Biology subjects

Cilli, E.

Publications and source records attributed to Cilli, E..

8 recordsLinked to original sources

bioRxiv2025

SARS-CoV-2 Spike Peptides Trigger Nociceptive Responses Through Spinal TLR4 Pathways

COVID-19 has affected over 700 million people worldwide, with a significant portion of the population experiencing severe pulmonary and circulatory complications, often accompanied by symptoms such as prostration and pain. Moreover, the manifestation of these symptoms and other COVID-19-related complications varies depending on viral mutations, particularly those occurring in the spike (S) protein of SARS-CoV-2. Therefore, the present study aimed to investigate the effects of three different S proteins on nociceptive threshold, as well as the spinal involvement of TLR4 and microglia in this process. Male C57BL/6 mice received intrathecal administration of three synthetic peptides (PSPD2001, PSPD2002 and PSPD2003) derived from the SARS-CoV-2 S protein or saline. Nociceptive threshold was assessed using the von Frey filament test before and after peptide administration. The spinal involvement of Toll-like receptor 4 (TLR4), microglia, p38 MAPK, and NF-{kappa}B was evaluated using specific antagonists and inhibitors. mRNA expression of TLR4 was assessed by RT-PCR, pro-inflammatory cytokine levels by ELISA, and microglial activation in the dorsal horn of the spinal cord was analyzed by immunofluorescence in wild-type, CX3CR1GFP{square}/{square}, and TLR4{square}/{square} mice. In addition, molecular dynamics analysis was performed to assess the temporal stability of the PSPD2003-TLR4 complex. Pharmacological data demonstrated that the peptides induced nociception involving TLR4, microglia, p38 MAPK, and NF-{kappa}B. Notably, PSPD2003 increased TLR4 mRNA expression and elevated TNF- and IL-6 levels in the spinal cord. PSPD2003 also enhanced microglial activation in the spinal cord, which was abolished in TLR4{square}/{square} mice. Molecular dynamics analysis results robustly demonstrate that PSPD2003 forms a stable and functionally relevant complex with TLR4. These findings suggest that SARS-CoV-2 S protein-derived peptides contribute to pain during COVID-19 infection, with spinal TLR4 and microglia playing key roles in this process.

pharmacology and toxicology↗

bioRxiv2025

Ecology and demographic structure of an extinct ibex population in Upper Palaeolithic Italian Alps

Alpine Upper Palaeolithic contexts exhibit specialised subsistence strategies, heavily dependent on Capra ibex. Among them, the rock shelter Riparo Dalmeri stands out, with C. Ibex dominating faunal remains across all occupation phases, spanning the Pleistocene/Holocene transition. This evidence positions Riparo Dalmeri as a key site for exploring the interdependence between human groups and C. ibex during one of the most critical climatic and cultural shifts in human evolution. Here, we present the first multidisciplinary study on Late Palaeolithic C. ibex teeth from Riparo Dalmeri, integrating direct radiocarbon dating, isotope (87Sr/86Sr, {delta}13C, {delta}18O), proteomic, and aDNA analyses. We generated the earliest aDNA sequences for C. ibex and contextual evidence on mobility, seasonality, and sex ratios. We found that most C. ibex were local to the area despite consistent human presence. They reveal significant dietary differences between sexes as well as increased seasonality at the Pleistocene-Holocene transition. Our results identify Riparo Dalmeri as an extinct branch of the ibex mtDNA phylogeny, offering unprecedented insights into ibex ecology and evolution that resonate with present-day issues on the conservation of this species in the face of climate change.

ecology↗

bioRxiv2024

Ancient DNA reveals historical demographic decline and genetic erosion in the Atlantic bluefin tuna

Overexploitation has depleted fish stocks during the past century, nonetheless its genomic consequences remain poorly understood. Characterising the spatiotemporal patterns of these consequences may provide baseline estimates of past diversity and productivity to aid management targets, help predict future dynamics, and facilitate the identification of evolutionary factors limiting fish population recovery. Here, we evaluate human impacts on the evolution of the iconic Atlantic bluefin tuna (Thunnus thynnus), one of the longest and most intensely exploited marine fishes, with a tremendous cultural and economic importance. We sequenced whole genomes from modern (n=49) and ancient (n=41) specimens dating up to 5000 years ago, uncovering several novel findings. First, we identify temporally stable patterns of population admixture, as bluefin tuna caught off Norway and in the eastern Mediterranean share a greater degree of ancestry with Gulf of Mexico bluefin tuna than western and central Mediterranean bluefin tuna. This suggests that Atlantic spawning areas are important mixing grounds for the genetic diversity of Mediterranean bluefin tuna. We model effective population size to show that Mediterranean bluefin tuna began to undergo a demographic decline by the year 1900 to an extent not observed across the previous millennia. Coinciding with this, we found that heterozygosity and nucleotide diversity was significantly lower in modern (2013-2020), than ancient (pre-1941) Mediterranean bluefin tuna, suggesting bluefin tuna underwent a genetic bottleneck. With this work we show how ancient DNA provides novel perspectives on ecological complexity with the potential to inform the management and conservation of fishes. SignificanceAchieving the aim of the current UN Ocean Decade to "protect and restore ecosystems and biodiversity" is stymied by a lack of historical knowledge on how human exploitation has impacted and therefore what should be restored. Here, we sequence DNA in ancient fish bones to evaluate the historical diversity of the Atlantic bluefin tuna; which has been of great commercial importance for centuries. We find that bluefin tuna began to undergo demographic decline by 1900, 70 years earlier than currently recognised. Correspondingly, we find modern bluefin tuna had lower levels of genetic diversity than historical ones. This suggests that human impacts on the diversity of marine fishes are likely to have begun earlier and be more complex than previously thought.

ecology↗

bioRxiv2024

Five millennia of mitochondrial introgression in Atlantic bluefin tuna identified using ancient DNA

Mitogenomic (MT) introgression between species is readily documented in marine fishes. Such introgression events may either be long-term natural phenomena or the result of human-driven shifts in spatial distributions of previously separated species. Determining the drivers behind MT introgression is stymied by the difficulty of directly observing patterns of interbreeding over long timescales. Using ancient DNA spanning five millennia, we here investigate the long-term presence of MT introgression from Pacific bluefin tuna (Thunnus orientalis) and albacore (Thunnus alalunga) into Atlantic bluefin tuna (Thunnus thynnus), a species with extensive exploitation history and observed shifts in abundance, and demographic distribution. Comparing ancient (n=130) and modern (n=78) mitogenomes of specimens covering most of the range of Atlantic bluefin tuna we detect no significant spatial or temporal population structure. This lack of spatiotemporal genomic differentiation is indicative of ongoing gene flow between populations and large effective population sizes over millennia. Moreover, we identify introgressed MT genomes in ancient specimens up to 5000 years old and find that this rate of introgression has remained similar through time. We therefore conclude that MT introgression in the Atlantic bluefin tuna is to date unaffected by anthropogenic impacts. By providing the oldest example of directly observed MT introgression in the marine environment, our results highlight the utility of ancient DNA to obtain temporal insights in the long-term persistence of such phenomena.

evolutionary biology↗

bioRxiv2024

The Genomic portrait of the Picene culture: new insights into the Italic Iron Age and the legacy of the Roman expansion in Central Italy.

BackgroundThe Italic Iron Age was characterized by the presence of various ethnic groups partially examined from a genomic perspective. To explore the evolution of Iron Age Italic populations and the genetic impact of Romanization, we focused on the Picenes, one of the most fascinating pre-Roman civilizations, who flourished on the Middle Adriatic side of Central Italy between the 9th and the 3rd century BCE, until the Roman colonization. ResultsWe analyzed more than 50 samples, spanning more than 1,000 years of history from the Iron Age to Late Antiquity. Despite cultural diversity, our analysis reveals no major differences between the Picenes and other coeval populations, suggesting a shared genetic history of the Central Italian Iron Age ethnic groups. Nevertheless, a slight genetic differentiation between populations along the Adriatic and Tyrrhenian coasts can be observed, possibly due to genetic contacts between populations residing on the Italian and Balkan shores of the Adriatic Sea. Additionally, we found several individuals with ancestries deviating from their general population. Lastly, In the Late Antiquity period, the genetic landscape of the Middle Adriatic region drastically changed, indicating a relevant influx from the Near East. ConclusionsOur findings, consistently with archeological hypotheses, suggest genetic interactions across the Adriatic Sea during the Bronze/Iron Age and a high level of individual mobility typical of cosmopolitan societies. Finally, we highlighted the role of the Roman Empire in shaping genetic and phenotypic changes that greatly impacted the Italian peninsula.

genomics↗

bioRxiv2022

Genomes of the extinct Sicilian wolf reveal a complex history of isolation and admixture with ancient dogs

The Sicilian wolf represented the only population of wolves living on a Mediterranean island until the first half of the twentieth century (1930s-1960s) 1-7. Previous studies hypothesised that they remained isolated from mainland wolves from the end of the Last Glacial Maximum (LGM) 8,9, until human persecutions led them to extinction 1-7. There are only seven known Sicilian wolf specimens from the 19th and 20th century preserved in museums in Italy and recent morphometric analyses assigned them to the new subspecies Canis lupus cristaldii 10. To better understand the origins of the Sicilian wolf, and its relationship to other wolf populations, we sequenced four whole genomes (3.8x-11.6x) and five mitogenomes. We investigated the relationship between Sicilian wolves and other modern breeds to identify potential admixture. Furthermore, considering that the last land-bridge between Sicily and Italy disappeared after the LGM 11, around 17 kya, we explored the possibility that the Sicilian wolf retained ancestry from ancient wolf and dog lineages. Additionally, we explored whether the long-term isolation might have affected the genomic diversity, inbreeding levels and genetic load of the Sicilian wolf. Our findings show that the Sicilian wolves shared most ancestry with the modern Italian wolf population but are better modelled as admixed with European dog breeds, and shared traces of Eneolithic and Bronze age European dogs. We also find signatures of severe inbreeding and low genomic diversity at population and individual levels due to long-term isolation and drift, suggesting also low effective population size.

genomics↗

bioRxiv2021

An insight into neurotoxic and toxicity of spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health?

The Spike protein (S protein) is a critical component in the infection of the new coronavirus (SARS-CoV-2). The objective of this work was to evaluate whether peptides from S protein could cause negative impact in the aquatic animals. The aquatic toxicity of SARS-CoV-2 spike protein peptides derivatives has been evaluated in tadpoles (n = 50 tadpoles / 5 replicates of 10 animals) from species Physalaemus cuvieri (Leptodactylidae). After synthesis, purification, and characterization of peptides (PSDP2001, PSDP2002, PSDP2003) an aquatic contamination has been simulatedwith these peptides during 24 hours of exposure in two concentrations (100 and 500 ng/mL). The control group ("C") was composed of tadpoles kept in polyethylene containers containing de-chlorinated water. Oxidative stress, antioxidant biomarkers and neurotoxicity activity were assessed. In both concentrations, PSPD2002 and PSPD2003 increased catalase and superoxide dismutase antioxidants enzymes activities, as well as oxidative stress (nitrite levels, hydrogen peroxide and reactive oxygen species). All three peptides also increased acetylcholinesterase activity in the highest concentration. These peptides showed molecular interactions in silico with acetylcholinesterase and antioxidant enzymes. Aquatic particle contamination of SARS-CoV-2 has neurotoxics effects in P. cuvieri tadpoles. These findings indicate that the COVID-19 can constitute environmental impact or biological damage potential. HIGHLIGHTSO_LISARS-CoV-2 spike protein peptides (PSDP) were synthesized, purified, and characterized by solid phase peptide synthesis. C_LIO_LIPSDP peptides promoted REDOX imbalance and acute neurotoxicity in tadpoles (Physalaemus cuvieri) C_LIO_LIIn silico studies have shown interactionsbetween peptides and acetylcholinesterase and antioxidant enzymes C_LIO_LIAquatic particle contamination of SARS-CoV-2 can constitute additional environmental damage C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/425914v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1b86f96org.highwire.dtl.DTLVardef@1a6225corg.highwire.dtl.DTLVardef@19d953org.highwire.dtl.DTLVardef@10af7ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2018

The Sicilian wolf: genetic identity of a recently extinct insular population

During historical times many local grey wolf (Canis lupus) populations underwent a substantial reduction of their sizes or became extinct. Among these, the wolf population once living in Sicily, the biggest island of the Mediterranean Sea, was completely eradicated by human persecution in the early decades of the XX century.\n\nIn order to understand the genetic identity of the Sicilian wolf, we applied ancient DNA techniques to analyse the mitochondrial DNA of six specimens actually stored in Italian museums.\n\nWe successfully amplified a diagnostic mtDNA fragment of the control region (CR) in four of the samples. Results showed that two samples shared the same haplotype, that differed by two substitutions from the currently most diffused Italian wolf haplotype (W14) and one substitution from the only other Italian haplotype (W16). The third sample showed a wolf-like haplotype never described before and the fourth a haplotype commonly found in dogs.\n\nFurthermore, all the wolf haplotypes detected in this study belonged to the mitochondrial haplogroup that includes haplotypes detected in all the known European Pleistocene wolves and in several modern southern European populations.\n\nUnfortunately, this endemic island population, bearing unique mtDNA variability, was definitively lost before it was possible to understand its taxonomic uniqueness and conservational value.

genetics↗