First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human–environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26, 000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe. © 2021, The Author(s)

First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human?environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26,000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe.Tis research was carried out in the context of the ERC MULTIPALEOIBERIA project, funded by the European Research Council (ERC-2018-STG-805478), and the PALEOINTERIOR project, funded by the Spanish Ministry of Science and Innovation (HAR2017-82483-C3-3-P)

Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis

Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARSCoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+ /K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1b were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1b was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence

Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis

Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence

A context for the last Neandertals of interior Iberia: Los Casares cave revisited.

Introduction and objectives Although the Iberian Peninsula is a key area for understanding the Middle to Upper Paleolithic transition and the demise of the Neandertals, valuable evidence for these debates remains scarce and problematic in its interior regions. Sparse data supporting a late Neandertal persistence in the Iberian interior have been recently refuted and hence new evidence is needed to build new models on the timing and causes of Neandertal disappearance in inland Iberia and the whole peninsula. In this study we provide new evidence from Los Casares, a cave located in the highlands of the Spanish Meseta, where a Neandertal-associated Middle Paleolithic site was discovered and first excavated in the 1960’s. Our main objective is twofold: (1) provide an updated geoarcheological, paleoenvironmental and chronological framework for this site, and (2) discuss obtained results in the context of the time and nature of the last Neandertal presence in Iberia. Methods We conducted new fieldwork in an interior chamber of Los Casares cave named ‘Seno A’. Our methods included micromorphology, sedimentology, radiocarbon dating, Uranium/Thorium dating, palinology, microfaunal analysis, anthracology, phytolith analysis, archeozoology and lithic technology. Here we present results on site formation processes, paleoenvironment and the chronological setting of the Neandertal occupation at Los Casares cave-Seno A. Results and discussion The sediment sequence reveals a mostly in situ archeological deposit containing evidence of both Neandertal activity and carnivore action in level c, dated to 44,899–42,175 calendar years ago. This occupation occurred during a warm and humid interval of Marine Isotopic Stage 3, probably correlating with Greenland Interstadial 11, representing one of the latest occurrences of Neandertals in the Iberian interior. However, overlying layer b records a deterioration of local environments, thus providing a plausible explanation for the abandonment of the site, and perhaps for the total disappearance of Neandertals of the highlands of inland Iberia during subsequent Greenland Stadials 11 or 10, or even Heinrich Stadial 4. Since layer b provided very few signs of human activity and no reliable chronometric results, and given the scarce chronostratigrapic evidence recorded so far for this period in interior Iberia, this can only be taken as a working hypothesis to be tested with future research. Meanwhile, 42,000 calendar years ago remains the most plausible date for the abandonment of interior Iberia by Neandertals, possibly due to climate deterioration. Currently, a later survival of this human species in Iberia is limited to the southern coasts.Peer Reviewe

Level of discomfort in critically ill paediatric patients and its correlation with sociodemographic and clinical variables, analgosedation and withdrawal syndrome. COSAIP multicentre study (Phase 2)

Introduction: There are clinical and sociodemographic factors that have an impact on the comfort of the critically ill paediatric patient. The main aim of this study was to determine the level of discomfort of paediatric patients admitted to different national hospitals, and to analyse its correlation with sociodemographic and clinical variables, analgosedation, and withdrawal syndrome. Methods: An observational, analytical, cross-sectional, and multicentre study was conducted in five Spanish hospitals. The level of analgosedation was assessed once per shift over a 24 h period, using a BIS sensor, and pain with scales adapted to paediatric age population. The intensity of withdrawal syndrome was determined using the Withdrawal Assessment Tool (WAT-1) scale once per shift for 3 days. Discomfort level was simultaneous assessed using COMFORT Behaviour Scale-Spanish version (CBS-S). Results: A total of 261 critically ill paediatric patients with median age of 1.61 years (IQR = 0.35-6.55) were included. An overall discomfort score of 10.79 ± 3.7 was observed during morning compared to 10.31 ± 3.3 observed during the night. When comparing analgosedation and non-analgosedation groups, statistically differences were found in both shifts (χ2: 45.48; P =.001). At the same time, an association was observed (P <.001) between low discomfort scores and development of withdrawal syndrome development assessed with WAT-1. Conclusions: As there is a percentage of the studied population with discomfort, specific protocols need to be developed, guided by valuated and clinically tested tools, like the COMFORT Behaviour Scale-Spanish version.Introducción: Existen factores clínicos o sociodemográficos que pueden tener un impacto en el confort del paciente crítico pediátrico. El objetivo principal fue determinar el grado de disconfort de los pacientes pediátricos ingresados en las UCIP de diversos hospitales nacionales y analizar su relación con variables ocio demográficas y clínicas, sedoanalgesia y síndrome de abstinencia. Métodos: Estudio observacional, analítico, transversal y multicéntrico en 5 hospitalesespañoles. Se valoró el grado de analgosedación mediante el sensor BIS y las escalas de dolora daptadas a la edad pediátrica, una vez por turno durante 24 h. El grado de abstinencia se determinó con la escala Withdrawal Assessment Tool (WAT-1), una vez por turno durante 3 días consecutivos. Además, se valoró simultáneamente el grado de disconfort mediante la COMFORTBehavior Scale-versión española (CBS-ES).Resultados: Se incluyeron un total de 261 pacientes críticos pediátricos con una mediana de edad de 1,61 años (RIQ = 0,35-6,55). Se objetivaron puntuaciones globales de disconfort de10,79 ± 3,7 en el turno de mañana versus 10,31 ± 3,3 en el de noche. Se observó asociación estadística al comparar al grupo de pacientes analgosedados con el grupo de no analgosedadosen ambos turnos ( 2: 45,48; p = 0,001). A la vez, también se observó una relación estadística-mente significativa (p < 0,001) entre puntuaciones bajas de disconfort y menor desarrollo desíndrome de abstinencia

Restos de caballos fósiles cuaternarios en la depresión Prados-Guatén (Pantoja de la Sagra, Toledo)

Durante la primera reunión de campo del Grupo Madrileño de Cuaternario (GQM-AEQUA) se localizaron restos fragmentarios de dentición de caballos fósiles en los antiguos areneros de Pantoja de La Sagra (Toledo), actualmente en proceso de desmantelamiento y relleno. Ante la posibilidad de deterioro y pérdida los restos fueron recolectados y trasladados al Museo Nacional de Ciencias Naturales (CSIC, Madrid) donde se ha procedido a su análisis. Las piezas fósiles analizadas responden a un maxilar izquierdo con tres piezas dentales in situ (molares y premolares), y otras siete más aisladas. Todos los dientes aislados, junto con el fragmento de maxilar existente, corresponden a un adulto joven. Los restos fósiles se encontraban asociados a un nivel de arenas fluviales situado unos cuatro metros por debajo de la superficie de la Terraza de +15 m de la Depresión Prados-Guatén definida como un nivel perteneciente al tránsito Pleistoceno inferior-medio, del antiguo Sistema fluvial Manzanares-Guatén por Silva (1988). En concreto los niveles superiores de esta terraza han sido interpretados como resultado de la superposición de los últimos depósitos del antiguo sistema fluvial y los primeros asociados al relleno de la Depresión por tributarios de área fuente más local tras su abandono como consecuencia del proceso de captura del valle inferior del Manzanares por parte del Río Jarama al SW de la Ciudad de Madrid (Silva et al., 1988). Los caracteres morfológicos y morfométricos de las piezas dentarias permiten identificarlos como Equus ferus cf. mosbachensis cuya distribución bioestratigráfica abarca la parte final del Pleistoceno Medio (c.a. 500-200 ka B.P.). Junto a los restos fósiles aparecieron también escasos fragmentos líticos correspondientes a productos de lascado en sílex de difícil atribución tecnológica. Los restos fósiles analizados, indican que el depósito extensivo de arenas fluviales en el eje de la Depresión, culminó durante el final del Pleistoceno medio, y que la dinámica fluvial de la Depresión tras su proceso de abandono fue de hecho más activa de lo que se pensaba con la instalación de sistemas de arroyos relevantes alimentados por cabeceras locales antes del encajamiento definitivo actual de los arroyos Prados y Guatén.Peer reviewe

Territoriality and the organization of technology during the Last Glacial Maximum in southwestern Europe

Climate changes that occurred during the Last Glacial Maximum (LGM) had significant consequences in human eco-dynamics across Europe. Among the most striking impacts are the demographic contraction of modern humans into southern refugia and the potential formation of a population bottleneck. In Iberia and southern France transformations also included the occurrence of significant technological changes, mostly marked by the emergence of a diverse set of bifacially-shaped stone projectiles. The rapid dissemination of bifacial technologies and the geographical circumscription of specific projectile morphologies within these regions have been regarded as evidence for: (1) the existence of a system of long-distance exchange and social alliance networks; (2) the organization of human groups into cultural facies with well-defined stylistic territorial boundaries. However, the degree and modes in which cultural transmission have occurred within these territories, and how it may have influenced other domains of the adaptive systems, remains largely unknown. Using southern Iberia as a case-study, this paper presents the first quantitative approach to the organization of lithic technology and its relationship to hunter-gatherers' territorial organization during the LGM. Similarities and dissimilarities in the presence of morphological and metric data describing lithic technologies are used as a proxy to explore modes and degrees of cultural transmission. Statistical results show that similarities in technological options are dependent on the chronology and geographical distance between sites and corroborate previous arguments for the organization of LGM settlement in Southern Iberia into discrete eco-cultural facies.STSM COST action (ref. COST-STSM-TD0902-10855); FCT, contract ref. DL 57/2016/CP1361/ CT0026. Work at Vale Boi is funded by the project ALG-01-0145-FEDER-27833 - PTDC/HAR-ARQ/27833/2017.info:eu-repo/semantics/publishedVersio

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model