Using total internal reflection fluorescence (TIRF) microscopy, we further showed that ZC4H2 accelerates TRPV4 turnover at the plasma membrane. Overall, these data demonstrate that ZC4H2 is a positive modulator of TRPV4, and suggest a link between TRPV4 and ZC4H2-associated rare disorders, which have several neuromuscular symptoms in common with TRPV4-pathies.Protein degradation is tightly regulated inside cells because of its utmost importance for protein homeostasis (proteostasis). The two major intracellular proteolytic pathways are the ubiquitin-proteasome and the autophagy-lysosome systems which ensure the fate of proteins when modified by various members of the ubiquitin family. These pathways are tightly interconnected by receptors and cofactors that recognize distinct chain architectures to connect with either the proteasome or autophagy under distinct physiologic and pathologic situations. The degradation of proteasome by autophagy, known as proteaphagy, plays an important role in this crosstalk since it favours the activity of autophagy in the absence of fully active proteasomes. Recently described in several biological models, proteaphagy appears to help the cell to survive when proteostasis is broken by the absence of nutrients or the excess of proteins accumulated under various stress conditions. Emerging evidence indicates that proteaphagy could be permanently activated in some types of cancer or when chemoresistance is observed in patients.Upper airway abnormalities increase the risk of pediatric morbidity in infants. A multidisciplinary approach to obstructive sleep apnea syndrome (OSAS) poses challenges to clinical practice. The incidence and causes of OSA are poorly studied in children under 2 years of age.  https://www.selleckchem.com/products/Temsirolimus.html  To fill this gap, we performed this retrospective observational study to determine the causes of obstructive sleep apnea (OSA) in children admitted to our hospital between January 2016 and February 2018, after a brief unexplained event (BRUE) or for OSA. We reviewed the medical charts of 82 patients (39 males; BRUE n = 48; OSAS n = 34) and divided them into two age groups 12-24 months; n = 23). Assessment included nap polysomnography, multichannel intraluminal impedance-pH, and nasopharyngoscopy. Sleep disordered breathing was comparable between the two groups. Omega-shaped epiglottis, laryngomalacia, and nasal septum deviation were more frequent in the younger group, and nasal congestion in older group. Tonsillar and adenoidal hypertrophy was more frequent in the older group, while laryngomalacia and gastroesophageal reflux was more frequent in the younger group. Tonsil and adenoid size were associated with grade of apnea-hypopnea index severity in the older group, and laryngomalacia and gastroesophageal reflux in the younger group. The main causes of respiratory sleep disorders differ in children before or after age 1 year. Our findings have potential clinical utility for assessing the pathophysiology of obstructive sleep disordered breathing in patients less than 2 years old.The role played by adenosine A2B receptors (A2BRs) in the regulation of enteric glial cell (EGC) functions remains unclear. This study was aimed at investigating the involvement of A2BRs in the control of EGC functions in a model of obesity. C57BL/6 mice were fed with standard diet (SD) or high fat diet (HFD) for eight weeks. Colonic tachykininergic contractions were recorded in the presence of BAY60-6583 (A2BRs agonist), MRS1754 (A2BRs antagonist), and the gliotoxin fluorocitrate. Immunofluorescence distribution of HuC/D, S100β, and A2BRs was assessed in whole mount preparations of colonic myenteric plexus. To mimic HFD, EGCs were incubated in vitro with palmitate (PA) and lipopolysaccharide (LPS), in the absence or in the presence of A2BR ligands. Toll-like receptor 4 (TLR4) expression was assessed by Western blot analysis. Interleukin-1β (IL-1β), substance P (SP), and glial cell derived neurotrophic factor (GDNF) release were determined by enzyme-linked immunosorbent assay (ELISA) assays. MRS1754 enhanced electrically evoked tachykininergic contractions of colonic preparations from HFD mice. BAY60-6583 decreased the evoked tachykininergic contractions, with higher efficacy in HFD mice. Such effects were blunted upon incubation with fluorocitrate. In in vitro experiments on EGCs, PA and LPS increased TLR4 expression as well as IL-1β, GDNF, and SP release. Incubation with BAY60-6583 reduced TLR4 expression as well as IL-1β, GDNF, and SP release. Such effects were blunted by MRS1754. The present results suggest that A2BRs, expressed on EGCs, participate in the modulation of enteric inflammation and altered tachykininergic responses associated with obesity, thus representing a potential therapeutic target.The host-vector shuttle and the bottleneck in dengue transmission is a significant aspect with regard to the study of dengue outbreaks. As mosquitoes require 100-1000 times more virus to become infected than human, the transmission of dengue virus from human to mosquito is a vulnerability that can be targeted to improve disease control. In order to capture the heterogeneity in the infectiousness of an infected patient population towards the mosquito population, we calibrate a population of host-to-vector virus transmission models based on an experimentally quantified infected fraction of a mosquito population. Once the population of models is well-calibrated, we deploy a population of controls that helps to inhibit the human-to-mosquito transmission of the dengue virus indirectly by reducing the viral load in the patient body fluid. We use an optimal bang-bang control on the administration of the defective virus (transmissible interfering particles (TIPs)) to symptomatic patients in the course of their febrile period and observe the dynamics in successful reduction of dengue spread into mosquitoes.As one of Gavi, the Vaccine Alliance (previously the Global Alliance for Vaccines and Immunization), graduating countries, Indonesia is still eligible to access Gavi price for PCV13, PCV10 A and B. This study aims to estimate the economic impact of switch from the existing product/presentation of PCV (single-dose of PCV13) to the new product/presentation of PCV (multi-dose of PCV13, PCV10 A and B) since PCV is one of the most expensive vaccines in the Expanded Program on Immunization (EPI) schedule. Assuming that Gavi-Advance Market Commitment (AMC) price for all PCVs can be accessed in 2021, the use of multi-dose PCV13, PCV10 A and PCV10 B with Gavi-AMC price in 2021-2024 were considered as respective scenarios. The result showed that the scenario assuming the use of single-dose of PCV13 with contract price in 2019-2020 that would be switched into multi-dose of PCV10 B with Gavi-AMC price in 2021-2024 resulted in the highest potential saving, compared with other scenarios. Our analysis suggests an economic advantage to switch from single-dose into a multi-dose presentation.