Biology subjects

Pastor, S.

Publications and source records attributed to Pastor, S..

8 recordsLinked to original sources

bioRxiv2026

Region-specific patterns of sexual shape variation in the human bony labyrinth: 3D geometric morphometric analysis of a sample with known genomic sex

The human bony labyrinth has attracted increasing interest because of its taxonomic, evolutionary, and functional significance. Although sexual dimorphism has been reported in several aspects of the temporal bone, the extent to which sex, age, size, and allometry contribute to labyrinth shape variation remains poorly understood. Here, we investigated patterns of sexual shape variation in the human bony labyrinth using three-dimensional geometric morphometrics in a sample of 98 archaeological individuals from South America with known genomic sex. Centroid size and allometric effects were assessed in a subset of 90 individuals with comparable metric scaling. In addition to analysing the complete labyrinth, the cochlea and semicircular canals were examined separately to evaluate region-specific patterns of sexual shape variation. Principal Component Analysis showed extensive overlap between females and males, and overall labyrinth shape did not differ significantly between sexes. Males exhibited significantly larger labyrinths than females, and centroid size explained a small but significant proportion of overall shape variation. Regional analyses showed no evidence of significant sexual shape differences in the cochlea or in any individual semicircular canal when analysed separately. In contrast, the combined semicircular canal system exhibited subtle but significant sexual shape variation independent of centroid size, whereas morphological disparity did not differ between sexes. The geometric comparison of the female and male consensus configurations further showed that sexual shape variation was regionally heterogeneous. Whereas the cochlea exhibited a pattern of localized changes with low directional coherence, the semicircular canals displayed more coordinated regional shape changes. The male consensus also exhibited slightly higher canal circularity across all three semicircular canals, particularly the posterior canal, while differences in canal-plane orientation remained minimal. These findings demonstrate that sexual shape variation in the human bony labyrinth is subtle and anatomically partitioned among its components. Although significant sex differences in centroid size were detected across most anatomical regions, overall labyrinth shape and cochlear morphology were primarily influenced by allometry, whereas significant sex-related shape differences were detected only when the semicircular canals were considered as an integrated anatomical system. These findings demonstrate that sexual dimorphism in the human bony labyrinth is subtle but regionally heterogeneous, with the cochlea and semicircular canals exhibiting distinct patterns of shape variation, suggesting that these structures are influenced by different developmental, functional, and evolutionary processes.

evolutionary biology↗

bioRxiv2025

{micro}CT Scanning Effects on DNA and a Multi-Step Workflow for Archaeological Petrous Bones

The petrous portion of the temporal bone is a key element in human evolutionary studies due to its exceptional preservation of biomolecules and morphological information. However, intensive and often redundant sampling has raised concerns about sustainability and long-term conservation. Here we present the first systematic evaluation of whether micro-Computed Tomography ({micro}CT)--a widely used tool for digital preservation--affects ancient DNA (aDNA) integrity in human petrous bones. We analyzed 93 archaeological samples from Argentina, of which 50 had been scanned using {micro}CT and 43 had not. We compared six molecular parameters, including endogenous content, read length, cytosine deamination patterns and contamination estimates. No statistically significant differences were observed between scanned and unscanned samples across any parameter (Mann-Whitney/Wilcoxon tests, p <0.05). Although mitochondrial contamination was marginally higher in scanned samples (p = 0.051), this was not driven by contamination estimates above the widely accepted 5% threshold for genomic analysis, Moreover, this pattern was not observed when considering nuclear contamination. These results indicate that, under appropriate scanning conditions, {micro}CT imaging does not compromise DNA preservation. Building on this evidence, we propose a sustainable, multi-step workflow that integrates biological profiling, osteobiography, imaging, and compositional pre-screening prior to molecular sampling. This interdisciplinary approach maximizes the scientific information obtained from skeletal collections while minimizing destructive practices, thereby promoting ethical and sustainable research on irreplaceable anthropological remains, and fosters collaboration across research fields.

paleontology↗

bioRxiv2025

Endophytic bacteria Bacillus velezensis NKG50 as a potential biocontrol agent of Ascochyta blight on chickpea

One of chickpea crops most devastating and economically relevant fungal diseases is Ascochyta rabiei, the causal agent of Ascochyta blight. The traditional agricultural management of the disease requires a complex combination of cultural, chemical, and genetic strategies. To develop a more effective management strategy, with low economic and environmental costs, we isolated 43 endophytic bacteria from asymptomatic chickpea plants native to our soils region. We tested their antifungal effect with mycelial growth and conidia germination inhibition tests. Our best candidate was NKG50 isolate, which inhibited A. rabiei growth by more than 85% in the dual test, more than 65% by cell-free supernatants, and inhibited conidia germination by 90%. This antagonistic ability was confirmed in leaflet and greenhouse assays, with a significant reduction in disease severity in both scales. The isolated NKG50 genome was completely sequenced and identified as Bacillus velezensis NKG50. We found 13 gene clusters associated with secondary metabolites, and five of them with an unknown function and or nature previously reported for B. velezensis. This study demonstrated for the first time that B. velezensis NKG50 is a strong candidate for the biocontrol of Ascochyta blight in Argentina.

microbiology↗

bioRxiv2024

Optically Mapped Black Genomes: Distinct Structures and 22q11.2 Deletion Syndrome Mechanisms

The genomic architecture of 22q11.2 Deletion Syndrome (22q11.2DS) has focused on analysis of white genomes. However, Black individuals appear to have a lower prevalence of 22q11.2DS compared to whites. To improve the understanding of different populations in relation to 22q11.2DS, optical mapping data from 106 genomes across various Black and white genomes were used to determine the organization of 22q11.2 genomic structures. This revealed extensive variability between the groups regarding copy number and orientation changes of the elements comprising the 22q11.2 low copy repeats (LCR22s). Several novel CNVs and whole haplotype configurations, private and of different prevalence to each group were detected. The diversity of CNVs within Black genomes compared to white genomes was especially striking. To determine the impact of this variability, Black families with de novo 22q11.2DS probands were compared to white families. The highly variable configurations of Black and white haplotypes led to several unique non-allelic homologous recombination (NAHR) scenarios with recombinations at different loci. In particular, Black families had unique recombinations yet to be observed. Thus, the unique and highly variable haplotype configurations of LCR22s in Black individuals may play a role in their decreased incidence of 22q11.2DS.

genomics↗

bioRxiv2022

Anti-HVEM mAb therapy improves antitumoral immunity both in vitro and in vivo, in a novel transgenic mouse model expressing human HVEM and BTLA molecules challenged with HVEM expressing tumors

BackgroundTNFRF-14/HVEM is the ligand for BTLA and CD160 negative immune co-signaling molecules as well as viral proteins. Its expression is dysregulated with an overexpression in tumors and a connection with tumors of adverse prognosis. MethodsWe developed C57BL/6 mouse models co-expressing human huBTLA and huHVEM as well as antagonistic monoclonal antibodies (mAbs) that completely prevent the interactions of HVEM with its ligands. ResultsHere, we show that the anti-HVEM18-10 mAb increases primary human {beta}-T cells activity alone (CIS-activity) or in the presence of HVEM-expressing lung or colorectal cancer cells in vitro (TRANS-activity). Anti-HVEM18-10 synergizes with anti-PD-L1 mAb to activate T cells in the presence of PDL-1 positive tumors, but is sufficient to trigger T cell activation in the presence of PD-L1 negative cells. In order to better understand HVEM18-10 effect in vivo and especially disentangle its CIS and TRANS effects, we developed a knock-in (KI) mouse model expressing human BTLA (huBTLA+/+) and a KI mouse model expressing both human BTLA and human HVEM (huBTLA+/+ /huHVEM+/+ (DKI)). In vivo pre-clinical experiments performed in both mouse models showed that HVEM18-10 treatment was efficient to decrease human HVEM+ tumor growth. In the DKI model, anti-HVEM 18-10 treatment induces a decrease of exhausted CD8+ T cells and regulatory T cells and an increase of Effector memory CD4+ T cells within the tumor. Interestingly, mice which completely rejected tumors ({+/-} 20%) did not develop tumors upon re-challenge in both settings, therefore showing a marked T cell-memory phenotype effect. ConclusionsAltogether, our preclinical models validate anti-HVEM18-10 as a promising therapeutic antibody to use in clinics as a monotherapy or in combination with existing immunotherapies (anti-PD1/anti-PDL-1/anti-CTLA-4).

immunology↗

bioRxiv2021

CISH targeting in NK cells activates natural cytotoxicity receptor signaling and reduce cell exhaustion to unsilence primary anti-tumor response

Cytokine inducible SH2-containing protein (CISH) is a natural killer (NK) cell negative regulator of cytokine signaling pathway. To further understand CISH functions in NK cells, we developed a conditional Cish-deficient mouse model in NK cells (Cishfl/flNcr1Ki/+). We detected no developmental or homeostatic difference in NK cells. However, global gene expression of Cishfl/flNcr1Ki/+ NK cells compared to Cish+/+Ncr1Ki/+ NK cells revealed upregulation of pathways and genes associated with NK cell cycling and activation. We show that CISH does not only regulate interleukin-15 (IL-15) signaling pathways but also natural cytotoxicity receptors (NCR) pathways. Indeed, CISH protein expression level increases upon NCR triggering. Primed Cishfl/flNcr1Ki/+ NK cells display increased activation upon NCR stimulation. Cishfl/flNcr1Ki/+ NK cells display lower activation thresholds and Cishfl/flNcr1Ki/+ mice are more resistant to tumor metastasis. Remarkably, we found that Cishfl/flNcr1Ki/+ mice were also more resistant to primary breast cancer growth in addition to superior control of spontaneous tumor metastasis. CISH deletion favors NK cell accumulation to the primary tumor, optimizes NK cell killing properties and decreases TIGIT immune checkpoint receptor expression, limiting NK cell exhaustion. Finally, we argue that specifically enhancing NK cell function is sufficient to boost anti-tumor response to both primary and secondary tumor models. Using CRISPRi, we then targeted CISH in human NK-92 or primary NK cells. According to the results in our mouse model, CISH deletion favors NCR signaling and anti-tumor functions in human NK cells. Our results validate CISH as an emerging therapeutic target to enhance NK cell immunotherapy.

immunology↗

bioRxiv2019

Complete genome sequence of Escherichia coli C - an old model organism with a new application in biofilm research

Escherichia coli C forms more robust biofilms than the other laboratory strains. Biofilm formation and cell aggregation under a high shear force depends on temperature and salt concentrations. It is the last of five E. coli strains (C, K12, B, W, Crooks) designated as safe for laboratory purposes whose genome has not been sequenced. Here we present the complete genomic sequence of this strain in which we utilized both long-read PacBio-based sequencing and high resolution optical mapping to confirm a large inversion in comparison to the other laboratory strains. Notably, DNA sequence comparison revealed the absence of several genes thought to be involved in biofilm formation, including antigen 43, waaSBOJYZUL for LPS synthesis, and cpsB for curli synthesis. The first main difference we identified that likely affects biofilm formation is the presence of an IS3-like insertion sequence in front of the carbon storage regulator csrA gene. This insertion is located 86 bp upstream of the csrA start codon inside the -35 region of P4 promoter and blocks the transcription from the sigma32 and sigma70 promoters P1-P3 located further upstream. The second is the presence of an IS5/IS1182 in front of the csgD gene, which may drive its overexpression in biofilm. And finally, E. coli C encodes an additional sigma70 subunit overexpressed in biofilm and driven by the same IS3-like insertion sequence. Promoter analyses using GFP gene fusions and total expression profiles using RNA-seq analyses comparing planktonic and biofilm envirovars provided insights into understanding this regulatory pathway in E. coli. IMPORTANCEBiofilms are crucial for bacterial survival, adaptation, and dissemination in natural, industrial, and medical environments. Most laboratory strains of E. coli grown for decades in vitro have evolved and lost their ability to form biofilm, while environmental isolates that can cause infections and diseases are not safe to work with. Here, we show that the historic laboratory strain of E. coli C produces a robust biofilm and can be used as a model organism for multicellular bacterial research. Furthermore, we ascertained the full genomic sequence as well as gene expression profiles of both the biofilm and planktonic envirovars of this classic strain, which provide for a base level of characterization and make it useful for many biofilm-based applications.

microbiology↗

bioRxiv2018

The 22q11 low copy repeats are characterized by unprecedented size and structure variability

AbstractLow copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The chromosome 22 LCRs (LCR22s) are amongst the most complex regions in the genome and their structure remains unresolved. These LCR22s mediate non-allelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS), causing the most frequent genomic disorder. Using fiber FISH optical mapping, we have de novo assembled the LCR22s in 33 cell lines. We observed a high level of variation in LCR22 structures, including 26 different haplotypes of LCR22A with alleles ranging from 250 Kb to over 2,000 Kb. An additional four haplotypes were detected using Bionano mapping. Further, Bionano maps generated from 154 individuals from different populations suggested significantly different LCR22 haplotype frequencies between populations. Furthermore, haplotype analysis in nine 22q11DS patients resulted in the localization of the NAHR site to a 160 Kb paralog between LCR22A and -D in seven patients and to a 31 Kb region in two individuals with a rearrangement between LCR22A and -B.. This 31 Kb region contains a palindromic AT-rich repeat known to be a driver of chromosomal rearrangements. Our study highlights an unprecedented level of polymorphism in the structure of LCR22s, which are likely still evolving. We present the most comprehensive map of LCR22 variation to date, paving the way towards investigating the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability in 22q11DS patients as well as in the general population.

genomics↗