La Piquera in central Iberian Peninsula : A new key vertebrate locality for the Early Pliocene of western Europe

Altres ajuts: CERCA Programme/Generalitat de CatalunyaWe introduce the new vertebrate site of La Piquera (Duero Basin, central Iberian Peninsula), provide a detailed description of the lithostratigraphy and present a preliminary faunal list. The fossil vertebrate association includes amphibians (with representatives of the families Salamandridae, Alytidae, Pelodytidae, and Bufonidae), squamate reptiles (with members of the families Agamidae, Lacertidae, Anguidae, Scincidae, Blanidae, ?Erycidae, and Colubridae/Psammophiidae), and mammals (with representatives of the families Soricidae, Erinaceidae, Muridae, Cricetidae, Gerbillidae, Gliridae, Sciuridae, Vespertilionidae, Rhinolophidae, Miniopteridae, Megadermatidae, Leporidae, Prolagidae, and Bovidae). The association indicates an intermediate biostratigraphic position between the southern Iberian sites of Sifón-413 (at about 5.33-5.23 Ma) and Botardo-D (between 4.79 and 4.63 Ma), the new locality being correlated with the earliest Ruscinian (lower part of the MN14 unit). The ecological affinities of the identified small vertebrates suggest the presence of a landscape dominated by open herbaceous meadows in the surroundings of the fossil-site during the earliest Pliocene, with the occasional presence of woodland patches and stable water bodies under relatively dry and warm environmental conditions. La Piquera therefore enhances our knowledge on the vertebrate community recorded in central Iberian Peninsula during the earliest Pliocene. With more than 1200 remains, La Piquera becomes a key locality for the Early Pliocene of southwestern Europe, central Spain, where this time-span is poorly represented

DigApp and TaphonomApp: Two new open-access palaeontological and archaeological mobile apps

Two new paleontological and archaeological Android applications, DigApp and TaphonomApp, are presented in this manuscript. DigApp is intended to aid data collection, storage and management in archaeological and palaeontological excavations. DigApp allows easily recording of common field information such as spatial data and fossil identification data. Online and offline versions of DigApp were developed to fit all needs, and they can be modified according to the excavation particularities. TaphonomApp was created in order to assist taphonomists while carrying out detailed taphonomical evaluations both in the field and in the laboratory, making data collection quicker, homogeneous and overall, more efficient. DigApp and TaphonomApp are free, open-access and flexible software, that can be easily modified by any user (without the need of expertise in computing or coding) as explained in this paper. An in-depth guide on how to modify the apps is provided within this paper. DigApp and TaphonomApp have been used during palaeontological excavations carried out at one of the Batallones Butte vertebrate sites (Batallones-10, Middle Miocene) in the Madrid basin (Spain)

A new assemblage of late Neanderthal remains from Cova Simanya (NE Iberia)

This study presents an exceptional collection of 54 Late Pleistocene human remains that correspond to at least three Neanderthal individuals from Simanya Gran, the main gallery of Cova Simanya, located in the northeastern Iberian Peninsula. The collection comprised 53 unpublished remains that were unearthed during the 1970s and an additional tooth discovered during 2021 excavations. The specimens represent an adult with a small stature, a periadolescent aged approximately 11.5 years, and an immature individual aged approximately 7.7 years, thus offering a more complete demographic perspective. The collection encompasses diverse anatomical parts including upper and lower dentition, mandible, vertebrae, and limb bones from both the upper and lower extremities. Attempts to extract aDNA were unsuccessful. Renewed archaeological investigations at Cova Simanya have facilitated the reevaluation of the original stratigraphic context of these remains, leading to the discovery of the additional tooth, aligning with the periadolescent individual. This assemblage is currently the most extensive Neanderthal collection from the northeastern Mediterranean Iberia, offering invaluable insights into the morphology and evolutionary trajectory of Late Pleistocene hominins. Hence, Simanya Neanderthals will enhance our understanding of Neanderthal demographics and evolution, paving the way for an in-depth examination of the morphological diversity and evolutionary context of Iberian Neanderthals

A new assemblage of late Neanderthal remains from Cova Simanya (NE Iberia)

This study presents an exceptional collection of 54 Late Pleistocene human remains that correspond to at least three Neanderthal individuals from Simanya Gran, the main gallery of Cova Simanya, located in the northeastern Iberian Peninsula. The collection comprised 53 unpublished remains that were unearthed during the 1970s and an additional tooth discovered during 2021 excavations. The specimens represent an adult with a small stature, a periadolescent aged approximately 11.5 years, and an immature individual aged approximately 7.7 years, thus offering a more complete demographic perspective. The collection encompasses diverse anatomical parts including upper and lower dentition, mandible, vertebrae, and limb bones from both the upper and lower extremities. Attempts to extract aDNA were unsuccessful. Renewed archaeological investigations at Cova Simanya have facilitated the reevaluation of the original stratigraphic context of these remains, leading to the discovery of the additional tooth, aligning with the periadolescent individual. This assemblage is currently the most extensive Neanderthal collection from the northeastern Mediterranean Iberia, offering invaluable insights into the morphology and evolutionary trajectory of Late Pleistocene hominins. Hence, Simanya Neanderthals will enhance our understanding of Neanderthal demographics and evolution, paving the way for an in-depth examination of the morphological diversity and evolutionary context of Iberian Neanderthals.This research was funded by the Spanish Ministry of Science and Innovation through the projects PID2021-122356NB-I00 (MNCN-CSIC, AR), PID2020-113960GB-I00 (UB, JF), PID2021-124590NB-I00 (MCNB, CL-F), PID2019-103987GB-C31 (IPHES-CERCA), and PID2021-126004NB-100 (IBE-UPF-CSIC, TM-B); the AGAUR through the research groups 2021 SGR 01237 (IPHES-CERCA, EA), 2021 SGR 00337 (UB, JF), and 2021 SGR 00177 (IBE-UPF-CSIC, TM-B); the Culture Department of the Generalitat de Catalunya through the project ARQ001SOL-172-2022; and the Diputació de Barcelona and the Fundación Palarq. MS was funded by the UAM Tomás y Valiente Program, JR by the European Union-Next Generation EU, Ministry of Universities and UA (MARSALAS21-22), and DL by the Xunta de Galicia Grant ED481B-2022-048. ST and TM-B received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement no. 803147 RESOLUTION, https://site.unibo.it/resolution-erc/en (ST), and no. 864203 (TM-B)]. IPHES-CERCA received financial support from the Spanish Ministry of Science and Innovation through the “María de Maeztu” program for Units of Excellence (CEX 2019-000945-M)

Revelando la geometría en profundidad de las fallas activas que limitan el valle del Guadalentín mediante sísmica de reflexión de alta resolución: resultados preliminares

[EN]: To produce seismic hazard assessments to the current state-of-the-art, it is essential to characterize the active faults in terms of geometry, interrelation and seismotectonic status. The Guadalentin Depression is the main basin within the Eastern Betic Shear Zone, which corresponds to a NE-SW tectonic corridor bounded by the Carrascoy, Alhama de Murcia and Palomares faults, from north to south. Although a number of active tectonics and paleoseismological studies have been carried out in these faults, almost nothing is known about their geometry at depth. To unveil the deep structure, geometry and upper Neogene deformation history of these faults we have carried out a high-resolution seismic reflection survey. The acquired seismic profiles will allow to improve our understanding of the deep geometry of the known active faults (up to 2 km depth), as well as to identify potential buried branches and will help to reduce the uncertainties in seismic hazard assessment.[ES]: Para producir evaluaciones del peligro sísmico actualizadas al estado del arte actual, es esencial caracterizar las fallas activas de una región en términos de geometría, interrelación y estado sismotectónico. La depresión del Guadalentín es la principal cuenca cuaternaria dentro de la Zona de Cizalla de las Béticas Orientales, la cual corresponde a un corredor tectónico con dirección NE-SW delimitado por las fallas de Carrascoy, Alhama de Murcia y Palomares, de norte a sur. Aunque varios estudios de tectónica activa y paleosismología se han centrado en estas fallas, su geometría en profundidad es bastante incierta. Para revelar la estructura profunda, la geometría y el historial de deformación desde el Neógeno superior de estas fallas, hemos llevado a cabo un estudio de sísmica de reflexión de alta resolución. Los perfiles sísmicos adquiridos permitirán mejorar nuestra comprensión de la geometría profunda de las fallas activas conocidas (hasta 2 km de profundidad), así como identificar posibles ramas ciegas, y ayudarán a reducir las incertidumbres en los cálculos de peligrosidad sísmicaHector Perea es un investigador postdoctoral del programa "Atracción de Talento" en la Universidad Complutense de Madrid financiado por la Comunidad de Madrid (2018-T1/AMB-11039). Paula Herrero y Júlia Molins han estado contratadas por el proyecto UNrIDDLE (2018-T1/AMB-11039). Juan Alcalde ha recibido financiación de las ayudas IJC2018-036074-I financiadas por MCIN/AEI/10.13039/501100011033.Peer reviewe

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Application of artificially intelligent systems for the identification of discrete fossiliferous levels

The separation of discrete fossiliferous levels within an archaeological or paleontological site with no clear stratigraphic horizons has historically been carried out using qualitative approaches, relying on two-dimensional transversal and longitudinal projection planes. Analyses of this type, however, can often be conditioned by subjectivity based on the perspective of the analyst. This study presents a novel use of Machine Learning algorithms for pattern recognition techniques in the automated separation and identification of fossiliferous levels. This approach can be divided into three main steps including: (1) unsupervised Machine Learning for density based clustering (2) expert-in-the-loop Collaborative Intelligence Learning for the integration of geological data followed by (3) supervised learning for the final fine-tuning of fossiliferous level models. For evaluation of these techniques, this method was tested in two Late Miocene sites of the Batallones Butte paleontological complex (Madrid, Spain). Here we show Machine Learning analyses to be a valuable tool for the processing of spatial data in an efficient and quantitative manner, successfully identifying the presence of discrete fossiliferous levels in both Batallones-3 and Batallones-10. Three discrete fossiliferous levels have been identified in Batallones-3, whereas another three have been differentiated in Batallones-10.This research has been funded by Project PGC2018-094122-B-100 of the Spanish Government (Science and Innovation Ministry). David Manuel Martín-Perea was funded by an FPI Predoctoral grant BES-2016-079460 from the Spanish Government associated to Project CGL2015-6833-P.We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe