Biology subjects

Sanz, M.

Publications and source records attributed to Sanz, M..

6 recordsLinked to original sources

bioRxiv2026

Co-occurrence of Yersinia pestis and other zoonoses during European prehistory

The infection of humans by the causal agent of Plague, Yersinia pestis, has been attested as far back as 5,500 BP. Although the specific patho-mechanism and ultimate origin of the disease caused by these prehistoric genomes remains unclear, the bacterium spread through Europe, likely during the Late Neolithic to Bronze Age (LNBA). In this study, we analysed 9 genomic samples originating from 8 different human individuals dating to around 4950 cal BP from the site of Grotta della Spinosa, Tuscany, Italy. Metagenomic screening of these samples reveals one individual (GSP013) to be co-infected by Yersinia pestis, Erysipelothrix rhusiopathiae, and Hepatitis B virus (HBV). At least three further individuals from the site were infected with HBV, indicating its wider presence within the community. The phylogenetic placement of Y. pestis in GSP013 shows that this strain is closely related to the earliest LNBA Caucasus genomes of the bacterium, basal to later European diversity. This represents the earliest evidence of Y. pestis in the Italian peninsula (and Southern Europe more widely) to date, predating previously discovered genomes by at least 200 years. Furthermore, we retrieved 60 newly reported ancient genomes of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum from animals and humans, dating back from 8,300 BP to 100 BP. Of these new genomes, 15 of which stem from individuals known to be infected by Y. pestis. This contributes to our understanding of Y. pestis transmission in prehistoric Europe and possible reservoirs, and offers insights into disease dynamics in communities during the 3rd millennium BCE.

evolutionary biology↗

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↗

bioRxiv2025

Viral transport in evaporating sessile model respiratory droplets

Viral particles, or virions, may remain infectious in the dry residue of respiratory droplets for times as long as hours. This is counterintuitive, since salt concentration increases dramatically as the drops water evaporates, making the drop a harsh environment for virions. It has been hypothesized that the drop components (mainly salt and the glycoprotein mucin) segregate during the evaporation process, with virions being transported away from salt deposits. This would protect them from the salts damaging effects. Thus, understanding where virions reside in a drop residue is essential to disentangle the physico-chemical mechanisms that drive their inactivation. However, determining the virion location in an environment as heterogeneous and complex as a respiratory drop is challenging. Here we show experimentally that virions in the drops dry residue are found mainly forming aggregates in protein-rich regions, outside salt crystals. The mechanism yielding the observed viral spatial distribution can be found in the internal flow phenomena within the droplet, which are described using numerical simulations. We anticipate our results to be relevant to explain the discrepancies in the infectivity decay rates measured in respiratory drops between previous reported studies.

biophysics↗

bioRxiv2023

Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1

Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in ex vivo assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.

microbiology↗

bioRxiv2021

Alu-mediated weak CEBPA binding and slow B cell transdifferentiation in human

Many developmental and differentiation processes take substantially longer in human than in mouse. To investigate the molecular mechanisms underlying this phenomenon, here we have specifically focused on the transdifferentiation from B cells to macrophages. The process is triggered by exactly the same molecular mechanism -- the induction by the transcription factor (TF) CEBPA -- but takes three days in mouse and seven in human (1, 2). In mouse, the speed of this process is known to be associated with Myc expression (3). We found that in this species, CEBPA binds strongly to the Myc promoter, efficiently down-regulating Myc. In human, in contrast, CEBPA does not bind this promoter, and MYC is indirectly and more slowly down-regulated. Attenuation of CEBPA binding is not specific to the MYC promoter, but a general trait of the human genome across multiple biological conditions. We traced back weak CEBPA binding to the primate-specific Alu repeat expansion. Many Alu repeats carry strong CEBPA binding motifs, which sequester CEBPA, and attenuate CEBPA binding genome-wide. We observed similar CEBPA and MYC dynamics in natural processes regulated by CEBPA, suggesting that CEBPA attenuation could underlie the longer duration in human processes controlled by this factor. Our work highlights the highly complex mode in which biological information is encoded in genome sequences, evolutionarily connecting, in an unexpected way, lineage-specific transposable element expansions to species-specific changes in developmental tempos.

bioinformatics↗

bioRxiv2020

Dynamics of gene expression and chromatin marking during cell state transition

We have monitored the transcriptomic and epigenomic status of cells at twelve time-points during the transdifferentiation of human pre-B cells into macrophages. Using this data, we have investigated some fundamental questions regarding the role of chromatin in gene expression. We have found that, over time, genes are characterized by a limited number of chromatin states (combinations of histone modifications), and that, consistently, chromatin changes over genes tend to occur in a coordinated manner. We have observed strong association between these changes and gene expression only at the time of initial gene activation. Activation is preceded by H3K4me1 and H3K4me2, and followed in a precise order by most other histone modifications. Further changes in gene expression, comparable or even stronger than those at initial activation, occur without associated changes in histone modifications. The data generated here constitutes, thus, a unique resource to investigate transcriptomic and epigenomic dynamics during a differentiation process.

genomics↗