart muscle are typically suppressed using pharmacological excitation-contraction uncoupling agents, such as Blebbistatin. The use of pharmacological agents, however, may influence cardiac electrophysiology. Recently, it has been shown that numerical motion tracking can significantly reduce motion-related artifacts in optical mapping, enabling the simultaneous optical measurement of cardiac electrophysiology and mechanics. imoxin Here, we combine ratiometric optical mapping with numerical motion tracking to further enhance the robustness and accuracy of these measurements. We evaluate the method's performance by imaging and comparing cardiac restiton of optical mapping data, and highlight that physiological conditions, such as oxygenation and metabolic demand, must be carefully considered in ex vivo imaging experiments.Individualizing physiological models to a patient can enable patient-specific monitoring and treatment in critical care environments. However, this task often presents a unique "practical identifiability" challenge due to the conflict between model complexity and data scarcity. Regularization provides an established framework to cope with this conflict by compensating for data scarcity with prior knowledge. However, regularization has not been widely pursued in individualizing physiological models to facilitate patient-specific critical care. Thus, the goal of this work is to garner potentially generalizable insight into the practical use of regularization in individualizing a complex physiological model using scarce data by investigating its effect in a clinically significant critical care case study of blood volume kinetics and cardiovascular hemodynamics in hemorrhage and circulatory resuscitation. We construct a population-average model as prior knowledge and individualize the physiological model via regularization to illustrate that regularization can be effective in individualizing a physiological model to learn salient individual-specific characteristics (resulting in the goodness of fit to individual-specific data) while restricting unnecessary deviations from the population-average model (achieving practical identifiability). We also illustrate that regularization yields parsimonious individualization of only sensitive parameters as well as adequate physiological plausibility and relevance in predicting internal physiological states.17β-estradiol is a neuronal survival factor against oxidative stress that triggers its protective effect even in the absence of classical estrogen receptors. The polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channel has been proposed as a steroid receptor implied in tissue protection against oxidative damage. We show here that TRPV1 is sufficient condition for 17β-estradiol to enhance metabolic performance in injured cells. Specifically, in TRPV1 expressing cells, the application of 17β-estradiol within the first 3 h avoided H2O2-dependent mitochondrial depolarization and the activation of caspase 3/7 protecting against the irreversible damage triggered by H2O2. Furthermore, 17β-estradiol potentiates TRPV1 single channel activity associated with an increased open probability. This effect was not observed after the application of 17α-estradiol. We explored the TRPV1-Estrogen relationship also in primary culture of hippocampal-derived neurons and observed that 17β-estradiol cell protection against H2O2-induced damage was independent of estrogen receptors pathway activation, membrane started and stereospecific. These results support the role of TRPV1 as a 17β-estradiol-activated ionotropic membrane receptor coupling with mitochondrial function and cell survival.Rheumatoid arthritis (RA), a chronic systemic inflammatory disease, is a primary cause of disability worldwide. The involvement of fibroblast-like synoviocytes (FLSs) in the regulation of the pathogenesis of RA has been highlighted. Mesenchymal stem cells (MSCs) are important candidates for cell-based treatment in many inflammatory autoimmune diseases. Herein, we identify whether MSC-derived exosomes loaded with microRNA-320a (miR-320a) regulate RA-FLSs. Synovial tissues from 22 patients with RA and 9 patients with osteoarthritis were collected. RA-FLSs were obtained from patients with RA, and their functions were evaluated by determining levels of interleukin-1β (IL-1β), IL-6, and IL-8 and by transwell migration and invasion assays. Dual luciferase reporter gene assays were employed to identify interaction between miR-320a and CXC chemokine ligand 9 (CXCL9). A co-culture system of MSC-derived exosomes and RA-FLSs were performed. The collagen-induced arthritis (CIA) mouse models with arthritis and bone damage were developed.