Biology subjects

Wright, H.

Publications and source records attributed to Wright, H..

7 recordsLinked to original sources

bioRxiv2026

Gut Microbiome Composition in Older Adults with PTSD Symptoms and Trauma-Exposed Controls: Findings from the GUMP Study

Background: Emerging evidence suggests that alterations in the gut microbiome may contribute to mental health outcomes through the gut-brain axis. However, older adults with post-traumatic stress disorder (PTSD) remain underrepresented in microbiome research. This pilot study investigated associations between PTSD symptoms, dietary fibre intake, cognitive function, and gut microbiome functional capacity in adults aged 50 years and older. Methods: Participants with PTSD symptoms and trauma-exposed controls (TEC) completed validated assessments of mental health, trauma exposure, and dietary fibre intake. A subset of participants provided stool samples for microbiome analysis and undertook cognitive function assessment. Quantitative PCR was used to assess phylum-level taxonomy and butyrate-producing bacterial pathways (terminal butyrate generating enzyme), with abundances normalised to the 16S rRNA gene. Results: Participants with PTSD demonstrated significantly greater mental health symptom burden and poorer performance on cognitive tasks related to executive function, working memory, and learning. Dietary fibre intake did not differ significantly between PTSD and TEC groups and no significant differences in overall microbial composition were identified at the phylum level. In contrast, differences were more apparent when assessing functional microbiome pathways, with butyrate kinase abundance significantly lower in PTSD participants than TEC participants. When stratified by fibre intake, a greater butyrogenic capacity was observed in the High fibre TEC participants compared to the Low fibre TEC participants, while little difference was observed in the PTSD fibre-stratified groups. Substantial inter-individual variation was also evident across both taxonomic and functional measures. Conclusions: These findings suggest that functional characteristics of the gut microbiome may provide greater insight into PTSD-related biological processes than broad taxonomic measures alone. Dietary fibre intake may be associated with greater butyrate-producing capacity in trauma-exposed older adults without PTSD symptoms, although this relationship appeared less evident among older adults living with PTSD symptoms. These findings support further investigation of microbiome function, diet, and cognition within the gut-brain axis. Larger studies incorporating metagenomic and metabolomic approaches are warranted.

microbiology↗

bioRxiv2026

Systematic mapping of emergent transcriptional states in interacting single-cell dyads by Cell-Cell-seq

Cell-cell interactions drive rapid and heterogeneous changes in gene expression, yet most transcriptomic methods either dissociate cells, losing pair identity and interaction timing, or infer communication indirectly from ligand-receptor co-expression. Here we present Cell-Cell-seq, a scalable workflow for profiling defined cell pairs ("dyads") with single-cell transcriptomic resolution. Cell-Cell-seq uses cavity-containing hydrogel microparticles (Nanovials) to confine two cells, synchronize contact onset, protect fragile conjugates during handling and sorting, and interface directly with droplet-based RNA sequencing. Using antigen-matched prostate tumor cells and engineered T cells as a model system, Cell-Cell-seq captured thousands of tumor-T cell dyads and revealed broad functional and transcriptional heterogeneity across interactions. Dyads unmasked transient activation programs that were obscured in standard well-plate co-culture, consistent with asynchronous contact in bulk assays. To distinguish interaction-induced programs from the composite nature of dyad transcriptomes, we developed a pseudo-mixing framework that generates in silico pseudo-dyads to construct an empirical null distribution under "no interaction," enabling statistically robust identification of emergent genes and partner-resolved attribution of responses. Dyad-resolved analysis further revealed coordinated cross-cell programs, including coupled chemokine expression consistent with bidirectional paracrine signaling and inverse coupling between tumor immunoregulatory programs and T cell activation. Finally, we introduce ccRepair to correct compositional dilution in mixed transcriptomes, improving interpretability while preserving genuine cross-cell coordination. Together, Cell-Cell-seq provides a generalizable platform for dissecting immune synapse biology and mapping interaction-dependent programs across heterogeneous cell populations, with applications in profiling tumor-immune communication and functionally screening immunotherapies.

bioengineering↗

bioRxiv2025

Pan-genome analyses of 226 finger millet-infecting Magnaporthe oryzae strains from eastern Africa reveal two lineages that differ in their genetic make-up, virulence and effector gene content with gene loss driven by homologous recombination between Pot2 elements

Blast disease, caused by the filamentous ascomycete Magnaporthe oryzae, is the main biotic constraint to finger millet production in eastern Africa. M. oryzae is a pathogen on many grass species, but the high host-specificity of blast isolates underscores the need to study pathogen diversity and virulence at the host level. Here, we fill a void on knowledge on finger millet-infecting strains of M. oryzae by sequencing 226 isolates pure-cultured from infected tissues, mainly peduncles and panicles, sampled from field-grown finger millet accessions across Ethiopia, Kenya, Tanzania and Uganda. Phylogenetic analysis showed that eastern African isolates are genetically distinct from Asian isolates, and differentiated into two groups potentially driven by climate variables. One group was dominated by isolates from Kenya and Uganda (KU group), and the other by isolates from Ethiopia and Tanzania (ET group). Analysis of the portfolio of 887 predicted effector genes showed that the KU group had significantly fewer effectors, concomitant with higher virulence levels on the two finger millet accessions tested. We demonstrate that homologous recombination between transposable elements, leading to genomic deletions, plays a key role in gene removal. Transcript profiling of fungal genes in compatible and incompatible interactions revealed upregulation in the incompatible interaction as a characteristic of an estimated 30% of effector genes, including seven of the eight homologs of known avirulence genes from rice-infecting M. oryzae identified in our study. Prioritization of these effectors for functional validation will pave the way for identifying cognate resistance genes and improving finger millet for resistance to blast disease.

plant biology↗

bioRxiv2024

Explicit and implicit locomotor learning in individuals with chronic hemiparetic stroke

Motor learning involves both explicit and implicit processes that are fundamental for acquiring and adapting complex motor skills. However, stroke may damage the neural substrates underlying explicit and/or implicit learning, leading to deficits in overall motor performance. While both learning processes are typically used in concert in daily life and rehabilitation, no gait studies have determined how these processes function together after stroke when tested during a task that elicits dissociable contributions from both. Here, we compared explicit and implicit locomotor learning in individuals with chronic stroke to age- and sex-matched neurologically intact controls. We assessed implicit learning using split-belt adaptation (where two treadmill belts move at different speeds). We assessed explicit learning (i.e., strategy-use) using visual feedback during split-belt walking to help individuals explicitly correct for step length errors created by the split-belts. The removal of visual feedback after the first 40 strides of split-belt walking, combined with task instructions, minimized contributions from explicit learning for the remainder of the task. We utilized a multi-rate state-space model to characterize individual explicit and implicit process contributions to overall behavioral change. The computational and behavioral analyses revealed that, compared to controls, individuals with chronic stroke demonstrated deficits in both explicit and implicit contributions to locomotor learning, a result that runs counter to prior work testing each process individually during gait. Since post-stroke locomotor rehabilitation involves interventions that rely on both explicit and implicit motor learning, future work should determine how locomotor rehabilitation interventions can be structured to optimize overall motor learning. New and noteworthyMotor learning involves both implicit and explicit processes, the underlying neural substrates of which could be damaged by after stroke. While both learning processes are typically used in concert in daily life and rehabilitation, no gait studies have determined how these processes function together after stroke. Using a locomotor task that elicits dissociable contributions from both processes and computational modeling, we found evidence that chronic stroke causes deficits in both explicit and implicit locomotor learning.

neuroscience↗

bioRxiv2020

Polycomb represses a gene network controlling puberty via modulation of histone demethylase Kdm6b expression

Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1, a puberty-activating gene, is a key target of this silencing mechanism. Using a gain-of-function approach and a systems biology strategy we now show that EED, an essential PcG component, acts in the arcuate nucleus of the hypothalamus to alter the functional organization of a gene network involved in the stimulatory control of puberty. A central node of this network is Kdm6b, which encodes an enzyme that erases the PcG-dependent histone modification H3K27me3. Kiss1 is a first neighbor in the network; genes encoding glutamatergic receptors and potassium channels are second neighbors. By repressing Kdm6b expression, EED increases H3K27me3 abundance at these gene promoters, reducing gene expression throughout a gene network controlling puberty activation. These results indicate that Kdm6b repression is a basic mechanism used by PcG to modulate the biological output of puberty-activating gene networks.

neuroscience↗

bioRxiv2019

Advancing clinical cohort selection with genomics analysis on a distributed platform

BackgroundThe affordability of next-generation genomic sequencing and the improvement of medical data management have contributed largely to the evolution of biological analysis from both a clinical and research perspective. Precision medicine is a response to these advancements that places individuals into better-defined subsets based on shared clinical and genetic features. The identification of personalized diagnosis and treatment options is dependent on the ability to draw insights from large-scale, multi-modal analysis of biomedical datasets. Driven by a real use case, we premise that platforms that support precision medicine analysis should maintain data in their optimal data stores, should support distributed storage and query mechanisms, and should scale as more samples are added to the system. ResultsWe extended a genomics-based columnar data store, GenomicsDB, for ease of use within a distributed analytics platform for clinical and genomic data integration, known as the ODA framework. The framework supports interaction from an i2b2 plugin as well as a notebook environment. We show that the ODA framework exhibits worst-case linear scaling for array size (storage), import time (data construction), and query time for an increasing number of samples. We go on to show worst-case linear time for both import of clinical data and aggregate query execution time within a distributed environment. ConclusionsThis work highlights the integration of a distributed genomic database with a distributed compute environment to support scalable and efficient precision medicine queries from a HIPAA-compliant, cohort system in a real-world setting. The ODA framework is currently deployed in production to support precision medicine exploration and analysis from clinicians and researchers at UCLA David Geffen School of Medicine.

bioinformatics↗

bioRxiv2017

Elucidating the genetic architecture of reproductive ageing in the Japanese population

Population studies over the past decade have successfully elucidated the genetic architecture of reproductive ageing. However, those studies were largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, in up to 67,029 women of Japanese ancestry, we report 26 loci (all P<5x10{macron}8) for puberty timing or age at menopause, representing the first loci for reproductive ageing in any non-European population. Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European populations, highlighting the benefits and challenges of large-scale trans-ethnic approaches.

genetics↗