Influence of cerebral vasodilation on blood reelin levels in growth restricted fetuses

Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

AO-4025 ITT ESA - Surface treatments and coatings for reduction of multipactor and Passive InterModulation (PIM) effect in RF components

This is the electronic version of a paper presented at the 4th International Workshop on Multipactor, Corona and Passive Intermodulation in Space RF Hardware (MULCOPIM 2003) held in Noordwijk, The Netherlands.ESA has initiated several activities with the aim to reduce the risk of multipaction and corona effects in space hardware. Within the activity Surface Treatment and Coating for the Reduction of Multipactor and Passive Intermodulation (PIM) Effects in RF Components a European group has been formed to investigate new surface coatings / treatments to improve the power handling capability of passive equipment with respect to multipactor and passive intermodulation. This paper presents an overview of the activities to be performed within this project and describes the first results

Actualización de las recomendaciones para la determinación de biomarcadores en el carcinoma de pulmón avanzado de célula no pequeña. Consenso Nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica

En el año 2011 se inició un proyecto conjunto entre la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) para establecer unas recomendaciones basadas en la evidencia actual con respecto a la determinación de biomarcadores en pacientes con carcinoma de pulmón de célula no pequeña (CPCNP) avanzado. La mayoría de estas recomendaciones siguen siendo válidas; sin embargo, existen nuevas evidencias que hacen necesaria la actualización de algunos aspectos. En concreto, se modifica la recomendación de qué biomarcadores hay que analizar y en qué pacientes, y se define el manejo óptimo de la muestra tumoral así como las características del material mínimo necesario para la determinación de biomarcadores. Además, se revisan las técnicas adecuadas para la determinación de las mutaciones de EGFR y el reordenamiento de ALK, y se consensúa en qué situaciones se debe llevar a cabo una re-biopsi

Klebsiella pneumoniae Strains Producing Extended-Spectrum B-Lactamases in Spain: Microbiological and Clinical Features

Extended-spectrum B-lactamases (ESBL) of the CTX-M, SHV, and TEM families were recognized in 76 (67%), 31 (27%), and 6 (5%) isolates, respectively, among 162 ESBL-producing Klebsiella pneumoniae (ESBLKp) strains obtained in a multicenter study in Spain. Predisposing factors for ESBL-Kp acquisition included invasive procedures, mechanical ventilation, and previous antimicrobial use

Necklace-structured high-harmonic generation for low-divergence, soft x-ray harmonic combs with tunable line spacing

The extreme nonlinear optical process of high-harmonic generation (HHG) makes it possible to map the properties of a laser beam onto a radiating electron wave function and, in turn, onto the emitted x-ray light. Bright HHG beams typically emerge from a longitudinal phased distribution of atomic-scale quantum antennae. Here, we form a transverse necklace-shaped phased array of linearly polarized HHG emitters, where orbital angular momentum conservation allows us to tune the line spacing and divergence properties of extreme ultraviolet and soft x-ray high-harmonic combs. The on-axis HHG emission has extremely low divergence, well below that obtained when using Gaussian driving beams, which further decreases with harmonic order. This work provides a new degree of freedom for the design of harmonic combs—particularly in the soft x-ray regime, where very limited options are available. Such harmonic beams can enable more sensitive probes of the fastest correlated charge and spin dynamics in molecules, nanoparticles, and materials.The JILA team graciously acknowledges support from the Department of Energy BES Award No. DE-FG02-99ER14982 for the experimental implementation, a MURI grant from the Air Force Office of Scientific Research under Award No. FA9550-16-1-0121 for the mid-infrared laser soft x-ray research, and a National Science Foundation Physics Frontier Center grant PHY-1734006 for theory. N.J.B. acknowledges support from National Science FoundationGraduate Research Fellowships (grant no. DGE-1650115). Q.L.D.N. acknowledges support from National Science Foundation Graduate Research Fellowships (grant no. DGE-1144083). J.S.R., L.P., and C.H.-G. acknowledge support from Ministerio de Ciencia e Innovación (FIS2016-75652-Pand PID2019-106910GB-I00). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 851201). J.S.R., L.P., and C.H.-G. also acknowledge support from Junta de Castilla y León FEDER funds (project no. SA287P18). L.R. acknowledges support from Ministerio de Educación, Cultura y Deporte (FPU16/02591). C.H.-G. acknowledges Ministerio de Ciencia, Innovación, y Universidades for Ramón y Cajal contract (RYC-2017-22745), cofunded by the European Social Fund. L.R., J.S.R., L.P., and C.H.-G. thankfully acknowledge the computer resources at MareNostrum and the technical support provided by Barcelona Supercomputing Center (FI-2020-3-0013)

4-Deoxyphorbol inhibits HIV-1 infection in synergism with antiretroviral drugs and reactivates viral reservoirs through PKC/MEK activation synergizing with vorinostat.

Latent HIV reservoirs are the main obstacle to eradicate HIV infection. One strategy proposes to eliminate these viral reservoirs by pharmacologically reactivating the latently infected T cells. We show here that a 4-deoxyphorbol ester derivative isolated from Euphorbia amygdaloides ssp. semiperfoliata, 4β-dPE A, reactivates HIV-1 from latency and could potentially contribute to decrease the viral reservoir. 4β-dPE A shows two effects in the HIV replication cycle, infection inhibition and HIV transactivation, similarly to other phorboids PKC agonists such PMA and prostratin and to other diterpene esters such SJ23B. Our data suggest 4β-dPE A is non-tumorigenic, unlike the related compound PMA. As the compounds are highly similar, the lack of tumorigenicity by 4β-dPE A could be due to the lack of a long side lipophilic chain that is present in PMA. 4β-dPE activates HIV transcription at nanomolar concentrations, lower than the concentration needed by other latency reversing agents (LRAs) such as prostratin and similar to bryostatin. PKCθ/MEK activation is required for the transcriptional activity, and thus, anti-latency activity of 4β-dPE A. However, CD4, CXCR4 and CCR5 receptors down-regulation effect seems to be independent of PCK/MEK, suggesting the existence of at least two different targets for 4β-dPE A. Furthermore, NF-κb transcription factor is involved in 4β-dPE HIV reactivation, as previously shown for other PKCs agonists. We also studied the effects of 4β-dPE A in combination with other LRAs. When 4β-dPE A was combined with another PKC agonists such as prostratin an antagonic effect was achieved, while, when combined with an HDAC inhibitor such as vorinostat, a strong synergistic effect was obtained. Interestingly, the latency reversing effect of the combination was synergistically diminishing the EC50 value but also increasing the efficacy showed by the drugs alone. In addition, combinations of 4β-dPE A with antiretroviral drugs as CCR5 antagonist, NRTIs, NNRTIs and PIs, showed a consistent synergistic effect, suggesting that the combination would not interefer with antiretroviral therapy (ART). Finally, 4β-dPE A induced latent HIV reactivation in CD4 + T cells of infected patients under ART at similar levels than the tumorigenic phorbol derivative PMA, showing a clear reactivation effect. In summary, we describe here the mechanism of action of a new potent deoxyphorbol derivative as a latency reversing agent candidate to decrease the size of HIV reservoirs.This work was supported by Ministry of Education of the Peruvian government (PRONABEC), the Universidad Complutense de Madrid (UCM-Santander PR87/19), the Instituto de Salud Carlos III (ISCIII-FIS PI16CIII/00034) and the Spanish AIDS Research Network RD12/0017/0015 that is included in the Spanish I D I Plan and is co-financed by ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). This work has also benefited from an “Investissement d’Avenir” grant managed by Agence Nationale de la Recherche (CEBA, ANR- 10-LABX-25-01).S

Revista de Vertebrados de la Estación Biológica de Doñana

Contribución al estudio de la bermejuela Rutilus arcasi, Steindachner, 1866 de la cuenca del Júcar (Osteichthyes: Cyprinidae)II. Edad y crecimientoSobre la taxonomía de Barbus comiza Steindachner, 1865 (Ostariophysi: Cyprinidae)Fenología de una comunidad de anfibios asociada a cursos fluviales temporales.Nueva especie para la ciencia de Anolis (Lacertilia: Iguanidae) de Cuba pertenecient eal complejo argillaceusSegregación ecológica en una comunidad de ofidios.El Aguila Imperial (Aquila adalberti): dispersión de los jóvenes, estructura de edades y mortalidaSobre diferencias individuales en la alimentación de Tyto albaInfluencia de las condiciones ambientales sobre la organización de la comunidad de aves invernantes en un bosque subalpino mediterráneoVariaciones en la agregación y distribución de la cabra montés (Capra pyrenaica Schinz,1838) detectadas con un muestreo de excrementosAlimentación del conejo (Oryctolagus cuniculus L. 1758) en Doñana. SO, EspañaSobre la distribución de Barbus meridionales Risso, 1826 (Ostariophysi: Cyprinidae) en la Península IbéricaSobre la distribución de Barbus meridionales Risso, 1826 (Ostariophysi: Cyprinidae) en la Península IbéricaNueva cita de Barbus microcephalus Almaça (Pisces, Cyprinidae) en España.Revisión taxonómica y distribución de Cobitis maroccana Pellegrin, 1929 (Osteichthyes, Cobitidae)Datos sobre una población de Lacerta viviparaSobre la presencia de Emys orbicularis en la provincia de León.Algunas observaciones sobre la captura de quirópteros por Falco subbuteo y Falco tinunculusNyctalus leisleri (Kuhk, 1818) (Mammalia: Chiroptera). Una nueva especie para las islas CanariaNuevos datos acerca de la distribución del topillo campesino Microtus arvalis, PALLAS 1778, en la Península IbéricaPeer reviewe

What role does the LPA1 receptor play in regulating emotional-like behaviours?

The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1–6) through which lysophosphatidic acid acts as an intercellular signalling molecule. It has been proposed that this receptor has a role in controlling anxiety-like behaviours and in the detrimental consequences of stress. In general, the neurobiological mechanism of fear extinction is strikingly similar to that of the adaptative stress response (distress regulation), sharing similar neuroanatomical, neuroendocrine, and neurochemical basis. Inadequate control of the stress response could precipitate or provoke anxiety disorders. In this context, we tried to elucidate the LPA1 receptor involvement in emotional regulation. For this purpose, we first examined fear extinction, a type of emotional regulation, in normal wild-type (wt) and maLPA1-null mice using two different extinction procedures (cued fear extinction and contextual fear extinction). Additionally, to study the role of the LPA1 receptor in the absence of developmental abnormalities induced by its permanent loss, the effect of the LPA1 antagonist Ki16425 administration was examined in contextual fear extinction on wild-type mice. Next, we studied the consequences of the absence of the LPA1 receptor in two key areas involved in emotional regulation, characterizing the structure and GABAergic composition of the medial prefrontal cortex (mPFC) and the amygdala by immunohistochemical detection of neuron specific nuclear protein (NeuN), GABA-positive cells and calcium-binding proteins (calretinin (CR), parvalbumin (PV), and calbindin (CB)). Lastly, we examined the corticosterone response and the expression of a marker of neuronal activity, c-Fos protein, in the amygdala and the mPFC after acute stress. Our results revealed that lack of the LPA1-receptor induces exaggerated amygdala reactivity and endocrine responses to emotional stimuli (e.g., an acute episode of stress), revealing a role of the LPA1 receptor in regulating emotional-like behaviours. Considering that a reduction of GABAergic inhibitory control in the amygdala may be a common mechanism to generate a heightened emotional state, the abnormal emotional response reported in LPA1-null mice could be explained, at least in part, by a significant reduction of GABAérgic composition of the amygdala observed in these animals. Taking together, the LPA1 receptor is involved in emotional behaviours and in the anatomical integrity of the corticolimbic circuit, the deregulation of which may be a susceptibility factor for anxiety disorders and a potential therapeutic target for the treatment of these diseases.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

IAA : Información y actualidad astronómica (33)

Sumario : Las estrellas jóvenes “imitan” a los agujeros negros.-- La Nebulosa de la Pipa.-- Galaxias “guisante verde”.-- HISTORIAS DE ASTRONOMÍA. Palomas y elefantes.-- DECONSTRUCCIÓN Y otros ENSAYOS. Misión Sunrise.-- EL “MOBY DICK” DE... Martín Guerrero Roncel (IAA-CSIC).-- ACTUALIDAD.-- ENTRE BASTIDORES.-- CIENCIA: PILARES E INCERTIDUMBRES : Agujeros negros.-- ACTIVIDADES IAA, AGENDA Y RECOMENDADOS.N

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc