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[ES] Introducción y objetivos Las secuelas cardiacas tras la infección por SARS-CoV-2 todavía están poco documentadas. Se realizó un estudio transversal en trabajadores sanitarios para estudiar la prevalencia de afección pericárdica y miocárdica tras la infección por SARS-CoV-2. Métodos Se estudió a 139 trabajadores sanitarios con infección previa confirmada por SARS-CoV-2. Los participantes se sometieron a evaluación clínica, electrocardiograma, laboratorio, incluido el perfil de células inmunitarias, y resonancia magnética cardiaca (RMC). El diagnóstico clínico de pericarditis se realizó ante la presencia de los criterios clásicos y el diagnóstico clínico de miocarditis ante la presencia de al menos 2 criterios de RMC. Resultados La mediana de edad fue de 52 (41–57) años, el 71,9% eran mujeres, y el 16,5% había sido hospitalizado previamente por neumonía por COVID-19. En la evaluación (10,4 [9,3–11,0] semanas después de los síntomas de infección), todos los participantes presentaban estabilidad hemodinámica. El 41,7% presentaba dolor torácico, disnea o palpitaciones; el 49,6%, alteraciones electrocardiográficas; el 7,9%, elevación de NT-proBNP; el 0,7%, elevación de troponina; y el 60,4%, alteraciones en la RMC. Un total de 30,9% de participantes cumplieron los criterios clínicos establecidos de pericarditis o miocarditis: pericarditis aislada en el 5,8%, miopericarditis en el 7,9% y miocarditis aislada en el 17,3%. La mayoría de los participantes (73,2%) mostraron recuentos de células inmunitarias alterados en sangre; en particular diminución de eosinófilos (27,3%; p < 0,001) y aumento del número de células T citotóxicas (17,3%; p < 0,001). La sospecha clínica de pericarditis se asoció (p < 0,005) particularmente con un elevado número de células T citotóxicas y recuento de eosinófilos disminuidos; mientras que los participantes con sospecha clínica de miopericarditis o miocarditis tenían recuentos de neutrófilos, células natural killer y células plasmáticas más bajos (p < 0,05). Conclusiones La afección pericárdica y miocárdica con estabilidad hemodinámica es frecuente después de la infección por SARS-CoV-2 y se asocia con perfiles de células inmunitarias específicas., [EN] Introduction and objectives The cardiac sequelae of SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in healthcare workers to report evidence of pericardial and myocardial involvement after SARS-CoV-2 infection. Methods We studied 139 healthcare workers with confirmed past SARS-CoV-2 infection. Participants underwent clinical assessment, electrocardiography, and laboratory tests, including immune cell profiling and cardiac magnetic resonance (CMR). Clinically suspected pericarditis was diagnosed when classic criteria were present and clinically suspected myocarditis was based on the combination of at least 2 CMR criteria. Results Median age was 52 (41-57) years, 71.9% were women, and 16.5% were previously hospitalized for COVID-19 pneumonia. On examination (10.4 [9.3-11.0] weeks after infection-like symptoms), participants showed hemodynamic stability. Chest pain, dyspnea or palpitations were present in 41.7% participants, electrocardiographic abnormalities in 49.6%, NT-proBNP elevation in 7.9%, troponin in 0.7%, and CMR abnormalities in 60.4%. A total of 30.9% participants met criteria for either pericarditis and/or myocarditis: isolated pericarditis was diagnosed in 5.8%, myopericarditis in 7.9%, and isolated myocarditis in 17.3%. Most participants (73.2%) showed altered immune cell counts in blood, particularly decreased eosinophil (27.3%; P < .001) and increased cytotoxic T cell numbers (17.3%; P < .001). Clinically suspected pericarditis was associated (P < .005) with particularly elevated cytotoxic T cells and decreased eosinophil counts, while participants diagnosed with clinically suspected myopericarditis or myocarditis had lower (P < .05) neutrophil counts, natural killer-cells, and plasma cells. Conclusions Pericardial and myocardial involvement with clinical stability are frequent after SARS-CoV-2 infection and are associated with specific immune cell profiles., Este estudio contó con el apoyo de CIBERCV (CB16/11/00374) y CIBERONC (CB16/12/00400) y la subvención COV20/00386 del Instituto de Salud Carlos III y FEDER, Ministerio de Ciencia e Innovación, Madrid, España, y por GRS COVID 26/A/20 de la Gerencia Regional de Salud, Junta de Castilla y León, España.

[EN] Objective Recently, we reported on a new MDD-like mouse model based on a regionally selective knockdown of astroglial glutamate transporters, GLAST/GLT-1, in infralimbic cortex (IL) which evokes widespread changes in mouse brain associated with the typical alterations found in MDD patients. To further characterize this new MDD-like mouse model, here we examine some transcriptional elements of glutamatergic/GABAergic neurotransmission and neuroplasticity in forebrain regions in the GLT-1 knockdown mice. Furthermore, we assess the acute ketamine effects on these transcriptional processes. Material and methods We used a small interfering RNA (siRNA) pool targeting GLT-1 mRNA to disrupt the GLT-1 transcription in mouse IL. Histological assays were performed to examine postsynaptic density protein-95 (PSD95), neuritin (NRN), glutamine acid descarboxilase-65 (GAD65), and GLT-1 mRNA expression in IL and hippocampus. Results Knockdown of GLT-1 in mouse IL leads to decreased expression of PSD95 and NRN neuroplasticity mRNAs in IL and hippocampus, which was reversed by an acute dose of ketamine antidepressant. Likewise, a single dose of ketamine also increased the mRNA levels of GAD65 and GLT-1 in IL of GLT-1 knockdown mice, reaching the basal values of control mice. Conclusions The glutamatergic neuronal hyperactivity and deficits in the GABA system resulting from siRNA-induced astroglial glutamate transporter knockdown in IL can compromise the integrity/plasticity of neurocircuits affected in MDD. Suitable depressive-like animal models to address the neurobiological changes in MDD are an unmet need and the development of the GLAST/GLT-1 knockdown mouse model may represent a better option to understand the rapid-acting antidepressant effects of ketamine., [ES] Objetivo Recientemente, informamos sobre un nuevo modelo de ratón de depresión basado en una reducción parcial de la transcripción de los transportadores de glutamato, GLAST/GLT-1, en los astrocitos de la corteza infralímbica (IL), que conduce a cambios generalizados de la función cerebral del ratón, que refleja alteraciones típicas encontradas en pacientes con depresión. Para caracterizar más detalladamente este nuevo modelo de ratón de depresión, aquí examinamos algunos elementos transcripcionales relacionados con la neurotransmisión glutamatérgica/GABAérgica y la neuroplasticidad en regiones corticales y subcorticales de los ratones con niveles reducidos de GLT-1. Además, evaluamos los efectos agudos de la ketamina, antidepresivo de acción rápida, en estos procesos transcripcionales. Material y métodos Utilizamos ARN de interferencia (siRNA) dirigido al mRNA de GLT-1 para interrumpir su transcripción en la IL de ratón. Se realizaron ensayos histológicos para examinar la expresión de los mRNA de las siguientes proteínas: proteína de densidad postsináptica-95 (PSD95), neuritina (NRN), descarboxilasa de ácido glutámico-65 (GAD65) y GLT-1 en la IL e hipocampo. Resultados La reducción de la expresión de GLT-1 en IL de ratón conduce a una disminución de la expresión de los mRNA de neuroplasticidad PSD95 y NRN en la IL y el hipocampo, efecto que se revirtió con una única administración del antidepresivo ketamina. Asimismo, una sola dosis de ketamina también aumentó los niveles de los mRNA de GAD65 y GLT-1 en la IL de ratones silenciados para GLT-1, que alcanzaron los valores basales de los ratones control. Conclusiones La hiperactividad neuronal glutamatérgica y los déficits en el sistema GABAérgico resultantes de la reducción de los niveles del transportador de glutamato astroglial inducida por siRNA en IL pueden comprometer la integridad/plasticidad de aquellos neurocircuitos afectados en la depresión. Sin embargo, no disponemos de modelos animales de depresión adecuados para abordar los cambios neurobiológicos que se suceden en esta enfermedad y su tratamiento. El desarrollo del modelo de ratón con reducción parcial de GLAST/GLT-1 puede representar una mejor opción para comprender los efectos antidepresivos de acción rápida de la ketamina., This study was supported by grants SAF2016-75797-R, PID2019-105136RB-100, Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (ERDF), UE; and CB/07/09/0034 Center for Networked Biomedical Research on Mental Health (CIBERSAM).

Spin pumping (SP) is a well-established method to generate pure spin currents allowing efficient spin injection into metals and semiconductors avoiding the problem of impedance mismatch. However, to disentangle pure spin currents from parasitic effects due to spin rectification effects (SRE) is a difficult task that is seriously hampering further developments. Here we propose a simple method that allows suppressing SRE contribution to inverse spin Hall effect (ISHE) voltage signal avoiding long and tedious angle-dependent measurements. We show an experimental study in the well-known Py/Pt system by using a coplanar waveguide (CPW). Results obtained demonstrate that the sign and size of the measured transverse voltage signal depends on the width of the sample along the CPW active line. A progressive reduction of this width evidences that SRE contribution to the measured transverse voltage signal becomes negligibly small for sample width below 200 μm. A numerical solution of the Maxwell equations in the CPW-sample setup, by using the Landau-Lifshitz equation with the Gilbert damping term (LLG) as the constitutive equation of the media, and with the proper set of boundary conditions, confirms the obtained experimental results., We acknowledge financial support from the Spanish Ministry of Science, Innovation and Universities through Severo Ochoa Program (CEX2019-000917-S), RTI2018-099960-B-I00 and funding from the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 645658 (DAFNEOX Project) and FEDER Program. CF thanks Prof. M. Kostylev for fruitful communications., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

In recent decades, our understanding of the molecular changes involved in neurodegenerative diseases has been transformed. Single-cell RNA sequencing and single-nucleus RNA sequencing technologies have been applied to provide cellular and molecular details of the brain at the single-cell level. This has expanded our knowledge of the central nervous system and provided insights into the molecular vulnerability of brain cell types and underlying mechanisms in neurodegenerative diseases. In this review, we highlight the recent advances and findings related to neurodegenerative diseases using these cutting-edge technologies., At the time of writing this review, N.V.T is funded by a postdoctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministerio de Ciencia, Innovación y Universidades – Spanish State Research Agency. Her research is also supported by the “la Caixa'' Foundation (LCF/PR/GN17/10300004) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016–2020 grant #SLT002/16/00201). J.D.G is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054). All CRG authors acknowledge the support of the Spanish Ministry of Science, Innovation, and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya.

The authors thankfully acknowledge the computer resources at MareNostrum 4 and the technical support provided by BSC (grant nos. RES-AECT-2019-3-0001 and RES-AECT-2020-1-0007). The authors also thank the Meteorological Service of Catalonia for providing the meteorological measurements. The MPLNET staff at NASA GSFC are warmly acknowledged, for the continuous help in keeping Barcelona MPL system and the data analysis up to date. Jose Maria Baldasano is acknowledged as the principal investigator (PI) of the Barcelona MPL.v, This paper investigates the mechanisms involved in the dispersion, structure, and mixing in the vertical column of atmospheric pollen. The methodology used employs observations of pollen concentration obtained from Hirst samplers (we will refer to this as surface pollen) and vertical distribution (polarization-sensitive lidar), as well as nested numerical simulations with an atmospheric transport model and a simplified pollen module developed especially for this study. The study focuses on the predominant pollen type, Pinus, of the intense pollination event which occurred in the region of Barcelona, Catalonia, NE Spain, during 27– 31 March 2015. First, conversion formulas are expressed to convert lidar-derived total backscatter coefficient and modelderived mass concentration into pollen grains concentration, the magnitude measured at the surface by means of aerobiological methods, and, for the first time ever, a relationship between optical and mass properties of atmospheric pollen through the estimation of the so-called specific extinction cross section is quantified in ambient conditions. Second, the model horizontal representativeness is assessed through a comparison between nested pollen simulations at 9, 3, and 1 km horizontal resolution and observed meteorological and aerobiological variables at seven sites around Catalonia. Finally, hourly observations of surface and column concentration in Barcelona are analyzed with the different numerical simulations at increasing horizontal resolution and varying sedimentation/deposition parameters. We find that the 9 or 3 km simulations are less sensitive to the meteorology errors; hence, they should be preferred for specific forecasting applications. The largest discrepancies between measured surface (Hirst) and column (lidar) concentrations occur during nighttime, where only residual pollen is detected in the column, whereas it is also present at the surface. The main reason is related to the lidar characteristics which have the lowest useful range bin at 225 m, above the usually very thin nocturnal stable boundary layer. At the hour of the day of maximum insolation, the pollen layer does not extend up to the top of the planetary boundary layer, according to the observations (lidar), probably because of gravity effects; however, the model simulates the pollen plume up to the top of the planetary boundary layer, resulting in an overestimation of the pollen load. Besides the large size and weight of Pinus grains, sedimentation/deposition processes have only a limited impact on the model vertical concentration in contrast to the emission processes. For further modeling research, emphasis is put on the accurate knowledge of plant/tree spatial distribution, density, and type, as well as on the establishment of reliable phenology functions., BSC RES-AECT-2019-3-0001 RES-AECT-2020-1-0007

The Free-Living Amoeba species, Naegleria fowleri is the causative agent of a lethal encephalitis known as Primary Amoebic Encephalitis (PAM). Moreover, most of the reported cases are often related to swimming and/or diving in aquatic environments. In addition, the current therapeutic options against PAM are not fully effective and hence, there is an urgent need to develop novel therapeutic agents against this disease. Previously isobenzofuranones compounds have been reported to present antiprotozoal and antifungal activity among others. However, to the best of our knowledge, these molecules have not been previously tested against N. fowleri. Therefore, the aim of this study was to evaluate the activity of 14 novel isobenzofuranones against this pathogenic amoeba. The most active and less toxic molecules, were assayed in order to check induction of Programmed Cell Death (PCD) in the treated amoebae. The obtained results showed that these molecules were able to eliminate N. fowleri trophozoites and also induced PCD. Therefore, the tested isobenzofuranones could be potential therapeutic candidates for the treatment of PAM., Graphical abstract Image 1, Highlights • A library of 14 new-aryl substituted isobezofuranones have been synthetized. • 8 isobenzofuranones showed high activity against Naegleria fowleri. • QOET-1, QOET-3, QOET-34 induced programmed cell death in treated amoebae.

Wastewater-based epidemiology (WBE) estimates collective consumption or exposure to chemicals or pathogens by monitoring the substances excreted in the population’s wastewater. Advances in mass spectrometry (MS) and the application of some clinical diagnostic tools and proteomics to wastewater fingerprinting have been linked to the discovery of new biomarkers and indicators of population health and are broadening the scope of WBE that nowadays cover not only small molecule biomarkers but also genetic biomarkers, large molecules, viruses, infection diseases, resistance, etc. This mini-review highlights recent WBE advances using MS and how this progress can create a fingerprint of a city’s health hazards, habits, and lifestyle, which is gaining in public health emphasis., This work has been supported by Grant RTI2018-097158-BC31 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”, Grant PID2020-114065RBC22 funded by MCIN/ AEI/ 10.13039/501100011033 and project ANTROPOCEN@ (PROMETEO/2018/155) funded by Generalitat Valenciana.

Despite the increasing evidence of links between human gut and health, the number of gut microbiomes that have been studied to date at a country level are surprisingly low. Mediterranean countries, including some of the most long-lived and healthy countries in the world, have not been considered so far in those studies at a large scale. The main objective of this work is to characterize the gut microbiome of a healthy adult population of a Mediterranean, paradigmatically healthy country: Spain. Stool samples from 530 healthy volunteers were collected, total metagenomic DNA extracted, and the microbial profiles determined through 16S rRNA metataxonomic sequencing. Our results confirm the associations between several microbial markers and different variables, including sex, age, BMI and diet choices, and bring new insights into the relationship between microbiome and diet in the Spanish population. Remarkably, some of the associations found, such as the decrease of Faecalibacterium with age or the link of Flavonifractor with less healthy dietary habits, have been barely noticed in other large-scale cohorts. On the other hand, a range of links between microorganisms, diet, and lifestyle coincide with those reported in other populations, thus increasing the robustness of such associations and confirming the importance of these microbial markers across different countries. Overall, this study describes the Spanish “normal” microbiome, providing a solid baseline for future studies investigating the effects of gut microbiome composition and deviations in the adherence to the Mediterranean diet., This study was funded by Instituto Central Lechera Asturiana de Nutrición Personalizada (ICLANP). Instituto de Desarrollo Económico del Principado de Asturias (IDEPA) also funded this work through "PROGRAMA RIS3-EMPRESA" (reference IDE/2020/000363). AL-P is a recipient of a Doctorado Industrial fellowship from the Spanish Ministerio de Ciencia, Innovación y Universidades (reference DI-17-09613).

Proteases are the most abundant enzyme gene family in vertebrates and they execute essential functions in all living organisms. Their main role is to hydrolase the peptide bond within proteins, a process also called proteolysis. Contrary to the conventional paradigm, proteases are not only random catalytic devices, but can perform highly selective and targeted cleavage of specific substrates, finely modulating multiple essential cellular processes. Lysosomal protease cathepsins comprise 3 families of proteases that preferentially act within acidic cellular compartments, but they can also be found in other cellular locations. They can operate alone or as part of signalling cascades and regulatory circuits, playing important roles in apoptosis, extracellular matrix remodelling, hepatic stellate cell activation, autophagy and metastasis, contributing to the initiation, development and progression of liver disease. In this review, we comprehensively summarise current knowledge on the role of lysosomal cathepsins in liver disease, with a particular emphasis on liver fibrosis, non-alcoholic fatty liver disease and hepatocellular carcinoma., AM’s research was supported by a “Research Challenges" R+D+i Project (RTI2018-097475-A-100) and a Ramon y Cajal contract (RYC-2016-19731) awarded by FEDER/Ministerio de Ciencia e Innovación - Agencia Estatal de Investigación. PRB is supported by a FPU PhD studentship (FPU19/05357) funded by Ministerio de Ciencia, Innovación y Universidades. VP held a PhD studentship funded by University of Naples Federico II. MFF salary was supported by JAE Intro fellowship (JAEINT_20_02409) from the Spanish National Research Council (CSIC) and FI AGAUR (2021 FI_B 00249).

Displaying a stress response to threatening stimuli is essential for survival. These reactions must be adjusted to be adaptive. Otherwise, even mental illnesses may develop. Describing the physiological stress response may contribute to distinguishing the abnormal responses that accompany the pathology, which may help to improve the development of both diagnoses and treatments. Recent advances have elucidated many of the processes and structures involved in stress response management; however, there is still much to unravel regarding this phenomenon. The main aim of the present research is to characterize the response of three brain areas deeply involved in the stress response (i.e., to an acute stressful experience). Specifically, the electrophysiological activity of the infralimbic division of the medial prefrontal cortex (IL), the basolateral nucleus of the amygdala (BLA), and the dorsal hippocampus (dHPC) was recorded after the infusion of 0.5 µl of corticosterone-releasing factor into the dorsal raphe nucleus (DRN), a procedure which has been validated as a paradigm to cause acute stress. This procedure induced a delayed reduction in slow waves in the three structures, and an increase in faster oscillations, such as those in theta, beta, and gamma bands. The mutual information at low theta frequencies between the BLA and the IL increased, and the delta and slow wave mutual information decreased. The low theta–mid gamma phase–amplitude coupling increased within BLA, as well as between BLA and IL. This electrical pattern may facilitate the activation of these structures, in response to the stressor, and memory consolidation., This work was supported by the Generalitat Valenciana (Emergent groups grant GV/2016/103), the Instituto de Salud Carlos III, and Subdirección General y Fomento de Investigación (FIS Grants PI13-00038, PI16-00217 and PI19-00170), which were co-funded by the European Regional Development Fund (‘A way to build Europe’). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III is also acknowledged. This work was also funded by the Spanish Ministry of Science and Innovation-FEDER (BFU2016-77691-C2-2-P and PID2019-108562GB-I00)

The concept of depth induces an ordering from centre outwards in multivariate data. Most depth definitions are unfeasible for dimensions larger than three or four, but the Modified Band Depth (MBD) is a notable exception that has proven to be a valuable tool in the analysis of high-dimensional gene expression data. This depth definition relates the centrality of each individual to its (partial) inclusion in all possible bands formed by elements of the data set. We assess (dis)similarity between pairs of observations by accounting for such bands and constructing binary matrices associated to each pair. From these, contingency tables are calculated and used to derive standard similarity indices. Our approach is computationally efficient and can be applied to bands formed by any number of observations from the data set. We have evaluated the performance of several band-based similarity indices with respect to that of other classical distances in standard classification and clustering tasks in a variety of simulated and real data sets. However, the use of the method is not restricted to these, the extension to other similarity coefficients being straightforward. Our experiments show the benefits of our technique, with some of the selected indices outperforming, among others, the Euclidean distance. This work has been financially supported by the FEDER/ Ministerio de Ciencia, Innovación y Universidades- Agencia Estatal de Investigación, Grant Numbers FIS2017-84440-C2-2-P and MTM2017-84446-C2-2-R, and by the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with UC3M in the line of Excellence of University Professors (EPUC3M23), and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation). Publicado

Keggin H3PW12O40 (PW12) and Wells-Dawson H6P2W18O60 (P2W18) heteropolyacids (HPAs) are photo(catalysts) for various acid-promoted and redox catalytic reactions. Their activity increases if they are deposited on certain supports as metal oxides or carbon materials. Although the surface area and acid-base interactions of the HPAs with supports are considered as key factors for the performance of the binary material, the role of the local structure changes in the HPAs upon their immobilization on solids must be also of primary importance, directly affecting both acidity and photoredox properties. Here, the (photo)catalytic performance of Keggin and Wells-Dawson heteropolytungstates supported on boron nitride (BN) and two types of carbon nitride (C3N4) in the gas-solid 2-propanol dehydration to propene has been studied. Apart from characterizing the materials by a set of conventional laboratory-scale structural and physical-chemical techniques, an insight into the variations of the local structure of supported HPAs is provided by means of X-ray absorption spectroscopy (XAS), and their influence on the supported HPAs (photo)catalytic activity is discussed. The irradiation with UV light increased the activity of both heteropolytungstates with respect to the catalytic experiments. The apparent activation energy calculated for the photo-assisted process resulted always lower with respect to that obtained for the catalytic one alone. Moreover, the materials that showed the highest apparent turnover frequency (TOF) were those in which the HPAs were impregnated on graphitic C3N4 or on BN and, in particular, the highest TOF values were observed at the highest temperature for the PW12/BN and P2W18/BN samples. Interestingly, the highest activity of HPAs supported on BN seems to be due to the stabilization of the W octahedral coordination, according to the XAS data., LFL is grateful to progetto di Ricerca ARS01_00637 Energie per l’Ambiente-TARANTO (PNR 2015-2020) for financial support. IK acknowledges support by Spanish MINECO (MAT2016-78155-C2-1-R), Gobierno del Principado de Asturias (GRUPIN-ID2018-170) and the Alexander von Humboldt Foundation through the Humboldt Research Fellowship. S.V.-R. and J.I.P. acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU), the Spanish Agencia Estatal de Investigación and European Regional Development Fund (ERDF) through project RTI2018-100832B-I00, and partial funding by Plan de Ciencia, Tecnología e Innovación (PCTI) 2013-2017 del Principado de Asturias and the ERDF (project IDI/2018/000233). A.S acknowledges financial support from the MCIU through the projects MAT2017-86540-C4-1-R and RTI2018-095303-A-C52 and from the Comunidad de Madrid for an “Atracción de Talento Investigador” contract (No. 2017t2/IND5395). The European Synchrotron (ESRF), MCIU and Consejo Superior de Investigaciones Científicas (CSIC) are also acknowledged for the provision of synchrotron radiation facilities. We also thank the BM25-SpLine staff for the technical support beyond their duties.

Listeria monocytogenes is a saprophytic gram-positive bacterium, and an opportunistic foodborne pathogen that can produce listeriosis in humans and animals. It has evolved an exceptional ability to adapt to stress conditions encountered in different environments, resulting in a ubiquitous distribution. Because some food preservation methods and disinfection protocols in food-processing environments cannot efficiently prevent contaminations, L. monocytogenes constitutes a threat to human health and a challenge to food safety. In the host, Listeria colonizes the gastrointestinal tract, crosses the intestinal barrier, and disseminates through the blood to target organs. In immunocompromised individuals, the elderly, and pregnant women, the pathogen can cross the blood-brain and placental barriers, leading to neurolisteriosis and materno-fetal listeriosis. Molecular and cell biology studies of infection have proven L. monocytogenes to be a versatile pathogen that deploys unique strategies to invade different cell types, survive and move inside the eukaryotic host cell, and spread from cell to cell. Here, we present the multifaceted Listeria life cycle from a comprehensive perspective. We discuss genetic features of pathogenic Listeria species, analyze factors involved in food contamination, and review bacterial strategies to tolerate stresses encountered both during food processing and along the host’s gastrointestinal tract. Then we dissect host–pathogen interactions underlying listerial pathogenesis in mammals from a cell biology and systemic point of view. Finally, we summarize the epidemiology, pathophysiology, and clinical features of listeriosis in humans and animals. This work aims to gather information from different fields crucial for a comprehensive understanding of the pathogenesis of L. monocytogenes., Graphical abstract

© The Author(s) 2021., In Parkinson’s disease, the dysfunction of the dopaminergic nigrostriatal tract involves the loss of function of dopaminergic neurons of the substantia nigra pars compacta followed by death of these neurons. The functional recovery of these neurons requires a deep knowledge of the molecules that maintain the dopaminergic phenotype during adulthood and the mechanisms that subvert their activity. Previous studies have shown that transcription factor NURR1, involved in differentiation and maintenance of the dopaminergic phenotype, is downregulated by α-synuclein (α-SYN). In this study, we provide a mechanistic explanation to this finding by connecting α-SYN-induced activation of glycogen synthase kinase-3 (GSK-3) with NURR1 phosphorylation followed by proteasomal degradation. The use of sequential deletion mutants and single point mutants of NURR1 allowed the identification of a domain comprising amino acids 123-PSSPPTPSTPS-134 that is targeted by GSK-3 and leads to subsequent ubiquitination and proteasome degradation. This study provides a detailed analysis of the regulation of NURR1 stability by phosphorylation in synucleinopathies such as Parkinson’s disease., This study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) (grant PID2019-110061RB-I00 for A.C and PID2019-105600RB-I00 for I.L.B.) and The Autonomous Community of Madrid (grant B2017/ BMD-3827 for A.C. and B2017/BMD-3813 for I.L.B.).

The cerebral cortex is responsible for the higher-order functions of the brain such as planning, cognition, or social behaviour. It provides us with the capacity to interact with and transform our world. The substrates of cortical functions are complex neural circuits that arise during development from the dynamic remodelling and progressive specialization of immature undefined networks. Here, we review the genetic and activity-dependent mechanisms of cortical wiring focussing on the importance of their interaction. Cortical circuits emerge from an initial set of neuronal types that engage in sequential forms of embryonic and postnatal activity. Such activities further complement the cells’ genetic programs, increasing neuronal diversity and modifying the electrical properties while promoting selective connectivity. After a temporal window of enhanced plasticity, the main features of mature circuits are established. Failures in these processes can lead to neurodevelopmental disorders whose treatment remains elusive. However, a deeper dissection of cortical wiring will pave the way for innovative therapies., L.B.G holds a fellowship from the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 713673 and “La Caixa” Foundation (ID 100010434, the fellowship code is LCF/BQ/IN17/11620044). This work was funded by grants from MCIU/AEI/FEDER, UE SAF2017-83117-R, and MCIU, PCI2019-111872-2/AEI/ 10.13039/501100011033 (FLAG-ERA-HBP), and RED2018-102553T.

Background: Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course. Methods: We recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided. Results: We identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02). Conclusions: We show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy., Supported by CERCA Programme/Generalitat de Catalunya, Health Department PERIS #SLT/002/16/00374, AGAUR-project #2017SGR1080; MCI/AEI/ERDF project #RTI2018-094049-B-I00; ERC EPIPHARM; Cellex Foundation; “la Caixa” Foundation (LCF/PR/GN18/51140001 and LCF/PR/GN18/50310007), RF-2016–02364388, Accelerator Award—Cancer Research UK/AIRC—INCAR Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC) Project 5 × 1000 no. 9962, AIRC IG 2018 id. 21724, AIRC MFAG id. 21769 and id. 20450; MIUR (Grant PRIN 2017); and RCR-2019–23669115.

Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [18F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate- functionalized 68Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T1)MRI during the vulnerable stages of the plaque progression., This work was supported by the Spanish Ministry of Science (grant nos. SAF2016-79593-P, RED2018-102469-T, and PID2019-104059RB-I00) and from the Gobierno Vasco, Dpto. Industria, Innovación, Comercio y Turismo under the ELKARTEK Program (grant no. KK-2019/bmG19). JR-C received funding from the BBVA Foundation (Ayudas a Equipos de investigación científica Biomedicina 2018). The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award SEV-2015-0505). CIC biomaGUNE is supported by the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agencygrant no. MDM-2017-0720. L.G. acknowledges financial support from the Ramón y Cajal program (RYC-2014-15512 0)

© The Author(s) 2021., LMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly in mice, Lmx1b has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of Lmx1b appears adequate for development, Lmx1b null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In Lmx1b functional knockouts (KOs), Lmx1b transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved Lmx1b-associated cis-regulatory modules (LARM1 and LARM2) that are bound by Lmx1b, amplify Lmx1b expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal LMX1B coding sequence, but with loss-of-function variations in the LARM1/2 region, stressing the role of regulatory modules in disease pathogenesis., This work was supported in part by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (M.A.R) (BFU2017-88265-P); the National Organization for Rare Disorders (K.C.O.), and the Loma Linda University Pathology Research Endowment Fund (K.C.O.).

The axon initial segment (AIS) is essential for maintaining neuronal polarity, modulating protein transport into the axon, and action potential generation. These functions are supported by a distinctive actin and microtubule cytoskeleton that controls axonal trafficking and maintains a high density of voltage-gated ion channels linked by scaffold proteins to the AIS cytoskeleton. However, our knowledge of the mechanisms and proteins involved in AIS cytoskeleton regulation to maintain or modulate AIS structure is limited. In this context, formins play a significant role in the modulation of actin and microtubules. We show that pharmacological inhibition of formins modifies AIS actin and microtubule characteristics in cultured hippocampal neurons, reducing F-actin density and decreasing microtubule acetylation. Moreover, formin inhibition diminishes sodium channels, ankyrinG and ßIV-spectrin AIS density, and AIS length, in cultured neurons and brain slices, accompanied by decreased neuronal excitability. We show that genetic downregulation of the mDia1 formin by interference RNAs also decreases AIS protein density and shortens AIS length. The ankyrinG decrease and AIS shortening observed in pharmacologically inhibited neurons and neuron-expressing mDia1 shRNAs were impaired by HDAC6 downregulation or EB1-GFP expression, known to increase microtubule acetylation or stability. However, actin stabilization only partially prevented AIS shortening without affecting AIS protein density loss. These results suggest that mDia1 maintain AIS composition and length contributing to the stability of AIS microtubules., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The work was supported by agrant from Ministerio de Ciencia y Universidades (RTI2018-095156-B-100) to JJG and INSERM funding to DD. Wei Zhang was supported by a fellowship from China Scholarship Council (No.201506300085) and Beatriz Achon by a Master fellowship from Universidad Autónoma de Madrid.

© The Author(s) 2021., Ketamine has rapid and robust antidepressant effects. However, unwanted psychotomimetic effects limit its widespread use. Hence, several studies examined whether GluN2B-subunit selective NMDA antagonists would exhibit a better therapeutic profile. Although preclinical work has revealed some of the mechanisms of action of ketamine at cellular and molecular levels, the impact on brain circuitry is poorly understood. Several neuroimaging studies have examined the functional changes in the brain induced by acute administration of ketamine and Ro 25-6981 (a GluN2B-subunit selective antagonist), but the changes in the microstructure of gray and white matter have received less attention. Here, the effects of ketamine and Ro 25-6981 on gray and white matter integrity in male Sprague–Dawley rats were determined using diffusion-weighted magnetic resonance imaging (DWI). In addition, DWI-based structural brain networks were estimated and connectivity metrics were computed at the regional level. Immunohistochemical analyses were also performed to determine whether changes in myelin basic protein (MBP) and neurofilament heavy-chain protein (NF200) may underlie connectivity changes. In general, ketamine and Ro 25-6981 showed some opposite structural alterations, but both compounds coincided only in increasing the fractional anisotropy in infralimbic prefrontal cortex and dorsal raphe nucleus. These changes were associated with increments of NF200 in deep layers of the infralimbic cortex (together with increased MBP) and the dorsal raphe nucleus. Our results suggest that the synthesis of NF200 and MBP may contribute to the formation of new dendritic spines and myelination, respectively. We also suggest that the increase of fractional anisotropy of the infralimbic and dorsal raphe nucleus areas could represent a biomarker of a rapid antidepressant response., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación (PI13/00038, PI16/00217 and PI19/00170 to A.A.) that were co-funded by the European Regional Development Fund (‘A way to build Europe’); Generalitat Valenciana, Conselleria d’ Educació, Investigació, Cultura i Esport (GV/2018/049 to A.B-S.); Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00 to F.P.-C.). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III is also acknowledged.

11 pags., 6 figs., 5 tabs., Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3 - also named eosinophil cationic protein - by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages., This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades: SAF2015-72518-EXP, SAF2017- ́ 82158-R and RYC-2012-09999 to M.T.; CTQ2017-84371-P to M.A.J.; AGL2014-52395-C2; AGL2017-84097-C2-2-R to D.A. and PID2019-106123GB-I00 to E.B. Additional financial support from the European Society for Clinical Microbiology and Infectious Disease, ESCMID 2016, to M.T., the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya, 2019 LLAV 00029 to M.T. and 2016 PROD 00060 to E.B. The “Marí a de Maeztu” Program for Units of Excellence in R&D from the Spanish Ministry of Innovation and Competitiveness (MINECO) for work at Pompeu Fabra University (D.A.) is acknowledged. This work was supported, in part, by the European Regional Development Fund ‘A Way to Achieve Europe’ [Spanish Network for Research in Infectious Diseases (Grant No. RD16/0016/0003)]. D.S. and B.C.-A. are recipients of pre-doctoral FPI scholarships (PRE2018-083243 and BES-2015-073383, respectively) from the Spanish Ministerio de Ciencia, Innovacion y Universidades.

Ratchet devices allow turning an ac input signal into a dc output signal. A ratchet device is set by moving particles driven by zero averages forces on asymmetric potentials. Hybrid nanostructures combining artificially fabricated spin ice nanomagnet arrays with superconducting films have been identified as a good choice to develop ratchet nanodevices. In the current device, the asymmetric potentials are provided by charged Néel walls located in the vertices of spin ice magnetic honeycomb array, whereas the role of moving particles is played by superconducting vortices. We have experimentally obtained ratchet effect for different spin ice I configurations and for vortex lattice moving parallel or perpendicular to magnetic easy axes. Remarkably, the ratchet magnitudes are similar in all the experimental runs; i. e. different spin ice I configurations and in both relevant directions of the vortex lattice motion. We have simulated the interplay between vortex motion directions and a single asymmetric potential. It turns out vortices interact with uneven asymmetric potentials, since they move with trajectories crossing charged Néel walls with different orientations. Moreover, we have found out the asymmetric pair potentials which generate the local ratchet effect. In this rocking ratchet the particles (vortices) on the move are interacting each other (vortex lattice); therefore, the ratchet local effect turns into a global macroscopic effect. In summary, this ratchet device benefits from interacting particles moving in robust and topological protected type I spin ice landscapes., This work was supported by Spanish MICINN grants FIS2016-76058 (AEI/FEDER, UE), EU COST- CA16218. IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MICINN, Grant SEV-2016-0686). MCO and AG acknowledges financial support from Spanish MICINN Grant ESP2017-86582-C4-1-R and IJCI-2017-33991; AMN acknowledges financial support from Spanish CAM Grant 2018-T1/IND-10360. MV acknowledges financial support from Spanish MICINN Grant PID2019-104604RB/AEI/10.13039/50110001103.

20 p.-7 fig.-1 tab., New drugs against visceral leishmaniasis with mechanisms of action differing from existing treatments and with adequate cost, stability, and properties are urgently needed. No antitubulin drug is currently in the clinic against Leishmania infantum, the causative agent of visceral leishmaniasis in the Mediterranean area. We have designed and synthesized a focused library of 350 compounds against the Leishmania tubulin based on the structure-activity relationship (SAR) and sequence differences between host and parasite. The compounds synthesized are accessible, stable, and appropriately soluble in water. We assayed the library against Leishmania promastigotes, axenic, and intracellular amastigotes and found 0, 8, and 16 active compounds, respectively, with a high success rate against intracellular amastigotes of over 10%, not including the cytotoxic compounds. Five compounds have a similar or better potency than the clinically used miltefosine. 14 compounds showed a host-dependent mechanism of action that might be advantageous as it may render them less susceptible to the development of drug resistance. The active compounds cluster in five chemical classes that provide structure-activity relationships for further hit improvement and facilitate series development. Molecular docking is consistent with the proposed mechanism of action, supported by the observed structure-activity relationships, and suggests a potential extension to other Leishmania species due to sequence similarities. A new family of diarylsulfonamides designed against the parasite tubulins is active against Leishmania infantum and represents a new class of potential drugs with favorable cost, stability, and aqueous solubility for the treatment of visceral leishmaniasis (VL). These results could be extended to other clinically relevant species of Leishmania spp., This work was supported by Consejería de Educación de la Junta de Castilla y León (SA030U16 and SA262P189) and the Spanish Ministry of Science, Innovation and Universities (RTI2018-099474-BI00) co-funded by the EU's European Regional Development Fund-FEDER, the EUROLISH NET project (Marie Sklodowska Curie ITN-ETN, EU H2020) and Fundación Ramón Areces (2017–2019). MG acknowledges a predoctoral grant EDU/602/2016 from Consejería de Educación de la Junta de Castilla y León.

[EN] [Introduction and objectives] Our objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations., [EN] [Methods] Unrelated individuals aged ≥ 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology., [EN] [Results] Of 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011)., [EN] [Conclusions] Our results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test., [ES] [Introducción y objetivos] Nuestro objetivo fue aproximar la prevalencia de mutaciones en los genes candidatos de hipercolesterolemia familiar (HF) en una población española de mediana edad, y determinar el valor predictivo de los criterios clínicos de sospecha de HF en la detección de mutaciones causales., [ES] [Métodos] Se seleccionaron individuos mayores de 18 años no relacionados de la cohorte Estudio de Salud de los Trabajadores de Aragón (AWHS) con colesterol unido a lipoproteínas de baja densidad (cLDL) > percentil 95, con enfermedad cardiovascular prematura o con cLDL > 130 mg/dl con tratamiento hipolipemiante, asumiendo que al menos una de las características estará presente en todos los individuos con HF. En estos participantes se secuenciaron los genes LDLR, APOB, PCSK9, APOE, STAP1 y LDLRAP1 mediante secuenciación masiva., [ES] [Resultados] De 5.400 individuos del AWHS, 4.514 tenían datos lipídicos y registro farmacológico hipolipemiante completo, 255 participantes (5,65%) cumplían los criterios de sospecha de HF, 24 de ellos (9,41%) fueron diagnosticados de hiperlipoproteinemia(a) y 16 (6,27% de los secuenciados) presentaron alguna mutación causal en genes candidatos: 12 participantes portaban 11 alelos patogénicos diferentes en LDLR y 4 participantes portaban una mutación patogénica en PCSK9. Las concentraciones de cLDL > 220 mg/dl y el cLDL > 130 mg/dl a pesar del tratamiento con estatinas mostraron la mayor asociación con la presencia de mutación (p = 0,011)., [ES] [Conclusiones] Nuestros resultados muestran que la prevalencia española de HF es 1:282 y sugieren que una concentración de cLDL elevado, y niveles altos de cLDL a pesar de la terapia con estatinas son los mejores predictores para un diagnóstico genético positivo de HF., Este trabajo contó con el apoyo de subvenciones del Gobierno de Aragón, B14-7R, España y del Ministerio de Economía y Competitividad de España PI15/01983, PI18/01777 y CIBERCV. Estos proyectos son cofinanciados por el Instituto de Salud Carlos III y el Fondo Europeo de Desarrollo Regional (FEDER) de la Unión Europea «Una manera de hacer Europa».

10 pags., 4 figs., 5 tabs., Objective: The aim of this study was to quantify the changes obtained when the molar intrusion movement is complemented by photobiomodulation (PBM). Background: A common problem in adult patients is the super-eruption of maxillary molars caused by the loss of the antagonist tooth. Super-erupted molars impair oral rehabilitation and can cause both occlusal and functional problems. There is increasing research confirming the benefits of adjunctive PBM during orthodontic treatment. Methods: Twenty patients with indication of a maxillary first molar intrusion for oral rehabilitation were selected. Patients were randomized into two groups to receive orthodontic intrusion (control group) or the same treatment complemented by PBM (PBM group) in repeated doses (days 0, 1, 2, 3, 4, and 7 from the start of the intrusion and in each monthly follow-up) by using a low-power red laser diode (670 nm, 150 mW, 12 min around the molar). Plaque index (PI), probing depth (PD), and bleeding of probing (BOP) were assessed at 0, 1, 2, 3, and 6 months. Stereolithography models generated from an intraoral scanner were taken at 0, 3, and 6 months and cone beam computed tomography (CBCT) records were taken at 0 and 6 months. Mean intrusion distance, mean intrusion velocity, and volumetric resorption were calculated. Results: Periodontal clinical assessments (PI, PD, and BOP) and mean intrusion distance or mean intrusion velocity yielded no differences ( p > 0.05) between groups. However, PBM group showed lower values of all these scores during the first 3 months. Intraoral scanner and CBCT were equally effective in accurately monitoring the intrusion distance ( p > 0.05). CBCT records allowed volumetric evaluation of the root resorption process, being lesser in the PBM group, but not significantly ( p > 0.05). Conclusions: During orthodontic intrusion process, the adjunctive application of PBM may provide better periodontal records and lower progression of root resorption at the expense of a little lower intrusion distance and velocity., This research was supported by a grant from the Eugenio Rodrıguez Pascual Foundation (Madrid, Spain) and by the Spanish Research Projects of MICINN (Ref. MAT 2017- 83856-C3 and Ref. PiD2020-114755GB-C31).

Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. The project was partially funded by a grant from the Catalan Society of Cardiology (Barcelona, Spain). Hospital Universitario Virgen de la Arrixaca (Murcia, Spain) was supported by a grant from the Foundation Marató TV3 (218/C/2015) (Barcelona, Spain). Hospital Universitario y Politécnico La Fe (Valencia, Spain) was partially supported by Fondo Europeo de Desarrollo Regional (“Unión Europea, Una forma de hacer Europa”) (Madrid, Spain) and the Instituto de Salud Carlos III (La Fe Biobank PT17/0015/ 0043) (Madrid, Spain). Dr Guala was supported by funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I) (Madrid, Spain). Dr La Mura was supported by a research grant from the Cardiopath PhD program (Naples, Italy). Prof de la Pompa was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities. Dr Bayes-Genis was supported by grants from CIBER Cardiovascular (CB16/11/00403 and 16/11/00420) (Madrid, Spain) and AdvanceCat 2014-2020 (Barcelona, Spain); and has received advisory board and lecture fees from Novartis, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Critical Diagnostics. Dr Pontone has received speaker honorarium and/or institutional research grants from GE Healthcare, Bracco, Boehringer Ingelheim, and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

2 figures., Cytotoxic lymphocytes (CLs), and more specifically Tc and NK cells, are the main executors of cell death in the immune system, playing a key role during both immunosurveillance and immunotherapy. These cells induce regulated cell death (RCD) by different mechanisms, being granular exocytosis and expression of death ligands the most prominent and best characterized ones. Apoptosis, a traditionally considered low-inflammatory type of cell death, has been accepted for years as the paradigm of RCD induced by CLs. However, several recent studies have demonstrated that NK cells and Tc cells can also induce more inflammatory forms of cell death, namely, necroptosis, pyroptosis, and ferroptosis. Activation of these highly inflammatory types of cell death appears to critically contribute to the activation of a successful antitumour immune response. Additionally, the role of specific cell death pathways in immunogenic cell death is still under intense debate, especially considering the interconnections with other inflammatory forms of cell death. These evidences, together with the advent of new cancer immunotherapies, highlight the necessity to deepen our understanding of the link between the cell death triggered by CLs and inflammation. This knowledge will be instrumental to maximize the antitumour potential of immunotherapies, minimizing deleterious effects associated with these treatments. In this review, we will briefly summarize the main features of apoptosis, necroptosis, pyroptosis and ferroptosis, to subsequently discuss the most recent evidences about the role of these RCD pathways during the elimination of cancer cells mediated by CLs and its modulation to increase the efficacy of cancer immunotherapy., Work in the JP laboratory is funded by the FEDER (Fondo Europeo de Desarrollo Regional, Gobierno de Aragón, Group B29_17R), Ministerio de Ciencia, Innovación e Universidades (MCNU), Health National Institute Carlos III, Agencia Estatal de Investigación (SAF2017-83120-C2-1-R; PID2020-113963RB-I00), Fundación Inocente Inocente, ASPANOA and Carrera de la Mujer de Monzón. EMG is funded by Agencia Estatal de Investigación (SAF2017-83120-C2-1-R and PID2020-113963RB-I00). DDM is supported by a postdoctoral fellowship ‘Sara Borrell’, LS by a PhD fellowship (FPI) from the Ministry of Science, Innovation and Universities. IUM and SH are supported by a PhD fellowship from Aragon Government. MA is supported by a postdoctoral fellowship ‘Juan de la Cierva-formación’ from the Ministry of Science, Innovation and Universities, and JP is supported by the ARAID Foundation.

© The Author(s) 2021., Serotonin (5-HT) is one of the principal neurotransmitters in the nervous system of vertebrates. It is initially synthesized by hydroxylation of tryptophan (Trp) by means of tryptophan hydroxylase or TPH which is the rate-limiting enzyme in the production of 5-HT. In most vertebrates, there are two isoforms of TPH present, TPH1 and TPH2, which exhibit different catalytic or substrate specificity as well as different expression domains. Studies carried out in mammals show that only tph2 is expressed in the brain whereas tph1-mRNA is primarily localized in the enterochromaffin cells and pineal gland. A large number of neurons are also considered to be serotonergic or “pseudo-serotonergic” as they accumulate and release 5-HT yet do not produce it as no amine-synthetic enzymes are expressed, yet a combination of 5-HT transporters is observed. Therefore, tph expression is considered to be the only specific marker of 5-HT-producing neurons that can discriminate true 5-HT from pseudo-serotonergic neurons. This work examined in situ hybridization to study the mRNA distribution of one paralogue for tph1 and tph2 in the central nervous system of rainbow trout. Results show a segregated expression for both paralogues that predominantly match previous immunocytochemical studies. This study thus adds valuable information to the scarce analyses focusing on the central distribution of the expression of serotonergic markers, particularly tphs, in the vertebrate brain thus characterizing the true serotonergic brain territories., This research was funded by the Spanish State Agency of Research (AEI), grant number AGL2016-74857-C3-3-R and PID2019-103969RB-C33 to JMCR and PID2019-103969RB-C31 to JMM. M.C. was recipient of a predoctoral fellowship (Program FPI) from Spanish Ministerio de Ciencia e Innovación (BES-2017-079708).

A mismatch exists between people’s mental representations of their own body and their real body measurements, which may impact general well-being and health. We investigated whether this mismatch is reduced when contextualizing body size estimation in a real-life scenario. Using a reverse correlation paradigm, we constructed unbiased, data-driven visual depictions of participants’ implicit body representations. Across three conditions—own abstract, ideal, and own concrete body— participants selected the body that looked most like their own, like the body they would like to have, or like the body they would use for online shopping. In the own concrete condition only, we found a significant correlation between perceived and real hip width, suggesting that the perceived/real body match only exists when body size estimation takes place in a practical context, although the negative correlation indicated inaccurate estimation. Further, participants who underestimated their body size or who had more negative attitudes towards their body weight showed a positive correlation between perceived and real body size in the own abstract condition. Finally, our results indicated that different body areas were implicated in the different conditions. These findings suggest that implicit body representations depend on situational and individual differences, which has clinical and practical implications. LDC was supported by Ministerio de Ciencia, Innovación y Universidades Juan de la Cierva-Incorporación Grant IJC2018-038347-I and the CONEX-Plus programme funded by Universidad Carlos III de Madrid and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 801538. ATJ was supported by Ministerio de Economía, Industria y Competitividad of Spain Ramón y Cajal Grant RYC-2014-15421. This research was partly funded by the Spanish Agencia Estatal de Investigación (PID2019-105579RB-I00/AEI/10.13039/501100011033). The authors would like to thank Martin Mojica-Benavides for his help in preparing the psychometric curve analyses.

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome., This work was supported by National Plan R+D+I 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Economy, Industry, and Competitiveness, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0009]; cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020; and supported by Grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-CoV-2 y la enfermedad COVID-19 [COV20/00370; COV20/00580]. J.S.C. is a researcher belonging to the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.

10 Pág. Centro de Biotecnología y Genómica de Plantas (CBGP), The synchronization is a recurring phenomenon in neuroscience, ecology, human sciences, and biology. However, controlling synchronization in complex eukaryotic consortia on extended spatial-temporal scales remains a major challenge. Here, to address this issue we construct a minimal synthetic system that directly converts chemical signals into a coherent gene expression synchronized among eukaryotic communities through rate-dependent hysteresis. Guided by chemical rhythms, isolated colonies of yeast Saccharomyces cerevisiae oscillate in near-perfect synchrony despite the absence of intercellular coupling or intrinsic oscillations. Increased speed of chemical rhythms and incorporation of feedback in the system architecture can tune synchronization and precision of the cell responses in a growing cell collectives. This synchronization mechanism remain robust under stress in the two-strain consortia composed of toxin-sensitive and toxin-producing strains. The sensitive cells can maintain the spatial-temporal synchronization for extended periods under the rhythmic toxin dosages produced by killer cells. Our study provides a simple molecular framework for generating global coordination of eukaryotic gene expression through dynamic environment., This work was supported by the Programa de Atraccion de Talento 2017 (Comunidad de Madrid, 2017-T1/BIO-5654 to K.W.), Severo Ochoa (SO) Programme for Centres of Excellence in R&D from the Agencia Estatal de Investigacion of Spain (grant SEV-2016-0672 (2017-2021) to K.W. via the CBGP). In the frame of SEV-2016-0672 funding M.A. received a PhD fellowship (SEV-2016-0672-18-3: PRE2018-084946) and O.P. is supported with a postdoctoral contract. K.W. was supported by Programa Estatal de Generacion del Conocimiento y Fortalecimiento Cientıfico y Tecnologico del Sistema de I + D + I 2019 (PGC2018-093387-A-I00) from MICIU (to K.W.). UPM Plan Propio Predoctoral fellow finances M. G.N.

Aims: To improve the nutri-functional quality of chickpea flour by fermentation with selected lactic acid bacteria (LAB) to formulate functional legume-derived products. Methods and Results: A Randomized Complete Block Design was carried out to assess the influence of experimental conditions (presence/absence of Lactiplantibacillus plantarum CRL2211 and/or Weissella paramesenteroides CRL2182, temperature, time and dough yield) on LAB population, acidification, antinutritional factors and total phenolic contents (TPCs) of chickpea flour. Fermentation with both strains for 24 h at 37°C produced an increase in LAB (up to 8.9 log CFU/g), acidity (final pH 4.06), TPC (525.00 mg GAE/100 g) and tannin and trypsin inhibitor removal (28.80 mg GAE/100 g and 1.60 mg/g, respectively) higher than the spontaneously fermented doughs. RAPD and Rep-PCR analysis revealed that fermentation was dominated by L. plantarum CRL2211. Molecular docking and dynamics simulations were useful to explain LAB enzyme behaviour during fermentation highlighting the chemical affinity of LAB tannases and proteinases to gallocatechin and trypsin inhibitors. Compared with other processing methods, fermentation was better than soaking, germination and cooking for increasing the techno-functional properties of chickpea flour. Fermented doughs were applied to the manufacture of crackers that contained 81% more TPC and 64% more antioxidant activity than controls. Conclusions: Fermentation for 24 h at 37°C with selected autochthonous LAB was the best method for improving the quality of chickpea flour and derived crackers type cookies. Significance and Impact of Study: Chickpea is suitable for the development of novel functional foods. Fermentation with selected LAB would improve the final product quality and bioactivity. The combination of experimental and simulation approaches can lead to a better understanding of the fermentation processes to enhance the properties of a food matrix., This work was supported by PIP 0319 from CONICET, PICT2014‐3583 and PICT2019‐3504 from ANPCyT and Projects IC‐601 and IC‐802 from Universidad de San Pablo‐Tucumán, Argentina. Carlos Sabater acknowledges his Postdoctoral research contract funded by the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) and Postdoctoral research contract Juan de la Cierva‐Formación from Spanish Ministry of Science and Innovation (FJC2019‐042125‐I).

Cutaneous leishmaniasis (CL) is one of the illnesses caused by Leishmania parasite infection, which can be asymptomatic or severe according to the infecting Leishmania strain. CL is commonly diagnosed by directly detecting the parasites or their DNA in tissue samples. New diagnostic methodologies target specific proteins (biomarkers) secreted by the parasite during the infection process. However, specific bioreceptors for the in vivo or in vitro detection of these novel biomarkers are rather limited in terms of sensitivity and specificity. For this reason, we here introduce three novel peptides as bioreceptors for the highly sensitive and selective identification of acid phosphatase (sAP) and proteophosphoglycan (PPG), which have a crucial role in leishmaniasis infection. These high-affinity peptides have been designed from the conservative domains of the lectin family, holding the ability to interact with the biological target and produce the same effect than the original protein. The synthetic peptides have been characterized and the affinity and kinetic constants for their interaction with the targets (sAP and PPG) have been determined by a surface plasmon resonance biosensor. Values obtained for K are in the nanomolar range, which is comparable to high-affinity antibodies, with the additional advantage of a high biochemical stability and simpler production. Pep2854 exhibited a high affinity for sAP (K = 1.48 nM) while Pep2856 had a good affinity for PPG (K 1.76 nM). This study evidences that these peptidomimetics represent a novel alternative tool to the use of high molecular weight proteins for biorecognition in the diagnostic test and biosensor devices for CL. Graphical abstract: [Figure not available: see fulltext.]., This study was supported by a Doctoral Fellowship from COLCIENCIAS in Colombia. The ICN2 is funded by the CERCA programme/Generalitat de Catalunya. ICN2 is supported by the Severo Ochoa program from Spanish Ministry of Science MICINN (Grant No. SEV-2017-0706). This work has made use of the Biodeposition and Biodetection Unit from ICTS NANBIOSIS (http://www.nanbiosis.es/portfolio/u4-biodeposition-andbiodetection-unit/) partially supported by MICINN/FEDER (FICTS-1420-27).

A facile imide coupling strategy for the one‐step preparation of G‐quadruplex ligands with varied core chemistries is described. The G‐quadruplex stabilization of a library of nine compounds was examined using FRET melting experiments, and CD, UV‐Vis, fluorescence and NMR titrations, identifying several compounds that were capable of stabilizing G‐quadruplex DNA with interesting selectivity profiles. The best G4 ligand was identified as compound 3, which was based on a perylene scaffold and exhibited 40‐fold selectivity for a telomeric G‐quadruplex over duplex DNA. Surprisingly, a tetra‐substituted flexible core, compound 11, also exhibited selective stabilization of G4 DNA over duplex DNA. The anticancer and antiparasitic activity of the library was also examined, with the lead compound 3 exhibiting nanomolar inhibition of Trypanosoma brucei with 78‐fold selectivity over MRC5 cells. The cellular localization of this compound was also studied via fluorescence microscopy. We found that uptake was time dependant, with localization outside the nucleus and kinetoplast that could be due to strong fluorescence quenching in the presence of small amounts of DNA., The rigid rules of G‐quadruplex stabilization: A library of amphiphiles has been synthesized in one step, using a simple imide condensation reaction. The G‐quadruplex stabilization, anti‐cancer and anti‐parasitic activity of the library has been investigated, uncovering the important factors that govern G‐quadruplex binding and selectivity, yielding a promising new core‐motif and a compound with potent trypanosomacidal activity.

During the previous Ebola and Zika outbreaks, researchers shared their data, allowing many published epidemiological studies to be produced only from open research data, to speed up investigations and control of these infections. This study aims to evaluate the dissemination of the COVID-19 research data underlying scientific publications. Analysis of COVID-19 publications from December 1, 2019, to April 30, 2020, was conducted through the PubMed Central repository to evaluate the research data available through its publication as supplementary material or deposited in repositories. The PubMed Central search generated 5,905 records, of which 804 papers included complementary research data, especially as supplementary material (77.4%). The most productive journals were The New England Journal of Medicine, The Lancet and The Lancet Infectious Diseases, the most frequent keyword was pneumonia, and the most used repositories were GitHub and GenBank. An expected growth in the number of published articles following the course of the pandemics is confirmed in this work, while the underlying research data are only 13.6%. It can be deduced that data sharing is not a common practice, even in health emergencies, such as the present one. High-impact generalist journals have accounted for a large share of global publishing. The topics most often covered are related to epidemiological and public health concepts, genetics, virology and respiratory diseases, such as pneumonia. However, it is essential to interpret these data with caution following the evolution of publications and their funding in the coming months., This work benefited from assistance by Spanish Ministry of Science and Innovation (PID2019-105708RB-C22, PID2019-108579RB-I00 and BES-2016–079394) and the CIBERONC (CB16/12/00350).

19 Pág. Centro de Investigación en Sanidad Animal (CISA), Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring., We thank the HUB-ICO-IDIBELL-Biobank and the CERCA Programme of the Generalitat de Catalunya for institutional support. This study was funded by the Instituto Carlos III (Grants Number CP16/00041 and PI19/00144) to FL. This project was also funded by la Fundació La Marató de TV3 (Grants No. 201821-30, 201821-31and 201821-32 to FL, JCE and EV, respectively) and by the Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V-A España-Francia-Andorra (POCTEFA 2014–2020) programme (at 65%) to IF. AVP is supported by the Beatriu de Pinós programme (2018-BP-00129) from the Ministry of Business and nowledge of the Government of Catalonia, and cofunded by the EU Horizon 2020 programme under an MSCA grant agreement (801370). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. KB is supported by the Swedish Research Council (#2017-00915), the Swedish State Support for Clinical Research (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and the European Union Joint Programme for Neurodegenerative Disorders (JPND2019-466-236). AL is supported by the Ministero della Salute, Italy, for the national surveillance of Creutzfeldt-Jakob disease. This research was also supported in part by the Alberta Synergies in Alzheimer’s and Related Disorders (SynAD) programme which is funded by the Alzheimer Society of Alberta and Northwest Territories through their Hope for Tomorrow programme and the University Hospital Foundation. SynAD operates in partnership with the Neuroscience and Mental Health Institute at the University of Alberta. JADR was supported by grants from the Spanish Ministry of Science, Innovation and Universities (MICINN/FEDER) (RTI2018-099773-B-I00), the CERCA Programme, and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (SGR2017-648) and CIBERNED (CMED2018-2)

The design of a planar slot array in groove gap waveguide technology implemented by glide-symmetric holes as Electromagnetic Band Gap structure is here presented. Despite the advantages of using holes instead of pins in terms of manufacturing simplicity and cost,the larger size of the holes compared to pins needs to be considered when designing slot arrays without grating lobes. A 1 to 4 corporate feed network is designed using this technology as well. Corrugations are included to further reduce the grating lobes. Experimental results support the viability of the proposed concept for designing glide-symmetric planar arrays of any size. This work has been partly funded by the Spanish Government through Projects TEC2016-79700-C2-2-R, PID2019-107688RB-C21 and TEC2017-86619-R. The authors would like to thank Qingbi Liao from KTH Royal Institute of Technology (Sweden) for the measurements in the anechoic chamber.

In Press., [EN]: The study of the human microbiome has led to an exceptional increase in the current understanding of the importance of microbiota for health throughout all stages of life. Human microbial colonization occurs in the skin, genitourinary system and, mainly, in the oral cavity and intestinal tract. In these locations, the human microbiota establishes a symbiotic relationship with the host and helps maintain the physiological homeostasis. Lifestyle, age, diet and use of antibiotics are the main regulators of the composition and functionality of human microbiota. Recent studies have indicated the reduction in microbial diversity as one of the contributors to the development of diseases. In addition to phylogenetic diversity studies, further metagenomic studies are needed at the functional level of the human microbiome to improve our understanding of its involvement in human health., [ES]: El estudio del microbioma humano ha incrementado de manera excepcional el conocimiento actual del que disponemos sobre la importancia de la microbiota en la salud durante todas las etapas de la vida. La colonización microbiana humana ocurre en la piel, en el sistema genitourinario y, principalmente, en la cavidad oral y el tracto intestinal. En todos estos lugares, la microbiota humana establece una relación simbiótica con el hospedador y ayuda a mantener la homeostasis fisiológica. El estilo de vida, la edad, la dieta y el uso de antibióticos son los principales reguladores de la composición y la funcionalidad de la microbiota humana. Estudios recientes apuntan al descenso de la diversidad microbiana como uno de los aspectos que contribuye al desarrollo de enfermedades. Además de los estudios de diversidad filogenética, es necesario profundizar en estudios metagenómicos a nivel funcional del microbioma humano para mejorar el conocimiento sobre su participación en la salud humana., The author would like to thank the Ministry of Science, Innovation and Universities of Spain for funding this study through projects AGL2016-75951-R, PCIN-2017-075 and AGL2004-07285-C02.

10 pages, 4 figures, supplementary information https://doi.org/10.1038/s41598-021-87767-x.-- The original data on sample location, individual fish characteristics and stable isotope composition, including amino acids, can be accessed through the PANGAEA repository (https://doi.org/10.1594/PANGAEA.930111), The importance of microbes for the functioning of oceanic food webs is well established, but their relevance for top consumers is still poorly appreciated. Large differences in individual size, and consequently in growth rates and the relevant spatial and temporal scales involved, make the integration of microorganisms and large metazoans in a common food web framework difficult. Using stable isotopes, this study estimated the trophic position of 13 species of micronektonic fishes to examine the microbial and metazoan contribution to mid trophic level consumers. Vertically migrant species displayed higher trophic positions than non-migrant species in all depth layers. The estimated trophic positions agreed well with those from the literature, but all species displayed mean increases between 0.5 and 0.8 trophic positions when taking into account microbial trophic steps. Trophic position, but not the relative importance of the microbial food web, increased with individual size, suggesting that current estimates of the trophic position of top consumers and of the length of oceanic food webs are too low because they are based only on metazoan trophic steps. This finding calls for a review of trophic position estimates and of the efficiency of trophic transfers along oceanic food webs, This research was funded by projects BATHYPELAGIC (CTM2016-78853-R) from the Plan Estatal de I+D+I (Spain), SUMMER (Grant Agreement 817806) and TRIATLAS (Grant Agreement 817578), from the European Union (Horizon 2020 Research and Innovation Programme), and Grant Number IN607A2018/2 from the Axencia Galega de Innovación (GAIN, Xunta de Galicia, Spain), With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

Cycloserine has in common with isoxazolidines the saturated five-membered ring, which is an important scaffold for drug design, exhibiting diverse biological activities. The most remarkable feature of these compounds is the presence of the N-O bond framed in a cyclic moiety. The lack of an accurate characterization of this structural feature in an isolated system calls for a state-of-the-art theoretical-experimental study. A quantum-chemical investigation of cycloserine unveiled the presence of 11 local energy minima, with only two of them being separated by significant barriers. This picture has been experimentally confirmed: two species have been unequivocally detected in the gas phase by means of laser ablation microwave spectroscopy, also disentangling the complicated hyperfine structure originating from the presence of two nitrogen atoms. A thorough characterization of cycloserine and isoxazolidine, benchmarked by the semiexperimental investigation of hydroxylamine, provided the first accurate determination of their structures and pointed out that the rev-DSD-PBEP86 functional is competitive with respect to explicitly correlated coupled-cluster computations. This outcome paves the way toward accurate studies of large flexible molecules., This work has been supported by the Ministerio de Ciencia e Innovación (CTQ2016-76393-P and PID2019-111396GB-I00), Junta de Castilla y León (grants VA077U16 and VA244P20), and the European Research Council ERC-2013-SyG, no. 610256 NANOCOSMOS, MIUR ‘PRIN 2017’ (grant number 2017A4XRCA), and by the Italian Space Agency (ASI; ‘Life in Space’ project, no. 2019-3-U.0). E.R.A. acknowledges the Fundación Biofísica Bizkaia for a postdoctoral grant.

[Background and purpose]: Gemcitabine is an antitumour agent currently used in the treatment of several types of cancer with known properties as a radiosensitizer. p38MAPK signalling pathway has been shown to be a major determinant in the cellular response to gemcitabine in different experimental models. However, the molecular mechanism implicated in gemcitabine-associated radiosensitivity remains unknown., [Materials and methods]: The human sarcoma cell lines A673 and HT1080, and a mouse cell line derived from a 3-methylcholanthrene induced sarcoma were used as experimental models. Modulation of p38MAPKs was performed by pharmacological approaches (SB203580) and genetic interference using lentiviral vectors coding for specific shRNAs. Viability was assessed by MTT. Gene expression was evaluated by western blot and RT-qPCR. Induction of apoptosis was monitored by caspase 3/7 activity. Response to ionizing radiation was evaluated by clonogenic assays., [Results]: Our data demonstrate that chemical inhibition of p38MAPK signalling pathway blocks gemcitabine radiosensitizing potential. Genetic interference of MAPK14 (p38¿), the most abundantly expressed and best characterized p38MAPK, despite promoting resistance to gemcitabine, it does not affect its radiosensitizing potential. Interestingly, specific knockdown of MAPK11 (p38ß) induces a total loss of the radiosensitivity associated to gemcitabine, as well as a marked increase in the resistance to the drug., [Conclusion]: The present work identifies p38ß as a major determinant of the radiosensitizing potential of gemcitabine without implication of p38¿, suggesting that p38ß status should be analysed in those cases in which gemcitabine is combined with ionizing radiation., This work was supported by grants from Fundación Leticia Castillejo Castillo, Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-094093-B-I00) to RSP and MJRH. OR holds a contract for accessing the Spanish System of Science, Technology and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013). RSP and MJRH’s Research Institute, and the work carried out in their laboratory, received partial support from the European Community through the FEDER. RSP is a researcher of CSIC temporarily adscribed to UCLM.

Deep brain stimulation (DBS) is a powerful neurostimulation therapy proposed for the treatment of several neuropsychiatric disorders. However, DBS mechanism of action remains unclear, being its effects on brain dynamics of particular interest. Specifically, DBS reversibility is a major point of debate. Preclinical studies in obesity showed that the stimulation of the lateral hypothalamus (LH) and nucleus accumbens (NAcc), brain centers involved in satiety and reward circuits, are able to modulate the activity of brain structures impaired in this pathology. Nevertheless, the long-term persistence of this modulation after DBS withdrawal was unexplored. Here we examine the in vivo presence of such changes 1 month after LH- and NAcc-DBS, along with differences in synaptic plasticity, following an exploratory approach. Thus, both stimulated and non-stimulated animals with electrodes in the NAcc showed a common pattern of brain metabolism modulation, presumably derived from the electrodes’ presence. In contrast, animals stimulated in the LH showed a relative metabolic invariance, and a reduction of neuroplasticity molecules, evidencing long-lasting neural changes. Our findings suggest that the reversibility or persistence of DBS modulation in the long-term depends on the selected DBS target. Therefore, the DBS footprint would be influenced by the stability achieved in the neural network involved during the stimulation. This research was supported by the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III (projects PI14/00860 and PI17/01766, and grant CPII14/00005), co-financed by European Regional Development Fund (ERDF), “A way of making Europe”, CIBERSAM, Delegación del Gobierno para el Plan Nacional sobre Drogas (2017/085), Fundación Mapfre and Fundación Alicia Koplowitz. MCV was supported by Fundación Tatiana Pérez de Guzmán el Bueno as scholarship holder of this institution. DRM was supported by Consejería de Educación e Investigación, Comunidad de Madrid, co-funded by European Social Fund “Investing in your future” (grant, PEJD-2018-PRE/BMD- 7899). NLR was supported by Instituto de Investigación Sanitaria Gregorio Marañón, "Programa Intramural de Impulso a la I+D+I 2019”. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV‐2015‐0505). Support for Nacher’s lab came from Ministry of Economy and Competitiveness (SAF2015- 68436-R), Generalitat Valenciana (PROMETEO2013/069) and Fundación Alicia Koplowitz (FAK2012/01).

Oxygen vacancies are common to most metal oxides and usually play a crucial role in determining the properties of the host material. In this work, we perform ab initio calculations to study the influence of vacancies in doped manganites La(1−x)SrxMnO3, varying both the vacancy concentration and the chemical composition within the ferromagnetic-metallic range (0.2, Work at ICN2 was funded by FEDER/Ministerio de Ciencia e Innovación – Agencia Estatal de Investigación (grant PGC2018-096955-B-C43), Generalitat de Catalunya (2017SGR1506), and the EU-H2020 programme (654360 and 824143) under the NFFA-Europe Transnational Access Activity and the EU MaX Center of Excellence. ICN2 is also supported by the Severo Ochoa Program (SEV--2013--0295) and the CERCA Program of Generalitat de Catalunya. D. J. and V. F. acknowledge support from CONICET (PIP 00020-2019) and ANPCyT (PICT1857), Argentina. D. J. acknowledges CONICET for a doctoral fellowship.

Background Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population. Methods In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity including confirmatory factor analysis. The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument. Results The scale had an adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is precise (standard error of measurement = 3.34, with values s = 0.56), quality of life (WHOQOL-BREF) (rs = 0.51–0.30) and ssatisfaction with life (SLS-6) (rs = 0.50–0.38). The original 26-items version of the scale did not support totally the confirmatory factor analysis. The COSMIN checklist is favourable for all the properties analysed, although weaknesses are detected for structural validity. Conclusions The LW-CI-T2DM is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.

B cell acute lymphoblastic leukaemia (B-ALL) is the most common form of childhood cancer. Although treatment has advanced remarkably in the past 50 years, it still fails in ~20% of patients. Recent studies revealed that more than 5% of healthy newborns carry preleukaemic clones that originate in utero, but only a small percentage of these carriers will progress to overt B-ALL. The drivers of progression are unclear, but B-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. Emerging evidence shows that a major driver for the conversion from the preleukaemic state to the B-ALL state is exposure to immune stressors, such as infection. Here, we discuss our current understanding of the environmental triggers and genetic predispositions that may lead to B-ALL, highlighting lessons from epidemiology, the clinic and animal models, and identifying priority areas for future research., Research at C.C.’s laboratory was partially supported by the European Regional Development Fund (FEDER)/MINECO (SAF2017-83061-R), Fundación Ramón Areces and a research contract with Fundación Síndrome de Wolf-Hirschhorn o 4p-. Institutional grants from Fundación Ramón Areces and Banco de Santander to Centro de Biología Molecular Severo Ochoa are also acknowledged. The C.C. and C.V.-D. laboratories are members of the EU COST Action LEGEND (CA16223). Research in the C.V.-D. group is partially supported by an FEDER Miguel Servet grant (CPII19/00024 — AES 2017-2020) from Instituto de Salud Carlos III (Ministerio de Economía y Competitividad), Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (PI17/00167). Research in the I.S.-G. group is partially supported by the FEDER and by MINECO/FEDER (SAF2015-64420-R), MCIU/AEI/FEDER (RTI2018-093314-B-I00), Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18 and CSI144P20), the German Carreras Foundation (DJCLS 07R/2019) and Fundacion Unoentrecienmil (CUNINA project). The I.S.-G. laboratory is a member of EuroSyStem and the DECIDE Network funded by the European Union under the Seventh Framework Programme. C.V.-D. and I.S.-G. have been supported by the German Federal Office for Radiation Protection (BfS) (FKZ: 3618S32274).

Pattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surface of neutrophils and macrophages. A soluble form (sTREM1) of this protein that can be detected in human body fluids has been identified. Here we investigated the role of TREM1 during invasive pulmonary aspergillosis (IPA). IPA patients displayed significantly higher levels of sTREM1 in bronchoalveolar lavages when compared to control patients. Functional analysis in TREM1 showed that the levels of sTREM1 and TREM1 pathway-related cytokines were influenced by single nucleotide polymorphisms in TREM1. In addition, we confirmed a role of TREM1 on antifungal host defense against A. fumigatus in a murine model of IPA. TREM1 deficiency increased susceptibility to infection in the immunosuppressed murine host. Deletion of TREM1 showed delayed innate and adaptive immune responses and impaired pro-inflammatory cytokine responses. The absence of TREM1 in primary macrophages attenuated the TLR signaling by altering the expression of both receptor and effector proteins that are critical to the response against A. fumigatus. In this study, and for the first time, we demonstrate the key role for the TREM1 receptor pathway during IPA. This work was supported by the Fundação para a Ciência e a Tecnologia [PTDC/SAU-SER/29635/2017]; Fundação para a Ciência e a Tecnologia [UIDB/50026/2020 and UIDP/50026/2020]; Fundação para a Ciência e a Tecnologia [PTDC/MED-GEN/28778/2017]; H2020 Excellent Science [NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023)]; Instituto de Salud Carlos III [RD16/CIII/0004/0003]; Instituto de Salud Carlos III [PI18CIII/00045]; Instituto de Salud Carlos III [MPY 1277/15]; Ministerio de Ciencia, Innovación y Universidades [RTI2018-099114-B-I00]; Associação Viver a Ciência (PT) [SFRH/BD/136814/2018]; “la Caixa” Foundation [ID 100010434]. Sí

[Background]: Obesity proceeds with important physiological and microstructural alterations in the brain, but the precise relationships between the diet and feeding status, its physiological responses, and the observed neuroimaging repercussions, remain elusive. Here, we implemented a mouse model of high fat diet (HFD) feeding to explore specific associations between diet, feeding status, phenotypic and endocrine repercussions, and the resulting microstructural and metabolic alterations in the brain, as detected by diffusion tensor imaging (DTI) and neurochemical metabolic profiling. [Methods]: Brain DTI images were acquired from adult male C57BL6/J mice after 6 weeks of HFD, or standard diet (SD) administrations, both under the fed, and overnight fasted conditions. Metabolomic profiles of the cortex (Ctx), hippocampus (Hipc), and hypothalamus (Hyp) were determined by 1H high-resolution magic angle spinning (HRMAS) spectroscopy, in cerebral biopsies dissected after microwave fixation. Mean diffusivity (MD), fractional anisotropy (FA) maps, and HRMAS profiles were complemented with determinations of phenotypic alterations and plasma levels of appetite-related hormones, measured by indirect calorimetry and multiplex assays, respectively. We used Z-score and alternating least squares scaling (ALSCAL) analysis to investigate specific associations between diet and feeding status, physiological, and imaging parameters. [Results]: HFD induced significant increases in body weight and the plasma levels of glucose and fatty acids in the fed and fasted conditions, as well as higher cerebral MD (Ctx, Hipc, Hyp), FA (Hipc), and mobile saturated fatty acids resonances (Ctx, Hipc, Hyp). Z-score and ASLCAL analysis identified the precise associations between physiological and imaging variables. [Conclusions]: The present study reveals that diet and feeding conditions elicit prominent effects on specific imaging and spectroscopic parameters of the mouse brain that can be associated to the alterations in phenotypic and endocrine variables. Together, present results disclose a neuro-inflammatory response to HFD, characterized primarily by vasogenic edema and compensatory responses in osmolyte concentrations., The authors disclosed receipt of the following financial support for research, authorship, and/or publication of this article; Ministry of Science and Innovation (SAF2017-83043-R), and Community of Madrid (S2017/BMD-3688), both to SC and PLL. IG is a predoctoral fellow of the Ministry of Innovation and Science (BES-2015-075202); BL holds a senior investigator contract from CSIC; PLL, SC, and LB are CSIC staff members.

The brain is endowed with a unique cellular composition and organization, embedded within a vascular network and isolated from the circulating blood by a specialized frontier, the so-called blood-brain barrier (BBB), which is necessary for its proper function. Recent reports have shown that increments in the permeability of the blood vessels facilitates the entry of toxic components and immune cells to the brain parenchyma and alters the phenotype of the supporting astrocytes. All of these might contribute to the progression of different pathologies such as brain cancers or neurodegenerative diseases. Although it is well known that BBB breakdown occurs due to pericyte malfunctioning or to the lack of stability of the blood vessels, its participation in the diverse neural diseases needs further elucidation. This review summarizes what it is known about BBB structure and function and how its instability might trigger or promote neuronal degeneration and glioma progression, with a special focus on the role of pericytes as key modulators of the vasculature. Moreover, we will discuss some recent reports that highlights the participation of the BBB alterations in glioma growth. This pan-disease analysis might shed some light into these otherwise untreatable diseases and help to design better therapeutic approaches. Work was supported by Ministerio de Economía y Competitividad and FEDER funds: PI13/01258 to AHL, by “Asociación Española contra el Cancer (AECC) grant: INVES192GARG to RG and by Ministerio de Ciencia, Innovación y Universidades and FEDER funds: RTI2018-093596 to PSG. Sí

Rationale: We recently demonstrated that the Metabesity factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-Treated astrocytes. The impact of ORY100. An Inhibitor Of The LSD1-CoREST Complex, On Hmg20a Expression, Reactive Astrogliosis And Glucose Metabolism Was Evaluated In Vitro And In Vivo In High-Fat High-Sucrose Fed Mice. Results: We Show That Hmg20a Is Predominantly Expressed In Hypothalamic Astrocytes, The Main Nutrient-Sensing Cell Type Of The Brain. Hmg20a Expression Was Upregulated In Diet-Induced Obesity And Glucose Intolerant Mice, Correlating With Increased Transcript Levels Of Gfap And Il1b Indicative Of Inflammation And Reactive Astrogliosis. Hmg20a Transcript Levels Were Also Increased In Adipose Tissue Of Obese Non-Diabetic Individuals As Compared To Obese Diabetic Patients. Hmg20a Silencing In Astrocytes Resulted In Repression Of Inflammatory, Cholesterol Biogenesis And Epithelial-To-Mesenchymal Transition Pathways Which Are Hallmarks Of Reactive Astrogliosis. Accordingly, Hmg20a Depleted Astrocytes Exhibited Reduced Mitochondrial Bioenergetics And Increased Susceptibility To Apoptosis. Neuron Viability Was Also Hindered In HMG20A-Depleted Astrocyte-Derived Conditioned Media. Ory1001 Treatment Rescued Expression Of Reactive Astrogliosis-Linked Genes In Hmg20a Ablated Astrocytes While Enhancing Cell Surface Area, Gfap Intensity And Stat3 Expression In Healthy Astrocytes, Mimicking The Effect Of Hmg20a. Furthermore, Ory1001 Treatment Protected Against Obesity-Associated Glucose Intolerance In Mice Correlating With A Regression Of Hypothalamic Hmg20a Expression, Indicative Of Reactive Astrogliosis Attenuation With Improved Health Status. Conclusion: Hmg20a Coordinates The Astrocyte Polarization State. Under Physiological Pressure Such As Obesity And Insulin Resistance That Induces Low Grade Inflammation, Hmg20a Expression Is Increased To Induce Reactive Astrogliosis In An Attempt To Preserve The Neuronal Network And Re-Establish Glucose Homeostasis. Nonetheless, A Chronic Metabesity State Or Functional Mutations Will Result In Lower Levels Of Hmg20a, Failure To Promote Reactive Astrogliosis And Increase Susceptibility Of Neurons To Stress-Induced Apoptosis. Such Effects Could Be Reversed By Ory1001 Treatment Both In Vitro And In Vivo, Paving The Way For A New Therapeutic Approach For Type 2 Diabetes Mellitus., The authors are supported by grants from the Consejería de Salud, Fundación Pública Andaluza Progreso y Salud, Junta de Andalucía (PI-0727-2010 and PI-0001-2020 to B.R.G.; PI-0085-2013 to P.I.L.; PI-0006-2016 to E.F.M.; PI-0574-2012 to S.Y.R.Z; PI-0247-2016 to F.J.B.S.), the Consejería de Economía, Innovación y Ciencia (P10.CTS.6359 to B.R.G.; CTS.8081 to E.G.F.), the Ministerio de Economía y Competitividad co-funded by Fondos FEDER (PI10/00871, PI13/00593 and BFU2017-83588-P to B.R.G.; PRE2018-084907 to M.E.M.V.G.; PI13/00309; PI17/01004 to F.J.B.S.; BFU2014-5343-P to J.C.R.; and AGL2017-86927-R to F.M.), Vencer el Cancer (B.R.G), DiabetesCero (B.R.G.) and the Juvenile Diabetes Research Foundation (17-2013-372 and 2-SRA-2019-837-S-B to B.R.G.). E.F.M. was a recipient of a Juan de la Cierva Incorporación Fellowship from the Ministerio de Economía y Competitividad (IJCI-2015-26238). S.Y.R.Z is a recipient of a postdoctoral fellowship from Consejería de Salud, Junta de Andalucía (RH-0070-2013). L.L.N. is supported by a Consejeria de Economia, Conocimiento, Empresas y Universidad postdoctoral fellowship (DOC_00652). F.J.B.S. and E.G.F. are recipients of "Nicolás Monardes" research contracts from Consejería de Salud Junta de Andalucía, (C-0070-2012 and C-0031-2016). A.M.M. is supported by CPII19/00023 and PI18/01590 from the Instituto de Salud Carlos III co-funded by Fondos FEDER. CIBERDEM is an initiative of the Instituto de Salud Carlos III. V.C. is supported by a AECC investigator award.

Background: Cauliflower (Brassica oleracea L. var. botrytis) inflorescences are composed mainly of meristematic tissue, which has a high cellular proliferation. This considerable cellular density makes the inflorescence an organ with a large proportion of membranes. However, little is known about the specific role of the lipid and protein composition of the plasma membrane present in this organ. Results: In this work, we analyzed the lipids and proteins present in plasma membrane from two different stages of development of cauliflower inflorescence and compared them with leaf plasma membrane. For this purpose, plasma membrane vesicles were obtained by centrifugation for each sample and the vesicular diameter and osmotic permeability (Pf) were analyzed by dynamic light scattering and the stopped-flow technique, respectively. In addition, fatty acids and sterols were analyzed by gas chromatography and HPLC. The protein composition of the inflorescences and leaves was characterized by HPLC-ESI-QTOF-MS and the data obtained were compared with Brassicaceae proteins present in the UniProt database in relation to the presence of aquaporins determined by western blot analysis. The highest Pf value was found in 90 day inflorescences-derived plasma membrane vesicles (61.4 ± 4.14 μms). For sterols and fatty acids, the concentrations varied according to the organ of origin. The protein profile revealed the presence of aquaporins from the PIP1 and PIP2 subfamilies in both inflorescences and leaves. Conclusion: This study shows that the composition of the sterols, the degree of unsaturation of the fatty acids, and the proteins present in the membranes analyzed give them high functionality for water passage. This represents an important addition to the limited information available in this field., This work was funded by the CDTI, Spain (BIOTAGUT) and by the Spanish Ministerio de Ciencia, Innovación y Universidades (AGL2016–80247-C2–1-R) for the study, collection, analysis, and in writing the manuscript. P. García-Ibañez was funded by a grant from the Fundación Séneca-CARM, Spain (21273/FPI/19) for the interpretation of data and in writing the manuscript