The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity

Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity

Healthy ageing education across Europe: a survey of ENPHE members

Background and Purpose Healthy ageing is an optimal status that people could achieve when they currently adapt their physical and psychological evolution that allow them to participate socially with a high level of autonomy. The process of becoming older is a personal process that can be very heterogeneous. This heterogeneity generates different approaches depending on the needs, capacities of adaptation and subject possibilities. Therefore, it is important that any kind of intervention should adapt specifically to each patient. Description With the goal to develop and offer updated education in Healthy Ageing, a group of five universities: Ecole d’Assas (France), Blanquerna-Universitat Ramón Lull (Spain), Univerzita Palackého v Olomouci (Czech Republic), Kolegji Heimerer (Kosovo) and Escola de Saúde do Alcoitão (Portugal) decided to set up a joint adventure as encouraged by ENPHE. Our first step is to benchmark and characterise within Europe the tendencies, the offers and models of best practices. Material / Methods An online questionnaire was developed and sent to all the ENPHE members between January and February of 2017. The survey was composed of twenty close and open questions related to the participant identification, course description and identification of institutional projects in healthy ageing Summary of Results From a population of 136 EMPHE member's we receive 39 complete responses (27%) and the main results are: 69% of the respondents offer courses about healthy ageing; 88% Integrated in the bachelor degree ; mainly for Physiotherapists students (92%); and with the most prevalent topics (above 80%) - Assessment and intervention of clients/populations, multidisciplinary issues and Prevention; the main pedagogical approaches used are lectures (88%), clinical training/field work (77%) and casebased learning (74%); being written or oral examination (81%) the main assessment strategies used. Importance It is very important to empower the individual to become autonomous in deciding how to manage their own ageing process in a healthy way. Any curricula should take in account this reality in order to transform the role of health care professionals and provide them competences to support individuals in this process.N/

Molecular gas in nearby low-luminosity QSO host galaxies

This paper addresses the global molecular gas properties of a representative sample of galaxies hosting low-luminosity quasistellar objects. An abundant supply of gas is necessary to fuel both the active galactic nucleus and any circum-nuclear starburst activity of QSOs. We selected a sample of nearby low-luminosity QSO host galaxies that is free of infrared excess biases. All objects are drawn from the Hamburg-ESO survey for bright UV-excess QSOs, have DEC>-30 degrees and redshifts that do not exceed z=0.06. The IRAM 30m telescope was used to measure the CO(1-0) and CO(2-1) transition in parallel. 27 out of 39 galaxies in the sample have been detected. The molecular gas masses of the detected sources range from 0.4E9 M_sun to 9.7E9 M_sun. We can confirm that the majority of galaxies hosting low-luminosity QSOs are rich in molecular gas. The properties of galaxies hosting brighter type I AGN and circumnuclear starformation regions differ from the properties of galaxies with fainter central regions. The overall supply of molecular gas and the spread of the line width distribution is larger. When comparing the far-infrared with the CO luminosities, the distribution can be separated into two different power-laws: one describing the lower activity Seyfert I population and the second describing the luminous QSO population. The separation in the L_FIR/L'_CO behavior may be explainable with differing degrees of compactness of the emission regions. We provide a simple model to describe the two power-laws. The sample studied in this paper is located in a transition region between the two populations

Does evidence support the high expectations placed in precision medicine? A bibliographic review

Background: Precision medicine is the Holy Grail of interventions that aretailored to a patient’s individual characteristics.  However, the conventional design of randomized trials assumes that each individual benefits by the same amount. Methods: We reviewed parallel trials with quantitative outcomes published in2004, 2007, 2010 and 2013. We collected baseline and final standard deviations of the main outcome. We assessed homoscedasticity by comparing the outcome variability between treated and control arms. Results: The review provided 208 articles with enough information to conductthe analysis. At the end of the study, 113 (54%, 95% CI 47 to 61%) papers find less variability in the treated arm. The adjusted point estimate of the mean ratio (treated to control group) of the outcome variances is 0.89 (95% CI 0.81 to 0.97). Conclusions: Some variance inflation was observed in just 1 out of 6 interventions, suggesting the need for further eligibility criteria to tailor precision medicine. Surprisingly, the variance was more often smaller in the intervention group, suggesting, if anything, a reduced role for precision medicine.  Homoscedasticity is a useful tool for assessing whether or not the premise of constant effect is reasonable.Peer ReviewedPostprint (author's final draft