Molecular basis of differential target regulation by miR-96 and miR-182: the Glypican-3 as a model

Besides the fact that miR-96 and miR-182 belong to the miR-182/183 cluster, their seed region (UUGGCA, nucleotides 2–7) is identical suggesting potential common properties in mRNA target recognition and cellular functions. Here, we used the mRNA encoding Glypican-3, a heparan-sulfate proteoglycan, as a model target as its short 3′ untranslated region is predicted to contain one miR-96/182 site, and assessed whether it is post-transcriptionally regulated by these two microRNAs. We found that miR-96 downregulated GPC3 expression by targeting its mRNA 3′-untranslated region and interacting with the predicted site. This downregulatory effect was due to an increased mRNA degradation and depended on Argonaute-2. Despite its seed similarity with miR-96, miR-182 was unable to regulate GPC3. This differential regulation was confirmed on two other targets, FOXO1 and FN1. By site-directed mutagenesis, we demonstrated that the miRNA nucleotide 8, immediately downstream the UUGGCA seed, plays a critical role in target recognition by miR-96 and miR-182. Our data suggest that because of a base difference at miRNA position 8, these two microRNAs control a completely different set of genes and therefore are functionally independent

Imaging assessment of children presenting with suspected or known juvenile idiopathic arthritis : ESSR-ESPR points to consider

Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease. It represents a group of heterogenous inflammatory disorders with unknown origin and is a diagnosis of exclusion in which imaging plays an important role. JIA is defined as arthritis of one or more joints that begins before the age of 16 years, persists for more than 6 weeks and is of unknown aetiology and pathophysiology. The clinical goal is early suppression of inflammation to prevent irreversible joint damage which has shifted the emphasis from detecting established joint damage to proactively detecting inflammatory change. This drives the need for imaging techniques that are more sensitive than conventional radiography in the evaluation of inflammatory processes as well as early osteochondral change. Physical examination has limited reliability, even if performed by an experienced clinician, emphasising the importance of imaging to aid in clinical decision-making. On behalf of the European Society of Musculoskeletal Radiology (ESSR) arthritis subcommittee and the European Society of Paediatric Radiology (ESPR) musculoskeletal imaging taskforce, based on literature review and/or expert opinion, we discuss paediatric-specific imaging characteristics of the most commonly involved, in literature best documented and clinically important joints in JIA, namely the temporomandibular joints (TMJs), spine, sacroiliac (SI) joints, wrists, hips and knees, followed by a clinically applicable point to consider for each joint. We will also touch upon controversies in the current literature that remain to be resolved with ongoing research

Multifunctional tribometer development and performance study of CuCrZr-316L material pair for ITER application

Radio-Frequency (RF) contacts are key components on the International Thermonuclear Experimental Reactor (ITER) Ion Cyclotron Resonance Heating (ICRH) antenna, and these components are facing big challenges such as 2 kA operation current load and intensive sliding under up to 250 °C in high vacuum. Stainless steel (SS) 316L and CuCrZr are most likely to be applied as base materials for the conductor and the RF contacts louvers. To evaluate the performance of the selected materials, their electrical and tribological behaviors have to be studied. A multifunctional tribometer which can mimic the ITER ICRH RF contacts' relevant working conditions was designed and built in CEA. The contact resistance (Rc) and coefficient of friction (CoF) of CuCrZr-316L pair were researched on this tribometer

The HOG Pathway Dictates the Short-Term Translational Response after Hyperosmotic Shock

In the global osmoshock translational response in yeast, some gene products were translationally mobilized without transcriptional up-regulation. Conversely, other transcriptionally up-regulated mRNAs were translationally inhibited. Analogous changes occurred on the protein level. These translational responses were strongly dependent on Hog1 and Rck2

Recent advances in ankylosing spondylitis: understanding the disease and management

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease

Analysis of post-transcriptional regulation using the FunREG method

International audienc

Depression among Adolescents, Aged 13–19 Years, Attending Secondary Schools in Trinidad Prevalence and Associated Factors

Objective: To determine the prevalence of depression and psychosocial factors associated with depression in secondary school students in Trinidad. Methods: This was a cross-sectional study of a stratified random sample of public secondary schools utilizing a modified pre-tested self-administered Beck Depression Inventory (BDI) to detect depression in students aged 13–19 years in Trinidad. Results: In this study, 1290 students participated, a response rate of 79.6%; 43% were aged 13–15 years; 53.6 % were Indo-Trinidadians; 82.5% were attending co-educational schools and 70.6% lived with both parents. The prevalence of depression was 25.3% ± 2.37%. Chi-square analysis revealed statistically significant associations between depression and the categories of age, gender, living arrangements and school type. Similar findings were observed for respondents who admitted to cigarette and alcohol use or to being afraid of, or being injured by their parent (p < 0.05). Logistic regression indicated that females were 1.7 times as likely to be depressed when compared with males; respondents not living with both parents were 1.5 times as likely to be depressed as those who were. Respondents reporting that they were afraid of parents or of being injured by parents were three times as likely to be depressed as respondents who had not had those experiences. Conclusions: One out of every four secondary school students in Trinidad was found to have significant depression. There were strong associations between depression and age, gender, school type and family structure. This study identifies that many adolescents experience violence in the home and those who did were more likely to be depressed. "Depresión Entre Adolescentes de 13 a 19 Años, que Asisten a las Escuelas Secundarias en Trinidad Prevalencia y Factores Asociados" RESUMEN Objetivo: Determinar la prevalencia de la depresión y los factores psicológicos asociados con la depresión en estudiantes de las escuelas secundarias de Trinidad. Métodos: El presente trabajo constituye un estudio transversal con muestreo aleatorio estratificado de escuelas secundarias públicas, utilizando un Inventario de Depresión de Beck modificado, auto-administrado y pre-probado, con el objeto de detectar depresión en estudiantes de 13 a 19 años de edad en Trinidad. Resultados: En este estudio, participaron 1290 estudiantes, lo cual constituye una tasa de respuesta de 79.6%; 43% tenían de 13 a 15 años; 53.6% eran indo-trinidenses; 82.5% asistían a escuelas coeducacionales y 70.6% vivían con el padre y la madre. La prevalencia de la depresión fue 25.3% ± 2.37%. El análisis de chi-cuadrado reveló asociaciones estadísticamente significativas entre la depresión y las categorías de edad, género, ordenamiento de la vida y tipo de escuela. Hallazgos similares se observaron en encuestados que admitieron el uso del alcohol y cigarrillos, o tener miedo de sus padres, o haber sido herido por sus padres (p < 0.05). La regresión logística indicó que las hembras tenían una tendencia a deprimirse 1.7 veces mayor en comparación con los varones; los encuestados que no vivían con el padre y la madre presentaban una probabilidad de deprimirse 1.5 veces mayor que aquellos que vivían con ambos progenitores. Los encuestados que reportaron tener miedo de sus padres o haber sido físicamente lastimados por sus padres, presentaban una tendencia tres veces mayor a deprimirse que los encuestados que no habían pasado por esas experiencias. Conclusiones: Se halló que uno de cada cuatro estudiantes de escuelas secundarias en Trinidad tenía una depresión significativa. Hubo fuerte asociaciones entre la depresión y la edad, el género, el tipo de escuela y la estructura de la familia. Este estudio identifica que muchos adolescentes experimentan violencia en sus hogares y los que tuvieron esa experiencia tenían una probabilidad mayor de sentirse deprimidos