Serological autoimmune profile of systemic lupus erythematosus in deep and non-deep endometriosis patients

Several studies have reported a high prevalence of autoimmune diseases such as systemic lupus erythematosus (SLE) in endometriosis patients. The aim of this study was to evaluate the SLE autoimmune antibody profile in patients with deep (DE) and non-deep endometriosis (Non-DE).Four groups of premenopausal patients were evaluated: patients with DE (n = 50); patients with ovarian endometriomas (Non-DE; n = 50); healthy patients without endometriosis (C group; n = 45); and SLE patients without endometriosis (SLE group; N = 46). Blood samples were obtained and the standard SLE autoimmune profile was evaluated in all patients. Pain symptoms related to endometriosis and clinical SLE manifestations were also recorded.The DE group presented a statistically significant higher proportion of patients with antinuclear antibodies (ANA) (20%) compared to the Non-DE group (4%) and C group (2.2%). Levels of complement were more frequently lower among DE and Non-DE patients although differences did not reach statistical significance. Similarly, anti-dsDNA antibodies and anticoagulant lupus were positive in more patients of the DE group but did not reach statistical significance. The DE group complained of more arthralgia and asthenia compared to the Non-DE and C groups.The results of this study showed higher positivity of ANA and greater arthralgia and asthenia in patients with DE compared with Non-DE patients and healthy controls, suggesting that they may have a higher susceptibility to autoimmune diseases and present more generalized pain.Copyright © 2023. Published by Elsevier B.V

Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis

Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of transthyretin (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, a rare, but fatal, disorder in which TTR aggregates in the brain. The disease remains intractable, since liver transplantation, the reference therapy for systemic ATTR, does not stop mutant TTR production in the brain. In addition, despite current pharmacological strategies have shown to be effective against in vivo TTR aggregation by stabilizing the tetramer native structure and precluding its dissociation, they display low brain permeability. Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently, inhibiting their aggregation. Because tolcapone is an FDA-approved drug that crosses the blood-brain barrier, our results suggest that it can translate into a first disease-modifying therapy for leptomeningeal amyloidosis. Databases PDB codes for A25T-TTR, V30G-TTR, and Y114C-TTR bound to tolcapone are 6TXV, 6TXW, and 6XTK, respectively

Cardiac troponin I release after a basketball match in elite, amateur and junior players

BACKGROUND: Available scientific data related to cardiac troponin I (cTnI) release after intermittent exercise is limited. It is also of interest to determine what personal or environmental factors mediate the exercise-induced release of cTnI. This study had two objectives: 1) to examine the individual release of cTnI to a basketball match; and 2) to establish the influence of athlete status as well as biological age on cTnI release. METHODS: Thirty-six basketball players (12 adult elite [PBA]: 27.3±4.1 years, 12 adult amateur [ABA]: 29.6±2.9 years, and 12 junior elite [JBA]: 16.6±0.9 years) participated in a simulated basketball match with serial assessment of cTnI at rest, immediately post- and at 1, 3, 6, 12, and 24 h post-exercise. RESULTS: The basketball match increased cTnI levels (pre: median [range]; 0.006 [0.001-0.026]; peak post: 0.024 [0.004-0.244] μg/L; p=0.000), with substantial individual variability in peak values. PBA and JBA players showed higher baseline and post-exercise cTnI values than ABA (all p<0.05). Peak cTnI exceeded the upper reference limit (URL) in the 26% of players (3 PBA; 6 JBA). CONCLUSIONS: The current results suggest that intermittent exercise can promote the appearance of cTnI and that this is potentially mediated by athlete status

Impact of Global Warming on the Severity of Viral Diseases: A Potentially Alarming Threat to Sustainable Aquaculture Worldwide

With an ever-increasing human population, food security remains a central issue for the coming years. The magnitude of the environmental impacts of food production has motivated the assessment of the environmental and health benefits of shifting diets, from meat to fish and seafood. One of the main concerns for the sustainable development of aquaculture is the emergence and spread of infectious animal diseases in a warming climate. We conducted a meta-analysis to investigate the influence of global warming on mortality due to viral infections in farmed aquatic animals. We found a positive trend between increasing temperature and increasing viral virulence, with an increase in water temperature of 1 °C resulting in an increase in mortality of 1.47–8.33% in OsHV-1 infected oysters, 2.55–6.98% in carps infected with CyHV-3 and 2.18–5.37% in fishes infected with NVVs. We suggest that global warming is going to pose a risk of viral disease outbreaks in aquaculture and could compromise global food security

The effects of death and post-mortem cold ischemia on human tissue transcriptomes

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.Peer ReviewedPostprint (published version

Moving towards more sustainable aquaculture practices: a meta-analysis on the potential of plant-enriched diets to improve fish growth, immunity and disease resistance

Aquatic animal diseases are one of the major limiting factors in aquaculture development, with disease emergence forecast to increase with global change. However, in order to treat increasing diseases in a context of global emergence of antimicrobial resistance and strengthening regulations on antimicrobial use, sustainable alternatives are urgently needed. The use of plant supplements to increase fish immunity and disease resistance has gained much popularity within the last decades. The use of functional supplements, such as plants, can also improve growth and feed assimilation, contributing to a better optimization of aquaculture resources (e.g. fish meal inclusion). We conducted a systematic review and meta-analysis in order to identify the research gaps in the use of plant-enriched diets in fish aquaculture and estimate, for the first time, the overall efficacy of plant-enriched diets on fish growth, immunity and disease resistance as well as the effect of intrinsic parameters (fish trophic level, type of plant material, dosage, treatment duration and pathogen species) on the treatment efficacy. We found that plant-enriched diets significantly enhanced growth, immunity and disease survival of treated fish, regardless of the fish trophic level, treatment duration and type of material used. We also show that plant supplements are a versatile alternative that can benefit different aquaculture sectors (from small-scale fish farmers to intensive productions). Finally, we observed that studies need to improve the information reported about the plant material used (e.g. origin, identification, chemical composition), in order to allow the comparison of different experiments and improve their repeatability

Genome-wide patterns of promoter sharing and co-expression in bovine skeletal muscle

Background: Gene regulation by transcription factors (TF) is species, tissue and time specific. To better understand how the genetic code controls gene expression in bovine muscle we associated gene expression data from developing Longissimus thoracis et lumborum skeletal muscle with bovine promoter sequence information.Results: We created a highly conserved genome-wide promoter landscape comprising 87,408 interactions relating 333 TFs with their 9,242 predicted target genes (TGs). We discovered that the complete set of predicted TGs share an average of 2.75 predicted TF binding sites (TFBSs) and that the average co-expression between a TF and its predicted TGs is higher than the average co-expression between the same TF and all genes. Conversely, pairs of TFs sharing predicted TGs showed a co-expression correlation higher that pairs of TFs not sharing TGs. Finally, we exploited the co-occurrence of predicted TFBS in the context of muscle-derived functionally-coherent modules including cell cycle, mitochondria, immune system, fat metabolism, muscle/glycolysis, and ribosome. Our findings enabled us to reverse engineer a regulatory network of core processes, and correctly identified the involvement of E2F1, GATA2 and NFKB1 in the regulation of cell cycle, fat, and muscle/glycolysis, respectively.Conclusion: The pivotal implication of our research is two-fold: (1) there exists a robust genome-wide expression signal between TFs and their predicted TGs in cattle muscle consistent with the extent of promoter sharing; and (2) this signal can be exploited to recover the cellular mechanisms underpinning transcription regulation of muscle structure and development in bovine. Our study represents the first genome-wide report linking tissue specific co-expression to co-regulation in a non-model vertebrate

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

Interactions in shrubsteppes: Implications for the maintenance of a threatened bird

The interactions between ecosystem components and their implications on birds have been poorly studied, especially in shrubsteppes. In this work, we evaluate the interactions between vegetation structure, arthropods availability and the use of space by the Dupont's lark (Chersophilus duponti) in important areas for the species in the Iberian Peninsula. To that end, between 20152018 springs, bird censuses and microhabitat samples were carried out in suitable areas for the species, which should be taken as a reference for habitat restoration tasks. The intensity of space use by the species was calculated by a kernel density function, which defines the probability of finding a territory from the spatial pattern of observations. The habitat quality was determined by sampling vegetation structure and food availability. Habitat structure variables were summarized by principal component analysis. Linear mixed models (LMMs) were adjusted to evaluate the relationships between variables. Shrub cover was positively and significantly related to total epigeous biomass and Coleoptera biomass, and positive but marginally significant with hypogeous biomass (mainly arthropods larvae). The biomass of order Araneae was positively and significantly related to the use of space by Dupont's lark, while total epigeous biomass and Coleoptera biomass were positively but marginally related to the use of space by Dupont's lark. This work provides new results about habitat and its quality for Dupont's lark in optimal habitat for the species, and it highlight the fundamental role of arthropod availability for the maintenance of the species which has to be taken into account in carrying out restoration actions for the speciesEste trabajo se ha realizado gracias a la Oficina de Educación, Juventud y Deporte (Comunidad de Madrid) y el Fondo Social Europeo para la Iniciativa de Empleo Juvenil (PEJD-2018-PRE/AMB-8063); el proyecto Life-Ricotí (LIFE15-NATES-000802), otorgado por la Comisión Europea; el proyecto BBVADron-Ricotí, otorgado por la Fundación BBV