21 research outputs found

    Quantifying How Staining Methods Bias Measurements of Neuron Morphologies

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    The process through which neurons are labeled is a key methodological choice in measuring neuron morphology. However, little is known about how this choice may bias measurements. To quantify this bias we compare the extracted morphology of neurons collected from the same rodent species, experimental condition, gender distribution, age distribution, brain region and putative cell type, but obtained with 19 distinct staining methods. We found strong biases on measured features of morphology. These were largest in features related to the coverage of the dendritic tree (e.g., the total dendritic tree length). Understanding measurement biases is crucial for interpreting morphological data

    Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

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    BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 Ă— coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

    Reconfiguring motor circuits for a joint manual and BCI task

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    MEA recordings supporting dual control BC

    Understanding Bcl-2 family interactions through computational modelling

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    © 2012 Benjamin James LansdellThe Bcl-2 family of 15 or more proteins are key regulators of the intrinsic apoptosis pathway. Elucidating the mechanisms of two of these proteins (Bak and Bax) used to control mitochondrial outer membrane permeabilisation and subsequent cytochrome c release is therefore the focus of significant research. The role played by the 'direct' and 'indirect' Bak activation mechanisms is yet to be fully elucidated. Insights can be gained, however, by studying a reduced experimental system in which only a subset of Bcl-2 family proteins are present. A mouse liver mitochondria (MLM) assay to monitor Bak-mediated permeabilisation provides such a system. This thesis develops a deterministic mass-action model of the relevant Bcl-2 family protein interactions in order to better understand the reduced mitochondrial system in vitro and therefore the intrinsic apoptosis pathway in vivo. By focusing on a simplified experimental system, a relatively complete, realistic model is constructed which is also tractable in terms of the number of unknown parameters and experimental verifiability. Issues in constructing a relevant and realistic model are discussed. The 'direct' and 'indirect' activation hypotheses are compared. The 'direct' activation mechanism is shown to be a required component of the model in matching with available experimental data. Previous studies have investigated the role bistability plays in apoptosis regulation. The models determined here do not exhibit any bistable phenomena while still being able to mimic the MLM experimental system and provide a mechanism for the regulation of cytochrome c release, calling into doubt the need for a Bcl-2 'bistable-switch' mechanism. A related model of Bcl-2 interactions in vivo is investigated and demonstrated to be capable of bistability. In this case the direct activation model is found to act as a more robust bistable switch, compared with an indirect activation model, in line with previous studies. Other properties of the models are investigated, such as their parametric robustness, which reveals the components of the models which are most sensitive to variation