19 research outputs found

    Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis.

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    Funder: Akademie Věd České Republiky; Grant(s): RVO:67985823The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process were disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII, and cIV were missing in COX4I1 knock-out (KO) due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labeling of mitochondrial DNA (mtDNA)-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates, indicating that cI biogenesis, rather than stability, was affected. We propose that attenuation of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms, which may impair biogenesis of cI

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

    The Use of Histological Techniques to Study the Reproductive Biology of the Hermaphroditic Mediterranean Fishes Coris julis, Serranus scriba, and Diplodus annularis

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    15 páginas, 11 figuras, 3 tablasThe usefulness and importance of histological techniques in reproductive studies have been widely discussed for gonochoristic fish species. In the case of hermaphroditic fishes, histology is a particularly important tool for the proper identification of sexual pattern (i.e., sequential, simultaneous, or nonfunctional hermaphroditism).We used a histological approach to describe hermaphroditism, dynamics of follicle development, and spawning patterns in three species from the northwestern Mediterranean Sea (Balearic Islands, Spain): the Mediterranean rainbow wrasse Coris julis (sequential hermaphrodite), painted comber Serranus scriba (simultaneous hermaphrodite), and annular sea bream Diplodus annularis (nonfunctional hermaphrodite). Development of secondary growth follicles was asynchronous in all three species, and similar peaks in spawning activity occurred between May and July. However, notable differences in sexual cycle and egg production were found. For the painted comber, hydrated follicles were present in ovarian tissue almost every day during the peak of the spawning season, suggesting daily spawning and increasing the chances of autofertilization unless a mechanism to avoid this action is present in this species. Intersexual Mediterranean rainbow wrasses were identified, and the size and age at sex change were estimated to be 132 mm total length and 4 years, respectively. Previous investigators have concluded that the annular sea bream is a protandric hermaphrodite, but our results indicate nonfunctional hermaphroditism. These three species are of little commercial interest and are considered to be bycatch by the artisanal fleet, but they are vulnerable to the impacts of some recreational angling activities. Currently, no specific management plan has been developed for these species. We address the importance of describing sexual pattern and its implications for future conservation efforts.Ministerio Español de Educación y Ciencia (CTM2005–00283/MAR). COST Action (FA0601)Peer reviewe

    Salud en red

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    Se describe el proyecto llevado a cabo en varios centros educativos de primaria y secundaria cuyo objetivo principal era que los alumnos adquirieran hábitos y costumbres saludables para su bienestar físico-mental y el de su entorno social. El proyecto se desarrolló sobre seis áreas temáticas: nutrición, consumo responsable y solidario, educación en igualdad de género entre hombres y mujeres, prevención del cáncer, salud y discapacidad, educación para la salud y salud medioambiental. Se detallan los objetivos de cada área, las actividades realizadas y un breve análisis de los resultados obtenidos.ExtremaduraConsejería de Sanidad y Dependencia; Calle Adriano, 4; 06800 Mérida (Badajoz); Tel. +34924004197; Fax +34924004122; [email protected]
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