RESUMO
Rates of cardiovascular mortality and morbidity in Russia have been among the highest in Europe. A comprehensive health system improvement program targeting better diagnosis and control of hypertension was undertaken in the Yaroslavl Region of Russia. This initiative was a joint program between clinicians, the Department of Health and Pharmacy of the Yaroslavl Region, and Novartis Pharma LLC. From 2011 to 2014, the blood pressure control rate improved substantially (94% relative improvement), the percentage of patients with a systolic blood pressure ≥180 mm Hg decreased (from 10% to 5%), and there was a reduction in stroke incidence rate from 4.6 to 3.7 per 1000 population. During this same period, significant changes were made to the way hypertension was diagnosed and treated across all regional government polyclinics, and the use of antihypertensive therapies increased.
Assuntos
Anti-Hipertensivos/uso terapêutico , Promoção da Saúde/organização & administração , Hipertensão/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Determinação da Pressão Arterial , Estudos Transversais , Gerenciamento Clínico , Diagnóstico Precoce , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Incidência , Masculino , Pessoa de Meia-Idade , Federação Russa/epidemiologia , Resultado do TratamentoRESUMO
During DNA replication, nucleosomes are rapidly assembled on newly synthesized DNA to restore chromatin organization. Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-like kinases (TLKs). Here, we identify TLK phosphorylation sites by mass spectrometry and dissect how phosphorylation has an impact on human Asf1 function. The divergent C-terminal tail of Asf1a is phosphorylated at several sites, and this is required for timely progression through S phase. Consistent with this, biochemical analysis of wild-type and phospho-mimetic Asf1a shows that phosphorylation enhances binding to histones and the downstream chaperones CAF-1 and HIRA. Moreover, we find that TLK phosphorylation of Asf1a is induced in cells experiencing deficiency of new histones and that TLK interaction with Asf1a involves its histone-binding pocket. We thus propose that TLK signalling promotes histone supply in S phase by targeting histone-free Asf1 and stimulating its ability to shuttle histones to sites of chromatin assembly.
