ADAR enzyme and miRNA story: A nucleotide that can make the difference

Adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine (A) to inosine (I) in double-stranded (ds) RNAs. Since Inosine is read as Guanosine, the biological consequence of ADAR enzyme activity is an A/G conversion within RNA molecules. A-to-I editing events can occur on both coding and non-coding RNAs, including microRNAs (miRNAs), which are small regulatory RNAs of ~20-23 nucleotides that regulate several cell processes by annealing to target mRNAs and inhibiting their translation. Both miRNA precursors and mature miRNAs undergo A-to-I RNA editing, affecting the miRNA maturation process and activity. ADARs can also edit 3' UTR of mRNAs, further increasing the interplay between mRNA targets and miRNAs. In this review, we provide a general overview of the ADAR enzymes and their mechanisms of action as well as miRNA processing and function. We then review the more recent findings about the impact of ADAR-mediated activity on the miRNA pathway in terms of biogenesis, target recognition, and gene expression regulation

Dynamical response of the "GGG" rotor to test the Equivalence Principle: theory, simulation and experiment. Part I: the normal modes

Recent theoretical work suggests that violation of the Equivalence Principle might be revealed in a measurement of the fractional differential acceleration $\eta$ between two test bodies -of different composition, falling in the gravitational field of a source mass- if the measurement is made to the level of $\eta\simeq 10^{-13}$ or better. This being within the reach of ground based experiments, gives them a new impetus. However, while slowly rotating torsion balances in ground laboratories are close to reaching this level, only an experiment performed in low orbit around the Earth is likely to provide a much better accuracy. We report on the progress made with the "Galileo Galilei on the Ground" (GGG) experiment, which aims to compete with torsion balances using an instrument design also capable of being converted into a much higher sensitivity space test. In the present and following paper (Part I and Part II), we demonstrate that the dynamical response of the GGG differential accelerometer set into supercritical rotation -in particular its normal modes (Part I) and rejection of common mode effects (Part II)- can be predicted by means of a simple but effective model that embodies all the relevant physics. Analytical solutions are obtained under special limits, which provide the theoretical understanding. A simulation environment is set up, obtaining quantitative agreement with the available experimental data on the frequencies of the normal modes, and on the whirling behavior. This is a needed and reliable tool for controlling and separating perturbative effects from the expected signal, as well as for planning the optimization of the apparatus.Comment: Accepted for publication by "Review of Scientific Instruments" on Jan 16, 2006. 16 2-column pages, 9 figure

Dispersion of elastic waves in a layer interacting with a Winkler foundation

ABSTRACT Dispersion of plane harmonic waves in an elastic layer interacting with a one- or two-sided Winkler foundation is analyzed. The long-wave low-frequency polynomial approximations of the full transcendental dispersion relations are derived for a relatively soft foundation. The validity of the conventional engineering formulation of a Kirchhoff plate resting on an elastic foundation is investigated. It is shown that this formulation has to be refined near the cutoff frequency of bending waves. The associated near cutoff expansion is obtained for both cases. A simple explicit formula demonstrating veering of bending and extensional waves is presented for a one-sided foundation

The GRAAL high resolution BGO calorimeter and its energy calibration and monitoring system

We describe the electromagnetic calorimeter built for the GRAAL apparatus at the ESRF. Its monitoring system is presented in detail. Results from tests and the performance obtained during the first GRAAL experiments are given. The energy calibration accuracy and stability reached is a small fraction of the intrinsic detector resolution.Comment: 19 pages, 14 figures, submitted to Nuclear Instruments and Method

Long term effect of gender affirming hormone treatment on depression and anxiety symptoms in transgender people: A prospective cohort study

BackgroundCross?sectional studies show that transgender people are more likely than cisgender people to experience depression and anxiety before Gender Affirming Hormone Treatment (GAHT). However, the effect of GAHT on mental health in transgender people, and the role of other factors that may have a predictive effect, is poorly explored.ObjectivesUsing a longitudinal methodology, this study investigated the effect of 18 months GAHT on depression and anxiety symptomatology and the predictors on mental health outcomes in a large population of transgender people.Materials and MethodsParticipants (n=178) completed a socio?demographic questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Scale of Perceived Social Support (MSPSS) and the Autism Spectrum Quotient Short Version (AQ?short) at pre?assessment (T0) and at 18 months after initiation of GAHT (T1).ResultsFrom T0 to T1, symptomatology was significantly decreased for depression (P[less than]0.001) and non?significantly reduced for anxiety (P=0.37). Scores on the MSPSS predicted reduction in depression, while scores on the AQ?short predicted reduction in anxiety.DiscussionGAHT reduces symptoms of depression which are predicted by having higher levels of social support. Although anxiety symptoms also reduce the changes are not significant and high levels of anxiety still remain post GAHT.ConclusionsThese results highlight the important mental health benefits of GAHT. Support services (professional, third sector or peer?support) aiming at increasing social support for transgender individuals should be made available

Development status of a Laue lens project for gamma-ray astronomy

We report the status of the HAXTEL project, devoted to perform a design study and the development of a Laue lens prototype. After a summary of the major results of the design study, the approach adopted to develop a Demonstration Model of a Laue lens is discussed, the set up described, and some results presented.Comment: 11 pages, 11 figures, 2007 SPIE Conference on Optics for EUV, X-Ray, and Gamma-Ray Astronomy II

High-Velocity Features: a ubiquitous property of Type Ia SNe

Evidence of high-velocity features such as those seen in the near-maximum spectra of some Type Ia Supernovae (eg SN 2000cx) has been searched for in the available SNIa spectra observed earlier than one week before B maximum. Recent observational efforts have doubled the number of SNeIa with very early spectra. Remarkably, all SNeIa with early data (7 in our RTN sample and 10 from other programmes) show signs of such features, to a greater or lesser degree, in CaII IR, and some also in SiII 6255A line. High-velocity features may be interpreted as abundance or density enhancements. Abundance enhancements would imply an outer region dominated by Si and Ca. Density enhancements may result from the sweeping up of circumstellar material by the highest velocity SN ejecta. In this scenario, the high incidence of HVFs suggests that a thick disc and/or a high-density companion wind surrounds the exploding white dwarf, as may be the case in Single Degenerate systems. Large-scale angular fluctuations in the radial density and abundance distribution may also be responsible: this could originate in the explosion, and would suggest a deflagration as the more likely explosion mechanism. CSM-interaction and surface fluctuations may coexist, possibly leaving different signatures on the spectrum. In some SNe the HVFs are narrowly confined in velocity, suggesting the ejection of blobs of burned material.Comment: 12 pages, 2 figures, ApJ Letters in pres

The I148M variant of PNPLA3 reduces the response to docosahexaenoic acid in children with non-Alcoholic fatty liver disease

The aim of this secondary analysis of a randomized controlled trial was to test whether the I148M variant of Patatin-like phospholipase domain-containing protein-3 (PNPLA3) is associated with the response to docosahexaenoic acid (DHA) in children with non-Alcoholic fatty liver disease (NAFLD). Sixty children with NAFLD were randomized in equal numbers to DHA 250 mg/day, DHA 500 mg/day or placebo. Coherently with the primary analysis, the probability of more severe steatosis after 24 months of DHA supplementation was 50% lower [95% confidence interval (CI) -59% to -42%)] in the combined DHA 250 and 500 mg/day groups versus placebo. The present secondary analysis revealed an independent effect of PNPLA3 status on the response to DHA. In fact, the probability of more severe steatosis was higher (37%, 95% CI 26-48%) for the PNPLA3 M/M versus I/M genotype and lower (-12%, 95% CI -21% to -3%) for the I/I versus I/M genotype (Somers' D for repeated measures). We conclude that the 148M allele of PNPLA3 is associated with lower response, and the 148I allele with greater response, to DHA supplementation in children with NAFLD. \ua9 Copyright 2013, Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition 2013