Biology subjects

Pandolfi, L.

Publications and source records attributed to Pandolfi, L..

6 recordsLinked to original sources

bioRxiv2025

Palaeoproteomic insights into the deep roots of the cave bear lineage in Europe

Palaeoproteomics has emerged as a powerful tool for reconstructing the evolutionary history of extinct species, particularly when ancient DNA is poorly preserved or beyond recovery. Here, we present the first large-scale enamel proteomic study focused on the cave bear, spanning specimens from the Early to Late Pleistocene. A primary objective was to determine whether the ursid population from level TD4 of Gran Dolina (Sierra de Atapuerca, Spain) belongs to the cave or the brown bear lineage, a long-standing taxonomic debate. We analyzed specimens from the Atapuerca sites, alongside comparative material from other southwestern European localities. Using LC-MS/MS and an acid demineralization protocol without enzymatic digestion, we successfully recovered enamel proteomes from all fossil samples, including the oldest specimens. Protein profiles were obtained for each extinct ursid, enabling the identification of taxonomically informative peptides across multiple individuals per taxon. Notably, two novel single amino acid polymorphisms (SAPs), found in ameloblastin (AMBN) and alpha-1 antitrypsin (SERPINA1), were restricted to Middle and Late Pleistocene cave bears and may represent new phylogenetic markers for this clade. This study provides the first molecular phylogenetic placement of Ursus dolinensis, supporting its basal position within the speloid lineage, consistent with its proposed ancestral status. Our results highlight the strong phylogenetic signal preserved in dental enamel and the exceptional biomolecular preservation at Atapuerca, providing a robust framework for reconstructing the evolutionary history of Ursidae. Moreover, the consistent recovery of systemic proteins, such as serpins, underscores the potential of enamel proteomes to capture not only evolutionary relationships but also physiological signals relevant to extinct ursids. SignificanceThe phylogenetic position of Ursus dolinensis within the Ursidae family has been a subject of long-standing debate. While some authors place it within the speloid lineage, others suggest affinities with arctoid bears. Here, we analyze the bear population from level TD4 of Gran Dolina (Sierra de Atapuerca, Spain) using palaeoproteomic methods for the first time. Molecular evidence supports the inclusion of U. dolinensis within the speloid lineage, in a basal position, supporting its potential ancestral position. These findings extend the evolutionary depth of the speloid clade in Europe and demonstrate the power of enamel palaeoproteomics to resolve deep-time relationships beyond the limits of ancient DNA, revealing the deep evolutionary roots of the lineage.

evolutionary biology↗

bioRxiv2023

Host-derived oxidized phospholipids initiate effector-triggered immunity fostering lethality upon microbial encounter.

Macrophages detect invading microorganisms via pattern recognition receptors that recognize pathogen-associated molecular patterns, or via sensing the activity of virulence factors that initiates effector-triggered immunity (ETI). Tissue damage that follows pathogen encounter leads to the release of host-derived factors that participate to inflammation. How these self-derived molecules are sensed by macrophages and their impact on immunity remain poorly understood. Here we demonstrate that, in mice and humans, host-derived oxidized phospholipids (oxPLs) are formed upon microbial encounter. oxPL blockade restricts inflammation and prevents the death of the host, without affecting pathogen burden. Mechanistically, oxPLs bind and inhibit AKT, a master regulator of immunity and metabolism. AKT inhibition potentiates the methionine cycle, and epigenetically dampens Il10, a pluripotent anti-inflammatory cytokine. Overall, we found that host-derived inflammatory cues act as "self" virulence factors that initiate ETI and that their activity can be targeted to protect the host against excessive inflammation upon microbial encounter.

immunology↗

bioRxiv2022

Reconstructing phylogeny of the hornless rhinoceros Aceratheriinae

This study presents the first phylogenetic analysis focused on the Subfamily Aceratheriinae to date, with 391 characters coded from 43 taxa at the species level. We added 77 newly defined and 33 revised characteristics, including features of the skull, teeth, and postcranial bones. In the present analysis, the tribe Teleoceratini, as well as the tribe Aceratheriini, was reclassified within Aceratheriinae, however, the traditionally established monophyly of each tribe was decomposed. Combined with detailed morphological comparisons, we reconstructed the phylogeny of Aceratheriinae and revised the diagnosis of Aceratheriinae. The reported skull and teeth specimens of Turkanatherium from the late Early Miocene indicate that it is not an acerathere and has been placed as a basal rhinocerotid. The Aceratheriinae has undergone evolutionary adaptation several times during the early stage of evolution, and several genera from the Oligocene to the Early Miocene have been reconstructed as early diverging taxa, such as Molassitherium, Protaceratherium, Plesiaceratherium and Chilotheridium; Aprotodon and Mesaceratherium from the Late Oligocene to the Early Miocene were united as the earliest divergent clade of Aceratheriinae; meanwhile, due to the limited materials, the phylogenies of Floridaceras and Dromoceratherium are unstable in this analysis, and both have been tentatively considered as the early diverging clades of Aceratheriinae. Alicornops was reclassified a member of Teleoceratini. Aceratheriini and Teleoceratini have been redefined as two highly specialized groups. Furthermore, Aceratheriini has been divided into two/three clades based on the difference in the skull outlines and the occlusal patterns of the cheek teeth.

paleontology↗

bioRxiv2021

Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients.

The COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally, with the most severe cases characterized by over-exuberant production of immune-mediators, the nature of which is not fully understood. Interferons of the type I (IFN-I) or type III (IFN-III) families are potent antivirals, but their role in COVID-19 remains debated. Our analysis of gene and protein expression along the respiratory tract shows that IFNs, especially IFN-III, are over-represented in the lower airways of patients with severe COVID-19, while high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity; also, IFN expression varies with abundance of the cell types that produce them. Our data point to a dynamic process of inter- and intra-family production of IFNs in COVID-19, and suggest that IFNs play opposing roles at distinct anatomical sites.

immunology↗

bioRxiv2020

Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis

The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs formation, induce both EMT and cell death in the lung epithelial cell line, A549. Notably, NETs isolated from PMA-Neu induce EMT without cell damage. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1{beta}, best-known inducers of NETosis. Lung tissues of COVID-19 deceased patients showed that epithelial cells are characterized by increased mesenchymal markers. These results show for the first time that NETosis plays a major role in triggering lung fibrosis in COVID-19 patients.

immunology↗

bioRxiv2018

Early Pleistocene enamel proteome sequences from Dmanisi resolve Stephanorhinus phylogeny.

Ancient DNA (aDNA) sequencing has enabled unprecedented reconstruction of speciation, migration, and admixture events for extinct taxa1. Outside the permafrost, however, irreversible aDNA post-mortem degradation2 has so far limited aDNA recovery within the {small tilde}0.5 million years (Ma) time range3. Tandem mass spectrometry (MS)-based collagen type I (COL1) sequencing provides direct access to older biomolecular information4, though with limited phylogenetic use. In the absence of molecular evidence, the speciation of several Early and Middle Pleistocene extinct species remain contentious. In this study, we address the phylogenetic relationships of the Eurasian Pleistocene Rhinocerotidae5-7 using {small tilde}1.77 million years (Ma) old dental enamel proteome sequences of a Stephanorhinus specimen from the Dmanisi archaeological site in Georgia (South Caucasus)8. Molecular phylogenetic analyses place the Dmanisi Stephanorhinus as a sister group to the woolly (Coelodonta antiquitatis) and Mercks rhinoceros (S. kirchbergensis) clade. We show that Coelodonta evolved from an early Stephanorhinus lineage and that this genus includes at least two distinct evolutionary lines. As such, the genus Stephanorhinus is currently paraphyletic and its systematic revision is therefore needed. We demonstrate that Early Pleistocene dental enamel proteome sequencing overcomes the limits of ancient collagen- and aDNA-based phylogenetic inference, and also provides additional information about the sex and taxonomic assignment of the specimens analysed. Dental enamel, the hardest tissue in vertebrates, is highly abundant in the fossil record. Our findings reveal that palaeoproteomic investigation of this material can push biomolecular investigation further back into the Early Pleistocene.

evolutionary biology↗