Biology subjects

Pacifici, M.

Publications and source records attributed to Pacifici, M..

12 recordsLinked to original sources

bioRxiv2026

Global threat abatement potential for terrestrial vertebrates

1.AimThe Species Threat Abatement and Restoration (STAR) metric was developed to support setting and measuring progress towards science-based targets for species conservation, in alignment with the Kunming-Montreal Global Biodiversity Framework. The STAR metric quantifies the potential reduction in species global extinction risk achievable through actions to abate threats (START) and restore habitat (STARR). The STAR metric is used across multiple sectors to assess contributions to nature-positive species outcomes and implement action for biodiversity. Here we present a substantially enhanced global estimate of START for terrestrial vertebrates. Developed in response to user demand, this work integrates advancements in methodology and data quality, increased spatial resolution, and addition of reptile species. LocationGlobal Time PeriodCurrent Major taxa studiedTerrestrial vertebrates MethodsSTART was estimated at 1km2 resolution for 9,100 species of threatened and Near Threatened birds, mammals, amphibians and reptiles, using IUCN Red List assessments (version 2025-1) and area of habitat (AOH) maps generated using an advanced data-driven methodology and satellite-derived land-cover data. AOH maps were validated using a two-stage protocol using species observation data. ResultsThe six countries with the highest estimated START scores, and therefore the largest individual potential to reduce global extinction risk via tackling threats nationally were Brazil, Madagascar, Indonesia, Mexico, Ecuador and Colombia (each contributing over 5% of global estimated START). The threat with the greatest individual potential to reduce extinction risk was annual and perennial non-timber crops (21.2% of global START). Main conclusionsTargeted actions to tackle a few high-impact threats in a few discrete locations, and cumulative effort across multiple areas with lower individual potential, are both required to meaningfully reduce species extinction risk through threat abatement. This global scale estimation of START enables consistent scoping of conservation opportunity over large areas and provides the critical initial data to support planning and action.

zoology↗

bioRxiv2025

A pivotal role for Wnt antagonists in constraining Wnt activity to promote digit joint specification.

Bmps and Wnts play opposing roles in several contexts during chondrogenesis and joint formation. Using genetic and genomic approaches, we found instead that canonical Wnts can cooperate with Bmps to enhance pSmad1/5 activity and initiate chondrogenic commitment in digit tip progenitors. 5Hoxd{Delta}/{Delta} mutant digits are characterized by elevated Bmp and pSmad1/5 activity and subsequent joint loss. We show that expressing stabilized {beta}catenin ({beta}catCA) in interdigit mesenchyme rescues 5Hoxd{Delta}/{Delta} digit joint loss non-autonomously, by inducing secreted Wnt antagonists and normalizing digit tip pSmad1/5 levels. Indeed, genetic removal of Dkk2 in 5Hoxd{Delta}/{Delta} prevented joint rescue by {beta}catCA. Furthermore, elevating Wnt activity with Gsk3{beta} antagonists in limb bud culture stabilized pSmad1/5 levels and enhanced Bmp activity. Elevated pSmad1/5, as seen in 5Hoxd{Delta}/{Delta}, accelerates chondrogenic commitment, impeding a switch of phalanx forming region (PFR) cells in the digit tip to interzone (joint progenitor) fate. We propose that, before progenitors transit into PFR, Wnt antagonists cooperate with Fgfs to prevent precocious pSmad1/5 accumulation by stabilizing Gsk3{beta} to promote Smad-linker phosphorylation and Smad1/5 degradation. Consequently, Wnt antagonists play a key role in modulating the pace of initial commitment of digit progenitors to chondrogenesis, together with Fgfs, and maintain mesenchymal plasticity to balance digit phalanx and joint formation.

developmental biology↗

bioRxiv2025

Improving the classification of wildlife conservation status to support nature protection in the European Union

Ensuring that species of conservation concern achieve favorable conservation status (FCS) is central to European Union (EU) biodiversity conservation targets. A key criterion for FCS is exceeding the favorable reference range (FRR)--the range extent needed for long-term species stability and full ecological variation. However, due to data limitations, FRRs are often unknown, undermining their applicability. We developed a machine-learning approach to estimate and standardize FRRs across the EU. Applied to amphibians, mammals, and reptiles, our method provided FRRs for 99.5% of species of conservation concern, compared to 17.5% previously available (with satisfactory modelling performance: R2 0.75). We reassessed conservation status using the estimated FRRs, finding that species in FCS (34.8%) are notably fewer than reported in official documentation (69.1%). The average proportional distance to FRR for species in unfavorable conservation status is -64.4%. Our approach may support periodic FCS reassessments and help refine the targets of EU conservation policies.

ecology↗

bioRxiv2025

Impacts of oil palm plantations expansion on the distribution of terrestrial mammals in South-East Asia

The recent expansion of oil palm plantations in Southeast Asia has caused significant range loss for many species. We examined the impact of this expansion on mammal distribution in Indonesia, Malaysia, and Thailand. Using historical range maps (1970s-1980s) and satellite imagery of oil palm plantations (1981 to 2017), we quantified the extent of species lost and retained ranges occupied by oil palm plantations before and after 1990. The siamang (+24%), tiger (+19%), and large-spotted civet (+14%) were the most impacted, considering plantations expansion in the lost range. All species, including endemic ones, have also seen an increase in their current range. Additionally, we found a significant correlation between the amount of range lost and the area occupied by plantations after 1990. Our findings underscore the urgent need for sustainable land management and conservation strategies to mitigate the adverse effects of agricultural expansion on biodiversity.

ecology↗

bioRxiv2025

Spatial instability affects Key Biodiversity Areas scoping for bumblebees across three decades

Identifying potential Key Biodiversity Areas (KBAs) using species occurrence records is crucial for integrating hyperdiverse taxa, such as insects, into the KBA network. To ensure the KBA network supports effective conservation decision-making, established KBAs need to be reassessed every 8 to 12 years. Realistically, reassessments for very high numbers of species will be based also on opportunistic occurrence points. However, how changes in species distribution data availability and completeness in different time periods influence the spatial stability of potential KBAs over time has not been investigated in any taxa yet. We performed potential KBA assessments for 28 species and subspecies of bumblebees in Italy using an expert-validated dataset of distribution data collected between 1990 and 2023, using 10-year cumulative and progressive time series. Our findings reveal that KBA scoping for species with distributional knowledge gaps does not ensure stability and reliability over time. Potential KBA turnover percentages between different time periods can be high ([~=]133%). While only seven species/subspecies could trigger potential KBAs, their turnover percentage ranged between 28.5% and 50%. We highlight the need for standardized and strategic monitoring of established KBAs and species distributions between reassessments. We also discuss strategies to optimize monitoring plans under resource constraints.

ecology↗

bioRxiv2024

Neglected predatory insects trigger potential Key Biodiversity Areas in threatened coastal habitats

Key Biodiversity Areas (KBAs) are poised to become a powerful tool for identifying regions that host unique biodiversity. With their great diversity, insects hold significant potential as indicators for global KBA mapping, even in highly specialized and narrowly distributed habitats. For instance, species adapted to fragmented ecosystems like coastal sand dunes--among the most heavily impacted habitats worldwide--can serve as critical indicators to trigger KBAs in these fragile environments. Despite their relevance as indicators, the inclusion of insects in KBA assessments remains limited, especially for neglected insect species such as antlions. We tested selected KBA criteria on 26 antlion and owlfly species (Neuroptera: Myrmeleontidae) in Italy, including dunes specialists, and performed COI based genetic analysis to identify potential weaknesses of the assessment. Several endemic and dune specialist species trigger potential KBAs, showing limited (< 20% of their extent) overlap with the current protected area network, confirming the great value of these taxa in narrowly distributed habitats. Genetic data provides evidence of misidentification for widely distributed species. We advise for the integration of both spatial and genetic data to increase reliability of potential KBA assessments using neglected insect taxa.

ecology↗

bioRxiv2024

Retinoid-impregnated nanoparticles enable control of bone growth by site-specific modulation of endochondral ossification in mice

Growth-plate (GP) injures in limbs and other sites can impair GP function and cause deceleration of bone growth, leading to progressive bone lengthening imbalance, deformities and/or physical discomfort, decreased motion and pain. At present, surgical interventions are the only means available to correct these conditions by suppressing the GP activity in the unaffected limb and/or other bones in the ipsilateral region. Here, we aimed to develop a pharmacologic treatment of GP growth imbalance that involves local application of nanoparticles-based controlled release of a selective retinoic acid nuclear receptor gamma (RAR{gamma}) agonist drug. When RAR{gamma} agonist-loaded nanoparticles were implanted near the medial and lateral sides of proximal tibial growth plate in juvenile C57BL/6j mice, the GP underwent involution and closure. Overall tibia length was shortened compared to the contralateral element implanted with drug-free control nanoparticles. Importantly, when the RAR{gamma} agonist nanoparticles were implanted on the lateral side only, the adjacent epiphysis tilted toward the lateral site, leading to apical angulation of the tibia. In contrast to the local selectivity of these responses, systemic administration of RAR{gamma} agonists led to GP closure at many sites, inhibiting skeletal growth over time. Agonists for RAR and RAR{beta} elicited no obvious responses over parallel regimens. Our findings provide novel evidence that RAR{gamma} agonist-loaded nanoparticles can control activity, function and directionality of a targeted GP, offering a potential and clinically-relevant alternative or supplementation to surgical correction of limb length discrepancy and angular deformities. Lay summaryGrowth-plates (physes), which are cartilage tissues near the ends of bones, support normal bone growth in children. Growth plate injures in limbs and other sites can impair growth plate function, leading to inhibited or imbalanced bone growth, skeletal deformities, decreased motion, discomfort or pain. At present, surgical interventions are the only means available to correct these conditions. Here, we aimed to develop a pharmacologic treatment for bone growth imbalance. Nanoparticles loaded with a selective agonist for the retinoic acid nuclear receptor gamma were prepared and implanted near the tibial growth plate in juvenile mice. The growth plate underwent involution and closure, and overall tibia length was shortened compared to the contralateral element implanted with drug-free control nanoparticles. Importantly, when the same drug nanoparticles were implanted in only one side of the tibia, the tibia was tilted toward the injection site. Our findings provide novel evidence that retinoic acid receptor gamma agonist-loaded nanoparticles can control activity, function and directionality of a targeted growth plate, offering a potential and clinically-relevant alternative or supplementation to surgical correction of limb length imbalances and deformities.

pharmacology and toxicology↗

bioRxiv2023

An automated approach for systematic detection of Key Biodiversity Areas

The new Key Biodiversity Areas (KBA) standard is an important method for identifying regions of the planet hosting unique biodiversity. KBAs are identified through the implementation of threshold-based criteria that can be applied to any target species and region. Efficient methods to rapidly assess the existence of potential KBAs in different areas of the planet are still missing, although they are needed to accelerate the KBA identification process for large numbers of species globally. We developed a methodology to scan geographical regions and detect potential KBAs under multiple criteria. We tested the methodology on 59 species of reptiles and amphibians in Italy through the application of selected KBA criteria. Potential KBAs were identified for multiple species under most criteria, covering 1.4% to 12% of the study area, depending on analytical settings. Unit size used to identify KBAs played an important role in shaping the distribution of potential KBAs, also affecting the degree of overlap between areas triggered by different criteria. New potential KBAs identified in this study are only partially nested within current KBAs in Italy (previously identified for birds) and within the national protected areas.

ecology↗

bioRxiv2022

Activin A promotes bone fracture repair and acts through a novel myofibroblastic cell population in callus

Insufficient bone fracture repair represents a significant clinical burden, and identification of novel therapeutics enhancing repair would have substantial clinical and societal impact. Activin A is a TGF-{beta} protein superfamily member known to stimulate ectopic bone formation, but its roles in fracture repair and its therapeutic potentials remain unclear. Using two mouse tibia fracture repair models, here we mapped activin A expression at the tissue and single cell levels, tested its requirement for normal repair and evaluated its ability to enhance repair when provided exogenously. Activin A was minimally expressed in periosteum of intact bones but was markedly upregulated in developing callus soon after fracture. Single cell RNA-sequencing revealed that the activin A-encoding gene Inhba marked a unique, highly proliferative progenitor cell (PPC) population with a myofibroblast character which emerged over repair time and lay at the center of a developmental trajectory bifurcation producing cartilage and bone cells within callus. Systemic administration of a neutralizing activin A antibody impaired fracture repair and its endochondral and intramembranous phases, whereas local delivery of recombinant activin A enhanced repair. Activin A delivery also induced SMAD2 phosphorylation in vivo and increased the fraction of SMA+ myofibroblasts within fracture callus. Gain- and loss-of-function experiments in vitro showed that activin A directly stimulated myofibroblast differentiation, chondrogenesis and osteogenesis in periosteal progenitor cells. Together, these data identify a unique population of Inhba-expressing proliferative progenitor cells that give rise to chondrocytes and osteoblasts during fracture healing and establish activin A as a potential new therapeutic tool to enhance it. One Sentence SummaryDeficits in bone fracture repair remain a clinical challenge and the present study provides evidence for the therapeutic potentials of activin A

pathology↗

bioRxiv2021

Activation of retinoic acid receptor reduces metastatic prostate cancer bone lesions through blocking endothelial-to-osteoblast transition

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions that contribute to progression and therapy resistance. Currently strategies targeting PCa-induced bone formation are lacking. We previously showed that PCa-induced bone originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition in response to tumor-secreted BMP4. Here, we show that activation of retinoic acid receptor (RAR) inhibits EC-to-OSB transition and reduces PCa-induced bone formation. We found that palovarotene, a RAR{gamma} agonist being tested for heterotopic ossification in fibrodysplasia ossificans progressiva, inhibited EC-to-OSB transition and osteoblast mineralization in vitro, and decreased tumor-induced bone formation and tumor growth in several osteogenic PCa models. RAR/{beta}/{gamma} isoform knockdown in 2H11 ECs blocked EC-to-OSB transition and osteoblast mineralization. Pan-RAR agonist ATRA inhibited MycCaP-BMP4-induced bone formation and tumor growth under castration. Furthermore, palovarotene or ATRA reduced plasma Tenascin C, a factor secreted by EC-OSB cells, which may be used to monitor treatment response. Mechanistically, BMP4-activated pSmad1 forms a complex with RAR in the nucleus of 2H11 cells. RAR activation by palovarotene or ATRA causes pSmad1 degradation by recruiting E3-ubiquitin ligase Smurf1 into the nuclear pSmad1/RAR{gamma} complex. Our findings suggest that palovarotene can be repurposed to target PCa-induced bone formation to improve clinical outcomes for bone metastasis.

cancer biology↗

bioRxiv2021

Primary cilia drive postnatal tidemark patterning in articular cartilage by coordinating responses to Indian Hedgehog and mechanical load

Articular cartilage (AC) is essential for body movement, but is highly susceptible to degenerative diseases and has poor self-repair capacity. To improve current subpar regenerative treatment, developmental mechanisms of AC should be clarified and, specifically, how postnatal multi-zone organization is acquired. Primary cilia are cell surface organelles crucial for mammalian tissue morphogenesis and while the importance of chondrocyte primary cilia is well appreciated their specific roles in postnatal AC morphogenesis remain unclear. To explore these mechanisms, we used a murine conditional loss-of-function approach (Ift88-flox) targeting joint-lineage progenitors (Gdf5Cre) and monitored postnatal knee AC development. Joint formation and growth up to juvenile stages were largely unaffected, however mature AC (aged 2 months) exhibited disorganized extracellular matrix, decreased aggrecan and collagen II due to reduced gene expression (not increased catabolism), and marked reduction of AC modulus by 30-50%. In addition, we discovered the surprising findings that tidemark patterning was severely disrupted and accompanied alterations in hedgehog signaling that were also dependent on regional load-bearing functions of AC. Interestingly, Prg4 expression was also increased in those loaded sites. Together, our data provide evidence that primary cilia orchestrate postnatal AC morphogenesis, dictating tidemark topography, zonal matrix composition and mechanical load responses.

developmental biology↗

bioRxiv2020

Drivers of change in the realised climatic niche of terrestrial mammal species

The breadth of a species climatic niche is an important ecological trait that allows adaptation to climate change, but human activities drive niche erosion. Life-history traits, such as dispersal ability and reproductive speed, instead allow species to cope with climate change. But how do these characteristics act in combination with human pressure to determine niche change? Here we investigate the patterns and drivers of change in the realised climatic niche of 589 terrestrial mammal species. Our goal is to disentangle the impacts of humans, climate change, and life history. We calibrated the past and present climatic niches of each species by considering past climatic conditions (Mid Holocene) within their pre-human impact distributions, and current climatic conditions within the current distributions. Depending on the relationship between past and current niche, we defined four categories of change: "shrink", "shift", "stable", and "expand". We found over half of the species in our sample have undergone niche shrink, while only 15-18% of species retained a stable niche. After controlling for biogeography, climatic factors were the strongest correlates of species niche change, followed by anthropogenic pressure and species life history. Factors that increased the probability of niche shrink include: overall climatic instability in the area (both intermediate or high), large body mass, long gestation time, highly carnivorous or herbivorous diets, historical land-use change, and current human population density. We identified the conditions under which species are less likely to maintain their niche breadth, potentially losing adaptation capacity under climate change. Species with these characteristics require interventions that facilitate natural dispersal or assisted colonisation, to survive to rapidly changing climates.

ecology↗