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Research On The Go

Peter Schmidt, Mark Turner, Adrian Harwood
2021 Zenodo  
Peter Schmidt, Mark Turner, Adrian Harwood, 2021. Research On The Go. International Series of Online Research Software Events (SORSE). https://doi.org/10.5281/zenodo.4537162  ...  Panelists • Adrian Harwood, University of Manchester, established and manages the Mobile Development Service (MDS) in the RSE group. • Peter Schmidt, University College London, has been an app developer  ... 
doi:10.5281/zenodo.4537162 fatcat:owiesdgiijhvnfg5rpmqw2tcpq

Research On The Go

Peter Schmidt, Mark Turner, Adrian Harwood
2021 Zenodo  
Peter Schmidt, Mark Turner, Adrian Harwood, 2021. Research On The Go. International Series of Online Research Software Events (SORSE). https://doi.org/10.5072/zenodo.715974  ...  Panelists • Adrian Harwood, University of Manchester, leads mobile development efforts in his RSE group. • Peter Schmidt, University College London, has been an app developer in the private sector and  ... 
doi:10.5281/zenodo.4439258 fatcat:xqkfpgajwzg7hcupikglyrm7nq

Nucleosome dynamics of human iPSC during the early stages of neurodevelopment [article]

Janet C Harwood, Nicholas A Kent, Nicholas D Allen, Adrian J Harwood
2018 bioRxiv   pre-print
Regulation of nucleosome positioning is important for neurodevelopment, and mutation of genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. Unicellular organisms possess arrays of highly positioned nucleosomes within their chromatin, occupying up to 80% of their genomes. These span gene-coding and regulatory regions, and can be associated with local changes of gene transcription. In the much larger genome of human cells, the roles of nucleosome
more » ... positioning are less clear, and this raises questions of how nucleosome dynamics interfaces with human neurodevelopment. We have generated genome-wide nucleosome maps from an undifferentiated human induced pluripotent stem cell (hiPSC) line and after its differentiation to the neuronal progenitor cell (NPC) stage. We found that approximately 3% of nucleosomes are highly positioned in NPC. In contrast, there are 8-fold less positioned nucleosomes in pluripotent cells, with the majority arising de novo or relocating during cell differentiation. Positioned nucleosomes do not directly correlate with active chromatin or gene transcription, such as marking Transcriptional Start Sites (TSS). Unexpectedly, we find a small population of nucleosomes that remain positioned after differentiation, occupying similar positions in pluripotent and NPC cells. They flank the binding sites of the key gene regulators NRSF/REST and CTCF, but remain in place whether or not their regulatory complexes are present. Together, these results present an alternative view in human cells, where positioned nucleosomes are sparse and dynamic, but act to alter gene expression at a distance via structural conformation at sites of chromatin regulation, not local changes in gene organisation.
doi:10.1101/398792 fatcat:akldqiho6rbn7cmtueanmsbp3u

Nucleosome dynamics of human iPSC during neural differentiation

Janet C Harwood, Nicholas A Kent, Nicholas D Allen, Adrian J Harwood
2019 EMBO Reports  
Nucleosome positioning is important for neurodevelopment, and genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. To investigate changes in nucleosome positioning during neural differentiation, we generate genome-wide nucleosome maps from an undifferentiated human-induced pluripotent stem cell (hiPSC) line and after its differentiation to the neural progenitor cell (NPC) stage. We find that nearly 3% of nucleosomes are highly positioned in NPC,
more » ... but significantly, there are eightfold fewer positioned nucleosomes in pluripotent cells, indicating increased positioning during cell differentiation. Positioned nucleosomes do not strongly correlate with active chromatin marks or gene transcription. Unexpectedly, we find a small population of nucleosomes that occupy similar positions in pluripotent and neural progenitor cells and are found at binding sites of the key gene regulators NRSF/REST and CTCF Remarkably, the presence of these nucleosomes appears to be independent of the associated regulatory complexes. Together, these results present a scenario in human cells, where positioned nucleosomes are sparse and dynamic, but may act to alter gene expression at a distance via the structural conformation at sites of chromatin regulation.
doi:10.15252/embr.201846960 pmid:31036712 pmcid:PMC6549019 fatcat:xrmrovuokvdp3byrvssoxcs7da

Regulation of GSK-3

Adrian J. Harwood
2001 Cell  
FRAT/GBP may however have an alternative effect by interfering with GSK-3 binding to axin (Farr et GSK3␤ (Harwood, 2000).  ... 
doi:10.1016/s0092-8674(01)00412-3 pmid:11439177 fatcat:hsigvoablrat5asghgcfadhsla

Signal Transduction in Development

Adrian J. Harwood
2002 Developmental Cell  
In this way, only Axin-bound ␤-catenin is effi-Adrian J. Harwood ciently phosphorylated by GSK-3 and degraded.  ...  The cell also strong preference for prior phosphorylated substrates employs similar high-security measures when it needs (Harwood, 2001) .  ... 
doi:10.1016/s1534-5807(02)00156-9 pmid:11970888 fatcat:doo5tvfahvelzbgxjnspoepagy

Signal transduction: Life, the universe and … development

Adrian J. Harwood
2000 Current Biology  
Acknowledgements Adrian J. Harwood is a Wellcome Senior Biomedical Research Fellow.  ... 
doi:10.1016/s0960-9822(00)00307-9 pmid:10679318 fatcat:e7f7nputkjhtxp7kahhkvkgxle

Search for a common mechanism of mood stabilizers

Adrian J. Harwood, Galila Agam
2003 Biochemical Pharmacology  
Harwood), agamg@netvision.net.il, galila@bgumail.bgu.ac.il (G. Agam).  ...  All rights reserved. doi:10.1016/S0006-2952(03)00187-4 Biochemical Pharmacology 66 (2003) 179-189 Ryves WJ and Harwood AJ, unpublished data. A.J. Harwood, G.  ... 
doi:10.1016/s0006-2952(03)00187-4 pmid:12826261 fatcat:nol6w6arszb4zhdoyelpzhitwe

A Stochastic Description of Dictyostelium Chemotaxis

Gabriel Amselem, Matthias Theves, Albert Bae, Eberhard Bodenschatz, Carsten Beta, Adrian John Harwood
2012 PLoS ONE  
Chemotaxis, the directed motion of a cell toward a chemical source, plays a key role in many essential biological processes. Here, we derive a statistical model that quantitatively describes the chemotactic motion of eukaryotic cells in a chemical gradient. Our model is based on observations of the chemotactic motion of the social ameba Dictyostelium discoideum, a model organism for eukaryotic chemotaxis. A large number of cell trajectories in stationary, linear chemoattractant gradients is
more » ... ured, using microfluidic tools in combination with automated cell tracking. We describe the directional motion as the interplay between deterministic and stochastic contributions based on a Langevin equation. The functional form of this equation is directly extracted from experimental data by angle-resolved conditional averages. It contains quadratic deterministic damping and multiplicative noise. In the presence of an external gradient, the deterministic part shows a clear angular dependence that takes the form of a force pointing in gradient direction. With increasing gradient steepness, this force passes through a maximum that coincides with maxima in both speed and directionality of the cells. The stochastic part, on the other hand, does not depend on the orientation of the directional cue and remains independent of the gradient magnitude. Numerical simulations of our probabilistic model yield quantitative agreement with the experimental distribution functions. Thus our model captures well the dynamics of chemotactic cells and can serve to quantify differences and similarities of different chemotactic eukaryotes. Finally, on the basis of our model, we can characterize the heterogeneity within a population of chemotactic cells.
doi:10.1371/journal.pone.0037213 pmid:22662138 pmcid:PMC3360683 fatcat:g2adid4nmvebxoobx34gt2lydy

Improved screening for oligonucleotide-directed mutant M13 phage

Adrian J. Harwood, Christopher J. Bostock
1988 Nucleic Acids Research  
doi:10.1093/nar/16.11.5193 pmid:3290848 pmcid:PMC336729 fatcat:rrcjyvutbnhurbe2o5pmn6nkem

Prolyl Oligopeptidase, Inositol Phosphate Signalling and Lithium Sensitivity

Adrian J. Harwood
2011 CNS and Neurological Disorders - Drug Targets  
Inhibition of prolyl oligopeptidase (PO) elevates inositol phosphate (IP) signalling and reduces cell sensitivity to lithium (Li + ). This review discusses recent evidence that shows PO acts via the multiple inositol polyphosphate phosphatase (MIPP) to regulate gene expression. As a consequence, PO inhibition causes both a transient, rapid increase in I(1,4,5)P3 and a long-term elevation of IP signalling. This pathway is evolutionary conserved, being present in both the social amoeba
more » ... um and human cell systems, and has potential implications for mental health.
doi:10.2174/187152711794653779 pmid:21222625 pmcid:PMC3267164 fatcat:gilq6vzcbfgrjiiqxne6ol5kwu

Innate Non-Specific Cell Substratum Adhesion

William F. Loomis, Danny Fuller, Edgar Gutierrez, Alex Groisman, Wouter-Jan Rappel, Adrian John Harwood
2012 PLoS ONE  
Adhesion of motile cells to solid surfaces is necessary to transmit forces required for propulsion. Unlike mammalian cells, Dictyostelium cells do not make integrin mediated focal adhesions. Nevertheless, they can move rapidly on both hydrophobic and hydrophilic surfaces. We have found that adhesion to such surfaces can be inhibited by addition of sugars or amino acids to the buffer. Treating whole cells with alpha-mannosidase to cleave surface oligosaccharides also reduces adhesion. The
more » ... indicate that adhesion of these cells is mediated by van der Waals attraction of their surface glycoproteins to the underlying substratum. Since glycoproteins are prevalent components of the surface of most cells, innate adhesion may be a common cellular property that has been overlooked.
doi:10.1371/journal.pone.0042033 pmid:22952588 pmcid:PMC3432024 fatcat:wmqd2lk4tbcwne5oy6jy5enpia

Passive separation control of a NACA0012 airfoil via a flexible flap

Alistair Revell, Adrian Harwood, Joseph O'Connor
2019 Physics of Fluids  
The incorporation of nature-inspired techniques to control or reduce boundary layer separation, to bring about performance enhancements on air/water vehicles, has been an active research area for many years. In this paper a baseline NACA0012 airfoil is modified using a short flap on its upper surface at Reynolds number Re=1000. The impact of the flap configurationdescribed by length, attachment position, deployment angle and material properties, on the aerodynamic performance of the
more » ... ified by mean and fluctuating forces, is investigated and the flow field is analysed. Inspired by the observation of pop-up feathers on a bird's wing, the flap is first set to be rigid for a range of location, size and inclination angles. After the optimal location of a rigid flap has been established, the flap is then allowed to be flexible, its motion coupled to the encircling flow field, and it is tested for a range of mass ratios and bending stiffness values. The fluid motion is obtained by solving the lattice Boltzmann equation while the dynamics of the flexible flap are calculated using the finite element method (FEM) and the coupling between flow and flap handled by the immersed boundary method (IBM). For the flexible flap, two flapping patterns are observed and the mechanism of separation control via rigid/flexible flap is explained. Compared to the flapless NACA0012 airfoil case, the case with a flap of optimal configuration, the mean lift coefficient is improved by 13.51%, the mean drag coefficient is decreased by 3.67%, the mean lift-drag ratio is improved by 17.84%, the maximum lift fluctuation is decreased by 40.90% and the maximum drag fluctuation is decreased by 56.90%.
doi:10.1063/1.5118933 fatcat:6m4iyq6jm5hs7nmjkvj2h6n4hm

ATP Competitive Protein Kinase C Inhibitors Demonstrate Distinct State-Dependent Inhibition

Ida M. Smith, Naoto Hoshi, Adrian John Harwood
2011 PLoS ONE  
We previously reported that some ATP competitive protein kinase C (PKC) inhibitors are either competitive or uncompetitive inhibitors with respect to substrate peptides. In this report, we demonstrate how the interactions between PKC and inhibitors change PKC activation kinetics. A substrate competitive inhibitor, bisindolylmaleimide I, targets activated PKC and stabilizes PKC in the activated conformation. This leads to transient activation and prolonged deactivation of PKC in the presence of
more » ... isindolylmaleimide I. In contrast, an uncompetitive substrate inhibitor, bisindolylmaleimide IV, targets quiescent PKC and stabilizes PKC in the quiescent conformation, which generates slower activation and suppressed translocation upon activation of PKC.
doi:10.1371/journal.pone.0026338 pmid:22043317 pmcid:PMC3197134 fatcat:lzekbdsxfbavbjyjzz4jnvryhm

Ehmt1 forebrain haploinsufficiency leads to impaired memory, sensory gating and information processing [article]

Brittany Ann Davis, Francois David, Ciara O'Regan, Manal Adam, Adrian Harwood, Vincenzo Crunelli, Anthony Isles
2018 bioRxiv   pre-print
Regulators of chromatin dynamics and transcription are increasingly implicated in the aetiology of neurodevelopmental disorders (NDDs). Haploinsufficiency of EHMT1 , encoding a histone methyl-transferase, is associated with several NDDs, including Kleefstra syndrome, developmental delay and autism spectrum disorder. In order to examine the brain role of EHMT1 we developed and tested a forebrain specific conditional Ehmt1 deletion mouse model ( Ehmt1 D6Cre/+ ). We find that Ehmt1D6Cre/+ mice
more » ... a number of abnormalities in spontaneous behaviours such as activity and anxiety. Of greater relevance to NDDs, we also show that Ehmt1 D6Cre/+ mice have deficits in information processing, evidenced by abnormal sensory-motor gating, a complete absence of object recognition memory and a reduced magnitude of auditory evoked potentials in both paired-pulse inhibition and mismatch negativity (MMN). The electrophysiological experiments show that differences in magnitude response to auditory stimulus were associated with marked reductions in total and evoked beta- and gamma-band oscillatory activity, as well as significant reductions in phase synchronisation. The pattern of electrophysiological deficits in Ehmt1 D6Cre/+ matches those seen in control mice following administration of the selective NMDA antagonist, ketamine. This, coupled with reduction of Grin1 mRNA expression in Ehmt1 D6Cre/+ hippocampus, suggests that Ehmt1 haploinsufficiency may lead to disruption in NMDA-R. Taken together, these data indicate that reduced Ehmt1 dosage during brain development leads to abnormal forebrain circuitry formation, which in turn results in profound information processing deficits. Such information processing deficits are likely paramount to our understanding of the cognitive and neurological dysfunctions shared across the NDDs associated with EHMT1 haploinsufficiency.
doi:10.1101/257626 fatcat:xqzv7low4bekrojhmamqi2kqdq
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