Showing papers by "University of Exeter published in 2008"

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

Direct imaging of multiple planets orbiting the star HR 8799.

Abstract: Direct imaging of exoplanetary systems is a powerful technique that can reveal Jupiter-like planets in wide orbits, can enable detailed characterization of planetary atmospheres, and is a key step toward imaging Earth-like planets. Imaging detections are challenging because of the combined effect of small angular separation and large luminosity contrast between a planet and its host star. High-contrast observations with the Keck and Gemini telescopes have revealed three planets orbiting the star HR 8799, with projected separations of 24, 38, and 68 astronomical units. Multi-epoch data show counter clockwise orbital motion for all three imaged planets. The low luminosity of the companions and the estimated age of the system imply planetary masses between 5 and 13 times that of Jupiter. This system resembles a scaled-up version of the outer portion of our solar system.

Constructive and Unconstructive Repetitive Thought.

Abstract: The author reviews research showing that repetitive thought (RT) can have constructive or unconstructive consequences. The main unconstructive consequences of RT are (a) depression, (b) anxiety, and (c) difficulties in physical health. The main constructive consequences of RT are (a) recovery from upsetting and traumatic events, (b) adaptive preparation and anticipatory planning, (c) recovery from depression, and (d) uptake of health-promoting behaviors. Several potential principles accounting for these distinct consequences of RT are identified within this review: (a) the valence of thought content, (b) the intrapersonal and situational context in which RT occurs, and (c) the level of construal (abstract vs. concrete processing) adopted during RT. Of the existing models of RT, it is proposed that an elaborated version of the control theory account provides the best theoretical framework to account for its distinct

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Abstract: Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

Evaluation of the terrestrial carbon cycle, future plant geography and climate‐carbon cycle feedbacks using five Dynamic Global Vegetation Models (DGVMs)

Abstract: This study tests the ability of five Dynamic Global Vegetation Models (DGVMs), forced with observed climatology and atmospheric CO2, to model the contemporary global carbon cycle. The DGVMs are also coupled to a fast ‘climate analogue model’, based on the Hadley Centre General Circulation Model (GCM), and run into the future for four Special Report Emission Scenarios (SRES): A1FI, A2, B1, B2. Results show that all DGVMs are consistent with the contemporary global land carbon budget. Under the more extreme projections of future environmental change, the responses of the DGVMs diverge markedly. In particular, large uncertainties are associated with the response of tropical vegetation to drought and boreal ecosystems to elevated temperatures and changing soil moisture status. The DGVMs show more divergence in their response to regional changes in climate than to increases in atmospheric CO2 content. All models simulate a release of land carbon in response to climate, when physiological effects of elevated atmospheric CO2 on plant production are not considered, implying a positive terrestrial climate-carbon cycle feedback. All DGVMs simulate a reduction in global net primary production (NPP) and a decrease in soil residence time in the tropics and extra-tropics in response to future climate. When both counteracting effects of climate and atmospheric CO2 on ecosystem function are considered, all the DGVMs simulate cumulative net land carbon uptake over the 21st century for the four SRES emission scenarios. However, for the most extreme A1FI emissions scenario, three out of five DGVMs simulate an annual net source of CO2 from the land to the atmosphere in the final decades of the 21st century. For this scenario, cumulative land uptake differs by 494 Pg C among DGVMs over the 21st century. This uncertainty is equivalent to over 50 years of anthropogenic emissions at current levels.

Collective resonances in gold nanoparticle arrays.

Abstract: We present experimental evidence of sharp spectral features in the optical response of 2D arrays of gold nanorods. A simple coupled dipole model is used to describe the main features of the observed spectral line shape. The resonance involves an interplay between the excitation of plasmons localized on the particles and diffraction resulting from the scattering by the periodic arrangement of these particles. We investigate this interplay by varying the particle size, aspect ratio, and interparticle spacing, and observe the effect on the position, width, and intensity of the sharp spectral feature.

Scaling laws of marine predator search behaviour

Abstract: Many free-ranging predators have to make foraging decisions with little, if any, knowledge of present resource distribution and availability. The optimal search strategy they should use to maximize encounter rates with prey in heterogeneous natural environments remains a largely unresolved issue in ecology. Levy walks are specialized random walks giving rise to fractal movement trajectories that may represent an optimal solution for searching complex landscapes. However, the adaptive significance of this putative strategy in response to natural prey distributions remains untested. Here we analyse over a million movement displacements recorded from animal-attached electronic tags to show that diverse marine predators-sharks, bony fishes, sea turtles and penguins-exhibit Levy-walk-like behaviour close to a theoretical optimum. Prey density distributions also display Levy-like fractal patterns, suggesting response movements by predators to prey distributions. Simulations show that predators have higher encounter rates when adopting Levy-type foraging in natural-like prey fields compared with purely random landscapes. This is consistent with the hypothesis that observed search patterns are adapted to observed statistical patterns of the landscape. This may explain why Levy-like behaviour seems to be widespread among diverse organisms, from microbes to humans, as a 'rule' that evolved in response to patchy resource distributions.

Genome-wide association analysis identifies 20 loci that influence adult height

Abstract: Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

The effectiveness of exercise interventions for people with Parkinson's disease: A systematic review and meta‐analysis

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder affecting the physical, psychological, social, and functional status of individuals Exercise programs may be an effective strategy to delay or reverse functional decline for people with PD and a large body of empirical evidence has emerged in recent years The objective is to systematically review randomized controlled trials (RCTs) reporting on the effectiveness of exercise interventions on outcomes (physical, psychological or social functioning, or quality of life) for people with PD RCTs meeting the inclusion criteria were identified by systematic searching of electronic databases Key data were extracted by two independent researchers A mixed methods approach was undertaken using narrative, vote counting, and random effects meta-analysis methods Fourteen RCTs were included and the methodological quality of most studies was moderate Evidence supported exercise as being beneficial with regards to physical functioning, health-related quality of life, strength, balance and gait speed for people with PD There was insufficient evidence support or refute the value of exercise in reducing falls or depression This review found evidence of the potential benefits of exercise for people with PD, although further good quality research is needed Questions remain around the optimal content of exercise interventions (dosing, component exercises) at different stages of the disease

Repetitive negative thinking as a transdiagnostic process

Abstract: The current paper provides an updated review of repetitive negative thinking as a transdiagnostic process. It is shown that elevated levels of repetitive negative thinking are present across a large range of Axis I disorders and appear to be causally involved in the maintenance of emotional problems. As direct comparisons of repetitive negative thinking between different disorders (e.g., GAD–type worry and depressive rumination) have generally revealed more similarities than differences, it is argued that repetitive negative thinking is characterized by the same process across disorders, which is applied to a disorder–specific content. On the other hand, there is some evidence that—within given disorders—repetitive negative thinking can be reliably distinguished from other forms of recurrent cognitions, such as obsessions, intrusive memories or functional forms of repeated thinking. An agenda for future research on repetitive negative thinking from a transdiagnostic perspective is presented.

Mindfulness-based cognitive therapy to prevent relapse in recurrent depression.

Abstract: For people at risk of depressive relapse, mindfulness-based cognitive therapy (MBCT) has an additive benefit to usual care (H. F. Coelho, P. H. Canter, & E. Ernst, 2007). This study asked if, among patients with recurrent depression who are treated with antidepressant medication (ADM), MBCT is comparable to treatment with maintenance ADM (m-ADM) in (a) depressive relapse prevention, (b) key secondary outcomes, and (c) cost effectiveness. The study design was a parallel 2-group randomized controlled trial comparing those on m-ADM (N = 62) with those receiving MBCT plus support to taper/discontinue antidepressants (N = 61). Relapse/recurrence rates over 15-month follow-ups in MBCT were 47%, compared with 60% in the m-ADM group (hazard ratio = 0.63; 95% confidence interval: 0.39 to 1.04). MBCT was more effective than m-ADM in reducing residual depressive symptoms and psychiatric comorbidity and in improving quality of life in the physical and psychological domains. There was no difference in average annual cost between the 2 groups. Rates of ADM usage in the MBCT group was significantly reduced, and 46 patients (75%) completely discontinued their ADM. For patients treated with ADM, MBCT may provide an alternative approach for relapse prevention.

Recent advances in stream and river temperature research

Abstract: Research on stream and river temperatures is reviewed with particular attention being given to advances in understanding gained since 1990 and on investigations of fundamental controls on thermal behaviour, thermal heterogeneity at different spatial scales, the influence of human impacts and the nature of past and future trends. Copyright  2008 John Wiley & Sons, Ltd.

Coral reef management and conservation in light of rapidly evolving ecological paradigms

Abstract: The decline of many coral reef ecosystems in recent decades surprised experienced managers and researchers. It shattered old paradigms that these diverse ecosystems are spatially uniform and temporally stable on the scale of millennia. We now see reefs as heterogeneous, fragile, globally stressed ecosystems structured by strong positive or negative feedback processes. We review the causes and consequences of reef decline and ask whether management practices are addressing the problem at appropriate scales. We conclude that both science and management are currently failing to address the comanagement of extractive activities and ecological processes that drive ecosystems (e.g. productivity and herbivory). Most reef conservation efforts are directed toward reserve implementation, but new approaches are needed to sustain ecosystem function in exploited areas.

Food for thought: supplementary feeding as a driver of ecological change in avian populations

Abstract: Every year, millions of households provide huge quantities of supplementary food to wild birds. While alteration of the natural dynamics of food supply represents a major intervention in avian ecology, we have a remarkably limited understanding of the impacts of this widespread pastime. Here, we examine the many and varied responses of birds to supplementary feeding at backyard feeders – in large-scale management projects and in focused academic studies – and evaluate population responses to the bird-feeding phenomenon. Our review encompasses a wide range of species, from songbirds to raptors, and compares provisioning with a variety of foods, at different times of year and in different locations. We consider positive impacts, such as aiding species conservation programs, and negative ones, such as increased risk of disease transmission. It seems highly likely that natural selection is being artificially perturbed, as feeding influences almost every aspect of bird ecology, including reproduction, behavior...

Large-scale structure of the molecular gas in Taurus revealed by high linear dynamic range spectral line mapping

Abstract: We report the results of a 100 deg2 survey of the Taurus molecular cloud region in 12CO and 13CO -->J = 1→ 0. The image of the cloud in each velocity channel includes -->3 × 106 Nyquist-sampled pixels on a 20 -->'' grid. The high sensitivity and large spatial dynamic range of the maps reveal a very complex, highly structured cloud morphology, including filaments, cavities, and rings. The axes of the striations seen in the 12CO emission from relatively diffuse gas are aligned with the direction of the magnetic field. We have developed a statistical method for analyzing the pixels in which 12CO but not 13CO is detected, which allows us to determine the CO column in the diffuse portion of the cloud, as well as in the denser regions in which we detect both isotopologues. Using a column-density-dependent model for the CO fractional abundance, we derive the mass of the region mapped to be -->2.4 × 104 M☉, more than twice as large as would be obtained using a canonical fixed fractional abundance of 13CO, and a factor of 3 greater than would be obtained considering only the high column density regions. We determine that half the mass of the cloud is in regions having column density below -->2.1 × 1021 cm−2. The distribution of young stars in the region covered is highly nonuniform, with the probability of finding a star in a pixel with a specified column density rising sharply for -->N(H2) = 6 × 1021 cm−2. We determine a relatively low star formation efficiency (mass of young stars/mass of molecular gas), between 0.3% and 1.2%, and an average star formation rate during the past 3 Myr of -->8 × 10−5 stars yr−1.

Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57

Abstract: We have previously described individuals presenting with transient neonatal diabetes and showing a variable pattern of DNA hypomethylation at imprinted loci throughout the genome. We now report mutations in ZFP57, which encodes a zinc-finger transcription factor expressed in early development, in seven pedigrees with a shared pattern of mosaic hypomethylation and a conserved range of clinical features. This is the first description of a heritable global imprinting disorder that is compatible with life.

Applications of stable isotope analyses to avian ecology

Abstract: In the past 20 years the use of stable isotope analysis has become increasingly common in ecological studies. In fact, in some instances these techniques have yielded remarkable insights into the foraging preferences and migrations of birds. Despite these advances and the potential of the approach, it is possibly still not as widely used as might be expected. In this paper we aim to illustrate the potential of the approach in the hope of encouraging more avian ecologists to think again about how these techniques might provide insights in the systems on which they work. We discuss some of the principles behind the approach, and review some of the more recent ornithological studies that have used stable isotope techniques to trace trophic pathways or infer migratory origins. We follow this by discussing some of the latest ideas on how stable isotopes may be used to generate community metrics and close by detailing the important assumptions and caveats that should be considered before undertaking any studies using this technique.

Double-blind review favours increased representation of female authors

Abstract: Double-blind peer review, in which neither author nor reviewer identity are revealed, is rarely practised in ecology or evolution journals However, in 2001, double-blind review was introduced by the journal Behavioral Ecology Following this policy change, there was a significant increase in female first-authored papers, a pattern not observed in a very similar journal that provides reviewers with author information No negative effects could be identified, suggesting that double-blind review should be considered by other journals

'Disruptive technologies', 'pedagogical innovation': What's new? Findings from an in-depth study of students' use and perception of technology

Abstract: The paper describes the findings from a study of students' use and experience of technologies. A series of in-depth case studies were carried out across four subject disciplines, with data collected via survey, audio logs and interviews. The findings suggest that students are immersed in a rich, technology-enhanced learning environment and that they select and appropriate technologies to their own personal learning needs. The findings have profound implications for the way in which educational institutions design and support learning activities.

Muscle metabolic responses to exercise above and below the "critical power" assessed using 31P-MRS.

Abstract: We tested the hypothesis that the asymptote of the hyperbolic relationship between work rate and time to exhaustion during muscular exercise, the “critical power” (CP), represents the highest const...

Plasmon spectroscopy of free-standing graphene films

Abstract: Plasmon spectroscopy of the thinnest possible membrane, a single layer of carbon atoms: graphene, has been carried out in conjunction with ab initio calculations of the low loss function. We observe pi and pi+sigma-surface plasmon modes in free-standing single sheets at 4.7 and 14.6 eV, which are substantially redshifted from their values in graphite. These modes are in very good agreement with the theoretical spectra, which find the pi- and pi+sigma in-plane modes of graphene at 4.8 and 14.5 eV. We also find that there is little loss caused by out-of-plane modes for energies less than about 10 eV.

Maintaining group memberships: Social identity continuity predicts well-being after stroke

Abstract: A survey study of patients recovering from stroke (N = 53) examined the extent to which belonging to multiple groups prior to stroke and the maintenance of those group memberships (as measured by the Exeter Identity Transitions Scales, EXITS) predicted well-being after stroke. Results of correlation analysis showed that life satisfaction was associated both with multiple group memberships prior to stroke and with the maintenance of group memberships. Path analysis indicated that belonging to multiple groups was associated with maintained well-being because there was a greater likelihood that some of those memberships would be preserved after stroke-related life transition. Furthermore, it was found that cognitive failures compromised well-being in part because they made it hard for individuals to maintain group memberships post-stroke. These findings highlight the importance of social identity continuity in facilitating well-being following stroke and, more broadly, show the theoretical contribution that a social identity approach to mental health can make in the context of neuropsychological rehabilitation.

Manufactured nanoparticles: their uptake and effects on fish—a mechanistic analysis

Abstract: There is an emerging literature reporting toxic effects of manufactured nanomaterials (NMs) and nanoparticles (NPs) in fish, but the mechanistic basis of both exposure and effect are poorly understood. This paper critically evaluates some of the founding assumptions in fish toxicology, and likely mechanisms of absorption, distribution, metabolism and excretion (ADME) of NPs in fish compared to other chemicals. Then, using a case study approach, the paper compares these assumptions for two different NPs; TiO2 and C60 fullerenes. Adsorption of NPs onto the gill surface will involve similar processes in the gill microenvironment and mucus layer to other substances, but the uptake mechanisms for NPs by epithelial cells are more likely to occur via vesicular processes (e.g., endocytosis) than uptake on membrane transporters or by diffusion through the cell membranes. Target organs may include the gills, gut, liver and sometimes the brain. Information on metabolism and excretion of NPs in fish is limited; but hepatic excretion into the bile seems a more likely mechanism, rather than mainly by renal or branchial excretion. TiO2 and C60 share some common chemical properties that appear to be associated with some similar toxic effects, but there are also differences, that highlight the notion that chemical reactivity can inform toxic effect of NPs in a fundamentally similar way to other chemicals. In this paper we identify many knowledge gaps including the lack of field observations on fish and other wildlife species for exposure and effects of manufactured NMs. Systematic studies of the abiotic factors that influence bioavailability, and investigation of the cell biology that informs on the mechanisms of metabolism and excretion of NMs, will greatly advance our understanding of the potential for adverse effects. There are also opportunities to apply existing tools and techniques to fundamental studies of fish toxicology with NPs, such as perfused organs and fish cell culture systems.

Weak localization in graphene flakes.

Abstract: We show that the manifestation of quantum interference in graphene is very different from that in conventional two-dimensional systems. Because of the chiral nature of charge carriers, it is not only sensitive to inelastic, phase-breaking scattering, but also to a number of elastic scattering processes. We study weak localization in different samples and at different carrier densities, including the Dirac region, and find the characteristic rates that determine it. We show how the shape and quality of graphene flakes affect the values of the elastic and inelastic rates and discuss their physical origin.

The road to the glass cliff: Differences in the perceived suitability of men and women for leadership positions in succeeding and failing organizations

Abstract: Research into gender and leadership has tended to focus on the inequalities that women encounter while trying to climb the corporate ladder, with particular emphasis on the role played by the so-called glass ceiling. However, recent archival evidence has identified an additional hurdle that women must often overcome once they are in leadership positions: the glass cliff [Ryan, M. K., & Haslam, S. A. (2005a). The glass cliff: Evidence that women are over-represented in precarious leadership positions. British Journal of Management, 16, 81–90; Ryan, M. K. & Haslam, S. A. (2007). The glass cliff: Exploring the dynamics surrounding women's appointment to precarious leadership positions. Academy of Management Review]. This refers to the phenomenon whereby women are more likely than men to be appointed to leadership positions associated with increased risk of failure and criticism because these positions are more likely to involve management of organizational units that are in crisis. This paper presents three experimental studies (Ns = 95, 85, 83) that represent the first experimental investigations of the glass cliff phenomenon. In these, management graduates (Study 1), high-school students (Study 2) or business leaders (Study 3) selected a leader for a hypothetical organization whose performance was either improving or declining. Consistent with predictions, results indicate that the likelihood of a female candidate being selected ahead of an equally qualified male candidate increased when the organization's performance was declining rather than improving. Study 3 also provided evidence that glass cliff appointments are associated with beliefs that they (a) suit the distinctive leadership abilities of women, (b) provide women with good leadership opportunities and (c) are particularly stressful for women. These findings define an important agenda for future research.

Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young

Abstract: Aims/hypothesis Mutations in the GCK and HNF1A genes are the most common cause of the monogenic forms of diabetes known as ‘maturity-onset diabetes of the young’. GCK encodes the glucokinase enzyme, which acts as the pancreatic glucose sensor, and mutations result in stable, mild fasting hyperglycaemia. A progressive insulin secretory defect is seen in patients with mutations in the HNF1A and HNF4A genes encoding the transcription factors hepatocyte nuclear factor-1 alpha and -4 alpha. A molecular genetic diagnosis often changes management, since patients with GCK mutations rarely require pharmacological treatment and HNF1A/4A mutation carriers are sensitive to sulfonylureas. These monogenic forms of diabetes are often misdiagnosed as type 1 or 2 diabetes. Best practice guidelines for genetic testing were developed to guide testing and reporting of results. Methods A workshop was held to discuss clinical criteria for testing and the interpretation of molecular genetic test results. The participants included 22 clinicians and scientists from 13 countries. Draft best practice guidelines were formulated and edited using an online tool (http://www. coventi.com). Results An agreed set of clinical criteria were defined for the testing of babies, children and adults for GCK, HNF1A and HNF4A mutations. Reporting scenarios were discussed and consensus statements produced. Conclusions/interpretation Best practice guidelines have been established for monogenic forms of diabetes caused by mutations in the GCK, HNF1A and HNF4A genes. The guidelines include both diagnostic and predictive genetic tests and interpretation of the results.