Celsius: a community resource for Affymetrix microarray data

Celsius is a new system that serves as a warehouse by aggregating Affymetrix files and associated metadata, and containing the largest publicly available source of Affymetrix microarray data

Aquatic Hemiptera in Southwest Cameroon: Biodiversity of Potential Reservoirs of Mycobacterium ulcerans and multiple wolbachia sequence types revealed by metagenomics

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical disease associated with freshwater habitats. A variety of limnic organisms harbor this pathogen, including aquatic bugs (Hemiptera: Heteroptera), which have been hypothesized to be epidemiologically important reservoirs. Aquatic Hemiptera exhibit high levels of diversity in the tropics, but species identification remains challenging. In this study, we collected aquatic bugs from emerging foci of BU in the Southwest Region of Cameroon, which were identified using morphological and molecular methods. The bugs were screened for mycobacterial DNA and a selection of 20 mycobacteria-positive specimens from the families Gerridae and Veliidae were subjected to next-generation sequencing. Only one individual revealed putative M. ulcerans DNA, but all specimens contained sequences from the widespread alphaproteobacterial symbiont, Wolbachia. Phylogenetic analysis placed the Wolbachia sequences into supergroups A, B, and F. Circularized mitogenomes were obtained for seven gerrids and two veliids, the first from these families for the African continent. This study suggests that aquatic Hemiptera may have a minor role (if any) in the spread of BU in Southwest Cameroon. Our metagenomic analysis provides new insights into the incursion of Wolbachia into aquatic environments and generated valuable resources to aid molecular taxonomic studies of aquatic Hemiptera. © 2019 by the authors

Convergent evolution of small molecule pheromones in pristionchus nematodes

This is the final version. Available from eLife Sciences Publications via the DOI in this recordData availability: All data generated during this study are included in the manuscript and supporting files. Source data files have been provided.The small molecules that mediate chemical communication between nematodes—so-called “nematode-derived-modular-metabolites” (NDMMs)—are of major interest due to their ability to regulate development, behavior, and life-history. Pristionchus pacificus nematodes produce an impressive diversity of structurally complex NDMMs, some of which act as primer pheromones capable of triggering irreversible developmental switches. Many of these NDMMs have only ever been found in P. pacificus but no attempts had been made to study their evolution by profiling closely related species. This study was designed to bring a comparative perspective to the biochemical study of NDMMs via the systematic MS/MS and NMR-based analysis of exo-metabolomes from over 30 Pristionchus species. We identified 36 novel compounds and found evidence for the convergent evolution of complex NDMMs in separate branches of the Pristionchus phylogeny. Our results demonstrate that biochemical innovation is a recurrent process in Pristionchus nematodes, a pattern likely typical across the animal kingdom.Max Planck Societ

Journey towards tiny perceptual super-resolution

Recent works in single-image perceptual super-resolution (SR) have demonstrated unprecedented performance in generating realistic textures by means of deep convolutional networks. However, these convolutional models are excessively large and expensive, hindering their effective deployment to end devices. In this work, we propose a neural architecture search (NAS) approach that integrates NAS and generative adversarial networks (GANs) with recent advances in perceptual SR and pushes the efficiency of small perceptual SR models to facilitate on-device execution. Specifically, we search over the architectures of both the generator and the discriminator sequentially, highlighting the unique challenges and key observations of searching for an SR-optimized discriminator and comparing them with existing discriminator architectures in the literature. Our tiny perceptual SR (TPSR) models outperform SRGAN and EnhanceNet on both full-reference perceptual metric (LPIPS) and distortion metric (PSNR) while being up to 26.4 × more memory efficient and 33.6 × more compute efficient respectively

Metabonomics and Intensive Care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Universal scaling properties of extremal cohesive holographic phases

We show that strongly-coupled, translation-invariant holographic IR phases at finite density can be classified according to the scaling behaviour of the metric, the electric potential and the electric flux introducing four critical exponents, independently of the details of the setup. Solutions fall into two classes, depending on whether they break relativistic symmetry or not. The critical exponents determine key properties of these phases, like thermodynamic stability, the (ir)relevant deformations around them, the low-frequency scaling of the optical conductivity and the nature of the spectrum for electric perturbations. We also study the scaling behaviour of the electric flux through bulk minimal surfaces using the Hartnoll-Radicevic order parameter, and characterize the deviation from the Ryu-Takayanagi prescription in terms of the critical exponents.Comment: v4: corrected a typo in eqn (3.29), now (3.28). Conclusions unchange

Structural and magnetic phase diagram of CeFeAsO1-xFx and its relationship to high-temperature superconductivity

We use neutron scattering to study the structural and magnetic phase transitions in the iron pnictides CeFeAsO1-xFx as the system is tuned from a semimetal to a high-transition-temperature (high-Tc) superconductor through Fluorine (F) doping x. In the undoped state, CeFeAsO develops a structural lattice distortion followed by a stripe like commensurate antiferromagnetic order with decreasing temperature. With increasing Fluorine doping, the structural phase transition decreases gradually while the antiferromagnetic order is suppressed before the appearance of superconductivity, resulting an electronic phase diagram remarkably similar to that of the high-Tc copper oxides. Comparison of the structural evolution of CeFeAsO1-xFx with other Fe-based superconductors reveals that the effective electronic band width decreases systematically for materials with higher Tc. The results suggest that electron correlation effects are important for the mechanism of high-Tc superconductivity in these Fe pnictides.Comment: 19 pages, 5 figure