Biology subjects

Oliveira, S.

Publications and source records attributed to Oliveira, S..

14 recordsLinked to original sources

bioRxiv2026

Data-driven forecasts of regional arrivals of non-native vertebrates worldwide

AimTo forecast near-future arrivals of non-native terrestrial and freshwater vertebrates at the regional level. LocationGlobal (geopolitical regions worldwide, including countries and main administrative divisions). MethodsWe compiled first regional record data and assembled functional and macroecological variables for 1,931 non-native vertebrate species. For each region, we identified recently arrived non-native species using retrospective windows of thirty and twenty years ending in 2015 (1986-2015; 1996-2015). We then fitted region-specific random-forest models classifying recently arrived species versus those not yet arrived using as predictors: (i) harmonised species traits (e.g., habitat, diet, body size and native-range attributes) and (ii) spread history, capturing time since first record elsewhere. Predictive performance was evaluated using leave-one-out cross-validation, comparing full models with trait-only and spread-only variants. We also assessed relationships between predictive accuracy, predictor importance, and the geographic positioning and trade connectedness of regions. Finally, we predicted region-specific probabilities of arrival for species not yet recorded. ResultsForecasting accuracy was consistently high across regions and taxa, with AUC values above 0.9 in more than half of the focal regions. Full models substantially outperformed models using either predictor set alone, and spread-history-only models typically exceeded trait-only models. Relative importance of spread-history predictors declined with geographic distance to the focal region, whereas predictability was lower in highly trade-connected regions. Predicted near-future high-risk arrivals were dominated by birds and freshwater fishes and showed strong regional structuring. A small set of species ranked highly across many regions (e.g., birds: Phasianus colchicus, Acridotheres tristis, Amandava amandava, Colinus virginianus, Corvus splendens and Lonchura malacca; fishes: Coregonus peled and Oreochromis mossambicus; mammal: Oryctolagus cuniculus), suggesting substantial unrealised spread potential. Main conclusionsNear-future regional arrivals of non-native vertebrates are predictable from spread history and species traits. This enables scalable, updateable regional watchlists to support prevention, early detection and horizon scanning.

ecology↗

bioRxiv2025

iPSC derived MSC secretome activates distinct neuroprotective pathways in a preclinical model of Parkinsons disease

Parkinsons disease (PD) is characterized by a progressive loss of dopaminergic neurons, which current therapies fail to address. Mesenchymal stem cells (MSCs) secretome holds promising therapeutic potential; however, the gold standard source - bone marrow (BM) - face scalability limitations. Induced pluripotent stem cells (iPSCs)-derived MSCs (iMSCs) are a rejuvenated and clinically attractive source, yet the effects of their secretome have not been studied in PD. Here, we directly compare the effects of BM-MSCs and iMSCs secretome in a 6-OHDA rat model. Despite few differences in secretome composition, both improved motor function and partially ameliorated anhedonia, but only iMSCs secretome significantly preserved dopaminergic neurons. Proteomic analysis revealed that BM-MSCs secretome activates antioxidant and proteostasis pathways, whereas iMSCs secretome activate broader pro-survival and regenerative pathways, including NRF2-mediated oxidative stress response and mTOR. In addition, iMSC-secretome treatment modulated glutamatergic and GABAergic neurotransmission, suggesting restoration of synaptic homeostasis beyond dopaminergic preservation. These findings demonstrate that iMSCs secretome exerts robust neuroprotective effects and shed light on the mechanisms underlying this scalable and clinically translatable therapy for PD.

neuroscience↗

bioRxiv2025

Efficacy of chronic 5-HT1A receptor agonism by NLX-112 in a mouse model of Spinocerebellar Ataxia type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by an elongated polyglutamine (polyQ) sequence in the ataxin-3 protein. This expansion triggers neuropathological events, leading to progressive motor disturbances. Currently, no approved therapy exists for this debilitating condition, but compelling evidence suggests that targeting the serotonergic system can significantly attenuate SCA3 disease progression in animal models. ObjectiveThis study aimed to assess the effects of NLX-112, a highly selective serotonin 1A receptor (5-HT1AR) full agonist, in the CMVMJD135 transgenic mouse model of SCA3. MethodsNLX-112 (0.625 and 5 mg/kg/day) and tandospirone (a 5-HT1AR partial agonist used as a comparator; 20 and 80 mg/kg/day) were administered chronically in drinking water for 34 weeks, starting prior to symptom onset. To evaluate the effects of the drugs on SCA3 mice, motor-related behavioral tests and neuropathological techniques were employed. ResultsTreatment with the higher dose of NLX-112 led to improvements in motor coordination and balance, and slowing of symptom deterioration as the disease progressed. These beneficial effects were not achieved with tandospirone. NLX-112 treatment also elicited neuroprotective effects, reducing dopaminergic (tyrosine hydroxylase-positive) cell loss and astrocyte reactivity in the substantia nigra. ConclusionsNLX-112 treatment, started pre-symptomatically, enhanced motor function, slowed disease progression and elicited neuroprotective effects in SCA3 mice, supporting its further development as a drug candidate for treatment of ataxia and related movement disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/671624v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@548b2corg.highwire.dtl.DTLVardef@7d2f51org.highwire.dtl.DTLVardef@ad8ee4org.highwire.dtl.DTLVardef@80213c_HPS_FORMAT_FIGEXP M_FIG C_FIG Key findingsO_LINLX-112 attenuated motor deficits of SCA3 mice, when administered chronically prior to disease onset. C_LIO_LINLX-112 reduced neuropathological biomarkers in SCA3 mice, namely by restoring dopaminergic neuron loss and decreasing astrocyte reactivity. C_LIO_LINLX-112 is a potential candidate for addressing ataxia-related deficits in SCA3 patients. C_LI

neuroscience↗

bioRxiv2025

Generation of a Three-dimensional Human Neurovascular Unit Model in a Microfluidic Chip

BackgroundThe well-functioning of the neurovascular unit (NVU) is supported by the 3D brain physiological microenvironment that allows for extensive neural-neural and neural-vascular interactions. This microenvironment is normally hard to create in traditional in-vitro models such as the transwell model. Organ-on-a-chip (OOC) emerges as advanced model systems by providing better physiological microenvironments. However, NVU modeling in many chip platforms has not met a full 3D condition for neural cultures. MethodsHere, we describe a novel NVU model generated in a microfluidic chip that reproduces the neural-neural and neural-vascular interactions in a full-3D format. The model features an extracellular matrix (ECM) environment that supports both a perfused brain endothelial vessel and 3D cultured neural cells (astrocytes and neurons) beside the tube. Culture conditions were comprehensively optimized for better endothelial tube integrity as well as ECM gel longevity. The model was used to model neuroinflammation-induced brain tube disruption and immune cell extravasation. Furthermore, as a drug testing platform, the model was explored for brain endothelial transcytosis of the heparin-binding EGF-like growth factor (HB-EGF) targeted nanobodies and the data was compared to a parallel transwell model. ResultsImmunofluorescent staining confirmed the expression of endothelial junctional proteins, as well as astrocytic and neuronal markers. The perfused brain endothelial tube exhibited resistance to paracellular leakage of 20 kDa FITC-dextran. Astrocytes and neurons growing in ECM gel developed extensive neural network and showed spontaneous neuronal firing. The neural-vascular interactions were formed through astrocyte migration and axonal outgrowth in the ECM gel towards the tube. Exposure to neuroinflammatory cytokines disrupted the tube barrier, resulting in increased barrier leakage and the recruitment of peripheral blood mononuclear cells (PBMCs) as well as their extravasation. Owing to full-3D model design, endothelial transcytosis and abluminal distribution of the fluorescently labeled HB-EGF targeting Nbs can be clearly visualized in situ. Compared to a transwell model counterpart, the NVU chip model performed better in revealing the binding and transcytosis specificity of the targeted nanobodies. ConclusionsWe demonstrate improved physiological relevance in this full-3D NVU-on-a-chip model. The model could become a faithful platform for NVU research under both healthy and diseased conditions, and can be used as a reliable drug testing platform that aims at developing novel brain-targeted therapeutics.

bioengineering↗

bioRxiv2024

Th17 cells require the DNA repair sensor XPC to control oxidative DNA damage

Th17 cells are critical for mucosal immunity, producing IL-17A, IL-17F, and IL-22, but dysregulated Th17 responses are implicated in autoimmune diseases. Despite their susceptibility to oxidative stress in certain conditions, Th17 cells exhibit reduced oxidative DNA damage and cell death compared to other T helper subsets. However, the mechanisms that protect Th17 cells from oxidative stress are poorly understood. Here, we identify Xeroderma Pigmentosum Complementation Group C (XPC) as a key regulator of DNA repair and genomic stability in Th17 cells. In XPC-deficient mice, we demonstrate that the absence of XPC impairs Th17 differentiation, as evidenced by reduced expression of key differentiation markers, including Rorc and Il17a, along with decreased IL-17A production. This deficiency leads to increased oxidative stress, DNA damage, and a metabolic shift from glycolysis to oxidative phosphorylation. Moreover, the transcription factor BATF directly regulates XPC expression, linking the BATF-XPC axis to the maintenance of Th17 cell function. Importantly, we find that restoring antioxidant capacity with N-Acetylcysteine (NAC) rescues IL-17A production and reduces DNA damage in XPC-deficient Th17 cells. Mechanistically, we find that XPC interacts with OGG1, a DNA glycosylase involved in the repair of oxidative DNA damage, highlighting XPCs role in maintaining genomic integrity during Th17 cell differentiation. Our findings reveal a previously unrecognized role for XPC in protecting Th17 cells from oxidative stress, ensuring their proper differentiation and function, with potential implications for targeting DNA repair pathways in autoimmune and inflammatory diseases.

immunology↗

bioRxiv2024

A Spike Trimer Dimer-Inducing Nanobody with Anti-Sarbecovirus Activity

The continued emergence and zoonotic threat posed by coronaviruses highlight the urgent need for effective antiviral strategies with broad reactivity to counter new emerging strains. Nanobodies (or single-domain antibodies) are promising alternatives to traditional monoclonal antibodies, due to their small size, cost-effectiveness and ease of bioengineering. Here, we describe 7F, a llama-derived nanobody, targeting the spike receptor binding domain of sarbecoviruses and SARS-like coronaviruses. 7F demonstrates potent neutralization against SARS-CoV-2 and cross-neutralizing activity against SARS-CoV and SARS-like CoV WIV16 pseudoviruses. Structural analysis reveals 7Fs ability to induce the formation of spike trimer dimers by engaging with two SARS-CoV-2 spike RBDs, targeting the highly conserved class IV region. Bivalent 7F constructs substantially enhance neutralization potency and breadth, up to more recent SARS-CoV-2 variants of concern. Furthermore, we demonstrate the therapeutic potential of 7F against SARS-CoV-2 in the fully differentiated 3D tissue cultures mirroring the epithelium of the human airway ex vivo. The broad sarbecovirus activity and distinctive structural features of 7F underscore its potential as promising antiviral against emerging and evolving sarbecoviruses.

microbiology↗

bioRxiv2023

Genome wide variation in the Angolan Namib desert reveals unique Pre-Bantu ancestry

The populations of the Angolan Namib Desert have been largely neglected in previous surveys of the genomic landscape of southern Africa. Although at present the Namib is culturally dominated by Southwest Bantu-speaking cattle-herders, the region exhibits an extraordinary ethnographic diversity which includes an array of semi-nomadic peoples whose subsistence strategies fall outside the traditional division between foraging and food production and can thus be referred to as "peripatetic". Among these small-scale populations are the last speakers of the Kwadi branch of the Khoe-Kwadi language family associated with the introduction of pastoralism into southern Africa (Kwepe), as well as a range of groups whose origins remain enigmatic (Kwisi, Twa and Tjimba). Using genome-wide data from 208 individuals belonging to nine ethnically diverse groups from the Angolan Namib and adjacent areas (Kwepe, Kwisi, Twa, Tjimba, !Xun, Kuvale, Himba, Nyaneka, Ovimbundu) in combination with published data from other regions of Africa, we reconstruct in detail the histories of contact emerging from pre-historic migrations to southern Africa and show that peripatetic groups from southwestern Angola stand out for exhibiting elevated levels of an unique, regionally-specific and highly divergent Pre-Bantu ancestry. These findings highlight the importance of the Namib for understanding the deep genetic structure of Africa.

genetics↗

bioRxiv2021

#COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy of Delta SARS-CoV-2 in a Respiratory Aerosol

We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus ob-scure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized. ACM Reference FormatAbigail Dommer1{dagger}, Lorenzo Casalino1{dagger}, Fiona Kearns1{dagger}, Mia Rosenfeld1, Nicholas Wauer1, Surl-Hee Ahn1, John Russo,2 Sofia Oliveira3, Clare Morris1, AnthonyBogetti4, AndaTrifan5,6, Alexander Brace5,7, TerraSztain1,8, Austin Clyde5,7, Heng Ma5, Chakra Chennubhotla4, Hyungro Lee9, Matteo Turilli9, Syma Khalid10, Teresa Tamayo-Mendoza11, Matthew Welborn11, Anders Christensen11, Daniel G. A. Smith11, Zhuoran Qiao12, Sai Krishna Sirumalla11, Michael OConnor11, Frederick Manby11, Anima Anandkumar12,13, David Hardy6, James Phillips6, Abraham Stern13, Josh Romero13, David Clark13, Mitchell Dorrell14, Tom Maiden14, Lei Huang15, John McCalpin15, Christo- pherWoods3, Alan Gray13, MattWilliams3, Bryan Barker16, HarindaRajapaksha16, Richard Pitts16, Tom Gibbs13, John Stone6, Daniel Zuckerman2*, Adrian Mulholland3*, Thomas MillerIII11,12*, ShantenuJha9*, Arvind Ramanathan5*, Lillian Chong4*, Rommie Amaro1*. 2021. #COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy ofDeltaSARS-CoV-2 in a Respiratory Aerosol. In Supercomputing 21: International Conference for High Perfor-mance Computing, Networking, Storage, and Analysis. ACM, New York, NY, USA, 14 pages. https://doi.org/finalDOI

biophysics↗

bioRxiv2021

Ancient genomes from the last three millennia support multiple human dispersals into Wallacea

Previous research indicates that the human genetic diversity found in Wallacea - islands in present-day Eastern Indonesia and Timor-Leste that were never part of the Sunda or Sahul continental shelves - has been shaped by complex interactions between migrating Austronesian farmers and indigenous hunter-gatherer communities. Here, we provide new insights into this regions demographic history based on genome-wide data from 16 ancient individuals (2600-250 yrs BP) from islands of the North Moluccas, Sulawesi, and East Nusa Tenggara. While the ancestry of individuals from the northern islands fit earlier views of contact between groups related to the Austronesian expansion and the first colonization of Sahul, the ancestry of individuals from the southern islands revealed additional contributions from Mainland Southeast Asia, which seems to predate the Austronesian admixture in the region. Admixture time estimates for the oldest individuals of Wallacea are closer to archaeological estimates for the Austronesian arrival into the region than are admixture time estimates for present-day groups. The decreasing trend in admixture times exhibited by younger individuals supports a scenario of multiple or continuous admixture involving Papuan- and Asian-related groups. Our results clarify previously debated times of admixture and suggest that the Neolithic dispersals into Island Southeast Asia are associated with the spread of multiple genetic ancestries.

genomics↗

bioRxiv2020

Precision design of single and multi-heme de novo proteins

The de novo design of simplified porphyrin-binding helical bundles is a versatile approach for the construction of valuable biomolecular tools to both understand and enhance protein functions such as electron transfer, oxygen binding and catalysis. However, the methods utilised to design such proteins by packing hydrophobic side chains into a buried binding pocket for ligands such as heme have typically created highly flexible, molten globule-like structures, which are not amenable to structural determination, hindering precise engineering of subsequent designs. Here we report the crystal structure of a de novo two-heme binding "maquette" protein, 4D2, derived from the previously designed D2 peptide, offering new opportunities for computational design and re-engineering. The 4D2 structure was used as a basis to create a range of heme binding proteins which retain the architecture and stability of the initial crystal structure. A well-structured single-heme binding variant was constructed by computational sequence redesign of the hydrophobic protein core, assessed by NMR, and utilised for experimental validation of computational redox prediction and design. The structure was also extended into a four-heme binding helical bundle resembling a molecular wire. Despite a molecular weight of only 24kDa, imaging by CryoEM illustrated a remarkable level of detail in this structure, indicating the positioning of both the secondary structure and the heme cofactors. The design and determination of atomic-level resolution in such de novo proteins is an invaluable resource for the continued development of novel and functional protein tools.

synthetic biology↗

bioRxiv2020

Cancer cells are uniquely susceptible to accumulation of MMBIR mutations

Microhomology-mediated break-induced replication (MMBIR) is a mechanism of polymerase template switching at microhomology, which can produce complex genomic rearrangements (CGRs), underlies neurological and metabolic diseases, and contributes to cancer development. Yet, the extent of MMBIR activity in genomes is poorly understood due to difficulty in directly identifying MMBIR events by whole genome sequencing (WGS). Here, by using our newly developed MMBSearch software, we directly detect MMBIR events in human genomes and report substantial differences in frequency and complexity of MMBIR events between normal and cancer cells. MMBIR events appear only as germline variants in normal human fibroblast cells but readily accumulate de novo across several cancer types. Detailed analysis of MMBIR mutations in lung adenocarcinomas revealed MMBIR-initiated chromosome fusions that disrupted potential tumor suppressor genes and induced CGRs. Our findings document MMBIR as a trigger for widespread genomic instability and highlight MMBIR as a potential driver of tumor evolution.

genetics↗

bioRxiv2019

Mozambican genetic variation provides new insights into the Bantu expansion

The Bantu expansion, which started in West Central Africa around 5,000 BP, constitutes a major migratory movement involving the joint spread of peoples and languages across sub-Saharan Africa. Despite the rich linguistic and archaeological evidence available, the genetic relationships between different Bantu-speaking populations and the migratory routes they followed during various phases of the expansion remain poorly understood. Here, we analyze the genetic profiles of southwestern and southeastern Bantu-speaking peoples located at the edges of the Bantu expansion by generating genome-wide data for 200 individuals from 12 Mozambican and 3 Angolan populations using [~]1.9 million autosomal single nucleotide polymorphisms. Incorporating a wide range of available genetic data, our analyses confirm previous results favoring a \"late split\" between West and East Bantu speakers, following a joint passage through the rainforest. In addition, we find that Bantu speakers from eastern Africa display genetic substructure, with Mozambican populations forming a gradient of relatedness along a North-South cline stretching from the coastal border between Kenya and Tanzania to South Africa. This gradient is further associated with a southward increase in genetic homogeneity, and involved minimum admixture with resident populations. Together, our results provide the first genetic evidence in support of a rapid North-South dispersal of Bantu peoples along the Indian Ocean Coast, as inferred from the distribution and antiquity of Early Iron Age assemblages associated with the Kwale archaeological tradition.

genetics↗

bioRxiv2018

The role of matrilineality in shaping patterns of Y chromosome and mtDNA sequence variation in southwestern Angola

Southwestern Angola is a region characterized by contact between indigenous foragers and incoming food-producers, involving genetic and cultural exchanges between peoples speaking Kxa, Khoe-Kwadi and Bantu languages. Although present-day Bantu-speakers share a patrilocal residence pattern and matrilineal principle of clan and group membership, a highly stratified social setting divides dominant pastoralists from marginalized groups that subsist on alternative strategies and have previously been though to have pre-Bantu origins. Here, we compare new high-resolution sequence data from 2.3 Mb of the non-recombining Y chromosome (NRY) from 170 individuals with previously reported mitochondrial genomes (mtDNA), to investigate the population history of seven representative southwestern Angolan groups (Himba, Kuvale, Kwisi, Kwepe, Twa, Tjimba, !Xun) and to study the causes and consequences of sex-biased processes in their genetic variation. We found no clear link between the formerly Kwadi-speaking Kwepe and pre-Bantu eastern African migrants, and no pre-Bantu NRY lineages among Bantu-speaking groups, except for small amounts of \"Khoisan\" introgression. We therefore propose that irrespective of their subsistence strategies, all Bantu-speaking groups of the area share a male Bantu origin. Additionally, we show that in Bantu-speaking groups, the levels of among-group and between-group variation are higher for mtDNA than for NRY. These results, together with our previous demonstration that the matriclanic systems of southwestern Angolan Bantu groups are genealogically consistent, suggest that matrilineality strongly enhances both female population sizes and interpopulation mtDNA variation.

genetics↗

bioRxiv2017

The maternal genetic history of the Angolan Namib Desert: a key region for understanding the peopling of southern Africa

Southern Angola is a poorly studied region, inhabited by populations that have been associated with different migratory movements into southern Africa. Besides the long-standing presence of indigenous Kxa-speaking foragers and the more recent arrival of Bantu-speaking pastoralists, ethnographic and linguistic studies have suggested that other pre-Bantu communities were also present in the Namib desert, including peripatetic groups like the Kwepe (formerly Kwadi speakers), Twa and Kwisi. Here we evaluate previous peopling hypotheses by analyzing the relationships between seven groups from the Namib desert (Kuvale, Himba, Tjimba, Kwisi, Twa, Kwepe) and Kunene Province (!Xun), based on newly collected linguistic data and 295 complete mtDNA genomes. We found that: i) all groups from the Namib desert have genealogically-consistent matriclanic systems that had a strong impact on their maternal genetic structure by enhancing genetic drift and population differentiation; ii) the dominant pastoral groups represented by the Kuvale and Himba were part of a Bantu proto-population that also included the ancestors of present-day Damara and Herero peoples from Namibia; iii) Tjimba are closely related to the Himba; iv) the Kwepe, Twa and Kwisi have a divergent Bantu-related mtDNA profile and probably stem from a single population that does not show clear signs of being a pre-Bantu indigenous group. Taken together, our results suggest that the maternal genetic structure of the different groups from the Namib desert is largely derived from endogamous Bantu peoples, and that their social stratification and different subsistence patterns are not indicative of remnant groups, but reflect Bantu-internal variation and ethnogenesis.

genetics↗