Biology subjects

Lucas, E.

Publications and source records attributed to Lucas, E..

14 recordsLinked to original sources

bioRxiv2026

Genomic connectivity and the spread of adaptive insecticide resistance alleles in Anopheles arabiensis from East Africa

Population connectivity and adaptive gene flow in disease vectors can shape the emergence and spread of insecticide resistance, with direct implications for control strategies such as insecticide spraying or the use of bed nets for malaria control. Using whole-genome sequencing, we first resolved the geographic population structure of the major but understudied malaria vector, Anopheles arabiensis, across the East African region, including the geographically diverse country of Ethiopia. We then assessed evidence for adaptive gene flow of insecticide resistance alleles across the region. Within Ethiopia, Central Rift Valley populations flanked by mountainous terrain were subject to restricted gene flow, although higher connectivity with the southwestern populations suggests an intermediate point of genetic exchange with the rest of Ethiopia. Anopheles arabiensis from western and northernmost Ethiopia were connected to populations from a similarly arid environment in Turkana - Kenya. Furthermore, broad-scale analysis revealed that populations from the rest of Kenya were connected with those from Uganda and Tanzania, but finer-scale analysis revealed more subtle structuring along the Rift Valley flanks, underscoring the role of landscape features in shaping patterns of gene flow. Adaptive gene flow analyses of diplotype clustering revealed that resistance alleles such as Cyp6aa/p and Gste2 copy number variants (CNV) were widely spread across East Africa despite the geographical population structuring we observed. At the Gste2 locus, An. arabiensis from Ethiopia and Kenya carried a newly annotated CNV spanning chromosome position 3R:28,596,832-28,606,222 linked to the non-synonymous SNP V47L, which was only at a low frequency in Kenya. Collectively, our findings demonstrate that An. arabiensis is subject to transboundary movement of resistance alleles, highlighting the need for coordinated cross-country vector management. Although areas of high connectivity may challenge genetic control technologies such as gene drives, more isolated populations may provide opportunities for targeted deployment. SignificanceMosquitoes movement across landscapes determines how insecticide resistance spreads, yet the genomic connectivity of Anopheles arabiensis populations in East Africa is understudied. Using whole genome data, we show that geographic features such as the Rift Valley restrict gene flow in Ethiopia, with western and northernmost Ethiopia connecting to Turkana, while Kenyan populations outside Turkana connect further south with Tanzania and Uganda. Despite these geographic barriers, resistance variants at genes such as Cyp6aa/p and Gste2 spread widely through adaptive gene flow, including a newly annotated CNV allele at Gste2 in Ethiopia and Kenya. These findings demonstrate that resistance alleles move across national borders, underscoring the need for coordinated regional vector management. They also highlight that while broader connectivity may limit genetic control tools such as gene drive, more isolated populations offer opportunities for targeted deployment.

genomics↗

bioRxiv2025

Setting priorities for the acquisition of primary plant occurrence data

AimEffective implementation of the Global Biodiversity Framework and Global Strategy for Plant Conservation depends on accurate species distribution data. Current vascular plant distribution data, while crucial for understanding terrestrial ecosystems, is often sparse and biased and requires significant expansion. This study developed a scalable approach to prioritize areas for plant occurrence data acquisition, adaptable to national priorities and providing a framework for botanical institutions to coordinate efforts and allocate resources. LocationGlobal. MethodsUsing a Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) analysis, we prioritized areas based on: (a) ecosystem service value; (b) floristic value threatened by climate or land-use change; and (c) uncertainty in species richness estimates, stratified by biome and region. Regional prioritization maps for Africa & Madagascar; East, South and Southeast Asia; Siberia and the Russian Far East; South America; and North & Central America were reviewed by botanical experts for validation. Scalability was assessed by comparing regional and global analyses. ResultsData-driven priority maps, divided into tree-dominated and grassland/deforested areas, largely received expert support. High similarity between global and regional maps demonstrated scalability. Main conclusionsOur approach provides a framework for supporting national implementation of the Global Biodiversity Framework. Variables and their weights can be tailored to national or local needs. The methods flexibility and adaptability extend to other taxonomic groups and objectives, such as protected area selection By prioritizing data acquisition, whether field-based or digital, this research promotes the efficient use of resources. A key advantage of this approach is its capacity to systematically translate expert opinion into explicit and quantitative criteria, which in turn facilitates clear communication with policymakers and funders.

plant biology↗

bioRxiv2025

Big angiosperm genera are priorities for conservation

Species in big angiosperm genera ([≥]500 species) are often considered to be less well-known than those in smaller genera. Consequently, species in big genera are likely underrepresented in conservation at all levels, from analyses to actions. However, emerging evidence indicates that species in larger genera tend to have smaller geographic ranges (a strong correlate of increased extinction risk). Here, we test the generality of this pattern by quantifying the relationships between plant taxon size, extinction risk and climatic zone on a global scale. We find that species in larger genera are more likely to have small ranges, less likely to have a global Red List assessment, and, when assessed, are more likely to be threatened. Persistent obstacles to improving conservation documentation of big genera include taxonomic uncertainty, data shortfalls and number of species involved, requiring continued collaboration between taxonomy and conservation to reduce this bias and enable effective conservation of the quarter of plant species that big genera encompass. Article Impact StatementSpecies in big angiosperm genera are under-studied, under-assessed, and their extinction risk has been underestimated.

ecology↗

bioRxiv2025

An evolutionarily conserved microRNA, miR-185, regulates key pathways that may contribute to implantation failure.

Recurrent implantation failure (RIF) is defined after three or more good quality embryo transfers following in vitro fertilisation without a successful pregnancy outcome. Many factors contribute to RIF however, the endometrial contribution remains unclear. Previous work by our group has identified a micro-RNA (miRNA) miR-185-5p as conserved across placental mammal irrespective of implantation strategies. We tested the hypothesis that miR-185-5p and the pathways it regulates, may be disrupted in the endometria of women with RIF. A human endometrial epithelial cells line (Ishikawa cells) was transfected with mimics or inhibitors for miR-185-5p for 24 (for implantation assay) or 48 hr (for proteomic analysis) along with non-targeting controls. There was a significant different in percentage attachment of BeWoW spheroids to cells transfected with miR-185-5p mimic compared to inhibitor (P<0.05). Transfection of epithelial cells with miR-185-5p altered expression of 1450 (mimic alone) and 509 (inhibitor alone) proteins respective of which, 146 were modified by both. Comparison of predicted targets of miR-185-5p, proteins modified by this study, and key endometrial genes from the literature determined genes and proteins associated with CNP family were further investigated in biopsies from individuals with (n=10) and without RIF (n=9) with CSNK1D expression significantly lower (p<0.05) in individuals with RIF. Collectively these data demonstrate that miR-185-5p modifies pathways that are important for successful implantation in humans.

cell biology↗

bioRxiv2024

PAX2 is Transcriptionally Silenced by a Distinct Mechanism of Epigenetic Reprogramming to Initiate Endometrial Carcinogenesis

In most cancers, including endometrial cancer, tumor suppressor genes harboring inactivating mutations have been systematically cataloged. However, locus-specific epigenetic alterations contributing to cancer initiation and progression remain only partly described, creating knowledge gaps about functionally significant tumor suppressors and underlying mechanisms associated with their inactivation. Here, we show that PAX2 is an endometrial tumor suppressor recurrently inactivated by a distinct epigenetic reprogramming event not associated with promoter hypermethylation. PAX2 is expressed throughout normal endometrial glands; however, microscopic clones with PAX2 protein loss arise spontaneously in adulthood and progress to endometrial precancers and cancers. Here we show that PAX2 protein loss occurs via transcriptional silencing in 80% of endometrial cancers. Mechanistically, transcriptomic, epigenomic, 3D genomic, and machine learning analyses showed that silencing is associated with replacement of open/active chromatin features (H3K27ac/H3K4me3) with inaccessible/repressive features (H3K27me3). The spread of the H3K27me3 signal is restrained by cohesin loops, preventing transcriptional dysregulation of neighboring genes. Functionally, PAX2 loss promoted endometrial carcinogenesis by rewiring the transcriptional landscape via global enhancer reprogramming. Genetically engineered mouse models together with organoid and human cell line studies established Pax2 as an in vivo endometrial tumor suppressor that cooperates with Pten to produce lethal cancers. Our discovery of a specific and recurring epigenetic alteration that transcriptionally silences PAX2 to initiate most endometrial cancers opens new lines of investigation into the origins of endometrial cancer with diverse implications for its diagnosis and treatment. One Sentence SummaryWe demonstrate that PAX2 is silenced by a highly recurrent epigenetic mechanism to initiate most endometrial cancers, establishing a novel mechanism of tumor suppressor inactivation.

cancer biology↗

bioRxiv2024

Stalling of the endometrial decidual reaction determines the recurrence risk of miscarriage risk

In each menstrual cycle, progesterone acting on estrogen-primed endometrium elicits an inflammatory decidual reaction, rendering it poised for embryo implantation and transformation into the decidua of pregnancy. Here, we show that the sequential functions of the decidual reaction - implantation and decidualization - pivot on the time-sensitive loss of progesterone-resistant stromal cells that form a transient implantation niche and reciprocal expansion of progesterone-responsive pre-decidual cells. In parallel, proliferation and differentiation increase the abundance of immunotolerant uterine natural killer (uNK) cells. Examination of pre-pregnancy endometrial biopsies from 924 women revealed that the frequency of cycles culminating in a blunted or stalled decidual reaction closely aligns with the age-independent recurrence risk of miscarriage. Further, analysis of 632 biopsies obtained in different cycles from 316 women indicated that prior miscarriages disrupt intercycle endometrial homeostasis, an observation supported by modelling the impacts of prolonged decidual inflammation in three-dimensional endometrial assembloids. Although stalling of the decidual reaction is often accompanied by a poor expansion of immunotolerant uNK cells, miscarriages do not impact intercycle uNK cell dynamics. Our findings indicate that intrinsic uterine mechanisms hardwire the recurrence risk of miscarriage, underscoring the need for pre-pregnancy diagnostics and therapeutics. One Sentence SummaryThe frequency of menstrual cycles culminating in a suboptimal decidual reaction determines the recurrence risk of miscarriage.

physiology↗

bioRxiv2024

The catheterized bladder environment induces dysregulation of macrophage polarization exacerbating bacterial UTI

Urinary catheterization causes bladder damage, predisposing hosts to catheter-associated urinary tract infections (CAUTIs). CAUTI pathogenesis is mediated by bladder damage-induced inflammation, resulting in accumulation and deposition of the blood-clotting protein fibrinogen (Fg) and its matrix form fibrin, which are exploited by uropathogens as biofilm platforms to establish infection. Catheter-induced inflammation also results in robust immune cell recruitment, including macrophages (M{phi}s). A fundamental knowledge gap is understanding the mechanisms by which the catheterized-bladder environment suppresses the M{phi} antimicrobial response, allowing uropathogen persistence. Here, we found that Fg and fibrin differentially modulate M1 and M2 M{phi} polarization, respectively. We unveiled that fibrin accumulation in catheterized mice induced an anti-inflammatory M2-like M{phi} phenotype, correlating with pathogen persistence. Even GM-CSF treatment of wildtype mice to promote M1 polarization was not sufficient to reduce bacterial burden and dissemination, indicating that the catheterized-bladder environment provides mixed signals, dysregulating M{phi} polarization, hindering its antimicrobial response against uropathogens.

immunology↗

bioRxiv2023

Towards a species-level phylogeny for Neotropical Myrtaceae: notes on topology and resources for future studies

Premise of the studyIncreasingly complete phylogenies underpin studies in systematics, ecology, and evolution. Myrteae (Myrtaceae), with c. 2,500 species, is a key component of the exceptionally diverse Neotropical flora, but given its complicated taxonomy, automated assembling of molecular supermatrices from public databases often lead to unreliable topologies due to poor species identification. MethodsHere, we build a taxonomically verified molecular supermatrix of Neotropical Myrteae by assembling 3,954 published and 959 unpublished sequences from two nuclear and seven plastidial molecular markers. We infer a time calibrated phylogenetic tree that covers 712 species of Myrteae (c. 28% of the total diversity in the clade) and evaluate geographic and taxonomic gaps in sampling. Key resultsThe tree inferred from the fully concatenated matrix mostly reflects the topology of the plastid dataset and there is a moderate to strong incongruence between trees inferred from nuclear and plastid partitions. Large, species-rich genera are still the poorest sampled within the group. Eastern South America is the best-represented area in proportion to its species diversity, while Western Amazon, Mesoamerica, and the Caribbean are the least represented. ConclusionsWe provide a time-calibrated tree that can be more reliably used to address finer-scale eco-evolutionary questions that involve this group in the Neotropics. Gaps to be filled by future studies include improving representation of taxa and areas that remain poorly sampled, investigating causes of conflict between nuclear and plastidial partitions and the role of hybridization and incomplete lineage sorting in relationships that are poorly supported.

plant biology↗

bioRxiv2023

Trials and tribulations of Neotropical plant taxonomy: pace of tree species description

O_LIOne of the main aspects of taxonomic research is the description of new species. Identifying how to describe new species more efficiently is key to completing the inventory of the Neotropical flora in an era of massive biodiversity loss. C_LIO_LIHere we calculate the interval between first specimen collection and new species publication for a group of 2126 Neotropical trees, and discuss the historical context surrounding specimen collection and new species publication events. C_LIO_LIOur results reveal that on average, it takes almost 16 years from specimen collection to publication of a new Neotropical tree species, which is considerably shorter than previous estimates for other tropical groups. The central Andes is the region that had the longest average time lags, while the Choco had the shortest. Peru had the longest average time lags by country, while Haiti had the shortest. The average time lags increased until the early 1900s, when a decrease was observed, with the shortest lags between 1941 to 1960. C_LIO_LIWe found that the majority of the species described more rapidly are from plants collected and described by the same researcher. We demonstrate how political instability and conflict can delay or impede the completion of research initiatives in the region. We argue that enhancing international collaboration and training opportunities in Latin American countries, as well as ensuring safe plant collection campaigns, are critical to complete the inventory of the Neotropical flora. C_LI Societal Impact StatementThis study aims to answer the question of how long it takes to describe a new species of tree in the Neotropics by calculating the time elapsed from collection of the first specimen to the publication of a new species. Given the current unprecedented concerns for global biodiversity loss, it is critical to identify best practices for describing new species more efficiently so we can complete the inventory of the Neotropical flora and implement appropriate conservation strategies in a timely manner.

plant biology↗

bioRxiv2021

Trait-environment relationship in tadpoles of the southern Atlantic Forest

O_LIEnvironmental predictors select individuals by their functional traits, shaping the anuran assembly patterns. Individuals respond to environmental filters that can be on a local or regional scale. C_LIO_LIIn this study, we investigated the association between local (water and microhabitat) and landscape variables and the morphological traits of tadpoles of ponds and streams. The study was conducted in the southern region of the Brazilian Atlantic Forest. We sampled 28 waterbodies and recorded 22 anurans species. We performed RLQ and fourth-corner analyses to determine the patterns of trait-environment relationships and determine which environmental and landscape variables influence the morphological characteristics of tadpoles from streams and ponds. C_LIO_LIWe found that the morphological traits of tadpoles are influenced mainly by physicochemical and microhabitat attributes, being distinct between ponds and streams. In ponds, water depth, pH, and the presence of vegetation influence the morphological traits of the tadpoles, while in the streams water pH, temperature, conductivity, total alkalinity, Alk HCO3, and microhabitat variables played a major role in defining the traits. C_LIO_LIOur results indicate that local components of habitat (water characteristics and microhabitat) influence functional traits of tadpoles in both ponds and streams, especially those supposedly related to locomotory, foraging and prey-detection abilities. C_LI

ecology↗

bioRxiv2020

Involvement of uterine natural killer cells in the natural selection of human embryos at implantation.

Decidualizing endometrial stromal cells (EnSC) critically determine the maternal response to an implanting conceptus, triggering either menstruation-like disposal of low-fitness embryos or creating an environment that promotes further development. However, the mechanism that couples maternal recognition of low-quality embryos to tissue breakdown remains poorly understood. Recently, we demonstrated that successful transition of the cycling endometrium to a pregnancy state requires selective elimination of pro-inflammatory senescent decidual cells by activated uterine natural killer (uNK) cells. Here we report that uNK cells express CD44, the canonical hyaluronan (HA) receptor, and demonstrate that high-molecular weight HA (HMWHA) inhibits uNK cell-mediated killing of senescent decidual cells. By contrast, low-molecular weight HA (LMWHA) did not attenuate uNK cell activity in co-culture experiments. Killing of senescent decidual cells by uNK cells was also inhibited upon exposure to medium conditioned by IVF embryos that failed to implant, but not successful embryos. Embryo-mediated inhibition of uNK cell activity was reversed by recombinant hyaluronidase 2 (HYAL2), which hydrolyses HMWHA. We further report a correlation between the levels of HYAL2 secretion by human blastocysts, morphological scores, and implantation potential. Taken together, the data suggest a pivotal role for uNK cells in embryo biosensing and endometrial fate decisions at implantation.

cell biology↗

bioRxiv2019

Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior

Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have a wide variety of negative effects on patients, their families, and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, repeated domination of subordinate social targets is reinforcing. Here, we show that orexin neurons originating from the lateral hypothalamus activate a small population of GABAergic interneurons in the lateral habenula (LHb) via orexin receptor 2 (OxR2) to promote aggression and conditioned place preference (CPP) for aggression-paired contexts. Our study suggests that the orexin system is a potential target for the development of novel therapies aimed at reducing aggressive behaviors and provides the first functional evidence of a local inhibitory circuit within the LHb.

neuroscience↗

bioRxiv2019

A high throughput multi-locus insecticide resistance marker panel for tracking resistance emergence and spread in Anopheles gambiae

The spread of resistance to insecticides in the mosquito vectors of diseases such as malaria and dengue poses a threat to the effectiveness of control programmes, which rely largely on insecticide-based interventions. Monitoring the resistance status of mosquito populations is therefore essential, but obtaining direct phenotypic measurements of resistance is laborious and error-prone. In contrast, high-throughput genotyping offers the prospect of quick and repeatable estimates of resistance, while also allowing the genotypic markers of resistance to be tracked and studied. We developed a panel of 28 known or putative markers of resistance in the major malaria vector Anopheles gambiae, which we use to test the association of these markers with resistance and to study their geographic distribution. We screened resistance-phenotyped An. gambiae from populations from a wide swathe of Sub-Saharan Africa (Burkina Faso, Ghana, Democratic Republic of Congo (DRC) and Kenya), and found evidence of resistance association for four mutations, including a novel mutation in the detoxification gene Gste2 (Gste2-119V). We also identified a gene duplication in Gste2 which combines a resistance-associated mutant form of the gene with its wild-type counterpart, potentially alleviating the costs of resistance. Finally, we describe the distribution of the multiple evolutionary origins of kdr resistance, finding unprecedented levels of diversity in the DRC. This panel represents the first step towards developing a quantitative predictive genotypic model of insecticide resistance that can be used to screen An. gambiae populations and predict resistance status.

evolutionary biology↗

bioRxiv2018

When an insecticide affects the adaptive value of Intraguild predation by an invader

Biological invasions can generate major ecological disturbances, such as changes in species diversity and structure of communities. It is believed that the multicolored Asian ladybeetle, Harmonia axyridis Pallas (Col, Coccinellidae), recognized as one of the most invasive insects in the world, has reduced native coccinellids populations in several areas and is considered as a threat for biodiversity at large. A significant trait, favoring its invasiveness and its dominance over indigenous ladybeetles, is intraguild predation (IGP). IGP has advantageous adaptive value for individuals, removing competitors, potential predators and providing an alternative nutritive resource, when main resources are scarce. Previous research demonstrated that this invasive ladybeetle is highly susceptible to the reduced-risk insecticide novaluron, a chitin synthesis inhibitor, whereas the North American indigenous competitor, Coleomegilla maculata DeGeer (Col, Coccinellidae), is not. Our study explores the adaptive value of IGP for each of the two coccinellids after preying on each others larvae, previously treated with insecticide. Our first hypothesis is that the invasive ladybeetle, susceptible to the insecticide, should lose the adaptive value of IGP, while the native predator not. Our second hypothesis is that the adaptive value of IGP for the invasive predator will be recovered over time, as a result of neutralisation of the insecticide by the intraguild prey (native species). The results support both hypotheses, and show that an insecticide can completely remove the adaptive value of IGP for the invader, while it does not change for the indigenous ladybeetle. Moreover, the study demonstrates that if the intraguild prey (non-susceptible to the insecticide) undergoes molt after being exposed to the insecticide, the adaptive value for the intraguild predator is restored.

ecology↗