bioRxiv Science⌕ Search

Biology subjects

Oliveira, N.

Publications and source records attributed to Oliveira, N..

7 recordsLinked to original sources

Multi-scale Transcriptional Characterization of HPV16 and HPV18 in Cervical Cancer: Host Pathway Alterations and Links With Viral Gene Expression Programs

High-risk HPV is central to cervical carcinogenesis, but whether individual genotypes drive distinct tumor biology or converge on a shared oncogenic state remains unclear. Profiling viral and host gene expression across two independent cohorts (n = 93; 76 HPV16, 17 HPV18), we show that HPV16- and HPV18-associated cervical cancers differ in host transcriptional programs. A 55-gene signature discriminated the two genotypes, and 293 genes were concordantly differentially expressed across cohorts. Pathway and transcription-factor activity inference organized these differences along genotype-specific axes: HPV16 tumors were enriched for epithelial polarity and RTK-RAS-MAPK signatures, with elevated inferred CDX2 regulon activity, a transcription factor not normally active in cervical epithelium, suggesting an aberrant lineage-identity program not previously linked to this genotype. HPV18 tumors instead showed metabolic reprogramming and inflammatory signaling (STAT3, HIF1A), alongside reduced CASP8 and increased FDX1 expression, a pattern consistent with sensitization to immunogenic cell death. Both genotypes also organized along a continuum of early-to-late viral gene expression correlating with distinct host pathways: extracellular-matrix and translation-related in HPV16, interferon/antiviral and cell-cycle/mitochondrial in HPV18, indicating that viral transcriptional state associates with host biology beyond genotype alone. These results point to candidate genotype-specific vulnerabilities that merit functional validation.

cancer biology↗

Integrating dedicated and opportunistic surveys to estimate seasonal common dolphin density off mainland Portugal

1. Common dolphins (Delphinus delphis) are the most abundant cetaceans off mainland Portugal and a species of conservation and bycatch concern, so reliable abundance estimates are a management priority. Yet no single survey provides adequate spatiotemporal coverage: dedicated programmes offer sparse snapshots, while opportunistic programmes are spatially constrained by their routes. Integrating them is methodologically demanding, and the existing methods that do so in a single model estimate the density of animal groups, not of the individual animals that management often requires. 2. We develop a spatiotemporal marked log-Gaussian Cox process that integrates four structurally distinct surveys through a shared intensity surface, comprising environmental covariates, a latent spatial field, and survey-specific detection functions. Group size enters as a zero-truncated negative binomial mark with its own spatiotemporal field. We apply it to a dedicated aerial survey and three opportunistic ship-based programmes off mainland Portugal, comprising 162,514 km of on-effort transects and 1,756 sightings of 17,000 animals. We fit the model in a Bayesian framework with integrated nested Laplace approximations, yielding seasonally resolved group and animal density surfaces across the Portuguese Exclusive Economic Zone, and abundance estimates with fully propagated uncertainty. 3. Predicted animal density concentrated over the shelf and upper slope in every season, peaking northwest, and increased in shallower, cooler, more productive waters and over steeper seabed. Abundance nearly doubled from summer (77,000 [95% credible interval: 60,000, 98,000]) to winter (146,000 [99,000, 208,000]). Seasons shared 56% of the spatial field's variance, so effort from any programme in any season informed all others, and the seasonal contrast remained estimable despite uneven coverage. 4. Synthesis and applications. Our framework allows managers to combine dedicated surveys with existing platforms of opportunity to estimate animal density by season. Because group size is modelled explicitly, densities are estimated in animals rather than groups, as required for bycatch risk assessment and marine spatial planning. Because each survey enters through its own observation model, the approach accommodates programmes that differ in platform and protocol and transfers to any species or region where several surveys each cover part of a population.

ecology↗

Diet and breeding productivity in European Shag (Gulosus aristotelis): insights from two Portuguese colonies

Climate change and anthropogenic pressures are reshaping marine food webs, altering prey availability and affecting top predators. The European Shag (Gulosus aristotelis), a coastal demersal seabird, provides a valuable model for examining environmentally mediated dietary variation, given its trophic plasticity and capacity to adjust prey use according to local availability, while also allowing assessment of potential demographic consequences. This study investigated spatial and temporal variation in diet at two Portuguese colonies (Berlengas and Arrabida) between 2016 and 2024 and assessed long-term reproductive productivity at Berlengas. A total of 468 regurgitated pellets were analysed, and diet composition was quantified using the Index of Relative Importance (IRI). Generalised additive models were applied to assess environmental, spatial, and period-specific effects on diet composition, while reproductive productivity was modelled in relation to prey biomass. Diet variation was primarily explained by environmental predictors, including sea surface temperature, chlorophyll-a concentration, and zooplankton, whereas year per se had no significant effect, indicating environmentally mediated bottom-up effects. Spatial differences between colonies reflected contrasting prey field structures, and period-specific patterns suggested increased specialisation during breeding. Higher biomass of sandeels (Ammodytidae) was positively associated with reproductive output, whereas shifts toward lower-energy prey were associated with reduced productivity. These findings demonstrate that environmentally driven dietary change has measurable demographic consequences, underscoring the importance of bottom-up processes in shaping seabird population dynamics and informing conservation strategies under ongoing climate change.

ecology↗

Spatiotemporal data integration for marine megafauna SDMs in dynamic environments: A point process approach

Species distribution models (SDMs) are widely used to predict where and when species occur, but the data available to fit them often resolve space and time unevenly. Designed surveys, such as line-transect distance-sampling surveys, provide structured spatial coverage and the detection information needed to estimate detectability, but logistical and funding constraints often limit them to short, infrequent periods. Opportunistic or citizen-science records are collected more frequently across the year, but from areas shaped by observer access and interest rather than survey design, and usually without comparable detection information. As a result, models built from either source alone tend to capture spatial structure or temporal dynamics well, but not both, limiting predictions for mobile species in dynamic environments. Here, we present a general framework, based on a log-Gaussian Cox process (LGCP) fitted using integrated nested Laplace approximations (INLA), that links multiple data sources to a shared spatiotemporal measure of species density through source-specific observation models: a detection function for survey transects, and spatial constraints reflecting the footprint of opportunistic effort. We apply the framework to cetacean line-transect surveys and whale-watching records. In a simulation with one month of survey data and twelve months of opportunistic data, the integrated model recovered spatiotemporal distribution patterns well (median correlation with the true pattern = 0.91) and estimated monthly abundance with a mean error of +10.7%, outperforming single-source models. In a case study of common dolphins (Delphinus delphis) off mainland Portugal, integration improved the spatial accuracy of predictions, although weak covariate effects limited the temporal variation the model could resolve. These results show that integration adds the most value when the two data sources resolve complementary aspects of distribution, in this case broad spatial structure from the survey and temporal replication from whale-watching, while temporal predictions remain limited when covariates carry weak seasonal signal. The framework is general and can be extended to other taxa, systems, and combinations of structured and opportunistic data by substituting the relevant observation models.

ecology↗

Seasonal and interannual variation of common dolphin densities in Portuguese waters

Modelling a species ecology and abundance provides important insights into its habitat preferences, population trends and distribution. This can be used to inform conservation efforts, highlighting populations at risk of extinction and regions in need of protection. Here, we studied how environmental factors relate to common dolphins (Delphinus delphis) densities in the waters off mainland Portugal. We analyzed an opportunistic dataset collected using European Seabirds At Sea (ESAS) methodology with distance sampling, spanning from 2004 to 2020. There were 1151 sightings of common dolphins, 737 of which were during effort. Detection functions were fitted to model the dolphins detectability as a function of the distance to the track line. We used smooths of static (depth, slope, and distance to the coast, 200m and 1000m isobaths) and dynamic (sea surface temperature, salinity, chlorophyll-a concentration with and without a time lag, zooplankton, and sardine biomass) environmental factors, relating them to counts corrected for detectability and survey effort, to fit habitat-based Density Surface Models. We then predicted and mapped common dolphin densities seasonally (winter, spring, summer autumn) throughout the sample years. The results show how different environment variables relate to dynamic common dolphin densities. In general, common dolphins had higher densities in coastal environments, especially during the summer due to high productivity and lower sea surface temperature in shelf waters, associated with seasonal upwelling. During the summer, there were predicted local peaks in common dolphin densities, in areas with high zooplankton and chlorophyll-a concentration. In the other seasons, its range expands to more offshore waters, with less local density peaks. The interannual variation of this species densities is mostly explained by the annual sardine biomass. Overall, this brings important insights into this species conservation and potential impacts from anthropogenic activities, such as climate change and overfishing.

ecology↗

HIV-1 Vpr alters cellular transcription by targeting the PAF1 complex

Innate immunity represents the first line of defence against viral infections, and successful pathogens like HIV-1 have evolved mechanisms to bypass these barriers. The PAF1 complex (PAF1c) has emerged as a key regulator of antiviral innate immune responses, inhibiting the replication of various viruses, including HIV-1. While its role in transcription regulation is well documented, little is known about how PAF1c inhibits HIV-1 and how HIV-1 circumvents this antiviral activity. Here we demonstrate that Vpr induces the rapid and transient downmodulation of PAF1c shortly after infection, a process that correlates with significant transcriptomic changes within the host cell. Transcriptomic profiling reveals that PAF1 knockdown mirrors many of the gene expression changes induced by HIV-1 infection, indicating that Vpr antagonism of PAF1c is a means by which HIV-1 may modulate host gene expression to favour replication. Further, we show that the loss of PAF1c leads to the suppression of interferon-stimulated genes (ISGs) and several known HIV-1 restriction factors. Overall, the evidence supports the emerging role of PAF1 as a regulator of a broad antiviral transcriptional program, but also suggests a specific anti-HIV activity that is countered by HIV-1 Vpr.

microbiology↗

Systematic determination of in vitro phenotypic resistance to HIV-1 integrase strand transfer inhibitors from clinical samples

Phenotypic resistance data is relatively sparse for the newest HIV-1 integrase strand transfer inhibitors (INSTIs), dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB). In this study, we report the phenotypic susceptibility of a large panel of oligo-clonal patient-derived HIV-1 integrase viruses. Representative clinical samples (N=141) were selected from a large database (N=17,197) of clinically-derived HIV integrase sequences, based on the presence of permutations of substitutions at 27 pre-defined positions in integrase (N=288). HIV-1 RNA was extracted from patient samples and diluted to approximately 500 HIV RNA copies/mL. Using an \"oligo-clonal\" amplification approach to achieve single-copy amplification, these dilutions were subjected to 12 parallel RT-PCR reactions to amplify integrase. Confirmed clonal amplicons were co-transfected with linearized pNL4.3{triangleup}int into CEM-GXR cells. In total, 162 HIV-1 viruses that carried no mixtures and had a unique sequence were harvested, and phenotyped in MT4-LTR-EGFP cells subsequently. Variants with the highest fold change (FC) had G140S and Q148R/H and resistant to all five drugs; R263K was the only single variant conferring >3-FC to DTG, BIC and CAB. There was extensive cross-resistance between DTG, BIC, and CAB and phenotypic resistance values for all the three INSTIs were almost collinear. The greatest exceptions were variants with N155H/G163E or L74I/T97M/F121C/V151I/E157Q/G163K, where both had >70-FC for CAB, while <3-FC for DTG and BIC. While site-directed mutagenesis is invaluable; the systematic selection of representative mutational patterns observed in vivo provides an efficient way to identify clinically relevant drug resistance.

molecular biology↗