Cambios en la expresión de neurotransmisores inhibidores en respuesta a la lesión y durante la regeneración espinal en la lamprea de mar

En humanos, las lesiones medulares causan daños permanentes e irreversibles, constituyendo un grave problema personal, social y económico, para el que, hasta el momento, no existen terapias adecuadas. La identificación de los cambios que tienen lugar en la médula espinal en vertebrados que, como las lampreas, recobran espontáneamente la locomoción después de una lesión medular, puede ayudar a determinar los factores clave que conducen a la recuperación de la función y a descifrar los mecanismos de plasticidad que tienen lugar durante el proceso de regeneración. La glicina y el GABA son los principales sistemas inhibidores rápidos en el cerebro y la médula espinal de los vertebrados. En la médula espinal de la lamprea los sistemas GABAérgico y glicinérgico constan de un componente intrínseco, constituido por neuronas espinales y sus prolongaciones, y, en el caso del sistema glicinérgico, también de un componente extrínseco formado por fibras descendentes procedentes de neuronas localizadas en el tronco cerebral. La glicina tiene un importante papel en los circuitos espinales involucrados en la locomoción. Así, las interneuronas glicinérgicas cuyo axón cruza la línea media coordinan la acción de las interneuronas excitadoras en el lado contralateral y son responsables de la emergencia del patrón alternante derecha/izquierda. El GABA es un modulador de la locomoción e interviene, además, en determinados procesos durante el desarrollo. La lesión medular provoca la liberación masiva de neurotransmisores al espacio extracelular. El incremento de los niveles extracelulares de glicina después de la lesión puede potenciar la excitotoxicidad causada por el glutamato, debido a su acción como co-agonista de los receptores NMDA. La liberación de GABA, sin embargo, parece tener un efecto neuroprotector. Los objetivos principales de este proyecto son: 1.- Estudiar el patrón de distribución de las neuronas reticulares glicinérgicas de proyección espinal. 2.- Conocer si existen neuronas reticulares GABAérgicas que proyecten a la médula espinal y, en caso afirmativo, estudiar su patrón de distribución. 3.- Conocer si hay neuronas reticuloespinales inhibidoras que colocalicen glicina y GABA. 4.- Analizar los cambios de expresión de los neurotrasmisores inhibidores en respuesta a la lesión. Para ello, analizaremos el patrón de expresión espaciotemporal de la inmunorreactividad a GABA y glicina durante la primera semana después de la sección completa de la médula espinal. 5.- Analizar los cambios de expresión de los neurotransmisores inhibidores durante la regeneración medular en larvas de lamprea de mar

Viral oncolysis that targets raf-1 signaling control of nuclear transport

The central role of Raf protein kinase isoforms in human cancer demands specific anti-Raf therapeutic inhibitors. Parvoviruses are currently used in experimental cancer therapy due to their natural oncotropism and lytic life cycle. In searching for mechanisms underlying parvovirus oncolysis, we found that trimers of the major structural protein (VP) of the parvovirus minute virus of mice (MVM), which have to be imported into the nucleus for capsid assembly, undergo phosphorylation by the Raf-1 kinase. Purified Raf-1 phosphorylated the capsid subunits in vitro to the two-dimensional pattern found in natural MVM infections. VP trimers isolated from mammalian cells translocated into the nucleus of digitonin-permeabilized human cells. In contrast, VP trimers isolated from insect cells, which are devoid of Raf-1, were neither phosphorylated nor imported into the mammalian nucleus. However, the coexpression of a constitutively active Raf-1 kinase in insect cells restored VP trimer phosphorylation and nuclear transport competence. In MVM-infected normal and transformed cells, Raf-1 inhibition resulted in cytoplasmic retention of capsid proteins, preventing their nuclear assembly and progeny virus maturation. The level of Raf-1 activity in cancer cells was consistent with the extent of VP specific phosphorylation and with the permissiveness to MVM infection. Thus, Raf-1 control of nuclear translocation of MVM capsid assembly intermediates provides a novel target for viral oncolysis. MVM may reinforce specific therapies against frequent human cancers with deregulated Raf signaling. © 2010, American Society for Microbiology. All Rights Reserved.This study was supported by grants from the Spanish Ministerio de Ciencia e Innovación (SAF2008-03238) and Comunidad de Madrid (S-SAL/0185/2006) to the laboratory of J.M.A. and by an institutional grant from Fundación Ramón Areces to the Centro de Biología Molecular “Severo Ochoa.” L.R. was supported in part by a short-term EMBO fellowship.Peer Reviewe

Data on the recovery of glycinergic neurons afterspinal cord injury in lampreys

We used immunohistochemical methods to quantify changes inthe number of glycine-immunoreactive neurons of the dorsome-dial, lateral and cerebrospinalfluid contacting cell populations ofthe spinal cord of larval sea lampreys after a complete spinal cordinjury. The data presented here are quantifications of the numberof glycine-immunoreactive neurons located in the rostral andcaudal stumps of the spinal cord and the corresponding statisticalanalyses. These data show that, glycine immunoreactivity is lost inglycinergic neurons immediately after injury and that the numberof glycine-immunoreactive neurons is recovered in the followingtwo weeks. These data are useful for researchers investigatingdeterminants that underlie the spontaneous recovery of locomo-tion following spinal injuries in regenerating animal models, andfor analysing the role of glycinergic neurons in spinal cord repairafter an injuryGrant sponsors: FEDER/Ministerio de Ciencia, Innovación y Universidades - Agencia Estatal deInvestigación (Grant number: BFU-2017-87079-P)S

Anxiety and facial self-contacts: possible impact on COVID‐19 transmission in dental practice

Background The purpose was to analyse the associations between dental and trait anxiety, fear of COVID-19 and the duration and frequency of spontaneous hand-to-face contact (self-contact). Methods A cross-sectional design was carried out with 128 adult patients from four dental clinics in Madrid, during the confinement, from March 15 to May 15. The patients' movements in the waiting room were monitored with Microsoft Kinect Software, also completed the Trait anxiety subscale of the STAI, the COVID-19 Fear and the S-DAI questionnaire. Results Associations were observed between the duration and frequency of facial, mask and eye contact with trait anxiety and dental fear was determined only by the frequency of this self-contact. Trait anxiety is associated with dental anxiety and with fear of COVID-19. Although facial self-contact is higher in women, it also rises in men as dental fear increases. Moreover, dental anxiety is a good predictor of trait anxiety and the incidence of facial self-contact. Conclusions Understanding the possible associations between biopsychosocial factors, such as trait anxiety, dental anxiety and self-contact is important. It may help to prevent the spread of COVID-19 in the population as well as enabling the formulation of effective interventions to improve oral health care through the implementation of dental care programmes

Differential phosphorylation and n-terminal configuration of capsid subunits in parvovirus assembly and viral trafficking

publisher: Elsevier articletitle: Differential phosphorylation and n-terminal configuration of capsid subunits in parvovirus assembly and viral trafficking journaltitle: Virology articlelink: http://dx.doi.org/10.1016/j.virol.2018.02.018 content_type: article copyright: © 2018 Elsevier Inc. All rights reserved

Plasmodium vivax Cysteine-Rich Protective Antigen Polymorphism at Exon-1 Shows Recombination and Signatures of Balancing Selection

Plasmodium vivax Cysteine-Rich Protective Antigen (CyRPA) is a merozoite protein participating in the parasite invasion of human reticulocytes. During natural P. vivax infection, antibody responses against PvCyRPA have been detected. In children, low anti-CyRPA antibody titers correlated with clinical protection, which suggests this protein as a potential vaccine candidate. This work analyzed the genetic and amino acid diversity of pvcyrpa in Mexican and global parasites. Consensus coding sequences of pvcyrpa were obtained from seven isolates. Other sequences were extracted from a repository. Maximum likelihood phylogenetic trees, genetic diversity parameters, linkage disequilibrium (LD), and neutrality tests were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. In 22 sequences from Southern Mexico, two synonymous and 21 nonsynonymous mutations defined nine private haplotypes. These parasites had the highest LD-R2 index and the lowest nucleotide diversity compared to isolates from South America or Asia. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity and Rm values than those of exon-2. Exon-1 had significant positive values for Tajima’s D, β-α values, and for the Z (HA: dN > dS) and MK tests. These patterns were similar for parasites of different origin. The polymorphic amino acid residues at PvCyRPA resembled the conformational B-cell peptides reported in PfCyRPA. Diversity at pvcyrpa exon-1 is caused by mutation and recombination. This seems to be maintained by balancing selection, likely due to selective immune pressure, all of which merit further study

Hypoxia-inducible factor 2α drives hepatosteatosis through the fatty acid translocase CD36

Background & Aims: Molecular mechanisms by which hypoxia might contribute to hepatosteatosis, the earliest stage in non-alcoholic fatty liver disease (NAFLD) pathogenesis, remain still to be elucidated. We aimed to assess the impact of hypoxia-inducible factor 2α (HIF2α) on the fatty acid translocase CD36 expression and function in vivo and in vitro. Methods: CD36 expression and intracellular lipid content were determined in hypoxic hepatocytes, and in hypoxic CD36- or HIF2α -silenced human liver cells. Histological analysis, and HIF2α and CD36 expression were evaluated in livers from animals in which von Hippel-Lindau (Vhl) gene is inactivated (Vhl -deficient mice), or both Vhl and Hif2a are simultaneously inactivated (Vhl Hif2α -deficient mice), and from 33 biopsy-proven NAFLD patients and 18 subjects with histologically normal liver. Results: In hypoxic hepatocytes, CD36 expression and intracellular lipid content were augmented. Noteworthy, CD36 knockdown significantly reduced lipid accumulation, and HIF2A gene silencing markedly reverted both hypoxia-induced events in hypoxic liver cells. Moreover livers from Vhl -deficient mice showed histologic characteristics of non-alcoholic steatohepatitis (NASH) and increased CD36 mRNA and protein amounts, whereas both significantly decreased and NASH features markedly ameliorated in Vhl Hif2α -deficient mice. In addition, both HIF2α and CD36 were significantly overexpressed within the liver of NAFLD patients and, interestingly, a significant positive correlation between hepatic transcript levels of CD36 and erythropoietin (EPO), a HIF2α -dependent gene target, was observed in NAFLD patients. Conclusions: This study provides evidence that HIF2α drives lipid accumulation in human hepatocytes by upregulating CD36 expression and function, and could contribute to hepatosteatosis setup. f/f f/f /f f/f f/f f/fThis work was supported by PI13/01299, PI17/00535 and CIBEREHD from Instituto de Salud Carlos III (ISCIII/FEDER, Spain) to CGM; CP14/00181, PI16/00823 and PI19/00123 (ISCIII/FEDER, Spain), and Beca Eduardo Gallego 2016 (Fundación Francisco Cobos, Spain) to AGR; SAF2016-76815 (Ministerio de Economía y Competitividad/FEDER, Spain), 534/C/2016 (TV3 Marató, Spain) and CIBERCV (ISCIII/FEDER, Spain) to JA

Analysis of fifty years of severe malaria worldwide research

This study analyzed fifty years of severe malaria research worldwide. Malaria is a parasitic disease that continues to have a significant impact on global health, particularly in sub-Saharan Africa. Severe malaria, a severe and often fatal form of the disease, is a major public health concern. The study used different bibliometric indicators such as the number of publications, citations, authorship, and keywords to analyze the research trends, patterns, and progress made in the field of severe malaria. The study covers the period from 1974 to 2021 and includes articles from Scopus. The results of the study indicated that there has been a steady increase in the number of publications on severe malaria over the past fifty years, with a particular increase in the last decade. The study also showed that most of the publications are from USA and Europe, while the disease occurs in Africa, South-East Asia, and the Americas. The study also identified the most frequent keywords used in the publications, and the most influential journals and authors in the field. In conclusion, this bibliometric study provides a comprehensive overview of the research trends and patterns in the field of severe malaria over the past fifty years and highlights the areas that need more attention and research efforts