Biology subjects

Mancini, G.

Publications and source records attributed to Mancini, G..

12 recordsLinked to original sources

bioRxiv2026

Cortical excitability inversely modulates fMRI connectivity via low-frequency neuronal coupling

The neural mechanisms supporting fMRI connectivity are poorly understood. Leveraging an aggregated analysis of novel and existing chemogenetic manipulations and electrophysiological recordings in the mouse medial prefrontal cortex (PFC), we show that local cortical excitability inversely modulates large-scale fMRI connectivity. Specifically, we find that bidirectional chemogenetic manipulations of cortical excitability produce opposite effects on fMRI connectivity, resulting in fMRI hypoconnectivity when excitability is enhanced, and fMRI hyperconnectivity when excitability is suppressed, despite corresponding increases or decreases in local neuronal firing. Notably, while each chemogenetic manipulation produces a distinct profile of interareal electrophysiological coherence, only low-frequency (< 4Hz) coherence predicts the direction and magnitude of the ensuing fMRI connectivity changes. Biophysical network modelling shows that the observed electrophysiological coherence profiles can arise from the interaction between direct inter-area communication changes mediated by local firing-rate variations, and shared larger-scale low-frequency covariation of ongoing neuronal activity. Together, our results reveal an inverse relationship between regional cortical excitability and large-scale fMRI connectivity, and indicate that fMRI connectivity is primarily supported by low frequency (<4 Hz) electrophysiological coupling. These findings open new avenues for modeling and interpreting fMRI connectivity in health, and in response to pathological or exogenous perturbations linked to cortical excitability.

neuroscience↗

bioRxiv2025

How an arthropod-borne virus manages host switches: exploration of host-specific mutations and gene formula in bluetongue virus

Arthropod-borne viruses, also known as arboviruses, cause disease worldwide. These viruses alternate between vertebrates and arthropods, facing distinct selection pressures in each host type. Surprisingly, whether specific mechanisms facilitate host alternation remains unclear. Here, we use bluetongue virus (BTV) as a model to investigate two phenomena potentially facilitating host alternation: adaptive mutations and genome formula variation (GFV). First, we searched for mutations indicative of host adaptation in cattle, sheep, and midges infected during an epizooty. We found a limited number of parallel mutations. This result suggests that adaptive mutations are not a main mechanism facilitating host alternation in BTV. Second, we investigated a link of GFV with a proxy of viral fitness, the speed of virus dissemination in midges. We analyzed the genome formula (GF) in experimentally-infected Culicoides imicola midges, either with an infection disseminated into the head or not. GFs differed between dissemination levels, suggesting a link between GF and the speed of virus dissemination. Finally, we investigated the mechanisms underlying GF generation. Currently, two scenarios have been proposed: random generation followed by selection, or directed generation through molecular mechanisms. To limit the influence of selection, we analyzed the GF after a single replication cycle in cell culture. GF values converged towards specific values among replicates. Moreover, GFs differed between arthropod and vertebrate cells. Thus, GF generation is not purely stochastic and is probably influenced by host-specific mechanisms. Overall, our findings highlight GFV as a potential mechanism facilitating BTV alternation across hosts, but not classical mutation-driven evolution. Author SummaryArthropod-borne viruses are important public health problems in the world. These viruses follow a complex cycle involving alternation between arthropods and vertebrates. Surprisingly, we know little on the mechanisms that facilitate alternation between the two host types. Knowledge on such mechanisms could allow the development of antiviral tools. Here, using Bluetongue virus as a model, we investigated two potential mechanisms facilitating alternation: adaptive mutations and genome formula variation (GFV). We found limited evidence for host-specific mutations in natural populations. We observed a potential link between GFV and viral fitness. Moreover, our results suggest that molecular mechanisms generate GFV in a host-specific way from the first round of cell infection.

microbiology↗

bioRxiv2025

Opportunities and challenges for applying Key BiodiversityAreas Criterion E at large spatial scales

Key Biodiversity Areas (KBAs) are a cornerstone of global biodiversity conservation, influencing international strategic plans and helping protect thousands of species. KBAs are identified through quantitative criteria, among which the most recent is Criterion E. KBA Criterion E uses Spatial Conservation Prioritization techniques to identify highly irreplaceable sites, representing a promising tool for effective expansion of the KBA network. However, it has rarely been tested or applied at large scales. Here, we carried out a continental application of KBA Criterion E in Europe, using Species Distribution Models (SDMs) for 5,529 species of insects and 972 tetrapods. We stress-tested the application of Criterion E by changing the following settings: irreplaceability threshold, metrics of irreplaceability, representation targets, spatial resolution, and cost of planning units. Under the standard Criterion E settings, we identified 23 potential KBAs for insects, mostly along northern European coasts, and 88 for tetrapods, mostly concentrated in Mediterranean islands and southern Europe. These sites slightly overlapped with existing KBAs, showing that Criterion E can capture biodiversity patterns overlooked by other criteria. Our results also showed that the identification of highly irreplaceable areas is very sensitive to analytical choices. The strict irreplaceability threshold currently required, associated with the definition of representation targets, limited the selection of important sites almost exclusively to those containing very narrow-range species, and when such species were absent, important sites were preferentially selected on coasts, where the cost of planning units (represented by land extent) was minimized. Our analysis showed both opportunities and challenges of Criterion E and its applications with SDMs. We propose potential adjustments to the definition and guidelines of Criterion E, to improve its applicability at large spatial scales and on different taxa. Improvements of KBA Criterion E will ensure that KBAs continue to substantially contribute to the global conservation of biodiversity.

zoology↗

bioRxiv2024

Generation length of the world's amphibians and reptiles

Variation in life histories influences demographic processes from adaptive changes to population declines leading to extinction. Among life history traits, generation length offers a critical feature to forecast species demographic trajectories such as population declines (widely used by the IUCN Red List of Threatened Species) and adaptability to environmental change over time. Therefore, estimates of generation length are crucial to monitor demographic stability or future change in highly threatened organisms, particularly ectothermic tetrapods (amphibians and reptiles) - which rank among the most threatened groups - but for which uncertainty in future impacts remains high. Despite its importance, generation length for amphibians and reptiles is largely missing. Here, we aimed to fill-in this gap by modeling generation lengths for amphibians, squamates and testudines as a function of species size, climate, life history, and phylogeny using generalized additive models and phylogenetic generalized least squares. We obtained estimates of generation lengths for 4,543 (52%) amphibians, 8,464 (72%) squamates and 118 (32%) testudines. Our models performed well for most families, for example Bufonidae in amphibians, Lacertidae and Colubridae in squamates and Geoemydidae in testudines, while we found high uncertainty around the prediction of a few families, notably Chamaeleonidae. Species body size and mean temperature were the main predictors of generation length in all groups. Although our estimates are not meant to substitute robust and validated measurements from field studies or natural history museums, they can help reduce existing biases in conservation assessments until field data will be comprehensively available.

zoology↗

bioRxiv2023

Modelling the probability of meeting IUCN Red List criteria to support reassessments.

Comparative extinction risk analysis - which predicts species extinction risk from correlation with traits or geographical characteristics - has gained research attention as a promising tool to support extinction risk assessment in the IUCN Red List of Threatened Species. However, its uptake has been very limited so far, possibly because these models only predict a species Red List category, without indicating which Red List criteria may be triggered by which such approaches cannot easily be used in Red List assessments. We overcome this implementation gap by developing models that predict the probability of species meeting individual Red List criteria. Using data on the worlds birds, we evaluated the predictive performance of our criterion-specific models and compared it with the typical criterion-blind modelling approach. We compiled data on biological traits (e.g., range size, clutch size) and external drivers (e.g., change in canopy cover) often associated with extinction risk. For each specific criterion, we modelled the relationship between extinction risk predictors and species Red List category under that criterion using ordinal regression models. We found criterion-specific models were better at predicting threatened species compared to a criterion-blind model (higher sensitivity), but less good at predicting not threatened species (lower specificity). As expected, different covariates were important for predicting threat status under different criteria, for example change in annual temperature was important to predict criteria related to population trends, while clutch size was important for criteria related to restricted area of occupancy or small population size. Our criteria-specific method can support Red List assessors by producing outputs that identify species likely to meet specific criteria, and which are the most important predictors: these species can be prioritised for re-evaluation. We expect this new approach to increase the uptake of extinction risk models in Red List assessments, bridging a long-standing research-implementation gap.

ecology↗

bioRxiv2023

Testing the predictive performance of comparative extinction risk models to support the global amphibian assessment

Assessing the extinction risk of species through the IUCN Red List is key to guiding conservation policies and reducing biodiversity loss. This process is resource-demanding, however, and requires a continuous update which becomes increasingly difficult as new species are added to the IUCN Red List. The use of automatic methods, such as comparative analyses to predict species extinction risk, can be an efficient alternative to maintaining up to date assessments. Using amphibians as a study group, we predict which species were more likely to change status, in order to suggest species that should be prioritized for reassessment. We used species traits, environmental variables, and proxies of climate and land-use change as predictors of the IUCN Red List category of species. We produced an ensemble prediction of IUCN Red List categories by combining four different model algorithms: Cumulative Link Models (CLM), phylogenetic Generalized Least Squares (PGLS), Random Forests (RF), Neural Networks (NN). By comparing IUCN Red List categories with the ensemble prediction, and accounting for uncertainty among model algorithms, we identified species that should be prioritized for future reassessments due to high prediction versus observation mismatch. We found that CLM and RF performed better than PGLS and NN, but there was not a clear best algorithm. The most important predicting variables across models were species range size, climate change, and landuse change. We propose ensemble modelling of extinction risk as a promising tool for prioritizing species for reassessment while accounting for inherent models uncertainty.

ecology↗

bioRxiv2022

Spatial scale influences taxon conservation in the eukaryotic virome of a mosquito

Our knowledge on the diversity of eukaryotic viruses has recently undergone a massive expansion. This diversity could influence host physiology through yet unknown phenomena of potential interest to the fields of health and food production. However, the assembly processes in eukaryotic viromes of terrestrial animals remain elusive. This situation hinders hypothesis-driven tests of virome influence on host physiology. Here, we explore virome assembly at different spatial scales in the eukaryotic virome of the mosquito Culex pipiens. This mosquito is a vector of human pathogens worldwide. Several new aspects of virome assembly were unveiled through a sampling involving five countries in Africa and Europe and large sample sizes. A group of viruses was conserved in C. pipiens populations in all countries. This core group represented a relatively large and diverse fraction of the virome. However, core viruses were not shared by all host individuals in a given country, and their infection rates fluctuated between countries and years. Moreover, the distribution of co-infections in individual mosquitoes suggested random co-occurrence of certain core viruses. We also observed differences in the virome depending on geography, with viromes tending to cluster depending on the continent. Thus, our results unveil that taxon conservation in a eukaryotic virome changes with spatial scale. Thus, predictions on virome assembly seem possible at a large geographical scale in C. pipiens. IMPORTANCEThe study of the eukaryotic virome of mosquitoes is an emerging research field. Beyond its fundamental interest, this field could lead to the development of control tools against the transmission of mosquito-borne human pathogens. However, we yet know little on the assembly patterns in the eukaryotic viromes of mosquitoes, as well as of terrestrial animals in general. This situation hampers the design of hypothesis-driven studies on the influence of the virome on pathogen transmission. Here, we have analyzed virome assembly in the mosquito vector Culex pipiens within and between countries in Africa and Europe. Our results show that integrating contrasted spatial scales allows to identify deterministic patterns in virome assembly. Such patterns can guide future studies of virome influence on mosquito physiology.

ecology↗

bioRxiv2022

Insulin signaling and extended longevity in ants

In most organisms, the cost of reproduction is a shorter lifespan. However, the reproductive caste in eusocial insect species (queen) exhibits an extraordinarily longer lifespan than non-reproductive castes (workers) despite having a similar genome, thus contradicting the aging dogma. In the absence of the queen, Harpegnathos saltator ants can undergo a caste switch from workers to reproductive pseudo-queens (gamergates). Gamergates exhibit a dramatically prolonged lifespan. When placed in the presence of a reproductive, they revert to worker status and their lifespan is then shortened accordingly. To understand this unique relationship between reproduction and longevity, we analyzed tissue-specific gene expression between castes. Insulin is upregulated in the gamergate brain that leads to oogenesis, but surprisingly correlates with extended longevity. This correlates with increased lipid synthesis and elevated production of vitellogenin in the fat body, which are both transported to the egg. We show that the production of vitellogenin in the fat body is due to the systemic activation of the MAPK branch of the insulin/IGF signaling (IIS)-pathway. In contrast, reduced expression of insulin receptors in the fat body of gamergates and the production in their developing ovary of an anti-insulin (Imp-L2) lead to the downregulation of the AKT/FOXO branch of the IIS-signaling pathway in the fat body, and to the dramatically extended longevity. This reveals a dual-pathway mechanism that reconciles increased longevity in the context of active reproduction in eusocial insects. One Sentence SummaryInsulin-dependent reproduction in ants correlates with extended longevity through insulin inhibition by anti-insulin Imp-L2.

physiology↗

bioRxiv2022

Linking CFTR modulators to opportunistic bacterial infections in cystic fibrosis

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve clinical outcomes with variable efficacy in patients with cystic fibrosis (CF). However, changes produced by bacterial persistence and adaptation in addition to antibiotic regimens could influence CFTR modulator efficacy and vice versa and hence clinical outcomes. We first evaluated the effects of ivacaftor (IVA), lumacaftor (LUM), tezacaftor, elexacaftor and elexacaftor/tezacaftor/ivacaftor (ETI), alone or combined with antibiotics, on sequential Staphylococcus aureus and Pseudomonas aeruginosa CF isolates. IVA and ETI showed the most potent direct antimicrobial activity against S. aureus, while P. aeruginosa was not affected. Additive effects or synergies were observed between the CFTR modulators and antibiotics against both S. aureus and P. aeruginosa, independently of the stage of colonization. IVA and LUM were the most effective in potentiating antibiotic activity against S. aureus, while IVA and ETI enhanced mainly polymyxins activity against P. aeruginosa. Next, we evaluated the effect of P. aeruginosa pneumonia on the pharmacokinetics of IVA in mice. The time-concentration curves of IVA and its metabolites in plasma, lung and epithelial lining fluid were influenced by P. aeruginosa infection. The area under the concentration-time curve showed that airway exposure to IVA was greater in infected than non-infected mice. These results suggest that CFTR modulators can have direct antimicrobial properties and/or enhance antibiotic activity against S. aureus and P. aeruginosa. Furthermore, bacterial infection impacts the IVA concentration and airway exposure, potentially affecting its efficacy. Our findings suggest optimizing host- and pathogen-directed drug regimens to improve efficacy for personalized treatment.

microbiology↗

bioRxiv2021

Early mechanisms of whisker development: Prdm1 and its regulation in whisker development and evolutionary loss

Whiskers (vibrissae) are miniaturized organs that are designed for tactile sensing. Extremely conserved among mammals, they underwent a reduction in primates and disappeared in the human lineage. Furthermore, whiskers are highly innervated and their mechanoceptors signal to the primary somatosensory cortex, where a column of neurons called "barrel" represents each of them. This structure, known as barrel cortex, occupies a large portion of the somatosensory cortex of the rodent brain. Strikingly, Prdm1 conditional knockout mice are one of the rare transgenic strains that do not develop whisker hair follicles while still displaying a pelage (Robertson et al. 2007). Here we show that Prdm1 is expressed early on during whisker development, more precisely in clusters of mesenchymal cells before placode formation. Its conditional knockout leads to the loss of expression of Bmp2, Shh, Bmp4, Krt17, Edar, Gli1 though leaving the {beta}-catenin driven first dermal signal intact. Furthermore, we prove that Prdm1 expressing cells not only act as a signaling center but also as a multipotent progenitor population contributing to the formation of the dermal papilla, dermal sheath and pericytes of the vascular sinuses of vibrissae. We confirm by genetic ablation experiments that the absence of motile vibrissae (macro vibrissae) formation reverberates on the organization of nerve wiring in the mystacial pads and organization of the barrel cortex. We prove that Lef1 acts upstream of Prdm1 and identify a potential enhancer (named Leaf) that might be involved in the evolutionary process that led to the progressive reduction of snout size and vibrissae in primates.

developmental biology↗

bioRxiv2018

Deciphering copper coordination in the animal prion protein amyloidogenic domain

Prions are pathological isoforms of the cellular prion protein (PrPC) responsible for transmissible spongiform encephalopathies (TSE). PrPC interacts with copper through unique octarepeat and non-octarepeat (non-OR) binding sites. Previous works on human PrPC suggest that copper binding to the non-OR region may have a role during prion conversion. The molecular details of copper coordination within the non-OR region are not well characterized. By means of small angle X-ray scattering (SAXS) and extended X-ray absorption fine structure (EXAFS) spectroscopy, we have investigated the Cu(II) structural effects on the protein folding and its coordination geometries when bound to the non-OR region of recombinant PrPC (recPrP) from animal species considered high or less resistant to TSE. As TSE-resistant model, we used ovine PrPC carrying the protective polymorphism at residues A136, R154 and R171 (OvPrP ARR); while as highly TSE-susceptible PrPC models we employed OvPrP with polymorphism V136, R154 and Q171 (OvPrP VRQ) and Bank vole recPrP (BvPrP). Our results reveal that Cu(II) affects the structural plasticity of the non-OR region leading to a more compacted conformation of recPrP. We also identified two Cu(II) coordinations in the non-OR region of these animal species. In type-1 coordination present in OvPrP ARR, Cu(II) is coordinated by four residues (S95, Q98, M109 and H111). Conversely, the type-2 coordination is present in OvPrP VRQ and BvPrP, where Cu(II) is coordinated by three residues (Q98, M109 and H111) and by one water molecule, making the non-OR region more flexible and open to the solvent. These changes in copper coordination in prion resistant and susceptible species provide new insights into the molecular mechanisms governing the resistance or susceptibility of certain species to TSE.

biochemistry↗

bioRxiv2017

Olfactory Receptors Are Required For Social Behavior And Neural Plasticity In Ants, As Evidenced By CRISPR-Mediated Gene Knockout

The chemosensory system is key to establishing and maintaining social structure in eusocial insects. Ants exhibit cooperative colonial behaviors reflective of an advanced form of sociality with an extensive dependency on communication. Cuticular hydrocarbons (CHCs) serve as pheromones and cues that regulate multiple aspects of social interactions and behaviors in ants. The perception of CHCs entails odorant receptor neurons (ORNs) that express specific odorant receptors (ORs) encoded by a dramatically expanded Or gene family in ants. Until recently, studies of the biological functions of ORs in eusocial insects were stymied by the lack of genetic tools. In most eusocial insect species, only one or a few queens in a colony can transmit the genetic information to their progeny. In contrast, any worker in the ant Harpegnathos saltator can be converted into a gamergate (pseudo-queen), and used as a foundress to engender an entire new colony and be crossed for genetic experiments. This feature facilitated CRISPR-Cas9 gene targeting to generate a germline mutation in the orco gene that encodes the obligate co-receptor whose mutation should significantly impact ant olfaction. Our results show that Orco exhibits a conserved role in the perception of general odorants but also a role in reproductive physiology and social behavior plasticity in ants. Surprisingly, and in contrast to other insect systems, the loss of OR functionality also dramatically reduces the development of the ant antennal lobe where ORNs project. Taken together, these findings open the possibility of studying the genetics of eusociality and provide inroads towards understanding the function of the expanded ORs family in eusocial insects in regulating caste determination, social communication and neuronal plasticity.

neuroscience↗