Biology subjects

Antunes, M.

Publications and source records attributed to Antunes, M..

6 recordsLinked to original sources

bioRxiv2026

A Bio-inspired Synthetic Gene Circuit

Salinity exerts a major constraint on global crop production while seawater intrusion impacts coastal aquifers and surface waters. Using a blueprint from nature, we produced highly salt tolerant Arabidopsis and rice. Endodermal-like barriers, duplicated to the root epidermis and distally expanded to protect sensitive regions, provide salt tolerance to 600 mM NaCl, levels comparable to seawater. Two additional genetic modules are added to reduce adverse effects on ion uptake and provide osmotic protection. Arabidopsis and rice containing all three genetic modules can survive 600 mM NaCl and set seed. RNA-seq analysis suggests that our rational engineering primes plants for salt tolerance, even without salt exposure, while our ionic analysis provides means for improvement. Our results, duplicating suberin and the Casparian Strip to the epidermis, adding symplastic transport and providing a means to address osmotic stress, provides a new approach to salt tolerance and insight to genes involved in salt responses. One Sentence SummaryA bio-inspired approach engineering epidermal barriers, symplast transporters and osmotic enhancement produces salt tolerant Arabidopsis and rice

plant biology↗

bioRxiv2025

P2Y12-P-Selectin Mediated Platelet Activation Drives Dengue-Associated Thrombocytopenia

Dengue virus (DENV) infection frequently causes thrombocytopenia, a hallmark of severe disease. The underlying mechanisms of this condition remain incompletely understood. Using a murine model that mirrors human hematologic and inflammatory responses, we show that DENV impairs megakaryopoiesis, causing necrotic loss of bone marrow megakaryocytes and compensatory thrombopoietin elevation. Megakaryocyte-derived platelets exhibit mitochondrial dysfunction and phosphatidylserine exposure, consistent with apoptosis. Systemically, DENV drives P-selectin- dependent platelet activation and platelet-monocyte aggregates, accompanied by increased plasmatic chemokines (CXCL4, CCL5, CXCL1) and vascular leakage in target organs such as liver and lungs, reflecting heightened thromboinflammation. Pharmacologic blockade of P-selectin or inhibition of P2Y12 with clopidogrel restored platelet counts, rescued megakaryocyte numbers, and reduced systemic inflammation. Collectively, these findings demonstrate for the first time in an in vivo model that DENV-induced thrombocytopenia arises from combined megakaryocyte impairment and platelet hyperactivation and highlight platelet-targeted interventions as potential therapeutic strategies. KEY POINTSO_LIDENV disrupts platelet production and survival via megakaryocyte necrosis and intramedullary platelet apoptosis, driving thrombocytopenia. C_LIO_LIDENV triggers thrombocytopenia via P-selectin platelet activation; blocking it with antibody P-selectin or clopidogrel reduces inflammation. C_LI

immunology↗

bioRxiv2025

Gut3Gel as an in vitro model to investigate dietary modulation of the intestinal microbiota: An inulin supplementation case study

The intestinal microbiota plays a key role in human health, influencing digestion, immunity, and metabolism. While factors such as genetics and medications shape its composition, diet remains a primary driver of microbial modulation. Despite growing interest in using dietary interventions to beneficially alter the intestinal microbiota, assessing their effects in humans is challenging due to individual variability and the complexity of in vivo systems. This study explores Gut3Gel gradient colonic (G3GG) preclinical model as a tool to assess its representativeness on studying the effect of inulin supplementation on the intestinal microbiota of five healthy individuals compared to clinical evaluation studies. Significant inter-individual variability in baseline microbiota composition was observed, which strongly influenced microbiota response to inulin. While inulin supplementation led to a general decrease in alpha diversity, it significantly increased the abundance of health-associated genera such as Bifidobacterium and Lacticaseibacillus, along with enhanced microbial metabolic activity. Despite the intrinsic selectivity of G3GG for beneficial microbes, the model successfully captured inulins prebiotic effects and inter-individual differences, underscoring its relevance as a physiologically relevant high throughput tool for evaluating microbiota-targeting compounds and supporting personalized nutrition strategies.

microbiology↗

bioRxiv2025

Gut3Gel: A High Throughput Mucus Model for Culturing Human Intestinal Microbiota

The human intestinal microbiota plays a crucial role in health and disease, yet recreating its complex interactions in vitro remains a significant challenge. Gut3Gel introduced herein as a novel in vitro mucus model, designed for culturing complex microbial communities without the need for anaerobic conditions. Intestinal microbiota samples from five donors were individually inoculated in Gut3Gel and cultured for 72 hours. Taxonomic composition assessment revealed that Gut3Gel sustains diverse microbial species and particularly promotes the growth of mucus-associated bacteria including Bifidobacterium, Lactobacillus, and Faecalibacterium. Microbial metabolic activity within Gut3Gel was confirmed by the increased production of acetate and butyrate, as well as of exopolysaccharides. Gut3Gel reproduces physiological features of intestinal mucus, providing a reproducible and scalable culturing platform. These features make Gut3Gel a promising tool for advancing microbiota research with potential applications in drug screening, microbiome mining, and high throughput testing of microbiome-modulating molecules.

microbiology↗

bioRxiv2022

Biogeographical history shapes evolution of reproduction in a global warming scenario

Adaptive evolution might be critical for animal populations to thrive on the fast-changing natural environments. Ectotherms are particularly vulnerable to global warming and, although their limited coping ability has been suggested, few real-time evolution experiments have directly accessed their evolutionary potential. Here, we report a long-term experimental evolution study addressing the evolution of thermal reaction norms, after [~]30 generations under different thermal environments. We analyzed the evolutionary dynamics of Drosophila subobscura populations as a function of the thermally variable environments in which they evolved and their distinct biogeographical background. Our results showed clear differences between the historically differentiated populations: while the northern D. subobscura populations showed a temporal increase in performance at higher temperatures, their southern counterparts presented the opposite pattern. This suggests that the northern populations might be better equipped to cope with the current rising temperatures. Remarkably, no effect of thermal selection was found. The lack of a clear long-term adaptive response at higher temperatures after evolution under a global warming scenario raises concerns about the evolutionary potential of ectotherms. Our results highlight the complex nature of thermal responses in face of environmental heterogeneity and emphasize the importance of considering intra-specific variation in thermal evolution studies.

evolutionary biology↗

bioRxiv2020

The kallikrein-kinin system is falling into pieces: bradykinin fragments are biological active peptides

Background and purposeBradykinin [BK-(1-9)] is an endogenous peptide involved in many physiological and pathological processes, such as cardiovascular homeostasis and inflammation. The central dogma of the kallikrein-kinin system is that BK-(1-9) fragments are biologically inactive. In this manuscript, we proposed to test whether these fragments were indeed inactive. Experimental ApproachNitric oxide (NO) was quantified in human, mouse and rat cells loaded with DAF-FM after stimulation with BK-(1-9), BK-(1-7), BK-(1-5) and BK-(1-3). We used adult male rat aortic ring preparation to test vascular reactivity mediated by BK-(1-9) fragments. Changes in blood pressure and heart rate was measured in conscious adult male rats by intraarterial catheter method. Key resultsBK-(1-9) induced NO production in all cell types tested by B2 receptor activation. BK-(1-7), BK-(1-5) and BK-(1-3) also induced NO production in all tested cell types but this response was independent of the activation of B1 receptor and/or B2 receptor. BK-(1-7), BK-(1-5) or BK-(1-3) induced only vasorelaxant effect and in a concentration-dependent fashion. Vasorelaxant effects for BK-(1-7), BK-(1-5) or BK-(1-3) were independent of the kinin receptors. Different administration routes (i.e., intravenous or intra-arterial) did not affect the observed hypotension induced by BK-(1-7), BK-(1-5) or BK-(1-3). Importantly, these observations diverged from the BK-(1-9) results, highlighting that indeed the BK-(1-9) fragments do not seem to act via the classical kinin receptors. Conclusions and implicationsIn conclusion, BK-(1-7), BK-(1-5) and BK-(1-3) are biologically active components of the kallikrein-kinin system. Importantly, observed pathophysiological outcomes of these peptides are independent of B1R and/or B2R activation.

pharmacology and toxicology↗