41 research outputs found

    The middle-southern Adriatic basin in February 1999: the chemical and physical characteristics of the water column.

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    In the Southern Adriatic depression nitrogen and phosphorous salts are concentrated in the bottom water. The Redfield ratio, same 29, is higher at Pomo and D transect, mostly on the bottom, because phosphorous is limiting and nitrogen is abundant. Northern waters influence this southern area, together with surface and intermediate waters coming from Ionian sea, and western shelf waters which tend to sink to the bottom. Key-words: Adriatic Sea, thermohaline characteristics, nutrient salts, Redfield rati

    Anatomically and functionally distinct lung mesenchymal populations marked by Lgr5 and Lgr6

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    The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6+ cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6+ cells impairs airway injury repair in vivo. Distinct Lgr5+ cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung.This work was supported by (J.-H.L. and J.C.) Wellcome Trust and the Royal Society (107633/Z/15/Z), European Research Council Starting Grant (679411), and the Cambridge Stem Cell Institute Core grant (07922/Z/11/Z) from Wellcome Trust and Medical Research Council; (J.-H.L.) the Hope Funds for Cancer Research; (M.P.) American Lung Association (400553); (A.R.) Howard Hughes Medical Institute, the Klarman Cell Observatory, and NCI grant 1U24CA180922; (A.R., T.T., and T.J.) the Koch Institute Core grant P30-CA14051 from the NCI; (T.T.) the National Cancer InstituteK99 CA187317, the Sigrid Juselius Foundation, the Hope Funds for Cancer Research; (T.J.) a Howard Hughes Medical Institute Investigator, a David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar; and (C.F.K.) R01 HL090136, R01 HL132266, R01 HL125821, U01 HL100402, Harvard Stem Cell Institute, Alfred and Gilda Slifka, Gail and Adam Slifka, and the CFMS Fund

    El uso de glucocorticoides en neumonía grave adquirida de la comunidad

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    La neumonía es la inflamación del parénquima pulmonar debida a un agente infeccioso.Cuando afecta a la población no ingresada en un hospital, se denomina neumonía adquirida en la comunidad(NAC). La NAC grave suele representar entre el 3 y 18% de las NAC hospitalizadas con una mortalidadentre el 21 y 54%. Para evaluar la gravedad de la NAC se utilizan los criterios PSI (Pneumonia severityIndex). Los corticoesteroides son hormonas esteroideas, participan en diferentes procesos regulando lainflamación, el sistema inmunitario, así como la respuesta del organismo al estrés, etc. Los corticoidessintéticos y semisintéticos se utilizan en numerosos procesos patológicos.METODOLOGÍA: Desde la exposición de un escenario clínico, se planteó una pregunta estructurada paraluego realizar una búsqueda bibliográfica, con el objetivo de dar respuesta a la pregunta sobre si el uso decorticoterapia adyuvante en pacientes con NAC grave disminuye la mortalidad y la necesidad de asistenciarespiratoria mecánica.Se realizó una búsqueda en PubMed y se seleccionó el artículo: “Efficacy and safety of glucocorticoids inthe treatment of severe community-acquired pneumonia”ANALISIS DEL ARTICULO: Se realizó un análisis definiendo los valores de riesgo absoluto, riesgorelativo y el número necesario a tratar del grupo problema y grupo control tomando en cuenta las variablesmortalidad y necesidad de asistencia respiratoria mecánica. Por otro lado, se determinó el odds ratio con surespectivo intervalo de confianza del 95%.RECOMENDACIÓN FINAL: se recomienda el uso de corticoterapia adyuvante como tratamiento contrala NAC grave

    Candida albicans repetitive elements display epigenetic diversity and plasticity

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    Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation

    \u3cem\u3eLkb1\u3c/em\u3e Inactivation Drives Lung Cancer Lineage Switching Governed by Polycomb Repressive Complex 2

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    Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours

    Cell populations can use aneuploidy to survive telomerase insufficiency

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    Telomerase maintains ends of eukaryotic chromosomes, telomeres. Telomerase loss results in replicative senescence and a switch to recombination-dependent telomere maintenance. Telomerase insufficiency in humans leads to telomere syndromes associated with premature ageing and cancer predisposition. Here we use yeast to show that the survival of telomerase insufficiency differs from the survival of telomerase loss and occurs through aneuploidy. In yeast grown at elevated temperatures, telomerase activity becomes limiting: haploid cell populations senesce and generate aneuploid survivors—near diploids monosomic for chromosome VIII. This aneuploidy results in increased levels of the telomerase components TLC1, Est1 and Est3, and is accompanied by decreased abundance of ribosomal proteins. We propose that aneuploidy suppresses telomerase insufficiency through redistribution of cellular resources away from ribosome synthesis towards production of telomerase components and other non-ribosomal proteins. The aneuploidy-induced re-balance of the proteome via modulation of ribosome biogenesis may be a general adaptive response to overcome functional insufficiencies
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