Biology subjects

Marini, G.

Publications and source records attributed to Marini, G..

10 recordsLinked to original sources

bioRxiv2026

Beyond competence: a mechanistic model of avian demographic drivers in West Nile virus dynamics

BackgroundWest Nile virus (WNV) is a vector-borne zoonotic pathogen maintained in an enzootic cycle between birds and mosquitoes which is considered a significant public health concern in Europe, particularly in relation to its recent increase in reported human cases and range expansion. While a comprehensive understanding of the viruss epidemiological dynamics is essential to inform effective prevention and control strategies, to date significant knowledge gaps remain in quantifying interspecific differences within the complex avian communities involved in WNV circulation. Globally, WNV-infection has indeed been documented across more than 300 bird species, however, whether and how inter-specific differences in avian hosts traits affect the spread of WNV is still largely unknown. A substantial body of research has investigated how epidemiological traits, such as the duration of infection and competence, influence WNV dynamics. However, much less is known about the role of avian demography. Methodology/Principal findingsWe therefore investigated through mathematical modelling the role of avian demographic traits in shaping patterns of mosquito WNV infection dynamics in northern Italy (Lombardy Region, 2016-2018). We focused on the effects of annual offspring production, timing and synchrony of breeding which ultimately affect seasonal abundance of competent avian hosts. We highlighted that timing of breeding has the greatest effect on the number of infected mosquitoes, while annual offspring production influences the timing of the infection peak. Our simulations provide evidence that non-corvid species can have a key impact on WNV transmission. Conclusion/SignificanceThese results can support future research by providing priority bird species to direct further studies and by suggesting that the acknowledgment of spatio-temporal variation in the abundance of competent avian hosts plays a key role in the development of effective surveillance strategies and mosquito control actions. Author summaryWest Nile virus (WNV) is endemic in Italy and represents a significant public health threat in Europe, with increasing cases of severe neuroinvasive disease in humans in recent years. Surveillance data reveal marked spatial and temporal variability in infection dynamics, suggesting that key drivers of WNV transmission remain poorly understood. The contribution of different bird species (over 300 are implicated in the WNV cycle) is often overlooked despite evidence that species-specific traits are critical determinants of WNV infection dynamics. Few studies have examined birds demographic traits, despite their well-established importance in shaping infection dynamics across diseases. Given the challenges in collecting detailed wildlife data, we employed mechanistic models to explore transmission scenarios and test whether avian demographic traits influence bird species roles in WNV transmission and maintenance in Lombardy. Our findings demonstrate that brood size, hatching synchrony, and hatching time significantly affect estimated WNV prevalence in mosquitoes.

ecology↗

bioRxiv2025

Association of avian biodiversity and West Nile virus circulation in Culex mosquitoes in Emilia-Romagna, Italy

West Nile Virus (WNV) is a zoonotic arbovirus maintained in a transmission cycle between Culex mosquitoes and birds, occasionally spilling over into humans. The impact of avian biodiversity on WNV circulation remains debated, with studies reporting both negative and positive correlations (dilution and amplification effects respectively) across different settings. In Europe, this relationship remains largely unexplored, particularly in regions with high WNV transmission, such as Emilia-Romagna in Northern Italy. We explored the association between avian biodiversity and WNV circulation in Culex mosquitoes in Emilia-Romagna using 11 consecutive years (2013-2023) of entomological surveillance data paired with two avian data sources. We calculated avian biodiversity indices (Shannons, Simpsons, and Chao2) from observation records from the Farmland Bird Index project and applied linear regression models to assess their relationship with WNV circulation levels. Moreover, we used Bayesian spatiotemporal regression models and gridded weekly avian abundance estimates from the eBird project, to analyse the associations between avian species richness indices and WNV-positivity rates at 68 geolocated mosquito traps across the region. We observed consistent negative associations between WNV circulation in the Culex population and avian biodiversity indices, supporting the dilution effect hypothesis (DEH). We found that non-passerine species richness was negatively associated with WNV mosquito circulation, whereas passerine species richness exhibited a positive association after adjusting for environmental factors and spatial random effects. These findings suggest that passerines may amplify WNV transmission, while the presence of non-passerine species is associated with reductions in WNV circulation. This study provides the first empirical evidence supporting the DEH for WNV in Europe. These findings have important implications for avian surveillance and future WNV modelling studies, and can inform regional, national and European policies on biodiversity conservation and public health planning. Author summaryWest Nile Virus (WNV) is a zoonotic, vector-borne disease maintained in a mosquito-bird-mosquito transmission cycle. The role of avian biodiversity in WNV transmission remains debated, with studies reporting both dilution effects (negative associations) and amplification effects (positive associations) across different settings. Here, we examined the impact of avian biodiversity on WNV circulation in Culex mosquitoes in Emilia-Romagna, Italy, one of Europes WNV hotspots. We analysed 11 years (2013-2023) of entomological surveillance data alongside two ornithological datasets, respectively collected by the Farmland Bird Index project and the citizen science project eBird. These different datasets allowed us to test the dilution effect hypothesis (DEH) at broad and fine spatiotemporal resolutions. Our findings provide support for the DEH for WNV, revealing that higher bird community diversity is associated with reduced WNV circulation. Additionally, we found that non-passerine species richness is linked to lower levels of WNV circulation in the vector, whereas passerine species richness is positively associated with WNV transmission from entomological surveillance. These results point towards the potential amplifying role of passerine species and the protective role of non-passerine species in WNV transmission dynamics, which has important implications for species conservation, public health policy and future modelling studies.

ecology↗

bioRxiv2024

Modeling the spatio-temporal annual changes in human tick-borne encephalitis (TBE) risk in Europe

IntroductionTick-borne encephalitis (TBE), caused by tick-borne encephalitis virus (TBEV), is a zoonotic disease that can cause severe neurological symptoms. Given the increasing number of reported human TBE cases in Europe, a spatio-temporal predictive model to infer the year-to-year probability of human TBE occurrence across Europe at the regional and municipal administrative levels was developed. MethodsThe distribution of human TBE cases at the regional (NUTS-3) level during the period 2017-2022, was derived by using data provided by the European surveillance system (TESSy, ECDC), and at the municipal level by using data from Austria, Finland, Italy, Lithuania, and Slovakia. The probability of presence of human TBE cases at the regional and municipal levels for the period 2017-2024 was modeled with a boosted regression trees model, including covariates that affect both the natural hazard of virus circulation and human exposure to tick bites. ResultsAreas with the highest probability of human TBE infections are primarily located in central-eastern Europe, the Baltic states, and along the coastline of Nordic countries up to the Bothnian Bay. Our results also highlight a statistically significant rising trend in the probability of human TBE infections not only in north-western, but also in south-western European countries, offering a spatio-temporal predictive framework for the assessment of areas where human TBE infection are most likely to occur. The model showed good predictive performance, with a mean AUC of 0.85 (SD = 0.02), sensitivity of 0.82, and specificity of 0.80 at the regional level, and a mean AUC of 0.82 (SD = 0.03), sensitivity of 0.80, and specificity of 0.69 at the municipal level. DiscussionWith ongoing climate and land use changes, the number of human TBE cases is likely to increase and expand into new areas, as trends are already indicating. This underscores the need for predictive models that can help prioritize intervention efforts. The approach adopted, by leveraging lagged covaries, enables timely one-year-ahead predictions, thus supporting surveillance, prevention, and control of human TBE infections by public health authorities. StatementsO_ST_ABSEthical statementC_ST_ABSEthical approval was not needed. Funding statementThis project has received funding from the European Unions Horizon 2020 research and innovation programme under grant agreement No 874850 and is catalogued as MOOD 081. The contents of this publication are the sole responsibility of the authors and dont necessarily reflect the views of the European Commission. Conflict of interestNone. Authors contributionsFrancesca Dagostin: Conceptualization, Methodology, Data Curation, Formal Analysis, Writing - Original Draft. Diana Erazo: Conceptualization, Methodology, Writing - Review & Editing. Giovanni Marini: Conceptualization, Methodology, Writing - Review & Editing. Daniele Da Re: Conceptualization, Methodology, Writing - Review & Editing. Valentina Tagliapietra: Conceptualization, Methodology, Writing - Review & Editing. Maria Avdicova: Resources, Writing - Review & Editing. Tatjana Av[s]i[c] - [Z]upanc: Resources, Writing - Review & Editing. Timothee Dub: Conceptualization, Resources, Writing - Review & Editing. Nahuel Fiorito: Resources, Writing - Review & Editing. Nata[s]a Knap: Resources, Writing - Review & Editing. Celine M. Gossner: Resources, Writing - Review & Editing. Jana Kerlik: Resources, Writing - Review & Editing. Henna Makela: Resources, Writing - Review & Editing. Mateusz Markowicz: Resources,Writing - Review & Editing. Roya Olyazadeh: Resources, Writing - Review & Editing. Lukas Richter: Resources, Writing - Review & Editing. William Wint: Resources, Writing - Review & Editing. Maria Grazia Zuccali: Resources, Writing - Review & Editing. Milda [Z]ygutiene: Resources, Writing - Review & Editing. Simon Dellicour: Methodology, Writing - Review & Editing. Annapaola Rizzoli: Conceptualization, Methodology, Writing - Review & Editing. Data availabilityThe data that support the findings of this study were provided by ECDC, Azienda Provinciale per i Servizi Sanitari Provincia Autonoma di Trento (APSS), Unita Locale Socio Sanitaria Dolomiti (ULSS N.1 Dolomiti), Public Health Authority of the Slovak Republic, Austrian Agency for Health and Food Safety (AGES), Finnish Institute for Health and Welfare (THL), National Public Health Center under the Ministry of Health (Lithuania) and University of Ljubljana. Restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. The interactive risk maps can be explored in detail at https://mood-platform.avia-gis.com. DisclaimerThe views and opinions of the authors expressed herein do not necessarily state or reflect those of ECDC. The accuracy of the authors statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data.

ecology↗

bioRxiv2022

Structural journey of an insecticidal pore-forming protein targeting western corn rootworm

Broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against western corn rootworm larvae and a novel site of action. By integrating X-ray crystallography, cryo-EM, and modelling, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at atomic resolution. We discovered a monomer inhibition mechanism, a molecular "switch" associated with pre-pore activation/oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings provide a mechanistic basis for Mpf2Ba1 effectiveness as an insecticidal protein with potential for biotechnology development. One-Sentence SummaryThe molecular mechanism of an insecticidal protein is revealed through 3D structures of the three main pore formation states

molecular biology↗

bioRxiv2022

Understanding West Nile virus spread: Mathematical modelling to determine the mechanisms with the most influence on infection dynamics.

West Nile disease is a vector-borne disease caused by West Nile virus (WNV), involving mosquitoes as vectors and birds as maintenance hosts. Humans and other mammals can be infected via mosquito bites, developing symptoms ranging from mild fever to severe neurological infection. Due to the worldwide spread of WNV, human infection risk is high in several countries. Nevertheless, there are still several knowledge gaps regarding WNV dynamics. Several aspects of transmission taking place between birds and mosquitoes, such as the length of the infectious period in birds or mosquito biting rates, are still not fully understood, and precise quantitative estimates are still lacking for the European species involved. This lack of knowledge affects the precision of parameter values when modelling the infection, consequently resulting in a potential impairment of the reliability of model simulations and predictions. Further investigations are thus needed to better understand these aspects, but field studies, especially those involving several wild species, such as in the case of WNV, can be challenging. Thus, it becomes crucial to identify which mechanisms most influence the dynamics of WNV transmission. In the present work, we propose a sensitivity analysis to identify the parameters that have the largest impact on the spread of the infection. Based on a mathematical model simulating WNV spread into the Lombardy region (northern Italy), the basic reproduction number of the infection was estimated and used to quantify infection spread into mosquitoes and birds. Then, we quantified how variations in the duration of the infectious period in birds, the mosquito biting rate on birds, and the competence and susceptibility to infection of different bird species might affect WNV transmission. Our study highlights that all considered parameters can affect the spread of WNV, but the duration of the infectious period in birds and mosquito biting rate are the most impactful, highlighting the need for further studies to better estimate these parameters. In addition, our study suggests that a WNV outbreak is very likely to occur in all areas with suitable temperatures, highlighting the wide area where WNV represents a serious risk for public health. Author SummaryInfectious communicable diseases are currently one of the main burdens for human beings and public health. The comprehension of their spread and maintenance is one of the main goals to facilitate their control and eradication, but due to the complexity of their cycles and transmission mechanisms, obtaining this information is often difficult and demanding. The control of vector-borne diseases in particular represents an important and very complex challenge for public health. Mathematical models are suitable tools to investigate disease dynamics and their transmission mechanisms. To build a suitable model that can simulate transmission dynamics, a reliable and precise estimate of parameters for measuring transmission mechanisms is fundamental. We thus propose a sensitivity analysis of four unknown epidemiological parameters (bird recovery rate, mosquito biting rate, avian susceptibility to infection and avian competence to infection) that play a crucial role in driving West Nile virus (WNV) infection to determine which of them have the greatest impact on infection spread. This analysis allows us to identify the investigated parameters that need the most accurate estimate and to further investigate mechanisms that majorly affect WNV spread.

ecology↗

bioRxiv2021

dynamAedes: a unified modelling framework for invasive Aedes mosquitoes

O_LIMosquito species belonging to the genus Aedes have attracted the interest of scientists and public health officers for their invasive species traits and efficient capacity of transmitting viruses affecting humans. Some of these species were brought outside their native range by human activities such as trade and tourism, and colonised new regions thanks to a unique combination of eco-physiological traits. C_LIO_LIConsidering mosquito physiological and behavioural traits to understand and predict the spatial and temporal population dynamics is thus a crucial step to develop strategies to mitigate the local densities of invasive Aedes populations. C_LIO_LIHere, we synthesised the life cycle of four invasive Aedes species (Ae. aegypti, Ae. albopictus, Ae. japonicus and Ae. koreicus) in a single multi-scale stochastic modelling framework which we coded in the R package dynamAedes. We designed a stage-based and time-discrete stochastic model driven by temperature, photo-period and inter-specific larval competition that can be applied to three different spatial scales: punctual, local and regional. These spatial scales consider different degrees of spatial complexity and data availability, by accounting for both active and passive dispersal of mosquito species as well as for the heterogeneity of the input temperature data. C_LIO_LIOur overarching aim was to provide a flexible, open-source and user-friendly tool rooted in the most updated knowledge on species biology which could be applied to the management of invasive Aedes populations as well as for more theoretical ecological inquiries. C_LI

ecology↗

bioRxiv2021

Aedes koreicus, a vector on the rise: pan-European genetic patterns, mitochondrial and draft genome sequencing

BackgroundThe mosquito Aedes koreicus (Edwards, 1917) is a recent invader on the European continent that was introduced to several new places since its first detection in 2008. Compared to other exotic Aedes mosquitoes with public health significance that invaded Europe during the last decades, this species biology, behavior, and dispersal patterns were poorly investigated to date. Methodology/Principal FindingsTo understand the species population relationships and dispersal patterns within Europe, a fragment of the COI gene was sequenced from 130 mosquitoes, collected from five countries where the species has been introduced and/or established. Oxford Nanopore and Illumina sequencing techniques were combined to generate the first complete nuclear and mitochondrial genomic sequences of Ae. koreicus from the European region. The complete genome of Ae. koreicus is 879 Mb. COI haplotype analyses identified five major groups (altogether 31 different haplotypes) and revealed a large-scale dispersal pattern between European Ae. koreicus populations. Continuous admixture of populations from Belgium, Italy, and Hungary was highlighted, additionally, haplotype diversity and clustering clearly indicate a separation of German sequences from other populations, pointing to an independent introduction of Ae. koreicus to Europe. Finally, a genetic expansion signal was identified, suggesting the species might be present in more locations than currently detected. Conclusions/SignificanceOur results highlight the importance of genetic research of invasive mosquitoes to understand general dispersal patterns, reveal main dispersal routes and form the baseline of future mitigation actions. The first complete genomic sequence also provides a significant leap in the general understanding of this species, opening the possibility for future genome-related studies, such as the detection of Single Nucleotide Polymorphism markers. Considering its public health importance, it is crucial to further investigate the species population genetic dynamic, including a larger sampling and additional genomic markers. Author SummaryIn the present context of globalization and changing environment, the rapid spread of Invasive Mosquito Species (IMS) across Europe represents a serious public health threat because some species are competent vectors for several pathogens. A better knowledge of the IMS population relationships, demographic trends, and dispersal patterns can help the relevant authorities mitigating further spread. Aedes koreicus is an IMS that invaded the continent and has been expanding its geographic range over the last decade. In the present study, one of the most popular DNA marker (COI) was used to investigate the pan-European haplotype diversity and phylogenetic relatedness within and between Ae. koreicus populations. Also, the first complete mitochondrial genome and draft nuclear genome of Ae. koreicus were generated using combined high-throughput sequencing techniques (Oxford Nanopore, Illumina). This provides a significant leap in the general understanding of this species and opens the possibility for future genomic studies.

genetics↗

bioRxiv2021

A Focused Small-Molecule Screen Identifies PHA-680626 as an Amphosteric Inhibitor Disrupting the Interaction between Aurora-A and N-Myc

Neuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcriptional factor, is an essential marker correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), also frequently overexpressed in cancer, prevents N-Myc degradation, by directly binding to a highly conserved N-Myc region, i.e. Myc Box I. As a result, elevated levels of N-Myc, which are required for the growth of MYCN amplified cells, are observed. During the last years, it has been demonstrated that the ATP competitive inhibitors of AURKA CD532, MLN8054 and Alisertib also cause essential conformational changes in the structure of the activation loop of the kinase that prevent N-Myc binding, thus impairing the formation of the AURKA/N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complex with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Myc in vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were investigated. Our results, identifying PHA-680626 as an amphosteric inhibitor both in vitro and MYCN overexpressing cell lines, expand the repertoire of known conformational disrupting inhibitors of the AURKA/N-Myc complex, and confirm that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.

cancer biology↗

bioRxiv2018

Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells

Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. The mechanism by which starved cells regulate the process of protein synthesis is largely unknown. Here, we report that the essential translation initiation factor eIF2B forms filaments in starved budding yeast cells. We demonstrate that filamentation is triggered by starvation-induced acidification of the cytosol, which is caused by an influx of protons from the extracellular environment. We show that filament assembly by eIF2B is necessary for rapid and efficient downregulation of translation. Importantly, this mechanism does not require the kinase Gcn2. Furthermore, analysis of site-specific variants of eIF2B suggests that eIF2B assembly results in enzymatically inactive filaments that promote stress survival and fast recovery of cells from starvation. We propose that translation regulation through protein assembly is a widespread mechanism that allows cells to adapt to fluctuating environments.

cell biology↗

bioRxiv2018

Adaptive reorganization of the cytoplasm upon stress in budding yeast

Yeast cells, when exposed to stress, can enter a protective state in which cell division, growth and metabolism are downregulated. They remain viable in this state until nutrients become available again. How cells enter this protective survival state and what happens at a cellular and subcellular level is largely unknown. In this study, we used electron tomography to investigate the stress-induced ultrastructural changes in the cytoplasm of yeast cells. After ATP depletion, we observed a significant cytosolic compaction and an extensive cytoplasmic reorganization, as well as the emergence of distinct membrane-bound and membrane-less organelles. By using correlative light and electron microscopy (CLEM), we further demonstrate that one of these membrane-less organelles is generated by the reversible polymerization into large bundles of filaments of the eukaryotic translation initiation factor 2B (eIF2B), an essential enzyme in the initiation of protein synthesis. The changes we observe are part of a stress-induced survival strategy, allowing yeast cells to save energy, protect proteins from degradation, and inhibit protein functionality by forming assemblies of said proteins.

cell biology↗