RESUMEN
Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor-transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis.
Asunto(s)
Cromatina , Leucemia , Humanos , Cromatina/genética , Linaje de la Célula/genética , Hematopoyesis/genética , Diferenciación Celular/genética , Factores de Transcripción/genéticaRESUMEN
On January 12, 2020, Taal volcano in Philippines erupted, 43 years after its previous eruption in 1977. This eruption was preceded by diffuse CO2 degassing precursory signals. Significant temporal variations in diffuse CO2 emission from Taal Main Crater Lake (TMLC) were observed across the ~ 12 years reaching high CO2 degassing rates in 2011 and 2017, with values typical of plume degassing volcanoes. In addition to these CO2 surveys at the TCML, soil CO2 efflux continuous monitoring was implemented at Taal volcano since 2016 and a clear increasing trend of the soil CO2 efflux in 2017 was observed. These geochemical observations are most simply explained by magma recharge to the system, and represent the earliest warning precursor signals to the January 2020 eruptive activity.
RESUMEN
OBJECTIVES: To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients. DESIGN: Controlled study comparing an intervention in a geriatric unit (GI) with usual care in two internal medicine services (UC). SETTING: University hospital in Madrid, Spain. PARTICIPANTS: Five hundred forty-two consecutive patients (170 GI, 372 UC), aged 70 and older, with any of the risk criteria for delirium (cognitive impairment, visual impairment, acute disease severity, dehydration). INTERVENTION: Educational measures and specific actions in seven risk areas (orientation, sensory impairment, sleep, mobilization, hydration, nutrition, drug use). Daily monitoring of adherence. MEASUREMENTS: Baseline characteristics, risk factors for delirium, and quality care indicators were analyzed. The primary endpoint was incidence of delirium assessed daily. The secondary endpoint was functional decline, defined as loss of independence in any of the activities of daily living. The intervention effect was evaluated using logistic regression analysis. RESULTS: Delirium affected 11.7% of the GI group and 18.5% of the UC group (P=.04). After adjustment for confounders, the intervention was associated with lower incidence of delirium (odds ratio=0.4, 95% confidence interval=0.24-0.77; P=.005). In the patients who experienced delirium, severity, length, and recurrence of episodes were similar in both groups. Adherence to the intervention protocols was 75.7%. The intervention reduced the rate of functional decline (45.5% in GI vs 56.3% in UC, P=.03) and improved other quality indicators (e.g., mobilization and physical restraints reduction). CONCLUSION: A multicomponent, nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients, improves quality of care, and can be implemented without additional resources in a public healthcare system.