Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

Background: Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion: The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response.

European Union

Determination of shadow notifications of domestic support for agriculture in the European Union under the WTO (World Trade Organization) Agreement on Agriculture, and consideration of the potential impact of an agreement in the Doha Round of multilateral trade negotiations.

Code-switching and transfer: an exploration of similarities and differences

This handbook article gives an historical overview of the development of research into code-switching and discusses its relationship to other language contact phenomena.

British pharmacy professionals’ beliefs and participation in continuing professional development: a review of the literature.

Objectives Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

British pharmacy professionals' beliefs and participation in continuing professional development: a review of the literature

Objectives:  Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods:  A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings:  Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions:  If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

Wind generation's contribution to supporting peak electricity demand: meteorological insights

Wind generation’s contribution to meeting extreme peaks in electricity demand is a key concern for the integration of wind power. In Great Britain (GB), robustly assessing this contribution directly from power system data (i.e. metered wind-supply and electricity demand) is difficult as extreme peaks occur infrequently (by definition) and measurement records are both short and inhomogeneous. Atmospheric circulation-typing combined with meteorological reanalysis data is proposed as a means to address some of these difficulties, motivated by a case study of the extreme peak demand events in January 2010. A preliminary investigation of the physical and statistical properties of these circulation types suggests that they can be used to identify the conditions that are most likely to be associated with extreme peak demand events. Three broad cases are highlighted as requiring further investigation. The high-over-Britain anticyclone is found to be generally associated with very low winds but relatively moderate temperatures (and therefore moderate peak demands, somewhat in contrast to the classic low-wind cold snap that is sometimes apparent in the literature). In contrast, both longitudinally extended blocking over Scotland/Scandinavia and latitudinally extended troughs over western Europe appear to be more closely linked to the very cold GB temperatures (usually associated with extreme peak demands). In both of these latter situations, wind resource averaged across GB appears to be more moderate.

Boosting the globalization of plant proteomics through INPPO: current developments 3 and future prospects

The International Plant Proteomics Organization (INPPO) is a non-profit-organization consisting of people who are involved or interested in plant proteomics. INPPO is constantly growing in volume and activity, which is mostly due to the realization among plant proteomics researchers worldwide for the need of such a global platform. Their active participation resulted in the rapid growth within the first year of INPPO’s official launch in 2011 via its website (www.inppo.com) and publication of the ‘viewpoint paper’ in a special issue of PROTEOMICS (May 2011). Here, we will be highlighting the progress achieved in the year 2011 and the future targets for the year 2012 and onwards. INPPO has achieved a successful administrative structure, the Core Committee (CC; composed of President, Vice-President, and General Secretaries), Executive Council (EC), and General Body (GB) toward achieving the INPPO objectives by its proposed initiatives. Various committees and subcommittees are in the process of being functionalized via discussion amongst scientists around the globe. INPPO’s primary aim to popularize the plant proteomics research in biological sciences has also been recognized by PROTEOMICS where a new section has been introduced to plant proteomics starting January 2012, following the very first issue of this journal devoted to plant proteomics in May 2011. To disseminate organizational activities to the scientific community, INPPO has launched a biannual (in January & July) newsletter entitled “INPPO Express: News & Views” with the first issue published in January 2012. INPPO is also planning to have several activities in 2012, including programs within the Education Outreach committee in different countries, and the development of research ideas and proposals with priority on crop and horticultural plants, while keeping tight interactions with proteomics programs on model plants such as Arabidopsis thaliana, rice, or Medicago truncatula. Altogether, the INPPO progress and upcoming activities are because of immense support, dedication, and hard work of all members of the INPPO family, and also due to the wide encouragement and support from the communities (scientific and non-scientific).

The sources of phosphorus in the waters of Great Britain

Total phosphorus (TP) and soluble reactive phosphorus (SRP) loads to watercourses of the River Basin Districts (RBDs) of Great Britain (GB) were estimated using inventories of industrial P loads and estimates of P loads from sewage treatment works and diffuse P loads calculated using region-specific export coefficients for particular land cover classes combined with census data for agricultural stocking densities and human populations. The TP load to GB waters was estimated to be 60 kt yr(-1), of which households contributed 73, agriculture contributed 20, industry contributed 3, and 4 came from background sources. The SRP load to GB waters was estimated to be 47 kt yr(-1), of which households contributed 78, agriculture contributed 13, industry contributed 4, and 6 came from background Sources. The 'average' area-normalized TP and SRP loads to GB waters approximated 2.4 kg ha(-1) yr(-1) and 1.8 kg ha(-1) yr(-1), respectively. A consideration of uncertainties in the data contributing to these estimates suggested that the TP load to GB waters might lie between 33 and 68 kt yr(-1), with agriculture contributing between 10 and 28 of the TP load. These estimates are consistent with recent appraisals of annual TP and SRP loads to GB coastal waters and area-normalized TP loads from their catchments. Estimates of the contributions of RBDs to these P loads were consistent with the geographical distribution of P concentrations in GB rivers and recent assessments of surface waters at risk from P Pollution.

Towards radiocarbon calibration beyond 28ka using speleothems from the Bahamas

We present a new speleothem record of atmospheric Δ14C between 28 and 44 ka that offers considerable promise for resolving some of the uncertainty associated with existing radiocarbon calibration curves for this time period. The record is based on a comprehensive suite of AMS 14C ages, using new low-blank protocols, and U–Th ages using high precision MC-ICPMS procedures. Atmospheric Δ14C was calculated by correcting 14C ages with a constant dead carbon fraction (DCF) of 22.7 ± 5.9%, based on a comparison of stalagmite 14C ages with the IntCal04 (Reimer et al., 2004) calibration curve between 15 and 11 ka. The new Δ14C speleothem record shows similar structure and amplitude to that derived from Cariaco Basin foraminifera (Hughen et al., 2004, 2006), and the match is further improved if the latter is tied to the most recent Greenland ice core chronology (Svensson et al., 2008). These data are however in conflict with a previously published 14C data set for a stalagmite record from the Bahamas — GB-89-24-1 (Beck et al., 2001), which likely suffered from 14C analytical blank subtraction issues in the older part of the record. The new Bahamas speleothem ∆14C data do not show the extreme shifts between 44 and 40 ka reported in the previous study (Beck et al., 2001). Causes for the observed structure in derived atmospheric Δ14C variation based on the new speleothem data are investigated with a suite of simulations using an earth system model of intermediate complexity. Data-model comparison indicates that major fluctuations in atmospheric ∆14C during marine isotope stage 3 is primarily a function of changes in geomagnetic field intensity, although ocean–atmosphere system reorganisation also played a supporting role.

An aggregated wind power generation model based on MERRA reanalysis data: MATLAB model and example data for the April 2014 wind farm distribution of Great Britain.

The MATLAB model is contained within the compressed folders (versions are available as .zip and .tgz). This model uses MERRA reanalysis data (>34 years available) to estimate the hourly aggregated wind power generation for a predefined (fixed) distribution of wind farms. A ready made example is included for the wind farm distribution of Great Britain, April 2014 ("CF.dat"). This consists of an hourly time series of GB-total capacity factor spanning the period 1980-2013 inclusive. Given the global nature of reanalysis data, the model can be applied to any specified distribution of wind farms in any region of the world. Users are, however, strongly advised to bear in mind the limitations of reanalysis data when using this model/data. This is discussed in our paper: Cannon, Brayshaw, Methven, Coker, Lenaghan. "Using reanalysis data to quantify extreme wind power generation statistics: a 33 year case study in Great Britain". Submitted to Renewable Energy in March, 2014. Additional information about the model is contained in the model code itself, in the accompanying ReadMe file, and on our website: http://www.met.reading.ac.uk/~energymet/data/Cannon2014/