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423 result(s) for "Hartley, Matthew"
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\To serve a larger purpose\
\"To Serve a Larger Purpose\"calls for the reclamation of the original democratic purposes of civic engagement and examines the requisite transformation of higher education required to achieve it. The contributors to this timely and relevant volume effectively highlight the current practice of civic engagement and point to the institutional change needed to realize its democratic ideals.Using multiple perspectives,\"To Serve a Larger Purpose\"explores the democratic processes and purposes that reorient civic engagement to what the editors call \"democratic engagement.\" The norms of democratic engagement are determined by values such as inclusiveness, collaboration, participation, task sharing, and reciprocity in public problem solving and an equality of respect for the knowledge and experience that everyone contributes to education, knowledge generation, and community building. This book shrewdly rethinks the culture of higher education.
Diffusion-mediated HEI10 coarsening can explain meiotic crossover positioning in Arabidopsis
In most organisms, the number and distribution of crossovers that occur during meiosis are tightly controlled. All chromosomes must receive at least one ‘obligatory crossover’ and crossovers are prevented from occurring near one another by ‘crossover interference’. However, the mechanistic basis of this phenomenon of crossover interference has remained mostly mysterious. Using quantitative super-resolution cytogenetics and mathematical modelling, we investigate crossover positioning in the Arabidopsis thaliana wild-type, an over-expressor of the conserved E3 ligase HEI10, and a hei10 heterozygous line. We show that crossover positions can be explained by a predictive, diffusion-mediated coarsening model, in which large, approximately evenly-spaced HEI10 foci grow at the expense of smaller, closely-spaced clusters. We propose this coarsening process explains many aspects of Arabidopsis crossover positioning, including crossover interference. Consistent with this model, we also demonstrate that crossover positioning can be predictably modified in vivo simply by altering HEI10 dosage, with higher and lower dosage leading to weaker and stronger crossover interference, respectively. As HEI10 is a conserved member of the RING finger protein family that functions in the interference-sensitive pathway for crossover formation, we anticipate that similar mechanisms may regulate crossover positioning in diverse eukaryotes. Crossover numbers and positions are tightly controlled but the mechanism involved is still obscure. Here, the authors, using quantitative super-resolution cytogenetics and mathematical modelling, show that diffusion mediated coarsening of HEI10, an E3-ligase domain containing protein, may explain meiotic crossover positioning in Arabidopsis.
Using AI in bioimage analysis to elevate the rate of scientific discovery as a community
The future of bioimage analysis is increasingly defined by the development and use of tools that rely on deep learning and artificial intelligence (AI). For this trend to continue in a way most useful for stimulating scientific progress, it will require our multidisciplinary community to work together, establish FAIR (findable, accessible, interoperable and reusable) data sharing and deliver usable and reproducible analytical tools.
STARCH SYNTHASE 4 is required for normal starch granule initiation in amyloplasts of wheat endosperm
• Starch granule initiation is poorly understood at the molecular level. The glucosyltransferase, STARCH SYNTHASE 4 (SS4), plays a central role in granule initiation in Arabidopsis leaves, but its function in cereal endosperms is unknown. We investigated the role of SS4 in wheat, which has a distinct spatiotemporal pattern of granule initiation during grain development. • We generated TILLING mutants in tetraploid wheat (Triticum turgidum) that are defective in both SS4 homoeologs. The morphology of endosperm starch was examined in developing and mature grains. • SS4 deficiency led to severe alterations in endosperm starch granule morphology. During early grain development, while the wild-type initiated single ‘A-type’ granules per amyloplast, most amyloplasts in the mutant formed compound granules due to multiple initiations. This phenotype was similar to mutants deficient in B-GRANULE CONTENT 1 (BGC1). SS4 deficiency also reduced starch content in leaves and pollen grains. • We propose that SS4 and BGC1 are required for the proper control of granule initiation during early grain development that leads to a single A-type granule per amyloplast. The absence of either protein results in a variable number of initiations per amyloplast and compound granule formation.
dtool and dserver: A flexible ecosystem for findable data
Making data FAIR-findable, accessible, interoperable, reproducible-has become the recurring theme behind many research data management efforts. dtool is a lightweight data management tool that packages metadata with immutable data to promote accessibility, interoperability, and reproducibility. Each dataset is self-contained and does not require metadata to be stored in a centralised system. This decentralised approach means that finding datasets can be difficult. dtool's lookup server, short dserver, as defined by a REST API, makes dtool datasets findable, hence rendering the dtool ecosystem fit for a FAIR data management world. Its simplicity, modularity, accessibility and standardisation via API distinguish dtool and dserver from other solutions and enable it to serve as a common denominator for cross-disciplinary research data management. The dtool ecosystem bridges the gap between standardisation-free data management by individuals and FAIR platform solutions with rigid metadata requirements.
A data science roadmap for open science organizations engaged in early-stage drug discovery
The Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery. We present here the recommendations of a working group composed of experts from both the public and private sectors. Robust data management requires precise ontologies and standardized vocabulary while a centralized database architecture across laboratories facilitates data integration into high-value datasets. Lab automation and opening electronic lab notebooks to data mining push the boundaries of data sharing and data modeling. Important considerations for building robust machine-learning models include transparent and reproducible data processing, choosing the most relevant data representation, defining the right training and test sets, and estimating prediction uncertainty. Beyond data-sharing, cloud-based computing can be harnessed to build and disseminate machine-learning models. Important vectors of acceleration for hit and chemical probe discovery will be (1) the real-time integration of experimental data generation and modeling workflows within design-make-test-analyze (DMTA) cycles openly, and at scale and (2) the adoption of a mindset where data scientists and experimentalists work as a unified team, and where data science is incorporated into the experimental design. Artificial intelligence is greatly accelerating research in drug discovery, but its development is still hindered by the lack of available data. Here the authors present data management and data science recommendations to help reach AI’s potential in the field.
dtool and dserver: A flexible ecosystem for findable data
Making data FAIR— f indable, a ccessible, i nteroperable, r eproducible—has become the recurring theme behind many research data management efforts. dtool is a lightweight data management tool that packages metadata with immutable data to promote a ccessibility, i nteroperability, and r eproducibility. Each dataset is self-contained and does not require metadata to be stored in a centralised system. This decentralised approach means that finding datasets can be difficult. dtool’s lookup server, short dserver , as defined by a REST API, makes dtool datasets f indable, hence rendering the dtool ecosystem fit for a FAIR data management world. Its simplicity, modularity, accessibility and standardisation via API distinguish dtool and dserver from other solutions and enable it to serve as a common denominator for cross-disciplinary research data management. The dtool ecosystem bridges the gap between standardisation-free data management by individuals and FAIR platform solutions with rigid metadata requirements.
Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory
The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replication. However, for some PRC2 targets, a purely histone-based system for epigenetic inheritance may be insufficient. We address this issue at the Polycomb target FLOWERING LOCUS C (FLC) in Arabidopsis thaliana , as a narrow nucleation region of only ~three nucleosomes within FLC mediates epigenetic state switching and subsequent memory over many cell cycles. To explain the memory’s unexpected persistence, we introduce a mathematical model incorporating extra protein memory storage elements with positive feedback that persist at the locus through DNA replication, in addition to histone modifications. Our hybrid model explains many features of epigenetic switching/memory at FLC and encapsulates generic mechanisms that may be widely applicable.
Local chromatin environment of a Polycomb target gene instructs its own epigenetic inheritance
Inheritance of gene expression states is fundamental for cells to ‘remember’ past events, such as environmental or developmental cues. The conserved Polycomb Repressive Complex 2 (PRC2) maintains epigenetic repression of many genes in animals and plants and modifies chromatin at its targets. Histones modified by PRC2 can be inherited through cell division. However, it remains unclear whether this inheritance can direct long-term memory of individual gene expression states (cis memory) or instead if local chromatin states are dictated by the concentrations of diffusible factors (trans memory). By monitoring the expression of two copies of the Arabidopsis Polycomb target gene FLOWERING LOCUS C (FLC) in the same plants, we show that one copy can be repressed while the other is active. Furthermore, this ‘mixed’ expression state is inherited through many cell divisions as plants develop. These data demonstrate that epigenetic memory of FLC expression is stored not in trans but in cis. Genetic material is contained within molecules of DNA. In plants and many other organisms, these DNA molecules are packaged around proteins called histones to make a structure known as chromatin. Altering how the DNA is packaged in chromatin can control the activity of genes. For example, a group of proteins called the Polycomb Repressive Complex 2 (PRC2) adds methyl tags to histones, which can alter the packaging of chromatin to lower the activity of particular genes. When a cell divides, it is sometimes important that genes in the daughter cells have similar levels of activity as the parent cell. This allows individual cells to ‘remember’ past events, such as exposure to cold temperatures or other environmental conditions. The pattern of methyl tags on histones can be passed onto the daughter cells, but it is not clear if this is actually responsible for providing the memory. One gene that PRC2 regulates is called FLC, which influences when a plant called Arabidopsis produces flowers. If the plants are exposed to cold temperatures, the activity of FLC is repressed. FLC activity remains low after the period of cold has ended to ensure that the plants produce flowers at an appropriate time. If this 'memory of cold' is held locally in the chromatin of the FLC gene, then it should be possible for two copies of the FLC gene in the same cell to show different gene activities. However, if the memory is stored more globally inside each cell by other proteins, then the two copies should have identical gene activities. To distinguish between these two possibilities, Berry et al. added different fluorescent tags to two copies of the FLC gene in Arabidopsis plants, which allowed the activity of each gene copy to be tracked in individual cells under a microscope. The experiments show that one copy of FLC may be switched off, while the other remains switched on inside the same cell. Furthermore, it was found that this pattern of gene activity is passed onto the daughter cells when the original cell divides. Berry et al.'s findings show that the memory of FLC gene activity is stored locally in the chromatin of the FLC gene itself. The alteration of histones by PRC2 is one important aspect of the packaging of chromatin. The next challenge is to identify what other features of chromatin are required for a gene to be able to store this memory locally.