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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events. In addition, it regulates cell-to-cell adhesion, AMPK signaling, autophagy and apoptosis in different cell types. In this study we examined the expression pattern of α-SNAP in ovarian tissue and the consequences of α-SNAP (M105I) mutation (hyh mutation) in folliculogenesis and female fertility. Our results showed that α-SNAP protein is highly expressed in GCs and its expression is modulated by gonadotropin stimuli. On the other hand, α-SNAP-mutant mice show a reduction in α-SNAP protein levels. Moreover, increased apoptosis of GCs and follicular atresia, reduced ovulation rate, and a dramatic decline in fertility is observed in α-SNAP-mutant females. In conclusion, α-SNAP plays a critical role in the balance between follicular development and atresia. Consequently, a reduction in its expression/function (M105I mutation) causes early depletion of ovarian follicles and female subfertility.
Asunto(s)
Fertilidad/fisiología , Regulación de la Expresión Génica , Células de la Granulosa/metabolismo , Transducción de Señal/fisiología , Proteínas Solubles de Unión al Factor Sensible a la N-Etilmaleimida/biosíntesis , Animales , Apoptosis , Adhesión Celular/fisiología , Femenino , Atresia Folicular/genética , Atresia Folicular/metabolismo , Células de la Granulosa/citología , Fusión de Membrana/fisiología , Ratones , Ratones Mutantes , Mutación , Proteínas Solubles de Unión al Factor Sensible a la N-Etilmaleimida/genéticaRESUMEN
Over the years many prevention management practices have been implemented to prevent and mitigate accidents at the construction site. However, there is little evidence of the effectiveness of individual or combined practices used by companies to manage occupational health and safety issues. The authors selected a sample of 1180 construction firms and 221 individual practices applied in these companies to analyze their effectiveness reducing injury rates over a period of four years in Chile. Different methods were used to study this massive database including: visual analyses of graphical information, statistical analyses and classification techniques. Results showed that practices related to safety incentives and rewards are the most effective from the accident rate viewpoint, even though they are seldom used by companies; on the other hand, practices related to accidents and incidents investigation had a slight negative impact on the accident rate because they are frequently used as a reactive measure. In general, the higher the percentage of prevention practices implemented in a strategy, the lower the accident rate. However, the analysis of the combined effect of prevention practices indicated that the choice of the right combination of practices was more important than just the number of practices implemented.
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Accidentes de Trabajo/prevención & control , Industria de la Construcción/normas , Traumatismos Ocupacionales/prevención & control , Administración de la Seguridad/métodos , Accidentes de Trabajo/estadística & datos numéricos , Chile/epidemiología , Industria de la Construcción/estadística & datos numéricos , Bases de Datos Factuales , Humanos , Salud Laboral/normas , Salud Laboral/estadística & datos numéricos , Traumatismos Ocupacionales/epidemiología , Administración de la Seguridad/normas , Administración de la Seguridad/estadística & datos numéricosRESUMEN
Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes.
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Neoplasias de la Mama/patología , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , 1-Fosfatidilinositol 4-Quinasa/metabolismo , Animales , Línea Celular Tumoral , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/biosíntesis , Femenino , Células HeLa , Humanos , Células MCF-7 , Ratones , Trasplante de Neoplasias , Fosfatos de Fosfatidilinositol/metabolismo , Ratas , Trasplante Heterólogo , Red trans-Golgi/metabolismoRESUMEN
RESUMEN Se presenta el caso de un paciente, sin comorbilidades, que se interna por cuadro de infarto agudo de miocardio a repetición. En todas las ocasiones presentó dolor precordial típico y elevación de troponinas. En su primera cinecoronariografía no se encontraron lesiones angiográficas. Meses después vuelve a internarse por cuadro similar, se repite cinecoronariografía que informa nuevamente vasos coronarios sin lesiones angiográficas pero como hallazgo describe una imagen compatible con un puente muscular a nivel del tercio medio de la arteria descendente anterior, con efecto compresivo durante las sístoles y como responsable de las isquemias del miocardio. Finalmente se concluye como un infarto agudo de miocardio tipo 2 y se instaura tratamiento médico específico, respondiendo favorablemente.
ABSTRACT We present the case of a patient, without comorbidities, who is hospitalized due to recurrent acute myocardial infarction. On all occasions he presented typical precordial pain and elevated troponins. In his first cinecoronariography no angiographic lesions were found. Months later, he returned to hospital for a similar case, cinecoronariography is repeated that again reports coronary vessels without angiographic lesions but as a finding describes an image compatible with a muscular bridge at the level of the middle third of the anterior descending artery, with compressive effect during systoles and responsible for the myocardial ischemia. Finally, it is concluded as an acute type 2 myocardial infarction and specific medical treatment is established, responding favorably.
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La endocarditis trombótica no bacteriana (ETNB) se define como la presencia de trombos estériles sobre las válvulas cardiacas, corresponden a agregados de plaquetas y fibrina no infectados asociados a estados de hipercoagulabilidad como las neoplasias malignas, en donde se denomina también endocarditis marántica. Se presenta el caso de un paciente con historia de síndrome febril prolongado al que se le inició tratamiento antibiótico por una endocarditis infecciosa (EI) por presentar una imagen compatible con vegetación en el ecocardiograma transtorácico. Sin embargo, el paciente persistió febril y sin mejoría clínica, hasta que la biopsia de un ganglio cervical diagnosticó un linfoma de Hodgkin mejorando posteriormente con el tratamiento hemato específico(AU)
Non-bacterial thrombotic endocarditis (NBTE) is defined as the presence of sterile thrombi on the heart valves, correspond to non-infected platelet and fibrin aggregates associated with hypercoagulable states such as malignant neoplasms, which is also called Marantic Endocarditis. We present the case of a patient with a history of prolonged febrile syndrome who underwent antibiotic treatment for an Infective Endocarditis (EI) due to a compatible image with vegetation in the transthoracic echocardiogram. However, the patient persisted feverish and without clinical improvement, until the biopsy of a cervical ganglion diagnosed a Hodgkin lymphoma, improving later with the specific hemato treatment(AU)