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14 pages, 5 figures, 2 tables.-- This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, Ocean acidification produces significant changes on phytoplankton physiology that can affect their growth and primary production. Among them, a downregulation of the enzymatic activity and the production of different cellular metabolites, including chlorophyll a (Chl a), has been observed in high CO2 cultures under stable conditions. However, the extent of how phytoplankton metabolism regulation under high CO2 conditions affects pigment pools and patterns is unknown. This study shows the effect of the atmospheric CO2 increase on pigment concentration of three important marine primary producers: Thalassiosira pseudonana, Skeletonema costatum, and Emiliania huxleyi. Cultures grown under saturating photosynthetically active radiation were aerated for at least 3 weeks with current concentrations of atmospheric CO2 (0.04% CO2 in air) and with CO2 concentrations expected for future scenarios of climate change (0.1% CO2 in air) to assess the effect of CO2 under acclimated metabolism and stable conditions. Moreover, cultures were also subjected to a perturbation (4 h without aeration) to assess responses under non-stable conditions. The results showed that light harvesting and photoprotective pigment concentrations (i.e., Chl a, Chl c2, ββ-carotene, diadinoxanthin, diatoxanthin, fucoxanthin, among others) decreased significantly under high CO2 and stable conditions, but the response reversed after the perturbation. The de-epoxidation state of xanthophylls, also showed similar patterns, indicating an increase in phytoplankton sensitivity under high CO2 and stable conditions. The results demonstrate the relevance of CO2 concentration and acclimation status for phytoplankton light absorption and photoprotective response. They also identify fucoxanthin and Chl c2 as suitable biomarkers of phytoplankton carbon metabolism under ocean acidification conditions, This work was funded by the Spanish Ministry of Economy, Industry and Competitiveness (grant number CTM201459345-R)

16 Figuras, 29 Páginas, [EN] Despite the large number of magnetostratigraphic studies in the South Pyrenean Basin aiming to calibrate the basin chronostratigraphy and the biostratigraphic scales, the South Eastern Jaca Basin remains unexplored from this perspective, and its relation with the Ainsa Basin is not fully understood. In this work we contribute with new magnetostratigraphic data from the 950m thick Las Bellostas section, located in the northern hinge of the Balzes anticline. Well-proven primary signal (positive fold test and two pseudo-antiparallel polarities) supported by numerous primary data in the surroundings allow us building a reliable local polarity sequence of eight magnetozones (from R1 to N4). Additionally, seven new biostratigraphic samples (Nummulites and Assilina) in the lower part of the section (marine environment) allows tightening the section to the Geomagnetic Polarity Time Scale (GPTS) and proposing a refined age model for the southeastern Jaca Basin. The section starts in the Boltaña Fm., of Cuisian age (Shallow Benthic Zone, SBZ11), is followed by a sedimentary gap from C22n to C20n as witnessed by biostratigraphic data (SBZ11 underneath the hiatus and SBZ16 just atop). The deltaic Sobrarbe Fm can be tracked until the C19n (Late Lutetian). From this point (200m) until the top of the section (950m), at least, the entire C18n chron can be recognized within the molassic Campodarbe Fm (C18n.2n-C18n.1r and C18n.1n) (Bartonian) equivalent to the West to the prodeltaic Arguis marls Fm. The Middle Cusian (SBZ11) to Middle Lutetian (SBZ15) stratigraphic hiatus is, in part, enhanced by the structural position at the hinge of the Balzes anticline. These new chronostratigraphic constraints help refining the W-E and N-S stratigraphic relationships in the eastern Jaca Basin and in the Ainsa Basin. This section also allows us to accurately refine the kinematics of the rotational activity in the eastern External Sierras. The important difference in magnetic declination along the section and neighboring paleomagnetic data from the Balzes anticline (from ≈70º clockwise at the base of the stratigraphic section to non-significant at the top) together with the new age model for the Eastern Jaca Basin help characterizing the rotational activity of the Balzes thrust sheet. The rotation took place between chrons C20r (Middle Lutetian; 45Ma) and C17 (Lower Priabonian 37-38Ma) in agreement to nearby structures (Boltaña, Pico del Aguila anticlines) but clearly diachronic to western ones (Santo Domingo anticline). Besides, the rotational activity seems to follow a linear and continuous pattern (velocity 9-11º/Ma, R: 0.83-0.96) in contrast to closer structures that show two distinct rotational velocities (i.e. Boltaña). These new data still let open the debate on the rotational kinematics along the South Pyrenean basal thrust., This work was financed by the Sobrarbe County Research fellow-UNESCO Global Geopark (ARP) and by some projects ESS from the Spanish Science National Plan (UKRIA4D-PID2019-104693GB-I00/CTA, DR3AM. CGL2014 54118-C2-2-R and MAGIBER-II. CGL2017-90632-REDT)

14 Pág. Centro de Biotecnología y Genómica de Plantas, Chloroplast biogenesis is crucial in plant development, as it is essential for the transition to autotrophic growth. This process is light-induced and relies on the orchestrated transcription of nuclear and plastid genes, enabling the effective assembly and regulation of the photosynthetic machinery. Here we reveal a new regulation level for this process by showing the involvement of chromatin remodelling in the nuclear control of plastid gene expression for proper chloroplast biogenesis and function. The two Arabidopsis homologues of yeast EPL1 protein, components of the NuA4 histone acetyltransferase complex, are essential for plastid transcription and correct chloroplast development and performance. We show that EPL1 proteins are light-regulated and necessary for concerted expression of nuclear genes encoding most components of chloroplast transcriptional machinery, directly mediating H4K5ac deposition at these loci and promoting the expression of plastid genes required for chloroplast biogenesis. These data unveil a NuA4-mediated mechanism regulating chloroplast biogenesis that links the transcription of nuclear and plastid genomes during chloroplast development., This work was funded by the Spanish Ministry of Economy, Industry, and Competitiveness (grant Nos. BIO2016-77559-R and PID2019-104899GB-I00 to M.P. and J.A.J. from MCIN/AEI/10.13039/501100011033 and FEDER; FPI fellowship No. BES-2017-07992 from MCIN/AEI/10.13039/501100011033 and FSE to L.B-M.) and INIA (FPI fellowship No. FPI-SGIT-2016-08 to L.E.-C.). We acknowledge the ‘Severo Ochoa Program for Centres of Excellence in R&D’ from the Agencia Estatal de Investigación of Spain (grant No. SEV-2016-0672 (2017-2021) from MCIN/AEI/10.13039/501100011033) for supporting the scientific services used in this work.

In this work, we report the use of bioorthogonal chemistry, specifically the strain-promoted click azide–alkyne cycloaddition (SPAAC) for the covalent attachment of magnetic nanoparticles (MNPs) on living cell membranes. Four types of MNPs were prepared, functionalized with two different stabilizing/passivation agents (a polyethylene glycol derivative and a glucopyranoside derivative, respectively) and two types of strained alkynes with different reactivities: a cyclooctyne (CO) derivative and a dibenzocyclooctyne (DBCO) derivative. The MNPs were extensively characterized in terms of physicochemical characteristics, colloidal stability, and click reactivity in suspension. Then, the reactivity of the MNPs toward azide-modified surfaces was evaluated as a closer approach to their final application in a living cell scenario. Finally, the DBCO-modified MNPs, showing superior reactivity in suspension and on surfaces, were selected for cell membrane immobilization via the SPAAC reaction on the membranes of cells engineered to express azide artificial reporters. Overall, our work provides useful insights into the appropriate surface engineering of nanoparticles to ensure a high performance in terms of bioorthogonal reactivity for biological applications., This work has been supported by the European Commission, MagicCellGene Project (M-ERA.NET COFUND call 2016, funded by Ministerio de Economía y Competitividad, MINECO, Spain in the framework of the PCIN-2017-060 project), Ministerio de Innovación, Ciencia y Universidades (MCIU, PGC2018-096016-B-I00 to R.M.F), Ministerio de Economía, Industria y Competitividad (BIO 2017-84246-C2-1R to V.G. and J.M.F.), and MINECO and FSE/Agencia Estatal de Investigación (Ramón y Cajal subprogram, grant RYC-2015-17640 to R.M.F.). J.I.L. and E.M.A acknowledge financial support for their predoctoral fellowships from Gobierno de Aragón (DGA 2017–2021 call, co-funded by the Programa Operativo Fondo Social Europeo de Aragón 2014–2020) and Ministerio de Universidades (FPU17/02024), respectively. Authors also acknowledge support from Gobierno de Aragón and Fondos Feder for funding the Bionanosurf (E15_20R) research group. J.M.A. and M.E. acknowledge support from the Basque Government (GIC-2015_IT-1033-16).

In the present work, electron backscatter diffraction was used to determine the microscopic dislocation structures generated during creep (with tests interrupted at the steady state) in pure 99.8% aluminium. This material was investigated at two different stress levels, corresponding to the power-law and power-law breakdown regimes. The results show that the formation of subgrain cellular structures occurs independently of the crystallographic orientation. However, the density of these cellular structures strongly depends on the grain crystallographic orientation with respect to the tensile axis direction, with 111 grains exhibiting the highest densities at both stress levels. It is proposed that this behaviour is due to the influence of intergranular stresses, which is different in 111 and 001 grains., This project was partially financed by the Spanish MINECO program, corresponding to Project MAT2017-83825-C4-1-R, and by the project Y2018/NMT-4668 Micro-Stress-MAP-C from Comunidad Autónoma de Madrid, Spain.

14 p.-7 fig.-3 tab., Aryl-alcohol oxidases (AAOs) are members of the glucose-methanol-choline oxidase/dehydrogenase (GMC) superfamily. These extracellular flavoproteins have been described as auxiliary enzymes in the degradation of lignin by several white-rot basidiomycetes. In this context, they oxidize fungal secondary metabolites and lignin-derived compounds using O2 as an electron acceptor, and supply H2O2 to ligninolytic peroxidases. Their substrate specificity, including mechanistic aspects of the oxidation reaction, has been characterized in Pleurotus eryngii AAO, taken as a model enzyme of this GMC superfamily. AAOs show broad reducing-substrate specificity in agreement with their role in lignin degradation, being able to oxidize both nonphenolic and phenolic aryl alcohols (and hydrated aldehydes). In the present work, the AAOs from Pleurotus ostreatus and Bjerkandera adusta were heterologously expressed in Escherichia coli, and their physicochemical properties and oxidizing abilities were compared with those of the well-known recombinant AAO from P. eryngii. In addition, electron acceptors different from O2, such as p-benzoquinone and the artificial redox dye 2,6-Dichlorophenolindophenol, were also studied. Differences in reducing-substrate specificity were found between the AAO enzymes from B. adusta and the two Pleurotus species. Moreover, the three AAOs oxidized aryl alcohols concomitantly with the reduction of p-benzoquinone, with similar or even higher efficiencies than when using their preferred oxidizing-substrate, O2. IMPORTANCE In this work, quinone reductase activity is analyzed in three AAO flavooxidases, whose preferred oxidizing-substrate is O2. The results presented, including reactions in the presence of both oxidizing substrates-benzoquinone and molecular oxygen-suggest that such aryl-alcohol dehydrogenase activity, although less important than its oxidase activity in terms of maximal turnover, may have a physiological role during fungal decay of lignocellulose by the reduction of quinones (and phenoxy radicals) from lignin degradation, preventing repolymerization. Moreover, the resulting hydroquinones would participate in redox-cycling reactions for the production of hydroxyl free radical involved in the oxidative attack of the plant cell-wall. Hydroquinones can also act as mediators for laccases and peroxidases in lignin degradation in the form of semiquinone radicals, as well as activators of lytic polysaccharide monooxygenases in the attack of crystalline cellulose. Moreover, reduction of these, and other phenoxy radicals produced by laccases and peroxidases, promotes lignin degradation by limiting repolymerization reactions. These findings expand the role of AAO in lignin biodegradation., This work was supported by the EnzOx2 (H2020-BBI-PPP-2015-2-720297) EU project; the BIO2017-86559-R (GenoBioref) project of the Spanish Ministry of Economy, Industry and Competitiveness, co-financed by FEDER funds; the PID2021-126384OB-I00 (Lig2Plast) project of the Spanish Ministry of Science and Innovation; the CSIC project PIE-202120E019 and interdisciplinary platform on sustainable plastics (SusPlast) and grant PID2019-103901GB-I00 funded by MCIN/AEI/10.13039/501100011033. Funding from the CSIC program for the Spanish Recovery, Transformation, and Resilience Plan funded by the Recovery and Resilience Facility of the European Union, established by Regulation (EU) 2020/2094 is also acknowledged.

There is a dearth of information regarding prehistoric foraging societies from the intermontane longitudinal valleys of the South-Central Andes. Due to the intense anthropization of the landscape or the scarce research efforts on prehistoric populations of hunter-gatherers in the intermontane valleys of the Andes, occupation sites have been found on very few occasions. However, new perspectives in the Abra del Toro rock shelter in the Yocavil Valley (Catamarca province, Argentina) have opened up from recent and ongoing excavations. This rock shelter is the first archaeological case in which it is possible to analyze the relationship between a large-scale natural catastrophe and the prehistoric populations living in the Andean intermontane valleys of the southern Central Andes. This rock shelter's stratigraphy and archaeological remains contain the record of interactions between human communities and volcanism. The stratigraphic record of the rock shelter shows a 1-m-thick volcanic ash deposit formed by aeolian transport from primary outer ashfall deposits. Geomorphological and sedimentological context, texture, glass and mineral content, whole-rock chemical composition, and radiocarbon dating prove that the tephra was derived from the 4.2 ka BP eruption of the Cerro Blanco Volcanic Complex in southern Puna (NW Argentina). This volcanic eruption is the largest documented in the world in the last five thousand years and covered the surroundings of the archaeological site with an ash layer of approximately 1 meter thick. The stratigraphic sequence of the Abra del Toro rock shelter allows us to hypothesize that there were three main occupational moments: two hunter-gatherer moments, separated by the record of the large volcanic eruption, and a subsequent agro-pottery period (Carbonelli et al. 2022. J. Archaeol. Sci. Rep. 45, 103629). The rock shelter after the eruption remained in the memory of the hunter-gatherer groups. Good visibility, accessibility, and proximity to water were attributes of this space that made it possible for it to be re-occupied after the eruptive event. Our next objective is to reconstruct, using proxy analysis, how the paleoenvironment was in the intermontane valleys before and after the eruption. The evidence of this Mid-Holocene catastrophic volcanic event in the Abra del Toro rock shelter opens the possibility of knowing its impact on the contemporary hunter-gatherer community and drawing conclusions for similar future volcanic crises., CONICET (Grant PIP 112-201301-00178) Universidad de Buenos Aires (Grant UBACYT 20020170100318BA) ( Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Grant 2019-01229) QUECA Project (MINECO, Grant CGL2011-23307)

Detectability of morphs in different light environments is one of the mechanisms favoring the persistence of color polymorphism via disruptive selection. This mechanism predicts that different morphs should be more active and successful when light conditions make them more cryptic. In nocturnal birds, no study has analyzed yet whether morphs show a different degree of nocturnality, showing different circadian activity rhythms in relation to night and day light. We analyze activity patterns and hunting efficiency of color morphs in relation to day/night light in the nocturnal polymorphic scops owl (Otus scops). Forty-four percent of owl activity took place in the first hours after sunrise and before sunset. Also, we found that nocturnal activity decreased from grey to brown females and that grey males fed their chicks more than brown ones at night. Visual modeling revealed that grey individuals would be more conspicuous to their prey than brownish ones during the day. These findings suggest that part of the activity of nocturnal scops owls may occur during the day and that grey individuals would be better adapted to forage during night-light than brownish ones. However, brown morphs seemed not to be better adapted to forage at day, suggesting that other mechanisms than visual detection by predators or prey contribute to the persistence of color polymorphism in the species., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The study was funded by the Spanish Ministry of Economy, Industry and Competitiveness through the project CGL2017-83503-P.

This note reports a trophic interaction of a passerine consuming lichens. On the islet of Daphne Major (Galápagos Archipelago), we made five observations of the Large Ground-Finch Geospiza magnirostris eating the fruticose lichen Roccella gracilis. This is an example of how island birds broaden their feeding niche in resource-poor environments., We thank Ruben Heleno, Anna Traveset, and Peter and Rosemarie Grant for their valuable comments on an early version of the manuscript. Jens Olesen revised the manuscript, Roberto Jiménez (PNG) facilitated our work during the field expedition, Sergio Pérez Ortega and Frank Bungartz provided us with general information about lichens, and Aurelio Marwn provided us with interesting references. We thank the Charles Darwin Foundation and the Galápagos National Park (research permit numbers: PC-88-18, PC-03-22-01). This research was undertaken within the project CGL2017-88122-P, funded by the Ministerio de Economía, Industria y Competitividad, Spain. The manuscript was proof-edited by Guido Jones.

Extant terrestrial vertebrates, including birds, have a panoply of symbiotic relationships with many insects and arachnids, such as parasitism or mutualism. Yet, identifying arthropod¿vertebrate symbioses in the fossil record has been based largely on indirect evidence; findings of direct association between arthropod guests and dinosaur host remains are exceedingly scarce. Here, we present direct and indirect evidence demonstrating that beetle larvae fed on feathers from an undetermined theropod host (avian or nonavian) 105 million y ago. An exceptional amber assemblage is reported of larval molts (exuviae) intimately associated with plumulaceous feather and other remains, as well as three additional amber pieces preserving isolated conspecific exuviae. Samples were found in the roughly coeval Spanish amber deposits of El Soplao, San Just, and Peñacerrada I. Integration of the morphological, systematic, and taphonomic data shows that the beetle larval exuviae, belonging to three developmental stages, are most consistent with skin/hide beetles (family Dermestidae), an ecologically important group with extant keratophagous species that commonly inhabit bird and mammal nests. These findings show that a symbiotic relationship involving keratophagy comparable to that of beetles and birds in current ecosystems existed between their Early Cretaceous relatives., This work was supported by the project CRE, funded by the Spanish Agencia Estatal de Investigación (AEI)/European Regional Development Fund (FEDER)/European Union (EU) Grant CGL2017-84419, the project PGC2018-094034-B-C22 (Ministerio de Ciencia, Innovación y Universidades/AEI/FEDER, UE), the project CGL2014-52163, funded by the Spanish Ministry of Economy, Industry, and Competitiveness, and by the Consejería de Industria, Turismo, Innovación, Transporte y Comercio of the Gobierno de Cantabria through the public enterprise EL SOPLAO S.L. (research contract REF VAPC 20225428 to Centro Nacional Instituto Geológico y Minero de España-Consejo Superior de Investigaciones Científicas and research agreement #20963 with University of Barcelona, both for the period 2022 to 2025). S.Á.-P. is funded by a grant from the Secretary of Universities and Research of the Government of Catalonia and European Social Fund (2021FI_B2 00003), Results Amber Samples Studied Description of the Larval Exuviae Discussion Affinities of the Larvae Taphonomy Keratophagy Concluding Remarks Materials and Methods Amber Pieces Imaging Data, Materials, and Software Availability Acknowledgments Supporting Information References

9 Pág., Recent studies have reported on the importance of RBCs in fish responses to viral infections and DNA vaccines. Surface-displaying recombinant bacterins (spinycterins) are a safe and adaptable prototype for viral vaccination of fish and represent an alternative method of aquaculture prophylaxis, since have been reported to enhance fish immune response. We evaluated the innate immune response of rainbow trout (Oncorhynchus mykiss) red blood cells (RBCs), head kidney, and spleen to spinycterins expressing a fragment of the glycoprotein G of viral haemorrhagic septicemia virus (VHSV), one of the most devastating world-wide diseases in farmed salmonids. We first selected an immunorelevant downsized viral fragment of VHSV glycoprotein G (frg16252–450). Then, spinycterins expressing frg16252–450 fused to Nmistic anchor-motif (Nmistic+frg16252–450) were compared to spinycterins expressing frg16252–450 internally without the anchor motif. Nmistic+frg16252–450 spinycterins showed increased attachment to RBCs in vitro and modulated the expression of interferon- and antigen presentation–related genes in RBCs in vitro and in vivo, after intravenous injection. In contrast, the head kidney and spleen of fish injected with frg16252–450, but not Nmistic+frg16252–450, spinycterins demonstrated upregulation of interferon and antigen-presenting genes. Intravenous injection of Nmistic+frg16252–450 spinycterins resulted in a higher innate immune response in RBCs while frg16252–450 spinycterins increased the immune response in head kidney and spleen. Although more studies are required to evaluate the practicality of using spinycterins as fish viral vaccines, these results highlight the important contribution of RBCs to the fish innate immune response to antiviral prophylactics., This work was supported by European Research Council funding to MOV (ERC Starting Grant GA639249) and by a grant from the Ministerio de Economía, Industria y Competitividad of Spain BIO2017-82851-C3-2-R. Cecelia Wall (Wall Medical Writing, Wake Forest, North Carolina, USA) provided editorial services.

Tesis doctoral para optar al grado de Doctora por la Universidad de Sevilla, Soils represent an essential natural, practically non-renewable resource that provides many critical ecosystem services necessary for life. Furthermore, soils play a critical role in maintaining the balance of the carbon cycle, acting as the largest terrestrial carbon pool which made them crucial in mitigating climate change. Understanding the complexity and dynamics of soils is, therefore, apart from preserving and managing this valuable natural resource, critical for the benefit of current and future generations. However, the changing climate and increasing intensity of agricultural production pose significant threats to the sustainability and role of soils, mainly by contributing to a depletion in soil organic matter (SOM) and altering its dynamics. Indeed, Mediterranean soils face these threats in a more severe way due to their geographic location, particular climate and inherent low content of SOM. It is critical to shedding light on this respect by combining different analytical procedures and providing complementary and valuable information on processes that regulate the accumulation, decomposition, and transformation of SOM. The main objective of this thesis was to investigate and deepen our knowledge about the two main threads affecting carbon dynamics in Mediterranean soils i.e., climate change and intensive agricultural practices. For this, advanced analytical techniques appropriate for the study of complex matrices such are soils were tested and combined to study SOM in two distinct and representative Mediterranean soils, in terms of extension and ecosystem relevance: Mediterranean savannahs, commonly known as “dehesas” (Section I) and agricultural soils (Section II)., El presente trabajo se ha realizado en el marco del proyecto titulado “Intercambio y flujos de carbono en suelos de ecosistemas mediterráneos naturales y manejados (bosques, dehesas y cultivos” (INTERCARBON, CGL2016-78937-R), así como en colaboración activa con el proyecto titulado “Las dehesas frente al cambio global: una aproximación multi-funcional (DECAFUN, CGL2015-70123-R)”. Ambos proyectos han sido financiados por el Ministerio de Economía y Competitividad (MINECO), así como el contrato predoctoral de Layla Márquez San Emeterio dentro del proyecto INTERCARBON como parte del Programa Estatal de Promoción del Talento y su Empleabilidad en I+D+I para la formación de doctores (FPI, BES-2017-07968). La Unión Europea ha colaborado con el aporte de fondos de cohesión (FEDER) a los anteriores proyectos y mediante los proyectos MAXRoot-C y MIXRoot-C. European Joint Programme EJP SOIL “Towards climate-smart sustainable management of agricultural soils” 2nd Internal Call topic: CM1 — Plant below-ground inputs to enhance soil carbon sequestration (Grant Agr. Nr. 862695).

15 páginas, 5 figuras, 1 tabla, Outbreak strains of Mycobacterium tuberculosis are promising candidates as targets in the search for intrinsic determinants of transmissibility, as they are responsible for many cases with sustained transmission; however, the use of low-resolution typing methods and restricted geographical investigations represent flaws in assessing the success of long-lived outbreak strains. We can now address the nature of outbreak strains by combining large genomic data sets and phylodynamic approaches. We retrospectively sequenced the whole genome of representative samples assigned to an outbreak circulating in the Canary Islands (the GC strain) since 1993, which accounts for ~20% of local tuberculosis cases. We selected a panel of specific single nucleotide polymorphism (SNP) markers for an in-silico search for additional outbreak-related sequences within publicly available tuberculosis genomic data. Using this information, we inferred the origin, spread, and epidemiological parameters of the GC strain. Our approach allowed us to accurately trace the historical and more recent dispersion of the GC strain. We provide evidence of a highly successful nature within the Canarian archipelago but limited expansion abroad. Estimation of epidemiological parameters from genomic data disagree with a distinctive biology of the GC strain. With the increasing availability of genomic data allowing for the accurate inference of strain spread and critical epidemiological parameters, we can now revisit the link between Mycobacterium tuberculosis genotypes and transmission, as is routinely carried out for SARS-CoV-2 variants of concern. We demonstrate that social determinants rather than intrinsically higher bacterial transmissibility better explain the success of the GC strain. Importantly, our approach can be used to trace and characterize strains of interest worldwide. IMPORTANCE Infectious disease outbreaks represent a significant problem for public health. Tracing outbreak expansion and understanding the main factors behind emergence and persistence remain critical to effective disease control. Our study allows researchers and public health authorities to use Whole-Genome Sequencing-based methods to trace outbreaks, and shows how available epidemiological information helps to evaluate the factors underpinning outbreak persistence. Taking advantage of all the freely available information placed in public repositories, researchers can accurately establish the expansion of an outbreak beyond original boundaries, and determine the potential risk of a strain to inform health authorities which, in turn, can define target strategies to mitigate expansion and persistence. Finally, we show the need to evaluate strain transmissibility in different geographic contexts to unequivocally associate spread to local or pathogenic factors, an important lesson taken from genomic surveillance of SARS-CoV-2., This project has been funded by the European Research Council (101001038-TBRECONNECT), the Ministerio de Economía, Industria y Competitividad (PID2019-104477RB-I00), and the European Commission–NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global) to I.C. This project has been funded by the Instituto de Salud Carlos III (FIS18/0336) and the Gobierno de Aragón/Fondo Social Europeo “Construyendo Europa desde Aragón” to SS

Background: We estimated the association between the level of restriction in nine different fields of activity and SARS-CoV-2 transmissibility in Spain, from 15 September 2020 to 9 May 2021. Methods: A stringency index (0–1) was created for each Spanish province (n = 50) daily. A hierarchical multiplicative model was fitted. The median of coefficients across provinces (95% bootstrap confidence intervals) quantified the effect of increasing one standard deviation in the stringency index over the logarithmic return of the weekly percentage variation of the 7-days SARS-CoV-2 cumulative incidence, lagged 12 days. Results: Overall, increasing restrictions reduced SARS-CoV-2 transmission by 22% (RR = 0.78; one-sided 95%CI: 0, 0.82) in 1 week, with highest effects for culture and leisure 14% (0.86; 0, 0.98), social distancing 13% (0.87; 0, 0.95), indoor restaurants 10% (0.90; 0, 0.95) and indoor sports 6% (0.94; 0, 0.98). In a reduced model with seven fields, culture and leisure no longer had a significant effect while ceremonies decreased transmission by 5% (0.95; 0, 0.96). Models R2 was around 70%. Conclusion: Increased restrictions decreased COVID-19 transmission. Limitations include remaining collinearity between fields, and somewhat artificial quantification of qualitative restrictions, so the exact attribution of the effect to specific areas must be done with caution. This work has been partially supported by GAIN (Galician Innovation Agency) and the Regional Ministry of Economy, Employment and Industry, Xunta de Galicia IN845D 2020/26 (Grant COV20/00604) through the ERDF (2014-2020). The research of DGU has been financed in part by the Spanish Agencia Estatal de Investigación under grants PID2021-122154NB-I00 and TED2021-129455B-I00, and by a 2021 BBVA Foundation project for research in Mathematics. He also acknowledges support from the EU under the 2014-2020 ERDF Operational Programme and the Department of Economy, Knowledge, Business and University of the Regional Government of Andalusia (FEDER-UCA18-108393). Sí

11 páginas, 5 tablas, 4 figuras, Reducing the toxicity caused by antibiotics on bacterial communities in the soil is one of the great challenges of this century. For this, the effectiveness of amending the soil with different bioadsorbents such as crushed mussel shell (CMS), pine bark (PB) and biomass ash (BA), as well as combinations of them (CMS + PB and PB + BA) was studied at different doses (0 g kg-1 to 48 g kg-1). Soil samples were spiked, separately, with increasing doses (0-2000 mg kg-1) of cefuroxime (CMX), amoxicillin (AMX), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP) and trimethoprim (TMP). Their toxicity on bacterial growth was estimated using the tritium-labeled leucine (3H) incorporation method. Toxicity was observed to behave differently depending on the antibiotic family and bioadsorbent, although in different magnitude and at different doses. The toxicity of β-lactams (AMX and CXM) was reduced by up to 54% when the highest doses of bio-adsorbents were added due to the increase in pH (CMS and BA) and carbon (PB) contribution. Macrolides (CLA and AZI) showed slight toxicity in un-amended soil samples, which increased by up to 65% with the addition of the bio-adsorbents. The toxicity of CIP (a fluoroquinolone) increased with the dose of the bio-adsorbents, reaching up to 20% compared with the control. Finally, the toxicity of TMP (a diaminopyrimidine) slightly increased with the dose of bio-adsorbents. The by-products that increase soil pH are those that showed the highest increases of CLA, AZI, CIP and TMP toxicities. These results could help to prevent/reduce environmental pollution caused by different kinds of antibiotics, selecting the most appropriated bio-adsorbents and doses., This study has been funded by the Spanish Ministry of Science,Innovation and Universities through the projects RTI2018-099574-B-C21 and RTI2018-099574-B-C22 (FEDER Funds). David Fernández Calviño holds a Ramón y Cajal contract (RYC-2016-20411) financed by the Spanish Ministry of Economy, Industry and Competitiveness. Vanesa Santás Miguel holds a postdoctoral fellowship (ED481B-2022-081) financed by Xunta de Galicia. Laura Rodríguez González holds a predoctoral fellowship (ED481A-2021/309) financed by Xunta de Galicia. Funding for open access charge: Universidade de Vigo/CISUG.

10 Páginas.-- 4 Figuras.-- 4 Tablas, According to recent studies, the anaerobic digestion of strawberry extrudate is a promising option with potential in the berry industry biorefinery. However, the lack and/or unbalance of concentrations of metals in some agro-industrial residues could hamper methane production during the anaerobic digestion of these kinds of wastes. In this study, a fractional factorial design was applied to screen the supplementation requirements regarding six metals (Co, Ni, Fe, Cu, Mn, and Zn) for methane production from strawberry extrudate (SE). The logistic model was used to fit the experimental data of methane production-time. It allowed identifying two different stages in the anaerobic process and obtaining the kinetic parameters for each step. Maximum methane production obtained in the first (Bmax) kinetic stage, the methane production in the second stage (P), and the maximum methane production rates (Rmax) concluded a statistically significant effect for Ni and Zn. The second set of experiments was carried out with Ni and Zn through a central composite design to study the concentration effect in the anaerobic digestion process of the strawberry extrudate. The parameters P and Rmax demonstrated a positive interaction between Ni and Zn. Although, Bmax did not prove a statistically significant effect between Ni and Zn., This research was funded by the Spanish Ministry of Economy, Industry, and Competitiveness through the Research Project CTM 2017-83870-R.

11 figures, 3 tables.-- Supplementary information available., Carbon nanostructures provide a unique platform for the synthesis of novel catalysts for biomass conversion. In this work, a set of graphene oxide (GO)-based materials (nanofibers (GONF), sheets of few-layers (FLGO), and quantum dots (GOQD)), differing structurally in morphology and size, was prepared from fishbone-carbon nanofibers (CNF) and their catalytic behavior was compared on the hydrolysis of amorphous cellulose under microwave (MW) radiation. First, the influence of the reaction temperature (135–180 ºC), holding time (0–120 min), catalyst morphology and cellulose/water ratio (0.25–2.0 wt%) was thoroughly screened and compared with conventional heating mode. The use of GO morphologies in concert with MW energy showed the potential to achieve similar kinetic profiles than previously reported sulfonated carbons (110 kJ/mol) but using considerably less amount of catalyst (cellulose-to-catalyst ratio 12-fold lower). Overall, the reactivity of the GO-catalyst was related to their degree of oxidation/exfoliation, decreasing as follows: GOQD > FLGO > GONF. Compared with conventional heating, MW-technology enabled higher loadings of cellulose (2.0 vs. 0.25 wt%) to be processed in a shorter time (20 min instead of 24 h), which is a landmark achievement toward process intensification., The authors are grateful for the financial support from the Spanish Ministry of Economy and Competitiveness (MINECO, Project ENE2017–83854-R) and the I+D+i project PID2020–115053RB-I00, funded by MCIN/ AEI/10.13039/501100011033. E.F. also thanks Ibercaja bank entity for a grant-in-aid for foreign research stays (CB 7/19). J.R. is grateful to the Spanish Ministry of Science, Innovation and Universities for the Juan de la Cierva Incorporación (JdC-I) fellowship (Grant Number: IJC2018–037110-I) awarded. DT is grateful for the Juan de la Cierva Incorporación (JdC-I) fellowship (Grant Number: IJC2020–045553-I) funded by MCIN/AEI/ 10.13039/501100011033 and by “European Union NextGenerationEU/PRTR”.

12 páginas, 4 figuras, 4 tablas., Toxoplasma gondii is a major cause of reproductive failure in small ruminants. Genotypic diversity of T. gondii strains has been associated with variations in phenotypic traits in in vitro and murine models. However, whether such diversity could influence the outcome of infection in small ruminants remains mostly unexplored. Here, we investigate the outcome of oral challenge in sheep at mid-pregnancy with 10 sporulated oocysts from three different T. gondii isolates belonging to archetypal II and III and selected according to their genetic and phenotypic variations shown in previous studies. Seventy-three pregnant sheep were divided in four groups: G1 infected with TgShSp1 isolate (type II, ToxoDB#3), G2 with TgShSp16 isolate (type II, ToxoDB#3), G3 with TgShSp24 isolate (type III, ToxoDB#2) and G4 of uninfected control sheep. Two different approaches were carried out within this study: (i) the outcome for the pregnancy after infection (n = 33) and (ii) the lesions and parasite tropism and burden at 14 and 28 days post infection (dpi) (n = 40). The onset of hyperthermia and seroconversion occurred one and two days later, respectively in G1 when compared to G2 and G3. However, sheep that suffered from reproductive failure, either by abortion, foetal dead at the time of euthanasia or stillbirth were similar among infected groups (50%, 40% and 47%, respectively). Histological lesions in placentomes and foetal tissues from euthanized animals from the second approach were only detected at 28 dpi and mainly in G1. At 14 dpi, T. gondii-DNA was only detected in G1 in the 11% of the placentomes. However, at 28 dpi the frequency of detection in placentomes was higher in G1 (96%) than in G2 and G3 (7% and 47%, respectively) besides in foetuses was lower in G2 (20%) than in G1 and G3 (100% and 87%, respectively). Regarding late abortions, stillbirths, and lambs of G1, G2 and G3, the frequency of microscopic lesions was similar between groups (79%, 78% and 67%, respectively) whereas T. gondii-DNA was evidenced in 100%, 55% and 100%, respectively. These recently obtained T. gondii isolates led to similar reproductive losses but intra- and intergenotype variations in the rise of hyperthermia, dynamics of antibodies, frequency of lesions and parasite detection and distribution. Thus, the different phenotypic traits of the isolates could influence the outcome of the infection and mechanisms responsible for it, and further investigations are warranted., This work was supported by research projects from the “Junta de Castilla y Leon´ ” (LE080U16) and FEDER/Spanish Ministry of Economy, Industry and Competitiveness-Spanish State Research Agency, AEI (AGL2016-75935-C2-1-R and AGL2016-75935-C2-2-R).Raquel Vallejo, Noive Arteche-Villasol and Miguel Criado are the recipients of a predoctoral contract from the Ministry of Science and Innovation (grant no. FPU-1705346, BES-2016076513 and PRE2019–087309, respectively).

This chapter examines the Zaydi uṣūl work Ḥāshiyat al-Fuṣūl al-luʾluʾiyya of Aḥmad b. ʿAbdallāh Ibn al-Wazīr (d. 985/1577). This work is a gloss on Ṣārim al-Dīn al-Wazīr’s (d. 914/1508) al-Fuṣūl al-luʾluʾiyya. In his commentary, Aḥmad b. ʿAbdallāh explains points of interpretive disagreement among the schools of law and clarifies linguistic and terminological details of genre-specific vocabulary introduced by al-Wazīr in al-Fuṣūl. We surmise that the brevity of al-Fuṣūl and the Ḥāshiya’s focus on foundational explanations suggest that these two texts were written for teaching purposes. The topic under discussion in this chapter is analogy (qiyās). Contrary to the Twelvers, we demonstrate, Zaydi Uṣūlis consider qiyās to be a valid juridical tool of interpretation., Jan Thiele’s work on this publication was conducted under the aegis of the grant RYC-2015–18346, funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro.”

Medina played a crucial role in the ways Muslims of the Islamic West constructed their religiosity and followed the law, as well as in the political legitimization of their rulers. This paper, building upon previous studies of mine, offers an overview of this crucial role. It includes an innovative practice, the sending of letters to be read at the Prophet’s grave in Medina, the development of a ‘virtual’ visitation of this grave, and a curious tale of how two Iberian Christians attempted to destroy it. Special attention is paid to how Cordoba was represented as a new Medina through its mosque, the minbar, the spread of the nisba ‘al-Ansari,’ and the adoption of the legal school founded by the Medinese scholar Malik b. Anas., This research has been carried out in the framework of the research project Contextos locales y dinámicas globales: al-Andalus y el Magreb en el Oriente islámico (AMOI), FFI2016-78878-R AEI/FEDER, UE.

14 figures, 6 tables., The synthesis of sorbitol from cellulose over Ni catalysts is a promising valorisation route in the biorefinery scenario, applying relatively simple preparation methods and earth-abundant metals. The overall selectivity, however, depends on the kinetic control of a complex reaction network, involving the hydrolysis of cellulose to monosaccharides via cello-oligomers, glucose hydrogenation into sorbitol and hydrogenolysis side-reactions of sugars and sorbitol to low molecular weight polyols. Therein, subtle changes in the catalyst composition and process conditions might have a strong impact on the final product distribution. Driven by these challenges, this work first-time provides novel insights into the hydrothermal hydrogenation of cellulose over a carbon nanofibre supported Ni catalyst (Ni/CNF). Firstly, the impact of the duration of a ball-milling pre-treatment step and the influences of the hydrothermal time and temperature were thoroughly analysed. The experimental results obtained highlighted the importance of process control to promote the first transformation of cellulose to glucose and its subsequent hydrogenation to sorbitol to minimise the extension of side reactions. Finally, an additional study was conducted to palliate the recalcitrant nature of cellulose by decreasing mass transfer limitations to a minimum extent. This was achieved by including an additional mix-milling of the amorphous cellulose produced in the first pre-treatment with the catalyst and increasing the H2 pressure of the hydrothermal hydrogenation process. This allowed attaining a sorbitol yield as high as 62% at 190 ºC using an initial H2 pressure of 8 MPa for 26 h, which is one of the best results reported in the literature., The authors are grateful for the financial support from the Spanish Ministry of Economy and Competitiveness (MINECO, Project ENE2017-83854-R) and the I+D+i project PID2020-115053RB-I00, funded by MCIN/ AEI/10.13039/501100011033. J.R. and D.T. are grateful to the Spanish Ministry of Science, Innovation and Universities for the Juan de la Cierva Incorporación (JdC-I) fellowships (Grant Numbers: IJC2018-037110-I and IJC2020-045553-I, respectively) awarded.

Multiple viral infection is an important issue in health and agriculture with strong impacts on society and the economy. Several investigations have dealt with the population dynamics of viruses with different dynamic properties, focusing on strain competition during multiple infections and the effects on viruses’ hosts. Recent interest has been on how multiple infections respond to abiotic factors such as temperature (T). This is especially important in the case of plant pathogens, whose dynamics could be affected significantly by global warming. However, few mathematical models incorporate the effect of T on parasite fitness, especially in mixed infections. Here, we investigate simple mathematical models incorporating thermal reaction norms (TRNs), which allow for quantitative analysis. A logistic model is considered for single infections, which is extended to a Lotka-Volterra competition model for mixed infections. The dynamics of these two models are investigated, focusing on the roles of T-dependent replication and competitive interactions in both transient and asymptotic dynamics. We determine the scenarios of co-existence and competitive exclusion, which are separated by a transcritical bifurcation. To illustrate the applicability of these models, we ran single- and mixed-infection experiments in plants growing at 20º C and 30º C using two strains of the plant RNA virus Pepino mosaic virus. Using a macroevolutionary algorithm, we fitted the models to the data by estimating the TRNs for both strains in single infections. Then, we used these TRNs to feed the mixed-infection model estimating the strength of competition. We found an asymmetrical pattern in which each strain dominated at different T values due to differences in their TRNs. We also identified that T can modify competition interference greatly for both isolates. The models proposed here can be useful for investigating the outcomes of multiple-infection dynamics under abiotic changes and have implications for the understanding of viral responses to global warming., J.S. has been partially funded by the CERCA Program of the Generalitat de Catalunya, by the Ministry of Economy, Industry and Competitiveness (MINECO) grant MTM2015-71509-C2-1-R, by Agencia Estatal de Investigación (AEI) grant RTI2018-098322-B-I00, and by a Ramón y Cajal contract (RYC-2017-22243). C.A. was funded by the MINECO within a PhD program grant (FPU16/02569). This work was also supported by the AEI-FEDER grants AGL2014-59556-R and AGL2017-89550-R to P.G. and PID2019-103998GB-I00 to S.F.E.

The electroweak (EW) sector of the Minimal Supersymmetric Standard Model (MSSM), with the lightest neutralino as Dark Matter (DM) candidate, can account for a variety of experimental data. This includes the DM content of the universe, DM direct detection limits, EW SUSY searches at the LHC and in particular the so far persistent 3−4σ discrepancy between the experimental result for the anomalous magnetic moment of the muon, (g−2)μ, and its Standard Model (SM) prediction. The recently published “MUON G-2” result is within 0.8σ in agreement with the older BNL result on (g−2)μ. The combination of the two results was given as aexpμ=(11659206.1±4.1)×10−10, yielding a new deviation from the SM prediction of Δaμ=(25.1±5.9)×10−10, corresponding to 4.2σ. Using this improved bound we update the results presented in Chakraborti et al. (Eur Phys J C 80(10):984, 2020) and set new upper limits on the allowed parameters space of the EW sector of the MSSM. We find that with the new (g−2)μ result the upper limits on the (next-to-) lightest SUSY particle are in the same ballpark as previously, yielding updated upper limits on these masses of ∼750GeV. In this way, a clear target is confirmed for future (HL-)LHC EW searches, as well as for future high-energy e+e− colliders, such as the ILC or CLIC., The work of I.S. is supported by World Premier International Research Center Initiative (WPI), MEXT, Japan. The work of S.H. is supported in part by the MEINCOP Spain under contract PID2019-110058GB-C21 and in part by the AEI through the grant IFT Centro de Excelencia Severo Ochoa SEV-2016-0597. The work of M.C. is supported by the project AstroCeNT: Particle Astrophysics Science and Technology Centre, carried out within the International Research Agendas programme of the Foundation for Polish Science financed by the European Union under the European Regional Development Fund.

Recently, the emergence of an international lineage of the CTX-M-27-producing clade C1 of Escherichia coli ST131 is being observed. The aim is to see if this strain has also been introduced in our area. Twenty-eight (33%) out of 86 individuals from two LTCFs in Seville were found to be colonized with fluoroquinolone-resistant E. coli ST131 and 46% isolates were ESBL/pAmpC producers. C1 isolates were more common than C2 and more frequently produced blaESBL/pAmpC genes (53% vs 33%). Strain sharing was observed in 6 groups of 2–5 cases (61%). A differentiated cluster of 5 C1-CTX-M-27 isolates was found which lacked the M27PP1 region., This work was funded by the Plan Nacional de I + D + i 2013–2016 and the Instituto de Salud Carlos III (Acciones Complementarias AC16/00072) supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) with a One Health approach; and Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI; RD16/0016/0001 and REIPI RD16/0016/0009) co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020.

Most available prognostic nomograms in metastatic castration-resistant prostate cancer (mCRPC) are derived from datasets not representative of the current treatment landscape. A prognostic nomogram for first-line mCRPC treatment was developed from patients treated in the PREVAIL study. To validate the Armstrong model in the COU-AA-302 trial. A post hoc analysis of mCRPC patients treated in the COU-AA-302 trial was carried out (NCT00887198). The Armstrong prognostic model was applied to patients treated in COU-AA-302. A continuous risk score was derived from coefficients from the original model. Time-dependent area under the curve (tAUC) was used to evaluate the overall predictive ability of the model. Patients were categorized according to the number of risk factors present into those at a low (three or fewer risk factors), intermediate (four to six risk factors), and high (seven to ten risk factors) risk. The association with survival was assessed with Cox regression models. Interaction tests were used to assess the impact of treatment arm in each of the prognostic groups. A total of 1088 patients were analyzed. The risk score was associated with overall survival (OS; tAUC 0.733). Most patients were at a low (49%) or intermediate (41%) risk. Risk category was significantly associated with OS (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.9-2.4; p

8 figuras.- refefencias.- Versión aceptada del artículo.- Supplementary data kiab469_Suppl. https://academic.oup.com/plphys/advance-article/doi/10.1093/plphys/kiab469/6400262#supplementary-data, Recent studies demonstrate that several polyphenolic compounds produced from beyond the canonical monolignol biosynthetic pathways can behave as lignin monomers, participating in radical coupling reactions and being incorporated into lignin polymers. Here, we show various classes of flavonoids, the chalconoid naringenin chalcone, the flavanones naringenin and dihydrotricin, and the flavone tricin, incorporate into the lignin polymer of papyrus (Cyperus papyrus L.) rind. These flavonoids were released from the rind lignin by DFRC, a chemical degradative method that cleaves the β-ether linkages, indicating that at least a fraction of each was integrated into the lignin as β-ether linked structures. Due to the particular structure of tricin and dihydrotricin, whose C-3ʹ and C-5ʹ positions at their B-rings are occupied by methoxy groups, these compounds can only be incorporated into the lignin through 4ʹ–O–β bonds. However, naringenin chalcone and naringenin have no substituents at these positions and can therefore form additional carbon-carbon linkages, including 3ʹ– or 5ʹ–β linkages that form phenylcoumaran structures not susceptible to cleavage by DFRC. Furthermore, NMR analysis indicated that naringenin chalcone can also form additional linkages through its conjugated double bond. The discovery expands the range of flavonoids incorporated into natural lignins, further broadens the traditional definition of lignin, and enhances the premise that any phenolic compound present at the cell wall during lignification could be oxidized and potentially integrated into the lignin structure, depending only on its chemical compatibility. This study indicates that papyrus lignin has a unique structure as it is the only lignin known to date that integrates such a diversity of phenolic compounds from different classes of flavonoids. This discovery will open up new ways to engineer and design lignins with specific properties and for enhanced value., This work was funded by the Spanish State Research Agency and the European Regional 51 Development Fund (project AGL2017-83036-R), the Consejería de Transformación 52 Económica, Industria, Conocimiento y Universidades, Junta de Andalucía (project P20-53 00017), the DOE Great Lakes Bioenergy Research Center (DOE BER Office of Science DE54 SC0018409), and the Austrian Biorefinery Center Tulln (ABCT). MJR thanks the Spanish 55 Ministry of Science, Innovation and Universities for a FPI fellowship (PRE2018-083267).

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on retinal degeneration and microglia activation in rd10 mice, a model of RP, as well as on LPS-stimulated BV2 cells. The EFA supplement was orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behavior in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabeling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR, ELISA and histology. Redox status was analyzed by measuring antioxidant enzymes and markers of oxidative damage. Interestingly, the EFA supplement ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss. The EFA supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas and LPS-stimulated BV2 cells. It also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities based on resolving inflammation with oral supplementation with SPMs such as the EFA supplement., This work was funded by the Spanish Ministry of Economy, Industry, and Competitiveness (MINECO), Carlos III Health Institute (ISCIII), grant numbers PI18/00252, PI20/01305, and co-funded by the European Union—European Regional Development Fund (ERDF) and the European Social Fund (FSE) ‘A way of making Europe’. It was also funded by Junta de Andalucía, grant number PE-0002-2018, CIBERER Cooperative and complementary intramural actions (ACCI) 2018, and RETINA CV. R.R. had an ISCIII Spanish National Health System (SNS) Miguel Servet Type II research contract CP15/00019. S.V. was funded by a Conselleria de Innovación, Universidades, Ciencia y Sociedad, GVA predoctoral contract (ACIF/2021/430). C.L. was funded by a Junta de Andalucía, postdoctoral contract (PAIDI2020- DOC_00350) and co-funded by the FSE 2014–2020.

We checked the effect of biochar addition to a fertile temperate soil on plant growth and the quantity and quality of seeds of four varieties of wheat (Triticum spp., two “ancient” varieties, Verna and Senatore Cappelli, and two “modern” varieties, Bologna and Claudio) and a high oleic hybrid of sunflower (Helianthus annuus L.). Relatively novel is the qualitative investigation of the marketable product, as few are the works on this topic. We tested three different doses of biochar—1, 4, and 20 t ha−1—versus an untreated soil (“control”) in a 2-year open field trial in Central Italy, where wheat was grown the first year and sunflower the second year. Biochar addition did not change the soil characteristics save for the carbon content, which increased significantly with the highest dose of biochar. Also, we did not find any significant biochar-induced effect on plant growth and yields of both wheat and sunflower. Regarding the qualitative aspects, adding biochar to the soil implied an increase in total polyphenols in the middlings and bran of wheat and, with the highest dose of biochar, also in total proteins and in flavonoids and caffeic acid derivatives. Instead, no difference in carotenoids concentration and antiradical activity was observed in middlings or bran. As for the sunflower, no significant difference in seeds’ composition was detected at any of the biochar doses. The addition of biochar to a fertile, well-drained soil as the one we investigated is not detrimental to the quantity and quality of wheat and sunflower seeds. Rather, the concentration of some polyphenols in wheat appears to be positively affected by biochar addition., The work benefited of a doctoral fellowship (XXXIII cycle) by the University of Firenze. Marco Panettieri acknowledges the Spanish Ministry of Science, Innovation and Universities for his post-doctoral fellowship number IJCI-2016-27693. The formerly Spanish Ministry of Economy, Industry and Competitiveness (MINEICO) and AEI/FEDER are thanked for funding the project CGL2015-64811-P.

12 páginas, 6 figuras, Coenzyme A (CoA) is an essential cofactor involved in a range of metabolic pathways including the activation of long-chain fatty acids for catabolism. Cells synthesize CoA de novo from vitamin B5 (pantothenate) via a pathway strongly conserved across prokaryotes and eukaryotes. In humans, it involves five enzymatic steps catalyzed by four enzymes: pantothenate kinase (PANK [isoforms 1-4]), 4'-phosphopantothenoylcysteine synthetase (PPCS), phosphopantothenoylcysteine decarboxylase (PPCDC), and CoA synthase (COASY). To date, inborn errors of metabolism associated with all of these genes, except PPCDC, have been described, two related to neurodegeneration with brain iron accumulation (NBIA), and one associated with a cardiac phenotype. This paper reports another defect in this pathway (detected in two sisters), associated with a fatal cardiac phenotype, caused by biallelic variants (p.Thr53Pro and p.Ala95Val) of PPCDC. PPCDC enzyme (EC 4.1.1.36) catalyzes the decarboxylation of 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine in CoA biosynthesis. The variants p.Thr53Pro and p.Ala95Val affect residues highly conserved across different species; p.Thr53Pro is involved in the binding of flavin mononucleotide, and p.Ala95Val is likely a destabilizing mutation. Patient-derived fibroblasts showed an absence of PPCDC protein, and nearly 50% reductions in CoA levels. The cells showed clear energy deficiency problems, with defects in mitochondrial respiration, and mostly glycolytic ATP synthesis. Functional studies performed in yeast suggest these mutations to be functionally relevant. In summary, this work describes a new, ultra-rare, severe inborn error of metabolism due to pathogenic variants of PPCDC., This work was funded by the Instituto de Salud Carlos (ISCIII), the European Regional Development Fund [PI19/01155], the Ministerio de Economía, Industria y Competitividad, Spain (BFU2017-82574-P), and the Consejería de Educacion, Juventud y Deporte, Comunidad de Madrid [B2017/BMD3721].

La dopamina (DA) es un neurotransmisor ampliamente distribuido en el cerebro que interviene en el control del movimiento, en el sistema de recompensa, sueño, atención y procesos de memoria y aprendizaje. Además, regula estados emocionales, motivación y toma de decisiones. La DA es el neurotransmisor que controla las neuronas estriatales de proyección (NEP), que son el principal tipo de neuronas del estriado y del núcleo accumbens (NAc). Estudios previos han mostrado el papel clave de la DA en la regulación de la plasticidad estructural y sináptica de las NEP. Los astrocitos, establecen una comunicación bidireccional con las neuronas, conocida como Sinapsis Tripartita. Sin embargo, debido a la complejidad de las interacciones de las NEP y los astrocitos en múltiples circuitos, muchos de estos mecanismos aún siguen siendo desconocidos. En esta tesis, se han establecido algunos de estos mecanismos mediante el estudio de los siguientes objetivos: I) relación entre la concentración de DA liberada en el estriado y la densidad de espinas dendríticas, II) papel de los receptores dopaminérgicos D1 y D2 en la regulación estructural y sináptica de las neuronas estriatales de proyección, III), relación entre la liberación de DA y la activación de diferentes grupos de astrocitos, IV), modulación de la plasticidad sináptica de las NEP por los astrocitos. Para el abordaje de estos objetivos se emplearon: registros de patch-clamp en la configuración célula entera in vitro en secciones coronales de estriado y NAc, estudios de optogenética, registros electroquímicos de medición en la liberación de DA y estudios morfológicos mediante microinyecciones por iontoforesis de las NEP. Nuestros resultados demuestran que la densidad de espinas dendríticas en las NEP está regulada por los niveles de DA en función del grado de inervación proveniente de la sustancia negra. Además, demostramos que el uso de drogas psicoestimulantes modifica la plasticidad sináptica de la vía dopaminérgica ATV-NAc a través de los transportadores de glutamato GLT-1 astrocitarios y proponemos un nuevo mecanismo de plasticidad sináptica inducido por drogas adictivas. Finalmente, mostramos que existe una comunicación bidireccional astrocito- neurona específico y dependiente del tipo de receptor dopaminérgico. Este proceso ocurre debido a un incremento en la actividad de la señalización dopaminérgica por drogas psicoestimulantes que activa selectivamente una población de astrocitos que sólo se comunica con las NEP-D1. Nuestro trabajo contribuye a una mejor comprensión de los mecanismos por los cuales la DA modula la plasticidad estructural y sináptica proponiendo así posibles dianas terapéuticas en las patologías asociadas con fallos en el sistema dopaminérgico, como la enfermedad de Parkinson y las adicciones, Este trabajo se realizó con la ayuda económica del Ministerio de Economía, Industria y Competitividad (SAF2016-78207-R); Ministerio de Ciencia, Innovación y Universidades (BFU2017-88393-P); Ministerio de Ciencia e Innovación (PID2020-116327GB-I00). El doctorando fue dotado con una Ayuda Predoctoral para la formación de personal investigador del Ministerio de Economía, Industria y Competitividad (BES-2017-080872)

Lactobacilli are well-studied bacteria that can undergo oxidative selective pressures by plant phenolic compounds (PPCs) in plants, during some food fermentations or in the gastrointestinal tract of animals via dietary inputs. Lactobacilli are known to be more tolerant to PPCs than other bacterial groups and, therefore, must have mechanisms to cope with the effects of these metabolites. In this review, we intend to present what is currently known about the basics beyond the responses of Lactobacillus spp. to individual PPCs. We review the molecular mechanisms that are engaged in the PPC-modulated responses studied to date in these bacteria that have been mainly characterized by system-based strategies, and we discuss their differences and similarities. A wide variety of mechanisms are induced to increase the oxidative stress response highlighting the antimicrobial nature of PPCs. However other uncovered mechanisms that are involved in the response to these compounds are reviewed, including the capacity of PPCs to modulate the expression of molecular functions used by lactobacilli to adapt to host environments. This shows that these phytochemicals can act as more than just antimicrobial agents in the dual interaction with lactobacilli., This work was supported by the Spanish Ministerio de Economía, Industria and Competitividad under Grant numbers AGL2017-84614-C2-2-R and AGL2014-52911 (AEI/FEDER, UE) and CSIC under Grant number ICOOPB20412.

Surfactants are commonly used as disinfection agents in personal care products against bacteria and viruses, including SARS-CoV-2. However, there is a lack of understanding of the molecular mechanisms of the inactivation of viruses by surfactants. Here, we employ coarse grain (CG) and all-atom (AA) molecular dynamics simulations to investigate the interaction between general families of surfactants and the SARS-CoV-2 virus. To this end, we considered a CG model of a full virion. Overall, we found that surfactants have only a small impact over the virus envelope, being inserted into the envelope without dissolving it or generating pores, at the conditions considered here. However, we found that surfactants may induce a deep impact on the spike protein of the virus (responsible for its infectivity), easily covering it and inducing its collapse over the envelope surface of the virus. AA simulations confirmed that both negatively and positively charged surfactants are able to extensively adsorb over the spike protein and get inserted into the virus envelope. Our results suggest that the best strategy for the design of surfactants as virucidal agents will be to focus on those strongly interacting with the spike protein., This work was supported by the Spanish Ministry of Science and Innovation through Grant No. PID2021-124297NBC33, the “Severo Ochoa” Grant No. CEX2019-000917-S for Centres of Excellence in R&D awarded to ICMAB and the FPI grant PRE2020-093689 awarded to M. D. We thank the CESGA supercomputing center for computer time and technical support at the Finisterrae supercomputer. We thank Dr. Alvin Yu and Prof. G.A.Voth (University of Chicago) for their help on the implementation of the virus model and for providing us the code for the "Two Gaussian" potential. M. D. is enrolled in the Material Sciences PhD program of the Universitat Autonoma de Barcelona

Rho1p is a membrane-associated protein that belongs to the Rho family of small GTPases. These proteins coordinate processes such as actin remodelling and polarised secretion to maintain the shape and homeostasis of yeast cells. In response to extracellular stimuli, Rho1p undergoes conformational switching between a guanosine triphosphate (GTP)-bound active state and a guanosine diphosphate (GDP)-bound inactive state. Cycling is improved with guanine nucleotide exchange factor (GEF) activity necessary to activate signalling and GTPase activating protein (GAP) activity required for subsequent signal depletion. This review focuses on fission yeast Rho1p GEFs, Rgf1p, Rgf2p, and Rgf3p that belong to the family of DH-PH domain-containing Dbl-related GEFs. They are multi-domain proteins that detect biological signals that induce or inhibit their catalytic activity over Rho1p. Each of them activates Rho1p in different places and times. Rgf1p acts preferentially during polarised growth. Rgf2p is required for sporulation, and Rgf3p plays an essential function in septum synthesis. In addition, we outline the noncanonical roles of Rho1p-GEFs in genomic instability., PG was supported by a postdoctoral Programa II contract granted by the University of Salamanca. RC was financially supported by an FPU fellowship from the Spanish Ministry of Education, and JPP was partially financed by the programme “Escalera de Excelencia,” from the Junta de Castilla y León (CLU-2017-03). Thanks to Proof-reading-service for the English revision of the manuscript. Funding sources: MEIC, Spain (BFU2017-84508-P), (PID2020-115111GB-I00), and the Regional Government of Castile and Leon (SA116G19). YS is also thankful for the financial support awarded to the Institute of Biological and Functional Genomics (IBFG) (CLU-2017-03) provided by the Junta de Castilla y León through the programme “Escalera de Excelencia,” co-financed by the PO FEDER of Castilla y León 14-20.

Despite being one of the most important crops in the recent prehistory of Eurasia, the arrival and exploitation of millets in the westernmost part of Europe are still largely underexplored. Here and for the first time, we report multipronged biomolecular evidence of millet consumption along the Atlantic façade of northern Iberia through a combination of radiocarbon dating, stable isotopes, and dental calculus analyses on the human individuals found in the burial site of El Espinoso cave (Asturias, Spain). The high-resolution chronological framework established for individuals placed the burials between 1235 and 1099 cal. BC. The discovery of high δC values on their bone collagen and the identification of polyhedral starch grains within their dental plaque underline the relevance of C plants in their diet and highlights the timing of the systematic consumption of millets in the Late Bronze Age. Our data support previous regional archaeobotanical evidence and establish a more precise chronology of the dispersal of millets into northern Iberia during the Bronze Age, becoming an essential crop until the arrival of maize from America after AD 1492. This study emphasizes the importance of multidisciplinary methods to ascertain the origin and development of agricultural practices during recent prehistory., This study is part of B.G.R.’s Doctoral dissertation, supervised by A.B.M.A. and M.R.G.M. This research is funded by the research projects of the Spanish Economy, Industry and Competitiveness Ministry HAR2016-75605-R to M.R.G.M. and HAR2017- 84997-P to A.B.M.A. Part of this research, including the stable isotope analyses, was funded by the ERC Consolidator Grant (SUBSILIENCE ref. 818299), awarded to A.B.M.A. Analysis of dental calculus was carried out in the framework of the ERC Starting Grant (HIDDEN FOODS ref. 639286), awarded to E.C. T

The soluble epoxide hydrolase (sEH) has been suggested as a pharmacological target for the treatment of several diseases, including pain-related disorders. Herein, we report further medicinal chemistry around new benzohomoadamantane-based sEH inhibitors (sEHI) in order to improve the drug metabolism and pharmacokinetics properties of a previous hit. After an extensive in vitro screening cascade, molecular modeling, and in vivo pharmacokinetics studies, two candidates were evaluated in vivo in a murine model of capsaicin-induced allodynia. The two compounds showed an anti-allodynic effect in a dose-dependent manner. Moreover, the most potent compound presented robust analgesic efficacy in the cyclophosphamide-induced murine model of cystitis, a well-established model of visceral pain. Overall, these results suggest painful bladder syndrome as a new possible indication for sEHI, opening a new range of applications for them in the visceral pain field., Spanish Government SAF2017-82771-R RTI2018-093955-B-C21 PGC2018-102192-B-I00 RTI2018-101032-J-I00 Spanish MCIN/AEI, ERDF A way of making Europe - MCIN/AEI PID2020-118127RB-I00, PID2019-106285RB, ERDF A way of making Europe, Xunta de Galicia, European Commission ED431G 2019/02, ED431C 2018/21, Fundacio Bosch i Gimpera, Universitat de Barcelona (F2I grant) Generalitat de Catalunya 2017 SGR 106 2017 SGR 1707, European Research Council (ERC) European Commission ERC-2015-StG-679001-NetMoDEzyme European Commission MSCA-IF-2014-EF661160-MetAccembly, Universitat de Barcelona (APIF grant), Spanish Society of Medicinal Chemistry (SEQT) and Lilly FWO 12Y0720N, Ministry of Science and Innovation, Spain (MICINN) Spanish Government RYC2020-029552-I, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R35 ES03443 P42 ES004699, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) R01 DK107767 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01 DK103616

We have used near linear-scaling density functional theory (LS-DFT) methods including dispersion, for the first time, to study the interaction of two isomers, equatorial (Eq) and axial (Ax), of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with the DNA G-quadruplexes (GQ) to gain insight into its cytotoxicity. The LMKLL/DZDP level of calculation, which includes van der Waals contributions, with the SIESTA software was used to treat by means of first-principles computations the whole biological studied model system with ∼1000 atoms. Computed formation energies point to systems containing the Ax isomer as the most stable although the nearest system in energy containing the Eq isomer is only 7.5 kcal mol−1 above. On the other hand, the energy decomposition analysis (EDA) favours interaction energies for the systems containing the Eq isomer. However, when solvent effects are taken into account the systems containing the Ax isomer are again the most stable. This Ax isomer was found interacting by means of end-stacking with the GQ and surprisingly totally inside the non-canonical secondary structure, where all the ligands of the metal complex produce several weak interactions with the DNA structure. On the other hand, the Eq isomer prefers to interact from outside by means of intercalation in which the ancillary ligands also have some role in the interaction. Such features and comparison with the results regarding the interaction of the [Mo(η3-C3H5)Br(CO)2(phen)] metal complex with duplex DNA suggest that the [Mo(η3-C3H5)Br(CO)2(phen)] would have a higher affinity and eventual selectivity for non-canonical DNA GQ structures., This research was financially supported by the Fundação para a Ciência e a Tecnologia (FCT) by means of the projects PTDC/QUI-QFI/29236/2017, UIDB/04046/2020 and UIDP/04046/2020 and by the Spanish Ministry of Economy, Industry and Competitiveness under the Maria de Maeztu Units of Excellence Programme – MDM-2016-0618. A. G. is thankful to ARAID – Fundación Agencia Aragonesa para la Investigación y el Desarrollo for the current funding in the frame of ARAID researchers. The authors are also thankful for the technical and human support provided by IZO-SGI (SGIker) of UPV/EHU and the European funding (ERDF and ESF). Financial support comes also from Eusko Jaurlaritza (Basque Government) through the project IT1584-22, and grant PGC2018-099321-B-100 from the Ministry of Science, Innovation and Universities through the Office of Science Research (MINECO/FEDER). We also acknowledge PRACE for awarding us access to Marconi-KNL at CINECA, Italy. Pseudopotentials and Numerical Atomic Orbitals Basis Data set for SIESTA were provided by Simune Atomistics S. L. (www.simuneatomistics.com). I. O. d. L. is also very grateful to CIC-nanogune BRTA for his PhD grant.

Resumen de la comunicación oral presentada en: I Spanish-Portuguese Congress on Beneficial Plant-Microbe Interactions (BeMiPlant) and XVIII National Meeting of the Spanish Society of Nitrogen Fixation (XVIII SEFIN). Oeiras, Portugal, 17-19 octubre (2022), This research was supported by AEI BIO2017-83533-P, CSIC 2021AEP136 and grant PRE2018-083387(AEI).

Atherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction, and stroke and is the leading cause of mortality worldwide. Immunization of pro-atherogenic mice with malondialdehyde-modified low-density lipoprotein (MDA-LDL) neo-antigen is athero-protective. However, the immune response to MDA-LDL and the mechanisms responsible for this athero-protection are not completely understood. Here, we find that immunization of mice with MDA-LDL elicits memory B cells, plasma cells, and switched anti-MDA-LDL antibodies as well as clonal expansion and affinity maturation, indicating that MDA-LDL triggers a bona fide germinal center antibody response. Further, Prdm1fl/flAicda-Cre+/kiLdlr-/- pro-atherogenic chimeras, which lack germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization is not athero-protective in mice lacking germinal-center-derived plasma cells. Our findings give further support to the development of MDA-LDL-based vaccines for the prevention or treatment of atherosclerosis. We thank all members of the B Cell Biology Laboratory for useful discussions, A. Rodriguez-Ronchel for the design of the graphical abstract, V.G. de Ye´benes for critical reading of the manuscript, and V. Labrador for help with microscopy and image analysis. I.M.-F. and C.L. were fellows of the research training program funded by Ministerio de Economı´a y Competitividad (SVP-2014-068216 and SVP-2014-068289, respectively), A.d.M.M. is funded by ‘‘la Caixa’’ Foundation HR17–00247, and A.R.R. was supported by Centro Nacional de Investigaciones Cardiovasculares (CNIC). The project leading to these results has received funding from la Caixa Banking Foundation under the project code HR17-00247 and from SAF2016-75511-R and PID2019-106773RB-I00/AEI/10.13039/501100 011033 grants to A.R.R. (Plan Estatal de Investigacio´ n Cientı´fica y Te´ cnica y de Innovacio´ n 2013–2016 Programa Estatal de I+D+i Orientada a los Retos de la Sociedad Retos Investigacio´ n: Proyectos I + D + i 2016, Ministerio de Economı´a,Industria y Competitividad) and co-funding by Fondo Europeo de Desarrollo Regional (FEDER). CIBERCV (J.L.M.-V.) and CIBERDEM (J.C.E.-G.) are Instituto de Salud Carlos III projects. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovacio´ n (MCIN), and the Pro CNIC Foundation and is a Severo Ochoa institute (CEX2020-001041-S grant funded by MCIN/AEI/10.13039/501100011033). Sí

El presente artículo refiere a las aproximaciones de la doctrina a la teoría de la pérdida de oportunidad en España. La otrora denominada «hermana pobre del derecho de daños» ha pasado de ser una figura poco atendida por parte de los agentes jurídicos a ser una construcción dogmática trascendente y relevante en el estudio de la responsabilidad civil. El presente estudio informa de los orígenes y las dos perspectivas que tratan la pérdida de oportunidad: el enfoque desde el daño y el enfoque desde la causalidad. A continuación, se analizará el desarrollo doctrinal en el ordenamiento jurídico español de esta teoría, mediante el estudio de la pérdida de oportunidad procesal en materia de abogados y la pérdida de oportunidad de curación en materia médica. Finalmente, consecuencia de lo expuesto, se proporcionan algunas reflexiones y aportes a la teoría de la pérdida de oportunidad. This article refers to the doctrinal approaches to the loss of chance in Spain. The formerly called «poor sister of tort law» has changed radically its importance in recent years, turning a fi gure slightly considered by legal agents into a transcendent and relevant dogmatic construction used in the study of civil liability. The present research examines its origins and the two perspectives that deal with the loss of chance: the damage approach and causation approach. In addition, this doctrinal development in the Spanish legal system is analyzed by studying the loss of procedural opportunity in matters of lawyers and the loss of chance of recovery in medical matters. Finally, as a consequence of the above, some refl ections and contributions to the loss of chance doctrine are provided. Este trabajo ha sido elaborado en el seno del Proyecto «Las fronteras del Derecho del enriquecimiento injustificado» (DER2017-85594-C2-1-P; IP Pedro del Olmo), financiado por la Agencia Estatal de Investigación dependiente del Ministerio de Economía, Industria y Competitividad (Gobierno de España)

Objectives: Little is known about IMP-producing Enterobacterales (IMP-Ent) in Europe. We analyzed at genomic and phenotypic level IMP-Ent isolates circulating in Spain in a 9-year period. Materials and methods: IMP-Ent isolates submitted to our reference laboratory were included. Antibiotic susceptibility was performed using microdilution method (EUCAST), and IMP-carbapenemase activity was measured with carbapenemase inhibitors, the β-CARBA method, the modified Hodge test (MHT), and the modified carbapenemase inhibition method (mCIM). All isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: Fifty IMP-Ent isolates, collected from 19 hospitals in 13 Spanish provinces, were detected: Klebsiella pneumoniae (IMP-Kpn) (24; 48%), Enterobacter roggenkampii (13; 26%), Enterobacter hormaechei (8, 16%), Klebsiella oxytoca (two; 4%), Enterobacter asburiae (one, 2%), Serratia marcescens (one; 2%) and Escherichia coli (one; 2%). All isolates were positive by the MHT and β-CARBA tests; 48 (96%) were mCIM positive; 12 (24%) and 26 (52%) displayed positive inhibition with dipicolinic (meropenem) and EDTA (ertapenem), respectively. Five IMP-carbapenemase types were identified: IMP-8 (22; 44%), IMP-22 (17; 34%), IMP-13 (7; 14%), IMP-28 (two; 4%), and IMP-15 (two; 4%), predominating IMP-8 in K. pneumoniae and IMP-22 in E. roggenkampii. IMP-28 was exclusively identified in K. oxytoca and IMP-15 in E. hormaechei. Predominant STs were ST405 (29.2%), ST15 (25%) and ST464 (20.8%) in IMP-Kpn; ST96 (100%) in E. roggenkampii and ST182 (62.5%) in E. hormachei. Colistin and amikacin were the most active non-carbapenem antibiotics against IMP-Ent. Conclusion: IMP-Ent isolates remain infrequent in Spain, although in recent years have been circulating causing nosocomial outbreaks, being IMP-8-producing K. pneumoniae and IMP-22-producing E. roggenkampii the most frequently detected in this study. Inhibition with EDTA or dipicolinic acid presented false negative results in some IMP-producing strains. Active microbiological and molecular surveillance is essential for a better comprehension and control of IMP-Ent dissemination. This research was supported by grants from the Instituto de Salud Carlos III (numbers PI18CIII/00030 and PI21CIII/00039). This research was also supported by CIBER-Consorcio Centro de Investigación Biomédica en Red (CB21/13/00095 and CB21/13/000968), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU. This work was supported by Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16CIII/0004/0002 and REIPI RD16/0016/0007) and co-financed by the European Development Regional Fund (EDRF), “A way to achieve Europe,” Operative program Intelligent Growth, 2014–2020. Sí

Poster del trabajo presentado en el XV Congreso Nacional de Micología, celebrado en Valencia del 7 al 9 de septiembre de 2022, El exómero es un complejo proteico que facilita el transporte de vesículas desde la red trans del Golgi (TGN) hasta la membrana plasmática (MP). En Saccharomyces cerevisiae su ausencia causa la retención de un conjunto específico de proteínas cargo en este orgánulo. El exómero de Schizosaccharomyces pombe está compuesto por Cfr1 y Bch1. Los mutantes cfr1¿ y bch1¿ son sensibles a estrés iónico pero no osmótico. Además, la actividad ATPasa en la MP es mayor en un mutante del exómero, lo que sugiere una hiperpolarización de la membrana. Además, en respuesta a estrés por K+, los niveles de Ca2+ intracelular aumentan significativamente más en cfr1¿ que en el silvestre. Los análisis por microscopía muestran una morfología endosomal defectuosa en los mutantes. Esto va acompañado de un incremento de los niveles intracelulares del exportador de K+ Cta3 y el canal de Ca2+ Pck2, que están parcialmente acumulados en el endosoma prevacuolar. Aun así, estos transportadores iónicos llegan a la membrana en los sitios de crecimiento polarizado, lo que demuestra que su transporte desde el TGN ocurre en ausencia del exómero. En los momentos posteriores a su expresión génica en presencia de KCl, la localización polarizada de Cta3 y Pkd2 en la membrana está alterada en los mutantes, de manera que su distribución es asimétrica y subapical. Finalmente, el uso de sondas fluorescentes sugiere que en los mutantes hay una distribución defectuosa de algunos lípidos de la MP en presencia de KCl. Por tanto, el exómero participa en muchos procesos celulares que están alterados en respuesta a estrés por K+. Estos resultados apoyan la idea de que el exómero juega un papel general en el mantenimiento del TGN, la secreción polarizada, y la respuesta a estrés que no está necesariamente relacionado con una función como adaptador de cargo., Este trabajo ha sido posible gracias al apoyo del Ministerio de Economía, Industria y Competitividad/Ciencia, Investigación y Universidades/ programa European Regional Development Fund—FEDER—(BFU2017-84508-P y PID2020-115111GB-I00 a M-HV y PGC2018-098924-B-I00 a PP), y de la Junta de Castilla y Leon/programa FEDER (CSI150P20 a PP, y Escalera de Excelencia CLU-2017-03/14-20 al IBFG). SM disfrutó de becas de la Universidad de Salamanca y el Ministerio de Educación, y EMR disfrutó de una beca de la Junta de Castilla y León. Las becas de la Agencia Española de Investigación (AEI) PID2019-104054 GB-I00 y RTC-2017-6468-2-AR financiaron a JM. QC y AP fueron financiados por la “University of Toledo start up fund” y una beca del “National Institute of Health” (R15GM134496).

29 p.2 fig.-3 tab.-1 graph.abst.+Sup. Inf. 4 p._4 tab., The Ames mutagenicity test constitutes the most frequently used assay to estimate the mutagenic potential of drug candidates. While this test employs experimental results using various strains of Salmonella typhimurium, the vast majority of the published in silico models for predicting mutagenicity do not take into account the test results of the individual experiments conducted for each strain. Instead, such QSAR models are generally trained employing overall labels (i.e., mutagenic and nonmutagenic). Recently, neural-based models combined with multitask learning strategies have yielded interesting results in different domains, given their capabilities to model multitarget functions. In this scenario, we propose a novel neural-based QSAR model to predict mutagenicity that leverages experimental results from different strains involved in the Ames test by means of a multitask learning approach. To the best of our knowledge, the modeling strategy hereby proposed has not been applied to model Ames mutagenicity previously. The results yielded by our model surpass those obtained by single-task modeling strategies, such as models that predict the overall Ames label or ensemble models built from individual strains. For reproducibility and accessibility purposes, all source code and datasets used in our experiments are publicly available., This work was partially supported by the Argentinean National Council of Scientific and Technological Research (CONICET for its acronym in Spanish) [Grant No.PIP 112-2017-0100829], by the National Agency for the Promotion of Research, Technological Development and Innovation of Argentina (AGENCIA I+D+i in Spanish),through the Fund for Scientific and Technological Research (FONCyT for its acronym in Spanish) [Grant No. PICT 2019-03350], by the Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina [Grant No. PGI 24/N042], Ministerio de Economía, Industria y Competitividad, Gobierno de España, under Grant No. RTI2018-096100B-100, and by a Google Latin America Research Award 2021−2022.

In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64-256 for imipenem and 16-128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing P. aeruginosa. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites., This study was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI18-01842), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, and the Spanish Network for Research in Infectious Diseases (REIPI, RD16/0016/0004, RD16/0016/0009)—co-financed by the European Development Regional Fund, A way to achieve Europe, Operative program Intelligent Growth 2014-2020. S.H.E is supported by the by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI18-01842). M.E.P.I. is a researcher belonging to the program “Nicolás Monardes” (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. R.A.M., J.M.C., and M.E.P.I. (CB21/13/00006) and A.O.P. (CB21/13/00099) also received support from the CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, co-financed by the European Development Regional Fund.

9 páginas, 2 tablas, 3 figuras., Soil-transmitted helminth (STH) cornerstone control strategy is mass drug administration (MDA) with benzimidazoles. However, MDA might contribute to selection pressure for anthelmintic resistance, as occurred in livestock. The aim of this study is to evaluate the treatment response to albendazole and the relationship with the presence of putative benzimidazole resistance single-nucleotide polymorphisms (SNPs) in the b-tubulin gene of STH in Southern Mozambique. After screening 819 participants, we conducted a cohort study with 184 participants infected with STH in Manhic¸ a district, Southern Mozambique. A pretreatment and a posttreatment stool samples were collected and the STH infection was identified by duplicate Kato-Katz and quantitative polymerase chain reaction (qPCR). Cure rate and egg reduction rates were calculated. Putative benzimidazole resistance SNPs (F167Y, F200T, and E198A) in Trichuris trichiura and Necator americanus were assessed by pyrosequencing. Cure rates by duplicate Kato-Katz and by qPCR were 95.8% and 93.6% for Ascaris lumbricoides, 28% and 7.8% for T. trichiura, and 88.9% and 56.7% for N. americanus. Egg reduction rate by duplicate Kato-Katz was 85.4% for A. lumbricoides, 34.9% for T. trichiura, and 40.5% for N. americanus. Putative benzimidazole resistance SNPs in the b-tubulin gene were detected in T. trichiura (23%) and N. americanus (21%) infected participants at pretreatment. No statistical difference was observed between pretreatment and posttreatment frequencies for none of the SNPs. Although treatment response to albendazole was low, particularly in T. trichiura, the putative benzimidazole resistance SNPs were not higher after treatment in the population studied. New insights are needed for a better understanding and monitoring of human anthelmintic resistance., This work was supported by the British Society for Antimicrobial Chemotherapy (Bsac-2018-0018) and Mundo Sano Foundation (www.mundosano.org). We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018- 000806-S), and support from the “Generalitat de Catalunya” through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). M. C. P. was funded by Junta de Castilla y Leon and Fondo Social Europeo (LE-135-19). J. G. was personally supported at the beginning of the work by the Ramon Areces Foundation and is now funded by the Spanish “Juan de la Cierva” Programme, Ministry of Economy and Competitiveness (FJC-2018-38305). M. M. V. by the “Ramon y Cajal ” Programme (RYC-2015-18368), Spanish Ministry of Economy, Industry and Competitiveness (MINECO). This project was in part funded by the EDCTP2 program supported by the European Union (Grant no. RIA2017NCT-1845-STOP; www.stoptheworm.org) Horizon 2020 European Union Funding for Research and Innovation.

Congresso SGI-SIMP 2022. Geosciences for a sustainable future, 19th-21st september 2021 (Italia), Soil pollution by trace element is a worldwide concern. One possibility for the remediation of these polluted soils is the application of organic amendments. Nevertheless, organic amendments are very diverse and their properties need to be studied prior to their use. Biochar, the solid residue produced by thermal treatment of biomass under absence of oxygen (pyrolysis), has diverse properties depending on feedstock and pyrolysis conditions (Campos et al., 2020). In this work, biochars were produced under different pyrolysis conditions, pyrolysis reactor and feedstock. The continuous pyrolysis reactor required only 12 minutes of residence time of the feedstock in the reactor to produce biochars with similar properties than those pyrolysed during at least 1 h in the fixed bed reactor. Produced biochars were tested for metal adsorption in batch experiment and greenhouse experiment. Among the biochars used, rice husk biochar may be considered the better tool to reduce metal pollution, as it showed a maximum adsorption capacity of 30.7 and 19.3 mg g-1 for Cu2+ and Pb2+, respectively. The most promising biochars for degraded soils remediation (rice husk biochar and olive pit biochar) were used as amendment (8 t ha-1) at a field experiment. The plots were located in Aznalcóllar (Spain). These soils were polluted in April 1998 by the massive dumping of mine sludge contaminated with heavy metals, called the Aznalcóllar disaster. Additionally, biochar was buried in nylon bags to determine changes in biochar composition and physical properties due to the ageing process. The experiment lasted 22 months and soil properties, enzymatic activities and plant development were periodically analysed. The biochar potential for carbon sequestration was also analysed. Soils were sampled after 6, 12 and 20 months for determining microbial diversity using the Illumina Miseq technology of the 16S rRNA gene. The application of 8 t ha-1 of RHB and OPB (produced at the continuous pyrolysis reactor) at field recovered soil ecological functionality in the studied polluted soils. The studied biochars significantly adsorbed the trace elements present in the studied soils after 2 years. Nevertheless, in these highly multicontaminated soils, the application of 8 t ha-1 of biochar was not enough for an effective reduction in trace element bioavailability, which is explained by the existence of an equilibrium in such polluted soils. Campos P., Miller A.Z., Knicker H., Costa-Pereira M.F., Merino A. & De la Rosa J.M. (2020) - Chemical, physical and morphological properties of biochars produced from agricultural residues: Implications for their use as soil amendment. J. Waste Manag.,105, 256-267., The former Spanish Ministry of Economy, Industry and Competitiveness (MINEICO) and AEI/FEDER are acknowledge for funding the project CGL2016-76498-R.

Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a expression in endothelial cells during blood vessel formation have reported conflicting results. Here, we have assessed the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. Transfection of miR-133a-3p or -5p mimics in primary human endothelial cells significantly inhibited proliferation, migration, and tubular morphogenesis of transfected cells. Screening of gene arrays related to angiogenic processes, and further validation by TaqMan qPCR, revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a collection of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. Our results suggest that controlled delivery of miR-133a-3p mimics, or antagomirs in diseased endothelial cells, might open new therapeutic interventions to treat patients suffering from cardiovascular pathologies that occur with excessive or insufficient angiogenesis. We thank Ben Small for technical assistance in the cell cycle fow cytometry experiments. Tis work was supported by the Research Institute in Healthcare Sciences, Faculty of Science and Engineering, University of Wolverhampton (to A.L.A) and by generous donations from the charities “Wolverhampton Coronary Afercare Support Group” (to A.L.A and J.C) and “Rotha Abraham Bequest” (to A.L.A and J.C). S.A. is the recipient of a University of Wolverhampton-Wolverhampton Royal NHS Trust joint PhD studentship. JMR has received funding from the “La Caixa” Banking Foundation HR18-00068 (to J.M.R.); Spanish Ministerio de Ciencia e Innovación grant RTI2018-099246-B-I00 (MICIU/AEI/FEDER, UE) to J.M.R and the Instituto de Salud Carlos III (CIBER-CV CB16/11/00264) to J.M.R. Te Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro-CNIC Foundation. Sí

10 Pág., RNA splicing and epigenetic gene mutations are the most frequent genetic lesions found in patients with myelodysplastic neoplasm (MDS). About 25% of patients present concomitant mutations in such pathways, suggesting a cooperative role in MDS pathogenesis. Importantly, mutations in the splicing factor ZRSR2 frequently associate with alterations in the epigenetic regulator TET2. However, the impact of these concurrent mutations in hematopoiesis and MDS remains unclear. Using CRISPR/Cas9 genetically engineered mice, we demonstrate that Zrsr2m/mTet2-/- promote MDS with reduced penetrance. Animals presented peripheral blood cytopenia, splenomegaly, extramedullary hematopoiesis, and multi-lineage dysplasia, signs consistent with MDS. We identified a myelo-erythroid differentiation block accompanied by an expansion of LT-HSC and MPP2 progenitors. Transplanted animals presented a similar phenotype, thus indicating that alterations were cell-autonomous. Whole-transcriptome analysis in HSPC revealed key alterations in ribosome, inflammation, and migration/motility processes. Moreover, we found the MAPK pathway as the most affected target by mRNA aberrant splicing. Collectively, this study shows that concomitant Zrsr2 mutation and Tet2 loss are sufficient to initiate MDS in mice. Understanding this mechanistic interplay will be crucial for the identification of novel therapeutic targets in the spliceosome/epigenetic MDS subgroup., This investigation was supported by the grant SAF2017-82171-R to ASP from the Spanish Ministry of Economy, Industry, and Competitiveness. CGR is founded by JAP Valencia AECC predoctoral fellowships. CMV is sponsored by a predoctoral fellowship from Generalitat Valenciana (ACIF/2018/255). AL is funded by Generalitat Valenciana (APOSTD/2021/212). AGA was funded by grant RTI2018-093548-B-I00 from the Spanish Ministry of Science and Innovation. ASP is supported by the Ramón y Cajal Program (RYC2015-17534)

Behavioural and psychological symptoms of dementia (BPSD) are presented in 95% of Alzheimer’s Disease (AD) patients and are also associated with neurotrophin deficits. The molecular mechanisms leading to age-related diseases are still unclear; however, emerging evidence has suggested that epigenetic modulation is a key pathophysiological basis of ageing and neurodegeneration. In particular, it has been suggested that G9a methyltransferase and its repressive histone mark (H3K9me2) are important in shaping learning and memory by modulating autophagic activity and synaptic plasticity. This work deepens our understanding of the epigenetic mechanisms underlying the loss of cognitive function and BPSD in AD. For this purpose, several tasks were performed to evaluate the parameters of sociability (three-chamber test), aggressiveness (resident intruder), anxiety (elevated plus maze and open field) and memory (novel object recognition test) in mice, followed by the evaluation of epigenetic, autophagy and synaptic plasticity markers at the molecular level. The behavioural alterations presented by senescence-accelerated mice prone 8 (SAMP8) of 12 months of age compared with their senescence-accelerated mouse resistant mice (SAMR1), the healthy control strain was accompanied by age-related cognitive deficits and alterations in epigenetic markers. Increased levels of G9a are concomitant to the dysregulation of the JNK pathway in aged SAMP8, driving a failure in autophagosome formation. Furthermore, lower expression of the genes involved in the memory-consolidation process modulated by ERK was observed in the aged male SAMP8 model, suggesting the implication of G9a. In any case, two of the most important neurotrophins, namely brain-derived neurotrophic factor (Bdnf) and neurotrophin-3 (NT3), were found to be reduced, along with a decrease in the levels of dendritic branching and spine density presented by SAMP8 mice. Thus, the present study characterizes and provides information regarding the non-cognitive and cognitive states, as well as molecular alterations, in aged SAMP8, demonstrating the AD-like symptoms presented by this model. In any case, our results indicate that higher levels of G9a are associated with autophagic deficits and alterations in synaptic plasticity, which could further explain the BPSD and cognitive decline exhibited by the model., This study was supported by the Ministerio de Economía, Industria y Competitividad (Agencia Estatal de Investigación, AEI) and Fondo Europeo de Desarrollo Regional (MINECO-FEDER) by the grants PDC2021-121096/AEI/10.13039/501100011033 and PID2020-118127RB-I00 funded by MCIN/AEI/10.13039/501100011033, and 2017SGR106 and 2019LLAV00017 from AGAUR.

5918 páginas.- 6 figuras.- 7 tablas.- 59 referencias, Endocarp residues remaining after coconut oil extraction from Acrocomia aculeate are traditionally used for combustion as fuel. As an alternative, we propose its conversion into biochar to substitute peat in planting substrates. To test the feasibility of this approach, untreated endocarp residues (particle size approx. 10 mm) and materials shredded into particles of 4 and 1 mm were pyrolyzed at 200 °C, 325 °C and 450 °C and were subsequently characterized. The pyrolysis-induced loss of organic matter increased the ash contents and pH. Nuclear magnetic resonance (NMR) spectroscopy confirmed the aromatization and a loss of carboxyl C with an increasing pyrolysis temperature. This is commonly associated with an enhanced biochemical recalcitrance. The particle size of the feedstock had no significant effect on the chemical composition or microporosity (BET-adsorption with COs) of the biochars, but affected their water holding capacity. With respect to macro- and micronutrients, only the potassium and Olsen P levels occurred in concentrations that are optimal for tomato seed growth. The low nitrogen level of the products may be advantageous for hydroponic culturing since it allows for a higher flexibility for the adaptation of nutrient contents based on the needs of the used culture., The former Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and AEI/FEDER are thanked for funding the project CGL2015-64811-P. The solid-state NMR spectroscopic analysis was provided and financed by the service unit “Solid-State NMR Spectroscopy (400 MHz) for Organic Matter Characterization” of the IRNAS-CSIC. Elemental, macro- and micro-elemental analysis, SEM and BET were performed at the Center for Research, Technology and Innovation (CITIUS) of the University of Seville

18 p.-7 fig.-2 tab., Relapsed or refractory T acute lymphoblastic leukemia (T-ALL) still carries poor prognosis. Aiming to improve outcomes, the therapeutic potential of an anti-CCR9 monoclonal antibody (mAb 92R), targeting the human chemokine-receptor CCR9 is analyzed on orthotopic xenotransplants. 92R mAb treatment of mice carrying human CCR9+ T-ALL cell lines or primary T cell leukemias inhibits tumor growth and increases survival. The therapeutic effects of 92R are specific and synergize with chemotherapeutic agents increasing survival. Furthermore, 92R decreases size of non-hematopoietic tumors with a forced CCR9 expression and of solid tumors generated by the pancreatic adenocarcinoma cell line AsPC-1. In addition, a humanized version of 92R mAb (Srb1) is also able to inhibit growth of CCR9+ T-ALL tumor cells in vivo, increasing survival 2.66-fold. Finally, 92R mAb prevents liver accumulation of infiltrates and reduces tumor cell numbers in already formed infiltrates. Thus, the humanized version of 92R mAb (Srb1), displays therapeutic potential for CCR9+ tumor treatment and might represent one of the first therapeutic antibodies for precision medicine on T-ALL patients., The work in the author’s laboratories was partially supported by grants from the PN2014-A from the ISCIII (PI14/00703, co-financed by FEDER funds from the EU, Operative program on Intelligent Growth 2014-2020, to LK); the Spanish Ministry of Economy, Industry and Competitiveness (RTC-2015-3786-1 to LK and JG-S), co-financed by FEDER funds from the EU and from the Spanish Ministry of Science and Innovation (PID2019-105404RB-I00 to JAGS and LK financed by MCIN/AEI/10.13039/501100011033). As well as the CSIC (PIE-201420E109 and PIE-201720E092, to LK).