A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2021; you can also visit the original URL.
The file type is application/pdf.
Filters
Research On The Go
2021
Zenodo
Preserved Fulltext
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
2021
Zenodo
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2021; you can also visit the original URL.
The file type is application/pdf.
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]
2018
bioRxiv
pre-print
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.1101/398792
fatcat:akldqiho6rbn7cmtueanmsbp3u
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.
Nucleosome dynamics of human iPSC during neural differentiation
2019
EMBO Reports
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
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,
doi:10.15252/embr.201846960
pmid:31036712
pmcid:PMC6549019
fatcat:xrmrovuokvdp3byrvssoxcs7da
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.
Regulation of GSK-3
2001
Cell
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2003; you can also visit the original URL.
The file type is application/pdf.
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
2002
Developmental Cell
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL.
The file type is application/pdf.
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
2000
Current Biology
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL.
The file type is application/pdf.
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
2003
Biochemical Pharmacology
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is application/pdf.
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
2012
PLoS ONE
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.1371/journal.pone.0037213
pmid:22662138
pmcid:PMC3360683
fatcat:g2adid4nmvebxoobx34gt2lydy
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.
Improved screening for oligonucleotide-directed mutant M13 phage
1988
Nucleic Acids Research
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
Prolyl Oligopeptidase, Inositol Phosphate Signalling and Lithium Sensitivity
2011
CNS and Neurological Disorders - Drug Targets
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.2174/187152711794653779
pmid:21222625
pmcid:PMC3267164
fatcat:gilq6vzcbfgrjiiqxne6ol5kwu
more »
... um and human cell systems, and has potential implications for mental health.
Innate Non-Specific Cell Substratum Adhesion
2012
PLoS ONE
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.1371/journal.pone.0042033
pmid:22952588
pmcid:PMC3432024
fatcat:wmqd2lk4tbcwne5oy6jy5enpia
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.
Passive separation control of a NACA0012 airfoil via a flexible flap
2019
Physics of Fluids
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.1063/1.5118933
fatcat:6m4iyq6jm5hs7nmjkvj2h6n4hm
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%.
ATP Competitive Protein Kinase C Inhibitors Demonstrate Distinct State-Dependent Inhibition
2011
PLoS ONE
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.1371/journal.pone.0026338
pmid:22043317
pmcid:PMC3197134
fatcat:lzekbdsxfbavbjyjzz4jnvryhm
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.
Ehmt1 forebrain haploinsufficiency leads to impaired memory, sensory gating and information processing
[article]
2018
bioRxiv
pre-print
Preserved Fulltext
A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2018; you can also visit the original URL.
The file type is application/pdf.
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
doi:10.1101/257626
fatcat:xqzv7low4bekrojhmamqi2kqdq
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.
« Previous
Showing results 1 — 15 out of 890 results