The Role of Deubiquitinating Enzymes in the Various Forms of Autophagy

Deubiquitinating enzymes (DUBs) have an essential role in several cell biological processes via removing the various ubiquitin patterns as posttranslational modification forms from the target proteins. These enzymes also contribute to the normal cytoplasmic ubiquitin pool during the recycling of this molecule. Autophagy, a summary name of the lysosome dependent self-degradative processes, is necessary for maintaining normal cellular homeostatic equilibrium. Numerous forms of autophagy are known depending on how the cellular self-material is delivered into the lysosomal lumen. In this review we focus on the colorful role of DUBs in autophagic processes and discuss the mechanistic contribution of these molecules to normal cellular homeostasis via the possible regulation forms of autophagic mechanisms

Health Literacy in the Everyday Lives of Older Adults in Greece, Hungary, and the Netherlands

Health literacy (HL) encompasses someone’s knowledge and abilities to access and use health information in order to make appropriate health decisions in life. HL is particularly valuable in later life when health challenges grow. An individual’s HL is typically considered a fixed and skills-based characteristic, without taking into account how these are situated in the context of everyday life. Also, lay perspectives on health literacy are relatively scarce. Therefore, the aim of this article is to explore the context-specific perspectives of older adults and health professionals on HL in later life in Greece, Hungary, and the Netherlands. We adopted a qualitative methodology and conducted 12 focus groups: seven with 50 older adults and five with 30 health professionals to gain insight into individual perspectives on HL as situated in the health care and everyday life contexts. An informed grounded theory approach was used in analyzing the data. The results are structured in three themes: (1) interactions with health professionals, (2) perceived quality of the health care system, and (3) managing health in the context of everyday life. An overarching finding is that, for older adults, HL reflects the demands placed on them when managing their health. In the experience of older adults, these demands are placed upon them by healthcare professionals, the healthcare system, as well as their everyday lives. Our findings underscore the importance of Critical Health Literacy (CHL) as that concept foregrounds that HL is context specific. Also, CHL has been argued to be a community characteristic, which is why we call for community-based approaches to improve H

The mechanism of non-blocking inhibition of sodium channels revealed by conformation-selective photolabeling

Sodium channel inhibitors can be used to treat hyperexcitability-related diseases, including epilepsies, pain syndromes, neuromuscular disorders, and cardiac arrhythmias. The applicability of these drugs is limited by their nonspecific effect on physiological function. They act mainly by sodium channel block and in addition by modulation of channel kinetics. While channel block inhibits healthy and pathological tissue equally, modulation can preferentially inhibit pathological activity. An ideal drug designed to target the sodium channels of pathological tissue would act predominantly by modulation. Thus far, no such drug has been described.Patch-clamp experiments with ultra-fast solution exchange and photolabeling-coupled electrophysiology were applied to describe the unique mechanism of riluzole on Nav1.4 sodium channels. In silico docking experiments were used to study the molecular details of binding.We present evidence that riluzole acts predominantly by non-blocking modulation. We propose that, being a relatively small molecule, riluzole is able to stay bound to the binding site, but nonetheless stay off the conduction pathway, by residing in one of the fenestrations. We demonstrate how this mechanism can be recognized.Our results identify riluzole as the prototype of this new class of sodium channel inhibitors. Drugs of this class are expected to selectively prevent hyperexcitability, while having minimal effect on cells firing at a normal rate from a normal resting potential

The Rapid Outbursting Star GM Cep: An EX-or in Tr 37?

We present optical, IR and millimeter observations of the solar-type star 13-277, also known as GM Cep, in the 4 Myr-old cluster Tr 37. GM Cep experiences rapid magnitude variations of more than 2 mag at optical wavelengths. We explore the causes of the variability, which seem to be dominated by strong increases in the accretion, being similar to EX-or episodes. The star shows high, variable accretion rates (up to ~10$^{-6}$ Msun/yr), signs of powerful winds, and it is a very fast rotator (Vsini~43 km/s). Its strong mid-IR excesses reveal a very flared disk and/or a remnant envelope, most likely out of hydrostatic equilibrium. The 1.3 millimeter fluxes suggest a relatively massive disk (Mdisk~0.1 Msun). Nevertheless, the millimeter mass is not enough to sustain increased accretion episodes over large timescales, unless the mass is underestimated due to significant grain growth. We finally explore the possibility of GM Cep having a binary companion, which could trigger disk instabilities producing the enhanced accretion episodes.Comment: 43 pages, including 10 figures, ApJ in pres

The effect of finite-range interactions in classical transport theory

The effect of scattering with non-zero impact parameters between consituents in relativistic heavy ion collisions is investigated. In solving the relativistic Boltzmann equation, the characteristic range of the collision kernel is varied from approximately one fm to zero while leaving the mean-free path unchanged. Modifying this range is shown to significantly affect spectra and flow observables. The finite range is shown to provide effective viscosities, shear, bulk viscosity and heat conductivity, with the viscous coefficients being proportional to the square of the interaction range

Power of wavelets in analyses of transit and phase curves in the presence of stellar variability and instrumental noise. I. Method and validation

Context. Stellar photometric variability and instrumental effects, such as cosmic ray hits, data discontinuities, data leaks, instrument aging, and so on, lead to difficulties in the characterisation of exoplanets. Therefore, they can impact the accuracy and precision of the modelling and the detectability of their transits, occultations, and phase curves. Aims. This paper is aimed at improving the transit, occultation, and phase-curve modelling in the presence of strong stellar variability and instrumental noise. To this end, we invoke the wavelet formulation. Methods. We explored the capabilities of the software package Transit and Light Curve Modeller (TLCM). It is able to perform (1) a joint radial-velocity and light-curve fit or (2) a light curve-only fit. It models the transit, occultation, beaming, ellipsoidal, and reflection effects in the light curves (including the gravity-darkening effect). Here, the red noise, stellar variability, and instrumental effects were modelled via wavelets. The wavelet fit was constrained by prescribing that the final white noise level must be equal to the average of the uncertainties of the photometric data points. This helps to avoid overfitting and regularises the noise model. The approach was tested by injecting synthetic light curves into short-cadence Kepler data and modelling them. Results. The method performs well over a certain signal-to-noise (S/N) ratio. We provide limits in terms of the S/N for every studied system parameter that is needed for accurate parameter retrieval. The wavelet approach is able to manage and remove the impact of data discontinuities, cosmic ray events, and long-term stellar variability and instrument ageing, as well as short-term stellar variability, pulsation, and flares (among others). Conclusions. We conclude that precise light-curve models combined with the wavelet method and with well-prescribed constraints on the white noise are able to retrieve the planetary system parameters, even in the presence of strong stellar variability and instrumental noise, including data discontinuities

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as due to the presence of a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We use CoRoT color information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy and preliminary results from Radial Velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star are derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. We examine carefully all conceivable cases of false positives, and all tests performed support the planetary hypothesis. Blends with separation larger than 0.40 arcsec or triple systems are almost excluded with a 8 10-4 risk left. We conclude that, as far as we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/- 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language corrections; version sent to the printer w few upgrade