Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma

In this study, reverse transcriptase polymerase chain reaction was used to amplify human endothelin receptor A (ETA) and ETB receptor mRNA. A truncated ETA receptor transcript with exons 3 and 4 skipped was found. The skipping of these two exons results in 109 amino acids being deleted from the receptor. The truncated receptor was expressed in all tissues and cells examined, but the level of expression varied. In melanoma cell lines and melanoma tissues, the truncated receptor gene was the major species, whereas the wild-type ETA was predominant in other tissues. A 1.9-kb ETA transcript was identified in melanoma cell lines by Northern blot, which was much smaller than the transcript in heart and in other tissues reported previously (4.3 kb). The cDNA coding regions of the truncated and wild-type ETA receptors were stably transfected into Chinese hamster ovary (CHO) cells. The truncated ETA receptor-transfected CHO cells did not show binding affinity to endothelin 1 (ET-1) or endothelin 3 (ET-3). The function and biological significance of this truncated ETA receptor is not clear, but it may have regulatory roles for cell responses to ETs

Circumstellar environment of RX Puppis

The symbiotic Mira, RX Pup, shows long-term variations in its mean light level due to variable obscuration by circumstellar dust. The last increase in extinction towards the Mira, between 1995 and 2000, has been accompanied by large changes in the degree of polarization in the optical and red spectral range. The lack of any obvious associated changes in the position angle may indicate the polarization variations are driven by changes in the properties of the dust grains (e.g. variable quantity of dust and variable particle size distribution, due to dust grain formation and growth) rather than changes in the viewing geometry of the scattering region(s), e.g. due to the binary rotation.Comment: Paper presented at Torun 2000 conference on Post-AGB objects as a phase of stellar evolution; 8 pages, 3 figure

Survey Analysis of Overall Job Satisfaction of Physician Assistants

Background: Over the last three decades, the physician assistant (PA) profession has seen an increase in the number of women in the profession, a decline in the age of new PA graduates, a movement toward specialty practice, and an exponential growth in the workforce as a whole. Historically, surveys reveal the majority of PAs are satisfied with their career choice and current job. Although a majority of PAs report high job satisfaction, career burnout is still significant within the profession. Career burnout among health care providers continues to rise due to the strains of the US healthcare system, growing patient populations, and increased administrative burden. Purpose: The purpose of this study is to examine overall career satisfaction and retention rates among physician assistants with 10 years of clinical experience or more versus less than 10 years of clinical experience. The results of this study will provide a means to analyze the various aspects of a PA’s career which contribute most significantly to long term job satisfaction and will ultimately serve to improve retention rates among all institutions. Methods: A survey addressing job characteristics, overall career satisfaction, and retention rates was sent to program directors of 254 varying PA programs across the country. The participants were split into two groups: Group A (participants with \u3c 10 years of clinical practice experience) and Group B (participants with \u3e 10 years of clinical practice experience). Results: Group A contained 127 participants (20 males, 107 females). The majority of the participants were aged 20-39 years old, began their PA career at 25-30 years of age, and had been working as a PA for 2-5 years. Group B contained 71 participants (26 males, 44 females, 1 undisclosed gender). The majority of the participants were 30-49 years old, began their PA careers between the ages of 25-30, and had been working as a PA for more than 15 years. Discussion: Overall, the majority of the participants in the study were females currently practicing in a surgical subspecialty at a non-academic institution in an outpatient setting, which correlates with national data from the American Academy of Physician Assistants (AAPA). Both groups rated job satisfaction a 4 out of 5. Autonomy from supervising physicians differed between Group A and Group B; these differences are likely due to an expansion of knowledge, refined clinical skills, and increasing rapport with the supervising physician that develops over years of clinical practice

SimHap GUI: An intuitive graphical user interface for genetic association analysis

<p>Abstract</p> <p>Background</p> <p>Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the <it>SimHap </it>package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool.</p> <p>Results</p> <p>We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the <it>SimHap </it>R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress.</p> <p>Conclusion</p> <p>SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.</p

Agreement between an online dietary assessment tool (myfood24) and an interviewer-administered 24-h dietary recall in British adolescents aged 11–18 years

myfood24 Is an online 24-h dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24-h multiple-pass recall (MPR) was conducted among seventy-five British adolescents aged 11–18 years. Participants were asked to complete myfood24 and an interviewer-administered MPR on the same day for 2 non-consecutive days at school. Total energy intake (EI) and nutrients recorded by the two methods were compared using intraclass correlation coefficients (ICC), Bland–Altman plots (using between and within-individual information) and weighted κ to assess the agreement. Energy, macronutrients and other reported nutrients from myfood24 demonstrated strong agreement with the interview MPR data, and ICC ranged from 0·46 for Na to 0·88 for EI. There was no significant bias between the two methods for EI, macronutrients and most reported nutrients. The mean difference between myfood24 and the interviewer-administered MPR for EI was −230 kJ (−55 kcal) (95 % CI −490, 30 kJ (−117, 7 kcal); P=0·4) with limits of agreement ranging between 39 % (3336 kJ (−797 kcal)) lower and 34 % (2874 kJ (687 kcal)) higher than the interviewer-administered MPR. There was good agreement in terms of classifying adolescents into tertiles of EI (κ w =0·64). The agreement between day 1 and day 2 was as good for myfood24 as for the interviewer-administered MPR, reflecting the reliability of myfood24. myfood24 Has the potential to collect dietary data of comparable quality with that of an interviewer-administered MPR

Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh

Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the ‘Wildlife Stakeholder Acceptance Capacity’ concept, to explore villagers’ tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers’ beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Holocene evolution of a barrier island system, Ria Formosa, South Portugal

Holocene evolution of the Ria Formosa barrier island system was studied through the examination of a large subsurface dataset acquired from 191 boreholes and five seismic refraction profiles. Two boreholes with total depths of 26 and 16.5 m were selected for a multi-proxy detailed laboratory analysis, including mean grain size distribution, organic matter (OM) content, color variation, shell identification, and benthic foraminifera assemblages. Selected cores are thought to be representative of the identified depositional sub-basins. Subsurface age data from 16 AMS C-14 dated samples were plotted against depth and resulted in a coherent age model of sedimentary infill. The system evolution was largely controlled by sediment availability, accommodation space, and Holocene sea level rise, first at a rapid rate of 7 mm/yr from 10 kcal yr BP to 7.25 kcal yr BP, followed by a slowdown to 1.1 mm/yr until present. A conceptual model for the origin and Holocene evolution of the Ria Formosa barrier island system implies three main steps, leading to the present system geomorphology: (1) marine flooding of incised palaeovalleys by the rapid transgression of palaeovalleys in the early Holocene(2) development of a proto-barrier island chain perched on Pleistocene detritic headlands and steeper interfluve areas during the early to middle Holoceneand (3) full development of the barrier islands chain and enclosing of the coastal lagoon, followed by the maturation of the system with subsequent siltation and salt marsh expansion from the middle Holocene until present. The onset of barrier system formation dates back to ca. 8 kcal yr BP, predating previously proposed age.SIHER project [PTDC/CTE-GIX112236/2009]EU Erasmus Mundus Joint Doctorate in Marine and Coastal Management (MACOMA) fellowship grant, under University of AlgarveEU Erasmus Mundus Joint Doctorate in Marine and Coastal Management (MACOMA) fellowship grant, under University of Cadi