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Ward, M. J.

Publications and source records attributed to Ward, M. J..

3 recordsLinked to original sources

The left midfusiform gyrus interacts with early visual cortex and the anterior temporal lobe to support word individuation.

The left mid-ventral temporal cortex (lmVTC) plays a dynamic role in reading. In this study we investigated the neural interactions that influence lmVTC dynamics and the lexical information these interactions are dependent on. We monitored activity with either intracranial electroencephalography or magnetoencephalography while participants viewed real words, pseudowords, consonant strings, and false fonts. A coarse level representation in early lmVTC activity allowed for decoding of visually dissimilar real words, pseudowords, and false fonts. Functional interactions between anterior ventral temporal regions, possibly containing stored knowledge about words, and low-order visual regions occurred after this initial stage of processing and was followed by the individuation of orthographically similar real words in lmVTC, but not similar pseudowords, letter strings, or false fonts. These results suggest that the individuation of real word representations in lmVTC is catalyzed by stored knowledge about word forms that emerges from network-level interactions with anterior regions of the temporal lobe.

neuroscience

Pan-cancer deconvolution of cellular composition identifies molecular correlates of antitumour immunity and checkpoint blockade response

The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a novel DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: immune hot and immune cold, which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity, and oncogenic driver events. We demonstrate the existence of such tumour subgroups pan-cancer, link clonal-neoantigen burden to hot tumours, and show that transcriptional signatures of hot tumours are selectively engaged in immunotherapy responders. We also find that treatment-naive hot tumours are markedly enriched for known immune-resistance genomic alterations and define a catalogue of novel and known mediators of active antitumour immunity, deriving biomarkers and potential targets for precision immunotherapy.

cancer biology

Spot dynamics in a reaction-diffusion model of plant root hair initiation

We study pattern formation in a 2-D reaction-diffusion (RD) sub-cellular model characterizing the effect of a spatial gradient of a plant hormone distribution on a family of G-proteins associated with root-hair (RH) initiation in the plant cell Arabidopsis thaliana. The activation of these G-proteins, known as the Rho of Plants (ROPs), by the plant hormone auxin, is known to promote certain protuberances on root hair cells, which are crucial for both anchorage and the uptake of nutrients from the soil. Our mathematical model for the activation of ROPs by the auxin gradient is an extension of the model of Payne and Grierson [PLoS ONE, 12(4), (2009)], and consists of a two-component Schnakenberg-type RD system with spatially heterogeneous coefficients on a 2-D domain. The nonlinear kinetics in this RD system model the nonlinear interactions between the active and inactive forms of ROPs. By using a singular perturbation analysis to study 2-D localized spatial patterns of active ROPs, it is shown that the spatial variations in the nonlinear reaction kinetics, due to the auxin gradient, lead to a slow spatial alignment of the localized regions of active ROPs along the longitudinal midline of the plant cell. Numerical bifurcation analysis, together with time-dependent numerical simulations of the RD system are used to illustrate both 2-D localized patterns in the model, and the spatial alignment of localized structures.

plant biology