Search bioRxiv⌕ Search

Biology subjects

Eritja, R.

Publications and source records attributed to Eritja, R..

6 recordsLinked to original sources

Integrating citizen science and field sampling into next-generation early warning systems for vector surveillance: Twenty years of municipal detections of Aedes invasive mos-quito species in Spain

The spread of invasive mosquitoes Aedes albopictus, Aedes aegypti and Aedes japonicus in Spain represents an increasing public health risk due to their capacity to transmit arboviruses such as dengue, Zika and chikungunya among others. Traditional field entomological surveillance remains essential for tracking their spread, but it faces limitations in terms of cost, scalability and labor intensity. Since 2014, the Mosquito Alert citizen science project has enabled public participation in the surveillance through the submission of geolocated images via a mobile app, which are identified using AI in combination to expert validation. While field surveillance provides high accuracy, citizen science offers low-cost, large-scale real-time data collection aligned to open data managment principles. It is particularly useful for detecting long-distance dispersal events and has contributed up to one-third of the municipal detections of invasive mosquito species since 2014. This study assesses the value of integrating both surveillance systems to capitalize on their complementary strengths while compensating weaknesses in the areas of taxonomic accuracy, scalability, spatial detection patterns, data curation and validation systems, geographic precision, interoperability and real-time output. We present the listing of municipal detections of these species from 2004 to 2024, integrating data from both sources. Spains integrated approach demonstrates a pioneering model for cost-effective, scalable vector surveillance tailored to the dynamics of invasive species and emerging epidemiological threats. Simple SummarySpain, with its diverse ecological and climatic landscapes, represents a key area for the introduction and establishment of invasive mosquito species, posing threats to public health due to their capacity to transmit human diseases. Field entomological surveillance conducted by experts remains the primary tool for tracking their spread, though it is limited by geographical scales and cost factors. Advances in smartphone technology allows citizen science strategies of data collection such as submitting mosquito photos via the Mosquito Alert app. This type of information is of a different nature from the field sampling and still needs expert interpretation, but offers significantly broader and faster geographical coverage. Two decades have passed since the first detection of the Asian tiger mosquito in Spain in 2004, and following the Mosquito Alert creation in 2014, citizen science has contributed with one-third of the discoveries of this species at the municipal level in Spain. We discuss integration of both approaches in order to harness their respective strengths while compensating their drawbacks, to develop faster and more powerful early warning surveillance systems, and also returning value to the society by empowering citizenship.

ecology↗

Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for Myotonic Dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by CTG repeat expansions in DMPK. Mutant transcripts containing expanded CUG repeats form ribonuclear foci that sequester muscleblind-like splicing regulator (MBNL) proteins, key regulators of RNA splicing and metabolism. This functional depletion leads to widespread mis-splicing and persistence of fetal transcript profiles, which underlie muscle weakness, myotonia, and muscle atrophy. In addition, miR-23b is upregulated in DM1 muscle and further represses MBNL1 translation, amplifying molecular defects. We developed chemically optimized miRNA-targeting antisense oligonucleotides (antimiRs) to inhibit miR-23b and restore functional MBNL1 levels. Using a multi-step screening process, we evaluated antimiRs with varying sequences, lengths, chemical modifications, and lipid conjugations. A key optimization was a 3-oleic acid conjugation combined with specific chemical modifications, which enhanced muscle uptake and efficacy. Lead candidates showed strong activity in preclinical models (HSALR and DMSXL mice, and human myoblasts), increasing MBNL1 levels, correcting mis-splicing, improving muscle strength, and reducing myotonia. They also exhibited efficient biodistribution to skeletal muscle, a critical DM1-affected tissue. In vitro toxicology indicated a favorable safety profile with minimal immune or renal toxicity. The antimiR mechanism was conserved in rat and pig fibroblasts. Overall, two lead antimiRs emerged as promising therapeutic candidates for DM1, with improved pharmacokinetics, tissue targeting, and safety, supporting the potential of microRNA-based approaches to correct key molecular defects in this disorder.

genetics↗

Targeted Tumor Microenvironment Delivery of Floxuridine Prodrug via Soluble Silica Nanoparticles in Malignant Melanoma as a Model for Aggressive Cancer Treatment

Malignant melanoma presents a significant challenge in oncology due to its aggressive nature and high metastatic potential. Conventional systemic treatments often fail to effectively reach tumor sites, limiting their therapeutic impact. This study introduces a groundbreaking triple-strategy approach for treating malignant melanoma. We developed a novel prodrug, an oligonucleotide, comprising 10 units of Floxuridine (5-fluoro-2-deoxyuridine) (FdU) nucleoside antimetabolites, to enhance half-life and reduce rapid metabolism. Encapsulated in soluble colloidal silica nanoparticles, this compound is protected and directed towards tumor neovasculature precursor endothelial cell receptors, ensuring local delivery. The strategy focuses on releasing the prodrug in the tumor microenvironment, aiming to eradicate both melanoma cells and their supportive structures. Efficacy was demonstrated in cell culture studies and preclinical models of malignant melanoma, showing a remarkable 50% reduction in tumor size after just three intravenous treatments. These findings underscore the transformative potential of targeting endothelial cell membrane proteins for drug delivery. Our study paves the way for innovative targeted therapies, promising significant advancements in treatment strategies and improved outcomes for patients with metastatic cancers. Key PointsO_LITriple-strategy for treating melanoma: FdU10 prodrug, silica nanoparticle and targeted delivery. C_LIO_LIOligonucleotide prodrug (Floxuridine units) enhances half-life and reduces metabolism. C_LIO_LISoluble silica nanoparticles protect therapeutic FdU10 from nucleases and decorated with protein ligands are directed to tumor neovasculature endothelial cells. C_LIO_LISignificant 50% tumor reduction in preclinical melanoma models after systemic administration with targeted therapies. C_LI

bioengineering↗

Present and future suitability of invasive and urban vectors through an environmentally-driven Mosquito Reproduction Number

1Temperature and water availability significantly influence mosquito population dynamics. Weve devised a method, integrating experimental data with insights from mosquito and thermal biology, to calculate the basic reproduction number (RM) for urban mosquito species, Aedes albopictus and Aedes aegypti. RM represents the number of female mosquitoes produced by one female during her lifespan, indicating suitability for growth. Environmental conditions, including temperature, rainfall and human density influence RM by altering key mosquito life cycle traits. Validation using data from Spain and Europe confirms the approachs reliability. Our analysis suggests that temperature increases may not uniformly benefit Ae. albopictus proliferation but could boost Ae. aegypti expansion. We suggest using vector RM maps, leveraging climate and environmental data, to predict areas susceptible to invasive mosquito population growth. These maps aid in resource allocation for intervention strategies, supporting effective vector surveillance and management efforts.

ecology↗

Systematic study of hybrid triplex topology and stability suggests a general triplex-mediated regulatory mechanism

By combining in-silico, biophysical and in-cellulo experiments, we decipher the topology, physical and potential biological properties of hybrid-parallel nucleic acids triplexes; an elusive structure at the basis of life. We found that hybrid triplex topology follows a stability order: r(Py)-d(Pu){middle dot}r(Py)> r(Py)-d(Pu){middle dot}d(Py)> d(Py)-d(Pu){middle dot}d(Py)> d(Py)-d(Pu){middle dot}r(Py). The r(Py)-d(Pu){middle dot}d(Py) triplex is expected to be the preferred in the cell as it avoids the need to open the duplex reducing the torsional stress required for triplex formation in the r(Py)-d(Pu){middle dot}r(Py) topology. Upon a massive collection of melting data, we have created the first predictor for hybrid triplex stability. Leveraging this predictor, we conducted a comprehensive scan to assess the likelihood of the human genome and transcriptome to engage in triplex formation. Our findings unveil a remarkable inclination - of both the human genome and transcriptome - to generate hybrid triplex formation, particularly within untranslated (UTRs) and regulatory regions, thereby corroborating the existence of a triplex-mediated regulatory mechanism. Furthermore, we found a correlation between nucleosome linkers and TFS which agree with a putative role of triplexes in arranging chromatin structure and local/global level.

molecular biology↗

Multiple invasions, Wolbachia and human-aided transport drive the genetic variability of Aedes albopictus in the Iberian Peninsula

The Asian tiger mosquito, Aedes albopictus, is a highly invasive species that has been spreading rapidly throughout tropical and temperate regions worldwide since the late 1970s. On the Iberian Peninsula, it was first recorded in 2004 near Barcelona. Since then, the species has spread along the Mediterranean coast and is now colonising the Peninsulas inner territories. As with other species of the genus Aedes, the spread of the tiger mosquito has been linked to global shipping routes and road networks. In particular, the transport of adult mosquitoes by car has been shown to augment its natural spreading capacity by orders of magnitude. Much remains unknown, however, about the impact of human-mediated dispersal on the genetic variability of this species. This study aimed to ascertain the factors that have contributed to the spread and the current genetic variation of Ae. albopictus across the Iberian Peninsula, through complex dispersal mechanisms and endosymbiosis with bacteria like Wolbachia. We do so through population genetic analysis of mitochondrial (COI) and nuclear (ITS2) DNA sequences. Overall, both COI and ITS2 markers showed a lack of genetic structure among sampled regions and the presence of worldwide dominant haplotypes, suggesting a pattern of multiple introductions from abroad. We found extremely low levels of variation in COI compared to ITS2, and this lack of mitochondrial polymorphism is likely explained by high Wolbachia prevalence (79%). Multilevel models revealed that greater mosquito fluxes (estimated from commuting patterns and tiger mosquito population distribution) and spatial proximity between sampling sites were associated with lower ITS2 genetic distance, suggesting that rapid short- and medium-distance dispersal is facilitated by humans through vehicular traffic. This study highlights the significant role of human transportation in shaping the genetic attributes of Ae. albopictus and promoting regional gene flow, and underscores the need for a territorially integrated surveillance across scales of this disease-carrying mosquito. Author SummaryThe tiger mosquito, Aedes albopictus, is one of the most invasive species in the world. Native to the tropical forests of Southeast Asia, over the past 30 years it has rapidly spread throughout tropical and temperate regions of the world. Its dramatic expansion has resulted in public health concerns as a consequence of its vector competence for at least 16 viruses. Previous studies showed that Ae. albopictus spread has been facilitated by human-mediated transportation, but much remains unknown about how this has affected its genetic attributes. Here we examined the factors that contributed to shaping the current genetic constitution of Ae. albopictus in the Iberian Peninsula, where the species was first found in 2004, by combining population genetics and Bayesian modelling. We found that both mitochondrial and nuclear DNA markers showed a lack of genetic structure and the presence of worldwide dominant haplotypes, suggesting regular introductions from abroad. Mitochondrial DNA showed little genetic diversity compared to nuclear DNA, likely explained by infection with maternally transmitted bacteria of the genus Wolbachia. Our models indicated that human transportation plays a role in shaping Ae. albopictus nuclear genetic structure by means of passive dispersal of adult tiger mosquitoes through the road network.

genetics↗