140 research outputs found

    Sex, Ecology and the Brain: Evolutionary Correlates of Brain Structure Volumes in Tanganyikan Cichlids

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    Analyses of the macroevolutionary correlates of brain structure volumes allow pinpointing of selective pressures influencing specific structures. Here we use a multiple regression framework, including phylogenetic information, to analyze brain structure evolution in 43 Tanganyikan cichlid species. We analyzed the effect of ecological and sexually selected traits for species averages, the effect of ecological traits for each sex separately and the influence of sexual selection on structure dimorphism. Our results indicate that both ecological and sexually selected traits have influenced brain structure evolution. The patterns observed in males and females generally followed those observed at the species level. Interestingly, our results suggest that strong sexual selection is associated with reduced structure volumes, since all correlations between sexually selected traits and structure volumes were negative and the only statistically significant association between sexual selection and structure dimorphism was also negative. Finally, we previously found that monoparental female care was associated with increased brain size. However, here cerebellum and hypothalamus volumes, after controlling for brain size, associated negatively with female-only care. Thus, in accord with the mosaic model of brain evolution, brain structure volumes may not respond proportionately to changes in brain size. Indeed selection favoring larger brains can simultaneously lead to a reduction in relative structure volumes

    A Structured Model of Video Reproduces Primary Visual Cortical Organisation

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    The visual system must learn to infer the presence of objects and features in the world from the images it encounters, and as such it must, either implicitly or explicitly, model the way these elements interact to create the image. Do the response properties of cells in the mammalian visual system reflect this constraint? To address this question, we constructed a probabilistic model in which the identity and attributes of simple visual elements were represented explicitly and learnt the parameters of this model from unparsed, natural video sequences. After learning, the behaviour and grouping of variables in the probabilistic model corresponded closely to functional and anatomical properties of simple and complex cells in the primary visual cortex (V1). In particular, feature identity variables were activated in a way that resembled the activity of complex cells, while feature attribute variables responded much like simple cells. Furthermore, the grouping of the attributes within the model closely parallelled the reported anatomical grouping of simple cells in cat V1. Thus, this generative model makes explicit an interpretation of complex and simple cells as elements in the segmentation of a visual scene into basic independent features, along with a parametrisation of their moment-by-moment appearances. We speculate that such a segmentation may form the initial stage of a hierarchical system that progressively separates the identity and appearance of more articulated visual elements, culminating in view-invariant object recognition

    A Reaction-Diffusion Model to Capture Disparity Selectivity in Primary Visual Cortex

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    Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization

    Single-cell analysis tools for drug discovery and development

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    The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed

    Power analysis of single-cell RNA-sequencing experiments

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    Single-cell RNA sequencing (scRNA-seq) has become an established and powerful method to investigate transcriptomic cell-to-cell variation, thereby revealing new cell types and providing insights into developmental processes and transcriptional stochasticity. A key question is how the variety of available protocols compare in terms of their ability to detect and accurately quantify gene expression. Here, we assessed the protocol sensitivity and accuracy of many published data sets, on the basis of spike-in standards and uniform data processing. For our workflow, we developed a flexible tool for counting the number of unique molecular identifiers (https://github.com/vals/umis/). We compared 15 protocols computationally and 4 protocols experimentally for batch-matched cell populations, in addition to investigating the effects of spike-in molecular degradation. Our analysis provides an integrated framework for comparing scRNA-seq protocols.The study was supported by Cancer Research UK grant number C45041/A14953 to A Cvejic and C Labalette, European Research Council project 677501-ZF_Blood to A Cvejic and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute. The ERC grant ThSWITCH to SA Teichmann (grant no. 260507) and a Lister Institute Research Prize to SA Teichmann. KN Natarajan was supported by the Wellcome Trust Strategic Award “Single cell ge nomics of mouse gastrulation”

    SC3: consensus clustering of single-cell RNA-seq data

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    Single-cell RNA-seq enables the quantitative characterization of cell types based on global transcriptome profiles. We present single-cell consensus clustering (SC3), a user-friendly tool for unsupervised clustering, which achieves high accuracy and robustness by combining multiple clustering solutions through a consensus approach (http://bioconductor.org/packages/SC3). We demonstrate that SC3 is capable of identifying subclones from the transcriptomes of neoplastic cells collected from patients.V.Y.K., T.A., A.Y. and M.H. are supported by Wellcome Trust Grants. K.N.N. is supported by the Wellcome Trust Strategic Award 'Single cell genomics of mouse gastrulation'. M.T.S. acknowledges support from FRS-FNRS; the Belgian Network DYSCO (Dynamical Systems, Control and Optimisation), funded by the Interuniversity Attraction Poles Programme initiated by the Belgian State Science Policy Office; and the ARC (Action de Recherche Concerte) on Mining and Optimization of Big Data Models, funded by the Wallonia-Brussels Federation. M.B. acknowledges support from EPSRC (grant EP/N014529/1). T.C. was funded through a core funded fellowship by the Sanger Institute and a Chancellor′s fellowship from the University of Edinburgh. K.K. and A.R.G. are supported by Bloodwise (grant ref. 13003), the Wellcome Trust (grant ref. 104710/Z/14/Z), the Medical Research Council, the Kay Kendall Leukaemia Fund, the Cambridge NIHR Biomedical Research Center, the Cambridge Experimental Cancer Medicine Centre, the Leukemia and Lymphoma Society of America (grant ref. 07037) and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. W.R. was supported by BBSRC (grant ref. BB/K010867/1), the Wellcome Trust (grant ref. 095645/Z/11/Z), EU BLUEPRINT and EpiGeneSys
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