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SUPERSEDED - Single-cell metabolic oscillations are pervasive and may alleviate a proteome constraint
## This item has been replaced by the one which can be found at [https://doi.org/10.7488/ds/7845] ## Biological rhythms not only coordinate cellular activity with external signals, but may also enable internal
coordination. The metabolic cycle in budding yeast is perhaps the most well-studied example. Historically
researchers have investigated this cycle in populations growing in chemostats, but more recently time-lapse
microscopy has revealed single-cell oscillations in the redox state of enzyme cofactors and in ATP levels.
How to relate the results of these two types of assays is however unclear. Here we report single-cell rhythms
too in intracellular pH and show that oscillations in the redox state of flavin molecules occur in auxotrophic
and prototrophic strains, in nutrients favouring respiration or fermentation, and in deletion mutants for
which oscillations in chemostats are either unobservable or disrupted. To explain the pervasiveness of
these rhythms, we postulate that cells generate oscillations to alleviate a proteome constraint – amino
acids cells use for one class of enzymes are unavailable for others. Using flux balance analysis with an
enzyme-constrained genome-scale metabolic model, we show that, with a finite proteome, sequential
synthesis of biomass components typically generates a shorter doubling time than synthesising components
in parallel. Our results suggest that the metabolic cycle drives growth and is potentially widespread because
all cells grow within a proteome constraint.File descriptions are included in README.tx
Neural networks weights related to "Super-resolution of turbulence with dynamics in the loss"
A set of routines to train neural networks to perform super-resolution, without necessarily requiring high-resolution data, along with network weights used to generate figures in the publication "Super-resolution of turbulence with dynamics in the loss", (J. Page, Journal of Fluid Mechanics, accepted 2024).
Implementation wraps around the spectral version of JAX-CFD (https://github.com/google/jax-cfd). Neural networks are written in Keras using the JAX backend.
This dataset consists of a series of python scripts and .h5 files of network weights, organised into subdirectories:
code/ # scripts used to train and analyse the networks (python, requires installation of keras + JAX backend, JAX-CFD)
paper_weights/ # weights for the neural networks as documented in the paper.
# subdirectories here point to different Reynolds numbers (100, 1000) with weights at M = 16 and M = 32 coarse-graining
# an additional subdirectory includes networks trained with noisy data
Neural network weights are saved as .h5 files. An example script is included ("load_weights.py") to illustrate how to load into a model.Please see README file for details of directory structure, along with example scripts
Single-cell metabolic oscillations are pervasive and may alleviate a proteome constraint
Biological rhythms not only coordinate cellular activity with external signals, but may also enable internal coordination. The metabolic cycle in budding yeast is perhaps the most well-studied example. Historically researchers have investigated this cycle in populations growing in chemostats, but more recently time-lapse microscopy has revealed single-cell oscillations in the redox state of enzyme cofactors and in ATP levels. How to relate the results of these two types of assays is however unclear. Here we report single-cell rhythms too in intracellular pH and show that oscillations in the redox state of flavin molecules occur in auxotrophic and prototrophic strains, in nutrients favouring respiration or fermentation, and in deletion mutants for which oscillations in chemostats are either unobservable or disrupted. To explain the pervasiveness of these rhythms, we postulate that cells generate oscillations to alleviate a proteome constraint – amino acids cells use for one class of enzymes are unavailable for others. Using flux balance analysis with an enzyme-constrained genome-scale metabolic model, we show that, with a finite proteome, sequential synthesis of biomass components typically generates a shorter doubling time than synthesising components in parallel. Our results suggest that the metabolic cycle drives growth and is potentially widespread because all cells grow within a proteome constraint.File descriptions are included in README.tx
Normal reference T1-weighted MR images for the brain at ages 65-70 and 75-80 years
As part of an early effort to provide reference images of healthy ageing in older subjects, two T1-weighted MR imaging templates were created as described by Farrell et al. in a previous publication [1]. Briefly, brain T1-weighted MRI from 79 community-dwelling older individuals, previously grouped in two age intervals, were aligned using affine registration. The images were considered representative of the normal human brain at ages 65-70 and 75-80 years. The individuals providing the data were considered normal as determined by a medical and psychiatric records as well as medical and cognitive assessment. The templates were tested by two neuroradiologists during routine interpretation of MR and CT brain images. Here, we provide the template files in nifti-1 format, to be used in further research.Please see Readme.pd
Nurse led Allergy Clinic in Edinburgh, Scotland
A mixed methods feasibility pilot Nurse-led allergy clinic ran for 4 years between 2016 and 2020 and was hosted by the University of Edinburgh and NHS Lothian and funded by Allergy UK. This novel clinic was initiated within the SE and SW area of Edinburgh, Scotland, to assess the feasibility of setting up an intermediary service in primary care, look at filling gaps in allergy service provision within Scotland and to measure the acceptability of the service to the patients, their families and health care professionals who used it.
The two specialist nurses, supported by local specialists, were required to diagnose, manage, carry out investigations where necessary, prescribe and provide follow-up for patients/parents. Referrals into the clinic were accepted, provided they fulfilled the inclusion criteria from all primary care practitioners within the cluster locality who saw patients with allergies.
The clinic started out offering face to face consultations with a phone review, but this was adapted to remote consultation as a result of the Covid pandemic during 2020.
Analysis of the quality of life data, indicated there was an improvement in the quality of life scores between baseline and 6-12 week follow-up in three of the four groups, however this should be interpreted with caution due to the small sample size of this study.The dataset is composed of:
- Data files;
- CSV version of the same files;
- README.txt fil
Task-anchored grid cell firing is selectively associated with successful path integration-dependent behaviour
Data for reproducing plots in Clark and Nolan (2024), "Task-anchored grid cell firing is selectively associated with successful path integration-dependent behaviour". eLife.
These files contain processed neural and behavioural data recording from mice performing a spatial navigation task in a virtual reality track environment, followed by free-exploration of an open arena.
To reproduce analysis for the publication, use this data and code found on the Nolan Lab Github and follow these steps:
(1) Clone the in_vivo_ephys_openephys (https://github.com/MattNolanLab/in_vivo_ephys_openephys/) repo that contains all code for preprocessing and spike sorting
(2) Clone eLife_Grid_anchoring_2024 (https://github.com/MattNolanLab/eLife_Grid_anchoring_2024.git)
(3) Move eLife_Grid_anchoring_2024 to within in_vivo_ephys_openephys
(4) Create a conda environment using grid_behaviour.yml (conda env create -f grid_behaviour.yml)
(4) Run code within eLife_Grid_anchoring_2024 using data provided here
(5) amend paths for saving plots where appropriat
Development of a questionnaire and safeguarding procedure for a national prevalence survey on child abuse and neglect
INTRODUCTION AND BACKGROUND
Abuse is a crime that can have long-lasting adverse individual, familial, and society-level effects (Browne & Finkelhor, 1986; Finkelhor et al., 2006; Norman et al., 2012). Accurate data is needed in order to monitor trends over time, develop effective prevention strategies, and support survivors of abuse appropriately (World Health Organization, 2006). The Office for National Statistics (ONS) conducted a consultation in 2021 which demonstrated a strong user need for survey data on the prevalence and nature of child abuse in the UK. At the end of 2022, the University of Edinburgh and the University of Greenwich were commissioned to develop the questionnaires and safeguarding procedures for a pilot in 2025/26. This report outlines the methods and findings of the mixed methods research conducted by the University of Edinburgh, through the Department of Social Work and Childlight – Global Child Safety Institute, and by the Institute for Lifecourse Development at the University of Greenwich, to develop a child abuse survey and accompanying safeguarding procedure for the ONS.
RESEARCH AIMS
The aim of this research, outlined by the ONS in the Statement of Requirement, was to design two questionnaires: one for children aged 11–16 to be conducted in schools, and one for adolescents and young adults aged 16–25 to be completed independently online. This aim evolved over the course of the project to become three questionnaires, as the research called for differences in questions for participants aged 11–15, 16–17, and 18–25 years. These three questionnaires will be facilitated across two modalities: the in-school survey, which will include both the 11–15 questionnaire and the 16–17 questionnaire; and the online survey, which will include both the 16–17 questionnaire and the 18–25 questionnaire. Alongside this, a second aim was to design an appropriate safeguarding procedure for use with the survey, which helps to ensure participants are safe both while they are completing the questionnaire and afterwards, particularly if they seek support.
METHODOLOGY
The project utilised a wide variety of methods. Online Delphi surveys and focus groups were conducted with violence research and child protection professionals. Focus groups were also conducted with adult survivors of childhood abuse. Children and young people aged 11 to 27 participated in both individual and group cognitive interviews, participatory group research sessions, and individual qualitative interviews. Individual consultations were conducted with government departments; prevalence researchers; safeguarding professionals and researchers; educational personnel; ethics board members; special educational and/or support needs (SESN) professionals; and abuse or violence support, prevention, and research organisations.
KEY FINDINGS
The outcome of these consultations is three questionnaires and associated safeguarding procedures. One questionnaire is for use in a school setting with children aged 11–16, and the first part of the safeguarding procedure details how to best partner with schools to safeguard children who are completing this survey. The other two questionnaires are for use online with children aged 16–17 and adults aged 18–25, and the remainder of the safeguarding procedure details how to best safeguard participants completing such a survey independently online.
The questionnaire includes both items on violence experiences and non-violence items, such as risk factors, protective factors, and outcomes. The violence items were developed by the Research Team and consulted on extensively via a Delphi survey and focus groups with professionals and adult survivors, before being tested in cognitive interviews with children and young people and further adapted based on their feedback. This included detailed feedback on specific item phrasing, terminology, and formatting of both screening questions for each violence type and follow-up questions on characteristics of violence. Participatory research sessions informed the ordering of the survey topics and the design of the questionnaire in a digital format. The non-violence items recommended for inclusion are existing measurement tools for risk factors and outcomes. Items on protective factors are an exception to this, as the Research Team did not find a suitable existing measure and chose to develop items on protective factors. The phrasing of the questionnaire is intentionally and strategically designed for use with any child in mainstream schooling, including those with SESN. Recommendations are made for operational adaptations which may be required for some pupils.
The safeguarding procedure began as an accompaniment to a partially anonymous or pseudo-anonymous survey, but over the course of the project and in light of feedback from child protection professionals, government departments, and most notably survivors of violence, this changed to a fully anonymous survey recommendation. In order to appropriately protect children and young people completing an anonymous survey, the safeguarding procedure details opt-in support options for participants to access before, during, and after survey completion. In schools, this includes pre-survey information sessions with teachers, parents, and participants; in-person support (in addition to the school’s existing safeguarding personnel); built-in digital options for during-survey support via anonymous chat; and post-survey access to safeguarding web resources, phone calls, and in-person follow-up conversations. Additional safeguarding measures for pupils with SESN are outlined. For the online survey, this includes pre-information when participants log into the survey; built-in digital options for during-survey support via anonymous chat; and post-survey access to safeguarding web resources and phone calls. In order to facilitate these safeguards in the most trauma-informed and appropriate manner, and to ease the burden on schools, the safeguarding procedure includes the recommendation that the ONS partners with a child abuse support organisation
SUPERSEDED - Codebook used to categorise media shown in corpus metadata
## This item has been replaced by the one which can be found at https://doi.org/10.7488/ds/7709 ## Codebook detailing how media items were coded in corpus metadata file. Details codes used for country, source, continent, medium, type of media, geographic market/reach, and ownership/funding model.This codebook describes the codes used in the corpus metadata file (FullCorpusMetadata.xlsx)
Data set from Bruce et al. (2023) "Optimising an in vitro model to isolate and fingerprint extracellular vesicles shed from neuroendocrine castrate resistant prostate cancer"
WITHDRAWN: This item has been withdrawn from DataShare at the request of Dr Jennifer Frazer and is no longer available. The abstract text has also been withdrawn
Supplementary material - Long-term, dynamic remodelling of the corticotroph transcriptome and excitability after a period of chronic stress
Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as “recovery”) are very poorly understood. Here we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this. We demonstrate that in mice spontaneous and corticotrophin releasing hormone (CRH)—stimulated electrical excitability of corticotrophs, essential for ACTH secretion, is suppressed for weeks-months of recovery following a period of chronic stress. Surprisingly, there are only modest changes in the corticotroph transcriptome during the period of stress but major alterations occur in recovery. Importantly, while transcriptional changes for a large proportion of mRNAs follow the time course suppression of corticotroph excitability, many other genes display highly dynamic transcriptional changes with distinct time courses throughout recovery. Taken together, this suggests that chronic stress results in complex dynamic transcriptional and functional changes in corticotroph physiology, which are highly dynamic for weeks following cessation of chronic stress. These insights provide a fundamental new framework to further understand underlying molecular mechanisms as well approaches to both diagnosis and treatment of stress-related dysfunction of the HPA axis