RNA Metabolism and Therapeutics in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder characterized by the selective death of upper and lowers motor neurons in spinal cord, brain stem, and motor cortex, which leads to paralysis and death within 2–3 years of onset. Deeply sequencing technologies, to simultaneously analyze the transcriptional expression of thousands of genes, offered new possibilities to focus on ALS pathogenesis and, most notably, to find new potential targets for novel treatments. The present book chapter illustrates recent advances in transcriptomic studies in animal models and human samples and in new molecular targets related to ALS pathogenesis and disease progression. Additionally, new insights into the involvement of altered transcriptional profiles of noncoding RNAs (microRNA and lncRNA) and ALS-associated ribosomal binding proteins have been investigated, to understand the functional consequences of extensive RNA dysregulation in ALS. Attention has been also turned on how transcriptome alterations could highlight new molecular targets for drug development

SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS

Copper-zinc superoxide dismutase (SOD1) is a detoxifying enzyme localized in the cytosol, nucleus, peroxisomes, and mitochondria. The discovery that mutations in SOD1 gene cause a subset of familial amyotrophic lateral sclerosis (FALS) has attracted great attention, and studies to date have been mainly focused on discovering mutations in the coding region and investigation at protein level. Considering that changes in SOD1 mRNA levels have been associated with sporadic ALS (SALS), a molecular understanding of the processes involved in the regulation of SOD1 gene expression could not only unravel novel regulatory pathways that may govern cellular phenotypes and changes in diseases but also might reveal therapeutic targets and treatments. This review seeks to provide an overview of SOD1 gene structure and of the processes through which SOD1 transcription is controlled. Furthermore, we emphasize the importance to focus future researches on investigating posttranscriptional mechanisms and their relevance to ALS

Dyadic associations between perceived social support and psychological well-being in caregivers and older care recipients

Caregiving can be burdensome for both family caregivers and older care recipients (i.e., adults 75 years or older with care needs). This study aimed to determine dyadic associations between caregivers' and care recipients' perceived social support from others (e.g., family and friends) and psychological well-being as a dyad. Caregivers and care recipients (N = 215 dyads) in this cross-sectional study were recruited by pensioner trade unions in Italy. Both members of the dyad completed the World Health Organization-Five Well-Being Index (WHO-5). Social support was measured with the Carers of Older People in Europe Index for caregivers and the Oslo-3 Scale for care recipients. Dyadic data were analyzed with the actor-partner interdependence model. Caregivers' and care recipients' well-being was moderately correlated (r = 0.41, p < .01), with care recipients reporting significant lower well-being (MCR = 30.95 vs. MCG = 46.45). Social support perceived by the caregivers was positively associated with their own well-being (actor effect; β = 3.31, p < .001) and with the care recipients' well-being (partner effect; β = 0.58, p < .001). No significant care recipient actor and partner effects were detected. This study provided evidence on crossover effects between social support and well-being in caregiving dyads. Findings have implications for research and clinical practice in familial aged care. Family interventions targeted at the caregivers' broader social environment might enhance both dyad members' well-being. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Sex-Dependent Outcome of Hepatitis B and C Viruses Infections: Synergy of Sex Hormones and Immune Responses?

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic viruses that differ in their genomic content, life cycle and molecular prognosis. HBV and HCV establish chronic lifespan infections that can evolve to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). This malignant liver cancer affects more commonly male patients than females, with a male-to-female incidence ratio of &lt;Capword&gt;2&lt;/Capword&gt;:1 up to 7:1. Sex significantly contributes to shape the immune responses, contributing to differences in the pathogenesis of infectious diseases, in males and females patients. Females usually develop more intense innate, humoral and cellular immune responses to viral infections and to vaccination compared to male subjects. Sex hormones, in turn, differentially affect the immune responses to viruses, by specific binding to the hormone receptors expressed on the immune cells. In general, estrogens have immune-stimulating effect, while androgens are immune-suppressing. However, sex hormones, such as androgen, can also directly interact with HBV genome integrated into the cell nucleus and activate transcription of HBV oncoproteins. On the other side, estradiol and estrogen receptors protect liver cells from inflammatory damage, apoptosis and oxidative stress, which contribute to fibrosis and malignant transformation preceding HCC. In HCV-associated cirrhosis and HCC the decreased expression of estrogen receptor alfa (ERα) in male patients may explain the worse outcome of HCV infection in men than in women. The synergistic action of male and female sex hormones and of immune responses, together with viral factors contribute to the mechanism of sex/gender disparity in the outcome and progression of hepatitis viruses infection

Estudios preliminares de la estructura genética del perro cimarrón uruguayo usando microsatélites

Analizar la estructura poblacional en una muestra de perros “Cimarrón Uruguayo” usando marcadores moleculares tipo microsatélites. Materiales y métodos. Se analizaron treinta caninos de diferentes zonas de Uruguay con un set de nueve marcadores moleculares microsatélites empleando PCR. La estructura poblacional se analizó con el software de distribución libre “Structure”. Resultados. Según nuestros datos, los resultados preliminares muestran que no es posible establecer una subdivisión entre los animales de la muestra. Conclusiones. El estudio realizado apoya la hipótesis de que los perros que existen en la actualidad derivan del núcleo fundador que se refugió en la región noreste del país. La distribución de la raza entre las distintas áreas de Uruguay continúa hoy en día, no existe aislamiento entre los diferentes grupos de animales y el intercambio es constante

Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyte.

Summary We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte dif- ferentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu- MoDC lack CD1 molecule expression, fail to upregu- late CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb- monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses

Características pessoais atribuídas por atletas a técnico de equipe de alto-rendimento

The purpose of this study was to identify the personal behavior characteristic of one top level handball teams’coach, under the athlete’s perception at three dimensions: professional behavior, task executions and social relations. The data were collected using the Coach Evaluation Questionnaire - "QA.T." - Lakehead University Thunder Bay/Ontario/Canada. The results obtained was capable of providing immediate feedback about athlete’s perceptions of their coach performance. It was also concluded that athletes considered the "Professional Behavior" as most important personal characteristic in coach’s evaluation in the process of personal behavior relationshipO presente estudo teve como principal objetivo identificar as caracaterísticas comportamentais de um técnico de equipe de handebol do mais alto nível técnico do Brasil, perante três dimensões: postura profissional, execução de tarefas e relação social. Os dados foram coletados utilizando o Questionário de Avaliação do Técnico " QA.T." Lakehead University Thunder Bay/Ontário/Canadá. Os resultados obtidos realçaram um imediato "feedback" sobre a "performance" pessoal do técnico no que diz respeito a percepção real dos atletas. Concluiu-se, que os atletas consideraram a "Postura Profissional" como a mais importante característica pessoal do técnico no processo das relações intercomportamentai