Fission yeast Ags1 confers the essential septum strength needed for safe gradual cell abscission

[EN]Fungal cytokinesis requires the assembly of a dividing septum wall. In yeast, the septum has to be selectively digested during the critical cell separation process. Fission yeast cell wall alpha (1-3) glucan is essential, but nothing is known about its localization and function inthe cell wall or about cooperation between the alpha - and beta (1-3) glucan synthases Ags1 and Bgs for cell wall and septum assembly. Here, we generate a physiological Ags1-GFP variant and demonstrate a tight colocalization with Bgs1, suggesting a cooperation in the important early steps of septum construction. Moreover, we define the essential functions of alpha(1-3) glucan in septation and cell separation. We show that alpha (1-3) glucan is essential for both secondary septum formation and the primary septum structural strength needed to support the physical forces of the cell turgor pressure during cell separation. Consequently, the absence of Ags1 and therefore alpha(1-3)glucan generates a special and unique side-explosive cell separation due to an instantaneous primary septum tearing caused by the turgor pressure

Soil organic carbon stocks in native forest of Argentina: a useful surrogate for mitigation and conservation planning under climate variability

Background The nationally determined contribution (NDC) presented by Argentina within the framework of the Paris Agreement is aligned with the decisions made in the context of the United Nations Framework Convention on Climate Change (UNFCCC) on the reduction of emissions derived from deforestation and forest degradation, as well as forest carbon conservation (REDD+). In addition, climate change constitutes one of the greatest threats to forest biodiversity and ecosystem services. However, the soil organic carbon (SOC) stocks of native forests have not been incorporated into the Forest Reference Emission Levels calculations and for conservation planning under climate variability due to a lack of information. The objectives of this study were: (i) to model SOC stocks to 30 cm of native forests at a national scale using climatic, topographic and vegetation as predictor variables, and (ii) to relate SOC stocks with spatial–temporal remotely sensed indices to determine biodiversity conservation concerns due to threats from high inter‑annual climate variability. Methods We used 1040 forest soil samples (0–30 cm) to generate spatially explicit estimates of SOC native forests in Argentina at a spatial resolution of approximately 200 m. We selected 52 potential predictive environmental covariates, which represent key factors for the spatial distribution of SOC. All covariate maps were uploaded to the Google Earth Engine cloud‑based computing platform for subsequent modelling. To determine the biodiversity threats from high inter‑annual climate variability, we employed the spatial–temporal satellite‑derived indices based on Enhanced Vegetation Index (EVI) and land surface temperature (LST) images from Landsat imagery. Results SOC model (0–30 cm depth) prediction accounted for 69% of the variation of this soil property across the whole native forest coverage in Argentina. Total mean SOC stock reached 2.81 Pg C (2.71–2.84 Pg C with a probability of 90%) for a total area of 460,790 km2, where Chaco forests represented 58.4% of total SOC stored, followed by Andean Patagonian forests (16.7%) and Espinal forests (10.0%). SOC stock model was fitted as a function of regional climate, which greatly influenced forest ecosystems, including precipitation (annual mean precipitation and precipitation of warmest quarter) and temperature (day land surface temperature, seasonality, maximum temperature of warmest month, month of maximum temperature, night land surface temperature, and monthly minimum temperature). Biodiversity was influenced by the SOC levels and the forest regions. Conclusions In the framework of the Kyoto Protocol and REDD+, information derived in the present work from the estimate of SOC in native forests can be incorporated into the annual National Inventory Report of Argentina to assist forest management proposals. It also gives insight into how native forests can be more resilient to reduce the impact of biodiversity loss.EEA Santa CruzFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Gaitan, Juan José. Universidad Nacional de Luján. Buenos Aires; Argentina.Fil: Gaitan, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Mastrangelo, Matias Enrique. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Nosetto, Marcelo Daniel. Universidad Nacional de San Luis. Instituto de Matemática Aplicada San Luis. Grupo de Estudios Ambientales; Argentina.Fil: Nosetto, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Villagra, Pablo Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Villagra, Pablo Eugenio. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Balducci, Ezequiel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Yuto; Argentina.Fil: Pinazo, Martín Alcides. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; Argentina.Fil: Eclesia, Roxana Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná; Argentina.Fil: Von Wallis, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; Argentina.Fil: Villarino, Sebastián. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Villarino, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Alaggia, Francisco Guillermo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Alaggia, Francisco Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Gonzalez-Polo, Marina. Universidad Nacional del Comahue; Argentina.Fil: Gonzalez-Polo, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. INIBIOMA; Argentina.Fil: Manrique, Silvana M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Energía No Convencional. CCT Salta‑Jujuy; Argentina.Fil: Meglioli, Pablo A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Meglioli, Pablo A. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Rodríguez‑Souilla, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina.Fil: Mónaco, Martín H. Ministerio de Ambiente y Desarrollo Sostenible. Dirección Nacional de Bosques; Argentina.Fil: Chaves, Jimena Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina.Fil: Medina, Ariel. Ministerio de Ambiente y Desarrollo Sostenible. Dirección Nacional de Bosques; Argentina.Fil: Gasparri, Ignacio. Universidad Nacional de Tucumán. Instituto de Ecología Regional; Argentina.Fil: Gasparri, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Alvarez Arnesi, Eugenio. Universidad Nacional de Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario; Argentina.Fil: Alvarez Arnesi, Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina.Fil: Barral, María Paula. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Barral, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Von Müller, Axel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Esquel Argentina.Fil: Pahr, Norberto Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; Argentina.Fil: Uribe Echevarría, Josefina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Quimilí; Argentina.Fil: Fernandez, Pedro Sebastian. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; Argentina.Fil: Fernandez, Pedro Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ecología Regional; Argentina.Fil: Morsucci, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Morsucci, Marina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Lopez, Dardo Ruben. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Lopez, Dardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Cellini, Juan Manuel. Universidad Nacional de la Plata (UNLP). Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Maderas; Argentina.Fil: Alvarez, Leandro M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Alvarez, Leandro M. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Barberis, Ignacio Martín. Universidad Nacional de Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina.Fil: Barberis, Ignacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina.Fil: Colomb, Hernán Pablo. Ministerio de Ambiente y Desarrollo Sostenible. Dirección Nacional de Bosques; Argentina.Fil: Colomb, Hernán. Administración de Parques Nacionales (APN). Parque Nacional Los Alerces; Argentina.Fil: La Manna, Ludmila. Universidad Nacional de la Patagonia San Juan Bosco. Centro de Estudios Ambientales Integrados (CEAI); Argentina.Fil: La Manna, Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Barbaro, Sebastian Ernesto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul; Argentina.Fil: Blundo, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ecología Regional; Argentina.Fil: Blundo, Cecilia. Universidad Nacional de Tucumán. Tucumán; Argentina.Fil: Sirimarco, Marina Ximena. Universidad Nacional de Mar del Plata. Grupo de Estudio de Agroecosistemas y Paisajes Rurales (GEAP); Argentina.Fil: Sirimarco, Marina Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Cavallero, Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Zalazar, Gualberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales (IANIGLA); Argentina.Fil: Zalazar, Gualberto. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Martínez Pastur, Guillermo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics