Autophagy-inducing peptides from mammalian VSV and fish VHSV rhabdoviral G glycoproteins (G) as models for the development of new therapeutic molecules

It has not been elucidated whether or not autophagy is induced by rhabdoviral G glycoproteins (G) in vertebrate organisms for which rhabdovirus infection is lethal. Our work provides the first evidence that both mammalian (vesicular stomatitis virus, VSV) and fish (viral hemorrhagic septicemia virus, VHSV, and spring viremia carp virus, SVCV) rhabdoviral Gs induce an autophagic antiviral program in vertebrate cell lines. The transcriptomic profiles obtained from zebrafish genetically immunized with either Gsvcv or Gvhsv suggest that autophagy is induced shortly after immunization and therefore, it may be an important component of the strong antiviral immune responses elicited by these viral proteins. Pepscan mapping of autophagy-inducing linear determinants of Gvhsv and Gvsv showed that peptides located in their fusion domains induce autophagy. Altogether these results suggest that strategies aimed at modulating autophagy could be used for the prevention and treatment of rhabdoviral infections such as rabies, which causes thousands of human deaths every year

Bibliotecas Académicas para el siglo XXI

Memorias: Seminario "Bibliotecas académicas para el siglo XXI"Memories: Seminar "Academic Libraries for the XXI century"Memórias: Seminário " Bibliotecas acadêmicas para o século XXI

Understanding 34 Years of Forest Cover Dynamics across the Paraguayan Chaco: Characterizing Annual Changes and Forest Fragmentation Levels between 1987 and 2020

Over the past 40 years, Paraguay has lost the majority of its natural forest cover, thus becoming one of the countries with the highest deforestation rates in the world. The rapid expansion of the agricultural frontier, cattle ranching, and illegal logging between 1987 and 2012 resulted in the loss of 27% of original forest cover, equivalent to almost 44,000 km2. Within this context, the present research provides the first yearly analysis of forest cover change in the Paraguayan Chaco between the years 1987 and 2020. Remote sensing data obtained from Landsat images were applied to derive annual forest cover masks and deforestation rates over 34 years. Part of this study is a comprehensive assessment of the effectiveness of protected areas, as well as an analysis of the degree of fragmentation of the forest. All classification results obtained accuracies above 80% and revealed a total forest cover loss of approximately 64,700 km2. Forest clearing within protected areas was not frequent; however, some natural reserves presented losses of up to 25% of their forest cover. Through the consideration of several landscape metrics, this study reveals an onward fragmentation of forest cover, which endangers the natural habitat of numerous species

Rag1 immunodeficiency‐induced early aging and senescence in zebrafish are dependent on chronic inflammation and oxidative stress [Poster]

12th European Zebrafish Meeting, Krakow, 9-13 July 2023In mammals, recombination activating gene 1 (RAG1) plays a crucial role in adaptive immunity, generating a vast range of immunoglobulins. Rag1−/− zebrafish (Danio rerio) are viable and reach adulthood without obvious signs of infectious disease in standard nonsterile conditions, suggesting that innate immunity could be enhanced to compensate for the lack of adaptive immunity. By using microarray analysis, we confirmed that the expression of immunity- and apoptosis-related genes was increased in the rag1−/− fish. This tool also allows us to notice alterations of the DNA repair and cell cycle mechanisms in rag1−/− zebrafish. Several senescence and aging markers were analyzed. In addition to the lower lifespan of rag1−/− zebrafish compared to their wild-type (wt) siblings, rag1−/− showed a higher incidence of cell cycle arrest and apoptosis, a greater amount of phosphorylated histone H2AX, oxidative stress and decline of the antioxidant mechanisms, an upregulated expression and activity of senescence-related genes and senescence-associated β-galactosidase, respectively, diminished telomere length, and abnormal self-renewal and repair capacities in the retina and liver. Metabolomic analysis also demonstrated clear differences between wt and rag1−/− fish, as was the deficiency of the antioxidant metabolite L-acetylcarnitine (ALCAR) in rag1−/− fish. Therefore, Rag1 activity does not seem to be limited to V(D)J recombination but is also involved in senescence and aging. Furthermore, we confirmed the senolytic effect of ABT-263, a known senolytic compound and, for the first time, the potential in vivo senolytic activity of the antioxidant agent ALCAR, suggesting that this metabolite is essential to avoid premature agingN

High Viral Fitness during Acute HIV-1 Infection

Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection

Péptido de miticina y su uso en regeneración celular

La presente invención se refiere a unos péptidos derivados de la micitina C y sus usos terapéuticos, más concretamente en la regeneración celular y/o tisular. [ES]The present invention relates to peptides derived from myticin C and to their therapeutic use, more specifically in cell and/or tissue regeneration. [EN]Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Miguel HernándezA1 Solicitud de patente con informe sobre el estado de la técnic

Péptido de miticina y su uso en regeneración celular

Péptido de miticina y su uso en regeneración celular. La presente invención se refiere a unos péptidos derivados de la micitina C y sus usos terapéuticos, más concretamente en la regeneración celular y/o tisular.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Miguel HernándezA1 Solicitud de patente con informe sobre el estado de la técnic

pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis

marine drug

Péptido de miticina y su uso en regeneración celular

La presente invención se refiere a unos péptidos derivados de la micitina C y sus usos terapéuticos, más concretamente en la regeneración celular y/o tisular.Peer reviewedConsejo Superior de Investigaciones Científicas (CSIC), Universidad Miguel HernándezB2 Patente con examen previ

Chromatin immunoprecipitation and high throughput sequencing of SVCV-infected zebrafish reveals novel epigenetic histone methylation patterns involved in antiviral immune response

8 pages, 4 figures, 1 tableChromatin immunoprecipitation (ChIP) and high throughput sequencing (ChIP-seq) have been used to assess histone methylation (epigenetic modification) dynamics within the internal organs of zebrafish after spring viremia of carp virus (SVCV) infection. Our results show H3K4me3 up-methylation in gene promoters associated with innate immune response during the first 5 days after SVCV infection. Gene Ontology (GO) enrichment analysis confirmed up-methylation in 218 genes in the “immune system process” category. In particular, the promoters of interferon (ifn), interferon stimulated genes (isg), Toll-like receptors (tlr) and c-reactive protein (crp) multi gene sets were marked with the permissive H3K4 methylation. Higher histone 3 methylation was associated with higher transcription levels of the corresponding genes. Therefore, the evidence presented here suggests that transcriptional regulation at the promoter level of key immune genes of the interferon signaling pathway and c-reactive proteins genes can be modulated by epigenetic modification of histones. This study emphasizes the importance of epigenetic control in the response of zebrafish to SVCV infectionThis study was supported by Spanish Ministerio de Educación y Competitividad Grant AGL2014-51773-C3 and grant BIO2017-82851-C3-1-R. Dr. Ortega-Villaizán is the holder of ERC Starting Grant 2014 GA639249. Melissa Belló-Pérez is the holder of GVAL fellowship ACIF/2016/207Peer reviewe