Interpretation of the upper crust from potential field methods in the region of Payenia and Malargüe fold and trhust belt

Se llevó a cabo un estudio gravi-magnetométrico a escala cortical para caracterizar los depocentros andinos del borde noroeste de la Cuenca Neuquina, situados enla provincia geológica de Payenia. Para ello se efectuaron mediciones (2240 estaciones) tanto del campo gravitatorio como magnético, apoyadas en mediciones de GPS diferencial (DGPS), valores de campo que fueron sumados a la extensa base de datos con la que cuenta el Instituto Geofísico Sismológico Volponi (IGSV). Se incorporaron datos de relevamientos aeromagnéticos suministrados por YPF S.A para cubrir las zonas sin datos terrestres. Se prepararon modelos 2D y 3D de inversión gravimétrica, con énfasis en la resolución de estructuras ubicas al este de la sierra de Palauco. Un modelo 3D de tres capas, apoyado en densidades de afloramientos y en valores de densidad de un pozo de exploración, permitió identificar con buena resolución geométrica altos y bajos estructurales del basamento y una subcuenca no reportada hasta el presente, en el borde este de la faja plegada y corrida de Malargüe y que se acuña con los afloramientos del basamento cristalino del bloque de San Rafael. Se modeló una sección gravimétrica de detalle que brinda información 2D de la estructura del mismo, especialmente al este de la sierra de Palauco donde se observa una profundización del relleno sedimentario. El espesor de la cubierta volcánico-clástica de este depocentro presenta su máximo hacia el este acuñándose bajo el bloque San Rafael.Different geophysical techniques, such as the potential field methods, were applied to characterize Andean depocenters along the northwestern border of the Neuquén basin, in the Payenia geological province. Around of 2240 new Differential Global Positioning System (DGPS) values supported gravimetric and magnetometric measurements were complemented with over 10000 gravity values from several survey campaigns carried out by researchers from the Volponi Geophysics and Seismological Institute through the last three decades. Additionally digital data from aeromagnetic reports by Servicio Geológico Minero Argentino (SEGEMAR) were provided by YPF S.A. Gravimetric and magnetometric maps were constructed to study the upper crustal sources. 2D and 3D inversion gravimetric models were prepared integrating geologic and geophysical information, with an emphasis in the resolution of structures placed to the east of Palauco. The 3D model of crystalline basement based on the average density values from a local well played a key role in identifying structural highs and lows structures already studied by other authors as well as a sub basin not yet reported. The detailed profile gives information about the 2D depocenter structure, showing a deepening and filling which wedges into a raised basement block belonging to San Rafael block. The volcanic-clastic infill of the newly reported depocenter reaches a maximum thickness of up to 4000 meters.Fil: Anci Araniti, Sheila Anabel. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ruiz, Francisco. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; ArgentinaFil: Lince Klinger, Federico Gustavo. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leiva, Maria Flavia. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Hector Pedro Antonio. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acosta, Gemma. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events

Glutamate receptors are divided in two unrelated families: ionotropic (iGluR), driving synaptic transmission, and metabotropic (mGluR), which modulate synaptic strength. The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades. Here we report an exhaustive phylogenetic study of GluRs in metazoans. Importantly, we demonstrate that GluRs have followed different evolutionary histories in separated animal lineages. Our analysis reveals that the present organization of iGluRs into six classes does not capture the full complexity of their evolution. Instead, we propose an organization into four subfamilies and ten classes, four of which have never been previously described. Furthermore, we report a sister class to mGluR classes I-III, class IV. We show that many unreported proteins are expressed in the nervous system, and that new Epsilon receptors form functional ligand-gated ion channels. We propose an updated classification of glutamate receptors that includes our findings

Interpretation of major structures of payenia applying the gravimetric potential method

Por medio de la aplicación de los métodos potenciales se pudieron caracterizar los depocentros andinos del borde noroeste de la Cuenca Neuquina, situados en la provincia geológica de Payenia, facilitando el estudio de estructuras emplazadas a nivel cortical. Para ello se efectuaron mediciones gravimétricas apoyadas con diferencial GPS en modo posproceso para obtener las coordenadas de las estaciones (DGPS-700 estaciones), se recopilaron y controlaron más de 10000 valores de gravedad provenientes de distintas campañas relevados durante las últimas tres décadas, que forman parte de la base de datos del Instituto Geofísico Sismológico Volponi (IGSV). Se construyeron mapas gravimétricos que luego fueron filtrados con el objetivo de estudiar las fuentes ubicadas en la corteza superior. Consecuentemente se prepararó un modelo en 3D obtenido por inversión gravimétrica, integrando información geológica y geofísica disponible. El modelo 3D del espesor sedimentario tiene en cuenta variaciones laterales y verticales de la densidad obtenidas de afloramientos y de pozos de exploración de hidrocarburos. Esto permitió identificar altos y bajos estructurales estudiados en 2D por otros autores e identificar una subcuenca, no reportada hasta el presente, en el borde este de la faja plegada y corrida de Malargüe y que se acuña con los afloramientos del basamento cristalino del Bloque de San Rafael.The Andean depocenters in the northwestern border of the Neuquén basin, in the geologic province of Payenia, were characterized by means of the analyzed methods to support hydrocarbon exploration in the area. These techniques allowed studying the upper crust structures to perform oil exploration. Gravity measurements were effected and supported with GDPS (700 stations). More than 10,000 gravity values, which were provided from several campaigns over the last three decades and which constitute the database of the Geophysics and Seismological Institute “Volponi”, were also used and checked. Bouguer gravity anomalies were mapped and filtered to study the upper crust sources. We made a 3D model (by gravity inversion) integrating geological and geophysical data that emphasized the resolution of the structures placed in this area. The 3D model of the sedimentary thickness takes into account lateral and vertical density variations obtained from local wells. This model allowed identification in 2D of high and low structures studied by other authors as wellas a sub-basin, not reported up to now, found on the eastern edge of the fold and thrust belt of Malargüe that is wedged into a raised basement block belonging to the San Rafael blockFil: Anci Araniti, Sheila Anabel. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Ruiz, Francisco. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; ArgentinaFil: Lince Klinger, Federico Gustavo. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Leiva, Maria Flavia. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Sanchez, Marcos Ariel. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Alvarez Pontoriero, Orlando. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Garcia, Hector Pedro Antonio. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Acosta, Gemma. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto Geofísico Sismológico Volponi; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentin

drLumi: An open-source package to manage data, calibrate, and conduct quality control of multiplex bead-based immunoassays data analysis

Multiplex bead-based immunoassays are used to measure concentrations of several analytes simultaneously. These assays include control standard curves (SC) to reduce between-plate variability and normalize quantitation of analytes of biological samples. Suboptimal calibration might result in large random error and decreased number of samples with analyte concentrations within the limits of quantification. Suboptimal calibration may be a consequence of poor fitness of the functions used for the SC, the treatment of the background noise and the method used to estimate the limits of quantification. Currently assessment of fitness of curves is largely dependent on operator and that may add additional error. Moreover, there is no software to automate data managing and quality control. In this article we present a R package, drLumi, with functions for managing data, calibrating assays and performing quality control. To optimize the assay the package implements: i) three dose-response functions, ii) four approaches for treating background noise and iii) three methods for estimating limits of quantifications. Other implemented functions are focused on the quality control of the fitted standard curve: detection of outliers, estimation of the confidence or prediction interval, and estimation of summary statistics. With demonstration purpose, we apply the software to 30 cytokines, chemokines and growth factors measured in a multiplex bead-based immunoassay in a study aiming to measure correlates of risk or protection from malaria of the RTS,S malaria vaccine nested in the Phase 3 randomized controlled trial of this vaccine

A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID)

Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and is a considerable burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection-related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by increased bradykinin synthesis. Methods: ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding icatibant to the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RTPCR or antigen test <= 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated 4 or 5' on the WHO's clinical status scale, are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is 120 patients (60 per group) from 2 sites in Spain. Primary outcomes are the efficacy and safety of Icatibant. The main efficacy outcome is the number of patients reaching grades 2 or 1 on the WHO scale within 10 days of starting treatment. Secondary outcomes include long-term efficacy: number of patients discharged who do not present COVID-19-related relapse or comorbidity up until 28 days after discharge, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin's action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with standard of care-plus-icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

COPPADIS Study Group.[Background and Objective] Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group.[Material and Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable).[Results] After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865).[Conclusions] Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.This research was funded by Fundación Española de Ayuda a la Investigación en Parkinson y otras Enfermedades Neuro-degenerativas (Curemos el Parkinson; www.curemoselparkinson.org).Peer reviewe

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

The global abundance of tree palms

Aim Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location Tropical and subtropical moist forests. Time period Current. Major taxa studied Palms (Arecaceae). Methods We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests