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Briggs, M.

Publications and source records attributed to Briggs, M..

3 recordsLinked to original sources

Why woodiness repeatedly evolves--and disappears

Derived woodiness--the evolution of woody growth from herbaceous ancestors--has arisen hundreds of times across flowering plants, yet the environmental conditions associated with its repeated evolution remain poorly understood. Here, we analyse woodiness evolution in the mustard family (Brassicaceae; ~4,150 species) using a time-calibrated phylogeny of 2,927 species, including 374 of the 385 known woody species, together with global growth-form and climatic niche data. We infer 231 independent origins of woodiness alongside 176 reversals to herbaceousness, indicating that woodiness evolves repeatedly but remains evolutionarily unstable. Although woody species are enriched on islands, most occur on the mainland, where woodiness is consistently associated with drought and reduced frost. Correlated-evolution analyses reveal that drought is associated primarily with the persistence of woodiness, whereas reduced frost is associated with gains of woodiness and increased frost with its loss. These findings identify distinct climatic associations with the gain, persistence, and loss of woody growth forms.

evolutionary biology↗

A spatiotemporal cancer cell trajectory underlies glioblastoma heterogeneity

Cancer cells display highly heterogeneous and plastic states in glioblastoma, an incurable brain tumour. However, how these malignant states arise and whether they follow defined cellular trajectories across tumours is poorly understood. Here, we generated a deep single cell and spatial multi-omic atlas of human glioblastoma that pairs transcriptomic, epigenomic and genomic profiling of 12 tumours across multiple regions. We identify that glioblastoma heterogeneity is driven by spatially-patterned transitions of cancer cells from developmental-like states towards those defined by a glial injury response and hypoxia. This cellular trajectory regionalises tumours into distinct tissue niches and manifests in a molecularly conserved manner across tumours as well as genetically distinct tumour subclones. Moreover, using a new deep learning framework to map cancer cell states jointly with clones in situ, we show that tumour subclones are finely spatially intermixed through glioblastoma tissue niches. Finally, we show that this cancer cell trajectory is intimately linked to myeloid heterogeneity and unfolds across regionalised myeloid signalling environments. Our findings define a stereotyped trajectory of cancer cells in glioblastoma and unify glioblastoma tumour heterogeneity into a tractable cellular and tissue framework.

cancer biology↗

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

BackgroundThe cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions. MethodsWe quantified cerebellar lobule volumes using structural magnetic resonance imaging in 4,215 adults (PTSD n= 1640; Control n=2575) across 40 sites from the from the ENIGMA-PGC PTSD working group. Using a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation, we obtained volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum total and subregional volume in PTSD compared to healthy controls. The Benjamini-Hochberg procedure was used to control the false discovery rate (p-FDR < .05). ResultsPTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume. In addition, people with PTSD showed reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), but also the vermis (VI, VIII), flocculonodular lobe (lobule X), and cerebellar white matter (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. ConclusionsThese findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in high-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

neuroscience↗