Palaeolithic rock art in Alkerdi 2 cave (Urdazubi/Urdax, Navarra)

En el marco del proyecto de «Caracterización del macizo y sistema kárstico de Alkerdi,de la cueva de Alkerdi y de su entorno de protección», se procede a la exploración de la cavidad de Alkerdi 2. Las labores coordinadas han permitido identificar un conjunto de arte parietal asociado a evidencias arqueológicas en superficie. El estilo de las grafías animales grabadas apunta hacia una atribución Gravetiense para la presencia humana. La datación por radiocarbono de uno de los motivos parietales y de un carbón procedente del contexto arqueológico, lo corroboran. Se trata así de la segunda cavidad decorada durante el Paleolítico en Navarra y la muestra artística más antigua de la Comunidad Foral.Within the framework of the characterization project of the massif and karst system of Alkerdi, the Alkerdi cave and its protective environment, the Alkerdi 2 cavity was explored. The coordinated work has made it possible to identify a set of parietal art associated with archaeological evidence on the surface. The style of the engraved animal points towards a Gravettian attribution for human presence. Radiocarbon dating of one of the parietal motifs and a charcoal from the archaeological context corroborate this idea. This is the second cavity decorated during the Paleolithic in Navarre and the oldest artistic remain in the Autonomous Community

A new decorated gallery at the Alkerdi 2 cave (Urdazubi/Urdax)

En el marco del proyecto de «Caracterización del macizo y sistema kárstico de Alkerdi, de la cueva de Alkerdi y de su entorno de protección», se continúa con el estudio científico de la cavidad de Alkerdi 2. Las labores de prospección espeleológica del desarrollo kárstico de la cavidad han permitido localizar una galería decorada inédita en 2020. En un primer estudio se ha identificado en su interior un conjunto de pinturas y de grabados compuestos principalmente por representaciones animales de bisontes, caballos y uros, a los que se unen un panel decorado con vulvas y dos conjuntos de trazos pareados en rojo.Within the framework of the characterization project of the karstic massif of Alkerdi and its system, the cave of Alkerdi and its protected environment, we have continued with the scientific study of the cave of Alkerdi 2. The speleological prospecting work of the karstic development of the cave has allowed locating an unknown decorated gallery in 2020. In a first study, a set of paintings and engravings has been detected inside, composed mainly of animal representations of bison, horses and aurochs, to which a panel decorated with vulvas and two sets of paired red traits are adde

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

Background: We 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 ~ 80% of cases. Methods: We 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. Results: No 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 = 1.1 × 10−4) 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 = 2.1 × 10−4). 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 = 3.4 × 10−3), 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 = 7.7 × 10−8). 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 = 1.68 × 10−5). Conclusions: Rare 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

Calcretas, espeleotemas y depósitos aluviales: tres registros de una misma historia geológica (Nerja, Málaga)

In this work we study the genetic link between calcretes, speleothems and alluvial deposits developed on the epikarst and endokarst of the Nerja Cave (Nerja, Málaga, Spain) and the adjacent Quaternary (Pleistocene) alluvial fan. Field and petrographic observations, and δ.18O and δ.13C isotopic data analysis of the host rock, distinct calcrete types and epikarst speleothems indicate that these deposits are the result of arid and more humid climatic episodes. Epikarstic and endokarstic speleothem U/Th absolute dating indicate that both endokarstic and epikarstic development of the Nerja Cave was coetaneous and genetically linked to the sedimentation of the adjacent Pleistocene alluvial fan, as a response to climatic changesAgradecimientos: A la Fundación Pública de Servicios Cueva de Nerja y a su Instituto de Investigación por su apoyo y financiación al proyecto “Estudio geológico de la Cueva de Nerja (Maro, Nerja)”, así como al Grupo de Investigación IT1029-16 del Gobierno Vasco. Queremos agradecer especialmente el apoyo y la colaboración incansable de D. Luis-Efrén Fernández, Conservador de la Cueva de Nerja.Peer reviewe

Arte parietal paleolítico de la cueva de Alkerdi 2 (Urdazubi/Urdax, Navarra)

Alkerdiko mendigune eta sistema karstikoaren zein Alkerdiko kobazuloaren eta bere babes eremuaren azterketarako proiektuaren barruan, Alkerdi 2 kobazuloaren miaketa burutu da. Ikerketa koordinatuek lurrazalean agerturiko aztarna arkeologikoekin erlazionaturiko labar arte multzo bat identifikatzea ahalbidetu dute. Grabaturiko animalien irudien estiloak Gravette aldiko giza presentzia bat frogatzen dute. Labar irudietako baten zein testuingurutik datorren ikatz baten erradiokarbonozko datazioek hau baieztatuko lukete. Beraz, Nafarroan agerturiko bigarren kobazulo apainduaren aurrean egongo ginateke, eta Foru Erkidegoko adibide artistiko zaharrenen aurrean.Within the framework of the characterization project of the massif and karst system of Alkerdi, the Alkerdi cave and its protective environment, the Alkerdi 2 cavity was explored. The coordinated work has made it possible to identify a set of parietal art associated with archaeological evidence on the surface. The style of the engraved animal points towards a Gravettian attribution for human presence. Radiocarbon dating of one of the parietal motifs and a charcoal from the archaeological context corroborate this idea. This is the second cavity decorated during the Paleolithic in Navarre and the oldest artistic remain in the Autonomous Community.En el marco del proyecto de «Caracterización del macizo y sistema kárstico de Alkerdi, de la cueva de Alkerdi y de su entorno de protección», se procede a la exploración de la cavidad de Alkerdi 2. Las labores coordinadas han permitido identificar un conjunto de arte parietal asociado a evidencias arqueológicas en superficie. El estilo de las grafías animales grabadas apunta hacia una atribución Gravetiense para la presencia humana. La datación por radiocarbono de uno de los motivos parietales y de un carbón procedente del contexto arqueológico, lo corroboran. Se trata así de la segunda cavidad decorada durante el Paleolítico en Navarra y la muestra artística más antigua de la Comunidad Foral

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases

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