Environmental and climatic proxies for the Cañadón Asfalto and Neuquén basins (Patagonia, Argentina): review of middle to upper jurassic continental and near coastal sequences

In this review, we include several proxies (sedimentology, palynology, invertebrates) from the Cañadón Asfalto and Neuquén basins, to infer the environments and regional climatic context during the Middle to Late Jurassic of Patagonia. In central Patagonia, early in the Middle Jurassic, and associated with a magmatic arc, began the sedimentary fi lling of Jurassic continental sub-basins in the Cañadón Asfalto Basin. Lacustrine and fl uvio-deltaic sediments, bearing a continental Middle Jurassic palynobiota, correspond to the Las Chacritas Member, while the sediments and palynobiota from the Late Jurassic Puesto Almada Member (both in the Cañadón Asfalto Formation) indicate a palustrine wetland subenvironment immersed within an arid macroenvironment. Paleoinvertebrates (conchostracans and sponges) of this formation suggest wet-dry cycles in the water bodies they inhabited. The sedimentological information together with the continental and coastal palynomorph assemblages of the back arc Neuquén Basin, allowed distinguishing a complete regressive-transgressive sequence for the Middle Jurassic Lajas Formation. For the Upper Jurassic in this basin, the thick gypsum and anhydrite deposits of the evaporitic coastal Auquilco Formation correlate with extended deposits of eolian sandstones corresponding to the Botucatú paleodesert, and a saltmarsh environment is inferred from the palynofl ora. The palynologic associations from both basins indicate a regional warm climate with seasonal aridity. Climatic conditions would have been drier in the continental interior (Cañadón Asfalto Basin), with strongly seasonally distributed temperatures, and moister in the western coast of the continent (Neuquén Basin), during the marine transgressions.Na presente revisão foram incluídos vários proxies (sedimentologia, palinologia, invertebrados), das bacias de Cañadón Asfalto e Neuquén, para inferir o contexto climático regional e ambiental durante o Jurássico Médio e Superior da Patagônia. Na região central da Patagônia, no início do Jurássico Médio, e associado a um arco magmático, começou o preenchimento sedimentar de sub-bacias continentais jurássicas na bacia Cañadón Asfalto. Os sedimentos flúvio-deitaico e lacustres, tendo uma palinobiota continental do Jurássico Médio correspondente ao Membro Las Chacritas, enquanto os sedimentos e a palinobiota do Jurássico Superior do Membro Puesto Almada (ambos na Formação Cañadón Asfalto) indicam um subambiente palustre úmido imerso em um macroambiente árido. Os paleoinvertebrados (conchostráceos e esponjas) desta formação sugerem ciclos úmidos-secos nos corpos de água por eles habitados. A informação sedimentológica juntamente com as assembleias de palinomorfos continentais e costeiros do “back arc” da bacia Neuquén permitiu distinguir uma sequência completa regressiva-transgressiva para o Jurássico Médio da Formação Lajas. Para o Jurássico Superior, os depósitos de anidrita e gesso espessos da Formação Auquilco costeira evaporítica correlacionam-se com depósitos extensos de arenitos eólicos correspondentes ao paleodeserto Botucatu. Um ambiente “saltmarsh” é inferido a partir da palinoflora. As associações palinológicas de ambas as bacias indicam um clima regional quente com aridez sazonal. As condições climáticas teriam sido mais secas no interior continental (bacia Cañadón Asfalto), com temperaturas fortemente distribuídas de forma sazonal, e úmidas na costa ocidental do continente (bacia de Neuquén), durante as transgressões marinhas.Fil: Volkheimer, Wolfang. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Quattrocchio, Mirta Elena. Universidad Nacional del Sur. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabaleri, Nora Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotopica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Narvaez, Paula Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Rosenfeld, U.. Westfälische Wilhelms-universität Münster; AlemaniaFil: Scafati, Laura Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Melendi, Daniel Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; Argentin

Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase

Ocular neovascularisation is a pathological hallmark of some forms of debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenic pathways other than, or in combination to VEGF, may lead to more effective and safer inhibitors of intraocular angiogenesis. In a small chemical screen using zebrafish, we identify LY294002 as an effective and selective inhibitor of both developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection, significantly inhibits ocular angiogenesis without systemic side-effects and without diminishing visual function. Thus, targeting of PI3 kinase pathways has the potential to effectively and safely treat neovascularisation in eye disease

Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline

Abstract Background Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Results Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates in their genomic neighbourhood, anchor points emerge as sites of evolutionary innovation, showing enrichment for structural variant (SV) breakpoints and a peak of SNVs at focal CTCF sites within the anchor points. Both CTCF-bound and non-CTCF anchor points harbour an excess of SV breakpoints in multiple tumour types and are prone to double-strand breaks in cell lines. Common fragile sites, which are hotspots for genome instability, also show elevated numbers of intersecting loop anchor points. Recurrently disrupted anchor points are enriched for genes with functions in cell cycle transitions and regions associated with predisposition to cancer. We also discover a novel class of CTCF-bound anchor points which overlap meiotic recombination hotspots and are enriched for the core PRDM9 binding motif, suggesting that the anchor points have been foci for diversity generated during recent human evolution. Conclusions We suggest that the unusual chromatin environment at loop anchor points underlies the elevated rates of variation observed, marking them as sites of regulatory importance but also genomic fragility

Sur, una revista en la tormenta : los años de formación: 1931-1944

Tesis (Doctor en Literatura Hispánica)--El Colegio de México, Centro de Estudios Linguísticos y Literarios, 200

Maintenance of the human memory T cell repertoire by subset and tissue site

Abstract Background Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity. Methods We analyzed the TCR repertoire of the major memory CD4+ and CD8+T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset, tissue, and individual were analyzed for clonal diversity, expansion and overlap between lineage, T cell subsets, and anatomic sites. TCR repertoires were further analyzed for TRBV gene usage and CDR3 edit distance. Results Across blood, lymphoid organs, and lungs, human memory, and effector CD8+T cells exhibit greater clonal expansion and distinct TRBV usage compared to CD4+T cell subsets. Extensive sharing of clones between tissues was observed for CD8+T cells; large clones specific to TEMRA cells were present in all sites, while TEM cells contained clones shared between sites and with TRM. For CD4+T cells, TEM clones exhibited the most sharing between sites, followed by TRM, while TCM clones were diverse with minimal sharing between sites and subsets. Within sites, TRM clones exhibited tissue-specific expansions, and maintained clonal diversity with age, compared to age-associated clonal expansions in circulating memory subsets. Edit distance analysis revealed tissue-specific biases in clonal similarity. Conclusions Our results show that the human memory T cell repertoire comprises clones which persist across sites and subsets, along with clones that are more restricted to certain subsets and/or tissue sites. We also provide evidence that the tissue plays a key role in maintaining memory T cells over age, bolstering the rationale for site-specific targeting of memory reservoirs in vaccines and immunotherapies