37 research outputs found

    Characterisation of peroxisome-organelle contacts and cooperation

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    Peroxisomes are organelles which are vital for human health and development. They represent dynamic subcellular compartments which play cooperative roles in essential cellular metabolic processes such as lipid metabolism and redox balance. For example, cooperation between peroxisomes and the endoplasmic reticulum (ER) is essential for the production of myelin lipids which are required for normal neurological function. We recently discovered that peroxisome-ER interaction is mediated by physical linkages in the form of membrane contact sites. These contact sites are mediated by the interaction of peroxisomal ACBD5 and ER-resident VAPB proteins. ACBD5-deficient patients have recently been identified who display retinal dystrophy, white matter disease and accumulation of very-long-chain fatty acids, which can only be degraded in peroxisomes. There is currently a need to develop simple and robust tools to allow efficient visualisation and quantification of these membrane contact sites to further their characterisation and investigate their function. Moreover, these should allow the dynamics of membrane contact sites under physiological conditions to be assessed. This study presents the optimisation of two systems to investigate peroxisome-ER interactions, the proximity ligation assay, DuolinkÂź and a split fluorescent reporter system, split superfolder green fluorescent protein. These allow peroxisome-ER interactions to be visualised and measured in situ with a fluorescence-based readout when the organelles are in close proximity. These systems are powerful and modifiable and will help further characterise peroxisome-ER (or other organelle) membrane contacts and shed light on the interplay between peroxisomes and the ER

    Turduckenℱ Legal Writing: Deconstructing the Multi-State Performance Test Genre

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    The Multistate Performance Test (MPT) has been praised as the most redeeming part of the otherwise unredeemable bar exam because it most aligns with what new attorneys do in practice. It has also been praised, along with other performance tests, as a useful teaching tool throughout the law school curriculum. This article builds on prior scholarship about the MPT by analyzing the MPT as a tool for teaching and testing legal writing and professional communication skills. The new insight that this article brings is that the testing aspect of the MPT tends to engulf the teaching aspect; understanding both of these attributes of the MPT and how they complement one another enhances the efficacy of the MPT as a teaching tool. To get the most out of the MPT as a bar taker or a law teacher, view the MPT as a legal writing assignment stuffed inside a teaching tool that is then stuffed inside a time-pressured test. To help convey this layering, you might think of the MPT as a legal writing Turducken, which is a layered dish with “a chicken stuffed inside a duck that’s then stuffed inside a turkey.” From the outside, the MPT is a test—a timed test. That’s the turkey part of the Turducken. But somewhere inside that test is a decent legal writing assignment. That’s the chicken part of the Turducken. And the chicken is pretty great for teaching legal writing skills! Because these two layers currently clash more than they complement each other, we suggest connecting the two with thoughtful teaching. That’s the duck—a rich, juicy layer of pedagogy that can keep the testing turkey from overwhelming and compromising the benefits of the legal writing chicken. This article deconstructs the MPT by examining each layer, with the goal of teaching bar takers to develop best legal writing practices while also preparing for a time-pressured test of “minimal competency.” The article also offers serving suggestions! The National Conference of Bar Examiners recently announced that it plans to remake the Uniform Bar Exam into a performance test, so the last part of the article details how to improve the MPT to better assess bar takers’ professional communication skills and practice readiness

    Gender Issues: Through the Glass Ceiling, Human Trafficking, and Domestic Violence

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    The overall purpose of this research paper is to look more in depth into the problem of Gender Issues in the workplace by focusing on three main issues that are present in today’s society and how a light can be shed on them. We start explaining the Glass Ceiling and how it can hold back not just women, but other minorities as well. Then we look into Human Trafficking and how it’s important to look at the signs in the workplace before it gets severely dangerous for that individual. Lastly, we touch on the issue that is summarized as Domestic Violence by explaining that it does not just affect the person\u27s private life, but can also affect the person\u27s work life and even the employers business, if not later taken care of. We will explain each of these issues in depth and provide recommendations to lessen these issues for employers, organizations and even individuals alike. Surveys performed will also present the knowledge that individuals have on the different issue

    A transdisciplinary complex adaptive systems (T-CAS) approach to developing a national school-based culture of prevention for health improvement: the school health research network (SHRN) in Wales

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    The paper reflects on a transdisciplinary complex adaptive systems (T-CAS) approach to the development of a school health research network (SHRN) in Wales for a national culture of prevention for health improvement in schools. A T-CAS approach focuses on key stages and activities within a continuous network cycle to facilitate systems level change. The theory highlights the importance of establishing transdisciplinary strategic partnerships to identify and develop opportunities for system reorientation. Investment in and the linking of resources develops the capacity for key social agents to take advantage of disruption points in the re-orientated system, and engagement activities develop the network to facilitate new social interactions and opportunities for transdisciplinary activities. A focus on transdisciplinary action research to co-produce interventions, generate research evidence and inform policy and practice is shown to play an important part in developing new normative processes that act to self-regulate the emerging system. Finally, the provision of reciprocal network benefits provides critical feedback loops that stabilise the emerging adaptive system and promote the network cycle. SHRN is shown to have embedded itself in the system by securing sustainability funding from health and education, a key role in national and regional planning and recruiting every eligible school to the network. It has begun to reorient the system to one of evidence generation (56 research studies co-produced) and opportunities for data-led practice at multiple levels. Further capacity development will be required to capitalise on these. The advantages of a complex systems approach to address barriers to change and the transferability of a T-CAS network approach across settings and cultures are highlighted

    A transdisciplinary complex adaptive systems (T-CAS) approach to developing a national school-based culture of prevention for health improvement: the school health research network (SHRN) in Wales

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    The paper reflects on a transdisciplinary complex adaptive systems (T-CAS) approach to the development of a school health research network (SHRN) in Wales for a national culture of prevention for health improvement in schools. A T-CAS approach focuses on key stages and activities within a continuous network cycle to facilitate systems level change. The theory highlights the importance of establishing transdisciplinary strategic partnerships to identify and develop opportunities for system reorientation. Investment in and the linking of resources develops the capacity for key social agents to take advantage of disruption points in the re-orientated system, and engagement activities develop the network to facilitate new social interactions and opportunities for transdisciplinary activities. A focus on transdisciplinary action research to co-produce interventions, generate research evidence and inform policy and practice is shown to play an important part in developing new normative processes that act to self-regulate the emerging system. Finally, the provision of reciprocal network benefits provides critical feedback loops that stabilise the emerging adaptive system and promote the network cycle. SHRN is shown to have embedded itself in the system by securing sustainability funding from health and education, a key role in national and regional planning and recruiting every eligible school to the network. It has begun to reorient the system to one of evidence generation (56 research studies co-produced) and opportunities for data-led practice at multiple levels. Further capacity development will be required to capitalise on these. The advantages of a complex systems approach to address barriers to change and the transferability of a T-CAS network approach across settings and cultures are highlighted

    The deuteron: structure and form factors

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    A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

    Genome-wide analysis of Sphingomonas wittichii RW1 behaviour during inoculation and growth in contaminated sand.

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    The efficacy of inoculation of single pure bacterial cultures into complex microbiomes, for example, in order to achieve increased pollutant degradation rates in contaminated material (that is, bioaugmentation), has been frustrated by insufficient knowledge on the behaviour of the inoculated bacteria under the specific abiotic and biotic boundary conditions. Here we present a comprehensive analysis of genome-wide gene expression of the bacterium Sphingomonas wittichii RW1 in contaminated non-sterile sand, compared with regular suspended batch growth in liquid culture. RW1 is a well-known bacterium capable of mineralizing dibenzodioxins and dibenzofurans. We tested the reactions of the cells both during the immediate transition phase from liquid culture to sand with or without dibenzofuran, as well as during growth and stationary phase in sand. Cells during transition show stationary phase characteristics, evidence for stress and for nutrient scavenging, and adjust their primary metabolism if they were not precultured on the same contaminant as found in the soil. Cells growing and surviving in sand degrade dibenzofuran but display a very different transcriptome signature as in liquid or in liquid culture exposed to chemicals inducing drought stress, and we obtain evidence for numerous 'soil-specific' expressed genes. Studies focusing on inoculation efficacy should test behaviour under conditions as closely as possible mimicking the intended microbiome conditions

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Turduckenℱ Legal Writing: Deconstructing the Multi-State Performance Test Genre

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    The Multistate Performance Test (MPT) has been praised as the most redeeming part of the otherwise unredeemable bar exam because it most aligns with what new attorneys do in practice. It has also been praised, along with other performance tests, as a useful teaching tool throughout the law school curriculum. This article builds on prior scholarship about the MPT by analyzing the MPT as a tool for teaching and testing legal writing and professional communication skills. The new insight that this article brings is that the testing aspect of the MPT tends to engulf the teaching aspect; understanding both of these attributes of the MPT and how they complement one another enhances the efficacy of the MPT as a teaching tool. To get the most out of the MPT as a bar taker or a law teacher, view the MPT as a legal writing assignment stuffed inside a teaching tool that is then stuffed inside a time-pressured test. To help convey this layering, you might think of the MPT as a legal writing Turducken, which is a layered dish with “a chicken stuffed inside a duck that’s then stuffed inside a turkey.” From the outside, the MPT is a test—a timed test. That’s the turkey part of the Turducken. But somewhere inside that test is a decent legal writing assignment. That’s the chicken part of the Turducken. And the chicken is pretty great for teaching legal writing skills! Because these two layers currently clash more than they complement each other, we suggest connecting the two with thoughtful teaching. That’s the duck—a rich, juicy layer of pedagogy that can keep the testing turkey from overwhelming and compromising the benefits of the legal writing chicken. This article deconstructs the MPT by examining each layer, with the goal of teaching bar takers to develop best legal writing practices while also preparing for a time-pressured test of “minimal competency.” The article also offers serving suggestions! The National Conference of Bar Examiners recently announced that it plans to remake the Uniform Bar Exam into a performance test, so the last part of the article details how to improve the MPT to better assess bar takers’ professional communication skills and practice readiness
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