Oliveira, D. | Search bioRxiv

bioRxiv2025

Gene Loss DB: A curated database for gene loss in vertebrate species.

Molecular databases are essential resources for both experimental and computational biologists. The rapid increase in high-quality genome assemblies has led to a surge in publications describing secondary gene loss events associated with lineage-specific adaptations across diverse vertebrate groups. This growing volume of information underscores the urgent need for organized, searchable, and curated resources that facilitate data discovery, allow detection of broad evolutionary patterns, and support downstream analyses. Currently, no existing database compiles manually curated and validated information on published secondary gene loss events. Here, we introduce the Gene Loss Database (GLossDB), a platform designed to centralize and present this data in an easy-to-search and user-friendly format (https://geneloss.org/). GLossDB compiles gene loss events alongside supporting evidence, including the inferred mechanism of gene loss (exon deletion, gene deletion, loss of function mutation), the type of data used to support inactivation (genomic, transcriptomic, single/multiple individual sequence reads, synteny maps) and, when available, whether the event is shared across all lineages within a taxon. Each entry also includes a short excerpt from the original publication to provide context. This information is structured in the database to be searchable by species, gene, taxa, or by GO-terms linked to the gene in question. The initial release of GLossDB focuses on cetaceans, a lineage with numerous gene loss events linked to aquatic adaptations. This first collection comprises 1866 gene loss events identified across 57 cetacean species. In addition, the database includes 1321 gene loss events from other taxa, which were also reported in the same studies and collected simultaneously.

bioinformatics↗

bioRxiv2025

Ghrelin and Mboat4 are lost in Serpentes

Exploring the evolution of gene networks associated with metabolic/energetic homeostasis can yield key insights into the adaptive landscapes governing the physioology of extant lineages. Here, we investigate a key hormonal module of energy metabolism in reptiles. Ghrelin (GHRL), also known as the "hunger hormone", is a multifunctional gastric peptide, involved in appetite, food intake and body weight regulation. We examined the genomes of 112 species comprising members of the Squamata, Testudines, Crocodilia and Rhynchocephalia and provide ample evidence that GHRL was independently lost in snakes, chameleons and toadhead agamas. In accordance, the enzyme responsible for ghrelin acylation and essential for its activity (membrane bound O-acyltransferase domain containing 4), is also eroded in these lineages. We suggest that the loss of this hormonal signalling system parallels critical modifications in energy metabolism, including a lower need to stimulate fatty acid oxidation during fasting in the locomotor muscles of snakes compared to other groups.

evolutionary biology↗

bioRxiv2025

Abdominal symptoms of invasive meningococcal disease are associated with the induction of plasminogen activator inhibitor in omental adipocytes

Abdominal symptoms are increasingly reported in invasive meningococcal disease (IMD), but the underlying mechanisms remain unclear. We aimed to explore the pathophysiology of these presentations using an animal model. We utilized a collection of 20 meningococcal isolates that were either associated or not associated with abdominal presentations, which were injected intraperitoneally into transgenic mice expressing human transferrin. We employed histological examination, RNA sequencing (RNAseq) transcriptomic analysis, and reverse transcriptase real-time PCR to analyze tissue preparations of the mices omentum. The 20 tested isolates induced similar levels of bacteremia in mice. However, isolates associated with abdominal presentations (mainly serogroup W isolates of clonal complex 11) caused thrombotic lesions in the blood vessels of the omentum, and they also induced a higher inflammatory response in the omentum with elevated levels of IL-6, TNF-alpha, and KC. Furthermore, these isolates induced higher expression of several genes, some of which are involved in coagulopathy, such as plasminogen activator inhibitor 1 (PAI-1). We also demonstrated that the PAI-1 encoding gene is overexpressed in adipocyte cells of the omentum. Lipopolysaccharide from the isolates associated with abdominal presentations, instead of whole bacteria, induced similar pathological findings. During IMD, thrombosis formation in the omentums blood vessels is associated with a local induction of an inflammatory response and overexpression of the plasminogen activator inhibitor 1 encoding gene. These lesions can lead to thrombosis and hypoperfusion in the omentum, resulting in clinical abdominal presentations Author summaryNeisseria meningitidis, commonly known as meningococci, is a bacterium that is transmitted directly from person to person through respiratory droplets. This bacterium causes invasive meningococcal disease (IMD), which can manifest in various symptoms beyond just meningitis. Notably, abdominal presentations, including abdominal pain and diarrhea, are increasingly being reported. The aim of our investigation was to elucidate the underlying mechanism of these abdominal symptoms. To achieve this, we employed several experimental approaches and provided evidence that these symptoms are caused by the coagulation (clotting) of blood in the microvessels that surround the abdominal organs, such as the intestine. This clotting is triggered by the bacteriums induction of a human enzyme that promotes coagulation. Notably, this is the first study to explore a mechanism underlying an extra-meningeal clinical form of N. meningitidis infection. The enzyme responsible for this coagulation, plasminogen activator inhibitor 1, is a potential target for modulating the host response to IMD. Our findings have significant implications for the understanding of meningococcal pathophysiology and reveal additional potential targets for treatment.

microbiology↗

bioRxiv2025

Gene Editing for ATXN3 Inactivation in Machado-Joseph disease: CRISPR-Cas9 as a Therapeutic Alternative to TALEN-Induced Toxicity

Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder, caused by an over-repetition of the polyglutamine-codifying region in the ATXN3 gene. Strategies based on the suppression of the deleterious gene products have demonstrated promising results in pre-clinical studies. Nonetheless, these strategies do not target the root cause of the disease. In order to prevent the downstream toxic pathways, our goal was to develop gene editing-based strategies to permanently inactivate the human ATXN3 gene. TALENs and CRISPR-Cas9 systems were designed to target exon 2 of this gene and functional characterization was performed in a human cell line. After the demonstration of TALENs and CRISPR-Cas9 efficiency on gene disruption, a sequence of each system was selected for further in vivo experiments. Although both TALENs and CRISPR-Cas9 systems led to a drastic reduction of ATXN3 aggregates in the striatum of a lentiviral-based mouse model of MJD/SCA3, only CRISPR-Cas9 system allowed the improvement of key neuropathological markers of the disease. Importantly, the administration of the engineered system in YAC-MJD84.2/84.2 mice mediated a delay in disease progression, when compared with non-treated littermates. These data provide the first in vivo evidence of the efficacy of a CRISPR-Cas9-based approach to permanently inactivate the ATXN3 gene in the brain of two mouse models of the disease, supporting its potential as a new therapeutic avenue in the context of MJD/SCA3.

neuroscience↗

bioRxiv2024

Knowledge Innovation Ecosystem for the Promotion of User-Centre Health Innovations: Living Lab Methodology and Lessons Learned Through the Proposal of Standard Good Practices

Living Labs, experiencing a global surge in popularity over the past years, demands standardized guidance through the development of widely accepted good practices. While challenging due to the complex and evolving nature of Living Labs, this task remains essential. These knowledge innovation ecosystems facilitate a diverse array of interconnected and interacting end-users and stakeholder partners who engage collaboratively to co-create, embed, and/or leverage end-user-centric breakthroughs at one or more innovation phases within a real-world context. Based on the development of six Living Labs in the health domain, this study proposes a more general yet critical set of Living Labs good practices, emphasizing the importance of strong initial marketing and promotion strategies for Living Labs open calls, enforcing gender equality, carefully selecting stakeholders, devising and implementing effective framework strategies for end-user engagement and value creation, ensuring value creation for all Living Labs partners, prolonging the long-term viability of the Living Lab project, promoting and disseminating impactful actions and results, fostering environmental sustainability, and processing results data for Living Lab performance evaluation.

scientific communication and education↗

bioRxiv2022

IFNγ protects motor neurons from oxidative stress via enhanced global protein synthesis in FUS-associated Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis type 6 (ALS6) is a familial subtype of ALS linked to Fused in Sarcoma (FUS) gene mutation. FUS mutations lead to decreased global protein synthesis, but the mechanism that drives this has not been established. Here, we used ALS6 patient-derived induced pluripotent stem cells (hIPSCs) to study the effect of the ALS6 FUSR521H mutation on the translation machinery in motor neurons (MNs). We find, in agreement with findings of others, that protein synthesis is decreased in ALS6 MNs. Furthermore, ALS6 MNs are more sensitive to oxidative stress and display reduced expression of TGF-{beta} and mTORC gene pathways when stressed. Finally, we show that IFN{gamma} treatment reduces apoptosis of ALS6 MNs exposed to oxidative stress and partially restores the translation rates in ALS6 MNs. Overall, these findings suggest that a functional IFN{gamma} response is important for FUS-mediated protein synthesis, possibly by FUS nuclear translocation in ALS6. Highlights and eTOC blurbO_LIALS6 patient-derived motor neurons show decreased viability and reduced production of innate immune cytokines following oxidative stress C_LIO_LIFUS cytoplasmic localization coincides with decreased protein synthesis rates C_LIO_LIIFN{gamma} treatment of ALS6 patient-derived motor neurons reduces apoptosis and ameliorates translation rates resulting from oxidative stress C_LI

neuroscience↗

bioRxiv2018

Psychosocial stress and central adiposity: A Brazilian study with users of the public health system

ObjectiveTo assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil.\n\nMethodsThis cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (g/dL), symptoms suggestive of depression using the Beck Depression Inventory-II [≥] 17 (yes/no), and altered blood pressure [≥] 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were stratified by rural and urban location.\n\nResultsThe prevalence of weight excess was 68.3%, and 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 {+/-} 12.7 cm and 92.9 {+/-} 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population and altered blood pressure in the urban population. This occurred both in the raw analysis and in the models adjusted for confounding factors.\n\nConclusionThe associations between stress and adiposity were different between rural (cortisol - inverse association) and urban (altered blood pressure) lifestyles, confirming the influence of local and psychosocial subsistence on the modulation of stress and on how individuals react or restrain stressors. Stress reduction strategies can be useful in public health programs designed to prevent or treat obesity.

genetics↗

bioRxiv2018

Psychosocial stress and central adiposity: A Brazilian study with users of the public health system

ObjectiveTo assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil.\n\nMethodsThis cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (g/dL), symptoms suggestive of depression using the Beck Depression Inventory-II [≥] 17 (yes/no), and altered blood pressure [≥] 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were stratified by rural and urban location.\n\nResultsThe prevalence of weight excess was 68.3%, and 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 {+/-} 12.7 cm and 92.9 {+/-} 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population and altered blood pressure in the urban population. This occurred both in the raw analysis and in the models adjusted for confounding factors.\n\nConclusionThe associations between stress and adiposity were different between rural (cortisol - inverse association) and urban (altered blood pressure) lifestyles, confirming the influence of local and psychosocial subsistence on the modulation of stress and on how individuals react or restrain stressors. Stress reduction strategies can be useful in public health programs designed to prevent or treat obesity.

genetics↗

bioRxiv2018

A taxonomically-restricted Uric Acid transporter provides insight into antioxidant equilibrium

Nucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases and uric acid transporters, with a broad evolutionary distribution. In vertebrates, four members have been previously recognized, the ascorbate transporters Slc23a1 and Slc3a2, the nucleobase transporter Slc23a4 and an orphan transporter SLC23A3. Here we identify a fifth member of the vertebrate slc23 complement (slc23a5), expressed in neopterygians (gars and teleosts) and amphibians, and clarify the evolutionary relationships between the novel gene and known slc23 genes. Further comparative analysis puts forward uric acid as the preferred substrate for Slc23a5. Gene expression quantification suggests kidney and testis as major expression sites in Xenopus tropicalis (western clawed frog) and Danio rerio (zebrafish). Additional expression in brain was detected in D. rerio, while in the Neoteleostei Oryzias latipes (medaka) slc23a5 expression is restricted to brain. The biological relevance of the retention of an extra transporter in fish and amphibians is examined: with respect to the (1) antioxidant role of uric and ascorbic acid in seminal fluid and brain, (2) the ability to endogenously synthesize ascorbic acid and (3) the morphological adaptations of the male urogenital system.

evolutionary biology↗