176 research outputs found

    Structure and function of a spectrin-like regulator of bacterial cytokinesis

    Get PDF
    © 2014 Macmillan Publishers Limited. All rights reserved. Bacterial cell division is facilitated by a molecular machine - the divisome - that assembles at mid-cell in dividing cells. The formation of the cytokinetic Z-ring by the tubulin homologue FtsZ is regulated by several factors, including the divisome component EzrA. Here we describe the structure of the 60-kDa cytoplasmic domain of EzrA, which comprises five linear repeats of an unusual triple helical bundle. The EzrA structure is bent into a semicircle, providing the protein with the potential to interact at both N- and C-termini with adjacent membrane-bound divisome components. We also identify at least two binding sites for FtsZ on EzrA and map regions of EzrA that are responsible for regulating FtsZ assembly. The individual repeats, and their linear organization, are homologous to the spectrin proteins that connect actin filaments to the membrane in eukaryotes, and we thus propose that EzrA is the founding member of the bacterial spectrin family

    Somatic p16INK4a loss accelerates melanomagenesis

    Get PDF
    Loss of p16INK4a–RB and ARF–p53 tumor suppressor pathways, as well as activation of RAS–RAF signaling, is seen in a majority of human melanomas. Although heterozygous germline mutations of p16INK4a are associated with familial melanoma, most melanomas result from somatic genetic events: often p16INK4a loss and N-RAS or B-RAF mutational activation, with a minority possessing alternative genetic alterations such as activating mutations in K-RAS and/or p53 inactivation. To generate a murine model of melanoma featuring some of these somatic genetic events, we engineered a novel conditional p16INK4a-null allele and combined this allele with a melanocyte-specific, inducible CRE recombinase strain, a conditional p53-null allele and a loxP-stop-loxP activatable oncogenic K-Ras allele. We found potent synergy between melanocyte-specific activation of K-Ras and loss of p16INK4a and/or p53 in melanomagenesis. Mice harboring melanocyte-specific activated K-Ras and loss of p16INK4a and/or p53 developed invasive, unpigmented and nonmetastatic melanomas with short latency and high penetrance. In addition, the capacity of these somatic genetic events to rapidly induce melanomas in adult mice suggests that melanocytes remain susceptible to transformation throughout adulthood

    Socioeconomic status and health in the second half of life: findings from the German Ageing Survey

    Get PDF
    This study examined social inequalities in health in the second half of life. Data for empirical analyses came from the second wave of the German Ageing Survey (DEAS), an ongoing population-based, representative study of community dwelling persons living in Germany, aged 40–85 years (N = 2,787). Three different indicators for socioeconomic status (SES; education, income, financial assets as an indicator for wealth) and health (physical, functional and subjective health) were employed. It could be shown that SES was related to health in the second half of life: Less advantaged persons between 40 and 85 years of age had worse health than more advantaged persons. Age gradients varied between status indicators and health dimensions, but in general social inequalities in health were rather stable or increasing over age. The latter was observed for wealth-related absolute inequalities in physical and functional health. Only income-related differences in subjective health decreased at higher ages. The amount of social inequality in health as well as its development over age did not vary by gender and place of residence (East or West Germany). These results suggest that, in Germany, the influence of SES on health remains important throughout the second half of life

    Diseño de un manual de detección de ansiedad social en adolescentes

    Get PDF
    Curso de Especial InterésEl objetivo de este trabajo de grado ha sido diseñar un manual dirigido a padres y docentes, en el que se establezcan técnicas de detección de ansiedad social en adolescentes; el diseño de este manual permite un aprendizaje significativo de una forma diferente, en un lenguaje claro y preciso, en formato digital para un fácil acceso y portabilidad del material, logrando de esta forma, que la población adolescente sea beneficiada a través de las acciones que se emprenderán por parte de los padres de familia, docentes y profesionales.142 p.RESUMEN 1. JUSTIFICACIÓN 2. OBJETIVOS 3. ESTUDIO DEL MERCADO 4. PRESENTACIÓN DEL PRODUCTO 5. CLIENTES – SEGMENTACIÓN 6. COMPETENCIA 7. CANALES DE DISTRIBUCIÓN 8. RESULTADOS DEL ESTUDIO DE MERCADO 9. DISCUSIÓN DEL ESTUDIO DE MERCADO 10. PRESUPUESTO 11. RESULTADOS 12. CONCLUSIONES REFERENCIAS APÉNDICESPregradoPsicólog

    Recent Advances in Our Understanding of the Role of Meltwater in the Greenland Ice Sheet System

    Get PDF
    Nienow, Sole and Cowton’s Greenland research has been supported by a number of UK NERC research grants (NER/O/S/2003/00620; NE/F021399/1; NE/H024964/1; NE/K015249/1; NE/K014609/1) and Slater has been supported by a NERC PhD studentshipPurpose of the review:  This review discusses the role that meltwater plays within the Greenland ice sheet system. The ice sheet’s hydrology is important because it affects mass balance through its impact on meltwater runoff processes and ice dynamics. The review considers recent advances in our understanding of the storage and routing of water through the supraglacial, englacial, and subglacial components of the system and their implications for the ice sheet Recent findings:   There have been dramatic increases in surface meltwater generation and runoff since the early 1990s, both due to increased air temperatures and decreasing surface albedo. Processes in the subglacial drainage system have similarities to valley glaciers and in a warming climate, the efficiency of meltwater routing to the ice sheet margin is likely to increase. The behaviour of the subglacial drainage system appears to limit the impact of increased surface melt on annual rates of ice motion, in sections of the ice sheet that terminate on land, while the large volumes of meltwater routed subglacially deliver significant volumes of sediment and nutrients to downstream ecosystems. Summary:  Considerable advances have been made recently in our understanding of Greenland ice sheet hydrology and its wider influences. Nevertheless, critical gaps persist both in our understanding of hydrology-dynamics coupling, notably at tidewater glaciers, and in runoff processes which ensure that projecting Greenland’s future mass balance remains challenging.Publisher PDFPeer reviewe

    Deontic Justice and Organizational Neuroscience

    Full text link
    corecore