Biology subjects

James, A.

Publications and source records attributed to James, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Epidemiological model selection unravels the molecular processes of antiviral resistance from experimental phytoplankton-virus dynamics

Phytoplankton-virus interactions are pivotal in understanding the intertwined dynamics of these key players of the global carbon cycle. Although antiviral resistance is the main hypothesis to solve the apparent paradox of their coexistence, identifying its molecular determinisms and mechanisms, as well as their dynamical consequences, remains challenging. By combining hypotheses about such determinisms and mechanisms, we designed 36 dynamical models and fitted them to experimental infection kinetics in a pioneering selection model approach. Through such a multiple hypotheses testing, we identified that resistance in the model species Ostreococcus tauri is most likely to be predominantly intracellular, to control lysis through budding, and to be acquired by phenotypic plasticity. We further showed that viral kinetics are strongly impacted by both the antiviral resistance's molecular determinants and virions' inactivation through attachment to lysis detritus, as the latter generates a key negative feedback loop during the 'bust' stage of the interaction dynamics.

ecology↗

bioRxiv2026

TxNova: recovery of recurrent unannotated intergenic splice loci from existing bulk RNA-seq alignments

Background. Reference catalogs such as GENCODE capture most stably expressed mammalian genes but may not include condition-restricted or low-abundance transcripts. Reads supporting unannotated intergenic splice junctions are generally absent from annotation-restricted gene-count matrices; transcript assemblers may reconstruct a subset as novel models, but those models are typically handled separately from the annotated gene-count universe. TxNova is a lightweight command-line tool that directly indexes these unannotated splices from existing BAM files - without an external assembler, gffcompare, or workflow manager - yielding candidate leads for bench validation rather than standalone discovery claims. Methods. TxNova retains CIGAR N junctions from STAR/HISAT2 BAM files that recur in >= 2 samples and are absent from a comprehensive annotation, clusters them into residual loci, and counts each locus alongside annotated genes in a unified matrix. Structure gates - canonical splice motif, same-strand distance, coverage valley, bridging-junction absence, minimum length - remove likely artifacts to yield structure-pass models. An optional contrast filter retains loci detected in treatment but nearly silent in control. Results. A residual splice is a recurrent, unannotated CIGAR N junction that does not overlap any annotated gene body; intronic and antisense channels are out of scope. Across four published mouse treatment arms (GSE221720, GSE166522, GSE157460, GSE193335), harvest catalogs yielded 464, 657, 789, and 594 loci. On GSE221720, 45% of loci (209/464) shared an exact intron with another series, versus 0.074% for excluded junctions; a coordinate-placement control yielded 0/5,000 matches for length-matched intergenic decoys. Masked-gene recovery reached 87.6% (176/201) overall and 99.4% (176/177) among genes with a leak junction - sensitivity rather than precision estimates. An optional contrast provides a presence/absence screen on interval TPM. Residual models are partial reconstructions requiring cloning, RACE, or targeted proteomics for confirmation. Conclusions. TxNova produces a reproducible intergenic residual-locus catalog from existing BAM files, with four downloadable mouse injury/infection catalogs. Cross-series recurrence and coordinate-based null controls support reproducibility above simple placement backgrounds but do not by themselves establish biological validity. The optional contrast step offers a practical screen for candidate leads warranting experimental validation.

bioinformatics↗

bioRxiv2026

scATrans: annotating single-cell differential expression as transcription- or stabilization-weighted using unspliced RNA

Single-cell differential expression (DE) reports changes in mature mRNA abundance, but the same fold-change can reflect faster synthesis or slower decay. Metabolic labeling resolves this ambiguity but is costly and cannot be applied retrospectively to the vast majority of published scRNA-seq. scATrans closes this gap using layers every standard pipeline already generates: from DE-selected genes, a reference-corrected unspliced residual annotates each change as transcription- or stabilization-weighted, with no additional experiment. Benchmarked against metabolic-labeling systems with independent kinetic ground truth, the residual separates the two mechanisms at matched mature abundance (ROC-AUC 0.68-0.74, full-length NASC-seq2 K562; 0.59-0.63, 3' scEU-seq RPE1); effect size scales with intron capture, not model complexity, and explicit kinetic fitting adds nothing over the static contrast. Per-gene, the residual recovers the classical bulk exon-intron contrast (EISA); what scATrans adds is the inference layer single-cell reanalysis actually needs--DE-defined membership, gene-structure correction, a capture-regime reliability pre-flight, induction-matched testing, and a permutation-calibrated program score--so that confident calls are reserved for where the data support them: gene programs, not single genes. Applied to standard 10x data with no labeling, scATrans recovers textbook post-transcriptional biology: a curated AU-rich-element program is called stabilization-weighted in LPS-stimulated PBMCs (confirmed by per-donor pseudobulk DE in an independent four-donor cohort), while a glucocorticoid-response program is called transcription-weighted in dexamethasone-treated A549 cells-- opposite mechanisms recovered from unlabeled counts. scATrans turns any spliced/unspliced-resolved DE table into a mechanism-typed one, retrospectively and at scale. Availability and implementationscATrans requires Python [≥]3.9, interoperates with the scverse ecosystem (AnnData, Scanpy), and is released under the Apache-2.0 license. Install with pip install scatrans or from Bioconda. Documentation and tutorials: https://scatrans.readthedocs.io. Analyses in this manuscript use software version 0.10.9.

bioinformatics↗

bioRxiv2026

Nutrient flux governs osteogenic fate commitment through the SLC3A1-cystine Axis

Skeletal and mesenchymal cells have limited bone-forming potential due to their rarity, tendency for senescence and/or unstable osteogenic lineage commitment. We previously identified an osteopotent CXCR4 stem cell population with unclear mechanism for its differentiation potential. Here, we found that the cystine transporter SLC3A1 was selectively enriched in CXCR4+ stem cells, uncovering a role for amino acid transport in regulating osteogenic fate commitment. Enforced SLC3A1 expression reprogrammed mesenchymal cells toward a stable osteogenic state while suppressing adipogenic differentiation. Mechanistically, SLC3A1-mediated cystine flux established a glutathione-dependent metabolic program that preserved mitochondrial fitness and restrained stem cell senescence. SLC3A1 also stabilized IGF-1 through suppression of ZMYND8-mediated ubiquitination, uncovering ZMYND8 as a previously unrecognized E3 ligase regulating osteogenic commitment. Cystine supplementation phenocopied the effects of SLC3A1 activation, promoting osteogenic differentiation and skeletal regeneration without genetic manipulation. In vivo, cystine administration accelerated bone regeneration and attenuated ovariectomy-induced bone loss, while analyses of a human osteoporosis cohort, osteoporotic specimens, and single-cell transcriptomic datasets revealed coordinated suppression of the SLC3A1-cystine-IGF-1 pathway in osteoporotic mesenchymal cells. Taken together, these findings establish SLC3A1-mediated cystine transport as a programmable metabolic determinant of osteogenic fate commitment and identify cystine metabolism as a therapeutically targetable axis for skeletal regeneration and osteoporosis.

cell biology↗

bioRxiv2026

Microbial mechanistic requirements for eliciting a topical and intranasal immune response

The skin colonist Staphylococcus epidermidis elicits a potent antibody response that can be redirected against an antigen of interest, but this process relies on genetic engineering.1 Here, by adapting bioorthogonal chemistry methods to conjugate antigens to the cell surface, we make the process of generating a commensal vaccine rapid and efficient. A wide variety of bacteria displaying tetanus toxin fragment C (TTFC) elicit an antibody response when applied to mice topically, indicating that the inductive process is not limited to colonists. Colonization occurs at two different sites, the skin and nostril; by colonizing each with S. epidermidis-TTFC, we show that skin colonization yields a moderate IgG response, while nostril colonization elicits a highly potent systemic IgG response and an exuberant IgA response in the nostrils, lungs, and intestine. Two lines of evidence are consistent with the nasal-associated lymphoid tissue (NALT) as the inductive site for nostril colonization: imaging suggesting robust bacterial translocation, and the induction of commensal-specific B cells following colonization. On the skin, TTFC must be conjugated to live S. epidermidis to elicit an antibody response; in the nostrils, live S. epidermidis-TTFC and S. epidermidis mixed with TTFC are equally potent. Commensal vaccination yields a robust response in pet shop mice, and chemical conjugation facilitates antibody responses to a broad array of antigens, including a whole viral capsid and a rotavirus immunogen. Collectively, these findings provide compelling evidence of a translational path for commensal vaccines.

microbiology↗

bioRxiv2026

Heat-Triggered Dormancy Release in Low-ROS Pollen Grains Reveals a Conserved Reproductive Reserve

Pollen development and fertilization are considered the most heat-sensitive stages of plant reproduction. While heat stress severely impairs pollen germination and tube growth, the physiological diversity within a single flowers pollen load suggests that subpopulations may exhibit differential climate resilience. In this study, we tested the hypothesis that this heterogeneity reflects a dormancy-based reserve mechanism that preserves fertilization under heat stress. Using flow cytometry and fluorescence-activated cell sorting in Arabidopsis thaliana and Solanum lycopersicum (MicroTom), we resolved pollen subpopulations by reactive oxygen species (ROS) status and examined their behavior under increasing heat stress. In both species, ROS-defined metabolic state was tightly associated with pollen size: high-ROS pollen was larger and readily germination-competent, whereas low-ROS pollen was smaller and showed low basal germination, consistent with dormancy. Heat stress preferentially depleted the high-ROS fraction, whereas the low-ROS fraction persisted and, under heat stress, increased metabolic activity and size. By isolating low-ROS and high-ROS pollen, we further show that a brief heat treatment suppresses germination of active high-ROS pollen but promotes germination of dormant low-ROS pollen. These findings provide direct evidence that heat can release dormancy in low-ROS pollen and support a conserved model in which dormant pollen serves as a heat-resilient reproductive reserve.

plant biology↗

bioRxiv2026

The compounding costs of being female in academia: Individual-based modelling of career progression and interventions

We develop a novel individual-based population dynamics model of academic career progression, using 15 years of data from over 1,000 academics from one university. Our model improves on previous models, which, by homogenising career progression, may underestimate the costs of being female. We find multiple effects that compound to slow career progression for women. Women are hired at lower ranks than men, then face the sticky floor problem of getting stuck at the bottom for longer. Further, individuals in STEM fields are promoted more quickly; this disproportionately affects women who are more prevalent in non-STEM fields. Our model reveals age is more complicated than others have found with ODE-based models. Women are older when hired, and promotions favour the young; hence age costs women more. Finally, the probability of attrition rises with years spent at the same rank, regardless of gender. Since women are promoted slower, they experience higher attrition rates. We also deploy our model to test possible interventions. We find just hiring more women will not work. A more nuanced set of interventions is required. Gender parity will only be achieved at the highest ranks if hiring rates are jointly equalised across gender, academic rank, and discipline.

scientific communication and education↗

bioRxiv2026

Metabolomic and Transcriptomic rewiring between virus resistance and susceptibility in Ostreococcus mediterraneus

The genus Ostreococcus, comprising picoeukaryotic unicellular algae, plays a key role in many coastal marine ecosystems. These phytoplankton are infected by lytic double-stranded DNA prasinoviruses against whom they have the capacity to reliably evolve stable antiviral resistance. Regulation of virus resistance and susceptibility is hypothesized to arise through a phenotypic switch, as resistant cell lines can be isolated from susceptible lines after viral exposure and vice versa. To elucidate the molecular mechanisms underlying this resistance, we integrated untargeted metabolomic analyses and transcriptomics in virus-resistant and virus-susceptible lines of O. mediterraneus. Transcriptomic analyses corroborated previous findings in O. tauri, revealing that most gene expression changes were concentrated on a single chromosome. Specifically, a [~]530 kb region was over-transcribed in virus-resistant lines, while a distinct [~]110 kb region was over-expressed in virus-susceptible lines. Comparative metabolomics identified several oxidized galactolipids and oxidized sterols as biomarkers of the susceptible phenotype, while fewer biomarkers were identified for the resistant phenotype. By integrating transcriptomic and metabolomic signatures--focusing on the expression of genes within biosynthetic pathways linked to these metabolite biomarkers--we uncovered candidate molecular mechanisms underlying the cellular physiology of susceptible versus resistant phenotypes. Authors SummaryViruses are the most abundant biological entities in the ocean, shaping the dynamics of phytoplankton communities that underpin marine food webs. Ostreococcus, one of the smallest photosynthetic eukaryotes, is frequently infected by highly abundant prasinoviruses in its natural environment. In this study, we aimed to understand the physiological bases of virus-resistant and susceptible Ostreococcus mediterraneus lines. We compared gene expression and untargeted metabolite profiles between a resistant line and a susceptible line derived from it. The metabolic profiles were much more variable between replicates than the transcriptomic profiles and the most differentially expressed genes did not include those involved in the biosynthetic pathways of the metabolite biomarkers identified. We estimated the congruence between the metabolomes and transcriptomes as the percent of relative expression changes fitting to the relative change in the metabolite. This study provides evidence of the subtle links between gene expression and metabolomic signatures and the importance of integrating multiple levels of cellular processes.

microbiology↗

bioRxiv2025

Sensorineural regulation of skull healing implicates FGF1 signaling in non-healing bone

Bone injuries demonstrate rapid peripheral nerve ingrowth followed by nerve pruning as healing ensues. However, in non-healing bone injuries, peripheral innervation remains elevated, the implications of which remain unknown. Therefore, we investigated the neuroskeletal microenvironment in subcritical-and critical-sized calvarial defects using quantitative 3D fluorescence imaging. We identified elevated densities of peripheral nerves and Osterix positive (Osx+) osteoprogenitors in critical-sized defects, while osteogenic differentiation markers were severely diminished. Moreover, Osx+ osteoprogenitors in critical-sized defects exhibited enhanced proximity to peripheral nerves, which in turn was associated with increased osteoprogenitor cell proliferation. Using retrograde tracing in conjunction with single cell RNA-sequencing of sensory nerves from the innervating trigeminal ganglia, genes encoding for nerve-secreted proliferative and anti-differentiation factors were identified. Specifically, FGF-1/FGFR-1 signaling was identified as a significant neuroskeletal interaction with critical-sized defects demonstrating higher FGF-1 expression in fluorescence imaging. Presence of FGF-1 in neurons innervating the calvarial was confirmed, and neural conditioned media depleted for FGF1 showed enhanced induction of osteogenesis when placed on parietal bone cells. Collectively, we identify a sensorineural-skeletal signaling interaction elevated in critical-sized defects that can be leveraged as a potential therapeutic target for enhancing bone healing.

bioengineering↗

bioRxiv2025

The W-index: a novel tool to evaluate gender equity in STEM research

Gender inequities in scientific research persist, from citation indices to collaboration networks and funding success. Current estimates for achieving equal representation remain in timescales of decades to centuries. To help individuals and groups improve their gender representation in a shorter timeframe, we present the W-index, a simple metric to evaluate gender ratios, and specifically the representation of women, in research collaborations and other aspects of scientific life. Here it is applied to three case studies: internal collaborations derived from six years of research outputs across a university, co-author groups from 60 years of publications across a journal collection, and supervisor-student relationships over 60 years. Despite contrasting sources, these datasets show common features: W-index increases as the proportion of women increases W-index also increases with age or career stage, and women have a consistently higher W-index compared to men. We finish with reflections and recommendations for individuals, organisations, and funding bodies to action positive and timely change towards gender equity.

scientific communication and education↗

bioRxiv2025

Deep multiplexed 50-marker imaging of circulating tumor cells expands actionable biomarker profiling for precision oncology

Liquid biopsy-derived circulating tumor cells (CTCs) offer a minimally invasive avenue for precision oncology by enabling longitudinal monitoring of actionable molecular and cell-phenotypic biomarkers. However, conventional immunofluorescence imaging-based CTC profiling captures just 4-5 markers per cell, restricting crucial insights into oncogenic and resistance drivers, as well as tumor cell heterogeneity. Here we present an integrated pipeline employing deep multiplexed imaging to profile up to 50 molecular markers per CTC, capturing expression, phosphorylation, and subcellular localization of diverse biomarkers. Validated in a multi-stage prostate cancer resistance model and applied to prostate cancer patient-derived CTCs, this approach enhances CTC classification and reveals inter- and intra-patient heterogeneity correlating with therapy response. Machine learning identified therapeutically actionable signatures, suggesting patient-specific treatment strategies. This deep multiplexed imaging pipeline advances the utility of CTCs in guiding personalized cancer therapy by providing comprehensive molecular and phenotypic insights through minimally invasive liquid biopsies. Highlights- Multiplexed immunofluorescence imaging of circulating tumor cells captures up to 50 molecular markers per cell with subcellular localisation. - Single-cell and subcellular analyses identify quantitative signatures correlating with patient outcome, as well as therapeutically actionable biomarkers. - This method transforms the utility of CTCs for future use in patient stratification and for guiding personalised therapies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/684075v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@a36ff4org.highwire.dtl.DTLVardef@b06c1org.highwire.dtl.DTLVardef@1e8a572org.highwire.dtl.DTLVardef@c60753_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

cancer biology↗

bioRxiv2025

Spatial and spectral mapping of traffic-related air pollution (TRAP) nanoparticles in relation to plaques and inflammatory markers in an Alzheimer disease model

Chronic exposure to traffic-related air pollution (TRAP) is linked to increased risk of neurodegenerative diseases, including Alzheimer disease (AD). Ultrafine particulate matter (UFPM) is a suspected driver of TRAP neurotoxicity, but its spatial interactions with AD pathology remain poorly defined. We investigated the distribution, composition, and pathological context of TRAP-derived UFPM in the hippocampus of TgF344-AD rats chronically exposed to TRAP or filtered air (FA) for 14 months. Using a multimodal imaging workflow that combines enhanced darkfield hyperspectral imaging (EDF-HSI) with confocal immunofluorescence for microglia (CD68/Iba1) and amyloid beta (A{beta}) plaques (Thioflavin S), we mapped the localization and spectral properties of UFPM in situ. UFPM accumulation was elevated in TRAP-exposed females, suggesting sex-specific vulnerability in blood-brain barrier (BBB) permeability or particle retention. Particles near plaques showed red-shifted spectral signatures, consistent with biochemical transformation. Dimension reduction revealed clustering of particle spectra by TRAP exposure and plaque proximity. However, UFPM was rarely found within plaques or microglia, implying indirect neuroimmune modulation. These findings highlight a novel spatial and spectral imaging approach for characterizing environmental nanoparticle interactions in the brain and suggest that chronic TRAP exposure may influence AD-related inflammation and pathology in a sex-and region-dependent manner. SynopsisThis study shows that chronic traffic-related air pollution alters ultrafine particulate matter deposition and neuroinflammation in a rodent Alzheimer model, revealing region- and sex-specific vulnerability in the brains response to environmental exposure.

pharmacology and toxicology↗

bioRxiv2024

Targeting GOF p53 and c-MYC through LZK Inhibition or Degradation Suppresses Head and Neck Tumor Growth

The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by MAP3K13) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplified MAP3K13. A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules. Inhibition of LZK catalytic activity suppressed tumor growth in HNSCC PDX models with amplified MAP3K13. We found that the kinase activity of LZK stabilized c-MYC and that LZK stabilized gain-of-function (GOF) p53 through a kinase-independent mechanism. Therefore, we designed proteolysis-targeting chimeras (PROTACs) and demonstrate that our lead PROTAC promotes LZK degradation and suppresses expression of GOF p53 and c-MYC leading to impaired viability of HNSCC cell lines. This research provides a strong basis for development of therapeutics targeting LZK in HNSCCs with amplification of the gene. One Sentence SummaryThis study establishes the kinase LZK as a therapeutic target for HNSCC through regulation of c-MYC expression.

cancer biology↗

bioRxiv2024

Sex differences in deep brain shape and asymmetry persist across schizophrenia and healthy individuals: A meta-analysis from the ENIGMA-Schizophrenia Working Group

BackgroundSchizophrenia (SCZ) is characterized by a disconnect from reality that manifests as various clinical and cognitive symptoms, and persistent neurobiological abnormalities. Sex-related differences in clinical presentation imply separate brain substrates. The present study characterized deep brain morphology using shape features to understand the independent effects of diagnosis and sex on the brain, and to determine whether the neurobiology of schizophrenia varies as a function of sex. MethodsThis study analyzed multi-site archival data from 1,871 male (M) and 955 female (F) participants with SCZ, and 2,158 male and 1,877 female healthy controls (CON) from twenty-three cross-sectional samples from the ENIGMA Schizophrenia Workgroup. Harmonized shape analysis protocols were applied to each sites data for seven deep brain regions obtained from T1-weighted structural MRI scans. Effect sizes were calculated for the following main contrasts: 1) Sex effects;2) Diagnosis-by-Sex interaction; 3) within sex tests of diagnosis; 4) within diagnosis tests of sex differences. Meta-regression models between brain structure and clinical variables were also computed separately in men and women with schizophrenia. ResultsMass univariate meta-analyses revealed more concave-than-convex shape differences in all regions for women relative to men, across diagnostic groups (d = -0.35 to 0.20, SE = 0.02 to 0.07); there were no significant diagnosis-by-sex interaction effects. Within men and women separately, we identified more-concave-than-convex shape differences for the hippocampus, amygdala, accumbens, and thalamus, with more-convex-than-concave differences in the putamen and pallidum in SCZ (d = -0.30 to 0.30, SE = 0.03 to 0.10). Within CON and SZ separately, we found more-concave-than-convex shape differences in the thalamus, pallidum, putamen, and amygdala among females compared to males, with mixed findings in the hippocampus and caudate (d = -0.30 to 0.20, SE = 0.03 to 0.09). Meta-regression models revealed similarly small, but significant relationships, with medication and positive symptoms in both SCZ-M and SCZ-F. ConclusionsSex-specific variation is an overriding feature of deep brain shape regardless of disease status, underscoring persistent patterns of sex differences observed both within and across diagnostic categories, and highlighting the importance of including it as a critical variable in studies of neurobiology. Future work should continue to explore these dimensions independently to determine whether these patterns of brain morphology extend to other aspects of neurobiology in schizophrenia, potentially uncovering broader implications for diagnosis and treatment. Key PointsO_LIStatistical analyses revealed significant main effects for diagnosis and sex in deep brain shape morphology. Among patients with schizophrenia, there was a pattern of thinning and surface contraction in the bilateral hippocampus, amygdala, accumbens, and thalamus, and a pattern of significant thickening and surface expansion in the bilateral putamen and pallidum compared to healthy control participants. Between males and females, there was a pattern of significant thinning and surface contraction in the bilateral thalamus, pallidum, putamen, and amygdala in females compared to males. C_LIO_LIThere was no significant interaction between diagnosis and biological sex, suggesting that sex differences in deep brain shape and asymmetry among patients with schizophrenia reflect those observed in healthy individuals. C_LIO_LISmall but statistically significant relationships exist between brain structure and clinical correlates of schizophrenia were similar for both men and women with the disease, such that higher CPZ was associated with shape-derived thinning and surface contraction in the caudate, accumbens, hippocampus, amygdala, and thalamus, and elevated positive symptoms were associated with shape-derived thinning and surface contraction in the bilateral caudate, right hippocampus, and right amygdala. C_LI

neuroscience↗

bioRxiv2024

Illuminating root-soil mechanics

Soil compaction and escalating global drought increase soil strength and stiffness. It remains unclear which plant root biomechanical mechanisms/traits enable growth in these harsh conditions. Here, we combine synchrotron X-ray computed tomography with spatially resolved X-ray diffraction to characterize the biomechanics of a replica root-soil system. We map the strain field around the root tip, finding strong agreement with finite element simulations, thereby demonstrating a promising new in-vivo measurement protocol.

biophysics↗

bioRxiv2024

CRISPR activation of Tfeb, a master regulator of autophagy and lysosomal biogenesis, in osteoblast lineage cells increases bone mass and strength

Autophagy is a recycling pathway in which damaged or dysfunctional proteins, protein aggregates, and organelles are delivered to lysosomes for degradation. Insufficiency of autophagy is thought to contribute to several age-related diseases including osteoporosis. Consistent with this, elimination of autophagy from the osteoblast lineage reduces bone formation and causes low bone mass. However, whether increasing autophagy would benefit bone health is unknown. Here, we increased expression of the endogenous Transcription Factor EB gene (Tfeb) in osteoblast lineage cells in vivo via CRISPR activation. Tfeb overexpression stimulated autophagy and lysosomal biogenesis in osteoblasts. Tfeb overexpressing male mice displayed a robust increase in femoral and vertebral cortical thickness at 4.5 months of age. Histomorphometric analysis revealed that the increase in femoral cortical thickness was due to increased bone formation at the periosteal surface. Tfeb overexpression also increased femoral trabecular bone volume. Consistent with these results, bone strength was increased in Tfeb overexpressing mice. Female Tfeb overexpressing mice also displayed a progressive increase in bone mass over time and at 12 months of age had high cortical thickness and trabecular bone volume. This increase in vertebral trabecular bone volume was due to elevated bone formation. Osteoblastic cultures showed that Tfeb overexpression increased proliferation and osteoblast formation. Overall, these results demonstrate that stimulation of autophagy in osteoblast lineage cells promotes bone formation and strength and may represent an effective approach to combat osteoporosis.

physiology↗

bioRxiv2024

Female-dominated disciplines have lower evaluated research quality and funding success rates, for men and women

We use data from 30 countries and find that the more women in a discipline, the lower quality the research in that discipline is evaluated to be and the lower the funding success rate is. This affects men and women, and is robust to age, number of research outputs, and bibliometric measures where such data are available. Our work builds on others findings that womens work is valued less, regardless of who performs that work.

scientific communication and education↗

bioRxiv2023

Coding dynamics of the striatal networks during learning

The rat dorsomedial (DMS) and dorsolateral striatum (DMS), equivalent to caudate nucleus and putamen in primates, are generally required for goal-directed and habit behaviour, respectively. However, it is still unclear whether and how this functional dychotomy emerges in the course of learning. In this study we investigated this issue by recording DMS and DLS single neuron activity in rats performing a continuous spatial alternation task, from the acquisition to optimized performance. We first applied a classical analytical approach to identify task-related activity based on the modifications of single neuron firing rate in relation to specific task events or maze trajectories. We then used an innovative approach based on Hawkes process to reconstruct a directed connectivity graph of simultaneously recorded neurons, that was used to decode animal behavior. This approach enabled us to better unravel the role of DMS and DLS neural networks across learning stages. We showed that DMS and DLS display different task-related activity throughout learning stages, and the proportion of coding neurons over time decreases in the DMS and increases in the DLS. Despite theses major differences, the decoding power of both networks increases during learning. These results suggest that DMS and DLS neural networks gradually reorganize in different ways in order to progressively increase their control over the behavioral performance.

neuroscience↗