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p-tau Ser356 is associated with Alzheimer’s disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003
No full textTau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer’s disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease. This dataset refers to the publication ( https://doi.org/10.1007/s00401-023-02667-w )
Martian impact fracturing pervasively influences habitability
No full textThis file is a Jupiter notebook file of the data used to calculate the fracturing volume and surface area as laid out by Cockell, CS and Collins (2024) Martian impact fracturing pervasively influences habitability. Journal of Geophysical Research. The equations used to calculate that data are shown in that paper.This file is a Jupiter notebook file of the data used to calculate the fracturing volume and surface area as laid out by Cockell, CS and Collins (2024) Martian impact fracturing pervasively influences habitability. Journal of Geophysical Research. The equations used to calculate that data are shown in that paper
The behavioural profile of SYNGAP1- related Intellectual Disability - data and supplementary materials
No full textContains questionnaire data and the supplementary materials for the upcoming publication: Wright, D, Kenny, A., Mizen, L.A.M., McKechanie, A.G., & Stanfield, A.G. 'The behavioural profile of SYNGAP1-related Intellectual Disability'
This study aimed to describe the behavioural profile of individuals with SYNGAP1-ID. Parents/carers of 30 individuals aged 3-18 years old with a diagnosis of SYNGAP1-ID and 21 typically-developing individuals completed the Vineland-3 Adaptive Behaviour Scale and the Child Behavior Checklist. We found that those with SYNGAP1-ID showed fewer adaptive behaviours and higher levels of internalising and externalising behaviours across almost all domains compared to typically developing controls. There was some evidence that these differences were greatest in older children, and more apparent in those with co-occuring epilepsy. This characterisation of the phenotype of SYNGAP1-ID significantly aids our understanding of the behavioural profile of this population and is a step towards the development of tailored interventions
Supervised and unsupervised deep learning-based approaches for studying DNA replication spatiotemporal dynamics
No full textThis project aimed to demonstrate how deep learning could be leveraged for studying DNA replication spatiotemporal dynamics. Through well-characterised cellular models, we showed in both supervised and unsupervised settings how convolutional neural networks could successfully identify aberrant DNA replication dynamics, while additionally reconstructing progression through S-phase. We make the associated image datasets available here. Please refer to README.txt for further information
The type of carbon source not the growth rate it supports can determine diauxie
No full textHow cells choose between potential carbon sources is a classic example of cellular decision-making, and we know that many organisms prioritise glucose. Yet there has been little investigation of whether other sugars are also preferred, blinkering our view of carbon sensing. Here we study eukaryotic budding yeast and its growth on mixtures of sugars with palatinose, an isomer of sucrose that cells catabolise with the MAL regulon. We find that yeast prioritise galactose over palatinose, but sucrose and fructose only weakly if at all, despite each sugar being able to support faster growth than palatinose. Our results therefore suggest that the decision-making is more than carbon flux-sensing. By using genetic perturbations and transcriptomics, we show that there is repression of the MAL genes via Gal4, the master regulator of the GAL regulon. Mechanistically, cells enforce their preference for galactose over palatinose through preventing runaway positive feedback in the MAL regulon. They do so both by repressing MAL11, the gene encoding the palatinose transporter, and by early expression of the isomaltases IMA1 and IMA5. By cleaving palatinose, these enzymes prevent its intracellular concentration becoming sufficient to induce further MAL expression. Our results demonstrate that budding yeast actively maintain a preference for carbon sources other than glucose and that such preferences have been selected by more than differences in growth rates. They imply that carbon-sensing strategies even in unicellular organisms are more complex than previously thought.README.txt - A description of how the data is gathered and explanations of the column headings. combined_data.csv - A text file of time-series data of optical density and fluorescence in long table format
Topological Elasticity
No full textCodes to perform simulations, the topology analysis and data to generate the figures of our article: "Topological Linking Determines Elasticity in Limited Valence Networks". Giorgia Palombo, Simon Weir, Davide Michieletto and Yair Augusto Gutierrez Fosado.README.md files have a complete description of the dat
HEAL Asthma: Development of an intervention for people with limited health literacy to improve asthma self-management in Malaysia
No full textThere were 3 phases involved:
1. 1st phase: A qualitative study that explored the challenges faced by health care providers in delivering asthma care and implementing asthma self-management. was conducted.
2. 2nd phase: A pre-post feasibility study of paper-based pictorial asthma action plan (PAAP) to support asthma self-management among patients with low health literacy.
3. 3rd phase: A pre-post feasibility study of using mobile app to support asthma self-management among patients with low health literacy. The barriers and motivation to using the app was evaluated using a qualitative approach.
Documents shared are participants information sheet, questionnaires, participants sociodemographic data and the codebook for coding for qualitative
SUPERSEDED - Official Data Repository for DRED: Zero-Shot Transfer in Reinforcement Learning via Data-Regularised Environment Design
No full text## This item has been replaced by the one which can be found at [ https://doi.org/10.7488/ds/7769 ] ## Autonomous agents trained using deep reinforcement learning (RL) often lack the ability to successfully generalise to new environments, even when these environments share characteristics with the ones they have encountered during training. In this work, we investigate how the sampling of individual environment instances, or levels, affects the zero-shot generalisation (ZSG) ability of RL agents. We discover that, for deep actor-critic architectures sharing their base layers, prioritising levels according to their value loss minimises the mutual information between the agent's internal representation and the set of training levels in the generated training data. This provides a novel theoretical justification for the regularisation achieved by certain adaptive sampling strategies. We then turn our attention to unsupervised environment design (UED) methods, which assume control over level generation. We find that existing UED methods can significantly shift the training distribution, which translates to low ZSG performance. To prevent both overfitting and distributional shift, we introduce data-regularised environment design (DRED). DRED generates levels using a generative model trained to approximate the ground truth distribution of an initial set of level parameters. Through its grounding, DRED achieves significant improvements in ZSG over adaptive level sampling strategies and UED methods. Our code and experimental data are available at: Garcin et al, "DRED: Zero-Shot Transfer in Reinforcement Learning via Data-Regularised Environment Design", 2024, (https://github.com/uoe-agents/dred)
Summary of data retrieval process
No full textThis file contains a detailed discussion of how we went about corpus construction, with a particular focus on data retrieval. It discusses our use of Nexis and Factiva, Google and GDELT (via API), as well as the web scraping procedures used.This is a summary of the data retrieval process used in corpus construction, including the data included in our matrix, entitled 'Global English Language Corpus of Humanitarian News.
ASZ - As (ISO 639-3: asz) segmented files
No full textThis dataset contains segmented audio files from several of the raw recordings in the As (ISO 639-3: asz) collection; the full collection is available here: https://datashare.ed.ac.uk/handle/10283/8574. These segmented files are designed to facilitate searches for a particular word or construction in the As collection. Full information on how to navigate these segmented files using the filenames is given in the Documentation file. The audio files in this dataset come from recordings that were made during two trips: the first were recorded between 10 and 14 January 2020 in Asbaken village (Sorong regency, Southwest Papua province, Indonesia), and the second between 29 March and 4 April 2023 in locations in Sorong city (Southwest Papua province, Indonesia). This dataset relates to the British Academy Postdoctoral Fellowship 'Synchronic and diachronic investigations in Raja Ampat-South Halmahera, a little-known subbranch of Austronesian' (PF19\100004);additional fieldwork funds were provided by a Moray Endowment Grant from the University of Edinburgh. Further deposits are available in the related DataShare sub-community (https://datashare.ed.ac.uk/handle/10283/8573)