The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue

BACKGROUND: The murine ghrelin gene (Ghrl), originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0). We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. -----FINDINGS: 5' RACE revealed two transcription start sites (TSSs) in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR), we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. -----CONCLUSION: We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1) raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted

Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene

<p>Abstract</p> <p>Background</p> <p>The peptide hormone ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, gut motility and proliferation of cancer cells. We previously identified a gene on the opposite strand of the ghrelin gene, ghrelinOS (<it>GHRLOS</it>), which spans the promoter and untranslated regions of the ghrelin gene (<it>GHRL</it>). Here we further characterise <it>GHRLOS</it>.</p> <p>Results</p> <p>We have described <it>GHRLOS </it>mRNA isoforms that extend over 1.4 kb of the promoter region and 106 nucleotides of exon 4 of the ghrelin gene, <it>GHRL</it>. These <it>GHRLOS </it>transcripts initiate 4.8 kb downstream of the terminal exon 4 of <it>GHRL </it>and are present in the 3' untranslated exon of the adjacent gene <it>TATDN2 </it>(TatD DNase domain containing 2). Interestingly, we have also identified a putative non-coding <it>TATDN2-GHRLOS </it>chimaeric transcript, indicating that <it>GHRLOS </it>RNA biogenesis is extremely complex. Moreover, we have discovered that the 3' region of <it>GHRLOS </it>is also antisense, in a tail-to-tail fashion to a novel terminal exon of the neighbouring <it>SEC13 </it>gene, which is important in protein transport. Sequence analyses revealed that <it>GHRLOS </it>is riddled with stop codons, and that there is little nucleotide and amino-acid sequence conservation of the <it>GHRLOS </it>gene between vertebrates. The gene spans 44 kb on 3p25.3, is extensively spliced and harbours multiple variable exons. We have also investigated the expression of <it>GHRLOS </it>and found evidence of differential tissue expression. It is highly expressed in tissues which are emerging as major sites of non-coding RNA expression (the thymus, brain, and testis), as well as in the ovary and uterus. In contrast, very low levels were found in the stomach where sense, <it>GHRL </it>derived RNAs are highly expressed.</p> <p>Conclusion</p> <p><it>GHRLOS </it>RNA transcripts display several distinctive features of non-coding (ncRNA) genes, including 5' capping, polyadenylation, extensive splicing and short open reading frames. The gene is also non-conserved, with differential and tissue-restricted expression. The overlapping genomic arrangement of <it>GHRLOS </it>with the ghrelin gene indicates that it is likely to have interesting regulatory and functional roles in the ghrelin axis.</p

Researcher readiness for participating in community-engaged dissemination and implementation research: a conceptual framework of core competencies

Participating in community-engaged dissemination and implementation (CEDI) research is challenging for a variety of reasons. Currently, there is not specific guidance or a tool available for researchers to assess their readiness to conduct CEDI research. We propose a conceptual framework that identifies detailed competencies for researchers participating in CEDI and maps these competencies to domains. The framework is a necessary step toward developing a CEDI research readiness survey that measures a researcher's attitudes, willingness, and self-reported ability for acquiring the knowledge and performing the behaviors necessary for effective community engagement. The conceptual framework for CEDI competencies was developed by a team of eight faculty and staff affiliated with a university's Clinical and Translational Science Award (CTSA). The authors developed CEDI competencies by identifying the attitudes, knowledge, and behaviors necessary for carrying out commonly accepted CE principles. After collectively developing an initial list of competencies, team members individually mapped each competency to a single domain that provided the best fit. Following the individual mapping, the group held two sessions in which the sorting preferences were shared and discrepancies were discussed until consensus was reached. During this discussion, modifications to wording of competencies and domains were made as needed. The team then engaged five community stakeholders to review and modify the competencies and domains. The CEDI framework consists of 40 competencies organized into nine domains: perceived value of CE in D&I research, introspection and openness, knowledge of community characteristics, appreciation for stakeholder's experience with and attitudes toward research, preparing the partnership for collaborative decision-making, collaborative planning for the research design and goals, communication effectiveness, equitable distribution of resources and credit, and sustaining the partnership. Delineation of CEDI competencies advances the broader CE principles and D&I research goals found in the literature and facilitates development of readiness assessments tied to specific training resources for researchers interested in conducting CEDI research

Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research

BACKGROUND: Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. METHODS: We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996–2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. RESULTS: Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. CONCLUSION: There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research

The Vehicle, 1968, Vol. 10 no. 2

Vol. 10, No. 2 Table of Contents 1st Prize, ArtCorner of My MindGerry Moreheadpage 4 #1Clyde Simspage 5 Aesthetics for a VagabondByron Nelsonpage 5 1st Prize, Short StorySteam HeatCharles Whitepage 6 a drawingSally Roachpage 6 an untitled themeCatherine Waitepage 8 MoodKevin Sheapage 9 1st Prize, PoetryHome ThoughtsJane Careypage 10 an untitled poemCatherine Waitepage 11 a drawingSally Roachpage 11 GraceJames T. Jonespage 12 LonelinessSally Roachpage 14 Love, JimmyAstaire Pappaspage 14 CapturedJeff Nelsonpage 15 Winnie Davis Neely AwardUnconcernRoger Zulaufpage 17 an untitled poemDavid N. Deckerpage 17 Morality and American Foreign Policy: The Ever-widening GapBruce L. Berrypage 18 La LibertadChris Holavespage 19 1966Roger Zulaufpage 19 SinThomas W. Phippspage 20 a drawingRoger Perkinspage 20 Summer SweatJerry J. Carterpage 20 1st Prize, EssayCuriosityThomas W. Phippspage 21 A Bottle of DreamsMaurice Snivelypage 21 Chalk DustCatherine Waitepage 22 Diffused Existence or, a Meager Attempt at Helping You Over the Rough SpotsJan Gerlachpage 22 To *e.e.Paula Bresnanpage 22 A PoemThomas W. Phippspage 22 Beach PartyJerol Mikeworthpage 22 Wexford\u27s PartyRoy Lueckepage 23 The Four O\u27Clock ClubSally Roachpage 23 Chesterpage 24https://thekeep.eiu.edu/vehicle/1018/thumbnail.jp

24-Karat or fool’s gold? Consequences of real team and co-acting group membership in healthcare organizations

Although theory on team membership is emerging, limited empirical attention has been paid to the effects of different types of team membership on outcomes. We propose that an important but overlooked distinction is that between membership of real teams and membership of co-acting groups, with the former being characterized by members who report that their teams have shared objectives, and structural interdependence and engage in team reflexivity. We hypothesize that real team membership will be associated with more positive individual- and organizational-level outcomes. These predictions were tested in the English National Health Service, using data from 62,733 respondents from 147 acute hospitals. The results revealed that individuals reporting the characteristics of real team membership, in comparison with those reporting the characteristics of co-acting group membership, witnessed fewer errors and incidents, experienced fewer work related injuries and illness, were less likely to be victims of violence and harassment, and were less likely to intend to leave their current employment. At the organizational level, hospitals with higher proportions of staff reporting the characteristics of real team membership had lower levels of patient mortality and sickness absence. The results suggest the need to clearly delineate real team membership in order to advance scientific understanding of the processes and outcomes of organizational teamwork

Interdisciplinary project-based learning: technology for improving student cognition

The article studies a way of enhancing student cognition by using interdisciplinary project-based learning (IPBL) in a higher education institution. IPBL is a creative pedagogic approach allowing students of one area of specialisation to develop projects for students with different academic profiles. The application of this approach in the Ural State University of Economics resulted in a computer-assisted learning system (CALS) designed by IT students. The CALS was used in an analytical chemistry course with students majoring in Commodities Management and Expertise (‘expert’ students). To test how effective the technology was, the control and experimental groups were formed. In the control group, learning was done with traditional methods. In the experimental group, it was reinforced by IPBL. A statistical analysis of the results, with an application of Pearson χ 2 test, showed that the cognitive levels in both IT and ‘expert’ experimental groups improved as compared with the control groups. The findings demonstrated that IPBL can significantly enhance learning. It can be implemented in any institution of higher or secondary education that promotes learning, including the CALS development and its use for solving problems in different subject areas

Mapping post-glacial expansions: The peopling of Southwest Asia

Archaeological, palaeontological and geological evidence shows that post-glacial warming released human populations from their various climate-bound refugia. Yet specific connections between these refugia and the timing and routes of post-glacial migrations that ultimately established modern patterns of genetic variation remain elusive. Here, we use Y-chromosome markers combined with autosomal data to reconstruct population expansions from regional refugia in Southwest Asia. Populations from three regions in particular possess distinctive autosomal genetic signatures indicative of likely refugia: one, in the north, centered around the eastern coast of the Black Sea, the second, with a more Levantine focus, and the third in the southern Arabian Peninsula. Modern populations from these three regions carry the widest diversity and may indeed represent the most likely descendants of the populations responsible for the Neolithic cultures of Southwest Asia. We reveal the distinct and datable expansion routes of populations from these three refugia throughout Southwest Asia and into Europe and North Africa and discuss the possible correlations of these migrations to various cultural and climatic events evident in the archaeological record of the past 15,000 years

In Situ Spatiotemporal Mapping of Flow Fields around Seeded Stem Cells at the Subcellular Length Scale

A major hurdle to understanding and exploiting interactions between the stem cell and its environment is the lack of a tool for precise delivery of mechanical cues concomitant to observing sub-cellular adaptation of structure. These studies demonstrate the use of microscale particle image velocimetry (μ-PIV) for in situ spatiotemporal mapping of flow fields around mesenchymal stem cells, i.e. murine embryonic multipotent cell line C3H10T1/2, at the subcellular length scale, providing a tool for real time observation and analysis of stem cell adaptation to the prevailing mechanical milieu. In the absence of cells, computational fluid dynamics (CFD) predicts flow regimes within 12% of μ-PIV measures, achieving the technical specifications of the chamber and the flow rates necessary to deliver target shear stresses at a particular height from the base of the flow chamber. However, our μ-PIV studies show that the presence of cells per se as well as the density at which cells are seeded significantly influences local flow fields. Furthermore, for any given cell or cell seeding density, flow regimes vary significantly along the vertical profile of the cell. Hence, the mechanical milieu of the stem cell exposed to shape changing shear stresses, induced by fluid drag, varies with respect to proximity of surrounding cells as well as with respect to apical height. The current study addresses a previously unmet need to predict and observe both flow regimes as well as mechanoadaptation of cells in flow chambers designed to deliver precisely controlled mechanical signals to live cells. An understanding of interactions and adaptation in response to forces at the interface between the surface of the cell and its immediate local environment may be key for de novo engineering of functional tissues from stem cell templates as well as for unraveling the mechanisms underlying multiscale development, growth and adaptation of organisms

ELAC2 polymorphisms and prostate cancer risk: a meta-analysis based on 18 case–control studies

Polymorphisms in the elaC homolog-2 (ELAC2)/HPC2 gene have been hypothesized to alter the risk of prostate cancer. However, the results of the related published studies remained conflicting. We performed a meta-analysis of 18 studies evaluating the association between ELAC2 Ser217Leu and Ala541Thr polymorphisms and prostate cancer risk. Overall, ELAC2 Leu217 allele was associated with increased prostate cancer risk as compared with the Ser217 allele (odds ratio (OR)=1.13, 95% confidence interval (CI): 1.03–1.24, P=0.019 for heterogeneity), as well as in the heterozygote comparison (OR=1.21, 95% CI: 1.07–1.36, P=0.034 for heterogeneity) and the dominant genetic model (OR=1.20, 95% CI: 1.07–1.35, P=0.025 for heterogeneity). Furthermore, the ELAC2 Thr541 allele was associated with increased prostate cancer risk as compared with the Ala541 allele (OR=1.22, 95% CI: 1.00–0.48, P=0.131 for heterogeneity). In the stratified analyses for Ser217Leu polymorphism, there was significantly increased prostate cancer risk in Asian and Caucasian populations, and studies using sporadic and familial prostate cancer cases. Similar result was found in the Asian population in the stratified analyses for Ala541Thr polymorphism. This meta-analysis showed evidence that ELAC2 Ser217Leu and Ala541Thr polymorphisms were associated with prostate cancer risk, and might be low-penetrance susceptibility markers of prostate cancer