Mediator complex in transcription regulation and DNA repair: Relevance for human diseases.

The Mediator complex is an essential coregulator of RNA polymerase II transcription. More recent developments suggest Mediator functions as a link between transcription regulation, genome organisation and DNA repair mechanisms including nucleotide excision repair, base excision repair, and homologous recombination. Dysfunctions of these processes are frequently associated with human pathologies, and growing evidence shows Mediator involvement in cancers, neurological, metabolic and infectious diseases. The detailed deciphering of molecular mechanisms of Mediator functions, using interdisciplinary approaches in different biological models and considering all functions of this complex, will contribute to our understanding of relevant human diseases.

A genome-wide comprehensive analysis of nucleosome positioning in yeast.

In eukaryotic cells, the one-dimensional DNA molecules need to be tightly packaged into the spatially constraining nucleus. Folding is achieved on its lowest level by wrapping the DNA around nucleosomes. Their arrangement regulates other nuclear processes, such as transcription and DNA repair. Despite strong efforts to study nucleosome positioning using Next Generation Sequencing (NGS) data, the mechanism of their collective arrangement along the gene body remains poorly understood. Here, we classify nucleosome distributions of protein-coding genes in Saccharomyces cerevisiae according to their profile similarity and analyse their differences using functional Principal Component Analysis. By decomposing the NGS signals into their main descriptive functions, we compared wild type and chromatin remodeler-deficient strains, keeping position-specific details preserved whilst considering the nucleosome arrangement as a whole. A correlation analysis with other genomic properties, such as gene size and length of the upstream Nucleosome Depleted Region (NDR), identified key factors that influence the nucleosome distribution. We reveal that the RSC chromatin remodeler-which is responsible for NDR maintenance-is indispensable for decoupling nucleosome arrangement within the gene from positioning outside, which interfere in rsc8-depleted conditions. Moreover, nucleosome profiles in chd1Δ strains displayed a clear correlation with RNA polymerase II presence, whereas wild type cells did not indicate a noticeable interdependence. We propose that RSC is pivotal for global nucleosome organisation, whilst Chd1 plays a key role for maintaining local arrangement.

Multiple genomic solutions for local adaptation in two closely related species (sheep and goats) facing the same climatic constraints.

The question of how local adaptation takes place remains a fundamental question in evolutionary biology. The variation of allele frequencies in genes under selection over environmental gradients remains mainly theoretical and its empirical assessment would help understanding how adaptation happens over environmental clines. To bring new insights to this issue we set up a broad framework which aimed to compare the adaptive trajectories over environmental clines in two domesticated mammal species co-distributed in diversified landscapes. We sequenced the genomes of 160 sheep and 161 goats extensively managed along environmental gradients, including temperature, rainfall, seasonality and altitude, to identify genes and biological processes shaping local adaptation. Allele frequencies at putatively adaptive loci were rarely found to vary gradually along environmental gradients, but rather displayed a discontinuous shift at the extremities of environmental clines. Of the 430 candidate adaptive genes identified, only 6 were orthologous between sheep and goats and those responded differently to environmental pressures, suggesting different putative mechanisms involved in local adaptation in these two closely related species. Interestingly, the genomes of the 2 species were impacted differently by the environment, genes related to signatures of selection were most related to altitude, slope and rainfall seasonality for sheep, and summer temperature and spring rainfall for goats. The diversity of candidate adaptive pathways may result from a high number of biological functions involved in the adaptations to multiple eco-climatic gradients, and a differential role of climatic drivers on the two species, despite their co-distribution along the same environmental gradients. This study describes empirical examples of clinal variation in putatively adaptive alleles with different patterns in allele frequency distributions over continuous environmental gradients, thus showing the diversity of genetic responses in adaptive landscapes and opening new horizons for understanding genomics of adaptation in mammalian species and beyond.

Estado de ánimo, emociones y conductas de los niños durante la pandemia de COVID-19 en la Ciudad Autónoma de Buenos Aires / Mood, emotions, and behaviors of children during the COVID-19 pandemic in Autonomous City of Buenos Aires

Introducción. Los cambios en la rutina y en el entramado social que generó la pandemia por COVID-19 afectaron a los niños, niñas y adolescentes (NNyA). El objetivo de este trabajo fue conocer el estado de ánimo, las emociones y las conductas de los NNyA durante el aislamiento por COVID-19. Población y métodos . Estudio prospectivo, descriptivo y transversal. Se preguntó a los padres y/o cuidadores de niños de 3 a 15 años de edad, de la Ciudad Autónoma de Buenos Aires, cómo percibían el estado de ánimo, las conductas y las emociones de los NNyA durante el período de aislamiento. Resultados. Se incluyeron 1080 cuestionarios. El 81 % de los padres y/o cuidadores advirtió algún cambio en la salud emocional de los NNyA. El 76 % refirió que los niños de 3-5 años se mostraban aburridos, enojados y angustiados. Además, observaron un aumento de los episodios de llanto (52 %) y regresión a comportamientos ya superados (29 %). En el grupo de 6-11 años, el 43 % presentó dificultad en mantener la concentración. En 3 de cada 10 adolescentes, de 12 a 15 años de edad, los adultos percibieron abandono de actividades que antes disfrutaban, preocupación y tristeza. Conclusión. La pandemia de COVID-19 impactó en el estado de ánimo, las conductas y las emociones de los NNyA. Predominaron los sentimientos negativos, como aburrimiento, tristeza, angustia y preocupación.

Introduction. Changes in daily routine and social fabric resulting from the COVID-19 pandemic had an effect on children and adolescents. The objective of this study was to know the mood, emotions, and behaviors of children and adolescents during the COVID-19 lockdown. Population and methods. This was a prospective, descriptive, cross-sectional study. Parents and/or caregivers of children and adolescents aged 3-15 years in the Autonomous City of Buenos Aires were asked about their perceptions of the mood, behaviors, and emotions of children and adolescents during the lockdown. Results. A total of 1080 questionnaires were included. Results showed that 81% of parents and/or caregivers observed changes in children and adolescents emotional health; 76% referred that children aged 3-5 years were bored, angry, and upset. They also observed an increase in crying spells (52%) and regression to behaviors that had been outgrown (29%). In the 6-11-year-old group, 43% showed difficulty focusing. Adults noticed that 3 out of 10 adolescents aged 12-15 years discontinued activities they used to enjoy and were sad and worried. Conclusion. The COVID-19 pandemic impacted on the mood, behaviors, and emotions of children and adolescents. Negative feelings prevailed, such as boredom, sadness, anxiety, and worry.

Análisis descriptivo de los casos de gripe A (H1N1) notificados durante la pandemia de 2009 en la Región Sanitaria V de la Provincia de Buenos Aires, Argentina / Descriptive analysis of cases of Influenza A (H1N1) reported durig the pandemic of 2009 in the Health Region V of the province of Buenos Aires, Argentina

A partir de la transmisión sostenida del virus de Gripe A(H1N1) en distintos países, la Organización Mundial de la Salud declaró el comienzo de la primera pandemia de influenza del siglo XXI el 11de junio de 2009. En Argentina, la región sanitaria V de la provincia de Buenos Aires fue una de las primeras afectadas en todo el país. OBJETIVO:realizar un análisis descriptivo de las notificaciones registradas de los casos de Gripe A (H1N1) en dicha región hasta el 20 de septiembre de 2009. MÉTODO: se trabajó con fuentes secundarias. La confirmación de casos (PCR en tiempo real) fue realizada en instituciones autorizadas. Variables consideradas: casos sospechosos, confirmados y fallecidos, sexo, edad, municipios, antecedentes epidemiológicos, embarazadas, fecha de inicio de síntomas y circulación viral por semana epidemiológica. RESULTADOS: se registraron 1.332 notificaciones de casos sospechosos y 949 confirmados. El mayor número de confirmados se registró en los municipios de Gral. San Martín (94), San Isidro (90), Pilar (85) y Vicente López (80). Las semanas epidemiológicas 23, 24 y 25 registraron la mayor cantidad de casos confirmados. Los grupos de edad que más confirmados aportaron fueron: de 5 a 9 años (121), 1 a 4 (89) y 10 a 14 (75) (cuya mediana de edad fue de 30 años). Se registraron 64 casos confirmados fallecidos. La tasa más alta de mortalidad específica por grupo de edad correspondió a menores de un año. Se registraron 9 casos confirmados en embarazadas y una puérpera, 5 de ellas fallecieron. CONCLUSIÓN: todos los municipios presentaron casos confirmados y 11 reportaron fallecidos. El pico de la epidemia se adelantó en una semana al registrado a nivel nacional y la mediana de edad en fallecidos fue más baja que la de todo el país. El análisis de mortalidad mostró un mayor riesgo para varones, embarazadas y menores de un año.

From the sustained transmission of influenza virus A (H1N1) in different countries, the World Health Organization declared the beginning of the first influenza pandemic of the twenty first century on June 11, 2009. In Argentina, the Health Region V of the Province of Buenos Aires was one of the first affected across the country. OBJECTIVE: to conduct a descriptive analysis of notifications of cases of Influenza A (H1N1) in that region until September 20, 2009. METHODS: we worked with secondary sources. The confirmation of cases (real-time PCR) was carried out in authorized institutions. Variables considered: suspected cases, confirmed and diseased, sex, age, municipalities, epidemiological history, pregnant, date of on set of symptoms and viral movement by epidemiological week. RESULTS: there were 1.332 notifications of suspected cases and 949 confirmed. The highest number of confirmed cases was in the municipalities of Gral. San Martin (94), San Isidro (90),Pilar (85) and Vicente López (80). The epidemiological weeks 23,24 and 25 showed the highest number of confirmed cases. Giventhe age group, which contributed more confirmed cases was that of 5-9 years (121), followed by 1-4 (89) and 10-14 (75). The median age was 30 years. There were 64 confirmed cases dead. The high estrate of cause-specific mortality by age group accounted for less than one year. There were nine conf irmed cases in pregnant and puerperal women, five of them died. CONCLUSION: all municipalities had confirmed cases and 11 confirmed deaths reported. The peak of the epidemic one week a head of the national and the medianage was lower than the registered for the rest of the country. The analysis of mortality showed a higher risk for men, pregnant women and children under one year.