Biology subjects

David, S.

Publications and source records attributed to David, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Early Treatment with Oral Pirfenidone Improves Bladder Function after Contusive Spinal Cord Injury in Mice

Spinal cord injury (SCI) disrupts innervation to the lower urinary tract, resulting in bladder dysfunction that predisposes to urinary infections and renal impairment. While inflammation is central to bladder pathology after SCI, the molecular events linking acute to chronic remodeling are poorly defined. We hypothesized that early treatment with pirfenidone, an anti-inflammatory and anti-fibrotic drug, would attenuate bladder pathology after SCI. Adult female C57BL/6J mice underwent contusive SCI or sham laminectomy, and bladders were collected at 2, 7, 16, and 45 days later. SCI induced bladder hypertrophy, edema, hemorrhage, neutrophil infiltration, cell proliferation and loss of voiding function in the first 48 hours. Transcriptomic profiling at this timepoint was characterized by activation of inflammatory and cytokine pathways including TNFalpha, IL-6, the complement cascade, and TGFbeta. Although bladder function partially recovered by day 7, inflammatory pathways persisted and extracellular matrix (ECM) remodeling programs emerged. By day 16, robust activation of ECM-remodeling pathways was evident in all bladders. Treatment with pirfenidone during the acute inflammatory phase (day 2-7) reduced bladder hypertrophy and suppressed expression of pro-fibrotic, inflammatory, and neuroplasticity-associated genes including Bdnf and Chrm2 that encodes muscarinic receptor 2 (M2). Mechanistically, pirfenidone attenuated TGFbeta signaling as shown by downregulation of phosphoSmad2 protein in whole bladders and decreased M2 receptor expression in the urothelium. These molecular changes correlated with improved function in pirfenidone-treated mice as shown by fewer voiding events with larger urine volumes up until 45 days after SCI. Early treatment with pirfenidone limits inflammation and fibrosis, normalizes neural signaling, and improves bladder function after SCI.

physiology↗

bioRxiv2026

Frontal Eye Field Leads a Distributed Oculomotor Circuit for Abstract Categorical Decisions

Flexible decisions require the brain to transform sensory evidence into abstract, task-relevant variables and then into actions. Understanding this process requires identifying how distributed neural populations represent sensory, cognitive, and motor variables, and how interareal interactions mediate transformations between them. We simultaneously recorded population activity in frontal eye field (FEF), lateral intraparietal area (LIP) and superior colliculus (SC) while monkeys performed a flexible yet urgent visual motion-categorization task. Within this network, FEF first encoded abstract categories, followed by SC and then LIP. LIP showed the earliest encoding of visual stimulus features, but a later encoding of upcoming saccades. Single-trial analyses revealed directed information flow from FEF to LIP populations for category-and choice-related signals. Reversible FEF inactivation impaired categorization and saccadic choice, causally implicating FEF in category-guided action. These findings reveal a differentiated FEF-LIP-SC circuit for transforming sensory evidence into abstract categorical decisions and the actions used to report them.

neuroscience↗

bioRxiv2026

A novel nanobody-based approach for targeting heterogeneous Acinetobacter baumannii isolates and closely related pathogenic Acinetobacter spp.

Acinetobacter baumannii is a top-priority, ESKAPE pathogen that poses a major challenge to human health. The pathogen is difficult to combat due to its extensive arsenal of antibiotic resistance and its protective polysaccharide capsule. In addition, A. baumannii isolates are highly heterogeneous, which complicates the development of rapid detection methods or novel targeted therapeutic approaches. Here, we discovered and characterized a new biotechnological tool, the nanobody H7 (NbH7), along with its conserved target, the surface-exposed Omp25 protein of A. baumannii, and elucidated their interaction at the molecular level. Moreover, we demonstrate that NbH7-functionalized magnetic beads enable selective and efficient capture of A. baumannii from bacterial mixtures, including non-pathogenic intestinal bacteria. This provides proof of concept for a new targeting system that remains effective across diverse A. baumannii clinical isolates and capsule types and holds potential for use in diagnostic cell enrichment and targeted therapies.

molecular biology↗

bioRxiv2026

Personalized microbiotas (counter-)select for antibiotic resistant strains

Antibiotic resistant pathogens are an increasing public health threat, as development of novel therapeutics is outpaced by resistance emergence and dissemination. Approaches to slow down or even revert antibiotic resistance are necessary to maintain efficacy of both existing and new antibiotics. Such approaches exploit the fitness cost of resistance elements, but have largely relied on assessing this cost in laboratory conditions that poorly reflect the native context in which pathogens reside. Here we present a method that allows to investigate the influence of personalized human gut microbiota compositions on the competitive fitness of antibiotic resistant pathogens. Using fecal matter-derived microbiomes we identified a specific community that selected for a carbapenem-resistant Klebsiella pneumoniae strain. This selective advantage was due to mutations arising in a LacI-type transcriptional regulator, GlyR, which upregulated expression of the downstream glycoporin GlyP, causing the effect. By deconvoluting the microbiome composition, we identified a focal E. coli strain as a central driver of the selection, which was further modulated by other microbiota members. We further demonstrate that the selective advantage was due to carbohydrate competition, and in particular for glycerol-containing compounds. Importantly, glyR mutations are under strong positive but conditional selection in clinical K. pneumoniae isolates. This implies a reduced competitiveness in other environments, which we experimentally validated in vitro. Overall, this study offers a path to identify microbiome-specific interactions that modulate the competitiveness of antibiotic resistant pathogens.

microbiology↗

bioRxiv2026

PgaR is a positive regulator of the pgaABCD biosynthetic operon in Klebsiella pneumoniae

The biosynthetic locus encoding the exopolysaccharide poly-N-acetyl-glucosamine (PNAG) is widely conserved across bacteria, including the WHO critical-priority pathogen Klebsiella pneumoniae (Kp). In Kp, PNAG synthesis is mediated by the pgaABCD operon, yet its lineage-specific regulation remains incompletely defined. Using a comparative genomics approach to interrogate the pgaABCD locus across the high-risk clonal Kp complex 258 (CC258) lineage, we identified a previously uncharacterised positive transcriptional regulator located immediately upstream of pgaA, which we designate pgaR. Phylogenetic analysis revealed recurrent evolutionary events affecting this regulatory region, including repeated deletion or truncation of pgaR and a G>A substitution upstream of the pgaR start codon. Functional characterisation demonstrated that loss of pgaR abolishes pgaABCD expression and PNAG production, whereas the upstream G>A substitution drives PNAG hyper-production. In vitro, Kp produce extensive extracellular PNAG networks under static growth conditions, consistent with a role in biofilm architecture. Despite this, PNAG expression was dispensable in murine pneumonia and peritonitis models, while PNAG hyper-production significantly attenuated virulence and disease severity, indicating a fitness cost associated with sustained overexpression. Collectively, we discovered PgaR as a novel gene regulator of the pgaABCD operon. We show a previously unrecognised lineage-specific layer of PNAG regulation in Kp and demonstrate that opposing PNAG phenotypes: loss and hyper-production, have independently and repeatedly emerged among clinical CC258 isolates, highlighting dynamic selection acting on biofilm-associated traits in this high-risk pathogen. ImportanceThe exopolysaccharide poly-N-acetyl-glucosamine (PNAG) is widely conserved in bacteria, including the WHO critical-priority pathogen Klebsiella pneumoniae. However, how PNAG production is regulated in high-risk lineages has remained unclear. Here, we identify PgaR as a previously unrecognised positive regulator of the pgaABCD operon in clonal complex 258, a globally disseminated and drug-resistant lineage. We show that natural genetic variation within this regulatory region leads to strikingly different PNAG phenotypes: complete loss of production or hyper-production. While PNAG contributes to extracellular matrix formation in vitro, it is dispensable for virulence in murine infection models, and sustained overproduction imposes a fitness cost. The repeated and independent emergence of both loss- and gain-of-function variants among clinical isolates reveals dynamic evolutionary pressures acting on biofilm-associated traits. These findings uncover a lineage-specific layer of PNAG regulation and highlight how modulation of surface polysaccharide expression shapes pathogen fitness and adaptation.

microbiology↗

bioRxiv2025

Functional Equivalence of Gamma- and X-Ray Irradiation for Long-Term Hematopoietic and AML Transplant Outcomes in Mice

Total-body irradiation (TBI) is routinely used for myeloablation prior to mouse hematopoietic cell transplant. Widespread transition from 137Cs{gamma} -irradiators to X-ray systems has raised questions about whether these modalities yield equivalent biological outcomes. Although prior studies compared{gamma} and X-ray irradiation in healthy syngeneic transplants, their performance in reciprocal congenic models and in primary acute myeloid leukemia (AML) transplant remains unclear. Here, we systematically evaluated{gamma} and X-ray irradiation across dose and dose-rate conditions, and tested dose equivalents in CD45.1/CD45.2 reciprocal transplants and in AML transplant models. While each modality exhibited distinct early effects, both ultimately supported comparable long-term donor chimerism in congenic transplants and equivalent AML engraftment, leukemic burden, and disease progression. These findings indicate that, with proper dose calibration, X-ray irradiation is a functionally effective alternative to{gamma} -irradiation for normal and malignant transplant studies.

cell biology↗

bioRxiv2025

TraN variants mediate conjugation species specificity of IncA/C, IncH and Acinetobacter baumannii plasmids

IncA/C and IncH plasmids commonly carry antimicrobial resistance genes, notably blaNDM-1. Although these plasmids disseminate among Gram-negative pathogens via conjugation, the mechanisms underlying mating pair stabilisation (MPS) and conjugation species specificity remain poorly understood. In IncF plasmids, MPS is mediated by interactions between outer membrane proteins (OMP) encoded by the plasmids in the donor (TraN) and by the chromosome in the recipient. Using the Plascad database, we extracted 1,436 TraN sequences: 62.5% (898/1,436), mainly in IncF plasmids, are 550-660aa (we renamed TraN short, TraNS); 15% (216/1,436), in IncA/C plasmids, are 880-950aa (TraN medium, TraNM); and 11% (160/1,436), in IncH plasmids, are 1,050-1,070aa (TraN long, TraNL). A group of six TraN from Acinetobacter baumannii plasmids (891aa) were designated TraN V-shaped (TraNV). Like TraNS, TraNM and TraNL contain base and distal tip domains essential for conjugation, whereas TraNV has a base and two distinct tip domains forming a V-shaped structure. TraNM, TraNL and TraNV determine conjugation species specificity, with TraNL cooperating with OmpA. Tip swapping reverses conjugation specificity, revealing how TraNM and TraNL diversity influence plasmid host range and AMR dissemination. Our new data reveal the molecular basis of plasmid host specificity and broaden our understanding of how conjugation drives the dissemination of antimicrobial resistance genes among clinically relevant bacteria.

microbiology↗

bioRxiv2025

Ciprofloxacin resistance in Klebsiella pneumoniae: phenotype prediction from genotype and global distribution of resistance determinants

BACKGROUNDCiprofloxacin resistant Klebsiella pneumoniae is common or emerging in many geographies, and knowledge of local resistance rates is important for empirical therapy. Whilst there are known K. pneumoniae ciprofloxacin resistance determinants, there is a lack of systematic data on the effect of determinants, alone and in combination, and there are no publicly accessible tools for predicting resistance from whole genome sequence data. METHODSThe KlebNET-GSP AMR Genotype-Phenotype Group aggregated a matched genotype-phenotype dataset of n=12,167 K. pneumoniae species complex (KpSC) isolates from 27 countries between 2001-2021. We developed a rules-based classifier to predict ciprofloxacin resistance by categorizing the number of quinolone resistance determining regions mutations in gyrA and parC, the number of plasmid-mediated quinolone resistance genes, and the presence/absence of aac(6')-Ib-cr (which can acetylate ciprofloxacin). Predictive performance was assessed using the discovery dataset, for which we re-phenotyped discrepant isolates; and validated using externally contributed datasets (n=7,030 KpSC isolates). RESULTSThe rules-based classifier predicted R vs S/I with categorical agreement, sensitivity, and specificity >96%, and major/very major error rates <4%. Performance was similar across diverse KpSC sources (human, animal, other), species, and intra-species lineages. External validation of the classifier yielded overall 93.12% categorical agreement [95% confidence interval (CI), 92.50-93.74%], 8.65% major errors [95% CI, 7.34-9.97%], and 6.20% very major errors [95% CI, 5.51-6.90%]. We implemented the classifier in Kleborate, a command-line tool that is integrated into the Pathogenwatch web platform. Using this to assess the global distribution of ciprofloxacin resistance determinants in KpSC genomes available in Pathogenwatch (n=31,319, from 109 countries between years 2000-2023), we observed a significant positive association between national quinolone consumption rates and predicted ciprofloxacin resistance (R2=0.20, p=0.004). CONCLUSIONS Ciprofloxacin resistance phenotypes can be reasonably predicted from genotypes, which is sufficient for informing surveillance. However, unexplained resistance remains and accuracy is insufficient for clinical applications. We demonstrate the value of aggregating genotype-phenotype data to explore resistance mechanisms and develop predictors, but highlight complexities in combining phenotype data from different assays and standards.

genomics↗

bioRxiv2025

An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans

Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map revealed previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NF{kappa}B, AP-1) and quiescence within a single gene expression program. This program dominates an inflammatory HSC subpopulation that increases with age, highlighting a potential target for further experimental studies and anti-aging interventions.

cell biology↗

bioRxiv2025

Synergetic hallmark knockouts immortalize bovine muscle stem cells for cellular agriculture

Achieving scalable and sustainable production of cultivated meat hinges on developing robust livestock muscle and fat cell lines that can proliferate and differentiate effectively, while meeting regulatory standards and consumer expectations. In this study, bovine satellite cells (BSCs) were immortalized using CRISPR/Cas9 to knockdown PTEN (phosphatase and tensin homolog), TP53 (cellular tumor antigen) and SMAD4 (SMAD [Sma and Mad proteins] family member 4). The resulting cell line, named "CriBSC2," exhibited consistent growth, maintained muscle cell characteristics, and successfully differentiated into multinucleated myotubes after more than 150 cell divisions. In contrast, another cell line, "CriBSC1," achieved immortalization with TP53 knockout alone but lacked differentiation capacity. CriBSC2 were further cultured on gelatin scaffolds to evaluate their anchorage-dependent responses, laying the groundwork for their potential application in tissue engineering for cellular agriculture. Ultimately, CriBSC2 cells demonstrate suitable proliferation and differentiation capabilities crucial for advancing cellular agriculture and future food technologies.

cell biology↗

bioRxiv2025

Evaluation of Klebsiella pneumoniae antigen MrkA reveals expression-limited therapeutic potential

Klebsiella pneumoniae (KP) poses a major global health concern, particularly as hospital-acquired strains become increasingly antibiotic resistant. MrkA, the major type 3 fimbrial (T3F) subunit, is a recognised prospective vaccine and monoclonal antibody (mAb) target. We assessed T3F structural (mrkABCDF) and regulatory (mrkHIJ) gene prevalence and allelic variation across 1649 KP genomes, using 100 diverse isolates for detailed phenotypic characterisation. Despite high conservation MrkA expression itself is variable with genotype failing to predict phenotype. We constructed isogenic KP T3F mutants with absent and supraphysiological MrkA expression to investigate functional consequences and therapeutic responses during infection. In a severe pneumonia model blood dissemination inversely correlated with T3F expression. In vivo antigen profiling revealed only [~]20% of wild-type lung bacteria express MrkA, dropping to [~]5% in blood, with low MrkA expression defining bacteraemic KP irrespective of infection route. Critically, anti-MrkA mAb efficacy was contingent on antigen abundance, with therapeutic benefit restricted to supraphysiological MrkA expression. These findings reveal substantial in vivo MrkA expression variability with critical onward implications for vaccine and mAb development.

microbiology↗

bioRxiv2025

Fragaria ananassa DAM4 expression correlates with vegetative growth during endodormancy breaking

Dormancy-Associated MADS-BOX (DAM)3 and DAM4 have been described as potential regulators of winter dormancy in cultivated strawberry (Fragaria x ananassa Duch.). These genes are upregulated under short day conditions and downregulated under chilling conditions. The aim of the current work is to test the hypothesis that the expression of DAM3 and DAM4 correlates negatively with vegetative growth during dormancy induction and breaking. The expression of DAM3 and DAM4 as well as plant morphology and physiology were analyzed during a period of semi-dormancy induction and breaking. Furthermore, DAM3 and DAM4 expression was compared between cultivars with different chill requirements. Lastly, the DAM1, DAM2, DAM3, and DAM4 expression of concurrently growing summer and winter leaves was compared at multiple stages of dormancy-breaking. DAM3 and DAM4 expression negatively correlated with leaf area and petiole length. We conclude that DAM3 and DAM4 expression patterns are consistent with that of regulators of semi-dormancy. DAM4 expression in particular correlates strongly with vegetative growth during semi-dormancy breaking. DAM3 or DAM4 expression were not found to correlate with the cultivar-specific chill requirements. Lastly, no relevant differences in DAM expression were found between summer and winter leaves.

plant biology↗

bioRxiv2025

R27 pilus biogenesis is promiscuous and electrostatic perturbations impair functionality

During conjugation, plasmid DNA is transferred from donor to recipient bacteria via the plasmid-encoded mating pilus, formed as thin helical assemblies of polymerised pilin subunits. In the IncHI1 R27 plasmid-encoded pilus, the TrhA pilin undergoes cyclisation (via a peptide bond between Gly1 and Asp69), essential for conjugation. Gly1 and Asp69 are exposed on the pilus surface and conserved in all TrhA pilins in the Plascad database. Substituting Asp69 with Asn, Ala, Gly, or Arg did not prevent cyclisation or pilus formation, which remained structurally indistinguishable from the wild type. Conjugation efficiency of the Asp69 substitutions across multiple recipient species correlated with side chain size, in the order Asp69Asn > Asp69Ala > Asp69Gly. However, Asp69Arg, as well as Asp69Lys and Gly1Lys substitutions abolished conjugation, likely due to the positively charged pilus surface (opposite to the wild-type negative charge) forming unfavourable electrostatic interactions with the recipient outer membranes inner leaflet, composed solely of zwitterionic phosphatidylethanolamine (PE). Consistently, conjugation was rescued in recipients lacking PE. These findings indicate strong selective pressure to maintain Gly1 and Asp69, as efficient DNA transfer depends on precise electrostatic and steric constraints of the pilus surface.

microbiology↗

bioRxiv2025

Photoperiodic effects on early plant development in everbearing and seasonal flowering strawberry

In recent years, interest in vertical farming systems for strawberry cultivation has increased. Because of the increased costs associated with these systems, optimal use of resources, such as cultivation space and light, is a requirement. This necessitates a detailed understanding of plant development in different light conditions. The aim of this experiment was to analyze the effect of photoperiod on the early development of seasonal flowering and everbearing strawberry plants, and to compare the expression of genes known or suspected to be involved in the regulation of plant development between the two flowering types. Young, runner-propagated seasonal flowering and everbearing strawberry plants were grown under 10, 12, 14, or 16 h photoperiod in a climate-controlled vertical farm. Runners and flowers were removed throughout the experiment to limit their effects on assimilate balance. Morphological and physiological measurements were made weekly. Leaf material was collected for gene expression analysis. There were not many differences in plant growth and development between the short day conditions (10 and 12 h photoperiods), or long day conditions (14 and 16 h photoperiods). Short day conditions had a repressive effect on vegetative growth in all cultivars, but this effect was reduced in everbearing cultivars compared to seasonal flowering cultivars. No notable differences were found in gene expression between the two flowering types.

plant biology↗

bioRxiv2025

Monitoring of vaccine targets and interventions using global genome data: vaccines.watch

The expansion of pathogen genome sequencing into routine disease surveillance programmes is set to bring rapidly-growing volumes of increasingly structured data on a global scale. This has the potential to deliver exciting opportunities for accelerating vaccine development and monitoring. Here we present an interactive platform, vaccines.watch (https://vaccines.watch), which aims to support decision-making around vaccine formulations and roll-out by enabling interrogation of vaccine target diversity from global genome data. We have initially focused on targets included in existing or prospective multivalent polysaccharide- based vaccines for Streptococcus pneumoniae, Klebsiella pneumoniae (and related species) and Acinetobacter baumannii. The platform currently displays data for >100k high-quality genomes with geotemporal sampling information (post-2010), with new genomes assembled, analysed and incorporated on an ongoing basis (every 4 hours) as public data are newly deposited. Crucially, users can view vaccine target information in the broader context of genotypic variants (e.g. sequence types) and antimicrobial resistance markers. The platform also enables users to review the composite serotypes of pneumococcal vaccine formulations among the available genomes. For example, using data in vaccines.watch from 3 June 2025, we observed that serotypes included in the PCV13 and PCV21 formulations accounted for 36.2% (11,907/32,918) and 87.4% (28,764/32,918) of global public genomes, respectively. The platform also enables continuous review of the global genomic landscape of the included pathogens, enabling identification of gaps (e.g. in geographic coverage) that should be targeted with increased genomic surveillance. Indeed we demonstrate that substantial geographic gaps remain in the coverage of available genomes, with over half of countries contributing no genomes for each of the three pathogens. However, while caution in interpretation is important, as global representativeness of genome data grows, vaccines.watch is positioned to support different stages of the vaccine pipeline, from selection of target antigens to post-rollout monitoring of population changes.

genomics↗

bioRxiv2025

amr.watch - monitoring antimicrobial resistance trends from global genomics data

BackgroundWhole genome sequencing (WGS) is increasingly supporting routine pathogen surveillance at local and national levels, providing comparable data that can inform on the emergence and spread of antimicrobial resistance (AMR) globally. However, the potential for shared WGS data to guide interventions around AMR remains under-exploited, in part due to challenges in collating and transforming the growing volumes of data into timely insights. We present an interactive platform, amr.watch (https://amr.watch), that enables interrogation of AMR trends from public WGS data on an ongoing basis to support research and policy. MethodsThe amr.watch platform incorporates, analyses and visualises high-quality WGS data from WHO-defined priority bacterial pathogens. Analytics are performed using community-standard methods with bespoke species-specific curation of AMR mechanisms. FindingsBy 31 March 2025, amr.watch included data from 620,700 pathogen genomes with geotemporal information, with highly variable representation of different species and geographic regions. By integrating WGS data with sampling information, amr.watch enables users to assess geotemporal trends among genotypic variants (e.g. sequence types) and AMR mechanisms, with implications for interventions including antimicrobial prescribing and drug and vaccine development. Interpretationamr.watch is an information platform for scientists and policy-makers delivering ongoing situational awareness of AMR trends from genomic data. As broad adoption of WGS continues, amr.watch is positioned to monitor both pathogen populations and our global efforts in genomic surveillance, guiding control strategies tailored to each pathogens characteristics. FundingUK National Institute for Health Research & Gates Foundation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWhole genome sequencing (WGS) approaches enable us to track the spread of bacterial pathogens and antimicrobial resistance (AMR) with high resolution at local, national and global levels. To date, genomic studies assessing AMR dynamics have largely used retrospective data collected for specific research agendas. However, the growing volumes of publicly-shared WGS data, generated increasingly from routine surveillance, provide improved power to detect novel trends and guide interventions. Efforts to collate public bacterial genome data exist, such as AllTheBacteria, although these are aimed at the research community and do not facilitate data usage and interpretation by non-genomics experts, particularly those in public health. To our knowledge, no platforms exist for readily interrogating AMR dynamics from continuously updated public genome data across the array of different WHO priority bacterial pathogens. Of note, however, TyphiNet provides an interactive online dashboard for examining AMR trends exclusively from Salmonella Typhi using a periodically-updated data set from the Pathogenwatch platform. These findings are based on searching PubMed without language restrictions from Jan 1 2000 to December 31 2024, using terms related to "genomic surveillance" and "antimicrobial resistance". Added value of this studyWe have developed amr.watch which, to our knowledge, is the first platform that enables ongoing analysis and visualisation of AMR trends from public genome data across the spectrum of WHO priority bacterial pathogens via an accessible interface. Crucially, the platform incorporates processed genome data via a live always-on stream, enabling insights that are delayed only by the time to data deposition. We reviewed public genomes with available geotemporal information up until 31 March 2025, providing a contemporary global landscape of pathogen genome sequencing. While the number of genomes available annually grew over five-fold globally between 2010 and 2018, we also revealed the extent of differences in geographic representation, with 89.6% of genomes originating from high-income countries and 89 countries contributing no genome data from the priority pathogens. Implications of all the available evidenceRapid generation and sharing of global genome data enables us to more precisely track the spread and define the characteristics of contemporary circulating resistant pathogens. The amr.watch platform provides a solution for retrieving, curating and translating shared genomic data into relevant insights that are accessible and actionable by diverse stakeholders. It thereby forms a basis for monitoring progress in surveillance efforts, alerting on ongoing population changes and guiding enhanced precision for surveillance and interventional development. Additionally, our review of available bacterial genome data highlights the need for additional efforts to increase and sustain the implementation of genomic surveillance of AMR globally, and improve the timely sharing of WGS data and its associated metadata.

genomics↗

bioRxiv2025

An open-source, externally validated neural network algorithm to recognize daily life gait of older adults based on the lower-back sensor

BackgroundAccurate gait recognition from daily physical activities is a critical first step for further fall risk assessment and rehabilitation monitoring based on inertial sensors. However, most openly available models are based on healthy young adults ambulating in structured conditions. ObjectiveThis study aimed to develop an open-source and externally validated algorithm for daily-life gait recognition of older adults based on acceleration and angular velocity, as well as acceleration data only, and explore the effect of the use of data augmentation in the model training. MethodsA convolutional neural network was trained for gait recognition. The data for model training was lower-back inertial sensor data from 20 older adults (mean age 76 years old), with annotated synchronized activity labels in semi-structured and daily-life conditions. The data was randomly split into training, validation, and testing datasets by participants, and the model was trained multiple times using these different splits. The model was trained based on data from six channels (accelerations and angular velocities) and three channels (accelerations only) under conditions with and without data augmentation, respectively. External validation was evaluated based on lower-back sensor data collected from 47 stroke survivors (mean age 72.3 years old) in balance and walking tests. ResultsFor the testing dataset, the median accuracy ranged from 94 % to 98 %, precision from 63 % to 85 %, sensitivity from 95 % to 97 %, F1-score from 76 % to 90 %, and specificity from 94 % to 98 %. For the external validation dataset, the median accuracy ranged from 97 % to 100 %, precision from 99.9 % to 100 %, sensitivity from 71 % to 100 %, F1-score from 83 % to 100 %, and specificity 100 %. ConclusionsBased on lower-back-worn inertial sensor data, we provide an accurate, open-source, and externally validated daily-life gait recognition algorithm for older adults, with one model for six-axis input data and another for three-axis input data. Besides, we found when training the model, the use of data augmentation is especially helpful on the model based on acceleration data only.

bioengineering↗

bioRxiv2024

FaDAM3 and FaDAM4 are candidate genes for the regulation of seasonal dimorphism in cultivated strawberry

Cultivated strawberry (Fragaria ananassa) exhibits seasonal dimorphism between the summer and winter seasons. Under the influence of short day conditions, the winter morphology is induced, which includes shorter petioles, smaller and thicker leaves with higher concentrations of chlorophyll and higher density of trichomes. In peach (Prunus persica) the Dormancy-Associated MADS-box (DAM) gene family is involved in the regulation of winter dormancy, which closely resembles strawberry seasonal dimorphism in terms of timing and environmental regulation. In strawberry, six genes exist with close homology to the peach DAM genes. We analyzed the amino acid and coding sequences of these genes, and designated them FaDAM1-4 and FaSVP1-2. We found that there are three pairs of highly similar paralogs within the strawberry genome that exhibit similar expression patterns, although expression levels vary. FaDAM3 and FaDAM4 exhibit expression patterns that are consistent with seasonal dimorphism. We conclude that FaDAM3 and FaDAM4 are candidate genes for the regulation of seasonal dimorphism in strawberry.

plant biology↗