Direct and specific chemical control of eukaryotic translation with a synthetic RNA–protein interaction

Sequence-specific RNA–protein interactions, though commonly used in biological systems to regulate translation, are challenging to selectively modulate. Here, we demonstrate the use of a chemically-inducible RNA–protein interaction to regulate eukaryotic translation. By genetically encoding Tet Repressor protein (TetR)-binding RNA elements into the 5′-untranslated region (5′-UTR) of an mRNA, translation of a downstream coding sequence is directly controlled by TetR and tetracycline analogs. In endogenous and synthetic 5′-UTR contexts, this system efficiently regulates the expression of multiple target genes, and is sufficiently stringent to distinguish functional from non-functional RNA–TetR interactions. Using a reverse TetR variant, we illustrate the potential for expanding the regulatory properties of the system through protein engineering strategies

A Cross-National Analysis of the Psychometric Properties of the Geriatric Anxiety Inventory

10.1093/geronb/gbz002J Gerontol B Psychol Sci Soc Sc

The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse

estudos artísticos

A revista Gama parece agir como um revelador de imagens latentes: a sua ação é uma ativação social, sempre de reforço simbólico, que permite auxiliar a discernir, e a identificar, aquilo a que todos chamamos de arte. É um projeto de legitimação apoiado nos criadores: que sejam os artistas a apontar os caminhos da arte, onde eles se escondem, onde ela pode passar a ser. Como em Espinosa, na ‘Ética,’ a arte pode ser uma ‘qualia’ de uma substância potente, que ao ser percebida e reconhecida, nas páginas do número 14 da revista Gama, nos seus 16 artigos, se percebe como coisa, ocorrência valiosa, ou melhor, ‘valente.’info:eu-repo/semantics/publishedVersio

Genetic Variations Strongly Influence Phenotypic Outcome in the Mouse Retina

Variation in genetic background can significantly influence the phenotypic outcome of both disease and non-disease associated traits. Additionally, differences in temporal and strain specific gene expression can also contribute to phenotypes in the mammalian retina. This is the first report of microarray based cross-strain analysis of gene expression in the retina investigating genetic background effects. Microarray analyses were performed on retinas from the following mouse strains: C57BL6/J, AKR/J, CAST/EiJ, and NOD.NON-H2-nb1 at embryonic day 18.5 (E18.5) and postnatal day 30.5 (P30.5). Over 3000 differentially expressed genes were identified between strains and developmental stages. Differential gene expression was confirmed by qRT-PCR, Western blot, and immunohistochemistry. Three major gene networks were identified that function to regulate retinal or photoreceptor development, visual perception, cellular transport, and signal transduction. Many of the genes in these networks are implicated in retinal diseases such as bradyopsia, night-blindness, and cone-rod dystrophy. Our analysis revealed strain specific variations in cone photoreceptor cell patterning and retinal function. This study highlights the substantial impact of genetic background on both development and function of the retina and the level of gene expression differences tolerated for normal retinal function. These strain specific genetic variations may also be present in other tissues. In addition, this study will provide valuable insight for the development of more accurate models for human retinal diseases

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

We show in human immunodeficiency virus-positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular ris

LIBRO BLANCO PARA UNA ESTRATEGIA DE ESPECIALIZACIÓN INTELIGENTE EN BOSQUES COMPLEJOS DEL SUDOE

29 páginasEl objetivo del proyecto COMFOR-SUDOE es potenciar los bosques con estructuras complejas (mixtos e irregulares) así como la plantación con varias especies, como una estrategia de adaptación que dé respuesta al cambio climático y a la disminución de la biodiversidad. Entendemos como “bosque complejo” aquellas estructuras irregulares o disetáneas y/o de composición pluriespecífica gestionadas bajo un principio de persistencia y de acuerdo con objetivos de multifuncionalidad (producción, protección y uso social) y estabilidad. El proyecto ha sido financiado por INTERREG-SUDOE en el marco del IV Programa y se lanzó para fomentar las sinergias y fortalecer una red que una transnacionalmente la investigación y la innovación en sectores específicos del Sudoeste Europeo (SUDOE). Se trata de promover un crecimiento inteligente y sostenible mediante la promoción de la investigación, el desarrollo, la innovación y la transferencia tecnológica. El proyecto se desarrolló para definir prioridades de innovación, investigación y especialización entorno a los bosques complejos, abarcando ámbitos como la biodiversidad y bioeconomía, la participación ciudadana y acciones transformadoras para incrementar los paisajes resilientes. El presente informe recoge los principales resultados del proyecto y las recomendaciones para incluir los bosques complejos como una prioridad estratégica de especialización inteligenteProyecto financiado por el programa INTERREG-SUDOE a través del Fonde Europeo de Desarrollo Regional (FEDER). Presupuesto 1.289.211,57 €N

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns.

In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Correction to: Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases

In the original publication of the article, consortium author list was missing in the article