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Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease
Get PDFData from Colom-Cadena et al Published in Acta Neuropathologica in 2024. Abstract: Synapse loss correlates with cognitive decline in Alzheimer’s disease, and soluble oligomeric amyloid beta (Aβ) is implicated in synaptic dysfunction and loss. An important knowledge gap is the lack of understanding of how Aβ leads to synapse degeneration. In particular, there has been difficulty in determining whether there is a synaptic receptor that binds Aβ and mediates toxicity. While many candidates have been observed in model systems, their relevance to human AD brain remains unknown. This is in part due to methodological limitations preventing visualization of Aβ binding at individual synapses. To overcome this limitation, we combined two high resolution microscopy techniques: array tomography and Förster resonance energy transfer (FRET) to image over 1 million individual synaptic terminals in temporal cortex from AD (n=11) and control cases (n=9). Within presynapses and postsynaptic densities, oligomeric Aβ generates a FRET signal with transmembrane protein 97. Further, amyloid beta generates a FRET signal with cellular prion protein, and postsynaptic density 95 within postsynapses. Transmembrane protein 97 is also present in a higher proportion of postsynapses in Alzheimer’s brain compared to controls. We inhibited Aβ / transmembrane protein 97 interaction in a mouse model of amyloidopathy by treating with the allosteric modulator CT1812. CT1812 drug concentration correlated negatively with synaptic FRET signal between transmembrane protein 97 and Aβ. In human induced pluripotent stem cell derived neurons, transmembrane protein 97 is present in synapses and colocalizes with Aβ when neurons are challenged with human Alzheimer’s brain homogenate. Transcriptional changes are induced by Aβ including changes in genes involved in neurodegeneration and neuroinflammation. CT1812 treatment of these neurons caused changes in gene sets involved in synaptic function. These data support a role for transmembrane protein 97 in the synaptic binding of Aβ in human Alzheimer’s disease brain where it may mediate synaptotoxicity
Synaptic interactions between stellate cells and parvalbumin interneurons in layer 2 of the medial entorhinal cortex are organized at the scale of grid cell clusters
No full textElectrophysiological and anatomical datasets, analysed data and code for experiments described in Huang et al., Synaptic interactions between stellate cells and parvalbumin interneurons in layer 2 of the medial entorhinal cortex are organized at the scale of grid cell clusters
Dataset for Neuronal Multi Unit Activity Processing With Metal Oxide Memristive Devices
No full textIntra-cortical brain-machine interfaces, able to decode neural activity in real-time, represent a revolutionary opportunity for treating medical conditions. However, traditional systems focusing on single-neuron spike detection require high processing rates and power, hindering they up-scaling for neurons-population monitoring in clinical application. An intriguing proposition is the memristive integrating sensor (MIS) approach, which uses resistive RAM (RRAM) for threshold-based neural activity detection. MIS leverages analogue multi-state switching properties of metal-oxide RRAM to compress neural inputs by encoding above-threshold events in resistance displacement, facilitating efficient data down-sampling in the post-processing, enabling low-power, high-channel systems.
Initially tested on spikes and local field potentials, here MIS has been adapted to process multi-unit activity envelope (eMUA) - the envelope of entire spiking activity - which has recently been proposed as crucial input for real-time neuro-prosthetic control. Prior necessary modifications to the MIS for effective operation, this adaptation achieved over 95% sensitivity across two types of metal-oxide devices: Pt/TiOx/Pt and TiN/HfOx/TiN, proving its platform-agnostic capabilities. Furthermore, towards the integration of MIS with silicon chips, we show that it can reduce total system power consumption to below 1µW, as RRAM encoding stage relaxes the signal preservation and noise requirements that challenge traditional CMOS front-ends. This eMUA-MIS adaptation offers a viable pathway for developing more scalable and efficient BMIs for clinical use
Supplementary files from manuscript "Limiting pre-menstrual endometrial Hypoxia Inducible Factor 2 Alpha may fine-tune endometrial function at menstruation"
No full textHeavy menstrual bleeding (HMB) is common and debilitating, but the precise endometrial mechanisms causing increased menstrual blood loss (MBL) remain undefined. We have previously identified a role for hypoxia in endometrial repair following progesterone withdrawal.
Objective. As hypoxia inducible factor 2 alpha (HIF2A) is known to alter vascular function in other tissues, we hypothesised that endometrial HIF2A is involved in pre-menstrual optimisation of endometrial function during the secretory phase to limit MBL.
Results. Women with objective HMB had higher endometrial HIF2A during the mid-secretory phase when compared to those with normal MBL (p=0.0269). In a mouse model of simulated menses, genetic or pharmacological manipulation of HIF2A did not significantly affect endometrial breakdown/repair, volume of MBL or endometrial hypoxia. However, 88% of Hif2a heterozygote mice reached early-full repair by 24h versus only 65% of wild-type mice. Mean MBL was 0.39 μl (±0.67) in Hif2a heterozygote mice versus 0.98 μl (±0.79) in wild-type mice. Conversely, when we increased HIF2A pre-menstrually, 11% reached early repair at by 8h versus 30% of vehicle-treated mice. Mean MBL was 2.61 μl (±1.10) in mice with HIF2A stabilisation and 2.24 μl (±1.14) in vehicle-treated mice. These non-significant but consistent trends indicate that increased endometrial HIF2A may contribute to delayed endometrial repair and HMB.
Conclusions. Increased HIF2A in the secretory endometrium is unlikely to be sufficient to account for the phenotype of HMB, but limitation of HIF2 levels may optimise endometrial function at menstruation
The role of cavitation and gas bubbles in the non-photochemical laser-induced nucleation of sodium acetate
No full textThis dataset contains original images and measurements obtained during experiments on non-photochemical laser-induced nucleation of sodium acetate. An experimental study of the effects of the sodium salt of poly(methacrylic acid) (Na-PMAA) on non-photochemical laser-induced nucleation (NPLIN) of sodium acetate crystals is presented. Seeding of supersaturated aqueous solutions with anhydrous (AH) seeds always produced trihydrate (TH) crystals, with or without polymer additive. Using NPLIN, with no Na-PMAA and at low Na-PMAA concentrations (0.25% w/w) AH sodium acetate was produced, firstly as plate-like Form IV, but subsequently growing needles, likely to be Form I. At high Na-PMAA concentrations (0.73% w/w) we observe formation mostly of stable bubbles. In all samples at low laser peak power densities (< 26 MW cm–2) we show for the first time using NPLIN that both crystals and bubbles can be nucleated with a single laser pulse. Measurements of the dependence of bubble or crystal count on laser pulse power indicate a common mechanistic origin for nucleation, which is cavitation due to laser heating of impurity nanoparticles. The bubbles observed are attributed to laser heating of the nanoparticles to high temperatures, resulting in gas formed by thermochemical reactions or gas that was previously dissolved in the solution. Our results provide new insight into the particle-heating mechanism for NPLIN, but whether stable bubbles play a defining role in the nucleation of crystals remains to be resolved. The data have been published in the Royal Society of Chemistry journal CrystEngComm under the title “The role of cavitation and gas bubbles in the non-photochemical laser-induced nucleation of sodium acetate” by Eleanor R. Barber, Martin R. Ward and Andrew J. Alexander
Large intracranial artery regions in MRI head templates for calcium segmentation
Get PDFWe defined five rectangular ROIs around large intracranial arteries on two T1-weighted MRI templates of the head from Armitage et al., which are available online from the Edinburgh DataShare at https://doi.org/10.7488/ds/7763. The five ROIs are the following:
1. Vertebral arteries from the foramen magnum up to the termination.
2. Basilar artery from the joining of the vertebral arteries to the Circle of Willis.
3. Internal carotid artery, the cavernous segment up to the Circle of Willis.
4. The M1 segment of the left MCA.
5. The M1 segment of the right MCA.
The MRI templates are age-specific for ranges 65-70 and 75-80. We use these approximate regions for subsequent precise segmentation and quantification of intracranial arterial calcification in co-registered CT scans.Please see Readme.pd
Data for publication "Impact of sub-ambient temperature on aging rate and gas separation properties of polymers of intrinsic microporosity".
No full textAging in Polymers of Intrinsic Microporosity has slowed down exploitation as the decay in performance over time due to densification makes them not suitable for industrial application. This work aimed to study the impact of operation and storage temperature on the gas separation properties and aging rates of PIM-1 self-standing films. The permeability, diffusivity and solubility of the tested membranes were monitored through permeation tests for pure carbon dioxide and nitrogen at a maximum upstream pressure of 1.3 bar for temperatures ranging from -20 °C to 25 °C. This study showed significant benefits in the operation of glassy polymeric membranes at low temperatures, resulting in a favourable trade-off in separation performance and a reduction of aging rate by three orders of magnitude. This brings new opportunities for the industrial application of PIMs in innovative carbon capture processes.
This file presents the dataset obtained from the permeation measurement of polymeric membranes used for the separation of carbon dioxide and nitrogen at different age and temperature. From the measurement of a pure gas pressure build-up in a known volume downstream of a membrane, its separation properties (i.e., Permeability, Diffusivity and Solubility) can be obtained. The subsequent results obtained from this data are detailed in the corresponding publication listed in the metadata
Explainable Autonomous Vehicle Intelligence
No full text## This item has been replaced by the one which can be found at https://doi.org/10.7488/ds/7867 ## HEADD is a dataset of natural language explanations elicited from online participants via Prolific with corresponding annotations for each explanation similarly given by online (but different) participants. The data is about driving scenarios in which the behaviour and driving decisions of a single blue agent need to be explained, while the scenarios contain various other agents and environmental elements that influence the behaviour of the blue agent. The dataset contains 14 unique scenarios with qualitatively distinct and interesting driving scenarios including simulated video recordings, ASAM OpenDrive maps, and ASAM OpenScenario descriptions. In addition, HEADD includes 1308 explanations in natural language with 4 explanatory modes (descriptive, teleological, mechanistic, counterfactual) from 54 participants in each of the 14 scenarios, of which 947 non-descriptive explanations are annotated with 5 unique annotations regarding the causal content and trustworthiness of the explanations under the various circumstances in the scenarios.Please refer to the following files to get a full picture of how the data is structured:
(A) README.md: Contains a high-level overview of the dataset, its contents, a brief description of the collection process, and the exact questions asked to participants;
(B) scenarios_metadata.json: A semi-structured file in the JSON-format containing the description and metadata of the 14 scenarios;
(C) explanations_metadat.json: A semi-structured file in the JSON-format containing the description and metadata of the explanations elicited from participants for each of the 14 scenarios;
(D) annotations_metadata.json: A semi-structured file in the JSON-format containing the description and metadata of the annotations for each non-descriptive explanation
Renal injury in P2X7 knockout rats
No full textP2X7 receptors mediate immune and endothelial cell responses to extracellular ATP. Acute pharmacological blockade increases renal blood flow and filtration rate, suggesting that receptor activation promotes tonic vasoconstriction. P2X7 expression is increased in kidney disease and blockade/knockout is renoprotective. We generated a P2X7 knockout rat on F344 background, hypothesising enhanced renal blood flow and protection from angiotensin-II-induced renal injury.
CRISPR/Cas9 introduced an early stop codon into exon 2 of P2rx7, abolishing P2X7 protein in kidney and reducing P2rx7 mRNA abundance by ~60% in bone-marrow derived macrophages. The M1 polarisation response to lipopolysaccharide was unaffected but P2X7 receptor knockout suppressed ATP-induced IL-1β release. In male knockout rats, acetylcholine-induced dilation of the renal artery ex vivo was diminished but not the response to nitroprusside. Renal function in male and female knockout rats was not different from wild-type. Finally, in male rats infused with angiotensin-II for 6 weeks, P2X7 knockout did not reduce albuminuria, tubular injury, renal macrophage accrual, and renal perivascular fibrosis.
Contrary to our hypothesis, global P2X7 knockout had no impact on in vivo renal hemodynamics. Our study does not indicate a major role for P2X7 receptor activation in renal vascular injur
GOLD Depression Study
No full textInflammation has been linked to depression in the general population. People living with HIV are at three times greater risk for depression, and experience elevated inflammation despite antiretroviral therapy. We investigated whether inflammatory biomarkers in the brain and the blood may mediate the association between HIV status and depressive symptoms. We recruited 60 young people living with and without HIV in Cape Town, South Africa. Participants completed the nine-item Patient Health Questionnaire (PHQ-9) as a measure of depressive symptoms, underwent magnetic resonance spectroscopy to quantify choline and myo-inositol in three brain regions, and provided a blood serum sample in which we quantified concentrations of blood biomarkers of inflammation and neurogenesis