Biology subjects

Martins, A.

Publications and source records attributed to Martins, A..

12 recordsLinked to original sources

bioRxiv2026

CD160 is an inducible endothelial checkpoint that suppresses sprouting angiogenesis through LRP1-dependent autophagy

Pathological angiogenesis is a hallmark of cancer and other chronic diseases, yet therapeutic strategies remain largely focused on blocking pro-angiogenic signals rather than restoring endogenous mechanisms that restrain endothelial sprouting. The identification of endothelial checkpoints capable of limiting pathological vessel growth therefore remains an important unmet need. CD160 is a glycosylphosphatidylinositol-anchored immunoglobulin-superfamily receptor of cytotoxic lymphocytes and an inhibitory checkpoint receptor on CD4 T cells. It is also present on endothelium and has been targeted therapeutically. Here, we identify CD160 as an inducible endothelial checkpoint that emerges in response to pro-angiogenic cues and limits pathological angiogenesis. CD160 is absent in resting endothelium. It is induced by basic fibroblast growth factor (bFGF) and most strongly by combining VEGF-A and bFGF, and it is detected in the sprouting region of ex vivo mouse aortic rings. Targeting of CD160 using monoclonal antibody reduces tubulogenesis, scratch closure and aortic-ring sprouting, and softens the cell cortex, while viability and membrane integrity remain intact. Mechanistically, CD160 associates with the endocytic receptor LRP1 as demonstrated by proximity ligation assay, lipid-raft co-immunoprecipitation and super-resolution fluorescence microscopy. Both receptors appear in a common complex, and two independent computational methods converge on the first ligand-binding cluster of LRP1 as the interface. Silencing CD160 or LRP1 abolishes the anti-angiogenic response mediated by the antibody. Under a chloroquine clamp, engagement raises autophagic flux in a CD160- and LRP1-dependent manner, and lysosomal or LDL-receptor-family blockade removes the anti-sprouting effect. CD160 therefore acts as an inducible endothelial checkpoint that suppresses sprouting through autophagic flux. Thus, CD160 represents an inducible endothelial checkpoint that is activated in a pro-angiogenic environment, and targeting CD160 restrains pathological angiogensis.

immunology↗

bioRxiv2026

Genomic variation and ancestry of Helicobacter pylori in the admixed population of Cabo Verde reveal host adaptation, limited host-pathogen ancestry concordance, and signatures of trans-Atlantic slave trade migrations

The genomic structure of the stomach-colonising, gastric cancer-associated bacterium Helicobacter pylori mirrors human evolutionary history, making it difficult to disentangle shared ancestry from true host-pathogen interactions driving disease risk. Recently admixed populations offer opportunities for new coevolutionary trajectories between H. pylori and its host that may disrupt parallel evolution. Here, we analyse host H. pylori IgG, blood serum biomarkers, and paired host-bacterial genomic data from the general population (independent of dyspepsia symptoms) of Cabo Verde. Seropositivity is high (82.8%), as in neighbouring African populations. Serum biomarkers indicate that this unique cohort mainly comprises hosts with limited gastric inflammation. Genomic analyses show that Cabo Verdean H. pylori derive European (hspSWeurope) and West African (hspAfrica1WAfrica) ancestry. The delineation of a reference dataset that includes new strains from Ghana and Portugal, uncovered a distinct West-Central African cluster (hspAfrica1WCAfrica). This dataset allowed inference of within-Africa and within-Europe ancestries in Cabo Verdean and American strains that reflect historical migrations linked to European colonisation and the trans-Atlantic Slave Trade. European strains in Cabo Verde show additional population structure, including two low-diversity clusters. Approximate Bayesian Computation (ABC) inference indicates that the most common cluster represents a clonal expansion, likely driven by host adaptation leading to increased transmission within Cabo Verde. Notably, these strains lack known virulence genes and show significant divergence from gastric cancer strains. Finally, host and bacterial ancestry are uncoupled, indicating disruption of ancestral parallel evolution. Cabo Verde, therefore, provides a unique natural model for studying host-pathogen interactions underlying susceptibility to H. pylori.

evolutionary biology↗

bioRxiv2026

Adipose-Derived Extracellular Vesicles Mitigate Experimental Cutaneous Leishmaniasis Through an IL-10 Dependent Mechanism

Leishmaniasis, a neglected tropical disease caused by protozoa of the Leishmania genus, is characterized by an imbalanced immune response that promotes parasite survival while inducing tissue damage. We previously showed that adipose-derived mesenchymal stem cells (AD-MSCs) limited lesion progression in C57BL/6 mice infected with Leishmania amazonensis. In the current study, we examined whether extracellular vesicles released by AD-MSCs (AD-MSC-EVs) reproduce these therapeutic effects. AD-MSC-EVs were purified, expanded, and characterized, confirming their typical morphology and EV-associated surface markers. In vitro, treatment of infected macrophages with AD-MSC-EVs 4 hours post-infection reduced parasite load through the induction of reactive oxygen species (ROS), independent of nitric oxide (NO). However, treatment 24 hours post-infection failed to reproduce this effect. In vivo, intralesional administration of AD-MSC-EVs significantly reduced lesion size without altering parasite load, while also decreasing levels of specific IgM and IgG for Leishmania amazonensis antigens. AD-MSC-EV therapy also reduced proinflammatory cytokines production by CD4 and cytotoxicity CD8 T cells, while increasing IL-10 production by {gamma}{delta} T cells. Moreover, combined therapy with pentavalent antimonial further reduced lesion size but did not affect parasite load. Notably, AD-MSC-EVs failed to control lesions in IL-10-deficient mice, suggesting that their therapeutic effect is dependent on IL-10. In conclusion, these findings showed that AD-MSC-EVs modulated the host immune response to attenuate L. amazonensis-induced cutaneous pathology and may represent a promising adjunct or alternative therapy for cutaneous leishmaniasis. Significance StatementCutaneous leishmaniasis is a neglected tropical disease with limited therapeutic options and significant immunopathology. This study demonstrates that extracellular vesicles derived from adipose-derived mesenchymal stem cells (AD-MSC-EVs) can modulate host immune responses and reduce lesion severity in Leishmania amazonensis infection. Rather than directly eliminating parasites, AD-MSC-EVs attenuate tissue damage through IL-10 dependent immunoregulation, highlighting a novel host-directed therapeutic strategy. These findings advance understanding of EV-mediated immune modulation and support AD-MSC-EVs as a promising adjunct or alternative approach for treating cutaneous leishmaniasis and potentially other inflammatory infectious diseases.

immunology↗

bioRxiv2025

Hidden Diversity of Threatened Sharks and Rays in the Global Meat Trade

International wildlife trade is a major source of biodiversity loss, yet many species lie hidden within aggregated data that conceals trade impacts. We overcome this problem for the largest vertebrate wildlife trade globally - shark and ray meat - comprising 438 538 mt yr-1 across more than 150 species, 76% of which are Threatened. Revealed trade contains greater quantities of skates (+10%), hammerheads (+8%), and smoothhounds, dogfishes & tope (+5%), and fewer pelagic sharks (-38%) than previously known. Shorttail yellownose skate, smoothound, silky, mako, and blue sharks are the most underreported meat species, due to aggregated landings from China, Argentina, Japan, and Indonesia, demonstrating international trade in shark and ray meat as a diverse, pervasive, and previously hidden source of fishing mortality for many threatened species.

ecology↗

bioRxiv2024

The transcription factor Traffic jam orchestrates the somatic piRNA pathway in Drosophila ovaries

The PIWI-interacting RNA (piRNA) pathway is essential for transposable element (TE) silencing in animal gonads. While the transcriptional regulation of piRNA pathway components in germ cells has been documented in mice and flies, their control in somatic cells of Drosophila ovaries remains unresolved. Here, we demonstrate that Traffic jam (Tj), the Drosophila orthologue of large Maf transcription factors in mammals, is a master regulator of the somatic piRNA pathway. Tj binds to regulatory regions of somatic piRNA factors and the major piRNA cluster flamenco, which carries a Tj-bound enhancer downstream of its promoter. Depletion of Tj in somatic follicle cells causes downregulation of piRNA factors, loss of flam expression and de-repression of gypsy-family TEs. We propose that the arms race between the host and TEs led to the co-evolution of promoters in piRNA pathway genes as well as TE regulatory regions that both rely on a shared transcription factor. Highlights- Traffic jam (Tj) acts as a master regulator of the somatic piRNA pathway in Drosophila. - Tj regulates a network of piRNA pathway genes, mirroring the gene-regulatory mechanism of A-MYB in the mouse testis and Ovo in fly ovaries. - Cis-regulatory elements with Tj motifs are present at the promoters of somatic piRNA pathway genes. - The expression of the flamenco piRNA cluster is directly controlled by Tj.

molecular biology↗

bioRxiv2023

Predicting the impact of rare variants on RNA splicing in CAGI6

BackgroundVariants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variants impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact. ResultsThe performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum overall accuracy achieved was 82% from two different approaches, one weighting SpliceAI scores by minor allele frequency, and one applying the recently published Splicing Prediction Pipeline (SPiP). SPiP performed optimally in terms of sensitivity, while an ensemble method combining multiple prediction tools and information from databases exceeded all others for specificity. ConclusionsSeveral challenge methods equalled or exceeded the performance of SpliceAI, with ultimate choice of prediction method likely to depend on experimental or clinical aims. One quarter of the variants were incorrectly predicted by at least 50% of the methods, highlighting the need for further improvements to splicing prediction methods for successful clinical application.

bioinformatics↗

bioRxiv2022

The temporal regulation inter-leaves from domesticated-tomato contrasts with timelessness of its wild ancestors

Cells, tissues, and organs are characterized by harbouring complex systems allowing communication between one another. Plant domestication was demonstrated to have structured the circadian rhythms, while also synchronising flowering and metabolism. Here, we demonstrate that the domesticated tomato (Solanum lycopersicum) manifests more synchronized rhythmicity across the whole plant. Consequently, the leaf development program is more coordinated in this species than in its wild relatives, wherein S. lycopersicum young leaves develop slowly in comparison to mature leaves. Young leaves from wild tomatoes display higher photosynthesis than mature leaves, while large metabolite accumulations occur across plant segments. Consequently, the diel metabolite levels are rather similar between young and mature leaves in the wild tomato S. pennellii, whereas the expression patterns for circadian clock genes are widely contrasting between both leaves. We further demonstrated that additions of genes related to domestication into the wild tomato S. pimpinellifolium appear to synchronize the development of young and mature leaves to be rather similar to that observed for S. lycopersicum. Collectively, the strengthening of inter-organs relationships on domesticated tomato indicates a synchronized biology, which is most likely fundamental to explaining its elevated yield.

plant biology↗

bioRxiv2021

Evidence of post-domestication hybridization and adaptive introgression in Western European grapevine varieties

Grapevine (Vitis vinifera L.) is one of the most significant crops in the world. Todays richness in grapevine diversity results from a complex domestication history over multiple historical periods. Here, we employed whole genome resequencing to elucidate different aspects of the recent evolutionary history of this crop. Our results support a model in which a central domestication event in grapevine was followed by post-domestication hybridization with local wild genotypes, leading to the presence of an introgression signature in modern wine varieties across Western Europe. The strongest signal was associated with a subset of Iberian grapevine varieties, which show large introgression tracts. We targeted this study group for further analysis, demonstrating how regions under selection in wild populations from the Iberian Peninsula were preferentially passed on to the cultivated varieties by geneflow. Examination of underlying genes suggests that environmental adaptation played a fundamental role in both the evolution of wild genotypes and the outcome of hybridization with cultivated varieties, supporting a case of adaptive introgression in grapevine.

plant biology↗

bioRxiv2019

Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides

Antimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, with a chemical-genetic approach, we systematically assessed the resistance determinants of Escherichia coli against 15 different AMPs. Although generalizations about AMP resistance are common in the literature, we found that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, collateral sensitivity effects were common: numerous genes decreased susceptibility to one AMP while simultaneously sensitized to others. Finally, the chemical-genetic map predicted the cross-resistance spectrum of laboratory-evolved human-B-defensin-3 resistant lineages. Our work substantially broadens the scope of known resistance-modulating genes and explores the pleiotropic effects of AMP resistance. In the future, the chemicalgenetic map could inform efforts to minimize cross-resistance between therapeutic and human host AMPs.

microbiology↗

bioRxiv2018

In-season internal and external training load quantification of an elite European soccer team

Elite soccer teams that participate in European competitions often have a difficult schedule, involving weeks in which they play up to three matches, which leads to acute and transient subjective, biochemical, metabolic and physical disturbances in players over the subsequent hours and days. Inadequate time recovery between matches can expose players to the risk of training and competing whilst not fully recovered. Controlling the level of effort and fatigue of players to reach higher performances during the matches is therefore critical. Therefore, the aim of the current study was to provide the first report of seasonal internal and external training load (TL) that included Hooper Index (HI) scores in elite soccer players during an in-season period. Sixteen elite soccer players were sampled, using global position system, session rating of perceived exertion (s-RPE) and HI scores during the daily training sessions throughout the 2015-2016 in-season period. Data were analysed across ten mesocycles (M: 1 to 10) and collected according to the number of days prior to a match. Total daily distance covered was higher at the start (M1 and M3) compared to the final mesocycle (M10) of the season. M1 (5589m) reached a greater distance than M5 (4473m) (ES = 9.33 [12.70, 5.95]) and M10 (4545m) (ES = 9.84 [13.39, 6.29]). M3 (5691m) reached a greater distance than M5 (ES = 9.07 [12.36, 5.78]), M7 (ES = 6.13 [8.48, 3.79]) and M10 (ES = 9.37 [12.76, 5.98]). High-speed running distance was greater in M1 (227m), than M5 (92m) (ES = 27.95 [37.68, 18.22]) and M10 (138m) (ES = 8.46 [11.55, 5.37]). Interestingly, the s-RPE response was higher in M1 (331au) in comparison to the last mesocycle (M10, 239au). HI showed minor variations across mesocycles and in days prior to the match. Every day prior to a match, all internal and external TL variables expressed significant lower values to other days prior to a match (p<0.01). In general, there were no differences between player positions.\n\nConclusionsOur results reveal that despite the existence of some significant differences between mesocycles, there were minor changes across the in-season period for the internal and external TL variables used. Furthermore, it was observed that MD-1 presented a reduction of external TL (regardless of mesocycle) while internal TL variables did not have the same record during in-season match-day-minus.

physiology↗

bioRxiv2018

Towards an applied metaecology

The complexity of ecological systems is a major challenge for practitioners and decision-makers who work to avoid, mitigate and manage environmental change. Here, we illustrate how metaecology - the study of spatial interdependencies among ecological systems through fluxes of organisms, energy, and matter - can enhance understanding and improve managing environmental change at multiple spatial scales. We present several case studies illustrating how the framework has leveraged decision-making in conservation, restoration and risk management. Nevertheless, an explicit incorporation of metaecology is still uncommon in the applied ecology literature, and in action guidelines addressing environmental change. This is unfortunate because the many facets of environmental change can be framed as modifying spatial context, connectedness and dominant regulating processes - the defining features of metaecological systems. Narrowing the gap between theory and practice will require incorporating system-specific realism in otherwise predominantly conceptual studies, as well as deliberately studying scenarios of environmental change.

ecology↗

bioRxiv2017

Time calibrated tree of Dioscorea (Dioscoreaceae) indicated four origins of yams in the Neotropics since Eocene

The yam genus Dioscorea comprises circa 650 species of tropical vines with starch rich tubers, usefull as an energy source and often containing secondary metabolites. The Neotropical Region holds the highest diversity of species and morphology of yams. We generated a time-calibrated tree for Dioscorea using, for the first time, a dense sampling of Neotropical species (64 sp., 20% of all Neotropical sp. and 22 sections) to trace the biogeography of these plants in this region. Four origins of Dioscorea in the neotropics were estimated since the Eocene. The two most diverse lineages originated between the Eocene and Oligocene, respectively in the Southern Andes and eastern South America. Both lineages occupied the South American Dry Diagonal after the Miocene, but New World II clade remained associated with forest habitats. Several exchanges between Dry Diagonal and adjacent forested biomes occurred, corroborating the interchange between these vegetation types. Dispersals to Central America occurred before the closure of the Panama Isthmus. We highlight two important events of long distance dispersal, the colonization of Central American before the closure of Isthmus of Panama and the dispersal of D. antaly lineage to Madagascar. In addition, our phylogenetic tree evidenced the unnatural nature of the classical infrageneric classification of Dioscorea. The taxonomic implications of our results are also discussed.

evolutionary biology↗