Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Food, Nutrition and Agrobiodiversity Under Global Climate Change

Available evidence and predictions suggest overall negative effects on agricultural production as a result of climate change, especially when more food is required by a growing population. Information on the effects of global warming on pests and pathogens affecting agricultural crops is limited, though crop–pest models could offer means to predict changes in pest dynamics, and help design sound plant health management practices. Host-plant resistance should continue to receive high priority as global warming may favor emergence of new pest epidemics. There is increased risk, due to climate change, to food and feed contaminated by mycotoxin-producing fungi. Mycotoxin biosynthesis gene-specific microarray is being used to identify food-born fungi and associated mycotoxins, and investigate the influence of environmental parameters and their interactions for control of mycotoxin in food crops. Some crop wild relatives are threatened plant species and efforts should be made for their in situ conservation to ensure evolution of new variants, which may contribute to addressing new challenges to agricultural production. There should be more emphasis on germplasm enhancement to develop intermediate products with specific characteristics to support plant breeding. Abiotic stress response is routinely dissected to component physiological traits. Use of transgene(s) has led to the development of transgenic events, which could provide enhanced adaptation to abiotic stresses that are exacerbated by climate change. Global warming is also associated with declining nutritional quality of food crops. Micronutrient-dense cultivars have been released in selected areas of the developing world, while various nutritionally enhanced lines are in the release pipeline. The high-throughput phenomic platforms are allowing researchers to accurately measure plant growth and development, analyze nutritional traits, and assess response to stresses on large sets of individuals. Analogs for tomorrow’s agriculture offer a virtual natural laboratory to innovate and test technological options to develop climate resilience production systems. Increased use of agrobiodiversity is crucial to coping with adverse impacts of global warming on food and feed production and quality. No one solution will suffice to adapt to climate change and its variability. Suits of technological innovations, including climate-resilient crop cultivars, will be needed to feed 9 billion people who will be living in the Earth by the middle of the twenty-first century

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.status: publishe

Física I - MA466 - 202102

Descripción: Es el primer curso de la línea de Física que desarrolla los principios fundamentales de la mecánica (cinemática, dinámica, leyes de conservación, oscilaciones y elasticidad) basada en el cálculo, que son esenciales para el estudio de todas las Ciencias Naturales, su aplicación en la vida cotidiana y la tecnología. Propósito: El curso de Física I desarrolla la competencia de razonamiento cuantitativo en el nivel 2, Está dirigido a estudiantes del tercer ciclo para las carreras de Ingeniería Civil, Electrónica, Industrial, Mecatrónica, Gestión Minera, Sistemas de Información y Software y a estudiantes del cuarto ciclo para las carreras de Ingeniería de Gestión Empresarial y Ciencias de la Computación, cuenta con pre-requisitos como nivelación de Física y Cálculo I. Este curso brinda una base conceptual sólida de la mecánica, que le permite continuar con el curso de Física II de la Facultad de Ingeniería

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN