Showing papers by "University of East Anglia published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are 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 monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

The tomato genome sequence provides insights into fleshy fruit evolution

Abstract: Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit development. Solanum is one of the largest angiosperm genera1 and includes annual and perennial plants from diverse habitats. Here we present a high-quality genome sequence of domesticated tomato, a draft sequence of its closest wild relative, Solanum pimpinellifolium2, and compare them to each other and to the potato genome (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence and signs of recent admixture, but show more than 8% divergence from potato, with nine large and several smaller inversions. In contrast to Arabidopsis, but similar to soybean, tomato and potato small RNAs map predominantly to gene-rich chromosomal regions, including gene promoters. The Solanum lineage has experienced two consecutive genome triplications: one that is ancient and shared with rosids, and a more recent one. These triplications set the stage for the neofunctionalization of genes controlling fruit characteristics, such as colour and fleshiness.

Systematic identification of genomic markers of drug sensitivity in cancer cells

Abstract: Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

The landscape of cancer genes and mutational processes in breast cancer

Abstract: All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.

Performance comparison of benchtop high-throughput sequencing platforms

Abstract: Three benchtop high-throughput sequencing instruments are now available. The 454 GS Junior (Roche), MiSeq (Illumina) and Ion Torrent PGM (Life Technologies) are laser-printer sized and offer modest set-up and running costs. Each instrument can generate data required for a draft bacterial genome sequence in days, making them attractive for identifying and characterizing pathogens in the clinical setting. We compared the performance of these instruments by sequencing an isolate of Escherichia coli O104:H4, which caused an outbreak of food poisoning in Germany in 2011. The MiSeq had the highest throughput per run (1.6 Gb/run, 60 Mb/h) and lowest error rates. The 454 GS Junior generated the longest reads (up to 600 bases) and most contiguous assemblies but had the lowest throughput (70 Mb/run, 9 Mb/h). Run in 100-bp mode, the Ion Torrent PGM had the highest throughput (80–100 Mb/h). Unlike the MiSeq, the Ion Torrent PGM and 454 GS Junior both produced homopolymer-associated indel errors (1.5 and 0.38 errors per 100 bases, respectively).

Quantifying uncertainties in global and regional temperature change using an ensemble of observational estimates: The HadCRUT4 data set

Abstract: [1] Recent developments in observational near-surface air temperature and sea-surface temperature analyses are combined to produce HadCRUT4, a new data set of global and regional temperature evolution from 1850 to the present. This includes the addition of newly digitized measurement data, both over land and sea, new sea-surface temperature bias adjustments and a more comprehensive error model for describing uncertainties in sea-surface temperature measurements. An ensemble approach has been adopted to better describe complex temporal and spatial interdependencies of measurement and bias uncertainties and to allow these correlated uncertainties to be taken into account in studies that are based upon HadCRUT4. Climate diagnostics computed from the gridded data set broadly agree with those of other global near-surface temperature analyses. Fitted linear trends in temperature anomalies are approximately 0.07°C/decade from 1901 to 2010 and 0.17°C/decade from 1979 to 2010 globally. Northern/southern hemispheric trends are 0.08/0.07°C/decade over 1901 to 2010 and 0.24/0.10°C/decade over 1979 to 2010. Linear trends in other prominent near-surface temperature analyses agree well with the range of trends computed from the HadCRUT4 ensemble members.

Contributions of cultural services to the ecosystem services agenda.

Abstract: Cultural ecosystem services (ES) are consistently recognized but not yet adequately defined or integrated within the ES framework. A substantial body of models, methods, and data relevant to cultural services has been developed within the social and behavioral sciences before and outside of the ES approach. A selective review of work in landscape aesthetics, cultural heritage, outdoor recreation, and spiritual significance demonstrates opportunities for operationally defining cultural services in terms of socioecological models, consistent with the larger set of ES. Such models explicitly link ecological structures and functions with cultural values and benefits, facilitating communication between scientists and stakeholders and enabling economic, multicriterion, deliberative evaluation and other methods that can clarify tradeoffs and synergies involving cultural ES. Based on this approach, a common representation is offered that frames cultural services, along with all ES, by the relative contribution of relevant ecological structures and functions and by applicable social evaluation approaches. This perspective provides a foundation for merging ecological and social science epistemologies to define and integrate cultural services better within the broader ES framework.

Butterfly genome reveals promiscuous exchange of mimicry adaptations among species

Abstract: Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously.

Carbon emissions from land use and land-cover change

Abstract: . The net flux of carbon from land use and land-cover change (LULCC) accounted for 12.5% of anthropogenic carbon emissions from 1990 to 2010. This net flux is the most uncertain term in the global carbon budget, not only because of uncertainties in rates of deforestation and forestation, but also because of uncertainties in the carbon density of the lands actually undergoing change. Furthermore, there are differences in approaches used to determine the flux that introduce variability into estimates in ways that are difficult to evaluate, and not all analyses consider the same types of management activities. Thirteen recent estimates of net carbon emissions from LULCC are summarized here. In addition to deforestation, all analyses considered changes in the area of agricultural lands (croplands and pastures). Some considered, also, forest management (wood harvest, shifting cultivation). None included emissions from the degradation of tropical peatlands. Means and standard deviations across the thirteen model estimates of annual emissions for the 1980s and 1990s, respectively, are 1.14 ± 0.23 and 1.12 ± 0.25 Pg C yr−1 (1 Pg = 1015 g carbon). Four studies also considered the period 2000–2009, and the mean and standard deviations across these four for the three decades are 1.14 ± 0.39, 1.17 ± 0.32, and 1.10 ± 0.11 Pg C yr−1. For the period 1990–2009 the mean global emissions from LULCC are 1.14 ± 0.18 Pg C yr−1. The standard deviations across model means shown here are smaller than previous estimates of uncertainty as they do not account for the errors that result from data uncertainty and from an incomplete understanding of all the processes affecting the net flux of carbon from LULCC. Although these errors have not been systematically evaluated, based on partial analyses available in the literature and expert opinion, they are estimated to be on the order of ± 0.5 Pg C yr−1.

Toward Principles for Enhancing the Resilience of Ecosystem Services

Abstract: Enhancing the resilience of ecosystem services (ES) that underpin human well-being is critical for meeting current and future societal needs, and requires specific governance and management policies. Using the literature, we identify seven generic policy-relevant principles for enhancing the resilience of desired ES in the face of disturbance and ongoing change in social-ecological systems (SES). These principles are (P1) maintain diversity and redundancy, (P2) manage connectivity, (P3) manage slow variables and feedbacks, (P4) foster an understanding of SES as complex adaptive systems (CAS), (P5) encourage learning and experimentation, (P6) broaden participation, and (P7) promote polycentric governance systems. We briefly define each principle, review how and when it enhances the resilience of ES, and conclude with major research gaps. In practice, the principles often co-occur and are highly interdependent. Key future needs are to better understand these interdependencies and to operationalize and apply...

Hemispheric and large-scale land-surface air temperature variations: An extensive revision and an update to 2010

Abstract: [1] This study is an extensive revision of the Climatic Research Unit (CRU) land station temperature database that has been used to produce a grid-box data set of 5° latitude × 5° longitude temperature anomalies. The new database (CRUTEM4) comprises 5583 station records of which 4842 have enough data for the 1961–1990 period to calculate or estimate the average temperatures for this period. Many station records have had their data replaced by newly homogenized series that have been produced by a number of studies, particularly from National Meteorological Services (NMSs). Hemispheric temperature averages for land areas developed with the new CRUTEM4 data set differ slightly from their CRUTEM3 equivalent. The inclusion of much additional data from the Arctic (particularly the Russian Arctic) has led to estimates for the Northern Hemisphere (NH) being warmer by about 0.1°C for the years since 2001. The NH/Southern Hemisphere (SH) warms by 1.12°C/0.84°C over the period 1901–2010. The robustness of the hemispheric averages is assessed by producing five different analyses, each including a different subset of 20% of the station time series and by omitting some large countries. CRUTEM4 is also compared with hemispheric averages produced by reanalyses undertaken by the European Centre for Medium-Range Weather Forecasts (ECMWF): ERA-40 (1958–2001) and ERA-Interim (1979–2010) data sets. For the NH, agreement is good back to 1958 and excellent from 1979 at monthly, annual, and decadal time scales. For the SH, agreement is poorer, but if the area is restricted to the SH north of 60°S, the agreement is dramatically improved from the mid-1970s.

Genetically Distinct Subsets within ANCA-Associated Vasculitis

Abstract: BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS A genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). CONCLUSIONS This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)

Growing Grassroots Innovations: Exploring the Role of Community-Based Initiatives in Governing Sustainable Energy Transitions:

Abstract: The challenges of sustainable development (and climate change and peak oil, in particular) demand system-wide transformations in sociotechnical systems of provision. An academic literature around coevolutionary innovation for sustainability has recently emerged as an attempt to understand the dynamics and directions of such sociotechnical transformations, which are termed 'sustainability transitions'. This literature has previously focused on market-based technological innovations. Here we apply it to a new context of civil-society-based social innovation and examine the role of community-based initiatives in a transition to a low-carbon sustainable economy in the UK. We present new empirical research from a study of the UK's Transition Towns movement (a 'grassroots innovation') and assess its attempts to grow and infl uence wider societal sociotechnical systems. By applying strategic niche management theory to this civil society context, we deliver theoretically informed practical recommendations for this movement to diff use beyond its niche: to foster deeper engagement with resourceful regime actors; to manage expectations more realistically by delivering tangible opportunities for action and participation; and to embrace a community-based, action-oriented model of social change (in preference to a cognitive theory of behaviour change). Furthermore, our study indicates areas where theory can be refi ned to better explain the growth and broader impacts of grassroots innovations —namely, through a fuller appreciation of the importance of internal niche processes, by understanding the important role of identity and group formation, and by resolving how social practices change in grassroots innovations.

Rapid growth in CO2 emissions after the 2008-2009 global financial crisis

Abstract: Global carbon dioxide emissions from fossil-fuel combustion and cement production grew 5.9% in 2010, surpassed 9 Pg of carbon (Pg C) for the first time, and more than offset the 1.4% decrease in 2009. The impact of the 2008 2009 global financial crisis (GFC) on emissions has been short-lived owing to strong emissions growth in emerging economies, a return to emissions growth in developed economies, and an increase in the fossil-fuel intensity of the world economy.

Methods for detecting early warnings of critical transitions in time series illustrated using simulated ecological data

Abstract: Many dynamical systems, including lakes, organisms, ocean circulation patterns, or financial markets, are now thought to have tipping points where critical transitions to a contrasting state can happen. Because critical transitions can occur unexpectedly and are difficult to manage, there is a need for methods that can be used to identify when a critical transition is approaching. Recent theory shows that we can identify the proximity of a system to a critical transition using a variety of so-called ‘early warning signals’, and successful empirical examples suggest a potential for practical applicability. However, while the range of proposed methods for predicting critical transitions is rapidly expanding, opinions on their practical use differ widely, and there is no comparative study that tests the limitations of the different methods to identify approaching critical transitions using time-series data. Here, we summarize a range of currently available early warning methods and apply them to two simulated time series that are typical of systems undergoing a critical transition. In addition to a methodological guide, our work offers a practical toolbox that may be used in a wide range of fields to help detect early warning signals of critical transitions in time series data.

Obesity and socioeconomic status in developing countries: a systematic review.

Abstract: We undertook a systematic review of studies assessing the association between socioeconomic status (SES) and measured obesity in low- and middle-income countries (defined by the World Bank as countries with per capita income up to US$12,275) among children, men and women. The evidence on the subject has grown significantly since an earlier influential review was published in 2004. We find that in low-income countries or in countries with low human development index (HDI), the association between SES and obesity appears to be positive for both men and women: the more affluent and/or those with higher educational attainment tend to be more likely to be obese. However, in middle-income countries or in countries with medium HDI, the association becomes largely mixed for men and mainly negative for women. This particular shift appears to occur at an even lower level of per capita income than suggested by an influential earlier review. By contrast, obesity in children appears to be predominantly a problem of the rich in low- and middle-income countries.

Porous, Fluorescent, Covalent Triazine-Based Frameworks Via Room-Temperature and Microwave-Assisted Synthesis

Abstract: Porous, fluorescent, covalent triazine-based frameworks (CTFs) are obtained in an unprecedentedly mild reaction, opening up a scalable pathway for molecular building blocks previously thought incompatible with this chemistry. Choice of monomers and synthetic conditions determines the optical properties and nano-scale ordering of these highly microporous materials with BET surface areas exceeding 1100 m(2) g(-1) and exceptional CO(2) capacities (up to 4.17 mmol g(-1)).

Effect of telehealth on use of secondary care and mortality: findings from the Whole System Demonstrator cluster randomised trial

Abstract: Objective To assess the effect of home based telehealth interventions on the use of secondary healthcare and mortality. Design Pragmatic, multisite, cluster randomised trial comparing telehealth with usual care, using data from routine administrative datasets. General practice was the unit of randomisation. We allocated practices using a minimisation algorithm, and did analyses by intention to treat. Setting 179 general practices in three areas in England. Participants 3230 people with diabetes, chronic obstructive pulmonary disease, or heart failure recruited from practices between May 2008 and November 2009. Interventions Telehealth involved remote exchange of data between patients and healthcare professionals as part of patients’ diagnosis and management. Usual care reflected the range of services available in the trial sites, excluding telehealth. Main outcome measure Proportion of patients admitted to hospital during 12 month trial period. Results Patient characteristics were similar at baseline. Compared with controls, the intervention group had a lower admission proportion within 12 month follow-up (odds ratio 0.82, 95% confidence interval 0.70 to 0.97, P=0.017). Mortality at 12 months was also lower for intervention patients than for controls (4.6% v 8.3%; odds ratio 0.54, 0.39 to 0.75, P Conclusions Telehealth is associated with lower mortality and emergency admission rates. The reasons for the short term increases in admissions for the control group are not clear, but the trial recruitment processes could have had an effect. Trial registration number International Standard Randomised Controlled Trial Number Register ISRCTN43002091.

Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial.

Abstract: Context Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy. Palliation is achieved by fluid drainage, but the most effective first-line method has not been determined. Objective To determine whether indwelling pleural catheters (IPCs) are more effective than chest tube and talc slurry pleurodesis (talc) at relieving dyspnea. Design Unblinded randomized controlled trial (Second Therapeutic Intervention in Malignant Effusion Trial [TIME2]) comparing IPC and talc (1:1) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals. Patients were screened from April 2007-February 2011 and were followed up for a year. Intervention Indwelling pleural catheters were inserted on an outpatient basis, followed by initial large volume drainage, education, and subsequent home drainage. The talc group were admitted for chest tube insertion and talc for slurry pleurodesis. Main Outcome Measure Patients completed daily 100-mm line visual analog scale (VAS) of dyspnea over 42 days after undergoing the intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea; 10 mm represents minimum clinically significant difference). Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables. Results Dyspnea improved in both groups, with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc group, with a difference of 0.16 mm (95% CI, −6.82 to 7.15; P = .96). There was a statistically significant improvement in dyspnea in the IPC group at 6 months, with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm (95% CI, −25.2 to −2.8 mm; P = .01). Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days (interquartile range [IQR], 0-1 day) and 4 days (IQR, 2-6 days) for the talc group, with a difference of −3.5 days (95% CI, −4.8 to −1.5 days; P Conclusion Among patients with malignant pleural effusion and no previous pleurodesis, there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea. Trial Registration isrctn.org Identifier: ISRCTN87514420

Biodiversity soup: metabarcoding of arthropods for rapid biodiversity assessment and biomonitoring

Abstract: Summary 1. Traditional biodiversity assessment is costly in time, money and taxonomic expertise. Moreover, data are frequently collected in ways (e.g. visual bird lists) that are unsuitable for auditing by neutral parties, which is necessary for dispute resolution. 2. We present protocols for the extraction of ecological, taxonomic and phylogenetic information from bulk samples of arthropods. The protocols combine mass trapping of arthropods, mass-PCR amplification of the COI barcode gene, pyrosequencing and bioinformatic analysis, which together we call ‘metabarcoding’. 3. We construct seven communities of arthropods (mostly insects) and show that it is possible to recover a substantial proportion of the original taxonomic information. We further demonstrate, for the first time, that metabarcoding allows for the precise estimation of pairwise community dissimilarity (beta diversity) and within-community phylogenetic diversity (alpha diversity), despite the inevitable loss of taxonomic information inherent to metabarcoding. 4. Alpha and beta diversity metrics are the raw materials of ecology and the environmental sciences, facilitating assessment of the state of the environment with a broad and efficient measure of biodiversity.

The Mediterranean Sea under siege: spatial overlap between marine biodiversity, cumulative threats and marine reserves

Abstract: Aim A large body of knowledge exists on individual anthropogenic threats that have an impact on marine biodiversity in the Mediterranean Sea, although we know little about how these threats accumulate and interact to affect marine species and ecosystems. In this context, we aimed to identify the main areas where the interaction between marine biodiversity and threats is more pronounced and to assess their spatial overlap with current marine protected areas in the Mediterranean. Location Mediterranean Sea. Methods We first identified areas of high biodiversity of marine mammals, marine turtles, seabirds, fishes and commercial or well-documented invertebrates. We mapped potential areas of high threat where multiple threats are occurring simultaneously. Finally we quantified the areas of conservation concern for biodiversity by looking at the spatial overlap between high biodiversity and high cumulative threats, and we assessed the overlap with protected areas. Results Our results show that areas with high marine biodiversity in the Mediterranean Sea are mainly located along the central and north shores, with lower values in the south-eastern regions. Areas of potential high cumulative threats are widespread in both the western and eastern basins, with fewer areas located in the south-eastern region. The interaction between areas of high biodiversity and threats for invertebrates, fishes and large animals in general (including large fishes, marine mammals, marine turtles and seabirds) is concentrated in the coastal areas of Spain, Gulf of Lions, north-eastern Ligurian Sea, Adriatic Sea, Aegean Sea, south-eastern Turkey and regions surrounding the Nile Delta and north-west African coasts. Areas of concern are larger for marine mammal and seabird species. Main conclusions These areas may represent good candidates for further research, management and protection activities, since there is only a maximum 2% overlap between existing marine protected areas (which cover 5% of the Mediterranean Sea) and our predicted areas of conservation concern for biodiversity.

Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection

Abstract: Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS(+)) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS(+) B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial-host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts.

Information demand and stock market volatility

Abstract: We study information demand and supply at the firm and market level using data for 30 of the largest stocks traded on NYSE and NASDAQ. Demand is approximated in a novel manner from weekly internet search volume time series drawn from the recently released Google Trends database. Our paper makes contributions in four main directions. First, although information demand and supply tend to be positively correlated, their dynamic interactions do not allow conclusive inferences about the information discovery process. Second, demand for information at the market level is significantly positively related to historical and implied measures of volatility and to trading volume, even after controlling for market return and information supply. Third, information demand increases significantly during periods of higher returns. Fourth, analysis of the expected variance risk premium confirms for the first time empirically the hypothesis that investors demand more information as their level of risk aversion increases.

Use of the mouse aortic ring assay to study angiogenesis

Abstract: Here we provide a protocol for quantitative three-dimensional ex vivo mouse aortic ring angiogenesis assays, in which developing microvessels undergo many key features of angiogenesis over a timescale similar to that observed in vivo. The aortic ring assay allows analysis of cellular proliferation, migration, tube formation, microvessel branching, perivascular recruitment and remodeling-all without the need for cellular dissociation-thus providing a more complete picture of angiogenic processes compared with traditional cell-based assays. Our protocol can be applied to aortic rings from embryonic stage E18 through to adulthood and can incorporate genetic manipulation, treatment with growth factors, drugs or siRNA. This robust assay allows assessment of the salient steps in angiogenesis and quantification of the developing microvessels, and it can be used to identify new modulators of angiogenesis. The assay takes 6-14 d to complete, depending on the age of the mice, treatments applied and whether immunostaining is performed.