Biology subjects

Mira, A.

Publications and source records attributed to Mira, A..

10 recordsLinked to original sources

bioRxiv2026

Pdk1-dependent metabolic heterogeneity promotes aggressive colorectal cancer through cell-intrinsic interferon signaling

Tumor heterogeneity is a major determinant of tumor progression and therapeutic resistance, yet the contribution of metabolism to intratumoral heterogeneity still remains poorly explored. Here, we find that pyruvate dehydrogenase kinase-1 (Pdk1) expression defines metabolically distinct cancer cell populations in colorectal tumors. Image-based spatial single-cell phenotyping shows that Pdk1-high cells are associated with tumor progression in orthotopic models of colorectal cancer (CRC). Genetic ablation experiments demonstrate the role of Pdk1-high cells in tumor growth, 5-fluorouracil chemoresistance and tumor relapse. Mechanistically, we identify a link between Pdk1-driven metabolic states and specific cell phenotypes, where Pdk1-high cancer cells exhibit an EMT, stem cell-like phenotype characterized by increased interferon (IFN) signaling. Mitochondrial remodeling in Pdk1-high cells leads to the release of mitochondrial DNA to the cytosol and activation of IFN pathways, promoting Pdk1-driven phenotypes. Inhibition of IFN signaling impairs the tumorigenic and aggressive features of Pdk1-high cancer cells, thus establishing a functional connection between metabolic heterogeneity, cell-intrinsic IFN signaling and aggressive CRC.

cancer biology↗

bioRxiv2025

Oral Microbiota Composition in Children and Adults During Spanish COVID-19 Lockdown: Impact of Home Self-Confinement and SARS-CoV-2 infection

BackgroundThe COVID-19 pandemic changed societys habits and customs due to the social restrictions and health measures imposed during the first half of 2020. This study analyzes the composition of the oral microbiota in relation to age, household cohabitation, SARS-CoV-2 infection, and COVID-19 severity among children and adults under home confinement in Barcelona, Spain. MethodsA prospective study conducted involving children and adults confined during the COVID-19 pandemic in the Barcelona Metropolitan Area between April and June 2020 included multiple cases of several participants living within the same family household. Saliva samples were collected from all participants, and microbiota composition was characterized through 16S rRNA gene sequencing. ResultsA total of 142 adults and 265 children living in 121 family households were included in the study. All 142 adults had a prior confirmed SARS-CoV-2 infection, and 20 (14.08%) of them had a history of severe COVID-19. SARS-CoV2 infection was detected in 58/265 (21.89%) of children; all of them were asymptomatic. Oral microbiota composition and diversity did not differ by SARS-CoV-2 infection status in children. In contrast, adults with severe COVID-19 exhibited lower microbiota diversity and distinct microbiota composition compared to those with mild disease symptoms. Age-related differences in oral microbiota composition were marked in the younger children groups. Additionally, cohabiting individuals shared more Amplicon Sequence Variants (ASVs) than non-cohabitants. ConclusionsAge and cohabitation strongly influenced oral microbial composition. Our study demonstrates that oral microbiota composition in adults varies according to COVID-19 severity, whereas such microbial shifts are not observed in asymptomatic pediatric populations, regardless of infection status.

microbiology↗

bioRxiv2025

Reliability of self-reported catch and effort data via smartphone applications in a multi-species recreational fishery

The spatial and temporal heterogeneity of recreational anglers and the challenges associated with monitoring their activities often complicate their effective management. Angler smartphone applications (apps) offer a promising digital tool for self-reporting fishing effort (E) and captures per unit of effort (CPUE). However, despite their growing use for data collection in recreational fisheries, the existing literature on their performance remains limited, raising concerns about potential biases in the collected data. Since 2019, self-reporting of E and CPUE has been mandatory for recreational fishing trips within the network of partially-protected Marine Protected Areas (MPAs) in the Balearic Islands (Spain). A regional-scale App ("Diari de Pesca Recreativa") was developed to streamline data collection. This study aimed to evaluate the Apps performance in reporting recreational fisheries data over a six-year period. Data obtained via the App (3,672 trip self-reports) were compared to data collected through a traditional method (360 on-site creel surveys). Estimates of E and CPUE were compared across datasets overall, as well as by month, fishing modality, MPA, and for key target species. Significant differences were observed for E (hours {middle dot} angler {middle dot} trip, p < 0.001) and CPUE (captures{middle dot} E-1, p = 0.001) across datasets. However, when stratified by species, month, fishing modality, and MPA, most groups showed no statistically significant differences in E and CPUE estimates. Data from the App tended to overestimate E compared to creel surveys, likely due to inaccuracies in self-reported trip durations. Conversely, creel surveys appeared to underestimate E, reflecting intrinsic biases in trip duration collection. Assuming that the true values of E and CPUE lie between the estimates derived from the App and creel surveys, integrating both methods is recommended to improve the accuracy and reliability of data. The App not only generates a higher volume of trip data but also provides a user-friendly platform for self-reporting. Moreover, it digitizes data collection, enabling automation and advanced analytics for fisheries monitoring and management of recreational fisheries.

ecology↗

bioRxiv2025

Inhibitory effect of Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum on pneumococcal in vitro growth

BackgroundStreptococcus pneumoniae is a nasopharynx coloniser that can invade sterile tissues, causing Invasive Pneumococcal Disease (IPD). Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum are commensal bacteria commonly isolated from the nasopharynx of healthy children, potentially playing a protective role. This study aims to analyse the effects of D. pigrum and C. pseudodiphtheriticum on S. pneumoniae in vitro growth. MethodsPneumococcal strains were collected from IPD patients and healthy carriers in Catalonia (2016-2023). D. pigrum and C. pseudodiphtheriticum strains were isolated from a healthy childs nasopharynx. S. pneumoniae was co-cultured with each commensal bacterium in triplicate experiments. Pneumococcal growth was quantified using a real-time PCR assay targeting the lytA gene. The effect of commensal bacteria on pneumococcal growth was evaluated using a linear mixed-effect regression model. ResultsTwenty-eight pneumococcal strains expressing 24 different serotypes and 26 clonal types were analysed (18 isolated in blood and 10 in nasopharyngeal aspirate). Pneumococcal growth was decreased by D. pigrum ({beta} = -0.763, 95% CI: -0.94 to -0.59, p < 0.0001) and C. pseudodiphtheriticum ({beta} = -0.583, 95% CI: -0.76 to -0.41, p < 0.0001). The combined presence of both had a stronger inhibitory effect ({beta} = -0.971, 95% CI: -1.15 to -0.79, p < 0.0001). No association was found between isolation site or serotype with pneumococcal growth. ConclusionD. pigrum and C. pseudodiphtheriticum significantly reduced pneumococcal growth, with a synergic effect when combined. This antagonistic effect supports the potential protective factor of healthy nasopharyngeal microbiota against IPD and the development of these microorganisms as probiotics.

microbiology↗

bioRxiv2025

Chronic Staphylococcus aureus infection of osteocytes promotes an intracellular viable-but-non-culturable phenotype

Osteomyelitis associated with periprosthetic joint infection (PJI) is a serious and growing complication of orthopaedic joint replacement surgery, with a failure to cure rate within 2-years of between 15-46%. PJI is a severe chronic infectious disease with a 20% recurrence rate and culture-negativity in 7-39% of cases, of which 14-27% are PCR-positive, findings that remain poorly explained. Osteocytes, the most numerous bone cell type, have been identified as potential long-term intracellular reservoirs for Staphylococcus aureus, shielding it from antimicrobial treatment. Here we demonstrate that in chronic intra-osteocytic infections, S. aureus consistently adopts a viable-but-non-culturable (VBNC) state, capable of spontaneous host cell escape and reversion to active growth. Whole-genome sequencing identified single nucleotide polymorphisms (SNPs) in gene pairs between clones. Two revertant clones exhibited SNPs in srrB and murA2, and five exhibited SNPs in garR and upstream of tatB. While the functional importance of these changes is uncertain, they suggest that diverse genetic mechanisms underly entrance into and exit from the intracellular VBNC state. These findings provide a compelling explanation for culture-negative, PCR-positive osteomyelitis and have direct implications for the diagnosis and treatment of PJI.

microbiology↗

bioRxiv2022

Hunter-gatherer oral microbiomes are shaped by contact network structure

Ancestral humans evolved a complex social structure still observed in extant hunter-gatherers. Here we investigate the effects of extensive sociality and mobility on the oral microbiome of 138 Agta hunter-gatherers from the Philippines. Comparisons of microbiome composition showed that the Agta are more similar to Central African Bayaka hunter-gatherers than to neighboring farmers. We also defined the Agta social microbiome as a set of 137 oral bacteria (only 7% of 1980 amplicon sequence variants) significantly influenced by social contact (quantified through wireless sensors of short-range interactions). We show that interaction networks covering large areas, and their strong links between close kin, spouses, and even unrelated friends, can significantly predict bacterial transmission networks across Agta camps. Finally, more central individuals to social networks are also bacterial supersharers. We conclude that hunter-gatherer social microbiomes, which are predominantly pathogenic, were shaped by evolutionary tradeoffs between extensive sociality and disease spread.

microbiology↗

bioRxiv2022

The making of the oral microbiome in Agta hunter-gatherers

Ecological and genetic factors have influenced the composition of the human microbiome during our evolutionary history. We analyzed the oral microbiota of the Agta, a hunter-gatherer population where part of its members is adopting an agricultural diet. We show that age is the strongest factor modulating the microbiome, likely through immunosenescence as there is an increase of pathogenicity with age. Biological and cultural processes generate sexual dimorphism in the oral microbiome. A small subset of oral bacteria is influenced by the host genome, linking host collagen genes to bacterial biofilm formation. Our data also suggests that shifting from a fish/meat to a rice-rich diet transforms their microbiome, mirroring the Neolithic transition. All these factors have implications in the epidemiology of oral diseases. Thus, the human oral microbiome is multifactorial, and shaped by various ecological and social factors that modify the oral environment.

microbiology↗

bioRxiv2020

Cell-to-cell spread inhibiting antibodies constitute a correlate of protection against Herpes Simplex Virus Type 1 reactivations

Herpes simplex viruses (HSV) cause ubiquitous human infections. For vaccine development, knowledge concerning correlates of protection against HSV is essential. Therefore, we investigated if humans principally can produce highly protective cell-to-cell spread inhibiting antibodies upon natural infection and whether such antibody responses correlate with protection from HSV reactivation. We established a high-throughput HSV-1 GFP reporter virus-based assay and screened 2496 human plasma samples for HSV-1 cell-to-cell spread inhibiting antibodies. We conducted a survey among the blood donors to analyze the correlation between the presence of cell-to-cell spread inhibiting antibodies in plasma and the frequency of HSV reactivations. In total, 128 of 2496 blood donors (5.1 %) exhibited high levels of HSV-1 cell-to-cell spread inhibiting antibodies in the plasma. Such individuals showed a significantly lower frequency of HSV reactivations compared to subjects without sufficient levels of HSV-1 cell-to-cell spread inhibiting antibodies. This study provides two important findings: (I) a fraction of humans produce HSV cell-to-cell spread inhibiting antibodies upon natural infection and (II) such antibodies correlate with protection against recurrent HSV. Moreover, these elite neutralizers can provide promising material for hyperimmunoglobulin, the isolation of superior antiviral antibodies and information for the design of a vaccine against HSV. ImportanceHerpes simplex virus 1 infections can cause painful mucosal lesions at the oral or genital tract and severe, life threatening disease in immunosuppressed patients or neonates. There is no approved vaccine available, and the emergence of drug resistances especially in long time treated patients makes the treatment increasingly difficult. We tested 2496 people for HSV-1 cell-to-cell spread inhibiting antibodies. Five percent exhibited functional titers such antibodies and showed significantly lower risk of reactivations, uncovering cell-to-cell spread inhibiting antibodies as a correlate of protection against Herpes simplex virus reactivations. Isolation of the cell-to-cell spread inhibiting antibodies from B-cells of these donors may contribute to develop novel antibody-based interventions for prophylactic and therapeutic use and provide starting material for vaccine development.

immunology↗

bioRxiv2020

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

Molecular tests for viral diagnostics are essential to confront the COVID-19 pandemic, but their production and distribution cannot satisfy the current high demand. Early identification of infected people and their contacts is the key to being able to isolate them and prevent the dissemination of the pathogen; unfortunately, most countries are unable to do this due to the lack of diagnostic tools. Dogs can identify, with a high rate of precision, unique odors of volatile organic compounds generated during an infection; as a result, dogs can diagnose infectious agents by smelling specimens and, sometimes, the body of an infected individual. We trained six dogs of three different breeds to detect SARS-CoV-2 in respiratory secretions of infected patients and evaluated their performance experimentally, comparing it against the gold standard (rRT-PCR). Here we show that viral detection takes one second per specimen. After scent-interrogating 9,200 samples, our six dogs achieved independently and as a group very high sensitivity, specificity, predictive values, accuracy, and likelihood ratio, with very narrow confidence intervals. The highest metric was the negative predictive value, indicating that with a disease prevalence of 7.6%, 99.9% of the specimens indicated as negative by the dogs did not carry the virus. These findings demonstrate that dogs could be useful to track viral infection in humans, allowing COVID-19 free people to return to work safely.

microbiology↗

bioRxiv2019

Estimating a novel stochastic model for within-field disease dynamics of banana bunchy top virus via approximate Bayesian computation

The Banana Bunchy Top Virus (BBTV) is one of the most economically important vector-borne banana diseases throughout the Asia-Pacific Basin and presents a significant challenge to the agricultural sector. Current models of BBTV are largely deterministic, limited by an incomplete understanding of interactions in complex natural systems, and the appropriate identification of parameters. A stochastic network-based Susceptible-Infected model has been created which simulates the spread of BBTV across the subsections of a banana plantation, parameterising nodal recovery, neighbouring and distant infectivity across summer and winter. Findings from posterior results achieved through Markov Chain Monte Carlo approach to approximate Bayesian computation suggest seasonality in all parameters, which are influenced by correlated changes in inspection accuracy, temperatures and aphid activity. This paper demonstrates how the model may be used for monitoring and forecasting of various disease management strategies to support policy-level decision making.\n\nAuthor summaryThe Banana Bunchy Top Virus (BBTV) poses one of the greatest threats to the food security of developing nations and the banana industry throughout the Asia-Pacific Basin. Decision-makers face significant challenges in mitigating BBTV spread in banana plantations due to the vector-borne spread of this disease, which is significantly influenced by a vast array of external environmental factors that are unique to each plantation.\n\nWe propose a flexible network-based model that describes the spread of BBTV in a real banana plantation through a random process while accounting for individual plantation characteristics and utilise a principled methodology for estimating model parameters. Our findings quantify the effect of seasonal changes and plantation configuration on BBTV spread and predict for high-risk areas in this plantation. We believe that our model might be used by decision-makers to evaluate the effectiveness of current disease management strategies and explore opportunities for improvements.

systems biology↗