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

Pharmacist intervention program to enhance hypertension control: a randomised controlled trial

Objective Studies have demonstrated that hypertension remains inadequately managed throughout the world, with lack of adherence to BP-lowering medication being a major factor. The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control. Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre, Covilhã, located in the Eastern Central Region of Portugal. Method This report evaluates the pharmacist’s interventions during a prospective randomised controlled trial, from July 2009 to June 2010. Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were randomly allocated either to a control group (no pharmaceutical care) or to an intervention group (quarterly follow-up by a hospital pharmacist during a 9-month period). The pharmacist interventions, aimed to increase medication adherence and blood pressure control, involved educational interventions and counselling tips directed to the patient. Main outcome measure Systolic blood pressure, diastolic blood pressure and blood pressure control (according to JNC 7 guidelines) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures. Blood pressure measurements were performed by blinded nurses. Medication adherence was also evaluated, using a validated questionnaire at baseline and at the end of investigation. Results A total of 197 hypertensive patients were randomly assigned to the study (99 in the control group and 98 in the intervention group). Although there were no significant differences (P > 0.05) in both groups concerning mean age, gender, body mass index, and antihypertensive pharmacotherapy, blood pressure control was higher in the intervention group (P = 0.005) at the end of the study. Significant lower systolic blood pressure (−6.8 mmHg, P = 0.006) and diastolic blood pressure (−2.9 mmHg, P = 0.020) levels were observed in the intervention group. Medication adherence was also significantly higher in the intervention group at the end of the study (74.5% vs. 57.6%, P = 0.012).Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents

The effectiveness of therapeutic exercise for joint hypermobility syndrome: A systematic review

Background: Joint hypermobility syndrome (JHS) is a heritable connective tissue disorder characterised by excessive range of movement at multiple joints accompanied by pain. Exercise is the mainstay of management yet its effectiveness is unclear. Objectives: To establish the effectiveness of therapeutic exercise for JHS. Design: Systematic literature review. Data sources: A search of nine online databases, supplemented by a hand search and snowballing. Study eligibility criteria (participants and interventions): People diagnosed with JHS (rather than asymptomatic generalised joint laxity); therapeutic exercise (of any type) used as an intervention; primary data reported; English language; published research. Study appraisal and synthesis methods: Methodological quality was appraised by each reviewer using Critical Appraisal Skills Programme checklists. Articles were then discussed collectively and disagreements resolved through debate. Results: 2001 titles were identified. Four articles met the inclusion criteria, comprising one controlled trial, one comparative trial and two cohort studies. All studies found clinical improvements over time. However there was no convincing evidence that exercise was better than control or that joint-specific and generalised exercise differed in effectiveness. Limitations: The studies used heterogeneous outcome measures, preventing pooling of results. Only one study was a true controlled trial which failed to report between-group statistical analyses post-treatment. Conclusions and implications of key findings: There is some evidence that people with JHS improve with exercise but there is no convincing evidence for specific types of exercise or that exercise is better than control. Further high quality research is required to establish the effectiveness of exercise for JHS. © 2013 Chartered Society of Physiotherapy

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

Experimental Evaluation of Inlet Distortion on an Ejector Powered Hybrid Wing Body at Take-off and Landing Conditions

As part of the NASA Environmentally Responsible Aircraft project, an ultra high bypass ratio engine integration on a hybrid wing body demonstration was planned. The goal was to include engine and airframe integration concepts that reduced fuel consumption by at least 50% while still reducing noise 42 db cumulative on the ground. Since the engines would be mounted on the upper surface of the aft body of the aircraft, the inlets may be susceptible to vortex ingestion from the wing leading edge at high angles of attack and sideslip, and separated wing/body flow. Consequently, experimental and computational studies were conducted to collect flow surveys useful for characterizing engine operability. The wind tunnel tests were conducted at two NASA facilities, the 14- by 22-foot at NASA Langley and the 40- by 80-foot at NASA Ames Research Center. The test results included in this paper show that the distortion and pressure recovery levels were acceptable for engine operability. The CFD studies conducted to compare to experimental data showed excellent agreement for the angle of attacks examined, although failed to match the low speed experimental data at high sideslip angles

Reverse genetics screen identifies six proteins important for malaria development in the mosquito

Transmission from the vertebrate host to the mosquito vector represents a major population bottleneck in the malaria life cycle that can successfully be targeted by intervention strategies. However, to date only about 25 parasite proteins expressed during this critical phase have been functionally analysed by gene disruption. We describe the first systematic, larger scale generation and phenotypic analysis of Plasmodium berghei knockout (KO) lines, characterizing 20 genes encoding putatively secreted proteins expressed by the ookinete, the parasite stage responsible for invasion of the mosquito midgut. Of 12 KO lines that were generated, six showed significant reductions in parasite numbers during development in the mosquito, resulting in a block in transmission of five KOs. While expression data, time point of essential function and mutant phenotype correlate well in three KOs defective in midgut invasion, in three KOs that fail at sporulation, maternal inheritance of the mutant phenotype suggests that essential function occurs during ookinete formation and thus precedes morphological abnormalities by several days

Interventions for preventing oral mucositis for patients with cancer receiving treatment

Interventions for preventing oral mucositis for patients with cancer receiving treatmentTreatment for cancer (including bone marrow transplant) can cause oral mucositis (severe ulcers in the mouth). This painful condition can cause difficulties in eating, drinking and swallowing, and may also be associated with infections which may require the patient to stay longer in hospital. Different strategies are used to try and prevent this condition, and the review of trials found that some of these are effective. Two interventions, cryotherapy (ice chips) and keratinocyte growth factor (palifermin®) showed some benefit in preventing mucositis. Sucralfate is effective in reducing the severity of mucositis, and a further seven interventions, aloe vera, amifostine, intravenous glutamine, granulocyte‐colony stimulating factor (G‐CSF), honey, laser and antibiotic lozenges containing polymixin/tobramycin/amphotericin (PTA) showed weaker evidence of benefit. These were evaluated in patients with different types of cancer, undergoing different types of cancer treatment. Benefits may be restricted to the disease and treatment combinations evaluated