Discovering the Legacy of Hispanic/Spanish and South American Landscapes through Geohistorical Sources: The Geographical and Topographical Relations of Philip II

Landscapes have history and memory, which are eloquent generators of testimonies and traces on the processes of the landscape that take place today, and that will take place in the future. In recent years, numerous methods of analysing land and landscape patterns have been developed and evaluated, based on the multiplicity of these type of geographic and historical data sources, which have developed the concept of the geohistorical source. The goal of these sources of information allows us to historically reconstruct landscapes. With this in mind, the basic objective of the present research is to approach a geohistorical source with a wide spatial spectrum in Europe and America: the geographical and topographical relations of Philip II. This source has been chosen for the quality, quantity, variety and systematization of the data it provides on the territory and landscape of the crown of Castile. In addition, it ended up being the model of how to obtain organized and homogeneous knowledge of a large spatial area, considering the geographical, anthropological and historical data of the different territories. This geohistorical source is reliable, because the local authorities, both secular and ecclesiastical, are questioned, as they are the ones who inhabit, use, and, at different levels, govern the territory and its people

The Influence of Emissions from Maritime Transport on Air Quality in the Strait of Gibraltar (Spain)

Gaseous and particulate emissions from oceangoing ships have a significant effect on the quality of air in cities. This study estimates mainly the influence of NOx, SOx, and particulate matter (PM2.5) on air quality in the Strait of Gibraltar (Spain) using the authors' own Ship's Energy and Emissions Model (SENEM) and the California Puff air quality model (CALPUFF) in 2017. The Algeciras Bay Industrial Zone recorded the highest levels of pollutants, and the Palmones area was identified as a major hotspot, with mean daily ship-sourced SOx concentrations >215 mu g/m(3), while the highest concentrations of PM10 reached 8.5 mu g/m(3) inside the Strait, and the mean yearly contribution of PM2.5 reached 0.86 mu g/m(3) in the city of Algeciras. The incidence of maritime traffic emissions on the levels of particle emissions, CO, HC, NMVOC, and CO2 reached values of up to 20-25% in all the receivers defined in the study

Calculating a Drop in Carbon Emissions in the Strait of Gibraltar (Spain) from Domestic Shipping Traffic Caused by the COVID-19 Crisis

As a consequence of the COVID-19 pandemic, the Spanish government declared a State of Emergency, and domestic passenger ship traffic was restricted in Spanish ports. This manuscript presents scenarios of emissions from domestic shipping traffic in the seas of the Strait of Gibraltar (Spain) over three months of the COVID-19 pandemic. Emissions were estimated for only 90 days of the pandemic, and two scenarios were studied: emissions while vessels were berthed at the Algeciras Port and emissions as a consequence of the interruption of passenger ship transportation in the Strait of Gibraltar. To this end, the authors' own model was used, which has near zero uncertainties. This model was used for the first time in this study and takes into account both meteorological and sea condition parameters, as well as the efficiency of the propulsion system. The manuscript concentrates on the emissions of greenhouse gases (GHGs), nitrogen oxides (NOx), sulphur oxides (SOx), carbon dioxide (CO2), and particulate matter (PM) from six Ro-Pax ships that ceased to operate. The main finding is that as a consequence of the pandemic, reductions of up to 12% were found in the Strait of Gibraltar in all the pollutants and GHGs when taking into account all international traffic, while the decrease in emissions from domestic traffic only reached 51%

Extracellular cysteine disulfide bond break at Cys122 disrupts PIP2-dependent Kir2.1 channel function and leads to arrhythmias in Andersen-Tawil Syndrome

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Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.The authors thank the Centro Nacional de Investigaciones Cardiovasculares (CNIC) Viral Vectors Unit for producing the adeno-associated virus serotype 9. Confocal experiments were conducted at the CNIC Microscopy and Dynamic Imaging Unit. The authors thank the CNIC Bioinformatics Unit for generating the in silico homology modeling simulations, F-function analysis, and helpful discussions. The authors also thank the Centro de Supercomputación de Galicia for the use of the Finis Terrae III supercomputer to perform molecular dynamics studies. The CNIC was supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). This work was supported by the National heart, Lung and Blood Institute under National Institutes of Health (NIH) grant R01HL163943; the La Caixa Banking Foundation project code HR18-00304 (grant LCF/PR/HR19/52160013); grants PI-FIS-2020, PI20/01220, PI-FIS-2023, and PI23/01039 from the Instituto de Salud Carlos III and cofunded by the Fondo Europeo de Desarrollo Regional (FEDER) and the European Union, respectively; grants PID2020-116935RB-I00 and BFU2016-75144-R funded by MICIU/AEI/10.13039/501100011033; the Fundación La Marató de TV3 (736/C/2020) amb el suport de la Fundació La Marató de TV3; the CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (grant CB16/11/00458); the European Union’s Horizon 2020 grant agreement GA-965286; and the Program S2022/BMD7229-CM ARCADIACM funded by the Comunidad de Madrid to J. Jalife; grant PID2021-126423OB-C22 (to M. Martín-Martínez) funded by MICIU/AEI/10.13039/501100011033; and European Regional Development Fund (ERDF) grant PID2022-137214OB-C22 (to M. Gutierrez-Rodríguez) funded by MICIU/AEI/10.13039/501100011033. The imaging studies were performed in the TRIMA@CNIC (Infraestructura de Imagen Traslacional Avanzada del CNIC) node of the ICTS ReDIB (Infraestructuras Científicas y Técnicas Singulares: Red Distribuida de Imagen Biomédica) grant ICTS-2018- 04-CNIC-16 funded by MICIU/AEI/10.13039/501100011033 and ERDF, and project EQC2018-005070-P funded by MICIU/AEI/10.13039/501100011033 and FEDER. A.I. Moreno-Manuel holds an formación profesional universitaria (FPU) contract (FPU20/01569) from the Ministerio de Universidades. J.M. Ruiz Robles holds an FPU contract (FPU22/03253) from the Ministerio de Universidades. L.K. Gutiérrez holds an FPI contract (PRE2018-083530) from the Ministerio de Economía y Competitividad de España cofunded by the Fondo Social Europeo, attached to project SEV-2015-0505-18-2. I. Martínez-Carrascoso holds a PFIS (Contratos predoctorales de formación en investigación en salud) contract (FI21/00243) funded by Instituto de Salud Carlos III and the Fondo Social Europeo Plus cofunded by the European Union. M.L. Vera-Pedrosa held contract PEJD-2019-PRE/BMD15982 funded by the Consejería de Educación e Investigación de la Comunidad de Madrid y Fondo Social Europeo.S

Los Poyos del Molinillo (Frigiliana): new site of the Bronze Age in the East Axarquía (Málaga, Andalucía)

En este trabajo damos a conocer un nuevo yacimiento descubierto recientemente en el municipio de Frigiliana. La delimitación del área denominada Los Poyos del Molinillo permitió definir la existencia de un poblado y una covacha con restos de una inhumación. El estudio de los materiales arqueológicos, que incluye cerámica, piezas metálicas o elementos de molturación, o la datación AMS obtenida, permiten adscribir el yacimiento a la Edad del Bronce y ampliar el conocimiento de esta etapa en la Axarquía oriental (Málaga, Andalucía).In this work we present a new site recently discovered in the Frigiliana municipality (Málaga). The spatial delimitation of the so called Los Poyos del Molinillo area let us define a Bronze age settlement and an inhumation burial cave. The archaeological record includes ceramic, metallic items or grinding elements, all of them belonging to the Bronze Age, as well as an AMS Radiocarbon data. This site extends the knowledge about this period in the Eastern Axarquía (Málaga, Andalucía)

Microbioma y mediadores de inflamación intestinal en el síndrome de enterocolitis inducido por proteínas alimentarias

Trabajo presentado al XIV WorkShop de la Sociedad Española de Microbiota, Probióticos y Prebióticos, celebrado en Pamplona (España) del 8 al 10 de marzo de 202

Alergia a la proteína de leche de vaca en la infancia: microbiota, hidrolizados y tolerancia

Trabajo presentado al XIII Workshop Sociedad Española de Microbiota, Probióticos y Prebióticos, celebrado en Valencia (España), del 7 la 9 de junio de 2022.Introducción La alergia a proteínas de leche de vaca (APLV) es la alergia alimentaria más frecuente en la infancia, habiéndose descrito posibles relaciones con la microbiota intestinal y con el tipo de alimentación. El objetivo de este trabajo es profundizar en el estudio de la microbiota intestinal en menores de un año con APLV y su relación con la adquisición de tolerancia y dieta, comparando muestras al diagnóstico y a los 6 meses de seguimiento con dieta de exclusión láctea. Metodología Se reclutaron 22 pacientes diagnosticados con APLV (14 mediados por IgE y 8 no mediados) y un grupo control de 25 niños sanos. Se recogieron muestras de heces y se realizó un análisis metataxonómico del ADNr 16S y de las regiones ITS de bifidobacterias por secuenciación. Se evaluaron las características clínico-epidemiológicas de los pacientes y se realizó un seguimiento a los 6 meses para evaluar tolerancia y el uso de distintas fórmulas terapéuticas de sustitución alimentaria. Resultados Se detectó un mayor porcentaje de secuencias pertenecientes al filo Actinobacteria (¿60%) en controles frente a casos (¿30%) al diagnóstico. Además, el patrón de abundancias relativas de bifidobacterias fue diferente entre controles y pacientes no mediados por IgE, con una menor proporción de B. longum en estos últimos. Tras la dieta de exclusión, sólo 3 de los pacientes, que estaban tomando distintos tipos de fórmulas terapéuticas, adquirió tolerancia, de los cuales 2 eran casos no mediados por IgE. Conclusiones En los pacientes APLV no IgE mediada se observaron perfiles microbianos distintos de los lactantes sanos, encontrándose a su vez en este grupo una mayor tolerancia al cabo de 6 meses. En tratamiento y seguimiento de la APLV la determinación de la microbiota intestinal puede ser clave para establecer posibles vínculos con la adquisición de tolerancia y el tipo de hidrolizado

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma