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Foster, J. A.

Publications and source records attributed to Foster, J. A..

6 recordsLinked to original sources

Molecular and biological characterization of a distinct species of Lolavirus infecting different accessions of seashore paspalum, a turfgrass, widely grown in the United States

Seashore paspalum (Paspalum sp.), is an economically significant grass used in golf courses, sports fields, and landscaping in the United States. A novel Lolavirus, tentatively named paspalum latent virus (PaLV), was identified for the first time in seashore paspalum plants from the USDA National Plant Germplasm System (NPGS) using high-throughput sequencing. Three complete genome sequences of PaLV from different Paspalum accessions, with a length of 6,995 nucleotides (nt), not including the poly(A) tail, were obtained by Rapid Amplification of cDNA Ends and Sanger sequencing. Phylogenetic analysis based on the replicase protein sequences from the Alphaflexiviridae family revealed that PaLV grouped with the Lolavirus genus, with the closest relative being Lolium latent virus (LoLV). PaLV shares less than 72% nt identity to the replicase and coat protein genes of LoLV, which demarks PaLV as a new species and the second member of the genus. Furthermore, the coat protein region showed intense negative selection pressure and low spatially structured diversity. Host range analysis of PaLV showed that wheat, corn, sorghum, and Lolium are systemic hosts of PaLV. A one-step RT-PCR technique was developed to reliably detect PaLV infection.

pathology↗

Assigning Targetable Molecular Pathways to Transdiagnostic Subgroups Across Autism and Related Neurodevelopmental Disorders

The heterogeneity of autism and related neurodevelopmental conditions has impeded accurate prognoses and treatment discovery. Using translational neuroimaging across 135 mouse models (3,515 mice) and two human MRI datasets (n = 1,234 and n = 1,015), we derived participant subgroups from shared neuroanatomical features. These subgroups did not distinguish autism, ADHD, or OCD diagnoses and only modestly differentiated cognitive and behavioural phenotypes. Instead, they mapped onto four molecular pathways: (1) synaptic function; (2) MAPK and Wnt signalling; (3) chromatin modification and cellular stress responses; and (4) broader chromatin, immune, and second-messenger signalling pathways. This framework bridges preclinical models and idiopathic human neurodevelopmental conditions, linking patients to biologically relevant molecular mechanisms.

neuroscience↗

Comprehensive phylogenomics of Methylobacterium reveals four evolutionary distinct groups and underappreciated phyllosphere diversity.

Methylobacterium is a group of methylotrophic microbes associated with soil, fresh water, and particularly the phyllosphere, the aerial part of plants that has been well-studied in terms of physiology but whose evolutionary history and taxonomy are unclear. Recent work has suggested that Methylobacterium is much more diverse than thought previously, questioning its status as an ecologically and phylogenetically coherent taxonomic genus. However, taxonomic and evolutionary studies of Methylobacterium have mostly been restricted to model species, often isolated from habitats other than the phyllosphere, and have yet to utilize comprehensive phylogenomic methods to examine gene trees, gene content, or synteny. By analyzing 189 Methylobacterium genomes from a wide range of habitats, including the phyllosphere, we inferred a robust phylogenetic tree while explicitly accounting for the impact of horizontal gene transfers. We showed that Methylobacterium contains four evolutionary distinct groups of bacteria (namely A, B, C, D), characterized by different genome size, GC content, gene content and genome architecture, revealing the dynamic nature of Methylobacterium genomes. In addition of recovering 59 described species, we identified 45 candidate species, mostly phyllosphere-associated, stressing the significance of plants as a reservoir of Methylobacterium diversity. We inferred an ancient transition from a free-living lifestyle to association with plant roots in Methylobacteriaceae ancestor, followed by phyllosphere association of three of the major groups (A, B, D), which early branching in Methylobacterium history was heavily obscured by HGT. Together, our work lays the foundations for a thorough redefinition of Methylobacterium taxonomy, beginning with the abandon of Methylorubrum.

genomics↗

Mouse models of immune dysfunction: Their neuroanatomical differences reflect their anxiety-behavioural phenotype

Extensive evidence supports the role of the immune system in modulating brain function and behaviour. However, past studies have revealed striking heterogeneity in behavioural phenotypes produced from immune system dysfunction. Using magnetic resonance imaging (MRI), we studied the neuroanatomical differences among 11 distinct genetically-modified mouse lines (n=371), each deficient in a different element of the immune system. We found a significant and heterogeneous effect of immune dysfunction on the brains of both male and female mice. However, by imaging the whole brain and using bayesian hierarchical modelling, we were able to identify patterns within the heterogeneous phenotype. Certain structures -- such as the corpus callosum, midbrain, and thalamus -- were more likely to be affected by immune dysfunction. A notable brain-behaviour relationship was identified with neuroanatomy endophenotypes across mouse models clustering according to anxiety-like behaviour phenotypes reported in literature, such as altered volume in brains regions associated with promoting fear response (e.g., the lateral septum and cerebellum). Interestingly, genes with preferential spatial expression in the most commonly affected regions are also associated with multiple sclerosis and other immune-mediated diseases. In total, our data suggest that the immune system modulates anxiety behaviour through well-established brain networks.

neuroscience↗

FINE-SCALE ADAPTATIONS TO ENVIRONMENTAL VARIATION AND GROWTH STRATEGIES DRIVE PHYLLOSPHERE METHYLOBACTERIUM DIVERSITY.

Methylobacterium is a prevalent bacterial genus of the phyllosphere. Despite its ubiquity, little is known about the extent to which its diversity reflects neutral processes like migration and drift, versus environmental filtering of life history strategies and adaptations. In two temperate forests, we investigated how phylogenetic diversity within Methylobacterium was structured by biogeography, seasonality, and growth strategies. Using deep, culture-independent barcoded marker gene sequencing coupled with culture-based approaches, we uncovered a considerable diversity of Methylobacterium in the phyllosphere. We cultured different subsets of Methylobacterium lineages depending upon the temperature of isolation and growth (20 {degrees}C or 30 {degrees}C), suggesting long-term adaptation to temperature. To a lesser extent than temperature adaptation, Methylobacterium diversity was also structured across large (>100km; between forests) and small geographical scales (<1.2km within forests), among host tree species, and was dynamic over seasons. By measuring growth of 79 isolates at different temperature treatments, we observed contrasting growth performances, with strong lineage- and season-dependent variations in growth strategies. Finally, we documented a progressive replacement of lineages with a high-yield growth strategy typical of cooperative, structured communities, in favor of those characterized by rapid growth, resulting in convergence and homogenization of community structure at the end of the growing season. Together our results show how Methylobacterium is phylogenetically structured into lineages with distinct growth strategies, which helps explain their differential abundance across regions, host tree species, and time. This works paves the way for further investigation of adaptive strategies and traits within a ubiquitous phyllosphere genus. ImportanceMethylobacterium is a bacterial group tied to plants. Despite its ubiquity and importance to their hosts, little is known about the processes driving Methylobacterium community dynamics. By combining traditional culture-dependent and independent (metabarcoding) approaches, we monitored Methylobacterium diversity in two temperate forests over a growing season. On the surface of tree leaves, we discovered remarkably diverse and dynamic Methylobacterium communities over short temporal (from June to October) and spatial scales (within 1.2 km). Because we cultured different subsets of Methylobacterium diversity depending on the temperature of incubation, we suspected that these dynamics partly reflected climatic adaptation. By culturing strains in lab conditions mimicking seasonal variations, we found that diversity and environmental variations were indeed good predictors of Methylobacterium growth performances. Our findings suggest that Methylobacterium community dynamics at the surface of tree leaves results from the succession of strains with contrasted growth strategies in response to environmental variations.

microbiology↗

Neuron-derived extracellular vesicles extracted from plasma show altered size and miRNA cargo as a function of antidepressant drug response

Previous work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEVs) to circumvent these limitations and investigate neuronal miRNA changes associated with antidepressant response. Samples were collected at two time points (baseline and after 8 weeks of follow-up) from depressed patients who responded (N=20) and did not respond (N=20) to escitalopram treatment, as well as controls (N=20). Total extracellular vesicles (EVs) were extracted from plasma, and then further enriched for NDEVs by immunoprecipitation with L1CAM. EV size was measured using tunable resistive pulse sensing, and NDEV miRNA cargo was extracted and sequenced. Subsequently, studies in cell lines and postmortem tissue were conducted. Characterization of NDEVs revealed they were smaller than other EVs isolated from plasma (p<0.0001), had brain-specific neuronal markers, and contained miRNAs enriched for brain functions (p<0.0001) Furthermore, NDEVs from depressed patients were smaller than controls (p<0.05), and NDEV size increased with ADT response (p<0.01). Finally, changes in NDEV cargo, specifically changes in miR-21-5p, miR-30d-5p and miR-486-5p together (p<0.01), were associated with ADT response. Targets of these three miRNAs were altered in brain tissue from depressed individuals (p<0.05). Together, this study indicates that changes in peripherally isolated NDEVs can act as both a clinically accessible and informative biomarker of ADT response specifically through size and cargo.

neuroscience↗