Showing papers by "Cardiff University published in 2010"

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

Abstract: Summary Background Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK. Methods Enterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla NDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan. Findings We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. Interpretation The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed. Funding European Union, Wellcome Trust, and Wyeth.

The Herschel-SPIRE instrument and its in-flight performance

Abstract: The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz) The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 03 K The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired The spectrometer has an approximately circular field of view with a diameter of 26' The spectral resolution can be adjusted between 12 and 25 GHz by changing the stroke length of the FTS scan mirror Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 15-2

From filamentary clouds to prestellar cores to the stellar IMF: Initial highlights from the Herschel Gould Belt survey

Abstract: We summarize the first results from the Gould Belt survey, obtained toward the Aquila Rift and Polaris Flare regions during the 'science demonstration phase' of Herschel. Our 70-500 micron images taken in parallel mode with the SPIRE and PACS cameras reveal a wealth of filamentary structure, as well as numerous dense cores embedded in the filaments. Between ~ 350 and 500 prestellar cores and ~ 45-60 Class 0 protostars can be identified in the Aquila field, while ~ unbound starless cores and no protostars are observed in the Polaris field. The prestellar core mass function (CMF) derived for the Aquila region bears a strong resemblance to the stellar initial mass function (IMF), already confirming the close connection between the CMF and the IMF with much better statistics than earlier studies. Comparing and contrasting our Herschel results in Aquila and Polaris, we propose an observationally-driven scenario for core formation according to which complex networks of long, thin filaments form first within molecular clouds, and then the densest filaments fragment into a number of prestellar cores via gravitational instability.

The Einstein Telescope: a third-generation gravitational wave observatory

Abstract: Advanced gravitational wave interferometers, currently under realization, will soon permit the detection of gravitational waves from astronomical sources. To open the era of precision gravitational wave astronomy, a further substantial improvement in sensitivity is required. The future space-based Laser Interferometer Space Antenna and the third-generation ground-based observatory Einstein Telescope (ET) promise to achieve the required sensitivity improvements in frequency ranges. The vastly improved sensitivity of the third generation of gravitational wave observatories could permit detailed measurements of the sources' physical parameters and could complement, in a multi-messenger approach, the observation of signals emitted by cosmological sources obtained through other kinds of telescopes. This paper describes the progress of the ET project which is currently in its design study phase.

α-Synuclein promotes SNARE-complex assembly in vivo and in vitro

Abstract: Presynaptic nerve terminals release neurotransmitters repeatedly, often at high frequency, and in relative isolation from neuronal cell bodies. Repeated release requires cycles of soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE)–complex assembly and disassembly, with continuous generation of reactive SNARE-protein intermediates. Although many forms of neurodegeneration initiate presynaptically, only few pathogenic mechanisms are known, and the functions of presynaptic proteins linked to neurodegeneration, such as α-synuclein, remain unclear. Here, we show that maintenance of continuous presynaptic SNARE-complex assembly required a nonclassical chaperone activity mediated by synucleins. Specifically, α-synuclein directly bound to the SNARE-protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and promoted SNARE-complex assembly. Moreover, triple-knockout mice lacking synucleins developed age-dependent neurological impairments, exhibited decreased SNARE-complex assembly, and died prematurely. Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging.

The sequence and de novo assembly of the giant panda genome

Abstract: Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.

Rett syndrome: Revised diagnostic criteria and nomenclature

Abstract: Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research.

Predictions for the rates of compact binary coalescences observable by ground-based gravitational-wave detectors

Abstract: We present an up-to-date, comprehensive summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo. Astrophysical estimates for compact-binary coalescence rates depend on a number of assumptions and unknown model parameters and are still uncertain. The most confident among these estimates are the rate predictions for coalescing binary neutron stars which are based on extrapolations from observed binary pulsars in our galaxy. These yield a likely coalescence rate of 100 Myr−1 per Milky Way Equivalent Galaxy (MWEG), although the rate could plausibly range from 1 Myr−1 MWEG−1 to 1000 Myr−1 MWEG−1 (Kalogera et al 2004 Astrophys. J. 601 L179; Kalogera et al 2004 Astrophys. J. 614 L137 (erratum)). We convert coalescence rates into detection rates based on data from the LIGO S5 and Virgo VSR2 science runs and projected sensitivities for our advanced detectors. Using the detector sensitivities derived from these data, we find a likely detection rate of 0.02 per year for Initial LIGO–Virgo interferometers, with a plausible range between 2 × 10−4 and 0.2 per year. The likely binary neutron–star detection rate for the Advanced LIGO–Virgo network increases to 40 events per year, with a range between 0.4 and 400 per year.

Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION)

Abstract: Superparamagnetic iron oxide nanoparticles (SPION) are being widely used for various biomedical applications, for example, magnetic resonance imaging, targeted delivery of drugs or genes, and in hyperthermia. Although, the potential benefits of SPION are considerable, there is a distinct need to identify any potential cellular damage associated with these nanoparticles. Besides focussing on cytotoxicity, the most commonly used determinant of toxicity as a result of exposure to SPION, this review also mentions the importance of studying the subtle cellular alterations in the form of DNA damage and oxidative stress. We review current studies and discuss how SPION, with or without different surface coating, may cause cellular perturbations including modulation of actin cytoskeleton, alteration in gene expression profiles, disturbance in iron homeostasis and altered cellular responses such as activation of signalling pathways and impairment of cell cycle regulation. The importance of protein-SPION interaction and various safety considerations relating to SPION exposure are also addressed. Keywords: SPION; cellular stress; cytotoxicity; DNA damage (Published: 21 September 2010) Citation: Nano Reviews 2010, 1: 5358 - DOI: 10.3402/nano.v1i0.5358

Twenty-five pitfalls in the analysis of diffusion MRI data.

Abstract: Obtaining reliable data and drawing meaningful and robust inferences from diffusion MRI can be challenging and is subject to many pitfalls. The process of quantifying diffusion indices and eventually comparing them between groups of subjects and/or correlating them with other parameters starts at the acquisition of the raw data, followed by a long pipeline of image processing steps. Each one of these steps is susceptible to sources of bias, which may not only limit the accuracy and precision, but can lead to substantial errors. This article provides a detailed review of the steps along the analysis pipeline and their associated pitfalls. These are grouped into 1 pre-processing of data; 2 estimation of the tensor; 3 derivation of voxelwise quantitative parameters; 4 strategies for extracting quantitative parameters; and finally 5 intra-subject and inter-subject comparison, including region of interest, histogram, tract-specific and voxel-based analyses. The article covers important aspects of diffusion MRI analysis, such as motion correction, susceptibility and eddy current distortion correction, model fitting, region of interest placement, histogram and voxel-based analysis. We have assembled 25 pitfalls (several previously unreported) into a single article, which should serve as a useful reference for those embarking on new diffusion MRI-based studies, and as a check for those who may already be running studies but may have overlooked some important confounds. While some of these problems are well known to diffusion experts, they might not be to other researchers wishing to undertake a clinical study based on diffusion MRI.

Implementing shared decision making in the NHS

Abstract: Creation of a platform of tools to provide information to doctors and patients should be the first step in giving patients choice about their treatment, say Glyn Elwyn and colleagues.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

Clouds, filaments, and protostars: The Herschel Hi-GAL Milky Way

Abstract: We present the first results from the science demonstration phase for the Hi-GAL survey, the Herschel key program that will map the inner Galactic plane of the Milky Way in 5 bands. We outline our data reduction strategy and present some science highlights on the two observed 2° × 2° tiles approximately centered at l = 30° and l = 59°. The two regions are extremely rich in intense and highly structured extended emission which shows a widespread organization in filaments. Source SEDs can be built for hundreds of objects in the two fields, and physical parameters can be extracted, for a good fraction of them where the distance could be estimated. The compact sources (which we will call cores' in the following) are found for the most part to be associated with the filaments, and the relationship to the local beam-averaged column density of the filament itself shows that a core seems to appear when a threshold around AV ~ 1 is exceeded for the regions in the l = 59° field; a AV value between 5 and 10 is found for the l = 30° field, likely due to the relatively higher distances of the sources. This outlines an exciting scenario where diffuse clouds first collapse into filaments, which later fragment to cores where the column density has reached a critical level. In spite of core L/M ratios being well in excess of a few for many sources, we find core surface densities between 0.03 and 0.5 g cm-2. Our results are in good agreement with recent MHD numerical simulations of filaments forming from large-scale converging flows.

Cancer exosomes trigger fibroblast to myofibroblast differentiation

Abstract: There is a growing interest in the cell–cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. We show that TGF-β is expressed at the exosome surface in association with the transmembrane proteoglycan betaglycan. Although existing in a latent state, this complex was fully functional in eliciting SMAD-dependent signaling. Inhibiting either signaling or betaglycan expression attenuated differentiation. While the kinetics and overall magnitude of the response were similar to that achieved with soluble TGF-β, we identified important qualitative differences unique to the exosomal route of TGF-β delivery, as exemplified by a significant elevation in fibroblast FGF2 production. This hitherto unknown trigger for instigating cellular differentiation in a distinctive manner has major implications for mechanisms underlying cancer-recruited stroma, fibrotic diseases, and wound-healing responses.

A simple role for BDNF in learning and memory

Abstract: Since its discovery almost three decades ago, the secreted neurotrophin brain-derived neurotrophic factor (BDNF) has been firmly implicated in the differentiation and survival of neurons of the CNS. More recently, BDNF has also emerged as an important regulator of synaptogenesis and synaptic plasticity mechanisms underlying learning and memory in the adult CNS. In this review we will discuss our knowledge about the multiple intracellular signalling pathways activated by BDNF, and the role of this neurotrophin in long-term synaptic plasticity and memory formation as well as in synaptogenesis. We will show that maturation of BDNF, its cellular localisation and its ability to regulate both excitatory and inhibitory synapses in the CNS may result in conflicting alterations in synaptic plasticity and memory formation. Lack of a precise knowledge about the mechanisms by which BDNF influences higher cognitive functions and complex behaviours may constitute a severe limitation in the possibility to devise BDNF-based therapeutics for human disorders of the CNS.

The Herschel ATLAS

Abstract: The Herschel ATLAS is the largest open-time key project that will be carried out on the Herschel Space Observatory. It will survey 570 deg2 of the extragalactic sky, 4 times larger than all the other Herschel extragalactic surveys combined, in five far-infrared and submillimeter bands. We describe the survey, the complementary multiwavelength data sets that will be combined with the Herschel data, and the six major science programs we are undertaking. Using new models based on a previous submillimeter survey of galaxies, we present predictions of the properties of the ATLAS sources in other wave bands.

Framing and Communicating Climate Change: The Effects of Distance and Outcome Frame Manipulations

Abstract: Communications regarding climate change are increasingly being utilised in order to encourage sustainable behaviour and the way that these are framed can significantly alter the impact that they have on the recipient. This experimental study seeks to investigate how transferable existing research findings on framing from health and behavioural research are to the climate change case. The study (N = 161) examined how framing the same information about climate change in terms of gain or loss outcomes or in terms of local or distant impacts can affect perceptions. Text on potential climate change impacts was adapted from the 2007 Intergovernmental Panel on Climate Change report, alongside maps and images of potential flooding impacts. Participants then completed measures of various relevant socio-cognitive factors and questions assessing their responses to the information that they had received. Results indicated that, ceteris paribus, gain frames were superior to loss frames in increasing positive attitudes towards climate change mitigation, and also increased the perceived severity of climate change impacts. However, third variable analyses demonstrated that the superiority of the gain frame was partially suppressed by lower fear responses and poorer information recall within gain framed information. In addition, framing climate change impacts as distant (whilst keeping information presented the same) resulted in climate change impacts being perceived as more severe, while attitudes towards climate change mitigation were more positive when participants were asked to consider social rather than personal aspects of climate change. Implications for designing communications about climate change are outlined.

Green Consumption: Behavior and Norms

Abstract: Developing more environmentally sustainable consumption and production systems depends upon consumers' willingness to engage in “greener” consumption behaviors. Research efforts have sought to identify, analyze, and understand the “green consumer.” Initial marketing and economics research, focusing on purchasing activities, has been complemented by research from fields such as industrial ecology and sociology, providing a more holistic picture of green consumption as a process. Much of the research has focused on areas with the greatest environmental impacts, namely peoples' homes and household management, their food choices and behaviors, and their transport behaviors for work, leisure, and travel. The emerging picture of green consumption is of a process that is strongly influenced by consumer values, norms, and habits, yet is highly complex, diverse, and context dependent. There are opportunities for future research that provides greater interdisciplinarity and challenges our assumptions and expectations about consumption and the nature of the consumer society.

Peutz–Jeghers syndrome: a systematic review and recommendations for management

Abstract: Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.

Declines of managed honey bees and beekeepers in Europe

Abstract: Growing evidence indicates that European managed honey bees are in decline, but information for Europe remains patchy and localized. Here we compile data from 18 European countries to assess trends in the number of honey bee colonies and beekeepers between 1965 and 2005. We found consistent declines in colony numbers in central European countries and some increases in Mediterranean countries. Beekeeper numbers have declined in all of the European countries examined. Our data support the view that honey bees are in decline at least in some regions, which is probably closely linked to the decreasing number of beekeepers. Our data on colony numbers and beekeepers must, however, be interpreted with caution due to different approaches and socioeconomic factors in the various countries, thereby limiting their comparability. We therefore make specific recommendations for standardized methodologies to be adopted at the national and global level to assist in the future monitoring of honey bees.

Multiple stressors in freshwater ecosystems

Abstract: Summary 1. The fundamental importance of freshwater resources, the rapid extinction rate among freshwater species and the pronounced sensitivity of freshwater ecosystems to climate change together signal a pre-eminent need for renewed scientific focus and greater resources. Against this background, the Freshwater Biological Association in 2008 launched a new series of ‘summit’ Conferences in Aquatic Biology intended to develop and showcase the application of ecological science to major issues in freshwater management. 2. This collection of studies arose from the first summit entitled ‘Multiple Stressors in Freshwater Ecosystems’. Although freshwater science and management are replete with mutiple-stressor problems, few studies have been designed explicitly to untangle their effects. 3. The individual case studies that follow reveal the wide array of freshwaters affected by multiple stressors, the spatial and temporal scales involved, the species and ecosystem processes affected, the complex interactions between ecology and socioeconomics that engender such effects, the approaches advocated to address the problems and the challenges of restoring affected systems. The studies also illustrate the extent to which new challenges are emerging (e.g. through climate change), but also they develop a vision of how freshwaters might be managed sustainably to offset multiple stressors in future. 4. More generically, these case studies illustrate (i) how freshwaters might be at particular risk of multiple-stressor effects because of conflicts in water use, and because the hydrological cycle vectors stressor effects so effectively and so extensively; (ii) that dramatic, nonlinear, ‘ecological surprises’ sometimes emerge as multiple-stressor effects develop and (iii) that good ecology and good ecologists add considerable value to other freshwater disciplines in understanding multiple stressors and managing their effects.

Attitudes to Language

Abstract: Just about everyone seems to have views about language. Language attitudes and language ideologies permeate our daily lives. Our competence, intelligence, friendliness, trustworthiness, social status, group memberships, and so on, are often judged from the way we communicate. Even the speed at which we speak can evoke reactions. And we often try to anticipate such judgements as we communicate. In this lively introduction, Peter Garrett draws upon research carried out over recent decades in order to discuss such attitudes and the implications they have for our use of language, for social advantage or discrimination, and for social identity. Using a range of examples that includes punctuation, words, grammar, pronunciation, accents, dialects and languages, this book explores the intricate and fascinating ways in which language influences our everyday thoughts, feelings and behaviour.