Biology subjects

Alves, R.

Publications and source records attributed to Alves, R..

At least 19 recordsLinked to original sources

bioRxiv2025

Increased striatal coupling one week after ischemic stroke revealed by ultrafast functional MRI

BackgroundNetwork reorganization following ischemic stroke is thought to play a role in recovery. Although cortico-cortical reorganization is widely established, changes in interhemispheric striatal connections following ischemia remain poorly understood, even when stroke occurs in motor areas. Given the importance of the striatum to motor function, we investigated network-level striatal coupling in stroke using ultrafast resting-state fMRI, which has recently been shown to facilitate the dissection of synchronous oscillatory activity better than its conventional [~]1 sec time-resolution counterparts. MethodsA cohort of (N=18) sedated rats were randomized and N=9 rats underwent unilateral photothrombotic ischemic lesioning in motor cortex. One week after the lesion, when plasticity and recovery are well established, all animals were scanned on a 9.4T MRI scanner using a cryogenic coil using an ultrafast resting-state functional MRI sequence with temporal resolution of 90 ms. Data were collected for 24 minutes, and spectral power, phase locking, and functional connectivity were quantified. Histology was performed to confirm lesion extent. ResultsWhile cortico-cortical power, connectivity and synchrony were diminished one week post-stroke as expected, we surprisingly found increased striato-striatal power, synchrony and functional connectivity in the stroked group compared with the control group. In stroked animals, the spectral power in the ultraslow oscillation frequency band (0.02-0.4 Hz) significantly increased in the striatum while decreasing in the cortex. When data were undersampled to "conventional" fMRI temporal resolution (900 ms), the striatal effects were lost, revealing the power of ultrafast fMRI approaches in unveiling such phenomena. ConclusionsIncreased striato-striatal coupling, in the form of increased synchrony, spectral power, and functional connectivity, was revealed by ultrafast resting-state fMRI, but not conventional temporal resolution resting-state fMRI. Our findings suggest more involvement of subcortical areas in network reorganization than previously thought.

neuroscience↗

bioRxiv2025

Metalog: curated and harmonised contextual data for global metagenomics samples

Metagenomic sequencing enables the in-depth study of microbes and their functions in humans, animals and the environment. While sequencing data is deposited in public databases, the associated contextual data is often not complete and needs to be retrieved from primary publications. This lack of access to sample-level metadata like clinical data or in situ observations impedes cross-study comparisons and meta-analyses. We therefore created the Metalog database, a repository of manually curated metadata for metagenomics samples across the globe. It contains 73,082 samples from humans (including 58,506 of the gut microbiome), 10,703 animal samples, 5,146 ocean water samples, and 21,802 samples from other environmental habitats such as soil, sediment, or fresh water. Samples have been consistently annotated for a set of habitat-specific core features, such as demographics, disease status and medication for humans, host species and captivity status for animals, and filter sizes and salinity for marine samples. Additionally, all original metadata is provided in tabular form, simplifying focused studies e.g. into nutrient concentrations. Pre-computed taxonomic profiles facilitate rapid data exploration, while links to the SPIRE database enable genome-based analyses. The database is freely available for browsing and download at https://metalog.embl.de/.

microbiology↗

bioRxiv2025

The ATO gene family governs Candida albicans colonisation in the dysbiotic gastrointestinal tract

The fungal pathogen Candida albicans colonises the human gut where short-chain fatty acids (SCFAs) offer sources of carbon. This fungus harbours one of the largest microbial families of ATO (Acetate Transport Ortholog) genes, which encode putative SCFA transport proteins. Here, we generate C. albicans null mutants lacking individual or all known putative SCFA transporter genes and compare their phenotypes in vitro and in vivo. We show that blocking ATO function in C. albicans impairs SCFA uptake and growth, particularly on acetate. The uptake of acetate is largely dependent on a functional Ato1 (also known as Frp3/Ato3) and it is effectively abolished upon deletion of all ATO genes. We further demonstrate that deletion of the entire ATO gene family, but not inactivation of ATO1 alone, compromises the stable colonisation of C. albicans in the murine gastrointestinal tract following bacterial disruption by broad-spectrum antibiotics. Our data suggest that the ATO gene family has expanded and diversified during the evolution of C. albicans to promote the fitness of this fungal commensal during gut colonisation, in part through SCFA utilisation. IMPORTANCEThe human gut is rich in microbial fermentation products such as SCFAs, which serve as key nutrients for both bacteria and fungi. C. albicans, a common fungal resident of the gut and a cause of opportunistic infections, carries an unusually large family of ATO genes. This study reveals that this ATO gene family is required for the efficient uptake of acetate, the most abundant SCFA in the gut, and for stable colonisation of the gut. These findings uncover a new layer of metabolic adaptation in fungal commensals of humans and suggest that transporter gene expansion can shape microbial fitness in response to environmental nutrient signals.

microbiology↗

bioRxiv2025

Expansion, functional diversification and gene fusion events in the Ato protein family

Candida albicans, a commensal opportunistic pathogen, exhibits remarkable metabolic flexibility and adaptability to environmental changes. In glucose-limited niches, it utilizes alternative carbon sources such as carboxylic acids, which may influence its pathogenicity. In Saccharomyces cerevisiae, the uptake of monocarboxylates occurs through regulated plasma membrane (PM) transport proteins, such as Ato1 (Ady2), which belongs to the Acetate Uptake Transporter (AceTr) family. In C. albicans, these proteins are notably expanded, consisting of ten Ato-like proteins (ATO1-ATO10), whose functions remain unknown. Here, we investigated the role of Ato proteins in carboxylic acid utilization by C. albicans using in-silico and functional analysis. Our data revealed that several C. albicans Atos retain conserved AceTr motifs but possess distinct structural features, including differences in pore radius and binding sites for acetate and lactate. Expression analysis revealed that Ato1, Ato2, Ato3, and Ato6 exhibit distinct cellular localization and expression levels on the plasma membrane, depending on the presence or absence of monocarboxylates. Remarkably, deletion of ATO1 impaired Ato2 and Ato3 expression and caused ER retention of a distinct form of Ato2, suggesting a central regulatory role for Ato1 in the Ato transport system. Finally, we identified a novel Ato-related protein family in vertebrates. This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification. Overall, our data suggests that the Ato protein family might play a critical role in the utilization of acetic or lactic acids in C. albicans. It also proposes potential functional redundancy among its members, which may contribute to rapid environmental adaptation and pathogenicity.

microbiology↗

bioRxiv2024

ForestForward: visualizing and accessing integrated world forest data from the last fifty years

DATABASE URL: https://forestforward.udl.cat Mitigating the effects of environmental exploitation on forests requires robust data analysis tools to inform sustainable management strategies and enhance ecosystem resilience. Access to extensive, integrated plant biodiversity data, spanning decades, is essential for this purpose. However, such data is often fragmented across diverse datasets with varying standards, posing two key challenges: first, integrating these datasets into a unified, well-structured data warehouse, and second, handling the vast volume of data using big data technologies to analyze and monitor the temporal evolution of ecosystems. To address these challenges, we developed and used an ETL (Extract, Transform, Load) protocol that curated and integrates 4,482 forestry datasets from around the world, dating back to the 18th century, into a 100GB data warehouse containing over 172 million records sourced from the GBIF (Global Biodiversity Information Facility) repository. We implemented Python scripts and a NoSQL MongoDB database to streamline and automate the ETL process, using the data warehouse to create the ForestForward web platform. ForestForward is a free, user-friendly application developed using the Django framework, which enables users to consult, download, and visualize the curated data. The platform allows users to explore data layers by year and observe the temporal evolution of ecosystems through visual representations.

ecology↗

bioRxiv2024

Modeling the effect of daytime duration on the biosynthesis of terpenoid precursors

Terpenoids are valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. Circadian regulation affects MVA and MEP pathway activity at three levels: substrate availability, gene expression of pathway enzymes, and utilization of IPP and DMAPP for synthesizing complex terpenoids. There is a gap in understanding the interplay between the circadian rhythm and the dynamics and regulation of the two pathways. In this paper we create a mathematical model of the MVA and MEP pathways in plants that incorporates the effects of circadian rhythms. We then used the model to investigate how annual and latitudinal variations in circadian rhythm affect IPP and DMAPP biosynthesis. We found that, despite significant fluctuations in daylight hours, the amplitude of oscillations in IPP and DMAPP concentrations remains stable, highlighting the robustness of the system. We also examined the impact of removing circadian regulation from different parts of the model on its dynamic behavior. We found that regulation of pathway substrate availability alone results in higher sensitivity to daylight changes, while gene expression regulation alone leads to less robust IPP/DMAPP concentration oscillations. Our results suggest that the combined circadian regulation of substrate availability, gene expression, and product utilization, along with MVA- and MEP-specific regulatory loops, create an optimal operating regime. This regime maintains pathway flux closely coupled to demand and stable across a wide range of daylight hours, balancing the dynamic behavior of the pathways and ensuring robustness in response to cellular demand for IPP/DMAPP.

systems biology↗

bioRxiv2024

An almost chromosome-level assembly and annotation of the Alectoris rufa genome

The red-legged partridge, Alectoris rufa (n=38 chromosomes) plays a crucial role in the ecosystem of southwestern Europe, and understanding its genetics is vital for conservation and management. Here we sequence, assemble, and annotate a highly contiguous and nearly complete version of it genome (115 scaffolds, L90=23). This assembly contains 96.9% (8078 out of 8332) orthologous genes from the BUSCO aves_odb10 dataset of single copy orthologous genes. We identify RNA and protein genes, 95% of which with functional annotation. This near-chromosome level assembly revealed significant chromosome rearrangements compared to quail (Coturnix japonica) and chicken (Gallus gallus), suggesting that A. rufa and C. japonica diverged 21 M-years ago and that their common ancestor diverged from G. gallus 37 M-years ago. The reported assembly is a significant step towards a complete reference genome for A. rufa, contributing to facilitate comparative avian genomics, and providing a valuable resource for future research and conservation efforts for the red-legged partridge.

genomics↗

bioRxiv2023

Prefrontal cortex proteomic alteration after social instability stress in adolescents rats

Early life stress can have significant effects on the developing brain and lead to changes in the structure and function of brain regions involved in stress regulation, emotion and cognitive control. Here, we used the social instability stress (SIS) protocol to understand the impact of social stress during mild (PND30) and late (PND45) adolescence. Our results revealed that SIS can compromise the dominance-subordination coping strategy but does not affect social recognition and motivation in rats. Moreover, SIS can lead to subtle modifications at the molecular level that hamper normal development of the prefrontal cortex in a sex- and age-dependent manner. Understanding the impact of early life stress on brain organization is crucial for developing effective prevention and intervention strategies. By identifying those who are most vulnerable to the effects of stress and providing targeted support and resources, it may be possible to mitigate the negative consequences of early adversity and promote healthy brain development.

neuroscience↗

bioRxiv2023

Body size-dependent effects on the distribution patterns of phoretic mites of the multi-symbiont Rhynchophorus ferrugineus (Olivier, 1790) host

Phoretic mites have been found attached to different body parts of the red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier, 1790), to disperse. However, the question of how the patterns of attachment sites are formed remains intriguing. Here, we conducted the first study of RPW-associated phoretic mites in Portugal, particularly in the districts of Viana do Castelo, Braga, Porto and Aveiro in Northern Portugal (macrohabitat), and investigated the patterns of mite distribution on six body parts of RPW (microhabitat). At the macrohabitat level, we detected seven phoretic mite taxa actively using the RPW host in each of the four studied districts, all documented for the first time in association with this invasive exotic species in Portugal. However, their relative abundance (species evenness) varied between districts, as did species diversity. All examined weevils carried mites, and the prevalence of the different taxa did not differ between districts or sex of weevils. Measured by mean abundance and degree of aggregation, Centrouropoda sp. proved to be the common dominant taxon, while Acarus sp. And C. rhynchoporus were considered common subordinate taxa and Uroovobella sp., Mesostigmata, N. extremica and Dendrolaelaps sp. sparse taxa. At the microhabitat level, all taxa were present in all body parts of the RPW; the highest abundance was in a region encompassing the inner surface of the elytra and the membranous hind wings (subelytral space). Analysis of niche overlap revealed that the distribution patterns of phoretic mite taxa on the RPW were not randomly structured. In the subelytral space, interspecific coexistence of mites increased as a function of body size difference with the dominant Centrouropoda sp. We conclude that the distribution patterns of RPW-associated phoretic mites show body size-dependent effects that resulted in the dominant taxon displacing similar size taxa and accepting taxa with which it has the greatest size difference as co-habitants.

ecology↗

bioRxiv2023

Consistency across multi-omics layers in a drug-perturbed gut microbial community

Multi-omics analyses are increasingly employed in microbiome studies to obtain a holistic view of molecular changes occurring within microbial communities exposed to different conditions. However, it is not always clear to what extent each omics data type contributes to our understanding of the community dynamics and whether they are concordant with each other. Here we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers, namely 16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics, and metabolomics. Using this controlled setting, we find that all omics methods with species resolution in their readouts are highly consistent in estimating relative species abundances across conditions. Furthermore, different omics methods complement each other in their ability to capture functional changes in response to the drug perturbations. For example, while nearly all omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control and metabolomics revealed a decrease in polysaccharide uptake, likely caused by Bacteroidota depletion. Taken together, our study provides insights into how multi-omics datasets can be utilised to reveal complex molecular responses to external perturbations in microbial communities.

microbiology↗

bioRxiv2022

C. difficile is overdiagnosed in adults and a commensal in infants

Clostridioides difficile is an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated with C. difficile, in particular in C. difficile infection (CDI) cases, remains poorly characterised. To investigate the gut microbiome composition in CDI patients, we analysed 534 metagenomes from 10 publicly available CDI study populations. We then tracked C. difficile on a global scale, screening 42,900 metagenomes from 253 public studies. Among the CDI cohorts, we detected C. difficile in only 30% of the stool samples from CDI patients. However, we found that multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent. In addition, the majority of the investigated studies did not adhere to the recommended guidelines for a correct CDI diagnosis. In the global survey, we found that C. difficile prevalence, abundance and biotic context were age-dependent. C. difficile is a rare taxon associated with reduced diversity in healthy adults, but common and associated with increased diversity in infants. We identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typical of the healthy adult gut microbiome. C. difficile in healthy infants was therefore associated with multiple indicators of healthy gut microbiome maturation. Our analysis raises concerns about potential CDI overdiagnosis and suggests that C. difficile is an important commensal in infants and that its asymptomatic carriage in adults depends on microbial context.

microbiology↗

bioRxiv2021

Improving stroke detection via Correlation Tensor MRI

Noninvasively detecting and characterizing modulations in cellular scale micro-architecture is a desideratum for contemporary neuroimaging. Diffusion MRI (dMRI) has become the mainstay methodology for probing microstructure, and, in ischemia, its contrasts have revolutionized stroke management. However, the biological underpinnings of the contrasts observed in conventional dMRI in general and in ischemia in particular are still highly debated since the markers only indirectly reporter on microstructure. Here, we present Correlation Tensor MRI (CTI), a method that rather than measuring diffusion, harnesses diffusion correlations as its source of contrast. We show that CTI can resolve the sources of diffusional kurtosis, which in turn, provide dramatically enhanced specificity and sensitivity towards ischemia. In particular, the sensitivity towards ischemia nearly doubles, both in grey matter (GM) and white matter (WM), and unique signatures for neurite beading, cell swelling, and edema are inferred from CTI. The enhanced sensitivity and specificity endowed by CTI bodes well for future applications in biomedicine, basic neuroscience, and in the clinic.

neuroscience↗

bioRxiv2020

geneRFinder: gene finding in distinct metagenomic data complexities

MotivationMicrobes perform a fundamental economic, social and environmental role in our society. Metagenomics makes it possible to investigate microbes in their natural environments (the complex communities) and their interactions. The way they act is usually estimated by looking at the functions they play in those environments and their responsibility is measured by their genes. The advances of next-generation sequencing technology have facilitated metagenomics research however it also create a heavy computational burden. Large and complex biological datasets are available as never before. There are many gene predictors available which can aid gene annotation process though they lack of handling appropriately metagenomic data complexities. There is no standard metagenomic benchmark data for gene prediction. Thus, gene predictors may inflate their results by obfuscating low false discovery rates. ResultsWe introduce geneRFinder, a ML-based gene predictor able to outperform state-of-the-art gene prediction tools across this benchmark by using only one pre-trained Random Forest model. Average prediction rates of geneRFinder differed in percentage terms by 54% and 64%, respectively, against Prodigal and FragGeneScan while handling high complexity metagenomes. The specificity rate of geneRFinder had the largest distance against FragGeneScan, 79 percentage points, and 66 more than Prodigal. According to McNemars test, all percentual differences between predictors performances are statistically significant for all datasets with a 99% confidence interval. ConclusionsWe provide geneRFinder, a approach for gene prediction in distinct metagenomic complexities, available at github.com/railorena/geneRFinder, and also we provide a novel, comprehensive benchmark data for gene prediction -- which is based on The Critical Assessment of Metagenome Interpretation (CAMI) challenge, and contains labeled data from gene regions - avaliable at sourceforge.net/p/generfinder-benchmark.

bioinformatics↗

bioRxiv2020

What influences selection of native phosphorelay architectures?

Phosphorelays are signal transduction circuits that combine four different phosphorylatable protein domains for sensing environmental changes and use that information to adjust cellular metabolism to the new conditions in the milieu. Five alternative circuit architectures account for more than 99% of all phosphorelay operons annotated in over 9000 fully sequenced genomes, with one of those architectures accounting for more than 72% of all cases. Here we asked if there are biological design principles that explain the selection of preferred phosphorelay architectures in nature and what might those principles be. We created several types of data-driven mathematical models for the alternative phosphorelay architectures, exploring the dynamic behavior of the circuits in concentration and parameter space, both analytically and through over 108 numerical simulations. We compared the behavior of architectures with respect to signal amplification, speed and robustness of the response, noise in the response, and transmission of environmental information to the cell. Clustering analysis of massive Monte Carlo simulations suggests that either information transmission or metabolic cost could be important in selecting the architecture of the phosphorelay. A more detailed study using models of kinetically well characterized phosphorelays (Spo0 of Bacillus subtilis and Sln1-Ypd1-Ssk1-Skn7 of Saccharomyces cerevisiae) shows that information transmission is maximized by the natural architecture of the phosphorelay. In view of this we analyze seventeen additional phosphorelays, for which protein abundance is available but kinetic parameters are not. The architectures of 16 of these are also consistent with maximization of information transmission. Our results highlight the complexity of the genotype (architecture, parameter values, and protein abundance) to phenotype (physiological output of the circuit) mapping in phosphorelays. The results also suggest that maximizing information transmission through the circuit is important in the selection of natural circuit genotypes.

systems biology↗

bioRxiv2019

Combining genotype, phenotype, and environmental data to delineate site-adjusted provenance strategies for ecological restoration

Despite the importance of climate-adjusted provenancing to mitigate the effects of environmental change, climatic considerations alone are insufficient when restoring highly degraded sites. Here we propose a comprehensive landscape genomic approach to assist the restoration of moderately disturbed and highly degraded sites. To illustrate it we employ genomic datasets comprising thousands of single nucleotide polymorphisms from two plant species suitable for the restoration of iron-rich Amazonian Savannas. We first use a subset of neutral loci to assess genetic structure and determine the genetic neighborhood size. We then identify genotype-phenotype-environment associations, map adaptive genetic variation, and predict adaptive genotypes for restoration sites. Whereas local provenances were found optimal to restore a moderately disturbed site, a mixture of genotypes seemed the most promising strategy to recover a highly degraded mining site. We discuss how our results can help define site-adjusted provenancing strategies, and argue that our methods can be more broadly applied to assist other restoration initiatives.

ecology↗

bioRxiv2019

Simultaneous 3D super-resolution fluorescence microscopy and atomic force microscopy: combined SIM and AFM platform for cell imaging

Correlating data from different microscopy techniques holds the potential to discover new facets of signaling events in cellular biology. Here we report for the first time a hardware set-up capable of achieving simultaneous imaging of spatially correlated super-resolution fluorescence microscopy and atomic force microscopy, a feat only obtained until now by fluorescence microscopy set-ups with spatial resolution restricted to the Abbe resolution limit. We hereby remove the need to perform independent measurement and subsequent data averaging required to eliminate cell-to-cell variation in observed signals. We detail system integration, demonstrate system performance and report imaging of sub-resolution fluorescent beads and genome-engineered human bone osteosarcoma epithelial cells.

cell biology↗

bioRxiv2018

NG-meta-profiler: fast processing of metagenomes using NGLess, a domain-specific language

NGLess is a domain specific language for describing next-generation sequence processing pipelines. It was developed with the goal of enabling user-friendly computational reproducibility.\n\nUsing this framework, we developed NG-meta-profiler, a fast profiler for metagenomes which performs sequence preprocessing, mapping to bundled databases, filtering of the mapping results, and profiling (taxonomic and functional). It is significantly faster than either MOCAT2 or htseq-count and (as it builds on NGLess) its results are perfectly reproducible. These pipelines can easily be customized and extended with other tools.\n\nNGLess and NG-meta-profiler are open source software (under the liberal MIT licence) and can be downloaded from http://ngless.embl.de or installed through bioconda.

bioinformatics↗

bioRxiv2018

Febrile temperatures increase in vitro antibody affinity for malaria and dengue antigens

Fever is a regulated elevation in the body setpoint temperature and may arise as a result of infectious and noninfectious causes. While beneficial in modulating immune responses to infection, the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. We have investigated this process under in vitro conditions using selected malaria or dengue antigens and specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40{degrees}C, compared to physiological (37{degrees}C) or pathophysiological temperatures (42{degrees}C). Induced thermal equilibration of the protein partners at these temperatures, prior to measurements, further increased their binding affinity. These results may indicate an unexpected beneficial and adaptive role for fever in vivo, and highlight the positive role of thermal priming in enhancing protein-protein affinity for samples of scarce availability.

biochemistry↗