Human THO–Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability

R-loops, formed by co-transcriptional DNA–RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R-loop accumulation centers on the conserved THO/TREX complex, an RNA-binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R-loops, we searched for new THO-interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co-transcriptional R-loops, DNA damage, and replication impairment. Functional analyses show that histone hypo-acetylation prevents accumulation of harmful R-loops and RNA-mediated genomic instability. Diminished histone deacetylase activity in THO- and Sin3A-depleted cell lines correlates with increased R-loop formation, genomic instability, and replication fork stalling. Our study thus uncovers physical and functional crosstalk between RNA-binding factors and chromatin modifiers with a major role in preventing R-loop formation and RNA-mediated genome instability.European Research Council ERC2014 AdG669898 TARLOOPMinisterio de Economía y Competitividad BFU2013-42918-P, BFU2016-75058-PJunta de Andalucía BIO123

Análisis de la tasa de traducción mitocondrial de fibroblastos embrionarios de ratón con hepatoencefalopatía COXPD1

La hepatoencefalopatía por deficiencia combinada de fosforilación oxidativa de tipo 1 (COXPD1) es una enfermedad mitocondrial causada por mutaciones en el gen GFM1 que codifica el factor de elongación mitocondrial G1 (EFG1). El estudio de diversos pacientes reveló una alteración en la secuencia de GFM1, un cambio de aminoácidos en la posición p.671 de Arginina a Citosina (p.R671C). Se generaron modelos permitieran estudiar la enfermedad, ratones portadores de la mutación p.R671C en homocigosis (Gfm1R671C/R671C). Sin embargo, su leve fenotipo condujo al intento fallido de obtener modelos knock-out para Gfm1, pero estos ratones sufrían letalidad embrionaria con el alelo en homocigosis. Como alternativa se generaron ratones heterocigotos con uno de sus alelos knock-out y otro con la mutación p.R671C (Gfm1-/R671C). Los fibroblastos de estas líneas de ratones se estudiaron en este trabajo. El análisis de los fibroblastos embrionarios ratón (MEFs) reveló niveles de EFG1 reducidos en la línea Gfm1-/R671C. Sin embargo, los niveles de EFG1 en la línea con un fenotipo más leve (Gfm1R671C/R671C) incrementaron ligeramente. Las dos líneas celulares con Gfm1mutado mostraron reducción en los niveles de COI, subunidad I del complejo IV o Citocromo c oxidasa de la cadena de fosforilación oxidativa. Esta expresión disminuida pudo observarse en el análisis mediante Western Blot e inmunocitoquímica. COI, proteína del sistema OXPHOS, es codificada por el DNA mitocondrial y sintetizada en los ribosomas mitocondriales, proceso en el que EFG1, factor de elongación tiene un papel fundamental. No se logró medir la tasa de traducción mitocondrial con la química click. Aunque se observó marcaje, es necesario optimizar el protocolo para las líneas celulares en estudio. <br /

Uridine Prevents Negative Effects of OXPHOS Xenobiotics on Dopaminergic Neuronal Differentiation

Neuronal differentiation appears to be dependent on oxidative phosphorylation capacity. Several drugs inhibit oxidative phosphorylation and might be detrimental for neuronal differentiation. Some pregnant women take these medications during their first weeks of gestation when fetal nervous system is being developed. These treatments might have later negative consequences on the offspring’s health. To analyze a potential negative effect of three widely used medications, we studied in vitro dopaminergic neuronal differentiation of cells exposed to pharmacologic concentrations of azidothymidine for acquired immune deficiency syndrome; linezolid for multidrug-resistant tuberculosis; and atovaquone for malaria. We also analyzed the dopaminergic neuronal differentiation in brains of fetuses from pregnant mice exposed to linezolid. The drugs reduced the in vitro oxidative phosphorylation capacity and dopaminergic neuronal differentiation. This differentiation process does not appear to be affected in the prenatally exposed fetus brain. Nevertheless, the global DNA methylation in fetal brain was significantly altered, perhaps linking an early exposure to a negative effect in older life. Uridine was able to prevent the negative effects on in vitro dopaminergic neuronal differentiation and on in vivo global DNA methylation. Uridine could be used as a protective agent against oxidative phosphorylation-inhibiting pharmaceuticals provided during pregnancy when dopaminergic neuronal differentiation is taking place

Relationship between obesity and occupational stress: a systematic review

Revisión Sistemática[ES] Introducción y objetivos: Realizamos una revisión bibliográfica para determinar la relación entre el estrés laboral y la obesidad en el ámbito laboral. Material y métodos: Revisión sistemática. Bases de datos: Medline (Medlars Online International Literature a través de Pubmed), Web Of Science, LILACS, IBECS, Embase, SCOPUS y Cochrane. Se han utilizado los niveles de evidencia STROBE y CONSORT para evaluar la calidad de los artículos. Resultados: Se han obtenido 177 referencias. Sólo 12 cumplieron con los criterios de inclusión y exclusión. Obtuvimos 1 estudio de casos y controles, 3 estudios de cohortes y 8 estudios transversales. Conclusiones: Aún no se dispone de evidencia científica suficiente que apoye una relación directa entre el estrés laboral y el aumento del índice de masa corporal, por lo cual, resulta necesario realizar estudios a más largo plazo que aporten evidencia sobre este tema, en vista del aumento del estrés en el trabajo, así como de la obesidad en los últimos años. [EN] Introduction and objectives: We carried out a literature review to determine the relationship between exposure to occupational stress and obesity among workers. Material and methods: Systematic Review. Databases: Medline (Medlars Online International Literature through Pubmed), Web of Science, LILACS, IBECS, Embase, SCOPUS and Cochrane. We used STROBE and CONSORT evidence levels to evaluate the quality of the articles. Results: 177 references have been obtained. Only 12 satisfied the inclusion and exclusion criteria. We obtained onecase-control study, three cohort studies and eight cross-sectional studies. Conclusions: There is not enough scientific evidence to support a direct relationship between occupational stress and the increase of the body max index, therefore, it is necessary to conduct more long-term studies that provide evidence on this subject, in the view of the increase in job stress and obesity in the last years.N

The impact of the COVID-19 pandemic in diabetes and dyslipidemia management in a Spanish region: a retrospective study of the Aragon population

IntroductionPrevious research has indicated that the COVID-19 outbreak had a negative impact on the diagnosis and management of cardiometabolic diseases. Our aim was to analyze the impact of the COVID-19 pandemic on the management of dyslipidemia and type 2 diabetes (T2D) in the Aragon region of Spain.MethodsWe conducted an observational retrospective study, which included data from all patients diagnosed with active T2D or dyslipidemia in Aragon during 2019–2021. Data was collected from the BIGAN platform, a big database that includes all healthcare data from the Aragon population. Clinical, biochemical, and pharmacological prescription information was obtained for each patient and for each year.ResultsOut of the total population of 1,330,000 in the Aragon region, 90,000 subjects were diagnosed with T2D each year, resulting in a prevalence of approximately 7%. The COVID-19 pandemic resulted in a decrease in the prevalence of this disease and a lower incidence during the year 2020. In addition, patients with T2D experienced a deterioration of their glucose profile, which led to an increase in the number of patients requiring pharmacological therapy. The prevalence of dyslipidemia was approximately 23.5% in both 2019 and 2020 and increased to 24.5% in 2021. Despite the worsening of the anthropometric profile, the lipid profile improved significantly throughout 2020 and 2021 compared to 2019. Moreover, the number of active pharmacological prescriptions increased significantly in 2021.DiscussionOur findings suggest that the overload of the health system caused by the COVID-19 pandemic has resulted in an underdiagnosis of T2D. Moreover, patients with T2D experienced a worsening of their glycemic profile, an increase in their pharmacological requirements, and lower performance of their analytical determinations. Dyslipidemic subjects improved their lipid profile although the value of lipid profile determination decreased between 2020 and 2021

Brain pyrimidine nucleotide synthesis and Alzheimer disease

Many patients suffering late-onset Alzheimer disease show a deficit in respiratory complex IV activity. The de novo pyrimidine biosynthesis pathway connects with the mitochondrial respiratory chain upstream from respiratory complex IV. We hypothesized that these patients would have decreased pyrimidine nucleotide levels. Then, different cell processes for which these compounds are essential, such as neuronal membrane generation and maintenance and synapses production, would be compromised. Using a cell model, we show that inhibiting oxidative phosphorylation function reduces neuronal differentiation. Linking these processes to pyrimidine nucleotides, uridine treatment recovers neuronal differentiation. To unmask the importance of these pathways in Alzheimer disease, we firstly confirm the existence of the de novo pyrimidine biosynthesis pathway in adult human brain. Then, we report altered mRNA levels for genes from both de novo pyrimidine biosynthesis and pyrimidine salvage pathways in brain from patients with Alzheimer disease. Thus, uridine supplementation might be used as a therapy for those Alzheimer disease patients with low respiratory complex IV activity

Guia de recursos per al personal de control oficial

Control oficial; Recursos humans; Gestió del coneixementControl oficial; Recursos humanos; Gestión del conocimientoOfficial control; Human resources; Knowledge managementAquesta guia dona resposta tant al personal que s’incorpora de nou a l’Agència de Salut Pública de Catalunya, com als que ja estan treballant i necessiten un document de consulta on es recullen diferents aspectes com ara l'explicació de conceptes clau relacionats amb la seva tasca i relació de recursos informàtics (intranet..) i altres (programes, guies pràctiques...) que necessita per fer el control oficial; els relacionats amb la formació (formació específica, Comunitat de Pràctica...) i els aspectes relacionats amb recursos humans (jornada i horari, règim retributiu...).Esta guía da respuesta tanto al personal que se incorpora de nuevo a la Agencia de Salud Pública de Cataluña, como a los que ya están trabajando y necesitan un documento de consulta en el que se recojan diferentes aspectos como la explicación de conceptos clave relacionados con su labor y relación de recursos informáticos (intranet..) y otros (programas, guías prácticas...) que necesita para realizar el control oficial; los relacionados con la formación (formación específica, Comunidad de Práctica...) y los aspectos relacionados con recursos humanos (jornada y horario, régimen retributivo...).This guide responds both to personnel who are joining the Public Health Agency of Catalonia again, and to those who are already working and need a consultation document that includes different aspects such as the explanation of key concepts related to their work and list of computer resources (intranet...) and others (programs, practical guides...) that you need to carry out the official control; those related to training (specific training, Community of Practice...) and aspects related to human resources (day and schedule, remuneration regime...

Insect repellent and chemical agronomic treatments to reduce seed numberin'Afourer'mandarin. Effect on yield and fruit diameter

Obtaining citrus fruits without seeds is a recurrent objective for farmers as it is one of the most valued char-acteristics, especially in mandarins.'Afourer'tangor is a highly valuable well-established mandarin, and a highpercentage of seeded fruits are produced under cross-pollination conditions. Several agronomic techniques havebeen suggested to control presence of seeds, such as covering with nets and copper sulfate (CuSO4) and gib-berellic acid (GA3) treatments. Natural bee repellents are also proposed to reduce the number of seeds per fruit.In this study, we aimed to compare the effect of several agronomic treatments to reduce the seed number in'Afourer' mandarin. To this end, we assessed the effect of chemical and bee repellent treatments on the seednumber per fruit and the side effect on yield and fruit diameter. Under these experimental conditions the two beerepellents, one based on zinc and one based onCapsicum annuum, were not useful for reducing the seed numberper fruit in'Afourer'mandarin. The copper sulfate + GA3treatment reduced the seed number per fruit by only35%, and this efficiency was clearly not enough to reduce the seed number for commercial purposes. The mosteffective method to reduce the seed number per fruit was covering with nets, but this technique led to markedlyreduced yields. Yield data was highly variable. Fruit diameter correlated positively with the seed number, but itwas a weak relationship as the seed number explained only 15% of fruit size variability (R2= 0,15)

75 años como referente de la investigación agraria y medioambiental española en condiciones de clima mediterráneo [Sitio Web]

1 .pdf con imagen de acceso al “website”, su url y los créditos relacionados con su creación y diseño.-- Créditos: Organización, Estación Experimental de Aula Dei (EEAD-CSIC); Dirección, Jesús Val Falcón; Coordinación, Ana Álvarez-Fernandez, Jorge Álvaro-Fuentes, Ernesto Igartua; Contenido, Anunciación Abadía, Javier Abadía, Carlos Albiñana, Miguel Alfonso, Arancha Arbeloa, Raúl Arbués, Isabel Armillas, Manuel Becana, Santiago Beguería, Carmen Castañeda, Ana Castillo, José Cavero, Bruno Contreras, Azahara Díaz, Edgar García, Elena García, Juan Manuel Gascuñana, Leticia Gaspar, Yolanda Gogorcena, Juan Herrero, Victoria Lafuente, María Victoria López, Juan Antonio Marín, José Martínez, José Carlos Martínez-Giménez, Ana Pilar Mata, Manuel Matamoros, Pierre Mignard, María Ángeles Moreno, Paula Murillo, Ana Navas, Antonio Pérez, Rafael Picorel, María Pilar Vallés, Irene Villar, Inmaculada Yruela, Nery Zapata, Isabel Zarazaga; Diseño y programación: DigitalWorks (Juanjo Ascaso y Asun Dieste); Vídeo, Delegación del CSIC en Aragón (Sara Gutiérrez y Yolanda Hernáiz); Fotografía, Archivo EEAD-CSIC, Anunciación Abadía, Jorge Álvaro-Fuentes, Arancha Arbeloa, Juanjo Ascaso, Santiago Beguería, Elena García, Ernesto Igartua, Ignasi Iglesias, José Manuel Lasa, José Carlos Martínez-Giménez, Pierre Mignard, María Ángeles Moreno, Rubén Sancho, Kosana Suvocarev, María Pilar Vallés, Nery Zapata."Sitio web" de nueva creación y conmemorativo del 75 Aniversario de la EEAD-CSIC que contiene: 1) Foto esférica de su personal en activo; 2) Recopilación de sus hitos históricos más destacados, en orden cronológico; 3) Un vídeo con participación de su personal y muestra de algunas de sus instalaciones; 4) Un mapa con la distribución geográfica de los egresado del Instituto; 5) Algunas fotos, destacando las tomadas a su personal en las celebraciones del 25 y 50 Aniversarios de la EEAD-CSIC.Presentado durante la "Jornada. 75 Aniversario EEAD-CSIC (Zaragoza, Patio de la Infanta. 30 octubre 2019)".Financiación: CSIC, Vicepresidencia Adjunta de Organización y Cultura Científica.N