¿Qué sabemos sobre las turberas peruanas?

Proyecto Mainstreaming Wetlands into the Climate Agenda: A multi-level approach (SWAMP-II). Subproyecto A Global Comparative Study for achieving effective, efficient and equitable REDD+ results.El Perú es uno de los países del trópico más ricos en turberas. Cuenta con ellas en sus tres regiones, con una preponderancia marcada en la Amazonía. Sus turberas proveen importantes servicios ecosistémicos, como el almacenamiento de inmensas cantidades de carbono, la fijación de dióxido de carbono, una biodiversidad única, la regulación hídrica a nivel local y regional, y el suministro de medios de subsistencia y valores culturales para las poblaciones locales. Las turberas del país están siendo deterioradas por actividades antropogénicas que incluyen el desarrollo de infraestructura y la extracción de recursos (p. ej., petróleo, minerales), y usos o prácticas no sostenibles de intensidad variable (p. ej., sobrepastoreo, extracción de turba, tala de palmeras, sobrecaza) que las amenazan e incrementan su vulnerabilidad. De igual manera, los cambios climáticos comprometen su estabilidad. El marco normativo peruano incluye normas e instrumentos para una gestión sostenible de los humedales, pero falta desarrollar regulaciones específicas para las turberas. Entre los avances recientes está la elaboración de una definición normativa nacional del término “turbera”; sin embargo, aún se requiere su inclusión explícita en políticas relativas al cambio climático, como REDD+ y las Contribuciones Nacionalmente Determinadas (NDC, por sus siglas en inglés). Existe una falta fundamental de investigación científica sobre las turberas peruanas. En particular, se requiere cartografiarlas, inventariarlas y caracterizar sus propiedades ecológicas y sus valores económicos y sociales. También es esencial identificar y revalorar los conocimientos que las comunidades indígenas ponen en práctica para gestionarlas de manera sostenible. Las oportunidades para la conservación y buena gestión de estos ecosistemas claves son diversas e incluyen, por ejemplo, la consolidación de los mecanismos de pago por servicios ecosistémicos, la implementación de planes de manejo sostenible de recursos por las poblaciones locales, la extensión de las áreas naturales protegidas (ANP) y el reconocimiento de los derechos de tenencia de las comunidades.United States Agency for International Development (USAID); Norwegian Agency for Development Cooperation (NORAD)Revisión por pares

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease