Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Alterações morfofisiológicas de plantas jovens de Curatella americana L. submetidas ao sombreamento

Curatella americana, is the only representative of the genus Curatella found in Brazil. The species is regarded to have a high ecological importance value in the Brazilian Cerrado formations. Since plant species from this biome are under constant threat due to its degradation, studies aiming to elucidate the behavior of these species are important for future projects of land recovery. This study aimed to evaluate growth, development and gas exchange in C. americana saplings subjected to different shading levels. Ten samplings were subjected to two treatments: full sun and 76% shade, at 90 days after germination. At regular 60-day intervals, measurements of stem base height and diameter, and number of leaves, were taken. After 240 days from the beginning of the experiment, measurements of gas exchange (net photosynthesis, stomatal conductance, Ci/Ca ratio, and transpiration rate) were taken, and the content of photosynthetic pigments and stomatal density were determined. Plants under full sun showed higher development than plants under shading, presenting significantly higher values of number of leaves, stem base diameter, photosynthetic rate, stomatal conductance, transpiration rate, and Dickson Quality Index. Our results indicate that the species can be introduced along with pioneer species in land revegetation programs.Curatella americana, popularmente conhecida como lixeira, cajueiro-bravo ou sambaı́ba é o  único representante do gênero Curatella sp encontrado no Brasil, sendo uma espécie apontada como de alto valor de importância ecológica nas formações de Cerrado brasileiras. Considerando que cerca de 80% da área de Cerrado já sofreu alguma forma de modificação humana, e, portanto as espécies inseridas neste bioma estão sobre constante ameaça, estudos que busquem compreender os requerimentos destas espécies são importantes para futuros projetos de revegetação e recuperação de áreas. Diante deste fato e considerando que a luz é um fator determinante para o estabelecimento de uma espécie, foi conduzido o presente trabalho, que teve por objetivo avaliar o crescimento e desenvolvimento, bem como trocas gasosas de mudas de C. americana submetidas a diferentes níveis de sombreamento. Para tanto 10 mudas de C. americana foram submetidas a dois diferentes tratamentos, pleno sol e 76% de sombreamento, 90 dias após a germinação. Em intervalos regulares de 60 dias foram realizadas medidas de altura e diâmetro do coleto, bem como contagem do número de folhas e aos 240 dias após a instalação do experimento foram realizadas medidas de intercambio gasoso (taxa fotossintética líquida, condutância estomática, razão Ci/Ca e taxa transpiratória), bem como determinação do conteúdo de pigmentos fotossintéticos e densidade estomática. Plantas a pleno sol apresentaram melhor desenvolvimento que plantas sob sombreamento, apresentando maior número de folhas e diâmetro do coleto, bem como, taxa fotossintética, condutância estomática, taxa transpiratória e Índice de Qualidade de Dickson (IQD) significativamente maior que plantas sombreadas.  Os resultados obtidos apontam que a espécie pode ser introduzida juntamente com as espécies pioneiras em projetos de revegetação de área

Pensamiento Novohispano 16 (pdf)

Los trabajos de investigación aquí compilados son plurales y revelan la perspectiva propia de quienes lo realizan. Están a disposición de los estudiosos y del público en general; razón por la que, en cada uno de ellos, incluimos el correo electrónico de su autor con la finalidad de abrir caminos de diálogo..UAEMe

Calificación, Valorización y Turismo. Aproximaciones al patrimonio agroalimentario

Libro científico sobre los espacios rurales y sus procesos de revalorización y resignificación en el siglo XXI.A partir de la segunda mitad del siglo XXI, los espacios rurales han transformado su estructura y funcionalidad de cara a las sociedades de consumo de la economía postindustrial. Al respecto, se ha generado un proceso de revalorización y resignificación del espacio rural que se centra en la atención sobre sus aspectos sociales, culturales, ecológicos, económicos y recreativos. En ese sentido, puede observarse la emergencia de algunas prácticas trasversales que se presentan como tendencias globales de la planificación, política y económica, de los espacios rurales y el aprovechamientos recreativos del capital natural y cultural del campo. La presente obra constituye un compendio de estudios de caso sobre los procesos de calificación, valorización y turistificación de ciertos recursos locales diferenciados, característicos del altiplano central mexicano. En este primer volumen se abordan los procesos de valorización y diversificación productiva de los recursos rurales, desde el enfoque turístico metodológico de los Sistemas Agroalimentarios Localizados (SIAL). Este es un trabajo colectivo que refleja los esfuerzos invertidos en los procesos de trasformación socioeconómica del espacio rural, gestados desde la Maestría en Agroindustria Rural, Desarrollo Territorial y Turismo Agroalimentario, de la Universidad Autónoma del Estado de México

El siglo XIX: Bolivia y América latina

Este libro es resultado del Primer Encuentro Internacional de Historia sobre "El Siglo XIX en Bolivia y América Latina", organizado por la Coordinadora de Historia y el Instituto Francés de Estudios Andinos (IFEA) el año 1994 en la ciudad de Sucre en homenaje postumo a Gunnar Mendoza. Dedicado al siglo XIX, por ser un período poco abordado en general por la historiografía de los últimos años, tuvo el propósito de analizar, con mayor profundidad y rigor, tanto las continuidades coloniales como las rupturas que lo caracterizaron. En la medida en que participaron bolivianos y bolivianistas de Europa y Estados Unidos, así como investigadores latinoamericanos de Argentina, Perú, Chile, Ecuador y Colombia, esperamos que este volumen que hoy presentamos constituya un aporte y una referencia para el análisis de esta época fundacional de los estados-naciones de América Latina

Comparison of 1-year outcome in patients with severe aorta stenosis treated conservatively or by aortic valve replacement or by percutaneous transcatheter aortic valve implantation (data from a multicenter Spanish registry)

The factors that influence decision making in severe aortic stenosis (AS) are unknown. Our aim was to assess, in patients with severe AS, the determinants of management and prognosis in a multicenter registry that enrolled all consecutive adults with severe AS during a 1-month period. One-year follow-up was obtained in all patients and included vital status and aortic valve intervention (aortic valve replacement [AVR] and transcatheter aortic valve implantation [TAVI]). A total of 726 patients were included, mean age was 77.3 ± 10.6 years, and 377 were women (51.8%). The most common management was conservative therapy in 468 (64.5%) followed by AVR in 199 (27.4%) and TAVI in 59 (8.1%). The strongest association with aortic valve intervention was patient management in a tertiary hospital with cardiac surgery (odds ratio 2.7, 95% confidence interval 1.8 to 4.1, p <0.001). The 2 main reasons to choose conservative management were the absence of significant symptoms (136% to 29.1%) and the presence of co-morbidity (128% to 27.4%). During 1-year follow-up, 132 patients died (18.2%). The main causes of death were heart failure (60% to 45.5%) and noncardiac diseases (46% to 34.9%). One-year survival for patients treated conservatively, with TAVI, and with AVR was 76.3%, 94.9%, and 92.5%, respectively, p <0.001. One-year survival of patients treated conservatively in the absence of significant symptoms was 97.1%. In conclusion, most patients with severe AS are treated conservatively. The outcome in asymptomatic patients managed conservatively was acceptable. Management in tertiary hospitals is associated with valve intervention. One-year survival was similar with both interventional strategies