The RNA recognition motif protein RBM11 is a novel tissue-specific splicing regulator.

Mammalian tissues display a remarkable complexity of splicing patterns. Nevertheless, only few examples of tissue-specific splicing regulators are known. Herein, we characterize a novel splicing regulator named RBM11, which contains an RNA Recognition Motif (RRM) at the amino terminus and a region lacking known homology at the carboxyl terminus. RBM11 is selectively expressed in brain, cerebellum and testis, and to a lower extent in kidney. RBM11 mRNA levels fluctuate in a developmentally regulated manner, peaking perinatally in brain and cerebellum, and at puberty in testis, in concomitance with differentiation events occurring in neurons and germ cells. Deletion analysis indicated that the RRM of RBM11 is required for RNA binding, whereas the carboxyl terminal region permits nuclear localization and homodimerization. RBM11 is localized in the nucleoplasm and enriched in SRSF2-containing splicing speckles. Transcription inhibition/release experiments and exposure of cells to stress revealed a dynamic movement of RBM11 between nucleoplasm and speckles, suggesting that its localization is affected by the transcriptional status of the cell. Splicing assays revealed a role for RBM11 in the modulation of alternative splicing. In particular, RBM11 affected the choice of alternative 5' splice sites in BCL-X by binding to specific sequences in exon 2 and antagonizing the SR protein SRSF1. Thus, our findings identify RBM11 as a novel tissue-specific splicing factor with potential implication in the regulation of alternative splicing during neuron and germ cell differentiation

Beyond the DSM-IV: Assumptions, Alternatives, and Alterations

Current diagnostic processes reflect the limitations and utility of the framework of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). Clinical information in the DSM-IV\u27s 5-axis system almost exclusively focuses on weaknesses and pathology and is summarized in a flawed categorical system. Hence, the authors describe 3 adjunctive, or alternative, means of conceptualizing behavior; several means of altering the current DSM-IV system; and 2 future directions in the diagnosis of strengths

Conicoid Mirrors

The first order equation relating object and image location for a mirror of arbitrary conic-sectional shape is derived. It is also shown that the parabolic reflecting surface is the only one free of aberration and only in the limiting case of distant sources.Comment: 9 page

An analytical model for the control of silica grout penetration in natural groundwater systems

Over the last three decades, colloidal silica has been investigated and more recently adopted as a low viscosity grouting technology (e.g. for grouting rock fractures within geological disposal facilities nuclear waste). The potential of colloidal silica as a favourable grouting material exists due to: its initial low viscosity; its low hydraulic conductivity after gelling (of the order of 10-7 cm/s); the very low injection pressures required; its controllable set/gel times (from minutes to several days); the fact it is environmentally inert; its small particle size (less than hundreds of nanometres) and its cost-effectiveness. Despite the documented success of colloidal silica based grouts for hydraulic barrier formation, research has not translated into widespread industrial use. A key factor in this limited commercial uptake is the lack of a predictive model for grout gelling which controls grout penetration: whilst data are available to underpin design of a grouting campaign in laboratory conditions, little research has been done to underpin applications in natural environments. Here we develop and validate an analytical model of colloidal silica gelling in groundwaters with varying pH and background electrolyte concentrations. This paper presents an analytical model that accounts for changes in pH, electrolyte concentration, cation valency and molar mass, silica particle size and silica concentration giving predictive capability without the need for site-specific calibration. The model is validated against experimental observations for gel times of 32 minutes to 766 minutes, the model accurately predicts the log(gel time) with an average error of 4% which corresponds to an R2 value of 0.96 The model is then applied to a hypothetical case study to demonstrate its use in grout design, based on published in-situ groundwater data from the Olkiluoto area of Finland. The model successfully predicts the required accelerator concentration to achieve a grout gel time of approximately 50 minutes, taking into account the cations already present within the synthetic groundwater

A photonic bandgap resonator to facilitate GHz frequency conductivity experiments in pulsed magnetic fields

We describe instrumentation designed to perform millimeter-wave conductivity measurements in pulsed high magnetic fields at low temperatures. The main component of this system is an entirely non-metallic microwave resonator. The resonator utilizes periodic dielectric arrays (photonic bandgap structures) to confine the radiation, such that the resonant modes have a high Q-factor, and the system possesses sufficient sensitivity to measure small samples within the duration of a magnet pulse. As well as measuring the sample conductivity to probe orbital physics in metallic systems, this technique can detect the sample permittivity and permeability allowing measurement of spin physics in insulating systems. We demonstrate the system performance in pulsed magnetic fields with both electron paramagnetic resonance experiments and conductivity measurements of correlated electron systems.Comment: Submitted to the Review of Scientific instrument

Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes

Background: Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs. Aims: To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D. Methods: A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype-phenotype association analysis were performed. Results: The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and - 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and - 0.286, respectively). Conclusions: These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN

Perception of nurses’ professional identity during the first wave of COVID-19 pandemic infections

Background and aim of the work: The main purpose of this study is to investigate on the experience of nurses working in the Covid-19 area focusing on their role’s perception. In particular, we explored the nurses’ perception of job satisfaction in relation to the images sent back by public opinion through the mass media and social communication channels. During the first wave of Covid-19 nurses have acquired media visibility, but their feeling is represented more by the discomfort of finding themselves suddenly glorified in the face of a lack of professional, social, and economic recognition. Materials and methods: A Mix-Method methodology and convenience sampling was adopted, on the population of professionals and students in post-graduate specializations, belonging to the Department of Medicine and Surgery of the University of Parma, and by nurses from the ASST-Bergamo Est, Lombardia Italy, who worked in the Covid emergency during the first wave of the pandemic, from February 2020 to May 2020. In the quantitative phase Stamm’s Professional Quality of Life Scale - ProQOL was administered to 89 respondents through a Google Form, In the qualitative phase, 3 Focus Groups were conducted on a total of 17 students. Results: At the ProQOL questionnaire, a moderate score was found in the Compassion Satisfaction scale (CF = 38.28) and in the Secondary Traumatic Stress subscale (STS-24.33), while low values emerged in the Burnout subscale (BO = 16.02). Five specific topics emerged from the focus groups: Professional collaboration, Job satisfaction, Nurse’s personal skills, Failure to protect the public image and the nursing profession. Conclusions: The professional collaboration, union with the work team, sense of solidarity, job satisfaction, professional growth, and awareness of one’s role seem to have worked favorably on Compassion Satisfaction, while keeping Compassion Fatigue levels under control

Analysis of 19 Minerals and Cortisol in Red Deer Hair in Two Different Areas of the Stelvio National Park: A Preliminary Study

The aim of the study was to perform an investigation on the concentration of 19 minerals and cortisol in red deer (Cervuselaphus) hair, a matrix that is easy to collect with non-invasive and painless sampling, able to represent an integrative values of long-term substance concentrations, and able to give useful information, also when performed on dead animals, given its extreme stability over time. In the study thirty-five animals were included, coming from two different sides of a valley in the Stelvio National Park, where official water analysis had pointed out elevated concentrations of As in one of the two orographic sides. Hair cortisol concentrations were measured using a RIA(Radio Immuno Assay), while minerals were detected using ICP-MS (Inductively Coupled Plasma- Mass Spectrometry). Results showed a negative relationship between cortisol and some mineral concentrations (Li, Co, As, Cd, Cr and Tl) and significant differences in some mineral concentrations between park areas (Al, Co, Cu, Cd and Ni). As, Cr and cortisol differences approached statistical significance. This preliminary study represents a step forward in the study of wildlife allostatic load and a valid method for applications in wildlife management programs, in environmental studies and in public health programs

Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells

Translation of stored mRNAs accounts for protein synthesis during the transcriptionally inactive stages of spermatogenesis. A key step in mRNA translation is the assembly of the initiation complex EIF4F, which is regulated by the MTOR (mammalian target of rapamycin) and MNK1/2 (MAP kinase-interacting kinase 1 and 2) pathways. We investigated the expression and activity of regulatory proteins of these pathways in male germ cells at different stages of differentiation. All translation factors analyzed were expressed in germ cells throughout spermatogenesis. However, while EIF4G and PABP1 (poly[A]-binding protein 1) were more abundant in postmeiotic cells, MTOR and its target EIF4EBP1 (4E-BP1) decreased steadily during spermatogenesis. In vivo labeling showed that pachytene spermatocytes display higher rates of protein synthesis, which are partially dependent on MTOR and MNK activity. By contrast, haploid spermatids are characterized by lower levels of protein synthesis, which are independent of the activity of these pathways. Accordingly, MTOR and MNK activity enhanced formation of the EIF4F complex in pachytene spermatocytes but not in round spermatids. Moreover, external cues differentially modulated the activity of these pathways in meiotic and haploid cells. Heat shock decreased MTOR and MNK activity in pachytene spermatocytes, whereas round spermatids were much less sensitive. On the other hand, treatment with the phosphatase inhibitor okadaic acid activated MTOR and MNK in both cell types. These results indicate that translational regulation is differentially dependent on the MTOR and MNK pathways in mouse spermatocytes and spermatids and suggest that the late stages of germ cell differentiation display constitutive assembly of the translation initiation complex