Publications by authors named "Adam L Tyson"

8 Publications

  • Page 1 of 1

Visualizing anatomically registered data with Brainrender.

Elife 2021 Mar 19;10. Epub 2021 Mar 19.

Sainsbury Wellcome Centre, UCL, London, United Kingdom.

Three-dimensional (3D) digital brain atlases and high-throughput brain wide imaging techniques generate large multidimensional datasets that can be registered to a common reference frame. Generating insights from such datasets depends critically on visualization and interactive data exploration, but this a challenging task. Currently available software is dedicated to single atlases, model species or data types, and generating 3D renderings that merge anatomically registered data from diverse sources requires extensive development and programming skills. Here, we present : an open-source Python package for interactive visualization of multidimensional datasets registered to brain atlases. facilitates the creation of complex renderings with different data types in the same visualization and enables seamless use of different atlas sources. High-quality visualizations can be used interactively and exported as high-resolution figures and animated videos. By facilitating the visualization of anatomically registered data, should accelerate the analysis, interpretation, and dissemination of brain-wide multidimensional data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.65751DOI Listing
March 2021

Analysis of segmentation ontology reveals the similarities and differences in connectivity onto L2/3 neurons in mouse V1.

Sci Rep 2021 Mar 2;11(1):4983. Epub 2021 Mar 2.

Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, 25 Howland Street, London, W1T 4JG, UK.

Quantitatively comparing brain-wide connectivity of different types of neuron is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine and compare datasets from hierarchical segmentation ontologies, and applied it to long-range presynaptic connectivity onto excitatory and inhibitory neurons, mainly located in layer 2/3 (L2/3), of mouse primary visual cortex (V1). We find that the origins of long-range connections onto these two general cell classes-as well as their proportions-are quite similar, in contrast to the inputs on to a cell type in L6. These anatomical data suggest that distal inputs received by the general excitatory and inhibitory classes of neuron in L2/3 overlap considerably.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-82353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925549PMC
March 2021

Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids.

Cell 2020 06 18;181(7):1596-1611.e27. Epub 2020 Jun 18.

Signalling and Cancer Metabolism Team, Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Division of Systems Medicine, Department of Metabolism Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK. Electronic address:

Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction. VIDEO ABSTRACT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.05.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339148PMC
June 2020

Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint.

J Cell Biol 2020 06;219(6)

The Institute of Cancer Research, London, UK.

How the cell rapidly and completely reorganizes its architecture when it divides is a problem that has fascinated researchers for almost 150 yr. We now know that the core regulatory machinery is highly conserved in eukaryotes, but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major question. Cyclin B1-Cdk is the primary kinase that drives mitotic remodeling; here we show that it is targeted to the nuclear pore complex (NPC) by binding an acidic face of the kinetochore checkpoint protein, MAD1, where it coordinates NPC disassembly with kinetochore assembly. Localized cyclin B1-Cdk1 is needed for the proper release of MAD1 from the embrace of TPR at the nuclear pore so that it can be recruited to kinetochores before nuclear envelope breakdown to maintain genomic stability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1083/jcb.201907082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265330PMC
June 2020

Optimisation and validation of hydrogel-based brain tissue clearing shows uniform expansion across anatomical regions and spatial scales.

Sci Rep 2019 08 19;9(1):12084. Epub 2019 Aug 19.

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Imaging of fixed tissue is routine in experimental neuroscience, but is limited by the depth of tissue that can be imaged using conventional methods. Optical clearing of brain tissue using hydrogel-based methods (e.g. CLARITY) allows imaging of large volumes of tissue and is rapidly becoming commonplace in the field. However, these methods suffer from a lack of standardized protocols and validation of the effect they have upon tissue morphology. We present a simple and reliable protocol for tissue clearing along with a quantitative assessment of the effect of tissue clearing upon morphology. Tissue clearing caused tissue swelling (compared to conventional methods), but this swelling was shown to be similar across spatial scales and the variation was within limits acceptable to the field. The results of many studies rely upon an assumption of uniformity in tissue swelling, and by demonstrating this quantitatively, research using these methods can be interpreted more reliably.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-48460-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700094PMC
August 2019

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in deletion mice.

Mol Autism 2019 28;10. Epub 2019 Feb 28.

1School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT UK.

Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the knockout (KO) model.

Methods: Fixed brains of KO mice underwent DTI using 9.4 T MRI, and diffusion properties of socially relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified.

Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density.

Conclusions: Our findings demonstrate that deleting a single neurexin gene () induces atypical structural connectivity within socially relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13229-019-0261-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394023PMC
April 2019

Decreased functional connectivity within a language subnetwork in benign epilepsy with centrotemporal spikes.

Epilepsia Open 2017 06 27;2(2):214-225. Epub 2017 Apr 27.

Department of Basic and Clinical Neuroscience Institute of Psychiatry, Psychology & Neuroscience King's College London London United Kingdom.

Objective: Benign epilepsy with centrotemporal spikes (BECTS, also known as Rolandic epilepsy) is a common epilepsy syndrome that is associated with literacy and language impairments. The neural mechanisms of the syndrome are not known. The primary objective of this study was to test the hypothesis that functional connectivity within the language network is decreased in children with BECTS. We also tested the hypothesis that siblings of children with BECTS have similar abnormalities.

Methods: Echo planar magnetic resonance (MR) imaging data were acquired from 25 children with BECTS, 12 siblings, and 20 healthy controls, at rest. After preprocessing with particular attention to intrascan motion, the mean signal was extracted from each of 90 regions of interest. Sparse, undirected graphs were constructed from adjacency matrices consisting of Spearman's rank correlation coefficients. Global and nodal graph metrics and subnetwork and pairwise connectivity were compared between groups.

Results: There were no significant differences in graph metrics between groups. Children with BECTS had decreased functional connectivity relative to controls within a four-node subnetwork, which consisted of the left inferior frontal gyrus, the left superior frontal gyrus, the left supramarginal gyrus, and the right inferior parietal lobe (p = 0.04). A similar but nonsignificant decrease was also observed for the siblings. The BECTS groups had significant increases in connectivity within a five-node, five-edge frontal subnetwork.

Significance: The results provide further evidence of decreased functional connectivity between key mediators of speech processing, language, and reading in children with BECTS. We hypothesize that these decreases reflect delayed lateralization of the language network and contribute to specific cognitive impairments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/epi4.12051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719846PMC
June 2017

Rapid, simple and inexpensive production of custom 3D printed equipment for large-volume fluorescence microscopy.

Int J Pharm 2015 Oct 20;494(2):651-656. Epub 2015 Mar 20.

MRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, UK. Electronic address:

The cost of 3D printing has reduced dramatically over the last few years and is now within reach of many scientific laboratories. This work presents an example of how 3D printing can be applied to the development of custom laboratory equipment that is specifically adapted for use with the novel brain tissue clearing technique, CLARITY. A simple, freely available online software tool was used, along with consumer-grade equipment, to produce a brain slicing chamber and a combined antibody staining and imaging chamber. Using standard 3D printers we were able to produce research-grade parts in an iterative manner at a fraction of the cost of commercial equipment. 3D printing provides a reproducible, flexible, simple and cost-effective method for researchers to produce the equipment needed to quickly adopt new methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2015.03.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626572PMC
October 2015