WorldWideScience

Sample records for research gp perceptions

  1. Blended learning in CME: the perception of GP trainers.

    Science.gov (United States)

    Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

    2016-05-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

  2. GP and pharmacist inter-professional learning - a grounded theory study.

    Science.gov (United States)

    Cunningham, David E; Ferguson, Julie; Wakeling, Judy; Zlotos, Leon; Power, Ailsa

    2016-05-01

    Practice Based Small Group Learning (PBSGL) is an established learning resource for primary care clinicians in Scotland and is used by one-third of general practitioners (GPs). Scottish Government and UK professional bodies have called for GPs and pharmacists to work more closely together to improve care. To gain GPs' and pharmacists' perceptions and experiences of learning together in an inter-professional PBSGL pilot. Qualitative research methods involving established GP PBSGL groups in NHS Scotland recruiting one or two pharmacists to join them. A grounded theory method was used. GPs were interviewed in focus groups by a fellow GP, and pharmacists were interviewed individually by two researchers, neither being a GP or a pharmacist. Interviews were audio-recorded, transcribed and analysed using grounded theory methods. Data saturation was achieved and confirmed. Three themes were identified: GPs' and pharmacists' perceptions and experiences of inter-professional learning; Inter-professional relationships and team-working; Group identity and purpose of existing GP groups. Pharmacists were welcomed into GP groups and both professions valued inter-professional PBSGL learning. Participants learned from each other and both professions gained a wider perspective of the NHS and of each others' roles in the organisation. Inter-professional relationships, communication and team-working were strengthened and professionals regarded each other as peers and friends.

  3. Patients' perceptions of their general practitioner's health and weight influences their perceptions of nutrition and exercise advice received.

    Science.gov (United States)

    Fraser, Sally E; Leveritt, Michael D; Ball, Lauren E

    2013-12-01

    General practitioners (GPs) play an important role in the management of patients who are overweight or obese. Previous research suggests that GPs' physical characteristics may influence patients' perceptions of health care received during consultations, mediating the likelihood of patients following health advice provided by GPs. This study aimed to explore patients' perceptions of their GP's health status and its influence on patients' perceptions of healthy eating and exercise advice. An interpretive approach to phenomenology underpinned the qualitative inquiry and study design. Twenty-one participants (aged 55.9 ± 6.5 years; 14 females, 7 males) who had previously received healthy eating and/or exercise advice from a GP participated in an individual semi-structured interview. A constant comparison approach to thematic analysis was conducted. Participants identified three key indicators of perceived health of their GP. These included the GP's physical appearance, particularly weight status; perceived absence of ill health; and disclosure of a GP's health behaviours. Participants expressed favourable perceptions of the weight status of their GP. Participants expected their GP to be a healthy role model and often, but not always, felt more confident receiving advice from a GP that they perceived as healthy. The findings highlight that a GP's perceived health status influences patients' perceptions of the health advice received during consultations. These findings provide a foundation for future research that may allow GPs to modify patients' perceptions of their health status in order to facilitate behaviour change in overweight or obese patients.

  4. Patients' perceptions of their general practitioner's health and weight influences their perceptions of nutrition and exercise advice received

    Directory of Open Access Journals (Sweden)

    Fraser SE

    2013-12-01

    Full Text Available INTRODUCTION: General practitioners (GPs play an important role in the management of patients who are overweight or obese. Previous research suggests that GPs' physical characteristics may influence patients' perceptions of health care received during consultations, mediating the likelihood of patients following health advice provided by GPs. This study aimed to explore patients' perceptions of their GP's health status and its influence on patients' perceptions of healthy eating and exercise advice. METHODS: An interpretive approach to phenomenology underpinned the qualitative inquiry and study design. Twenty-one participants (aged 55.9 ± 6.5 years; 14 females, 7 males who had previously received healthy eating and/or exercise advice from a GP participated in an individual semi-structured interview. A constant comparison approach to thematic analysis was conducted. FINDINGS: Participants identified three key indicators of perceived health of their GP. These included the GP's physical appearance, particularly weight status; perceived absence of ill health; and disclosure of a GP's health behaviours. Participants expressed favourable perceptions of the weight status of their GP. Participants expected their GP to be a healthy role model and often, but not always, felt more confident receiving advice from a GP that they perceived as healthy. CONCLUSION: The findings highlight that a GP's perceived health status influences patients' perceptions of the health advice received during consultations. These findings provide a foundation for future research that may allow GPs to modify patients' perceptions of their health status in order to facilitate behaviour change in overweight or obese patients.

  5. Exploring resilience in rural GP registrars--implications for training.

    Science.gov (United States)

    Walters, Lucie; Laurence, Caroline O; Dollard, Joanne; Elliott, Taryn; Eley, Diann S

    2015-07-02

    Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care providers. This study sought to explore GP registrars' perceptions of their resilience and strategies they used to maintain resilience in rural general practice. In this qualitative interpretive research, semi-structured interviews were recorded, transcribed and analysed using an inductive approach. Initial coding resulted in a coding framework which was refined using constant comparison and negative case analysis. Authors developed consensus around the final conceptual model. Eighteen GP registrars from: Australian College of Rural and Remote Medicine Independent Pathway, and three GP regional training programs with rural training posts. Six main themes emerged from the data. Firstly, rural GP registrars described four dichotomous tensions they faced: clinical caution versus clinical courage; flexibility versus persistence; reflective practice versus task-focused practice; and personal connections versus professional commitment. Further themes included: personal skills for balance which facilitated resilience including optimistic attitude, self-reflection and metacognition; and finally GP registrars recognised the role of their supervisors in supporting and stretching them to enhance their clinical resilience. Resilience is maintained as on a wobble board by balancing professional tensions within acceptable limits. These limits are unique to each individual, and may be expanded through personal growth and professional development as part of rural general practice training.

  6. Patients' perceptions of GP non-verbal communication: a qualitative study.

    Science.gov (United States)

    Marcinowicz, Ludmila; Konstantynowicz, Jerzy; Godlewski, Cezary

    2010-02-01

    During doctor-patient interactions, many messages are transmitted without words, through non-verbal communication. To elucidate the types of non-verbal behaviours perceived by patients interacting with family GPs and to determine which cues are perceived most frequently. In-depth interviews with patients of family GPs. Nine family practices in different regions of Poland. At each practice site, interviews were performed with four patients who were scheduled consecutively to see their family doctor. Twenty-four of 36 studied patients spontaneously perceived non-verbal behaviours of the family GP during patient-doctor encounters. They reported a total of 48 non-verbal cues. The most frequent features were tone of voice, eye contact, and facial expressions. Less frequent were examination room characteristics, touch, interpersonal distance, GP clothing, gestures, and posture. Non-verbal communication is an important factor by which patients spontaneously describe and evaluate their interactions with a GP. Family GPs should be trained to better understand and monitor their own non-verbal behaviours towards patients.

  7. Blended learning in CME: the perception of GP trainers

    NARCIS (Netherlands)

    te Pas, E.; Meinema, J. G.; Visser, M. R. M.; van Dijk, N.

    2016-01-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical

  8. 'I need her to be a doctor': patients' experiences of presenting health information from the internet in GP consultations.

    Science.gov (United States)

    Bowes, Parvathy; Stevenson, Fiona; Ahluwalia, Sanjiv; Murray, Elizabeth

    2012-11-01

    Patients are increasingly using the internet for health-related information and may bring this to a GP consultation. There is scant information about why patients do this and what they expect from their GP. The aim was to explore patients' motivation in presenting information, their perception of the GP's response and what they wanted from their doctor. Qualitative study based in North London involving patients with experience of bringing health information from the internet to their GP. Semi-structured face-to-face and telephone interviews using a critical incident technique, recorded, transcribed verbatim, and subjected to thematic analysis by a multidisciplinary team of researchers. Twenty-six interviews were completed. Participants reported using the internet to become better informed about their health and hence make best use of the limited time available with the GP and to enable the GP to take their problem more seriously. Patients expected their GP to acknowledge the information; discuss, explain, or contextualise it; and offer a professional opinion. Patients tended to prioritise the GP opinion over the internet information. However, if the GP appeared disinterested, dismissive or patronising patients reported damage to the doctor-patient relationship, occasionally to the extent of seeking a second opinion or changing their doctor. This is the first in-depth qualitative study to explore why patients present internet information to their GP within the consultation and what they want when they do this. This information should help GPs respond appropriately in such circumstances.

  9. Asthma control in general practice -- GP and patient perspectives compared.

    Science.gov (United States)

    Henderson, Joan; Hancock, Kerry L; Armour, Carol; Harrison, Christopher; Miller, Graeme

    2013-10-01

    How general practitioners (GPs) and patients perceive asthma control, and concordance between these perceptions, may influence asthma management and medication adherence. The aims of this study were to determine asthma prevalence in adult patients, measure patient asthma control and the correlation between GP and patient perceptions of asthma control or impact. A Supplementary Analysis of Nominated Data (SAND) sub-study of the Bettering the Evaluation and Care of Health (BEACH) program surveyed 2563 patients from 103 GPs. Asthma control was measured using the Asthma Control Questionnaire 5-item version (ACQ-5), and medication adherence by patient self-report. Survey procedures in SAS software and Pearson's correlation statistics were used. Asthma prevalence was 12.7% (95% confidence interval: 10.9-14.5), with good correlation between GP and patient perceptions of asthma control/impact, and with raw ACQ-5 scores. Grouped ACQ-5 scores showed higher levels of uncontrolled asthma. Medication adherence was sub-optimal. The ACQ-5 questions are useful for assessing asthma control, for prompting medication reviews, and for reinforcing benefits of medication compliance to improve long-term asthma control.

  10. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    Science.gov (United States)

    Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

    2016-08-08

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

  11. Educational CPD: how UK GP trainers develop themselves as teachers.

    Science.gov (United States)

    Waters, Mark; Wall, David

    2007-09-01

    There is little in the literature giving the perspective of UK General Practice (GP) trainers on their development as teachers. What motivates GP trainers develop themselves as teachers? What obstacles to their professional development do GP trainers perceive? A questionnaire to all GP trainers in the West Midlands Deanery in 2004. 360/444 (81%) questionnaires were returned. 56.6% of GP trainers had another educational role in addition to training GP Registrars in the practice. 15.8% of trainers possessed an educational qualification. 13 had completed a Certificate in Medical Education and 28 were engaged in study towards that qualification. Trainers wanted more time to spend on their development as teachers than they presently have, and would then be interested in a wider variety of learning methods. However, 56.6% of trainers would still not choose to undertake a university-accredited course. Female GP trainers perceived more difficulty in obtaining protected time for their development as teachers (Educational CPD) (p = 0.021), were significantly less sure of their partners' support for this development (p = 0.033), and were more likely to agree with trainers undertaking a Certificate in Medical Education (p = 0.003). Having an additional educational role did not affect trainers' ability to take protected time, but significantly increased the amount of time aspired to (p = 0.005). Nothing made more difference to trainers' perception of their ability to undertake Educational CPD than did the perceived attitude of their partners. Educational CPD was very important to GP trainers, but getting protected time was difficult. Consideration of the needs and opinions of partners was a very strong barrier to trainers taking sufficient protected time. Given more available time, GP trainers would be more likely to consider gaining academic qualifications in education. However, this was not be something that all trainers wanted.

  12. Psychosocial factors in GP work: the effects of taking a GP position or leaving GP work.

    Science.gov (United States)

    Heponiemi, Tarja; Kouvonen, Anne; Aalto, Anna-Mari; Elovainio, Marko

    2013-06-01

    We examined the effects of leaving public sector general practitioner (GP) work and of taking a GP position on changes in work-related psychosocial factors, such as time pressure, patient-related stress, distress and work interference with family. In addition, we examined whether changes in time pressure and patient-related stress mediated the association of employment change with changes of distress and work interference with family. Participants were 1705 Finnish physicians (60% women) who responded to surveys in 2006 and 2010. Analyses of covariance were conducted to examine the effect of employment change to outcome changes adjusted for gender, age and response format. Mediational effects were tested following the procedures outlined by Baron and Kenny. Employment change was significantly associated with all the outcomes. Leaving public sector GP work was associated with substantially decreased time pressure, patient-related stress, distress and work interference with family. In contrast, taking a position as a public sector GP was associated with an increase in these factors. Mediation tests suggested that the associations of employment change with distress change and work interference with family change were partially explained by the changes in time pressure and patient-related stress. Our results showed that leaving public sector GP work is associated with favourable outcomes, whereas taking a GP position in the public sector is associated with adverse effects. Primary health-care organizations should pay more attention to the working conditions of their GPs, in particular, to time pressure and patient-related stress.

  13. Microsoft Dynamics GP 2013 implementation

    CERN Document Server

    Yudin, Victoria

    2013-01-01

    A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

  14. Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

    Science.gov (United States)

    Le Floch, B; Bastiaens, H; Le Reste, J Y; Lingner, H; Hoffman, R D; Czachowski, S; Assenova, R; Koskela, T H; Klemenc-Ketis, Z; Nabbe, P; Sowinska, A; Montier, T; Peremans, L

    2016-09-13

    Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

  15. Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Claudia A. Nold-Petry

    2017-12-01

    Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp

  16. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

    International Nuclear Information System (INIS)

    Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P.

    2007-01-01

    The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1 JR-FL . Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140 UNC ), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1 JR-FL . All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1 JR-FL were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes

  17. Medical students' perceptions of general practice as a career; a phenomenological study using socialisation theory.

    Science.gov (United States)

    Reid, Katherine; Alberti, Hugh

    2018-04-23

    The ageing population and push to community care has significantly increased the workload of General Practitioners (GPs) in the UK and internationally. In an attempt to tackle this, NHS England has promised 5000 more GPs by 2020/21; however, recruitment is in crisis with GP training posts remaining unfilled. Little research has been carried out to assess the fundamental questions of what medical students' perceptions of General Practice are and what shapes their perceptions at medical school. We aimed to explore medical students' conceptualisations of being a GP and specifically the role of the medical school in shaping their perceptions. Two focus groups of year one and year four medical students were undertaken using an interpretive phenomenological approach. Our study has revealed that medical students perceive General Practice to lack prestige and challenge. These perceptions come, at least in part, from a process of socialisation within medical school, whereby medical students internalise and adopt their role models' perceptions and values, and the values portrayed by the hidden curriculum in their medical school culture. Perceived external pressures to pursue a career in General Practice can have a negative influence and medical schools should be made aware of this.

  18. 'Just a GP': a mixed method study of undermining of general practice as a career choice in the UK.

    Science.gov (United States)

    Alberti, Hugh; Banner, Kimberley; Collingwood, Helen; Merritt, Kymberlee

    2017-11-03

    Failure to recruit sufficient applicants to general practice (GP) training has been a problem both nationally and internationally for many years and undermining of GP is one possible contributing factor. The aim of our study was to ascertain what comments, both negative and positive, are being made in UK clinical settings to GP trainees about GP and to further explore these comments and their influence on career choice. We conducted a mixed methods study. We surveyed all foundation doctors and GP trainees within one region of Health Education England regarding any comments they experienced relating to a career in GP. We also conducted six focus groups with early GP trainees to discuss any comments that they experienced and whether these comments had any influence on their or others career choice. Positive comments reported by trainees centred around the concept that choosing GP is a positive, family-focused choice which facilities a good work-life balance. Workload was the most common negative comment, alongside the notion of being 'just a GP'; the belief that GP is boring, a waste of training and a second-class career choice. The reasons for and origin of the comments are multifactorial in nature. Thematic analysis of the focus groups identified key factors such as previous exposure to and experience of GP, family members who were GPs, GP role models, demographics of the clinician and referral behaviour. Trainees perceived that negative comments may be discouraging others from choosing GP as a career. Our study demonstrates that negative comments towards GP as a career do exist within clinical settings and are having a potential impact on poor recruitment rates to GP training. We have identified areas in which further negative comments could be prevented by changing perceptions of GP as a career. Additional time spent in GP as undergraduates and postgraduates, and positive GP role models, could particularly benefit recruitment. We recommend that undermining of GP

  19. Patient influences on satisfaction and loyalty for GP services.

    Science.gov (United States)

    Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

    2010-04-01

    Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

  20. Association between patients' recommendation of their GP and their evaluation of the GP.

    Science.gov (United States)

    Vedsted, Peter; Heje, Hanne N

    2008-01-01

    Patient priorities and patient evaluations indicate that accessibility should receive more attention to increase quality in general practice. The definition of family medicine emphasizes the patient-centred approach, communication skills, continuity, and clinical skills. We aimed to explore the associations between the 23 items in the Europep questionnaire measuring patient evaluation of general practice and the patients' recommendation of their general practitioner (GP) to friends and to study the relationship of these items with the core competences of family medicine. Cross-sectional study where patients aged 18 years and over attending the practice were included. Patients completed the Danish version of the 23 item Europep questionnaire and an additional item about the degree to which they could recommend their GP to friends. Danish general practice (the DanPEP study). A total of 50 191 patients and 690 GPs were included in the analyses. For each item, associations were calculated between a positive answer and the degree to which the patient could recommend the GP. Analyses were made at patient and GP levels. We found 12 items that covered the 10 most strongly associated items from both analyses: four of six items from the "doctor-patient relationship", two of five items from "medical care", and all items from "information and support" and "organization of services". No items from "accessibility" were among the 12 items. Recommending the GP to others was most strongly associated with the "emphatic", "patient-oriented", "informative and coordinating", and "competent/skilled" GP and to a lesser degree with accessibility to general practice.

  1. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

    Science.gov (United States)

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

    2010-01-19

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  2. Microsoft Dynamics GP 2013 financial management

    CERN Document Server

    Grieve, Ian

    2013-01-01

    A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

  3. Marketing research of consumer perception

    Directory of Open Access Journals (Sweden)

    Rodić Jelena

    2011-01-01

    Full Text Available Perception involves the collection, processing and interpretation of information through sensory receptors and represents the reality of an individual. Collecting customer information is imperative for marketing, because consumers are in the focus of defining all its objectives, strategies and plans. The result of the perception depends on a number of factors and that is why people do not experience stimuli in the same way. A marketing research of consumer perceptions has been carried out in order to identify the habits and understand the behavior of consumers when choosing products with special emphasis on the influence of perception, stimuli from the environment and perceptions of risk in their decision. .

  4. On πgp-continuous functions in topological spaces

    International Nuclear Information System (INIS)

    Park, Jin Han; Park, Jin Keun

    2004-01-01

    The concept of πgp-closed sets was introduced by Park [On πgp-closed sets in topological spaces, Indian J. Pure Appl. Math., in press]. The aim of this paper is to consider and characterize πgp-irresolute and πgp-continuous functions via the concept of πgp-closed sets and to relate these concepts to the classes of πGPO-compact spaces and πGP-connected spaces

  5. GP registrar well-being: a cross-sectional survey.

    Science.gov (United States)

    Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

    2010-02-09

    To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Survey response rate of 51% (102/199). Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS) and 7% mild to moderately anxious (DASS). Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors); similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  6. Agency Researchers' Perception of the Users and Uses of Copy Research.

    Science.gov (United States)

    Reid, Leonard N.; Salmon, Charles T.

    A survey of 30 advertising agency researchers sought to determine (1) whether there are differences between agency researchers' perception of who benefits most from copy research and who should benefit most, and (2) whether there are differences between their perception of how copy research is used and how it should be used. Consistent with…

  7. Quantitative Research Attitudes and Research Training Perceptions among Master's-Level Students

    Science.gov (United States)

    Steele, Janeé M.; Rawls, Glinda J.

    2015-01-01

    This study explored master's-level counseling students' (N = 804) perceptions of training in the Council for Accreditation of Counseling and Related Educational Programs (2009) Research and Program Evaluation standard, and their attitudes toward quantitative research. Training perceptions and quantitative research attitudes were low to moderate,…

  8. Optional part-time and longer GP training modules in GP practices associated with more trainees becoming GPs - a cohort study in Switzerland.

    Science.gov (United States)

    Studerus, Lara; Ahrens, Regina; Häuptle, Christian; Goeldlin, Adrian; Streit, Sven

    2018-01-05

    Switzerland, like many other countries, has a shortage of General Practitioners (GPs). Optional GP training modules in GP practices were offered during the at least 5-year GP training program to increase student and trainee interest in becoming a GP. The training modules had not yet been evaluated. We determined how many Swiss GP trainees became practicing GPs after they completed optional training modules, and if longer modules were associated with higher rates of GP specialization. In this population-based cohort study, we included GP trainees who chose an optional GP training module in GP practice, provided by the Foundation to Promote Training in General Practice (WHM) between 2006 and 2015. GP trainees were invited to complete an online survey to assess the primary outcome (becoming a practicing GP by 2016). Data on non-responders was collected via an internet search. We calculated univariate time-to-event curves to become a practicing GP, stratified by trainee's gender, length, part-time training, and number of years after graduation until training modules were completed. We used a multivariate model to adjust for characteristics of participants, training, and satisfaction with training modules. We assessed primary outcome for 351 (92.1%) of 381 former GP trainees who participated in a WHM program between 2006 and 2015. Of these 218 (57%) were practicing GPs by 2016. When focusing on the trainees who had completed training between 2006 and 2010, the rate of practicing GPs was even 73%. Longer (p = 0.018) and part-time training modules (p = 0.003) were associated with higher rates of being a practicing GP. Most (81%) practicing GPs thought their optional GP training module was (very) important in their choice of specialty. GP trainees who spent more time training in a GP practice, or who trained part-time were more likely to become practicing GPs. Most (80%) rated their training module as (very) important in their choice of career, highlighting that

  9. How can educators support general practice (GP) trainees to develop resilience to prevent burnout?

    Science.gov (United States)

    Sales, Bryony; Macdonald, Alexandra; Scallan, Samantha; Crane, Sue

    2016-11-01

    Burnout impacts adversely on professional and personal life, and holds implications for patient care. Current research on burnout mainly focuses on established general practitioners but it is unclear how early the signs of burnout really start. This work seeks to identify whether specific GP trainee groups are particularly at risk of burnout and the aspects of training they find stressful. A longitudinal cohort study, collecting qualitative and quantitative data through a single mode of data collection (questionnaire) took place with trainees from all GP training years (ST1-3), across a vocational training scheme (n = 48). Data gathered included the Oldenburg Burnout Inventory (OLBI). Higher than anticipated levels of burnout were displayed by all trainees. A sub-group self reporting higher levels of burnout comprised all-female, UK-trained-at-undergraduate GP trainees, with a partner but no children. Top reported stressors included knowledge/uncertainty, workload/time pressures and ePortfolio. Less than 50% of trainees perceived their burnout levels to be as high as their OLBI showing potential lack of insight. This research demonstrates that high levels of burnout are experienced in GP trainees as early as the first year of training. Early identification of burnout amongst trainees is essential by GP educators to help protect the future GP workforce.

  10. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  11. Are there practical opportunities for developing leadership skills during GP training and beyond? A survey of GP trainees and trainers in South East Scotland.

    Science.gov (United States)

    Curry, Nicola; Denney, MeiLing

    2016-01-01

    There is currently a lack of formal training in leadership skills, particularly during GP training. This study aimed to explore the current training and practical opportunities which exist, specifically exploring the views of GP trainees and trainers. An electronic questionnaire was sent to 266 GP trainees and trainers in south-east Scotland. Questions focused on respondents' experience of leadership-specific training and opportunities to engage with leadership roles. There were a total of 76 respondents (28.6% response rate). Response rate was 19.0% in trainees and 34.6% in trainers. A majority of respondents (80.0%) were established GPs. Of those who had received training in leadership, most (72.1%) underwent this after qualifying as a GP. Respondents identified a range of leadership roles within and outside the practice covering clinical and non-clinical areas. Most were interested in future leadership roles (46.7% moderately interested; 28% very interested). More time, training opportunities and the presence of GP role models were motivating factors in terms of participants' readiness to take on future leadership roles. Signposting trainees, trainers and general practitioners to leadership opportunities and training would be relatively easy but addressing a lack of motivating factors at a local level is essential. The effectiveness of such training and opportunities for experiential learning in leadership roles requires further research.

  12. GP registrar well-being: a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Schattner Peter

    2010-02-01

    Full Text Available Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS, a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Results Survey response rate of 51% (102/199. Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS and 7% mild to moderately anxious (DASS. Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors; similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. Conclusions This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  13. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  15. [Eukaryotic Expression and Immunogenic Research of Recombination Ebola Virus Membrane Protein Gp-Fc].

    Science.gov (United States)

    Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi

    2016-01-01

    We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.

  16. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    Energy Technology Data Exchange (ETDEWEB)

    Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

    2015-02-15

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

  17. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    International Nuclear Information System (INIS)

    Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

    2015-01-01

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells

  18. Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH

    Energy Technology Data Exchange (ETDEWEB)

    Cingolani, Gino, E-mail: cingolag@upstate.edu; Andrews, Dewan [Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States); Casjens, Sherwood [Department of Pathology, Division of Cell Biology and Immunology, University of Utah Medical School, Salt Lake City, UT 84112 (United States); Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States)

    2006-05-01

    The crystallogenesis of bacteriophage P22 tail-fiber gp26 is described. To study possible pH-induced conformational changes in gp26 structure, native trimeric gp26 has been crystallized at acidic pH (4.6) and a chimera of gp26 fused to maltose-binding protein (MBP-gp26) has been crystallized at neutral and alkaline pH (7-10). Gp26 is one of three phage P22-encoded tail accessory factors essential for stabilization of viral DNA within the mature capsid. In solution, gp26 exists as an extended triple-stranded coiled-coil protein which shares profound structural similarities with class I viral membrane-fusion protein. In the cryo-EM reconstruction of P22 tail extracted from mature virions, gp26 forms an ∼220 Å extended needle structure emanating from the neck of the tail, which is likely to be brought into contact with the cell’s outer membrane when the viral DNA-injection process is initiated. To shed light on the potential role of gp26 in cell-wall penetration and DNA injection, gp26 has been crystallized at acidic, neutral and alkaline pH. Crystals of native gp26 grown at pH 4.6 diffract X-rays to 2.0 Å resolution and belong to space group P2{sub 1}, with a dimer of trimeric gp26 molecules in the asymmetric unit. To study potential pH-induced conformational changes in the gp26 structure, a chimera of gp26 fused to maltose-binding protein (MBP-gp26) was generated. Hexagonal crystals of MBP-gp26 were obtained at neutral and alkaline pH using the high-throughput crystallization robot at the Hauptman–Woodward Medical Research Institute, Buffalo, NY, USA. These crystals diffract X-rays to beyond 2.0 Å resolution. Structural analysis of gp26 crystallized at acidic, neutral and alkaline pH is in progress.

  19. CGP lil-gp 2.1;1.02 User's Manual

    Science.gov (United States)

    Janikow, Cezary Z.; DeWeese, Scott W.

    1997-01-01

    This document describes extensions provided to lil-gp facilitating dealing with constraints. This document deals specifically with lil-gp 1.02, and the resulting extension is referred to as CGP lil-gp 2.1; 1.02 (the first version is for the extension, the second for the utilized lil-gp version). Unless explicitly needed to avoid confusion, version numbers are omitted.

  20. The learner’s perspective in GP teaching practices with multi-level learners: a qualitative study

    Science.gov (United States)

    2014-01-01

    Background Medical students, junior hospital doctors on rotation and general practice (GP) registrars are undertaking their training in clinical general practices in increasing numbers in Australia. Some practices have four levels of learner. This study aimed to explore how multi-level teaching (also called vertical integration of GP education and training) is occurring in clinical general practice and the impact of such teaching on the learner. Methods A qualitative research methodology was used with face-to-face, semi-structured interviews of medical students, junior hospital doctors, GP registrars and GP teachers in eight training practices in the region that taught all levels of learners. Interviews were audio-recorded and transcribed. Qualitative analysis was conducted using thematic analysis techniques aided by the use of the software package N-Vivo 9. Primary themes were identified and categorised by the co-investigators. Results 52 interviews were completed and analysed. Themes were identified relating to both the practice learning environment and teaching methods used. A practice environment where there is a strong teaching culture, enjoyment of learning, and flexible learning methods, as well as learning spaces and organised teaching arrangements, all contribute to positive learning from a learners’ perspective. Learners identified a number of innovative teaching methods and viewed them as positive. These included multi-level learner group tutorials in the practice, being taught by a team of teachers, including GP registrars and other health professionals, and access to a supernumerary GP supervisor (also termed “GP consultant teacher”). Other teaching methods that were viewed positively were parallel consulting, informal learning and rural hospital context integrated learning. Conclusions Vertical integration of GP education and training generally impacted positively on all levels of learner. This research has provided further evidence about the

  1. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

    2017-01-11

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  2. Internalization and Axonal Transport of the HIV Glycoprotein gp120

    Science.gov (United States)

    Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

    2015-01-01

    The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

  3. Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

    Directory of Open Access Journals (Sweden)

    Kristin Kassler

    2011-01-01

    Full Text Available The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4. Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120.

  4. CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-12-01

    Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

  5. Perception of research and predictors of research career: a study ...

    African Journals Online (AJOL)

    Introduction: Acquisition of research experience by medical students is associated with good research pathway at the postgraduate level and also in the pursuit of a research career. Also, it assists the physician to make evidence based decisions in clinical practice. Objectives: Aim of study was to determine the perception of ...

  6. Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

    Directory of Open Access Journals (Sweden)

    Valeria Feinshtein

    2013-09-01

    Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

  7. Family effects on the rurality of GP's work location: a longitudinal panel study.

    Science.gov (United States)

    McGrail, Matthew R; Russell, Deborah J; O'Sullivan, Belinda G

    2017-10-19

    should be regularly reviewed as part of GP retention planning. This research supports investment in regional development for strong local secondary school and partner employment opportunities.

  8. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.

    Science.gov (United States)

    Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten; Derking, Ronald; Falkowska, Emilia; de la Peña, Alba Torrents; Cupo, Albert; Julien, Jean-Philippe; van Gils, Marit; Lee, Peter S; Peng, Wenjie; Paulson, James C; Poignard, Pascal; Burton, Dennis R; Moore, John P; Sanders, Rogier W; Wilson, Ian A; Ward, Andrew B

    2014-05-15

    All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Patient satisfaction with out-of-hours GP cooperatives: a longitudinal study.

    Science.gov (United States)

    Smits, Marleen; Huibers, Linda; Oude Bos, Anita; Giesen, Paul

    2012-12-01

    For over a decade, out-of-hours primary care in the Netherlands has been provided by general practitioner (GP) cooperatives. In the past years, quality improvements have been made and patients have become acquainted with the service. This may have increased patient satisfaction. The objective of this study was to examine changes in patient satisfaction with GP cooperatives over time. Longitudinal observational study. A validated patient satisfaction questionnaire was distributed in 2003-2004 (T1) and 2007-2008 (T2). Items were rated on a scale from 0 to 10 (1 = very bad; 10 = excellent). Eight GP cooperatives in the Netherlands. Stratified sample of 9600 patients. Response was 55% at T1 (n = 2634) and 51% at T2 (n = 2462). Expectations met; satisfaction with triage nurses, GPs, and organization. For most patients the care received at the GP cooperative met their expectations (T1: 86.1% and T2: 88.4%). Patients were satisfied with the triage nurses (overall grade T1: 7.73 and T2: 7.99), GPs (T1: 8.04 and T2: 8.25), and organization (overall grade T1: 7.60 and T2: 7.78). Satisfaction with triage nurses showed the largest increase over time. The quality and effectiveness of advice or treatment were given relatively low grades. Of all organizational aspects, the lowest grades were given for waiting times and information about the cooperative. In general, patients were initially satisfied with GP cooperatives and satisfaction had even increased four years later. However, there is room for improvement in the content of the advice, waiting times, and information supply. More research is needed into satisfaction of specific patient groups.

  10. Perception of low dose radiation risks among radiation researchers in Korea.

    Science.gov (United States)

    Seong, Ki Moon; Kwon, TaeWoo; Seo, Songwon; Lee, Dalnim; Park, Sunhoo; Jin, Young Woo; Lee, Seung-Sook

    2017-01-01

    Expert's risk evaluation of radiation exposure strongly influences the public's risk perception. Experts can inform laypersons of significant radiation information including health knowledge based on experimental data. However, some experts' radiation risk perception is often based on non-conclusive scientific evidence (i.e., radiation levels below 100 millisievert), which is currently under debate. Examining perception levels among experts is important for communication with the public since these individual's opinions have often exacerbated the public's confusion. We conducted a survey of Korean radiation researchers to investigate their perceptions of the risks associated with radiation exposure below 100 millisievert. A linear regression analysis revealed that having ≥ 11 years' research experience was a critical factor associated with radiation risk perception, which was inversely correlated with each other. Increased opportunities to understand radiation effects at perception of radiation exposure. In addition, radiation researchers conceived that more scientific evidence reducing the uncertainty for radiation effects perception of radiation exposure.

  11. Perception of low dose radiation risks among radiation researchers in Korea

    Science.gov (United States)

    Seo, Songwon; Lee, Dalnim; Park, Sunhoo; Jin, Young Woo; Lee, Seung-Sook

    2017-01-01

    Expert’s risk evaluation of radiation exposure strongly influences the public’s risk perception. Experts can inform laypersons of significant radiation information including health knowledge based on experimental data. However, some experts’ radiation risk perception is often based on non-conclusive scientific evidence (i.e., radiation levels below 100 millisievert), which is currently under debate. Examining perception levels among experts is important for communication with the public since these individual’s opinions have often exacerbated the public’s confusion. We conducted a survey of Korean radiation researchers to investigate their perceptions of the risks associated with radiation exposure below 100 millisievert. A linear regression analysis revealed that having ≥ 11 years’ research experience was a critical factor associated with radiation risk perception, which was inversely correlated with each other. Increased opportunities to understand radiation effects at risk perception of radiation exposure. In addition, radiation researchers conceived that more scientific evidence reducing the uncertainty for radiation effects risk perception of radiation exposure. PMID:28166286

  12. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  13. Malaysian and American Students' Perceptions of Research Ethics

    Science.gov (United States)

    Bowman, Laura L.; Anthonysamy, Angela

    2006-01-01

    Differences in perceptions of research ethics between Malaysian and American students were assessed using a questionnaire that measured perceptions of voluntary informed consent for adults and children, assessment of the risk/benefit ratio, issues of deception, and issues of privacy and confidentiality. As predicted, Malaysian students had less…

  14. Prediction of the Secondary Structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nielsen, Jens O.

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  15. Frequency and persistency of DNA vaccine encoding GP25 by oral on common carp

    Directory of Open Access Journals (Sweden)

    Sri Nuryati

    2015-05-01

    Full Text Available ABSTRACT Koi herpesvirus (KHV is a major viral pathogen that infects common carp and koi. KHV disease outbreak is happened in almost all centre of common carp culture in Indonesia and caused mass mortality. Deoxyribonucleic acid (DNA vaccination method is one of ways to cope with KHV infection. Vaccines were commonly given by injection. The aim of this research was to get frequency and persistency of DNA vaccine encoding GP25 given by oral delivery method in common carp. This research would like to determine dose, frequency of vaccination, persistency of DNA vaccine and culture medium for the bacterial host. DNA vaccine persistency test was done by using polymerase chain reaction (PCR method with the specific primer for GP25 gene. The results showed that level of DNA vaccine that could be detected in feed was 7.56 ng (equal to 1.598×1010 copies. Efficient culture medium for Escherichia coli DH5α carrying DNA vaccine was LB triptone. Feeding fish with diet supplemented with 1 mL E. coli DH5α containing DNA vaccine for each fish and two times a week allowed persistence of DNA vaccine in kindney and spleen. Keywords: common carp, KHV, DNA vaccine, GP25, persistance  ABSTRAK Koi herpesvirus (KHV adalah virus patogen utama yang menginfeksi ikan mas dan ikan koi. Wabah penyakit KHV terjadi di hampir semua sentra budidaya ikan mas di Indonesia dan menyebabkan kematian massal ikan. Metode vaksinasi DNA merupakan salah satu cara yang dapat dilakukan untuk menanggulangi serangan KHV. Pemberian vaksin umumnya dilakukan dengan cara injeksi. Tujuan penelitian ini adalah untuk menguji frekuensi dan persistensi vaksin DNA GP25 antivirus KHV yang diberikan melalui oral pada ikan mas. Pada penelitian ini dilakukan uji dosis, frekuensi pemberian vaksin, persistensi vaksin DNA, dan media kultur bakteri inang. Persistensi vaksin DNA dianalisis menggunakan metode PCR dengan primer spesifik gen GP25. Hasil penelitian menunjukkan bahwa dosis vaksin DNA yang

  16. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  17. Cloning, expression and preliminary crystallographic analysis of the equine infectious anaemia virus (EIAV) gp45 ectodomain

    International Nuclear Information System (INIS)

    Sun, Pei-Long; Lv, Shu-Xia; Zhou, Jian-Hua; Liu, Xin-Qi

    2011-01-01

    The equine infectious anaemia virus gp45 ectodomain was cloned, expressed and crystallized. Preliminary crystallographic analysis showed that the protein belonged to space group P6 3 and contained one molecule per asymmetric unit. Like human immunodeficiency virus (HIV), equine infectious anaemia virus (EIAV) belongs to the lentivirus genus. The first successful lentiviral vaccine was developed for EIAV. Thus, EIAV may serve as a valuable model for HIV vaccine research. EIAV glycoprotein 45 (gp45) plays a similar role to gp41 in HIV by mediating virus–host membrane fusion. The gp45 ectodomain was constructed according to the structure of HIV gp41, with removal of the disulfide-bond loop region. The protein was expressed in Escherichia coli and crystallized following purification. However, most of the crystals grew as aggregates and could not be used for data collection. By extensively screening hundreds of crystals, a 2.7 Å resolution data set was collected from a single crystal. The crystal belonged to space group P6 3 , with unit-cell parameters a = b = 46.84, c = 101.61 Å, α = β = 90, γ = 120°. Molecular replacement was performed using the coordinates of various lengths of HIV gp41 as search models. A long bent helix was identified and a well defined electron-density map around the long helix was obtained. This primary model provided the starting point for further refinement

  18. Changes in nursing students' perceptions of research and evidence-based practice after completing a research course.

    Science.gov (United States)

    Keib, Carrie N; Cailor, Stephanie M; Kiersma, Mary E; Chen, Aleda M H

    2017-07-01

    Nurses need a sound education in research and evidence-based practice (EBP) to provide patients with optimal care, but current teaching methods could be more effective. To evaluate the changes in nursing students 1) perceptions of research and EBP, 2) confidence in research and EBP, and 3) interest in research participation after completing a course in research and EBP. A pre-post assessment design was utilized to compare changes in students. This project was conducted at a small, private liberal arts institution with Bachelor of Science (BSN) students. Two cohorts of third-year BSN students (Year 1 N=55, Year 2 N=54) who were taking a required, semester-long Nursing Research and EBP course. Students' perceptions of and confidence in research and EBP were assessed pre- and post-semester using the Confidence in Research and EBP survey, which contained 7 demographic items, 9 Research Perceptions items, and 19 Confidence in Research items (5-point Likert scale; 1=Not at all confident, 5=Extremely confident). Two years of data were collected and analyzed in SPSS v.24.0. Wilcoxon signed-ranks tests and Mann-Whitney-U tests were utilized to examine the data. Students had significant improvements in perceptions of and confidence in research and EBP (pnursing practice. Copyright © 2017. Published by Elsevier Ltd.

  19. Critical review and hydrologic application of threshold detection methods for the generalized Pareto (GP) distribution

    Science.gov (United States)

    Mamalakis, Antonios; Langousis, Andreas; Deidda, Roberto

    2016-04-01

    Estimation of extreme rainfall from data constitutes one of the most important issues in statistical hydrology, as it is associated with the design of hydraulic structures and flood water management. To that extent, based on asymptotic arguments from Extreme Excess (EE) theory, several studies have focused on developing new, or improving existing methods to fit a generalized Pareto (GP) distribution model to rainfall excesses above a properly selected threshold u. The latter is generally determined using various approaches, such as non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data, graphical methods where one studies the dependence of GP distribution parameters (or related metrics) on the threshold level u, and Goodness of Fit (GoF) metrics that, for a certain level of significance, locate the lowest threshold u that a GP distribution model is applicable. In this work, we review representative methods for GP threshold detection, discuss fundamental differences in their theoretical bases, and apply them to 1714 daily rainfall records from the NOAA-NCDC open-access database, with more than 110 years of data. We find that non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data are generally not reliable, while methods that are based on asymptotic properties of the upper distribution tail lead to unrealistically high threshold and shape parameter estimates. The latter is justified by theoretical arguments, and it is especially the case in rainfall applications, where the shape parameter of the GP distribution is low; i.e. on the order of 0.1 ÷ 0.2. Better performance is demonstrated by graphical methods and GoF metrics that rely on pre-asymptotic properties of the GP distribution. For daily rainfall, we find that GP threshold estimates range between 2÷12 mm/d with a mean value of 6.5 mm/d, while the existence of quantization in the

  20. Screening and Identification of ssDNA Aptamer for Human GP73

    Directory of Open Access Journals (Sweden)

    Jingchun Du

    2015-01-01

    Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.

  1. Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

    Directory of Open Access Journals (Sweden)

    Johansson Ingegerd

    2007-06-01

    Full Text Available Abstract Background Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries, harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. Methods A case-referent study was performed in 12-year-old Swedish children with high (n = 19 or low (n = 19 caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. Results All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively. The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37 and saliva adhesion of S. mutans Ingbritt (VIP = 1.47. The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. Conclusion Gp-340 I behaves as a caries

  2. The league of extraordinary generalists: a qualitative study of professional identity and perceptions of role of GPs working on a national after hours helpline in Australia.

    Science.gov (United States)

    McKenzie, Rosemary; Williamson, Michelle

    2016-04-22

    Telephone triage and advice services (TTAS) have become commonplace in western health care systems particularly as an aid to patient access and demand management in the after hours period. In 2011 an after hours general practitioner (GP) helpline was established as a supplementary service to existing 24-h nurse-TTAS in Australia. Callers to the service in the after hours period who are triaged by a nurse as needing to see a GP immediately or within 24 h may speak with a GP on the line to obtain further assessment and advice. While much research has been undertaken on the roles of nurses in TTAS and the professional identities and attitudes to new technology of community-based GPs, little is known of the perceptions of role and identity of GPs providing after hours advice on primary care helplines. This qualitative study explored the perceptions of professional identity and role, motivations and contributions to the health system of GPs employed on the Australian afterhours GP helpline in 2011-2013. The study took a phenomenographic approach seeking to understand the essence of being a telephone GP, probing professional identity while also exploring role tensions. Twelve GPs, or 15% of the helpline GP workforce participated in the qualitative study. The GPs experienced both personal and professional benefits and believed they were strengthening patient care and the Australian health system. However the role required a re-alignment of practice that challenged professional autonomy, the doctor-patient relationship and commitment to continuity of care. Some GPs made this role realignment more readily than others and were well suited to the helpline role. There was a strong collegial bond amongst the helpline GPs which facilitated the maintenance of professional autonomy. Telephone GP assessment and advice does not demonstrate the same breadth as face-to-face practice and provides little opportunity for continuity of care, but this has not prevented those performing the

  3. Philippine Classroom Teachers as Researchers: Teachers' Perceptions, Motivations, and Challenges

    Science.gov (United States)

    Ulla, Mark B.; Barrera, Kenneth Ian B.; Acompanado, Meller M.

    2017-01-01

    This study explores teachers' perceptions and motivations, challenges, and needs of 50 teachers in Agusan del Norte, Philippines with regards to doing research. Methodologies used were survey questionnaire, and group and individual interviews. Findings revealed that teacher-respondents had a positive perceptions towards doing research and its…

  4. Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.

    Science.gov (United States)

    Lennemann, Nicholas J; Rhein, Bethany A; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

    2014-01-28

    Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Filovirus outbreaks occur sporadically throughout central Africa, causing high fatality rates among the general public and health care workers. These unpredictable hemorrhagic fever outbreaks are caused by multiple species of Ebola viruses, as well as Marburg virus. While filovirus

  5. Selection for Dutch postgraduate GP training; time for improvement

    NARCIS (Netherlands)

    Vermeulen, M.I.; Kuyvenhoven, M.M.; Zuithoff, N.P.; Tromp, F.; Graaf, Y. van der; Pieters, R.H.

    2012-01-01

    Background: In the Netherlands we select candidates for the postgraduate GP training by assessing personal qualities in interviews. Because of differences in the ratio of number of candidates and number of vacancies between the eight departments of GP training we questioned whether the risk of being

  6. Characterization of Human Colorectal Cancer MDR1/P-gp Fab Antibody

    Directory of Open Access Journals (Sweden)

    Xuemei Zhang

    2013-01-01

    Full Text Available In this study, the peptide sized 21 kDa covering P-gp transmembrane region was first prepared for generating a novel mouse monoclonal antibody Fab fragment with biological activity against multiple drug resistance protein P-gp21 by phage display technology. Phage-displayed antibody library prepared from mice spleen tissues was selected against the recombinant protein P-gp21 with five rounds of panning. A number of clones expressing Fab bound to P-gp21, showing neutralized activity in vitro, were isolated and screened by enzyme-linked immunosorbent assay based on its recognition properties to P-gp21 and human colorectal cancer tissue homogenate, resulting in identification of an optimal recombinant Fab clone (Number 29. Further characterization by recloning number 29 into an expression vector showed significant induction of the Fab antibody in the clone number 29 by Isopropyl β-D-1-thiogalactopyranoside (IPTG. After purified by HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also confirmed. Not only was the targeted region of this monoclonal Fab antibody identified as a 16-peptide epitope (ALKDKKELEGSGKIAT comprising residues 883–898 within the transmembrane (TM domain of human P-gp, but also the binding ability with it was verified. The clinical implication of our results for development of personalized therapy of colorectal cancer will be further studied.

  7. Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

    Directory of Open Access Journals (Sweden)

    Annie Albin Lumen

    Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

  8. Nurse telephone triage in out-of-hours GP practice: determinants of independent advice and return consultation

    Directory of Open Access Journals (Sweden)

    Klazinga Niek S

    2006-12-01

    Full Text Available Abstract Background Nowadays, nurses play a central role in telephone triage in Dutch out-of-hours primary care. The percentage of calls that is handled through nurse telephone advice alone (NTAA appears to vary substantially between GP cooperatives. This study aims to explore which determinants are associated with NTAA and with subsequent return consultations to the GP. Methods For the ten most frequently presented problems, a two-week follow-up cohort study took place in one cooperative run by 25 GPs and 8 nurses, serving a population of 62,291 people. Random effects logistic regression analysis was used to study the determinants of NTAA and return consultation rates. The effect of NTAA on hospital referral rates was also studied as a proxy for severity of illness. Results The mean NTAA rate was 27.5% – ranging from 15.5% to 39.4% for the eight nurses. It was higher during the night (RR 1.63, CI 1.48–1.76 and lower with increasing age (RR 0.96, CI 0.93–0.99, per ten years or when the patient presented >2 problems (RR 0.65; CI 0.51–0.83. Using cough as reference category, NTAA was highest for earache (RR 1.49; CI 1.18–1.78 and lowest for chest pain (RR 0.18; CI 0.06–0.47. After correction for differences in case mix, significant variation in NTAA between nurses remained (p Conclusion Important inter-nurse variability may indicate differences in perception on tasks and/or differences in skill to handle telephone calls alone. Future research should focus more on modifiable determinants of NTAA rates.

  9. Perception, understanding and practice of ethics during research on ...

    African Journals Online (AJOL)

    Background: Scandals have occurred over time involving conduct of research in different parts of the world. This study was aimed at exploring researchers' perception, understanding, appreciation and practice of research ethics during research on human subjects. Methods: A qualitative approach using the exploratory and ...

  10. Study and preparation of 99Tcm-GP kit for lung ventilation imaging

    International Nuclear Information System (INIS)

    Zhu Lin; Meng Fanmin; Zhang Jihong; Hong Tao; Liu Yunzhong; Liu Xiujie

    1997-01-01

    The preparation of the lyophilizing reagent, D-glucose-l-phosphate (GP) kit and the method of using this kit to label 99 Tc m to form 99 Tc m -GP for lung ventilation imaging at room temperature in a simple, rapid procedure are described. The stability of the lyophilizing reagent kit under various stock conditions is examined. The results show that all of the 99 Tc m -GP yields by the lyophilizing reagent kit are above 95% at 4 degree C (cold), 20-25 degree C (room temperature) and 40 degree C (oven) for 180, 90 and 3 days, respectively. The clinical practice indicates that in comparison with 99 Tc m -DTPA, 99 Tc m -GP has remarkable difference (P 99 Tc m -GP is an ideal radioaerosol for SPECT studies of lung ventilation. It has high alveolar deposition rate but low adhesion in the major airways compared to those of 99 Tc m -DTPA. 99 Tc m -GP also features prolonged pulmonary clearance time

  11. GP registrar well-being: a cross-sectional survey

    OpenAIRE

    Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

    2010-01-01

    Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potentia...

  12. Attitudes towards obesity treatment in GP training practices: a focus group study

    NARCIS (Netherlands)

    Jochemsen-van der Leeuw, H. G. A.; van Dijk, N.; Wieringa-de Waard, M.

    2011-01-01

    Both patients and government expect the GP to treat obesity. Previous studies reported a negative attitude of GPs towards this task. Little is known about the attitude of GP trainees. To assess the attitude and other factors that influence the willingness and ability of GP trainees to provide

  13. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    Energy Technology Data Exchange (ETDEWEB)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. (Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD (USA))

    1991-05-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

  14. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    International Nuclear Information System (INIS)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

    1991-01-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

  15. Determinants of a GP visit and cervical cancer screening examination in Great Britain.

    Directory of Open Access Journals (Sweden)

    Alexander Michael Labeit

    Full Text Available In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP.A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey.The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination.Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

  16. Social perception risk : evolution of research

    International Nuclear Information System (INIS)

    Prades, A.; Sola, R.

    2004-01-01

    This article shows an overview of the evolution of a research line: the Social Perception of Risk. It starts with a brief reference to the origin and main results of this research field to focus on the crucial challenges we have to face today. Right now we are witnessing a real turning point which is not exclusive of the radiological risk arena. A genuine social change phenomena is leading us a step forward towards the so called risk Governance. (Author)

  17. Pre-Service Science Teachers' Perception of the Principles of Scientific Research

    Science.gov (United States)

    Can, Sendil; Kaymakci, Güliz

    2016-01-01

    The purpose of the current study employing the survey method is to determine the pre-service science teachers' perceptions of the principles of scientific research and to investigate the effects of gender, grade level and the state of following scientific publications on their perceptions. The sampling of the current research is comprised of 125…

  18. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

  19. Perceptions about tissue donation for medical research among ...

    African Journals Online (AJOL)

    Background: Tissue banking refers to a structured and organized resource collection of tissue. Recent advances in research technology and knowledge in the fields of human genetics/ genomics highlights the need to maintain a steady supply of tissue for researchers. Objective: To assess the perception and willingness of ...

  20. Participants' perceptions of research benefits in an African genetic epidemiology study.

    Science.gov (United States)

    Appiah-Poku, John; Newton, Sam; Kass, Nancy

    2011-12-01

      Both the Council for International Organization of Medical Sciences and the Helsinki Declaration emphasize that the potential benefits of research should outweigh potential harms; consequently, some work has been conducted on participants' perception of benefits in therapeutic research. However, there appears to be very little work conducted with participants who have joined non-therapeutic research. This work was done to evaluate participants' perception of benefits in a genetic epidemiological study by examining their perception of the potential benefits of enrollment.   In-depth interviews lasting between 45 and 60 minutes were conducted with a convenient sample of 25 ill patients and 25 healthy accompanying relatives enrolled in a genetic epidemiological study of tuberculosis. Recorded interviews were transcribed and analyzed using content analysis.   Participants perceived that research was beneficial and some of the benefits included the generation of new knowledge, finding the cause of diseases, as well as the control, eradication and prevention of disease. Some thought that research was risky whilst others thought that the benefits outweighed the risks.   Participants perceived research to be beneficial and most of them thought that, though it was risky, the benefits outweighed the risks. It is our view that researchers need to give serious consideration to participant's perception of benefits in designing their consent forms, to see to the fulfillment of achievable goals. © 2011 Blackwell Publishing Ltd.

  1. Participants' perception of pharmaceutical clinical research: a cross-sectional controlled study

    Directory of Open Access Journals (Sweden)

    González-Saldivar G

    2016-04-01

    Full Text Available Gerardo González-Saldivar,1 René Rodríguez-Gutiérrez,2 José Luis Viramontes-Madrid,3 Alejandro Salcido-Montenegro,2 Kevin Erick Gabriel Carlos-Reyna,2 Andrés Marcelo Treviño-Alvarez,2 Neri Alejandro Álvarez-Villalobos,4 José Gerardo González-González2 1Ophthalmology Department, 2Endocrinology Division, Hospital Universitario “Dr. José E. González”, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, 3Instituto Nacional de Salud Pública, Cuernavaca, Morelos, 4Medical Statistics Department, Hospital Universitario “Dr. José E. González”, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico Background: There is scarce scientific information assessing participants’ perception of pharmaceutical research in developed and developing countries concerning the risks, safety, and purpose of clinical trials.Methods: To assess the perception that 604 trial participants (cases and 604 nonparticipants (controls of pharmaceutical clinical trials have about pharmaceutical clinical research, we surveyed participants with one of four chronic diseases from 12 research sites throughout Mexico.Results: Participation in clinical trials positively influences the perception of pharmaceutical clinical research. More cases (65.4% than controls (50.7% perceived that the main purpose of pharmaceutical research is to cure more diseases and to do so more effectively. In addition, more cases considered that there are significant benefits when participating in a research study, such as excellent medical care and extra free services, with this being the most important motivation to participate for both groups (cases 52%, controls 54.5%. We also found a sense of trust in their physicians to deal with adverse events, and the perception that clinical research is a benefit to their health, rather than a risk. More controls believed that clinical trial participants’ health is put at risk

  2. Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research

    OpenAIRE

    Harper, Liam D.; Fothergill, Melissa; West, Daniel J.; Stevenson, Emma; Russell, Mark

    2016-01-01

    Qualitative research investigating soccer practitioners’ perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open-ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time reg...

  3. Illness perception and related behaviour in lower respiratory tract infections—a European study

    Science.gov (United States)

    Hordijk, Patricia M; Broekhuizen, Berna D L; Butler, Chris C; Coenen, Samuel; Godycki-Cwirko, Maciek; Goossens, Herman; Hood, Kerry; Smith, Richard; van Vugt, Saskia F; Little, Paul; Verheij, Theo J M

    2015-01-01

    Background. Lower respiratory tract infection (LRTI) is a common presentation in primary care, but little is known about associated patients’ illness perception and related behaviour. Objective. To describe illness perceptions and related behaviour in patients with LRTI visiting their general practitioner (GP) and identify differences between European regions and types of health care system. Methods. Adult patients presenting with acute cough were included. GPs recorded co morbidities and clinical findings. Patients filled out a diary for up to 4 weeks on their symptoms, illness perception and related behaviour. The chi-square test was used to compare proportions between groups and the Mann-Whitney U or Kruskal Wallis tests were used to compare means. Results. Three thousand one hundred six patients from 12 European countries were included. Eighty-one per cent (n = 2530) of the patients completed the diary. Patients were feeling unwell for a mean of 9 (SD 8) days prior to consulting. More than half experienced impairment of normal or social activities for at least 1 week and were absent from work/school for a mean of 4 (SD 5) days. On average patients felt recovered 2 weeks after visiting their GP, but 21% (n = 539) of the patients did not feel recovered after 4 weeks. Twenty-seven per cent (n = 691) reported feeling anxious or depressed, and 28% (n = 702) re-consulted their GP at some point during the illness episode. Reported illness duration and days absent from work/school differed between countries and regions (North-West versus South-East), but there was little difference in reported illness course and related behaviour between health care systems (direct access versus gate-keeping). Conclusion. Illness course, perception and related behaviour in LRTI differ considerably between countries. These finding should be taken into account when developing International guidelines for LRTI and interventions for setting realistic expectations about illness course

  4. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

    Directory of Open Access Journals (Sweden)

    Berkhout Christophe

    2012-06-01

    Full Text Available Abstract Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152 of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study

  5. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the Diagest 3-GP motivation study.

    Science.gov (United States)

    Berkhout, Christophe; Vandaele-Bétancourt, Marie; Robert, Stéphane; Lespinasse, Solène; Mitha, Gamil; Bradier, Quentin; Vambergue, Anne; Fontaine, Pierre

    2012-06-21

    Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP

  6. The effect of gender medicine education in GP training: a prospective cohort study.

    Science.gov (United States)

    Dielissen, Patrick; Verdonk, Petra; Waard, Magreet Wieringa-de; Bottema, Ben; Lagro-Janssen, Toine

    2014-11-01

    The purpose of this study is to compare the change in general practitioner (GP) trainees' gender awareness following a modular gender medicine programme or a mainstream gender medicine programme. In 2007, a prospective study was conducted in three cohorts of in total 207 GP trainees who entered GP training in the Netherlands. The outcome measure was the Nijmegen Gender Awareness in Medicine Scale and a 16-item gender knowledge questionnaire. Two gender medicine teaching methods were compared: a modular approach (n = 75) versus a mainstream approach (n = 72). Both strategies were compared with a control cohort (n = 60). Statistical analysis included analysis of variance and t-tests. The overall response rates for the modular, mainstream and control cohort were 78, 72 and 82 %, respectively. There was a significant difference in change in gender knowledge scores between the modular cohort compared with the mainstream and control cohort (p = 0.049). There were no statistical differences between the cohorts on gender sensitivity and gender role ideology. At entry and end, female GP trainees demonstrated significantly higher gender awareness than male GP trainees. A modular teaching method is not a more favourable educational method to teach gender medicine in GP training. Female GP trainees are more gender aware, but male GP trainees are not unaware of gender-related issues.

  7. How international medical graduates view their learning needs for UK GP training.

    Science.gov (United States)

    Warwick, Christopher

    2014-03-01

    International medical graduates (IMGs) form a vital group of general practitioners (GPs) in the NHS. They are known to face additional challenges above and beyond those faced by UK medical graduates in the course of their GP training. Whilst they are a heterogeneous group of professionals, their views on what they need to learn, and how they are supported, are often distant from those of the educators responsible for planning their education. This study was undertaken, through narrative-based focus groups, to explore the issues which matter to the IMGs, in an attempt to empower their voices about their experiences in GP training, and to see what lessons could be drawn from these views. The findings confirmed the central importance, and considerable challenge involved, in making an effective transition into the culture of the NHS and UK general practice. The IMGs felt that induction needed to be an on-going, iterative process of learning which continued throughout training, with a more effective individualised learning needs analysis at the start of GP training. Lack of sophisticated language skills was highlighted as a real concern. Recognition that their lack of knowledge about the NHS at the start of training should not be seen as an indicator of deficiency, but a clue to what they needed to learn were also key messages. IMGs also felt the earlier in their training they undertook a GP placement, the quicker they would start to understand the culture of general practice in the UK. Further work following on from this research should include how to manage change in the educational network for these barriers to be overcome.

  8. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

    Directory of Open Access Journals (Sweden)

    Lowe Anson W

    2009-07-01

    Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

  9. Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2008-02-01

    Full Text Available Abstract Background Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. Results Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G, were established for Thogoto virus (THOV GP and Autographa california multiple NPV (AcMNPV GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. Conclusion These results suggest that proteins in the GP64 superfamily are class III penetrenes.

  10. Students' Perceptions of an Applied Research Experience in an Undergraduate Exercise Science Course.

    Science.gov (United States)

    Pearson, Regis C; Crandall, K Jason; Dispennette, Kathryn; Maples, Jill M

    2017-01-01

    Applied research experiences can provide numerous benefits to undergraduate students, however few studies have assessed the perceptions of Exercise Science (EXS) students to an applied research experience. The purpose of this study was two-fold: 1) to describe the rationale and implementation of an applied research experience into an EXS curriculum and 2) to evaluate EXS undergraduate students' perceptions of an applied research experience. An EXS measurement course was chosen for implementation of an applied research experience. The applied research experience required groups of students to design, implement, and evaluate a student-led research project. Fourteen questions were constructed, tailored to EXS undergraduate students, to assess students' perceptions of the experience. Qualitative analysis was used for all applicable data, with repeated trends noted; quantitative data were collapsed to determine frequencies. There was an overall positive student perception of the experience and 85.7% of students agreed an applied research experience should be continued. 84.7% of students perceived the experience as educationally enriching, while 92.8% reported the experience was academically challenging. This experience allowed students to develop comprehensive solutions to problems that arose throughout the semester; while facilitating communication, collaboration, and problem solving. Students believed research experiences were beneficial, but could be time consuming when paired with other responsibilities. Results suggest an applied research experience has the potential to help further the development of EXS undergraduate students. Understanding student perceptions of an applied research experience may prove useful to faculty interested in engaging students in the research process.

  11. 77 FR 73635 - Northwest Storage GP, LLC; Notice of Application

    Science.gov (United States)

    2012-12-11

    ...) 1254 to a proposed 346-megawatt (MW) power plant located within the north industrial area of the Port...] Northwest Storage GP, LLC; Notice of Application Take notice that on November 21, 2012, Northwest Storage GP, LLC. (Northwest) filed with the Federal Energy Regulatory Commission an application under section 7 of...

  12. Exploring perceptions and experiences of Bolivian health researchers with research ethics.

    Science.gov (United States)

    Sullivan, Sarah; Aalborg, Annette; Basagoitia, Armando; Cortes, Jacqueline; Lanza, Oscar; Schwind, Jessica S

    2015-04-01

    In Bolivia, there is increasing interest in incorporating research ethics into study procedures, but there have been inconsistent application of research ethics practices. Minimal data exist regarding the experiences of researchers concerning the ethical conduct of research. A cross-sectional study was administered to Bolivian health leaders with research experience (n = 82) to document their knowledge, perceptions, and experiences of research ethics committees and infrastructure support for research ethics. Results showed that 16% of respondents reported not using ethical guidelines to conduct their research and 66% indicated their institutions did not consistently require ethics approval for research. Barriers and facilitators to incorporate research ethics into practice were outlined. These findings will help inform a comprehensive rights-based research ethics education program in Bolivia. © The Author(s) 2015.

  13. Introducing a GP copayment in Australia: Who would carry the cost burden?

    Science.gov (United States)

    Elkins, Rosemary Kate; Schurer, Stefanie

    2017-05-01

    Recent policy changes designed to contain unsustainable health expenditure growth imply that many more Australians may soon be charged a copayment to consult a GP. We explore the distributional consequences associated with a range of hypothetical GP copayment scenarios using nationally-representative Australian survey data. For each scenario, we estimate the cost burden that individuals and households across the income distribution would need to absorb to maintain their current GP service utilisation. Even when concessional patients are charged a third or a quarter of the non-concessional copayment rate, the average estimated cost burden in the lowest income quartile is typically between three and six times that of the highest, and the average cost burden for women is significantly higher than for men within every income quartile. These disparities are intensified for those with a chronic illness. We conclude that the widespread implementation of GP copayments would disproportionately burden lower-income families, who experience higher rates of chronic illness, higher demand for GP services, and lower capacity to absorb price increases. The regressive nature of GP copayments is reduced when concessional and child patients are exempted entirely, highlighting the importance of supporting GPs-particularly in disadvantaged areas-to maintain bulk-billing arrangements for vulnerable patient groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Increasing the general level of academic capacity in general practice: introducing mandatory research training for general practitioner trainees through a participatory research process

    DEFF Research Database (Denmark)

    Tulinius, Anne-Charlotte; Nielsen, Anni Brit Sternhagen; Hansen, Lars Jørgen

    2012-01-01

    skills, and through the development and implementation of the mandatory programme to gradually empower the GP community to achieve academic capacity by creating a link between the GP researchers and the GP training community. This was done by developing a faculty, giving teaching skills to GP academics...... of the planning phase. RESULTS: From 2006 to 2009, we built a teaching faculty of 25 teachers among clinical GPs and GP academics; developed the training programme; and delivered the programme to 95 GP trainees. Some of the GP trainees later showed an interest in more substantial research projects, and GP...... and teaching. There is, however, a generic barrier in the regulation of academia itself....

  15. Cancer Center Clinic and Research Team Perceptions of Identity and Interactions.

    Science.gov (United States)

    Reimer, Torsten; Lee, Simon J Craddock; Garcia, Sandra; Gill, Mary; Duncan, Tobi; Williams, Erin L; Gerber, David E

    2017-12-01

    Conduct of cancer clinical trials requires coordination and cooperation among research and clinic teams. Diffusion of and confusion about responsibility may occur if team members' perceptions of roles and objectives do not align. These factors are critical to the success of cancer centers but are poorly studied. We developed a survey adapting components of the Adapted Team Climate Inventory, Measure of Team Identification, and Measure of In-Group Bias. Surveys were administered to research and clinic staff at a National Cancer Institute-designated comprehensive cancer center. Data were analyzed using descriptive statistics, t tests, and analyses of variance. Responses were received from 105 staff (clinic, n = 55; research, n = 50; 61% response rate). Compared with clinic staff, research staff identified more strongly with their own group ( P teams, we also identified key differences, including perceptions of goal clarity and sharing, understanding and alignment with cancer center goals, and importance of outcomes. Future studies should examine how variation in perceptions and group dynamics between clinic and research teams may impact function and processes of cancer care.

  16. The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

    Science.gov (United States)

    Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

    2016-01-01

    HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

  17. Mental health, stress and risk perception: insights from psychological research

    International Nuclear Information System (INIS)

    Renn, Ortwin

    1997-01-01

    Risk perceptions are only slightly correlated with the expected values of a probability distribution for negative health impacts. Psychometric studies have documented that context variables such as dread or personal control are important predictors for the perceived seriousness of risk. Studies about cultural patterns of risk perceptions emphasize different response set to risk information, depending on cultural priorities such as social justice versus personal freedom. This chapter reports the major psychological research pertaining to the factors that govern individual risk perception and discusses the psychometric effects due to people's risk perception and the experience of severe stress. The relative importance of the psychometric content variables, the signals pertaining to each health risks and symbolic beliefs are explained. (Author)

  18. Exploring resilience in rural GP registrars ? implications for training

    OpenAIRE

    Walters, Lucie; Laurence, Caroline O.; Dollard, Joanne; Elliott, Taryn; Eley, Diann S.

    2015-01-01

    Background Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care pr...

  19. The construction of a decision tool to analyse local demand and local supply for GP care using a synthetic estimation model.

    Science.gov (United States)

    de Graaf-Ruizendaal, Willemijn A; de Bakker, Dinny H

    2013-10-27

    This study addresses the growing academic and policy interest in the appropriate provision of local healthcare services to the healthcare needs of local populations to increase health status and decrease healthcare costs. However, for most local areas information on the demand for primary care and supply is missing. The research goal is to examine the construction of a decision tool which enables healthcare planners to analyse local supply and demand in order to arrive at a better match. National sample-based medical record data of general practitioners (GPs) were used to predict the local demand for GP care based on local populations using a synthetic estimation technique. Next, the surplus or deficit in local GP supply were calculated using the national GP registry. Subsequently, a dynamic internet tool was built to present demand, supply and the confrontation between supply and demand regarding GP care for local areas and their surroundings in the Netherlands. Regression analysis showed a significant relationship between sociodemographic predictors of postcode areas and GP consultation time (F [14, 269,467] = 2,852.24; P 1,000 inhabitants in the Netherlands covering 97% of the total population. Confronting these estimated demand figures with the actual GP supply resulted in the average GP workload and the number of full-time equivalent (FTE) GP too much/too few for local areas to cover the demand for GP care. An estimated shortage of one FTE GP or more was prevalent in about 19% of the postcode areas with >1,000 inhabitants if the surrounding postcode areas were taken into consideration. Underserved areas were mainly found in rural regions. The constructed decision tool is freely accessible on the Internet and can be used as a starting point in the discussion on primary care service provision in local communities and it can make a considerable contribution to a primary care system which provides care when and where people need it.

  20. Chinese TEFL Academics' Perceptions about Research: An Institutional Case Study

    Science.gov (United States)

    Bai, Li; Millwater, Jan

    2011-01-01

    Research capacity building has become a prominent theme in higher education institutions in China, as across the world. However, Chinese TEFL (Teaching English as a Foreign Language) academics' research capacity has been quite limited. In order to build their research capacity, it is necessary to understand their perceptions about research. This…

  1. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

    Science.gov (United States)

    Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

    2018-02-01

    In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The perception of Agricultural Researchers about the Role of ...

    African Journals Online (AJOL)

    Agricultural researchers in the Province of Isfahan were surveyed in order to explore their perception about role of nanotechnology in food security. The methodology used in this study involved a combination of descriptive and quantitative research and included the use of correlation, regression and descriptive analysis as ...

  3. Student Perceptions on Live-Case Projects: Undergraduate Marketing Research

    Science.gov (United States)

    Gundala, Raghava Rao; Singh, Mandeep; Baldwin, Andrew

    2014-01-01

    This paper is an investigation into undergraduate students' perceptions on use of live projects as a teaching pedagogy in marketing research courses. Students in undergraduate marketing research courses from fall 2009 to spring 2013 completed an online questionnaire consisting of 17 items. The results suggested that student understanding of…

  4. Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13 phage

    Directory of Open Access Journals (Sweden)

    Kuhn Andreas

    2011-09-01

    Full Text Available Abstract Background Filamentous M13 phage extrude from infected Escherichia coli with a tip structure composed of gp7 and gp9. This tip structure is extended by the assembly of the filament composed of the major coat protein gp8. Finally, gp3 and gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been the primary tool for phage display technology. However, gp7, gp8 and gp9 could also be used for phage display and these phage particles should bind to two different or more surfaces when the modified coat proteins are combined. Therefore, we tested here if the amino-terminal end of gp9 can be modified and whether the modified portion is exposed and detectable on the M13 phage particles. Results The amino-terminal region of gp9 was modified by inserting short sequences that encode antigenic epitopes. We show here that the modified gp9 proteins correctly integrate into the membrane using the membrane insertase YidC exposing the modified epitope into the periplasm. The proteins are then efficiently assembled onto the phage particles. Also extensions up to 36 amino acid residues at the amino-terminal end of gp9 did not interfere with membrane integration and phage assembly. The exposure of the antigenic tags on the phage was visualised with immunogold labelling by electron microscopy and verified by dot blotting with antibodies to the tags. Conclusions Our results suggest that gp9 at the phage tip is suitable for the phage display technology. The modified gp9 can be supplied in trans from a plasmid and fully complements M13 phage with an amber mutation in gene 9. The modified phage tip is very well accessible to antibodies.

  5. Are physical symptoms among survivors of a disaster presented to the general practitioner? A comparison between self-reports and GP data

    Directory of Open Access Journals (Sweden)

    Stellato Rebecca K

    2007-09-01

    Full Text Available Abstract Background Most studies examining medically unexplained symptoms (MUS have been performed in primary or secondary care and have examined symptoms for which patients sought medical attention. Disasters are often described as precipitating factors for MUS. However, health consequences of disasters are typically measured by means of questionnaires, and it is not known whether these self-reported physical symptoms are presented to the GP. It is also not known if the self-reported symptoms are related to a medical disorder or if they remain medically unexplained. In the present study, three research questions were addressed. Firstly, were self-reported symptoms among survivors presented to the GP? Secondly, were the symptoms presented to the GP associated with a high level of functional impairment and distress? Thirdly, what was the GP's clinical judgment of the presented symptoms, i.e. were the symptoms related to a medical diagnosis or could they be labeled MUS? Methods Survivors of a man-made disaster (N = 887 completed a questionnaire 3 weeks (T1 and 18 months (T2 post-disaster. This longitudinal health survey was combined with an ongoing surveillance program of health problems registered by GPs. Results The majority of self-reported symptoms was not presented to the GP and survivors were most likely to present persistent symptoms to the GP. For example, survivors with stomachache at both T1 and T2 were more likely to report stomachache to their GP (28% than survivors with stomachache at only T1 (6% or only T2 (13%. Presentation of individual symptoms to the GP was not consistently associated with functional impairment and distress. 56 – 91% of symptoms were labeled as MUS after clinical examination. Conclusion These results indicate that the majority of self-reported symptoms among survivors of a disaster are not presented to the GP and that the decision to consult with a GP for an individual symptom is not dependent on the level of

  6. Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Depetris, Rafael S.; Thomas, Antonia M.; Klasse, Per Johan; Moore, John P.

    2011-01-01

    Here, we describe the genetic pathways taken by a human immunodeficiency virus type 1 (HIV-1) isolate, D101.12, to become resistant to the small molecule CCR5 inhibitor, vicriviroc (VCV), in vitro. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. Studies of Env-chimeric and point-substituted viruses in peripheral blood mononuclear cells (PBMC) and TZM-bl cells showed that resistance can arise from the cooperative action of gp120 and gp41 changes, while retaining CCR5 usage. Modeling the VCV inhibition data from the two cell types suggests that D101.12 discriminates between high- and low-VCV affinity forms of CCR5 less than D1/85.16, a resistant virus with three FP substitutions.

  7. Compatibility of scientific research and specialty training in general practice. A cross-sectional study.

    Science.gov (United States)

    Kötter, Thomas; Carmienke, Solveig; Herrmann, Wolfram J

    2014-01-01

    In many departments of General Practice (GP) in Germany, young doctors who are trainees also work as researchers. Often these trainees work part time at the university and part time as a trainee in clinical practice. However, little is known about the situation of the actors involved. The aim of the study was to investigate the perspectives of GP trainees, heads of departments and GP trainers regarding the combination of research and GP training. We conducted a web-based survey with the heads of all German departments of General Practice, GP trainees who also conduct research and their GP trainers. The questionnaires consisted of open and closed questions. The results were analyzed using descriptive statistics and qualitative methods. 28 heads of GP departments and 20 GP trainees responded. The trainees were mostly very satisfied with their situation as a trainee. However, the trainees considered the combination of research and GP training as difficult. The respondents name as problems the coordination of multiple jobs and the lack of credibility given to research in General Practice. They name as solutions research-enabling training programs and uniform requirements in training regarding research. The combination of GP training and scientific research activity is perceived as difficult. However, well-organized and designed programs can improve the quality of the combination.

  8. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

  9. Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

    Directory of Open Access Journals (Sweden)

    Peng Sang

    Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

  10. Why are some patients in treatment for advanced cancer reluctant to consult their GP?

    DEFF Research Database (Denmark)

    Åbom, Birgit; Pfeiffer, Per

    2009-01-01

    and therefore consulted the doctor or the staff at the cancer treatment centre before seeking advice from their GP. Some patients found that the GP was not familiar enough with the treatments given; others that they did not want to inconvenience the busy GP with what they perceived to be minor non...

  11. Impact of Leishmania metalloprotease GP63 on macrophage signaling

    Science.gov (United States)

    Isnard, Amandine; Shio, Marina T.; Olivier, Martin

    2012-01-01

    The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

  12. Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

    Science.gov (United States)

    Dielissen, Patrick W; Bottema, Ben JAM; Verdonk, Petra; Lagro-Janssen, Toine LM

    2009-01-01

    Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness. PMID:19737396

  13. Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

    Directory of Open Access Journals (Sweden)

    Lagro-Janssen Toine LM

    2009-09-01

    Full Text Available Abstract Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness.

  14. 65 nm LP/GP mix low cost platform for multi-media wireless and consumer applications

    Science.gov (United States)

    Tavel, B.; Duriez, B.; Gwoziecki, R.; Basso, M. T.; Julien, C.; Ortolland, C.; Laplanche, Y.; Fox, R.; Sabouret, E.; Detcheverry, C.; Boeuf, F.; Morin, P.; Barge, D.; Bidaud, M.; Biénacel, J.; Garnier, P.; Cooper, K.; Chapon, J. D.; Trouiller, Y.; Belledent, J.; Broekaart, M.; Gouraud, P.; Denais, M.; Huard, V.; Rochereau, K.; Difrenza, R.; Planes, N.; Marin, M.; Boret, S.; Gloria, D.; Vanbergue, S.; Abramowitz, P.; Vishnubhotla, L.; Reber, D.; Stolk, P.; Woo, M.; Arnaud, F.

    2006-04-01

    A complete 65 nm CMOS platform, called LP/GP Mix, has been developed employing thick oxide transistor (IO), Low Power (LP) and General Purpose (GP) devices on the same chip. Dedicated to wireless multi-media and consumer applications, this new triple gate oxide platform is low cost (+1mask only) and saves over 35% of dynamic power with the use of the low operating voltage GP. The LP/GP mix shows competitive digital performance with a ring oscillator (FO = 1) speed equal to 7 ps per stage (GP) and 6T-SRAM static power lower than 10 pA/cell (LP). Compatible with mixed-signal design requirements, transistors show high voltage gain, low mismatch factor and low flicker noise. Moreover, to address mobile phone demands, excellent RF performance has been achieved with FT = 160 GHz for LP and 280 GHz for GP nMOS transistors.

  15. A research on motion design for APP's loading pages based on time perception

    Science.gov (United States)

    Cao, Huai; Hu, Xiaoyun

    2018-04-01

    Due to restrictions caused by objective reasons like network bandwidth, hardware performance and etc., waiting is still an inevitable phenomenon that appears in our using mobile-terminal products. Relevant researches show that users' feelings in a waiting scenario can affect their evaluations on the whole product and services the product provides. With the development of user experience and inter-facial design subjects, the role of motion effect in the interface design has attracted more and more scholars' attention. In the current studies, the research theory of motion design in a waiting scenario is imperfect. This article will use the basic theory and experimental research methods of cognitive psychology to explore the motion design's impact on user's time perception when users are waiting for loading APP pages. Firstly, the article analyzes the factors that affect waiting experience of loading APP pages based on the theory of time perception, and then discusses motion design's impact on the level of time-perception when loading pages and its design strategy. Moreover, by the operation analysis of existing loading motion designs, the article classifies the existing loading motions and designs an experiment to verify the impact of different types of motions on the user's time perception. The result shows that the waiting time perception of mobile's terminals' APPs is related to the loading motion types, the combination type of loading motions can effectively shorten the waiting time perception as it scores a higher mean value in the length of time perception.

  16. Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance

    Directory of Open Access Journals (Sweden)

    Yongchao Zhang

    2015-04-01

    Full Text Available Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1. Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers.

  17. The Astringency of the GP Algorithm for Forecasting Software Failure Data Series

    Directory of Open Access Journals (Sweden)

    Yong-qiang Zhang

    2007-05-01

    Full Text Available The forecasting of software failure data series by Genetic Programming (GP can be realized without any assumptions before modeling. This discovery has transformed traditional statistical modeling methods as well as improved consistency for model applicability. The individuals' different characteristics during the evolution of generations, which are randomly changeable, are treated as Markov random processes. This paper also proposes that a GP algorithm with "optimal individuals reserved strategy" is the best solution to this problem, and therefore the adaptive individuals finally will be evolved. This will allow practical applications in software reliability modeling analysis and forecasting for failure behaviors. Moreover it can verify the feasibility and availability of the GP algorithm, which is applied to software failure data series forecasting on a theoretical basis. The results show that the GP algorithm is the best solution for software failure behaviors in a variety of disciplines.

  18. A produção acadêmica publicada na revista Gestão & Produção de 1999 a 2010: tendências e direções para pesquisas futuras Academic research published in the Management & Production Journal (G&P, 1999-2010: trends and future research directions

    Directory of Open Access Journals (Sweden)

    Lucas Nogueira Bortollossi

    2012-01-01

    Full Text Available Esta pesquisa analisou as publicações da revista Gestão & Produção (G&P nos últimos doze anos. O objetivo foi identificar as tendências de pesquisa na área "Gestão da Produção e Operações" (POM: sua diversidade em termos de quantidade, tópico de interesse, fonte de dados, contribuição da pesquisa e redes sociais. Os artigos da revista G&P foram classificados quanto ao tipo de contribuição primária (conceitual, aplicação da teoria e construção de teoria, abordagem de coleta de dados (questionário, estudo de caso, pesquisa qualitativa, pesquisa de arquivo, pesquisa de laboratório, técnica de análise de dados (estatística básica, técnicas de análise multivariada e modelagem matemática e tópico de interesse (estratégia de operações, qualidade, gestão da cadeia de suprimento, entre outros. Com o levantamento realizado, observa-se que a pesquisa em gestão de operações cresceu consideravelmente na última década. O foco dos artigos amadureceu, passou de uma ênfase de artigos descritivos para uma vertente mais voltada à aplicação de teoria. A principal das fontes foram casos. Sugestões de direções para pesquisas futuras foram propostas.This study is a review and evaluation of studies published in a Brazilian journal of management & production (G&P from 1999 to 2010 in order to investigate the diversity of articles in terms of the purposes of research, data collection approaches, and data analysis techniques. The research articles were classified based on their primary purpose (theory building, application, and concepts, data collection approach (case study, qualitative research, archival research, survey-based research, laboratory research, and field research, data analysis technique (descriptive statistics, various multivariate statistical techniques, and mathematical modeling, and operations topics (strategy, quality, and supply chain management. The numbers of articles published increased substantially

  19. Leaf-GP: an open and automated software application for measuring growth phenotypes for arabidopsis and wheat.

    Science.gov (United States)

    Zhou, Ji; Applegate, Christopher; Alonso, Albor Dobon; Reynolds, Daniel; Orford, Simon; Mackiewicz, Michal; Griffiths, Simon; Penfield, Steven; Pullen, Nick

    2017-01-01

    Plants demonstrate dynamic growth phenotypes that are determined by genetic and environmental factors. Phenotypic analysis of growth features over time is a key approach to understand how plants interact with environmental change as well as respond to different treatments. Although the importance of measuring dynamic growth traits is widely recognised, available open software tools are limited in terms of batch image processing, multiple traits analyses, software usability and cross-referencing results between experiments, making automated phenotypic analysis problematic. Here, we present Leaf-GP (Growth Phenotypes), an easy-to-use and open software application that can be executed on different computing platforms. To facilitate diverse scientific communities, we provide three software versions, including a graphic user interface (GUI) for personal computer (PC) users, a command-line interface for high-performance computer (HPC) users, and a well-commented interactive Jupyter Notebook (also known as the iPython Notebook) for computational biologists and computer scientists. The software is capable of extracting multiple growth traits automatically from large image datasets. We have utilised it in Arabidopsis thaliana and wheat ( Triticum aestivum ) growth studies at the Norwich Research Park (NRP, UK). By quantifying a number of growth phenotypes over time, we have identified diverse plant growth patterns between different genotypes under several experimental conditions. As Leaf-GP has been evaluated with noisy image series acquired by different imaging devices (e.g. smartphones and digital cameras) and still produced reliable biological outputs, we therefore believe that our automated analysis workflow and customised computer vision based feature extraction software implementation can facilitate a broader plant research community for their growth and development studies. Furthermore, because we implemented Leaf-GP based on open Python-based computer vision, image

  20. Applying Equity Theory to Students' Perceptions of Research Participation Requirements

    Science.gov (United States)

    Miles, Shannon R.; Cromer, Lisa DeMarni; Narayan, Anupama

    2015-01-01

    Human subject pools have been a valuable resource to universities conducting research with student participants. However, the costs and benefits to student participants must be carefully weighed by students, researchers, and institutional review board administrators in order to avoid coercion. Participant perceptions are pivotal in deciding…

  1. Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

    Directory of Open Access Journals (Sweden)

    Priscila Oliveira Dos Santos

    2015-02-01

    Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

  2. HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

    Directory of Open Access Journals (Sweden)

    Kelly E Seaton

    Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

  3. Conformational alterations in the CD4 binding cavity of HIV-1 gp120 influencing gp120-CD4 interactions and fusogenicity of HIV-1 envelopes derived from brain and other tissues

    Directory of Open Access Journals (Sweden)

    Ramsland Paul A

    2011-06-01

    Full Text Available Abstract Background CD4-binding site (CD4bs alterations in gp120 contribute to HIV-1 envelope (Env mediated fusogenicity and the ability of gp120 to utilize low levels of cell-surface CD4. In a recent study, we constructed three-dimensional models of gp120 to illustrate CD4bs conformations associated with enhanced fusogenicity and enhanced CD4-usage of a modestly-sized panel of blood-derived HIV-1 Envs (n = 16. These conformations were characterized by a wider aperture of the CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop. Here, we sought to provide further validation of the utility of these models for understanding mechanisms that influence Env function, by characterizing the structure-function relationships of a larger panel of Envs derived from brain and other tissues (n = 81. Findings Three-dimensional models of gp120 were generated by our recently validated homology modelling protocol. Analysis of predicted CD4bs structures showed correlations between the aperture width of the CD4bs cavity and ability of the Envs to mediate cell-cell fusion, scavenge low-levels of cell-surface CD4, bind directly to soluble CD4, and bind to the Env mAb IgG1b12 whose epitope overlaps the gp120 CD4bs. These structural alterations in the CD4bs cavity were associated with repositioning of the V5 loop. Conclusions Using a large, independent panel of Envs, we can confirm the utility of three-dimensional gp120 structural models for illustrating CD4bs alterations that can affect Env function. Furthermore, we now provide new evidence that these CD4bs alterations augment the ability of gp120 to interact with CD4 by increasing the exposure of the CD4bs.

  4. Flexible but boring: medical students' perceptions of a career in general practice.

    Science.gov (United States)

    Koehler, Nicole; McMenamin, Christine

    2016-07-01

    Australia will continue to face a general practitioner (GP) shortage unless a significant number of medical students make general practice their chosen career. Perceptions regarding general practice may influence career choices. Thus this study investigated what Australian medical students perceived to be the advantages and disadvantages of pursuing a career in general practice via an anonymous online survey. Fifty-one students indicated general practice to be their first ranked career preference, 200 indicated a career other than general practice, and 106 were undecided. Two-hundred and two students reported having been on a GP placement, whereas 88 students had not. Flexibility, continuity of patient care and work-life balance were the three most common stated advantages to pursuing a career in general practice whereas general practice being boring, poorly paid, and of low prestige were the three most common disadvantages stated. Some disadvantages stated by those with a non-GP preference were not stated by those with a GP preference (e.g. lack of procedural skills, lack of career advancement opportunities). Students with more than 80 h of GP placement experience were more likely to list the advantages of work-life balance and a diversity of problems/illnesses/patients than those with no placement experience but were also more likely to list the disadvantage of low prestige. Negative stereotypes regarding general practice continue to exist which may influence students' career choices.

  5. Speech perception under adverse conditions: Insights from behavioral, computational and neuroscience research

    Directory of Open Access Journals (Sweden)

    Sara eGuediche

    2014-01-01

    Full Text Available Adult speech perception reflects the long-term regularities of the native language, but it is also flexible such that it accommodates and adapts to adverse listening conditions and short-term deviations from native-language norms. The purpose of this review article is to examine how the broader neuroscience literature can inform and advance research efforts in understanding the neural basis of flexibility and adaptive plasticity in speech perception. In particular, we consider several domains of neuroscience research that offer insight into how perception can be adaptively tuned to short-term deviations while also maintaining without affecting the long-term learned regularities for mapping sensory input. We review several literatures to highlight the potential role of learning algorithms that rely on prediction error signals and discuss specific neural structures that are likely to contribute to such learning. Already, a few studies have alluded to a potential role of these mechanisms in adaptive plasticity in speech perception. Better understanding the application and limitations of these algorithms for the challenges of flexible speech perception under adverse conditions promises to inform theoretical models of speech.

  6. The Teamwork Study: enhancing the role of non-GP staff in chronic disease management in general practice.

    Science.gov (United States)

    Black, D A; Taggart, J; Jayasinghe, U W; Proudfoot, J; Crookes, P; Beilby, J; Powell-Davis, G; Wilson, L A; Harris, M F

    2013-01-01

    There is evidence for a team-based approach in the management of chronic disease in primary health care. However, the standard of care is variable, probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients. This study aimed to evaluate the impact of a structured intervention involving non-GP staff in GP practices on the quality of care for patients with diabetes or cardiovascular disease. A cluster randomised trial was undertaken across 60 GP practices. The intervention was implemented in 30 practices with staff and patients interviewed at baseline and at 12-15 months follow up. The change in team roles was evaluated using a questionnaire completed by practice staff. The quality of care was evaluated using the Patient Assessment of Chronic Illness Care questionnaire. We found that although the team roles of staff improved in the intervention practices and there were significant differences between practices, there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up. Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores. Patients with multiple conditions were more likely to assess their quality of care to be better. Thus, although previous research has shown a cross-sectional association between team work and quality of care, we were unable to replicate these findings in the present study. These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care, or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed. The findings provide important information for researchers when designing similar studies.

  7. Triage of febrile children at a GP cooperative : determinants of a consultation

    NARCIS (Netherlands)

    Monteny, Miriam; Berger, Marjolein Y.; van der Wouden, Johannes C.; Broekman, Berth J.; Koes, Bart W.

    Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study

  8. Influences on GP coping and resilience: a qualitative study in primary care.

    Science.gov (United States)

    Cheshire, Anna; Ridge, Damien; Hughes, John; Peters, David; Panagioti, Maria; Simon, Chantal; Lewith, George

    2017-06-01

    'Neoliberal' work policies, austerity, NHS restructuring, and increased GP consultation rates provide the backdrop against increasing reports of GP burnout and an impending shortage of GPs. To explore GPs' experiences of workplace challenges and stresses, and their coping strategies, particularly focusing on understanding the impact of recent NHS workplace change. Study design was qualitative, with data collected from two focus groups and seven one-to-one telephone interviews. Focus groups and one-to-one telephone interviews explored the experiences of GPs currently practising in England, recruited through convenience sampling. Data were collected using a semi-structured interview approach and analysed using thematic analysis. There were 22 GP participants recruited: focus groups ( n = 15) and interviews ( n = 7). Interviewees understood GPs to be under intense and historically unprecedented pressures, which were tied to the contexts in which they work, with important moral implications for 'good' doctoring. Many reported that being a full-time GP was too stressful: work-related stress led to mood changes, sleep disruption, increases in anxiety, and tensions with loved ones. Some had subsequently sought ways to downsize their clinical workload. Workplace change resulted in little time for the things that helped GP resilience: a good work-life balance and better contact with colleagues. Although some GPs were coping better than others, GPs acknowledged that there was only so much an individual GP could do to manage their stress, given the external work issues they faced. GPs experience their emotional lives and stresses as being meaningfully shaped by NHS factors. To support GPs to provide effective care, resilience building should move beyond the individual to include systemic work issues. © British Journal of General Practice 2017.

  9. Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

    Science.gov (United States)

    Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

    2012-01-01

    Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

  10. Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

    Directory of Open Access Journals (Sweden)

    Manuel J Del Rey

    Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

  11. Toward a Research Agenda for the Study of Situation Perceptions: A Variance Componential Framework.

    Science.gov (United States)

    Rauthmann, John; Sherman, Ryne

    2018-04-01

    Situation perception represents the fulcrum of a "psychology of situations" because situation ratings are ubiquitous. However, no systematic research program exists so far, particularly because two competing traditions have not been integrated: Objectivist views stress situations' consensually shared meanings (social reality), and subjectivist views idiosyncratic meanings (personal reality). A componential framework can disentangle social from personal reality in situation perceptions: When multiple perceivers (P) rate multiple situations (S) on multiple situation characteristics (C), variance in those ratings can be decomposed according to S × C, P × S, and P × C breakdowns. Six grand questions of situation perception research are spawned from these decompositions: complexity, similarity, assimilation, consensus, uniqueness, and accuracy. Analyses of real data are provided to exemplify our ideas, along with customizable R codes for all methods. A componential framework allows novel and unique insights into different questions surrounding situation perceptions and provides a coherent research agenda.

  12. Designing and overproducing a tandem epitope of gp350/220 that shows a potential to become an EBV vaccine

    Directory of Open Access Journals (Sweden)

    Widodo

    2018-03-01

    Full Text Available Background: Epstein-Barr virus (EBV can cause cancer in people from around the world. There is no EBV vaccine available for use on a global scale. However, emerging evidence suggests that the epitope on the gp350/220 capsid protein may be developed into an EBV vaccine. Nevertheless, the production of small, single epitope is challenging of stability issues and possible alteration of peptide structure. In this study, a tandem epitope was developed consisting of three single epitopes, aimed to improve stability, antigenicity and preserve epitope structure. Materials and methods: A tandem epitope was designed using bioinformatics based on the epitope structure of the gp350/220 protein. The tandem epitope structure was analyzed using a protein folding method with Abalone software, which was further refined via YASARA force field and molecular repairing using a FoldX method. Immunogenicity was examined with Epitopia software, whereas allergen properties were tested using AlgPred. The pattern of the tandem epitope binding with anti-gp350/220 antibodies was performed using Z-dock and snugDock. The tandem epitope was then overproduced in E. coli strain BL21 as a host cell. Result: Our model demonstrated a successfully designed and overproduced tandem epitope. The tandem epitope demonstrated a similar structure compared with the epitope of whole protein gp350/220. Our epitope also demonstrated non-allergen and antigenicity properties, and possessed antibody binding patterns consistent with whole protein gp350/220. Conclusion and recommendation: These data suggest a novel tandem epitope composed of three similar epitopes demonstrates antigenicity, structure, and binding properties consistent with whole protein gp350/220. We also demonstrate successful production of the tandem epitope using E. coli strain BL21 as a host. Future in vivo experimental animal research is necessary to test the ability of this tandem epitope to stimulate antibody production

  13. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  14. Gravitational Physics Research

    Science.gov (United States)

    Wu, S. T.

    2000-01-01

    Gravitational physics research at ISPAE is connected with NASA's Relativity Mission (Gravity Probe B (GP-B)) which will perform a test of Einstein's General Relativity Theory. GP-B will measure the geodetic and motional effect predicted by General Relativity Theory with extremely stable and sensitive gyroscopes in an earth orbiting satellite. Both effects cause a very small precession of the gyroscope spin axis. The goal of the GP-B experiment is the measurement of the gyroscope precession with very high precision. GP-B is being developed by a team at Stanford University and is scheduled for launch in the year 2001. The related UAH research is a collaboration with Stanford University and MSFC. This research is focussed primarily on the error analysis and data reduction methods of the experiment but includes other topics concerned with experiment systems and their performance affecting the science measurements. The hydrogen maser is the most accurate and stable clock available. It will be used in future gravitational physics missions to measure relativistic effects such as the second order Doppler effect. The HMC experiment, currently under development at the Smithsonian Astrophysical Observatory (SAO), will test the performance and capability of the hydrogen maser clock for gravitational physics measurements. UAH in collaboration with the SAO science team will study methods to evaluate the behavior and performance of the HMC. The GP-B data analysis developed by the Stanford group involves complicated mathematical operations. This situation led to the idea to investigate alternate and possibly simpler mathematical procedures to extract the GP-B measurements form the data stream. Comparison of different methods would increase the confidence in the selected scheme.

  15. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

    Science.gov (United States)

    Kesby, James P.; Markou, Athina; Semenova, Svetlana

    2014-01-01

    Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

  16. A review of a GP registrar-run mobile health clinic for homeless people.

    Science.gov (United States)

    O'Carroll, A; Irving, N; O'Neill, J; Flanagan, E

    2017-08-01

    Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.

  17. Social relationships and GP use of middle-aged and older adults in Europe: a moderator analysis.

    Science.gov (United States)

    Bremer, Daniel; Lüdecke, Daniel; Vonneilich, Nico; von dem Knesebeck, Olaf

    2018-04-07

    This paper investigates (1) how social relationships (SRs) relate to the frequency of general practitioner (GP) visits among middle-aged and older adults in Europe, (2) if SRs moderate the association between self-rated health and GP visits, and (3) how the associations vary regarding employment status. Data stem from the Survey of Health, Ageing and Retirement in Europe project (wave 4, 56 989 respondents, 50 years or older). GP use was assessed by frequency of contacts with GPs in the last 12 months. Predictors were self-rated health and structural (Social Integration Index (SII), social contact frequency) and functional (emotional closeness) aspects of SR. Regressions were used to measure the associations between GP use and those predictors. Sociodemographic and socioeconomic factors were used as covariates. Additional models were computed with interactions. Analyses did not reveal significant associations of functional and structural aspects of SR with frequency of GP visits (SII: incidence rate ratio (IRR)=0.99, 95% CI 0.97 to 1.01, social contact frequency: IRR=1.04, 95% CI 1.00 to 1.07, emotional closeness: IRR=1.02, 95% CI 1.00 to 1.04). Moderator analyses showed that 'high social contact frequency people' with better health had more statistically significant GP visits than 'low social contact frequency people' with better health. Furthermore, people with poor health and an emotionally close network showed a significantly higher number of GP visits compared with people with same health, but less close networks. Three-way interaction analyses indicated employment status specific behavioural patterns with regard to SR and GP use, but coefficients were mostly not significant. All in all, the not employed groups showed a higher number of GP visits. Different indicators of SR showed statistically insignificantly associations with GP visits. Consequently, the relevance of SR may be rated rather low in quantitative terms for investigating GP use behaviour

  18. Using photography to enhance GP trainees' reflective practice and professional development.

    Science.gov (United States)

    Rutherford; Forde, Emer; Priego-Hernandez, Jacqueline; Butcher, Aurelia; Wedderburn, Clare

    2018-02-08

    The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most general practitioners (GP) training programmes. Teaching through the humanities is a growing area within medical education, but one which is often considered a voluntary 'add-on' for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees' reflective capacity, self-awareness and professional development. Photography was used as a tool to develop GP trainees' skills in recognising and articulating the attitudes, feelings and values that might impact on their clinical work and to enhance their confidence in their ability to deal with these concerns/issues. We submit that photography is uniquely well suited for facilitating insight and self-reflection because it provides the ability to record 'at the touch of a button' those scenes and images to which our attention is intuitively drawn without the need for-or the interference of-conscious decisions. This allows us the opportunity to reflect later on the reasons for our intuitive attraction to these scenes. These photography workshops were a compulsory part of the GP training programme and, despite the participants' traditional scientific backgrounds, the results clearly demonstrate the willingness of participants to accept-even embrace-the use of art as a tool for learning. The GP trainees who took part in this project acknowledged it to be beneficial for both their personal and professional development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

    Directory of Open Access Journals (Sweden)

    Shoufeng Ren

    2018-01-01

    Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

  20. The implementation of a quality system in the Dutch GP specialty training: barriers and facilitators; a qualitative study

    NARCIS (Netherlands)

    Buwalda, N.; Braspenning, J.C.; Roosmalen, S. van; Dijk, N. van; Visser, Machteld

    2017-01-01

    BACKGROUND: Quality assurance programs in medical education are introduced to gain insight into the quality of such programs and to trigger improvements. Although of utmost importance, research on the implementation of such programs is scarce. The Dutch General Practice (GP) specialty training

  1. The implementation of a quality system in the Dutch GP specialty training: barriers and facilitators; a qualitative study

    NARCIS (Netherlands)

    Buwalda, Nienke; Braspenning, Jozé; van Roosmalen, Sanne; van Dijk, Nynke; Visser, Mechteld

    2017-01-01

    Quality assurance programs in medical education are introduced to gain insight into the quality of such programs and to trigger improvements. Although of utmost importance, research on the implementation of such programs is scarce. The Dutch General Practice (GP) specialty training institutes used

  2. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine...... in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small...

  3. Investigation of the function of the putative self-association site of Epstein-Barr virus (EBV) glycoprotein 42 (gp42)

    International Nuclear Information System (INIS)

    Rowe, Cynthia L.; Matsuura, Hisae; Jardetzky, Theodore S.; Longnecker, Richard

    2011-01-01

    The Epstein-Barr virus (EBV) glycoprotein 42 (gp42) is a type II membrane protein essential for entry into B cells but inhibits entry into epithelial cells. X-ray crystallography suggests that gp42 may form dimers when bound to human leukocyte antigen (HLA) class II receptor (Mullen et al., 2002) or multimerize when not bound to HLA class II (Kirschner et al., 2009). We investigated this self-association of gp42 using several different approaches. We generated soluble mutants of gp42 containing mutations within the self-association site and found that these mutants have a defect in fusion. The gp42 mutants bound to gH/gL and HLA class II, but were unable to bind wild-type gp42 or a cleavage mutant of gp42. Using purified gp42, gH/gL, and HLA, we found these proteins associate 1:1:1 by gel filtration suggesting that gp42 dimerization or multimerization does not occur or is a transient event undetectable by our methods.

  4. Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

    Directory of Open Access Journals (Sweden)

    Meritxell Granell

    2017-06-01

    Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

  5. A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.

    Science.gov (United States)

    Saaby, Lasse; Brodin, Birger

    2017-09-01

    Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as K m and V max , for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC 50 ) and the disassociation constant for an inhibitor/P-gp complex (K i ) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  6. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Ling-ling Shen

    2015-01-01

    Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  7. Conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope

    International Nuclear Information System (INIS)

    Palker, T.J.; Matthews, T.J.; Clark, M.E.

    1987-01-01

    A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV + patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did react in RIA and neutralized HIV in vitro. Thus, ≅ 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays

  8. Gp120 stability on HIV-1 virions and Gag-Env pseudovirions is enhanced by an uncleaved Gag core

    International Nuclear Information System (INIS)

    Hammonds, Jason; Chen Xuemin; Ding Lingmei; Fouts, Timothy; De Vico, Anthony; Megede, Jan zur; Barnett, Susan; Spearman, Paul

    2003-01-01

    Human immunodeficiency virus type-1 (HIV-1) particles incorporate a trimeric envelope complex (Env) made of gp120 (SU) and gp41 (TM) heterodimers. It has been previously established that soluble CD4 (sCD4) interaction leads to shedding of gp120 from viral particles, and that gp120 may also be easily lost from virions during incubation or particle purification procedures. In the design of HIV particle or pseudovirion-based HIV vaccines, it may be important to develop strategies to maximize the gp120 content of particles. We analyzed the gp120 retention of HIV-1 laboratory-adapted isolates and primary isolates following incubation with sCD4 and variations in temperature. NL4-3 shed gp120 readily in a temperature- and sCD4-dependent manner. Surprisingly, inactivation of the viral protease led to markedly reduced shedding of gp120. Gp120 shedding was shown to vary markedly between HIV-1 strains, and was not strictly determined by whether the isolate was adapted to growth on immortalized T cell lines or was a primary isolate. Pseudovirions produced by expression of codon-optimized gag and env genes also demonstrated enhanced gp120 retention when an immature core structure was maintained. Pseudovirions of optimal stability were produced through a combination of an immature Gag protein core and a primary isolate Env. These results support the feasibility of utilizing pseudovirion particles as immunogens for the induction of humoral responses directed against native envelope structures

  9. Binding kinetics of aptamers to gp120 derived from HIV-1 subtype C

    CSIR Research Space (South Africa)

    Millroy, L

    2011-02-01

    Full Text Available aptamers with specific and strong affinity to the HIV-1 envelope glycoprotein gp120 and act as novel HIV-1 entry inhibitor drugs or as targeted drug delivery systems to HIV-1 infected cells. Prior to any downstream applications, novel gp120 aptamers need...

  10. Nurses' attitude to reading research articles and their perception of ...

    African Journals Online (AJOL)

    This descriptive study aimed at determining nurses' attitude to reading research articles and their ... Level of education of the nurses and years ofworking experience had an impact on their perception of ... AJOL African Journals Online.

  11. P-gp expression in brown trout erythrocytes: evidence of a detoxification mechanism in fish erythrocytes.

    Science.gov (United States)

    Valton, Emeline; Amblard, Christian; Wawrzyniak, Ivan; Penault-Llorca, Frederique; Bamdad, Mahchid

    2013-12-05

    Blood is a site of physiological transport for a great variety of molecules, including xenobiotics. Blood cells in aquatic vertebrates, such as fish, are directly exposed to aquatic pollution. P-gp are ubiquitous "membrane detoxification proteins" implicated in the cellular efflux of various xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which may be pollutants. The existence of this P-gp detoxification system inducible by benzo [a] pyrene (BaP), a highly cytotoxic PAH, was investigated in the nucleated erythrocytes of brown trout. Western blot analysis showed the expression of a 140-kDa P-gp in trout erythrocytes. Primary cultures of erythrocytes exposed to increasing concentrations of BaP showed no evidence of cell toxicity. Yet, in the same BaP-treated erythrocytes, P-gp expression increased significantly in a dose-dependent manner. Brown trout P-gp erythrocytes act as membrane defence mechanism against the pollutant, a property that can be exploited for future biomarker development to monitor water quality.

  12. N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

    International Nuclear Information System (INIS)

    Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

    2008-01-01

    The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

  13. Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

    International Nuclear Information System (INIS)

    Bellamy-McIntyre, Anna K.; Baer, Severine; Ludlow, Louise; Drummer, Heidi E.; Poumbourios, Pantelis

    2010-01-01

    The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1 QH1549.13 blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

  14. GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA.

    Science.gov (United States)

    Huang, Xing; Xu, Jing; Wang, Yu; Guo, Cheng; Chen, Lin; Gu, Xiaobin; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

    2016-12-01

    Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, we orally infected 20 goats with mature T. multiceps eggs. Praziquantel (10%) was given to 10 of the goats 45 days post-infection (p.i.). Blood samples were collected for 17 weeks p.i. from the 20 goats and anti-rTmGP50 antibodies were evaluated using the indirect ELISA established here. The TmGP50 contains an 897 bp open reading frame, in which signal sequence resides in 1 ~ 48 sites and mature polypeptide consists of 282 amino acid residues. Immunofluorescence staining showed that native TmGP50 was localized to the microthrix and parenchymatous zone of the adult parasite and coenurus, and the coenurus cystic wall. The indirect ELISA based on rTmGP50 exhibited a sensitivity of 95.0% and a specificity of 92.6% when detecting GP50 antibodies in sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmGP50 antibody was detectable from 2 to 17 weeks p.i. in the control group, while the antibody fell below the cut-off value about 3 weeks after praziquantel treatment. Our results indicate that recombinant TmGP50 is a suitable early diagnostic antigen for coenurus infection in goats.

  15. Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

    DEFF Research Database (Denmark)

    Sørensen, A L; Hey, A S; Kharazmi, A

    1994-01-01

    In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

  16. Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

    Science.gov (United States)

    d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

    2015-04-16

    ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Using photography to enhance GP trainees’ reflective practice and professional development.

    OpenAIRE

    Rutherford,; Forde, Emer; Priego-Hernández, J.; Butcher, Aurelia; Wedderburn, Clare

    2018-01-01

    The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most GP training programmes. Teaching through the Humanities is a growing area within medical education, but one which is often considered a voluntary ‘add on’ for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees’ reflective capacity, self awareness and professional developm...

  18. HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.

    Science.gov (United States)

    Silverstein, Peter S; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D P; Kumar, Anil

    2012-07-01

    HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs.

  19. Comparative Glycoprofiling of HIV gp120 Immunogens by Capillary Electrophoresis and MALDI Mass Spectrometry

    Science.gov (United States)

    Guttman, Miklós; Váradi, Csaba; Lee, Kelly K.; Guttman, András

    2015-01-01

    The Human Immunodeficiency Virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. Vaccine trials with the gp120 subunit of Env are ongoing with the recent RV144 trial showing moderate efficacy. gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by capillary electrophoresis with laser induced fluorescence detection and MALDI-MS. The glycosylation profiles were found to be similar for chronic vs. transmitter/founder isolates and only varied moderately between gp120s from different clades. This study revealed that the addition of specific tags, such as the gD tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. PMID:25809283

  20. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    International Nuclear Information System (INIS)

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.

    1987-01-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4 + and T8 + cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4 + cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo

  1. Evaluation of "credit card" libraries for inhibition of HIV-1 gp41 fusogenic core formation.

    Science.gov (United States)

    Xu, Yang; Lu, Hong; Kennedy, Jack P; Yan, Xuxia; McAllister, Laura A; Yamamoto, Noboru; Moss, Jason A; Boldt, Grant E; Jiang, Shibo; Janda, Kim D

    2006-01-01

    Protein-protein interactions are of critical importance in biological systems, and small molecule modulators of such protein recognition and intervention processes are of particular interest. To investigate this area of research, we have synthesized small-molecule libraries that can disrupt a number of biologically relevant protein-protein interactions. These library members are designed upon planar motif, appended with a variety of chemical functions, which we have termed "credit-card" structures. From two of our "credit-card" libraries, a series of molecules were uncovered which act as inhibitors against the HIV-1 gp41 fusogenic 6-helix bundle core formation, viral antigen p24 formation, and cell-cell fusion at low micromolar concentrations. From the high-throughput screening assays we utilized, a selective index (SI) value of 4.2 was uncovered for compound 2261, which bodes well for future structure activity investigations and the design of more potent gp41 inhibitors.

  2. Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

    International Nuclear Information System (INIS)

    Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

    2008-01-01

    Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS

  3. Influence of benefits, results and obstacles’ perceptions by research groups on interactions with companies

    Directory of Open Access Journals (Sweden)

    Veneziano de Castro Araujo

    2015-02-01

    Full Text Available The aim of this paper is to investigate how expected perceptions of academic research groups about results, benefits and obstacles influence the number of interactions with firms, based on a survey of university-industry interactions in Brazil. For this purpose, by means of a nonparametric Item Response Theory (NIRT, non ad hoc clusters were created from patterns of survey answers related with the analyzed perceptions. Using these clusters, a model was estimated to identify how perceptions influence the number of interactions of research groups. The results indicate that research groups that perceive intangible benefits and knowledge results as more important tend to have more interactions with firms. In addition, transactional obstacles imply in less interactions with firms. Finally, some implications on public policies are presented.

  4. The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation

    Directory of Open Access Journals (Sweden)

    Christoph Fickentscher

    2015-01-01

    Full Text Available To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.

  5. Applications of computer-graphics animation for motion-perception research

    Science.gov (United States)

    Proffitt, D. R.; Kaiser, M. K.

    1986-01-01

    The advantages and limitations of using computer animated stimuli in studying motion perception are presented and discussed. Most current programs of motion perception research could not be pursued without the use of computer graphics animation. Computer generated displays afford latitudes of freedom and control that are almost impossible to attain through conventional methods. There are, however, limitations to this presentational medium. At present, computer generated displays present simplified approximations of the dynamics in natural events. Very little is known about how the differences between natural events and computer simulations influence perceptual processing. In practice, the differences are assumed to be irrelevant to the questions under study, and that findings with computer generated stimuli will generalize to natural events.

  6. Researchers' perceptions of the ethical implications of pharmacogenomics research with children.

    Science.gov (United States)

    Avard, D; Silverstein, T; Sillon, G; Joly, Y

    2009-01-01

    This paper presents the results of an exploratory qualitative study that assesses Canadian pediatric researchers' perceptions of a pre-selected group of ethical issues raised by pharmacogenomics research with children. As a pilot study, we conducted semi-structured telephone interviews with Canadian pediatric pharmacogenomic researchers. The interviews were guided by the following themes: (1) benefits and risks of inclusion, (2) the consent/assent process, and (3) the return of research results. Issues about assent, consent, risks and benefits, as well as the communication of results were addressed by the respondents. Some issues, such as the unique vulnerability of children, the long term privacy concerns associated with biobanking, additional core elements that need to be discussed and included in the consent/assent forms, as well as the challenges of communicating research results in a pediatric research were not explicitly identified by the respondents. Further consideration should be given to address the ethical challenges of including children in pharmacogenomics research. This exploratory study indicates that further guidance is needed if children are to be protected and yet benefit from such research. Copyright 2009 S. Karger AG, Basel.

  7. Genome profiling (GP method based classification of insects: congruence with that of classical phenotype-based one.

    Directory of Open Access Journals (Sweden)

    Shamim Ahmed

    Full Text Available Ribosomal RNAs have been widely used for identification and classification of species, and have produced data giving new insights into phylogenetic relationships. Recently, multilocus genotyping and even whole genome sequencing-based technologies have been adopted in ambitious comparative biology studies. However, such technologies are still far from routine-use in species classification studies due to their high costs in terms of labor, equipment and consumables.Here, we describe a simple and powerful approach for species classification called genome profiling (GP. The GP method composed of random PCR, temperature gradient gel electrophoresis (TGGE and computer-aided gel image processing is highly informative and less laborious. For demonstration, we classified 26 species of insects using GP and 18S rDNA-sequencing approaches. The GP method was found to give a better correspondence to the classical phenotype-based approach than did 18S rDNA sequencing employing a congruence value. To our surprise, use of a single probe in GP was sufficient to identify the relationships between the insect species, making this approach more straightforward.The data gathered here, together with those of previous studies show that GP is a simple and powerful method that can be applied for actually universally identifying and classifying species. The current success supported our previous proposal that GP-based web database can be constructible and effective for the global identification/classification of species.

  8. Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

    Directory of Open Access Journals (Sweden)

    Long Wang

    2018-01-01

    Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

  9. Implementing Research in Professional Higher Education: Factors That Influence Lecturers' Perceptions

    Science.gov (United States)

    Griffioen, Didi M. E.; de Jong, Uulkje

    2015-01-01

    Higher professional education in Europe has changed from teaching-only institutes to hybrids of teaching and research. The purpose of this study was to examine factors that influence the judgements of lecturers about new organisational goals and perceptions of their new research-related competencies. Lecturers' judgements of new organisational…

  10. Involvement of CUL4A in Regulation of Multidrug Resistance to P-gp Substrate Drugs in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yunshan Wang

    2013-12-01

    Full Text Available CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression.

  11. Training in hospitals: what do GP specialist trainees think of workplace-based assessments?

    Science.gov (United States)

    Sabey, Abigail; Harris, Michael

    2011-03-01

    Workplace-based assessment (WBPA) was introduced in 2007 as a new approach to monitoring competence of GP specialist trainees (GPSTs). It includes a raft of assessments carried out in the workplace to assess what a trainee actually does in clinical practice. The assessment tools used are adapted from other contexts of doctors' training but little is known about how they function in day-to-day practice within GP training or how valid and useful they are found to be by trainees. To establish how the new system of WPBA is working in day-to-day practice for GPSTs in hospital posts. A mixed methods design including quantitative and qualitative phases of data collection. Two training locations within Severn Deanery. A questionnaire was completed by 52 GPSTs (67% response rate) currently in hospital posts. Twenty-two took part in focus groups and semi-structured interviews to explore key findings from the questionnaire in greater depth. There is value in the face-to-face contact between trainees and senior doctors. However, quality and depth of feedback are not consistent and there is evidence of poor use of the tools, reducing the value of the assessments. The system is further undermined by a clear perception of bias and lack of honesty in judgements which limit the scope for assessment to lead to learning. Overall, these weaknesses may impair the validity and usefulness of the system and its potential to improve the performance of doctors. General practice trainees in this study have a low opinion of how WPBA assessments function in the hospital setting. Changes are needed to optimise the potential of WPBA to improve the performance of doctors in training and to increase its credibility.

  12. Qualitative study of depression management in primary care: GP and patient goals, and the value of listening

    Science.gov (United States)

    Johnston, Olwyn; Kumar, Satinder; Kendall, Kathleen; Peveler, Robert; Gabbay, John; Kendrick, Tony

    2007-01-01

    Background Guidelines for depression management have been developed but little is known about GP and patient goals, which are likely to influence treatment offers, uptake, and adherence. Aim To identify issues of importance to GPs, patients, and patients' supporters regarding depression management. GP and patient goals for depression management became a focus of the study. Design of study Grounded theory-based qualitative study. Setting GPs were drawn from 28 practices. The majority of patients and supporters were recruited from 10 of these practices. Method Sixty-one patients (28 depressed, 18 previously depressed, 15 never depressed), 18 supporters, and 32 GPs were interviewed. Results GPs described encouraging patients to view depression as separate from the self and ‘normal’ sadness. Patients and supporters often questioned such boundaries, rejecting the notion of a medical cure and emphasising self-management. The majority of participants who were considering depression-management strategies wanted to ‘get out’ of their depression. However, a quarter did not see this as immediately relevant or achievable. They focused on getting by from day to day, which had the potential to clash with GP priorities. GP frustration and uncertainty could occur when depression was resistant to cure. Participants identified the importance of GPs listening to patients, but often felt that this did not happen. Conclusion Physicians need greater awareness of the extent to which their goals for the management of depression are perceived as relevant or achievable by patients. Future research should explore methods of negotiating agreed strategies for management. PMID:17976282

  13. Lessons learned from an Internet GP information system.

    Science.gov (United States)

    Briggs, J S; Bradley, M P

    1998-01-01

    We describe the prototype of an application that in actual use would allow GPs to find out more information about consultants at hospitals. This would aid the GP in making the decision about which consultant a patient should be referred to. The requirements of the application from the GP's perspective are described, together with some of the issues that have to be resolved before hospitals can provide the necessary information in a standard format. The application is implemented as a client--server system using standard Internet technologies such as Java and HTML. This architecture has a number of advantages but also revealed some issues concerning security and the format of data, among other things. The project showed that there is a desire for such a system and that that desire can be fulfilled at a relatively low cost.

  14. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  15. Admission and poor performance of trainees in the postgraduate GP training in the Netherlands

    NARCIS (Netherlands)

    Vermeulen, M.I.

    2014-01-01

    Until 2014 the selection for the Dutch postgraduate GP training was conducted locally, on the eight GP departments. The procedure consisted of a letter of application and a semi-structured interview. We investigated to what extend department of choice, candidates’ characteristics and qualities

  16. Perceptions that influence the maintenance of scientific integrity in community-based participatory research.

    Science.gov (United States)

    Kraemer Diaz, Anne E; Spears Johnson, Chaya R; Arcury, Thomas A

    2015-06-01

    Scientific integrity is necessary for strong science; yet many variables can influence scientific integrity. In traditional research, some common threats are the pressure to publish, competition for funds, and career advancement. Community-based participatory research (CBPR) provides a different context for scientific integrity with additional and unique concerns. Understanding the perceptions that promote or discourage scientific integrity in CBPR as identified by professional and community investigators is essential to promoting the value of CBPR. This analysis explores the perceptions that facilitate scientific integrity in CBPR as well as the barriers among a sample of 74 professional and community CBPR investigators from 25 CBPR projects in nine states in the southeastern United States in 2012. There were variations in perceptions associated with team member identity as professional or community investigators. Perceptions identified to promote and discourage scientific integrity in CBPR by professional and community investigators were external pressures, community participation, funding, quality control and supervision, communication, training, and character and trust. Some perceptions such as communication and training promoted scientific integrity whereas other perceptions, such as a lack of funds and lack of trust could discourage scientific integrity. These results demonstrate that one of the most important perceptions in maintaining scientific integrity in CBPR is active community participation, which enables a co-responsibility by scientists and community members to provide oversight for scientific integrity. Credible CBPR science is crucial to empower the vulnerable communities to be heard by those in positions of power and policy making. © 2015 Society for Public Health Education.

  17. GPs' experiences with out-of-hours GP cooperatives: a survey study from the Netherlands.

    Science.gov (United States)

    Smits, Marleen; Keizer, Ellen; Huibers, Linda; Giesen, Paul

    2014-09-01

    Out-of-hours primary care has been provided by general practitioner (GP) cooperatives since the year 2000 in the Netherlands. Early studies in countries with similar organizational structures showed positive GP experiences. However, nowadays it is said that GPs experience a high workload at the cooperative and that they outsource a considerable part of their shifts. To examine positive and negative experiences of GPs providing out-of-hours primary care, and the frequency and reasons for outsourcing shifts. A cross-sectional observational survey among 688 GPs connected to six GP cooperatives in the Netherlands, using a web-based questionnaire. The response was 55% (n = 378). The main reasons for working in GP cooperatives were to retain registration as GP (79%) and remain experienced in acute care (74%). GPs considered the peak hours (81%) and the high number of patients (73%) as the most negative aspects. Most GPs chose to provide the out-of-hours shifts themselves: 85% outsourced maximally 25% of their shifts. The percentage of outsourced shifts increased with age. Main reasons for outsourcing were the desire to have more private time (76%); the high workload in daytime practice (71%); and less the workload during out-of-hours (46%). GPs are motivated to work in out-of-hours GP cooperatives, and they outsource few shifts. GPs consider the peak load and the large number of (non-urgent) help requests as the most negative aspects. To motivate and involve GPs for 7 × 24-h primary care, it is important to set limits on their workload.

  18. Mutations in gp41 are correlated with coreceptor tropism but do not improve prediction methods substantially.

    Science.gov (United States)

    Thielen, Alexander; Lengauer, Thomas; Swenson, Luke C; Dong, Winnie W Y; McGovern, Rachel A; Lewis, Marilyn; James, Ian; Heera, Jayvant; Valdez, Hernan; Harrigan, P Richard

    2011-01-01

    The main determinants of HIV-1 coreceptor usage are located in the V3-loop of gp120, although mutations in V2 and gp41 are also known. Incorporation of V2 is known to improve prediction algorithms; however, this has not been confirmed for gp41 mutations. Samples with V3 and gp41 genotypes and Trofile assay (Monogram Biosciences, South San Francisco, CA, USA) results were taken from the HOMER cohort (n=444) and from patients screened for the MOTIVATE studies (n=1,916; 859 with maraviroc outcome data). Correlations of mutations with tropism were assessed using Fisher's exact test and prediction models trained using support vector machines. Models were validated by cross-validation, by testing models from one dataset on the other, and by analysing virological outcome. Several mutations within gp41 were highly significant for CXCR4 usage; most strikingly an insertion occurring in 7.7% of HOMER-R5 and 46.3% of HOMER-X4 samples (MOTIVATE 5.7% and 25.2%, respectively). Models trained on gp41 sequence alone achieved relatively high areas under the receiver-operating characteristic curve (AUCs; HOMER 0.713 and MOTIVATE 0.736) that were almost as good as V3 models (0.773 and 0.884, respectively). However, combining the two regions improved predictions only marginally (0.813 and 0.902, respectively). Similar results were found when models were trained on HOMER and validated on MOTIVATE or vice versa. The difference in median log viral load decrease at week 24 between patients with R5 and X4 virus was 1.65 (HOMER 2.45 and MOTIVATE 0.79) for V3 models, 1.59 for gp41-models (2.42 and 0.83, respectively) and 1.58 for the combined predictor (2.44 and 0.86, respectively). Several mutations within gp41 showed strong correlation with tropism in two independent datasets. However, incorporating gp41 mutations into prediction models is not mandatory because they do not improve substantially on models trained on V3 sequences alone.

  19. Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.

    Science.gov (United States)

    Bornholdt, Zachary A; Ndungo, Esther; Fusco, Marnie L; Bale, Shridhar; Flyak, Andrew I; Crowe, James E; Chandran, Kartik; Saphire, Erica Ollmann

    2016-02-23

    The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics. Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs. Copyright © 2016 Bornholdt et al.

  20. [Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

    Science.gov (United States)

    Li, Le; Su, Li-ping; Ma, Li; Zhao, Jin; Zhu, Lei; Zhou, Yong-an

    2009-03-01

    To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01). The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

  1. N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

    Directory of Open Access Journals (Sweden)

    Costa Nicola

    2007-12-01

    Full Text Available Abstract Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC. Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC, on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS in the imbalanced activity of glutamine synthase (GS, the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS. This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA. In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM, dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered

  2. Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

    Science.gov (United States)

    Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

    2012-01-01

    Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

  3. Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

    DEFF Research Database (Denmark)

    Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

    2006-01-01

    So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...... as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein-protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane...

  4. Elite perceptions of poverty and Nigeria's poverty reduction research ...

    African Journals Online (AJOL)

    The way the elite perceive poverty and the poor in any society constitutes a very important dimension of poverty research. This is because normally there are several areas of interrelationship and interdependence between the poor and the elite, and these form part of the basis for social life in all societies. Perceptions of the ...

  5. Staff perceptions of teaching and research at the University of the ...

    African Journals Online (AJOL)

    This article discusses the views of selected Heads of Departments at the University of the North, based on interviews conducted to explore their perceptions of research and teaching and link between the two. It was found that there were sharply divergent views on what constitutes research and teaching and different views ...

  6. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    International Nuclear Information System (INIS)

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan; Li, Lin; Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen; Jiang, Shibo

    2010-01-01

    Research highlights: → One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. → N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. → These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  7. Institutional transparency improves public perception of lab animal technicians and support for animal research.

    Science.gov (United States)

    Mills, Katelyn E; Han, Zetta; Robbins, Jesse; Weary, Daniel M

    2018-01-01

    The use of animals in research is controversial and often takes place under a veil of secrecy. Lab animal technicians responsible for the care of animals at research institutions are sometimes described as performing 'dirty work' (i.e. professions that are viewed as morally tainted), and may be stigmatized by negative perceptions of their job. This study assessed if transparency affects public perceptions of lab animal technicians and support for animal research. Participants (n = 550) were randomly assigned to one of six scenarios (using a 3x2 design) that described identical research varying only the transparency of the facility (low, high) and the species used (mice, dogs, cows). Participants provided Likert-type and open-ended responses to questions about the personal characteristics (warmth, competence) of a hypothetical lab technician 'Cathy' and their support for the described research. Quantitative analysis showed participants in the low-transparency condition perceived Cathy to be less warm and were less supportive of the research regardless of animal species. Qualitative responses varied greatly, with some participants expressing support for both Cathy and the research. These results suggest that increasing transparency in lab animal institutions could result in a more positive perception of lab animal researchers and the work that they do.

  8. Binding of radiolabeled asbestos fibers to guinea pig (gp) alveolar macrophages (AM)

    International Nuclear Information System (INIS)

    Giannotti, M.A.; Tewson, T.J.; Francsechini, M.P.; Scheule, R.K.; Holian, A.

    1990-01-01

    The mechanism by which fibrogenic particulates cause pulmonary fibrosis in humans is not understood, but is likely to involve the AM. Using two fibrogenic particulates, namely, chrysotile (CHR) and crocidolite (CRO) asbestos and gpAM as components of an in vitro model system, the authors have shown that CHR stimulates the gpAM to release superoxide anion, but CRO does not. To examine whether this difference in stimulatory abilities is a result of differences in cell-asbestos binding they have developed an efficient procedure that radiolabels asbestos fibers while retaining their bioactivity. The fibers are labeled with 68 Ge. The 68 Ge decays into 68 Ga, which then can be detected by its characteristic position emission. Both CHR and CRO asbestos were radiolabled successfully. Mild reaction conditions and short reaction times were found under which >90% of the added 68 Ge and 68 Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. A density gradient procedure was developed to quantitate the binding of asbestos to gpAM in suspension. The binding of both fibers increased with time over one hr. Thus, these results indicate that although both CHR and CRO interact with the gpAM, only CHR interacts productively to stimulate superoxide anion release

  9. 77 FR 20807 - Northwest Pipeline GP; Notice of Application

    Science.gov (United States)

    2012-04-06

    ... diameter pipelines away from an adjacent surface coal mine west of Kemmerer, Wyoming. Northwest also... directed to Pam Barnes, Manager Certificates and Tariffs, Northwest Pipeline GP, 295 Chipeta Way, Salt Lake...

  10. Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

    2010-07-13

    HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

  11. Commissioning of the iGp Feedback System at DAΦNE

    International Nuclear Information System (INIS)

    Drago, A.; Fox, J.D.; Teytelman, D.; Tobiyama, M.

    2011-01-01

    The iGp (Integrated Gigasample Processor) is an innovative digital bunch-by-bunch feedback system developed by a KEK / SLAC / INFN-LNF joint collaboration. The processing unit can sample at 500 MHz and compute the bunch-by-bunch output signal for up to ∼5000 bunches. The feedback gateware code is implemented inside just one FPGA (Field Programmable Gate Array) chip, a Xilinx Virtex-II. The FPGA implements two banks of 16-tap FIR (Finite Impulse Response) filters. Each filter is realtime programmable through the operator interface. At DAΦNE, the Frascati Φ-Factory, two iGp units have been commissioned in the April 2007. The iGp systems have substituted the previous betatron feedback systems. This insertion has been very fast and has shown no problems involving just a substitution of the old, less flexible, digital systems, letting unchanged the baseband analog frontend and backend. The commissioning has been very simple, due to the complete and powerful EPICS operator interface, working well in local and remote operations. The software includes also tools for analyzing post processor data. A description of the commissioning with the operations done is reported.

  12. Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHU Chen

    2014-10-01

    Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P<0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P>0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P<0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

  13. Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis.

    Science.gov (United States)

    Agrawal, L; Louboutin, J-P; Reyes, B A S; Van Bockstaele, E J; Strayer, D S

    2006-12-01

    Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. As they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells and primary fetal neurons were transduced with rSV40 vectors carrying human SOD1 and/or GPx1 cDNAs, then exposed to gp120. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Transduction efficiency of both neuron populations was >95%, as assayed by immunostaining. Transgene expression was also ascertained by Western blotting and direct assays of enzyme activity. Gp120 induced apoptosis in a high percentage of unprotected NT2-N. Transduction with SV(SOD1) and SV(GPx1) before gp120 challenge reduced neuronal apoptosis by >90%. Even greater protection was seen in cells treated with both vectors in sequence. Given singly or in combination, they protect neuronal cells from HIV-1-gp120 induced apoptosis. We tested whether rSV40 s can deliver antioxidant enzymes to the CNS in vivo: intracerebral injection of SV(SOD1) or SV(GPx1) into the caudate putamen of rat brain yielded excellent transgene expression in neurons. In vivo transduction using SV(SOD1) also protected neurons from subsequent gp120-induced apoptosis after injection of both into the caudate putamen of rat brain. Thus, SOD1 and GPx1 can be delivered by SV40 vectors in vitro or in vivo. This approach may merit consideration for

  14. A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

    International Nuclear Information System (INIS)

    Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko; Kobayashi, Michihiro

    2010-01-01

    We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinant AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.

  15. Culturally Diverse Undergraduate Researchers' Academic Outcomes and Perceptions of Their Research Mentoring Relationships

    Science.gov (United States)

    Byars-Winston, Angela M.; Branchaw, Janet; Pfund, Christine; Leverett, Patrice; Newton, Joseph

    2015-10-01

    Few studies have empirically investigated the specific factors in mentoring relationships between undergraduate researchers (mentees) and their mentors in the biological and life sciences that account for mentees' positive academic and career outcomes. Using archival evaluation data from more than 400 mentees gathered over a multi-year period (2005-2011) from several undergraduate biology research programs at a large, Midwestern research university, we validated existing evaluation measures of the mentored research experience and the mentor-mentee relationship. We used a subset of data from mentees (77% underrepresented racial/ethnic minorities) to test a hypothesized social cognitive career theory model of associations between mentees' academic outcomes and perceptions of their research mentoring relationships. Results from path analysis indicate that perceived mentor effectiveness indirectly predicted post-baccalaureate outcomes via research self-efficacy beliefs. Findings are discussed with implications for developing new and refining existing tools to measure this impact, programmatic interventions to increase the success of culturally diverse research mentees and future directions for research.

  16. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

    DEFF Research Database (Denmark)

    Meschi, Joseph; Crouch, Erika C; Skolnik, Paul

    2005-01-01

    The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate......-binding activity and was dependent on glycosylation of gp120. Native dodecameric SP-D bound to HIV gp120 more strongly than native trimeric SP-D. Since one common polymorphic form of SP-D is predominantly expressed as trimers and associated with lower blood levels, these individuals may have less effective innate...

  17. Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

    Science.gov (United States)

    Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

    2013-01-01

    An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357

  18. Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

    Science.gov (United States)

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

  19. Do practice nurse solve future GP capacity problems?

    NARCIS (Netherlands)

    Lamkaddem, M.; Haan, J. de; Bakker, D. de

    2003-01-01

    Background: Task delegation is viewed as an important policy instrument to counter foreseen future shortages in GP capacity in the Netherlands. Therefore, a national programme to introduce practice nurses in general practice was launched in 1998 by the National Association of General Practice. In

  20. Potable Water Treatment Facility General Permit (PWTF GP) ...

    Science.gov (United States)

    2017-08-28

    The Final PWTF GP establishes permit eligibility conditions, Notice of Intent (NOI) requirements, effluent limitations, standards, prohibitions, and best management practices for facilities that discharge to waters in the Commonwealth of Massachusetts (including both Commonwealth and Indian country lands) and the State of New Hampshire.

  1. Specific assay measuring binding of /sup 125/I-Gp 120 from HIV to T4/sup +//CD4/sup +/ cells

    Energy Technology Data Exchange (ETDEWEB)

    Lundin, K.; Nygren, A.; Ramstedt, U.; Gidlund, M.; Wigzell, H.; Arthur, L.O.; Robey, W.G.; Morein, B.

    1987-02-26

    The HIV (HTLV-III) envelope glycoprotein, Gp120, was isolated from virus-infected tissue culture cells using affinity chromatography. A radioimmunoassay was developed to determine the degree of iodinated Gp120 to target CD4/sup +/ (T4/sup +/) cells. /sup 125/I-Gp120 could be shown to selectively bind to CD4/sup +/ cells only. The Gp120 remained bound to these cells after repeated washes. Monoclonal anti-CD4 antibodies block the binding of Gp120 to CD4/sup +/ cells. Monoclonal antibodies to other cell surface components do not interfere with /sup 125/I-Gp120 binding. All IgG antibodies from HIV seropositive donors tested block /sup 125/I-GP120 binding, though with variable titers. The authors believe that this assay provides further proof for the use of CD4 (T4) as a component of the receptor for HIV. It represents a safe, objective and sensitive method for the analysis of Gp120-CD4 interactions, as well as the potential of antibodies to interfere with this binding. (Auth.). 24 refs.; 2 figs.; 8 tabs.

  2. Analysis of purified gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and tandem mass spectrometry.

    Science.gov (United States)

    Fairburn, B; Muthana, M; Hopkinson, K; Slack, L K; Mirza, S; Georgiou, A S; Espigares, E; Wong, C; Pockley, A G

    2006-09-01

    The stress protein gp96 exhibits a number of immunological activities, the majority of studies into which have used gp96 purified from a variety of tissues. On the basis of 1-D gel electrophoresis, the purity of these preparations has been reported to range between 70% and 99%. This study analyzed gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and liquid chromatography electrospray ionization tandem mass spectrometry (MS-MS). The procedure for purifying gp96 was reproducible, as similar protein profiles were observed in replicate gels of gp96 preparations. The purity of the preparations was typically around 70%, with minor co-purified proteins of varying molecular weights and mobilities being present. Dominant bands at 95-100 kDa in preparations from Wistar rats and C57BL/6 mice were identified as gp96 by ECL Western blotting. Multiple bands having similar, yet distinct molecular weights and differing pI mobility on ECL Western blots were confirmed as being gp96 in preparations from Wistar rats using MS-MS. The most striking feature of the 2-D gel analysis was the presence of additional dominant bands at 55 kDa in preparations from Wistar rats, and at 75-90 kDa in preparations from C57BL/6 mice. These were identified as gp96 by ECL Western blotting and, in the case of preparations from Wistar rats, by MS-MS. Although the lower molecular weight, gp96-related molecules might be partially degraded gp96, their reproducible presence, definition and characteristics suggest that they are alternative, species-specific isoforms of the molecule. A 55 kDa protein which exhibited a lower pI value than gp96 was present in all preparations and this was identified as calreticulin, another putative immunoregulatory molecule. This study confirms the reproducibility of the gp96 purification protocol and reveals the presence of multiple gp96 isoforms, some of which likely result from post-translational modifications such as differential glycosylation and

  3. Study of coherence strain of GP II zones in an aged aluminum composite

    International Nuclear Information System (INIS)

    Hernández-Rivera, J.L.; Rivera, J.J. Cruz; Koch, C.T.; Özdöl, V.B.; Martínez-Sánchez, R.

    2012-01-01

    Highlights: ► Precipitation sequence was changed in 2024 Al alloy. ► Image artifacts ought to the mask size and shape increased the real strain value. ► The strain distribution around experimental GP area was non uniform and more complex than reference. ► The origin of this strain distribution are related to mechanisms by which GP precipitates lose coherence. - Abstract: Strain mapping using the geometric phase analysis (GPA) technique was applied to Al–GP II (Guinier–Preston) nanoscale precipitates, using both high resolution transmission electron microscopy (HRTEM) micrographs as well as the exit wave function (EWF) obtained by focal series reconstruction. The experimental strain results were compared with strain maps obtained from an atomic model which consisted of an Al supercell containing a GP II precipitate. It was built as a reference from literature data. The experimental results demonstrate a complex strain distribution and larger fluctuations than the reference strain maps. These differences were found to be partly a consequence of image artifacts produced by the technique as well as complex microstructural events which were present at the development stage studied.

  4. Pre-Service Elementary Mathematics Teachers' Metaphors on Scientific Research and Foundations of Their Perceptions

    Science.gov (United States)

    Bas, Fatih

    2016-01-01

    In this study, it is aimed to investigate pre-service elementary mathematics teachers' perceptions about scientific research with metaphor analysis and determine the foundations of these perceptions. This phenomenological study was conducted with 182 participants. The data were collected with two open-ended survey forms formed for investigating…

  5. Risk perception and decision processes underlying informed consent to research participation.

    Science.gov (United States)

    Reynolds, William W; Nelson, Robert M

    2007-11-01

    According to the rational choice model, informed consent should consist of a systematic, step-by-step evaluation of all information pertinent to the treatment or research participation decision. Research shows that people frequently deviate from this normative model, however, employing decision-making shortcuts, or heuristics. In this paper we report findings from a qualitative study of 32 adolescents and (their) 31 parents who were recruited from two Northeastern US hospitals and asked to consider the risks of and make hypothetical decisions about research participation. The purpose of this study was to increase our understanding of how diabetic and at-risk adolescents (i.e., those who are obese and/or have a family history of diabetes) and their parents perceive risks and make decisions about research participation. Using data collected from adolescents and parents, we identify heuristic decision processes in which participant perceptions of risk magnitude, which are formed quickly and intuitively and appear to be based on affective responses to information, are far more prominent and central to the participation decision than are perceptions of probability. We discuss participants' use of decision-making heuristics in the context of recent research on affect and decision processes, and we consider the implications of these findings for researchers.

  6. Research ethics and approval process: A guide for new GP researchers.

    Science.gov (United States)

    Liaw, Siaw-Teng; Tam, Chun Wah Michael

    2015-06-01

    The underlying moral principles and values, and the virtues held as desirable for a researcher, should be reflected upon and embedded in the research. The foundation step is to download the National Health and Medical Research Council's (NHMRC's) National Statement on Ethical Conduct in Human Research and the NHMRC's Guidelines for Ethical Conduct in Aboriginal and Torres Strait Islander Health Research to use as references. This paper draws on the experience of The Royal Australian College of General Practitioners' (RACGP's) National Research and Evaluation Ethics Committee to provide an eight-step approach to the research ethics process. The researcher should use the research ethics process as an opportunity to foster and guide the development and conduct of ethical research.

  7. Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

    Directory of Open Access Journals (Sweden)

    Luyan Guo

    Full Text Available Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9 and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCP-1. HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+ current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+ current.

  8. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression

    International Nuclear Information System (INIS)

    Han Yi; Chin Tan, Theresa May; Lim, Lee-Yong

    2008-01-01

    Piperine, a major component of black pepper, is used as spice and nutrient enhancer. The purpose of the present study was to evaluate the effects of acute and prolonged piperine exposure on cellular P-gp expression and function in vitro and in vivo. Piperine at concentrations ranging from 10 to 100 μM, determined by MTT assay to be non-cytotoxic, was observed to inhibit P-gp mediated efflux transport of [ 3 H]-digoxin across L-MDR1 and Caco-2 cell monolayers. The acute inhibitory effect was dependent on piperine concentration, with abolishment of [ 3 H]-digoxin polarized transport attained at 50 μM of piperine. In contrast, prolonged (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 μM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels. The up-regulated protein was functionally active, as demonstrated by a higher degree of [ 3 H]-digoxin efflux across the cell monolayers, but the induction was readily reversed by the removal of the spice from the culture medium. Peroral administration of piperine at the dose of 112 μg/kg body weight/day to male Wistar rats for 14 consecutive days also led to increased intestinal P-gp levels. However, there was a concomitant reduction in the rodent liver P-gp although the kidney P-gp level was unaffected. Our data suggest that caution should be exercised when piperine is to be co-administered with drugs that are P-gp substrates, particularly for patients whose diet relies heavily on pepper

  9. Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

    International Nuclear Information System (INIS)

    Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

    2016-01-01

    Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4. (paper)

  10. Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

    Science.gov (United States)

    Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

    2016-10-01

    Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

  11. Structural and biochemical characterization of phage λ FI protein (gpFI) reveals a novel mechanism of DNA packaging chaperone activity.

    Science.gov (United States)

    Popovic, Ana; Wu, Bin; Arrowsmith, Cheryl H; Edwards, Aled M; Davidson, Alan R; Maxwell, Karen L

    2012-09-14

    One of the final steps in the morphogenetic pathway of phage λ is the packaging of a single genome into a preformed empty head structure. In addition to the terminase enzyme, the packaging chaperone, FI protein (gpFI), is required for efficient DNA packaging. In this study, we demonstrate an interaction between gpFI and the major head protein, gpE. Amino acid substitutions in gpFI that reduced the strength of this interaction also decreased the biological activity of gpFI, implying that this head binding activity is essential for the function of gpFI. We also show that gpFI is a two-domain protein, and the C-terminal domain is responsible for the head binding activity. Using nuclear magnetic resonance spectroscopy, we determined the three-dimensional structure of the C-terminal domain and characterized the helical nature of the N-terminal domain. Through structural comparisons, we were able to identify two previously unannotated prophage-encoded proteins with tertiary structures similar to gpFI, although they lack significant pairwise sequence identity. Sequence analysis of these diverse homologues led us to identify related proteins in a variety of myo- and siphophages, revealing that gpFI function has a more highly conserved role in phage morphogenesis than was previously appreciated. Finally, we present a novel model for the mechanism of gpFI chaperone activity in the DNA packaging reaction of phage λ.

  12. Metaphoric Perception of Coach Candidates towards Swimming Discipline: A Qualitative, Cognitive Research

    Science.gov (United States)

    Gündogdu, Cemal; Aygün, Yalin

    2018-01-01

    This research evinces the value of the multidimensional perceptions of the metaphors towards swimming discipline and its relevant certain contexts according to swimming coach candidates. In this article, we used qualitative research paradigm away from positivist approaches to describe and interpret stories and personal experiences of the…

  13. Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate.

    Science.gov (United States)

    Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume; Heyndrickx, Leo; Vanham, Guido; Jansson, Marianne; Fomsgaard, Anders; Grevstad, Berit; Ramaswamy, Meghna; Buonaguro, Franco M; Tornesello, Maria Lina; Biswas, Priscilla; Scarlatti, Gabriella; Buonaguro, Luigi

    2013-07-08

    Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.

  14. Leukemia: Derived heat shock protein gp96-peptide complex ...

    African Journals Online (AJOL)

    Jane

    2011-06-27

    Jun 27, 2011 ... Leukemia is a malignant clonal disease in hematopoietic stem cells that is typically treated with chemotherapy and radiotherapy. However ..... with autologous tumor-derived heatshock protein gp96 after liver resection for ...

  15. HIV-gp120 and physical dependence to buprenorphine.

    Science.gov (United States)

    Palma, J; Abood, M E; Benamar, K

    2015-05-01

    Opioids are among the most effective and commonly used analgesics in clinical practice for severe pain. However, the use of opioid medications is clinically limited by several adverse properties including dependence. While opioid dependence is a complex health condition, the treatment of HIV-infected individuals with opioid dependence presents additional challenges. The goal of this study was to examine the physical dependence to buprenorphine in the context of HIV. Young adult male rats (Sprague-Dawley) were pretreated with HIV-1 envelope glycoprotein 120 (gp120) injected into the periaqueductal gray area (PAG) and we examined the impact on physical dependence to opioid. It was found that the physical dependence to methadone occurred earlier than that to buprenorphine, and that gp120 did not enhance or precipitate the buprenorphine withdrawal. The results suggest that buprenorphine could be the better therapeutic option to manage opioid dependence in HIV. Copyright © 2015. Published by Elsevier Ireland Ltd.

  16. Studies on adsorptions of metallic ions in water by zirconium glyphosate (ZrGP): Behaviors and mechanisms

    International Nuclear Information System (INIS)

    Jia Yunjie; Zhang Yuejuan; Wang Runwei; Fan Faying; Xu Qinghong

    2012-01-01

    A new adsorbent named zirconium glyphosate [Zr(O 3 PCH 2 NHCH 2 COOH) 2 ·0.5H 2 O, denoted as ZrGP] and its selective adsorptions to Pb 2+ , Cd 2+ , Mg 2+ and Ca 2+ ions in water were reported in this paper. Compared to other zirconium adsorbents, such as zirconium phosphate [Zr(HPO 4 ) 2 ], ZrGP exhibited highly selective adsorption to Pb 2+ in solution which contained Pb 2+ , Cd 2+ , Mg 2+ and Ca 2+ ions. The loaded ZrGP with metallic ions can be efficaciously regenerated by aqueous solution of HCl (1.0 M) without any noticeable capacity loss, and almost all of it can be reused and recycled. The memory effect on structural regeneration of ZrGP was also found when Mg 2+ and Ca 2+ were adsorbed. To be specific, the structure of ZrGP was destroyed due to adsorbing these two ions, but it could be regenerated after the loaded materials were dipped in HCl solution (1.0 M) for several minutes to remove metallic ions.

  17. Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.

    Science.gov (United States)

    Durova, Oxana M; Vorobiev, Ivan I; Smirnov, Ivan V; Reshetnyak, Andrew V; Telegin, Georgy B; Shamborant, Olga G; Orlova, Nadezda A; Genkin, Dmitry D; Bacon, Andrew; Ponomarenko, Natalia A; Friboulet, Alain; Gabibov, Alexander G

    2009-11-01

    Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.

  18. Membrane topology analysis of HIV-1 envelope glycoprotein gp41

    Directory of Open Access Journals (Sweden)

    Xiao Dan

    2010-11-01

    Full Text Available Abstract Background The gp41 subunit of the HIV-1 envelope glycoprotein (Env has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD. An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model. We examined the membrane topology of the gp41 subunit in both prokaryotic and mammalian systems. We attached topological markers to the C-termini of serially truncated gp41. In the prokaryotic system, we utilized a green fluorescent protein (GFP that is only active in the cytoplasm. The tag protein (HaloTag and a membrane-impermeable ligand specific to HaloTag was used in the mammalian system. Results In the absence of membrane fusion, both the prokaryotic and mammalian systems (293FT cells supported the single MSD model. In the presence of membrane fusion in mammalian cells (293CD4 cells, the data obtained seem to support the multiple MSD model. However, the region predicted to be a potential MSD is the highly hydrophilic Kennedy sequence and is least likely to become a MSD based on several algorithms. Further analysis revealed the induction of membrane permeability during membrane fusion, allowing the membrane-impermeable ligand and antibodies to cross the membrane. Therefore, we cannot completely rule out the possible artifacts. Addition of membrane fusion inhibitors or alterations of the MSD sequence decreased the induction of membrane permeability. Conclusions It is likely that a single MSD model for HIV-1 gp41 holds true even in the presence of membrane fusion. The degree of the augmentation of membrane permeability we observed was dependent on the membrane fusion and sequence of the MSD.

  19. The characteristics of general practice and the attractiveness of working as a GP: medical students' views.

    Science.gov (United States)

    Landstrom, Bjorn; Mattsson, Bengt; Nordin, Per; Rudebeck, Carl E

    2014-03-15

    The aim of the study was to investigate medical students' views on general practice based on their experiences in training, and to find out whether there were certain views associated with the intention to become a GP. A questionnaire, based on our earlier studies about GP working behaviour, was handed out to medical students in terms 1, 3, 5, 7, 10 and 11 of undergraduate studies in Gothenburg, Sweden. The analysis comprised statistical descriptions and comparisons. The students regarded general practice positively. They found the work environment good, the GP's awareness of patients' living conditions necessary, and that GP work requires medical breadth. The status of the GP in the medical profession was not considered high. One-fourth of the students strongly agreed with the possibility of a future as a GP. This attitude was statistically associated with support to the statements that general practice offers a good work environment and should be a major component in undergraduate training. Students with a negative attitude to working as GPs were also negative to having a major component of general practice in undergraduate training. Medical students with a positive stated attitude towards becoming GPs support changes in undergraduate training to include more general practice. The risk of increasing a negative attitude should be considered when changes are discussed.

  20. Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region.

    Directory of Open Access Journals (Sweden)

    Laurent Verkoczy

    Full Text Available The membrane proximal external region (MPER of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR. To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (approximately 7% fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgM(hi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (approximately 15% of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igh(a (BALB/c and Igh(b (C57BL/6 congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igh(a locus. Mapping of MPER gp41 interactions with IgM(a identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc C(H regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgM(a determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses.

  1. Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

    International Nuclear Information System (INIS)

    Grose, C.; Jackson, W.; Traugh, J.A.

    1989-01-01

    Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

  2. Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Zachary A. Bornholdt

    2016-02-01

    Full Text Available The filovirus surface glycoprotein (GP mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

  3. The implementation of a quality system in the Dutch GP specialty training: barriers and facilitators; a qualitative study.

    Science.gov (United States)

    Buwalda, Nienke; Braspenning, Jozé; van Roosmalen, Sanne; van Dijk, Nynke; Visser, Mechteld

    2017-07-21

    Quality assurance programs in medical education are introduced to gain insight into the quality of such programs and to trigger improvements. Although of utmost importance, research on the implementation of such programs is scarce. The Dutch General Practice (GP) specialty training institutes used an implementation strategy to implement a quality system (QS), and we aimed to study the success of this strategy and to learn about additional facilitators and barriers. Seventeen structured interviews were conducted with the directors and quality coordinators (QCs) of the eight Dutch GP training institutes. A five-stage process model of implementation was used to structure these interviews and analyze the data. Two researchers analyzed the data with a framework approach. The strategy supported the institutes in implementing the QS. However, after the introduction of the QS, staff experienced the QS as demanding, although they noticed almost no concrete short-term results. Moreover, they experienced difficulties in integrating the QS into their local situation. Collectively working with the QS and following common deadlines did create a sense of commitment towards each other that appeared to be a true stimulus to the introduction of the QS. The implementation strategy focused mainly on the introduction of the QS in the GP specialty training, and it was, as such, rather successful. An important barrier concerned the acceptance of the QS and the integration of the QS into local structures, which suggests that there is a need for guidance on the translation of the QS to local contexts. All in all, we recommend more focus on the benefits of a QS.

  4. CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

    International Nuclear Information System (INIS)

    Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

    2011-01-01

    CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

  5. A functional F analogue of AcMNPV GP64 is from the Agrotis segetum granulovirus

    NARCIS (Netherlands)

    Yin, F.; Wang, M.; Tan, Y.; Deng, F.; Vlak, J.M.; Hu, Z.H.; Wang, H.

    2008-01-01

    The envelope fusion protein F of Plutella xylostella granulovirus is a computational analogue of the GP64 envelope fusion protein of Autographa californica nucleopolyhedrovirus (AcMNPV). Granulovirus (GV) F proteins were thought to be unable to functionally replace GP64 in the AcMNPV pseudotyping

  6. iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening

    DEFF Research Database (Denmark)

    Brodin, Birger; Ozgür, Burak; Saaby, Lasse

    that new API's are evaluated with respect to P-gp interactions.  Aim : The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp. Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17......Background : The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hinders uptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential "site" for drug-drug interaction. Regulatory agencies therefore recommend.......04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion : The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp....

  7. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP10025–33 peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    International Nuclear Information System (INIS)

    Chang, Xiaoli; Xia, Chang-Qing

    2015-01-01

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100 25–33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100 25–33 peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100 25–33 peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100 25–33 were significantly increased compared to control groups. Tumor antigen, GP100 25–23 specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100 25–33 -coupled spleen cells leads to potent anti-melanoma immunity. • GP100 25–33 -coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  8. Student and Staff Perceptions of a Vacation Research Assistantship Scheme

    Science.gov (United States)

    Penn, Felicity; Stephens, Danielle; Morgan, Jessica; Upton, Penney; Upton, Dominic

    2013-01-01

    There is a push for universities to equip graduates with desirable employability skills and "hands-on" experience. This article explores the perceptions of students and staff experiences of a research assistantship scheme. Nine students from the University of Worcester were given the opportunity to work as a student vacation researcher…

  9. The impact of perception and presence on emotional reactions: a review of research in virtual reality.

    Science.gov (United States)

    Diemer, Julia; Alpers, Georg W; Peperkorn, Henrik M; Shiban, Youssef; Mühlberger, Andreas

    2015-01-01

    Virtual reality (VR) has made its way into mainstream psychological research in the last two decades. This technology, with its unique ability to simulate complex, real situations and contexts, offers researchers unprecedented opportunities to investigate human behavior in well controlled designs in the laboratory. One important application of VR is the investigation of pathological processes in mental disorders, especially anxiety disorders. Research on the processes underlying threat perception, fear, and exposure therapy has shed light on more general aspects of the relation between perception and emotion. Being by its nature virtual, i.e., simulation of reality, VR strongly relies on the adequate selection of specific perceptual cues to activate emotions. Emotional experiences in turn are related to presence, another important concept in VR, which describes the user's sense of being in a VR environment. This paper summarizes current research into perception of fear cues, emotion, and presence, aiming at the identification of the most relevant aspects of emotional experience in VR and their mutual relations. A special focus lies on a series of recent experiments designed to test the relative contribution of perception and conceptual information on fear in VR. This strand of research capitalizes on the dissociation between perception (bottom-up input) and conceptual information (top-down input) that is possible in VR. Further, we review the factors that have so far been recognized to influence presence, with emotions (e.g., fear) being the most relevant in the context of clinical psychology. Recent research has highlighted the mutual influence of presence and fear in VR, but has also traced the limits of our current understanding of this relationship. In this paper, the crucial role of perception on eliciting emotional reactions is highlighted, and the role of arousal as a basic dimension of emotional experience is discussed. An interoceptive attribution model of

  10. The impact of perception and presence on emotional reactions: a review of research in virtual reality

    Science.gov (United States)

    Diemer, Julia; Alpers, Georg W.; Peperkorn, Henrik M.; Shiban, Youssef; Mühlberger, Andreas

    2015-01-01

    Virtual reality (VR) has made its way into mainstream psychological research in the last two decades. This technology, with its unique ability to simulate complex, real situations and contexts, offers researchers unprecedented opportunities to investigate human behavior in well controlled designs in the laboratory. One important application of VR is the investigation of pathological processes in mental disorders, especially anxiety disorders. Research on the processes underlying threat perception, fear, and exposure therapy has shed light on more general aspects of the relation between perception and emotion. Being by its nature virtual, i.e., simulation of reality, VR strongly relies on the adequate selection of specific perceptual cues to activate emotions. Emotional experiences in turn are related to presence, another important concept in VR, which describes the user’s sense of being in a VR environment. This paper summarizes current research into perception of fear cues, emotion, and presence, aiming at the identification of the most relevant aspects of emotional experience in VR and their mutual relations. A special focus lies on a series of recent experiments designed to test the relative contribution of perception and conceptual information on fear in VR. This strand of research capitalizes on the dissociation between perception (bottom–up input) and conceptual information (top-down input) that is possible in VR. Further, we review the factors that have so far been recognized to influence presence, with emotions (e.g., fear) being the most relevant in the context of clinical psychology. Recent research has highlighted the mutual influence of presence and fear in VR, but has also traced the limits of our current understanding of this relationship. In this paper, the crucial role of perception on eliciting emotional reactions is highlighted, and the role of arousal as a basic dimension of emotional experience is discussed. An interoceptive attribution

  11. Selected Thermophysical Properties of 2,2 Dimethylcyclopentyl Methylphosphonofluoridate (GP) and 2,2 Dimethylcyclopentanol (DMCP)

    Science.gov (United States)

    2016-09-01

    chromatography using a thermal conductivity detector (GC-TCD). Table 1. Sample Information for GP and DMCP Chemical Name Mole Fraction Purity...Proving Ground, MD, 1983; UNCLASSIFIED Report (ADC033491). 23. Weast, R.C. CRC Handbook of Chemistry and Physics, 53rd ed.; CRC Press: Boca Raton, FL...gas chromatography GD pinacolyl methylphosphonofluoridate GF cyclohexyl methylphosphonofluoridate GP 2,2-dimethylcyclopentyl

  12. Evaluation of “Credit Card” Libraries for Inhibition of HIV-1 gp41 Fusogenic Core Formation

    Science.gov (United States)

    Xu, Yang; Lu, Hong; Kennedy, Jack P.; Yan, Xuxia; McAllister, Laura; Yamamoto, Noboru; Moss, Jason A.; Boldt, Grant E.; Jiang, Shibo; Janda, Kim D.

    2008-01-01

    Protein-protein interactions are of critical importance in biological systems and small molecule modulators of such protein recognition and intervention processes are of particular interests. To investigate this area of research, we have synthesized small molecule libraries that can disrupt a number of biologically relevant protein-protein interactions. These library members are designed upon planar motifs, appended with a variety of chemical functions, which we have termed as “credit-card” structures. From two of our “credit-card” libraries, a series of molecules were uncovered which act as inhibitors against the HIV-1 gp41 fusogenic 6-helix bundle core formation, viral antigen p24 formation and cell-cell fusion at low micromolar concentrations. From the high-throughput screening assays we utilized, a selective index (SI) value of 4.2 was uncovered for compound 2261, which bodes well for future structure activity investigations and the design of more potent gp41 inhibitors. PMID:16827565

  13. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    DEFF Research Database (Denmark)

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...... recognizing gp63 can take part in the host defence against L. major infections....

  14. Research nurse manager perceptions about research activities performed by non-nurse clinical research coordinators.

    Science.gov (United States)

    Jones, Carolynn Thomas; Hastings, Clare; Wilson, Lynda Law

    2015-01-01

    There has been limited research to document differences in roles between nurses and non-nurses who assume clinical research coordination and management roles. Several authors have suggested that there is no acknowledged guidance for the licensure requirements for research study coordinators and that some non-nurse research coordinators may be assuming roles that are outside of their legal scopes of practice. There is a need for further research on issues related to the delegation of clinical research activities to non-nurses. This study used nominal group process focus groups to identify perceptions of experienced research nurse managers at an academic health science center in the Southern United States about the clinical research activities that are being performed by non-nurse clinical research coordinators without supervision that they believed should only be performed by a nurse or under the supervision of a nurse. A total of 13 research nurse managers volunteered to be contacted about the study. Of those, 8 participated in two separate nominal group process focus group sessions. The group members initially identified 22 activities that they felt should only be performed by a nurse or under the direct supervision of a nurse. After discussion and clarification of results, activities were combined into 12 categories of clinical research activities that participants believed should only be performed by a nurse or under the direct supervision of a nurse. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Comparative Research of Residents’ Effect Perception and Participation Capacity and Willingness on Pro-poor Tourism

    Institute of Scientific and Technical Information of China (English)

    Guoqing; HUANG; Hong; SHU

    2014-01-01

    In this article,comparative research on residents’ effect perception,participation capacity and willingness on Pro-poor Tourism( PPT) is given based on the questionnaire carried out in Wulong County and Fengjie County in Three Gorges Area,Chongqing,China. Some technologies,such as SPSS 13. 0,ANOVA and T-test are applied to analyze the data and results show Wulong residents’ perception behavior is better than that of Fengjie residents. Moreover,the residents with different demographic characteristics have different participation behavior.Finally,multiple regression analysis is applied to identify the key factors influencing residents’ perception behavior,that is participation willingness and positive economic effect perception,positive social and cultural effect perception and participation capacity.

  16. The methodology of risk perception research

    International Nuclear Information System (INIS)

    Sjoberg, L.

    1998-01-01

    Risk perception is frequently held to be crucial in the understanding and management of risk in policy contexts. The present paper takes as a starting point the notion that risk perception, of the public, of experts and other special groups, is important and hence the question arises how it should be investigated

  17. The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

    Science.gov (United States)

    Alvares, Stacy M.; Dunn, Clarence A.; Brown, Tod A.; Wayner, Elizabeth E.; Carter, William G.

    2008-01-01

    Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and Detergent-Resistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals- possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. PMID:18269919

  18. Knowledge and Perception about Clinical Research Shapes Behavior: Face to Face Survey in Korean General Public.

    Science.gov (United States)

    Choi, Yun Jung; Beck, Sung-Ho; Kang, Woon Yong; Yoo, Soyoung; Kim, Seong-Yoon; Lee, Ji Sung; Burt, Tal; Kim, Tae Won

    2016-05-01

    Considering general public as potential patients, identifying factors that hinder public participation poses great importance, especially in a research environment where demands for clinical trial participants outpace the supply. Hence, the aim of this study was to evaluate knowledge and perception about clinical research in general public. A total of 400 Seoul residents with no previous experience of clinical trial participation were selected, as representative of population in Seoul in terms of age and sex. To minimize selection bias, every fifth passer-by was invited to interview, and if in a cluster, person on the very right side was asked. To ensure the uniform use of survey, written instructions have been added to the questionnaire. Followed by pilot test in 40 subjects, the survey was administered face-to-face in December 2014. To investigate how perception shapes behavior, we compared perception scores in those who expressed willingness to participate and those who did not. Remarkably higher percentage of responders stated that they have heard of clinical research, and knew someone who participated (both, P perceptions and lack of knowledge will be effective in enhancing public engaged in clinical research.

  19. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  20. Studies on adsorptions of metallic ions in water by zirconium glyphosate (ZrGP): Behaviors and mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Jia Yunjie; Zhang Yuejuan [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China); Wang Runwei [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun 130012 (China); Fan Faying [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China); Xu Qinghong, E-mail: xuqh@mail.buct.edu.cn [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China)

    2012-01-15

    A new adsorbent named zirconium glyphosate [Zr(O{sub 3}PCH{sub 2}NHCH{sub 2}COOH){sub 2}{center_dot}0.5H{sub 2}O, denoted as ZrGP] and its selective adsorptions to Pb{sup 2+}, Cd{sup 2+}, Mg{sup 2+} and Ca{sup 2+} ions in water were reported in this paper. Compared to other zirconium adsorbents, such as zirconium phosphate [Zr(HPO{sub 4}){sub 2}], ZrGP exhibited highly selective adsorption to Pb{sup 2+} in solution which contained Pb{sup 2+}, Cd{sup 2+}, Mg{sup 2+} and Ca{sup 2+} ions. The loaded ZrGP with metallic ions can be efficaciously regenerated by aqueous solution of HCl (1.0 M) without any noticeable capacity loss, and almost all of it can be reused and recycled. The memory effect on structural regeneration of ZrGP was also found when Mg{sup 2+} and Ca{sup 2+} were adsorbed. To be specific, the structure of ZrGP was destroyed due to adsorbing these two ions, but it could be regenerated after the loaded materials were dipped in HCl solution (1.0 M) for several minutes to remove metallic ions.

  1. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  2. Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

    International Nuclear Information System (INIS)

    Usami, Katsuaki; Matsuno, Keita; Igarashi, Manabu; Denda-Nagai, Kaori; Takada, Ayato; Irimura, Tatsuro

    2011-01-01

    Highlights: → Ebola virus infection is mediated by binding to and fusion with the target cells. → Structural feature of the viral glycoprotein determines the infectivity. → Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. → GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. → There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

  3. Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

    Energy Technology Data Exchange (ETDEWEB)

    Usami, Katsuaki [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Matsuno, Keita; Igarashi, Manabu [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Denda-Nagai, Kaori [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Takada, Ayato [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Irimura, Tatsuro, E-mail: irimura@mol.f.u-tokyo.ac.jp [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)

    2011-04-01

    Highlights: {yields} Ebola virus infection is mediated by binding to and fusion with the target cells. {yields} Structural feature of the viral glycoprotein determines the infectivity. {yields} Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. {yields} GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. {yields} There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

  4. Music perception and cognition: a review of recent cross-cultural research.

    Science.gov (United States)

    Stevens, Catherine J

    2012-10-01

    Experimental investigations of cross-cultural music perception and cognition reported during the past decade are described. As globalization and Western music homogenize the world musical environment, it is imperative that diverse music and musical contexts are documented. Processes of music perception include grouping and segmentation, statistical learning and sensitivity to tonal and temporal hierarchies, and the development of tonal and temporal expectations. The interplay of auditory, visual, and motor modalities is discussed in light of synchronization and the way music moves via emotional response. Further research is needed to test deep-rooted psychological assumptions about music cognition with diverse materials and groups in dynamic contexts. Although empirical musicology provides keystones to unlock musical structures and organization, the psychological reality of those theorized structures for listeners and performers, and the broader implications for theories of music perception and cognition, awaits investigation. Copyright © 2012 Cognitive Science Society, Inc.

  5. Sebaran Generalized Extreme Value (GEV dan Generalized Pareto (GP untuk Pendugaan Curah Hujan Ekstrim di Wilayah DKI Jakarta

    Directory of Open Access Journals (Sweden)

    Achi Rinaldi

    2016-06-01

    Full Text Available Extreme event such as extreme rainfall have been analyzed and most concern for the country all around the world. There are two common distribution for extreme value which are Generalized Extreme Value distribution and Generalized Pareto distribution. These two distribution have shown good performace to estimate the parameter of  extreme value. This research was aim to estimate parameter of extreme value using GEV distribution and GP distribution, and also to characterized effect of extreme event such as flood. The rainfall data was taken from BMKG for 5 location in DKI Jakarta. Both of distribution shown a good perfromance. The resut showed that Tanjung Priok station has biggest location parameter for GEV and also the biggest scale parameter for GP, that mean the biggest probability to take flood effect of the extreme rainfall.

  6. A Research into Evaluation of Basketball Athletes' Risk Perception Level

    Science.gov (United States)

    Karatas, Ozgur

    2016-01-01

    The aim of this study is to compare the risk perception levels of Basketball athletes in Turkish League teams according to some variables. In this research the "general screening model," which is one of the descriptive screening methods, was used. While the population of the study consists of athletes actively engaged in the Turkish…

  7. Immunization With Fc-Based Recombinant Epstein–Barr Virus gp350 Elicits Potent Neutralizing Humoral Immune Response in a BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Bingchun Zhao

    2018-05-01

    Full Text Available Epstein–Barr virus (EBV was the first human virus proved to be closely associated with tumor development, such as lymphoma, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma. Despite many efforts to develop prophylactic vaccines against EBV infection and diseases, no candidates have succeeded in effectively blocking EBV infection in clinical trials. Previous investigations showed that EBV gp350 plays a pivotal role in the infection of B-lymphocytes. Nevertheless, using monomeric gp350 proteins as antigens has not been effective in preventing infection. Multimeric forms of the antigen are more potently immunogenic than monomers; however, the multimerization elements used in previous constructs are not approved for human clinical trials. To prepare a much-needed EBV prophylactic vaccine that is potent, safe, and applicable, we constructed an Fc-based form of gp350 to serve as a dimeric antigen. Here, we show that the Fc-based gp350 antigen exhibits dramatically enhanced immunogenicity compared with wild-type gp350 protein. The complete or partial gp350 ectodomain was fused with the mouse IgG2a Fc domain. Fusion with the Fc domain did not impair gp350 folding, binding to a conformation-dependent neutralizing antibody (nAb and binding to its receptor by enzyme-linked immunosorbent assay and surface plasmon resonance. Specific antibody titers against gp350 were notably enhanced by immunization with gp350-Fc dimers compared with gp350 monomers. Furthermore, immunization with gp350-Fc fusion proteins elicited potent nAbs against EBV. Our data strongly suggest that an EBV gp350 vaccine based on Fc fusion proteins may be an efficient candidate to prevent EBV infection in clinical applications.

  8. Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

    Directory of Open Access Journals (Sweden)

    Jerome E. Tanner

    2018-04-01

    Full Text Available Acute Epstein-Barr virus (EBV infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD. The EBV major virion surface glycoprotein (gp350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody.

  9. Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations.

    Directory of Open Access Journals (Sweden)

    Nathan W Cummins

    Full Text Available Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05, which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism.

  10. The GP problem: quantifying gene-to-phenotype relationships.

    Science.gov (United States)

    Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

    2002-01-01

    In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

  11. Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV Pentameric Complex Proteins GP129, 131 and 133

    Directory of Open Access Journals (Sweden)

    Josephine S. Gnanandarajah

    2014-02-01

    Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus (HCMV is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV, consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model.

  12. Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

    2010-03-08

    Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

  13. Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research.

    Directory of Open Access Journals (Sweden)

    Liam D Harper

    Full Text Available Qualitative research investigating soccer practitioners' perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open-ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time regulations, and ideas for future research. Using inductive content analysis, the following general dimensions were identified: 'importance of extra-time', 'rule changes', 'efficacy of extra-time hydro-nutritional provision', 'nutritional timing', 'future research directions', 'preparatory modulations' and 'recovery'. The majority of practitioners (63% either agreed or strongly agreed that extra-time is an important period for determining success in knockout football match-play. When asked if a fourth substitution should be permitted in extra-time, 67% agreed. The use of hydro-nutritional strategies prior to extra-time was predominately considered important or very important. However; only 41% of practitioners felt that it was the most important time point for the use of nutritional products. A similar number of practitioners account (50% and do not (50% account for the potential of extra-time when training and preparing players and 89% of practitioners stated that extra-time influences recovery practices following matches. In the five minute break prior to extra-time, the following practices (in order of priority were advocated to players: hydration, energy provision, massage, and tactical preparations. Additionally, 87% of practitioners advocate a particular nutritional supplementation strategy prior to extra-time. In order of importance, practitioners see the following as future research areas: nutritional interventions, fatigue responses, acute injury risk

  14. Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research.

    Science.gov (United States)

    Harper, Liam D; Fothergill, Melissa; West, Daniel J; Stevenson, Emma; Russell, Mark

    2016-01-01

    Qualitative research investigating soccer practitioners' perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open-ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time regulations, and ideas for future research. Using inductive content analysis, the following general dimensions were identified: 'importance of extra-time', 'rule changes', 'efficacy of extra-time hydro-nutritional provision', 'nutritional timing', 'future research directions', 'preparatory modulations' and 'recovery'. The majority of practitioners (63%) either agreed or strongly agreed that extra-time is an important period for determining success in knockout football match-play. When asked if a fourth substitution should be permitted in extra-time, 67% agreed. The use of hydro-nutritional strategies prior to extra-time was predominately considered important or very important. However; only 41% of practitioners felt that it was the most important time point for the use of nutritional products. A similar number of practitioners account (50%) and do not (50%) account for the potential of extra-time when training and preparing players and 89% of practitioners stated that extra-time influences recovery practices following matches. In the five minute break prior to extra-time, the following practices (in order of priority) were advocated to players: hydration, energy provision, massage, and tactical preparations. Additionally, 87% of practitioners advocate a particular nutritional supplementation strategy prior to extra-time. In order of importance, practitioners see the following as future research areas: nutritional interventions, fatigue responses, acute injury risk, recovery

  15. Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

    Directory of Open Access Journals (Sweden)

    Ouyang Handong

    2011-05-01

    Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

  16. Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

    Science.gov (United States)

    Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

    2018-06-05

    Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

  17. The Influences of Glycosylation on the Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines

    National Research Council Canada - National Science Library

    Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L; Garrison, Aura R; Smith, Jeffrey M; Paragas, Jason; Hogan, Robert J; Schmaljohn, Connie

    2006-01-01

    ... or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP...

  18. GP-9s are ubiquitous proteins unlikely involved in olfactory mediation of social organization in the red imported fire ant, Solenopsis invicta.

    Directory of Open Access Journals (Sweden)

    Walter S Leal

    Full Text Available The red imported fire ant (RIFA, Solenopsis invicta, is an invasive species, accidentally introduced in the United States that can cause painful (sometimes life-threatening stings to human, pets, and livestock. Their colonies have two social forms: monogyne and polygyne that have a single and multiple functional queens, respectively. A major gene (Gp-9, identified as a putative pheromone-binding protein on the basis of a modest amino acid sequence identity, has been suggested to influence the expression of colony social organization. Monogyne queens are reported to possess only the GP-9B alleles, whereas polygyne queens possess both GP-9B and GP-9b. Thus, both social forms are reported to express GP-9B, with GP-9b being a marker expressed in polygynes but it is absent in monogynes. Here, we report two types of polygyne colonies, one that does not express GP-9b (monogyne-like and the other expressing both proteins, GP-9B and GP-9b. Given their expression pattern, GP-9s are hemolymph proteins, which are more likely to be involved in the transport of lipids and small ligands within the homocoel. GP-9B existed in two forms, one of them is phosphorylated. The helical-rich content of the protein resembles the secondary structures of a beetle hemolymph protein and moth pheromone-binding proteins. An olfactory role is unlikely given the lack of specific expression in the sensillar lymph. In marked contrast to GP-9s, a chemosensory protein, SinvCSP, is demonstrated to be specifically expressed in the antennae. Within the antennae, expression of SinvCSP is restricted to the last two segments, which are known to house olfactory sensilla.

  19. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    Directory of Open Access Journals (Sweden)

    Neven A Knuistingh

    2006-11-01

    Full Text Available Abstract Background Preconception counselling (PCC can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods Randomised trial of usual care versus GP-initiated PCC for women aged 18–40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI before PCC (STAI-1 and after (STAI-2. After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3. Results The mean STAI-1-score (n = 466 was 36.4 (95% CI 35.4 – 37.3. Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4 – 4.8. Mean scores of the STAI-3 were 38.5 (95% CI 37.7 – 39.3 in the control group (n = 1090 and 38.7 (95% CI 37.9 – 39.5 in the intervention group (n = 1186. Conclusion PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety. Trial Registration: ISRCTN53942912

  20. Academics' Perceptions of the Challenges and Barriers to Implementing Research-Based Experiences for Undergraduates

    Science.gov (United States)

    Brew, Angela; Mantai, Lilia

    2017-01-01

    How can universities ensure that strategic aims to integrate research and teaching through engaging students in research-based experiences be effectively realised within institutions? This paper reports on the findings of a qualitative study exploring academics' perceptions of the challenges and barriers to implementing undergraduate research.…

  1. The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies.

    Science.gov (United States)

    Brinkmann, Constantin; Nehlmeier, Inga; Walendy-Gnirß, Kerstin; Nehls, Julia; González Hernández, Mariana; Hoffmann, Markus; Qiu, Xiangguo; Takada, Ayato; Schindler, Michael; Pöhlmann, Stefan

    2016-12-15

    The glycoprotein of Ebola virus (EBOV GP), a member of the family Filoviridae, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism. Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The

  2. Attitudes and perceptions of Conacyt researchers towards public communication of science and technology.

    Science.gov (United States)

    Sanz Merino, Noemí; Tarhuni Navarro, Daniela H

    2018-06-01

    This study aims to explore the perceptions and attitudes toward Public Communication of Science and Technology of the researchers of the National Council of Science and Technology (Conacyt), in order to provide a diagnosis about the ways the Mexican scientists are involved in public communication and to contribute to the visibility of researchers' needs in being able to popularize science. The results show significant differences among the researchers' opinions with respect to their perceptions about science communication, the ways they participate in PUS activities and their identified needs. In general, the researchers of Conacyt perceived public communication as very important. However, lack of time and of academic recognition stood out as determining factors in their low contribution to science popularization. We conclude that, to achieve a culture of Public Engagement in public communication of science and technology among R&D institutions, the Mexican Administration should address the above-mentioned unfavorable professional circumstances.

  3. Research on Tele2 campaign "Meteorite". The real and the desirable perception by target audience

    OpenAIRE

    Kalve, Anita

    2010-01-01

    The theme of the Bachelor work is: ‘’Research on Tele2 campaign ‘’Meteorite’’. The real and the desirable perception by target audience.’’’’. Several subjects are described in this work, such as – communication process from a marketing perspective, integrated marketing communication, campaig planning, guerilla marketing and it’s tools. The problematics – perception of the target audience, which leads to the objective: finding out if the desirable perception which was planned...

  4. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100{sub 25–33} peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiaoli [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610 (United States)

    2015-12-04

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100{sub 25–33} peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100{sub 25–33} peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100{sub 25–33} peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100{sub 25–33} were significantly increased compared to control groups. Tumor antigen, GP100{sub 25–23} specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100{sub 25–33}-coupled spleen cells leads to potent anti-melanoma immunity. • GP100{sub 25–33}-coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  5. Effects of local application of methylprednisolone delivered by the C/GP-hydrogel on the recovery of facial nerves.

    Science.gov (United States)

    Chao, Xiuhua; Fan, Zhaomin; Han, Yuechen; Wang, Yan; Li, Jianfeng; Chai, Renjie; Xu, Lei; Wang, Haibo

    2015-01-01

    Local administration of MP delivered by the C/GP-MP-hydrogel can improve the recovery of facial nerve following crush injury. The findings suggested that locally injected MP delivered by C/GP-hydrogel might be a promising treatment for facial nerve damage. In this study, the aim is to assess the effectiveness of locally administrating methylprednisolone(MP) loaded by chitosan-β-glycerophosphate hydrogel (C/GP-hydrogel) on the regeneration of facial nerve crush injury. After the crush of left facial nerves, Wistar rats were randomly divided into four different groups. Then, four different therapies were used to treat the damaged facial nerves. At the 1(st), 2(nd), 3(rd), and 4(th) week after injury, the functional recovery of facial nerves and the morphological changes of facial nerves were assessed. The expression of growth associated protein-43 (GAP-43) protein in the facial nucleus were also evaluated. Locally injected MP delivered by C/GP-hydrogel effectively accelerated the facial functional recovery. In addition, the regenerated facial nerves in the C/GP-MP group were more mature than those in the other groups. The expression of GAP-43 protein was also improved by the MP, especially in the C/GP-MP group.

  6. Development of Classification Models for Identifying “True” P-glycoprotein (P-gp Inhibitors Through Inhibition, ATPase Activation and Monolayer Efflux Assays

    Directory of Open Access Journals (Sweden)

    Anna Maria Bianucci

    2012-06-01

    Full Text Available P-glycoprotein (P-gp is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as “true” P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function.

  7. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Directory of Open Access Journals (Sweden)

    Luping Du

    2018-01-01

    Full Text Available Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide (PLGA nanoparticles (NPs with Ulex europaeus agglutinin 1 (UEA-1 and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5] or subunit vaccine ORF5-encoded glycoprotein (GP5 from exposure to the gastrointestinal (GI tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05. Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system.

  8. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Science.gov (United States)

    Du, Luping; Yu, Zhengyu; Pang, Fengjiao; Xu, Xiangwei; Mao, Aihua; Yuan, Wanzhe; He, Kongwang; Li, Bin

    2018-01-01

    Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells) within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Ulex europaeus agglutinin 1 (UEA-1) and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5)] or subunit vaccine ORF5-encoded glycoprotein (GP5) from exposure to the gastrointestinal (GI) tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05). Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system. PMID:29423381

  9. DNA unwinding by ring-shaped T4 helicase gp41 is hindered by tension on the occluded strand.

    Science.gov (United States)

    Ribeck, Noah; Saleh, Omar A

    2013-01-01

    The replicative helicase for bacteriophage T4 is gp41, which is a ring-shaped hexameric motor protein that achieves unwinding of dsDNA by translocating along one strand of ssDNA while forcing the opposite strand to the outside of the ring. While much study has been dedicated to the mechanism of binding and translocation along the ssDNA strand encircled by ring-shaped helicases, relatively little is known about the nature of the interaction with the opposite, 'occluded' strand. Here, we investigate the interplay between the bacteriophage T4 helicase gp41 and the ss/dsDNA fork by measuring, at the single-molecule level, DNA unwinding events on stretched DNA tethers in multiple geometries. We find that gp41 activity is significantly dependent on the geometry and tension of the occluded strand, suggesting an interaction between gp41 and the occluded strand that stimulates the helicase. However, the geometry dependence of gp41 activity is the opposite of that found previously for the E. coli hexameric helicase DnaB. Namely, tension applied between the occluded strand and dsDNA stem inhibits unwinding activity by gp41, while tension pulling apart the two ssDNA tails does not hinder its activity. This implies a distinct variation in helicase-occluded strand interactions among superfamily IV helicases, and we propose a speculative model for this interaction that is consistent with both the data presented here on gp41 and the data that had been previously reported for DnaB.

  10. Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

    Science.gov (United States)

    Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

    2014-06-30

    The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Feasibility, acceptability and effectiveness of an online alternative to face-to-face consultation in general practice: a mixed-methods study of webGP in six Devon practices.

    Science.gov (United States)

    Carter, Mary; Fletcher, Emily; Sansom, Anna; Warren, Fiona C; Campbell, John L

    2018-02-15

    online options. Greater uptake requires good communication between practice and patients, and organisation of systems to avoid conflicts and misuse. Further research is required to evaluate the full potential of webGP in managing practice workload. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition

    International Nuclear Information System (INIS)

    Koch, Markus; Pancera, Marie; Kwong, Peter D.; Kolchinsky, Peter; Grundner, Christoph; Wang Liping; Hendrickson, Wayne A.; Sodroski, Joseph; Wyatt, Richard

    2003-01-01

    The human immunodeficiency virus (HIV-1) exterior envelope glycoprotein, gp120, mediates receptor binding and is the major target for neutralizing antibodies. Primary HIV-1 isolates are characteristically more resistant to broadly neutralizing antibodies, although the structural basis for this resistance remains obscure. Most broadly neutralizing antibodies are directed against functionally conserved gp120 regions involved in binding to either the primary virus receptor, CD4, or the viral coreceptor molecules that normally function as chemokine receptors. These antibodies are known as CD4 binding site (CD4BS) and CD4-induced (CD4i) antibodies, respectively. Inspection of the gp120 crystal structure reveals that although the receptor-binding regions lack glycosylation, sugar moieties lie proximal to both receptor-binding sites on gp120 and thus in proximity to both the CD4BS and the CD4i epitopes. In this study, guided by the X-ray crystal structure of gp120, we deleted four N-linked glycosylation sites that flank the receptor-binding regions. We examined the effects of selected changes on the sensitivity of two prototypic HIV-1 primary isolates to neutralization by antibodies. Surprisingly, removal of a single N-linked glycosylation site at the base of the gp120 third variable region (V3 loop) increased the sensitivity of the primary viruses to neutralization by CD4BS antibodies. Envelope glycoprotein oligomers on the cell surface derived from the V3 glycan-deficient virus were better recognized by a CD4BS antibody and a V3 loop antibody than were the wild-type glycoproteins. Absence of all four glycosylation sites rendered a primary isolate sensitive to CD4i antibody-mediated neutralization. Thus, carbohydrates that flank receptor-binding regions on gp120 protect primary HIV-1 isolates from antibody-mediated neutralization

  13. Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

    2016-01-15

    The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

  14. Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.

    Directory of Open Access Journals (Sweden)

    Junji Sashihara

    2011-10-01

    Full Text Available Epstein-Barr virus (EBV is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350 or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]. No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a soluble rhesus LCV gp350, (b virus-like replicon particles (VRPs expressing rhesus LCV gp350, (c VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with

  15. Information literacy: perceptions of Brazilian HIV/AIDS researchers.

    Science.gov (United States)

    Alvarez, Maria do Carmo Avamilano; França, Ivan; Cuenca, Angela Maria Belloni; Bastos, Francisco I; Ueno, Helene Mariko; Barros, Cláudia Renata; Guimarães, Maria Cristina Soares

    2014-03-01

    Information literacy has evolved with changes in lifelong learning. Can Brazilian health researchers search for and use updated scientific information? To describe researchers' information literacy based on their perceptions of their abilities to search for and use scientific information and on their interactions with libraries. Semi-structured interviews and focus group conducted with six Brazilian HIV/AIDS researchers. Analyses comprised the assessment of researchers as disseminators, their interactions with librarians, their use of information and communication technology and language. Interviewees believed they were partially qualified to use databases. They used words and phrases that indicated their knowledge of technology and terminology. They acted as disseminators for students during information searches. Researchers' abilities to interact with librarians are key skills, especially in a renewed context where libraries have, to a large extent, changed from physical spaces to digital environments. Great amounts of information have been made available, and researchers' participation in courses does not automatically translate into adequate information literacy. Librarians must help research groups, and as such, librarians' information literacy-related responsibilities in Brazil should be redefined and expanded. Students must develop the ability to learn quickly, and librarians should help them in their efforts. Librarians and researchers can act as gatekeepers for research groups and as information coaches to improve others' search abilities. © 2013 Health Libraries Group of CILIP and John Wiley & Sons Ltd.

  16. GP2 is selectively expressed by small intestinal CD103+CD11b+ cDC

    DEFF Research Database (Denmark)

    Müller-Luda, Katarzyna; Ahmadi, Fatemeh; Ohno, Hiroshi

    DC in the small intestine. Moreover, GP2 expressing cDC in the small intestine were dramatically reduced in the setting of intestinal inflammation. We have previously shown that mice with an IRF4 deletion in CD11c+ cells (Cd11c-cre.Irf4 fl/fl mice) have reduced numbers of small intestinal CD103+CD11b+ c......DC. Interesting, we found that GP2+ CD103+CD11b+ cDC were dramatically reduced in these mice. Finally, to address the in vivo role of GP2 expression by cDC, we have generated mice with a selective deletion of GP2 in CD103+CD11b+ cDC (huLangerin-cre.gp2 fl/fl  mice). Results from these ongoing studies...

  17. Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

    Science.gov (United States)

    Yang, C-A; Lin, J-A; Chang, C-W; Wu, K-H; Yeh, S-P; Ho, C-M; Chang, J-G

    2016-10-01

    To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mi a ' records. The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mi a ') are identified in 1·24% of our population, and anti-'Mi a ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mi a ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mi a '-related transfusion reactions. Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mi a '-positive serum were selected for blood recipients with anti-'Mi a ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. The transfusion reaction rate was significantly higher in anti-'Mi a '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mi a ' became similar to total blood recipients. IgG form anti-'Mi a ' antibodies were present in all cases of probable anti-'Mi a '-related transfusion reactions. The time required for anti-'Mi a ' boosting after transfusion was around 4-21 days. Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mi a ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mi a ' is prevalent. © 2016 British Blood Transfusion Society.

  18. GP supervisors--an investigation into their motivations and teaching activities.

    Science.gov (United States)

    Ingham, Gerard; O'Meara, Peter; Fry, Jennifer; Crothers, Natalie

    2014-11-01

    There is little empirical information on how general practitioner (GP) supervisors teach and the reasons for the variation in their teaching methods. Could the variation be due to differing motivations to teach? Supervisors from one regional training provider who attended educational workshops in 2013 were surveyed, seeking infor-mation on their motivation to become and remain a supervisor, and the frequency of use of selected teaching activities. The majority of respondents cited intrinsic motivators, including enjoying teaching (84%), contribution to the profession and community (82%), adding variety (78%) and workforce/succession planning (69%), as reasons for becoming GP supervisors. The expected relationships between motivations and teaching activities were not found. Variation in teaching activities used by supervisors does not appear to be associated with differing motivations. Measuring the use of teaching activities is not a mechanism to determine a supervisor's commitment to teaching.

  19. Biometric Research in Perception and Neurology Related to the Study of Visual Communication.

    Science.gov (United States)

    Metallinos, Nikos

    Contemporary research findings in the fields of perceptual psychology and neurology of the human brain that are directly related to the study of visual communication are reviewed and briefly discussed in this paper. Specifically, the paper identifies those major research findings in visual perception that are relevant to the study of visual…

  20. Responsible Conduct of Research in Communication Sciences and Disorders: Faculty and Student Perceptions

    Science.gov (United States)

    Minifie, Fred D.; Robey, Randall R.; Horner, Jennifer; Ingham, Janis C.; Lansing, Charissa; McCartney, James H.; Alldredge, Elham-Eid; Slater, Sarah C.; Moss, Sharon E.

    2011-01-01

    Purpose: Two Web-based surveys (Surveys I and II) were used to assess perceptions of faculty and students in Communication Sciences and Disorders (CSD) regarding the responsible conduct of research (RCR). Method: Survey questions addressed 9 RCR domains thought important to the responsible conduct of research: (a) human subjects protections; (b)…

  1. Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract

    Directory of Open Access Journals (Sweden)

    Lixia Ji

    2017-01-01

    Full Text Available Objective. Lens osmotic expansion, provoked by overactivated aldose reductase (AR, is the most essential event of sugar cataract. Chloride channel 3 (Clcn3 is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract. Methods and Results. In vitro, lens epithelial cells (LECs were primarily cultured in gradient galactose medium (10–60 mM, more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day. Conclusion. Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

  2. Research advances in association between Golgi protein 73 and liver diseases

    Directory of Open Access Journals (Sweden)

    WEI Fengxian

    2017-08-01

    Full Text Available Golgi protein 73 (GP73 has a very low expression level in normal people, while it has a significantly higher expression level in patients with liver diseases and hepatocellular carcinoma (HCC, and therefore, it may become a new marker for HCC. This article introduces the distribution of GP73 in human body and definitions of different subtypes of GP73 and elaborates on its association with benign/malignant liver diseases and surgical operation based on the subtypes of GP73, as well as the application of GP73 in the differentiation of benign/malignant liver diseases. Since GP73 is closely associated with the development, progression, and prognosis of liver diseases, this article summarizes the latest advances in basic research, introduces the structural basis of fucosylated GP73 and proliferation, migration, and invasion of hepatoma cells and known signaling pathways, and lists the factors which affect the expression of GP73.

  3. Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.

    Directory of Open Access Journals (Sweden)

    Anitra L Farrow

    2014-08-01

    Full Text Available Trypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available. The results of inadequate treatment could lead to heart failure resulting in death. Therefore, a vaccine that elicits neutralizing antibodies mediated by cell-mediated immune responses and protection against Chagas disease is necessary.The "antigen capsid-incorporation" strategy is based upon the display of the T. cruzi epitope as an integral component of the adenovirus' capsid rather than an encoded transgene. This strategy is predicted to induce a robust humoral immune response to the presented antigen, similar to the response provoked by native Ad capsid proteins. The antigen chosen was T. cruzi gp83, a ligand that is used by T. cruzi to attach to host cells to initiate infection. The gp83 epitope, recognized by the neutralizing MAb 4A4, along with His6 were incorporated into the Ad serotype 5 (Ad5 vector to generate the vector Ad5-HVR1-gp83-18 (Ad5-gp83. This vector was evaluated by molecular and immunological analyses. Vectors were injected to elicit immune responses against gp83 in mouse models. Our findings indicate that mice immunized with the vector Ad5-gp83 and challenged with a lethal dose of T. cruzi trypomastigotes confer strong immunoprotection with significant reduction in parasitemia levels, increased survival rate and induction of neutralizing antibodies.This data demonstrates that immunization with adenovirus containing capsid-incorporated T. cruzi antigen elicits a significant anti-gp83-specific response in two different mouse models, and protection against T. cruzi infection by eliciting neutralizing antibodies mediated by cell-mediated immune responses, as evidenced by the production of several Ig isotypes

  4. HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces production of matrix metalloproteinases.

    Directory of Open Access Journals (Sweden)

    Sashaina E Fanibunda

    Full Text Available BACKGROUND: During sexual transmission of HIV in women, the virus breaches the multi-layered CD4 negative stratified squamous epithelial barrier of the vagina, to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have previously reported human mannose receptor (hMR as a CD4 independent receptor playing a role in HIV transmission on human spermatozoa. The current study was undertaken to investigate the expression of hMR in vaginal epithelial cells, its HIV gp120 binding potential, affinity constants and the induction of matrix metalloproteinases (MMPs downstream of HIV gp120 binding to hMR. PRINCIPAL FINDINGS: Human vaginal epithelial cells and the immortalized vaginal epithelial cell line Vk2/E6E7 were used in this study. hMR mRNA and protein were expressed in vaginal epithelial cells and cell line, with a molecular weight of 155 kDa. HIV gp120 bound to vaginal proteins with high affinity, (Kd = 1.2±0.2 nM for vaginal cells, 1.4±0.2 nM for cell line and the hMR antagonist mannan dose dependently inhibited this binding. Both HIV gp120 binding and hMR exhibited identical patterns of localization in the epithelial cells by immunofluorescence. HIV gp120 bound to immunopurified hMR and affinity constants were 2.9±0.4 nM and 3.2±0.6 nM for vaginal cells and Vk2/E6E7 cell line respectively. HIV gp120 induced an increase in MMP-9 mRNA expression and activity by zymography, which could be inhibited by an anti-hMR antibody. CONCLUSION: hMR expressed by vaginal epithelial cells has high affinity for HIV gp120 and this binding induces production of MMPs. We propose that the induction of MMPs in response to HIV gp120 may lead to degradation of tight junction proteins and the extracellular matrix proteins in the vaginal epithelium and basement membrane, leading to weakening of the epithelial barrier; thereby facilitating transport of HIV across the

  5. Access to and utilisation of GP services among Burmese migrants in London: a cross-sectional descriptive study.

    Science.gov (United States)

    Aung, Nyein Chan; Rechel, Bernd; Odermatt, Peter

    2010-10-12

    An estimated 10,000 Burmese migrants are currently living in London. No studies have been conducted on their access to health services. Furthermore, most studies on migrants in the United Kingdom (UK) have been conducted at the point of service provision, carrying the risk of selection bias. Our cross-sectional study explored access to and utilisation of General Practice (GP) services by Burmese migrants residing in London. We used a mixed-method approach: a quantitative survey using self-administered questionnaires was complemented by qualitative in-depth interviews for developing the questionnaire and triangulating the findings of the survey. Overall, 137 questionnaires were received (a response rate of 57%) and 11 in-depth interviews conducted. The main outcome variables of the study included GP registration, barriers towards registration, GP consultations, barriers towards consultations, and knowledge on entitlements to health care. Quantitative data were analysed using descriptive statistics, association tests, and a multivariate analysis using logistic regression. The qualitative information was analysed using content analysis. The respondents were young, of roughly equal gender (51.5% female), well educated, and had a fair level of knowledge on health services in the UK. Although the GP registration rate was relatively high (80%, 109 out of 136), GP service utilisation during the last episode of illness, at 56.8% (54 out of 95), was low. The statistical analysis showed that age being younger than 35 years, lacking prior overseas experience, having an unstable immigration status, having a shorter duration of stay, and resorting to self-medication were the main barriers hindering Burmese migrants from accessing primary health care services. These findings were corroborated by the in-depth interviews. Our study found that having formal access to primary health care was not sufficient to ensure GP registration and health care utilisation. Some respondents faced

  6. Access to and utilisation of GP services among Burmese migrants in London: a cross-sectional descriptive study

    Directory of Open Access Journals (Sweden)

    Rechel Bernd

    2010-10-01

    Full Text Available Abstract Background An estimated 10,000 Burmese migrants are currently living in London. No studies have been conducted on their access to health services. Furthermore, most studies on migrants in the United Kingdom (UK have been conducted at the point of service provision, carrying the risk of selection bias. Our cross-sectional study explored access to and utilisation of General Practice (GP services by Burmese migrants residing in London. Methods We used a mixed-method approach: a quantitative survey using self-administered questionnaires was complemented by qualitative in-depth interviews for developing the questionnaire and triangulating the findings of the survey. Overall, 137 questionnaires were received (a response rate of 57% and 11 in-depth interviews conducted. The main outcome variables of the study included GP registration, barriers towards registration, GP consultations, barriers towards consultations, and knowledge on entitlements to health care. Quantitative data were analysed using descriptive statistics, association tests, and a multivariate analysis using logistic regression. The qualitative information was analysed using content analysis. Results The respondents were young, of roughly equal gender (51.5% female, well educated, and had a fair level of knowledge on health services in the UK. Although the GP registration rate was relatively high (80%, 109 out of 136, GP service utilisation during the last episode of illness, at 56.8% (54 out of 95, was low. The statistical analysis showed that age being younger than 35 years, lacking prior overseas experience, having an unstable immigration status, having a shorter duration of stay, and resorting to self-medication were the main barriers hindering Burmese migrants from accessing primary health care services. These findings were corroborated by the in-depth interviews. Conclusions Our study found that having formal access to primary health care was not sufficient to ensure GP

  7. Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge

    International Nuclear Information System (INIS)

    Churchill, R. M.; Theiler, C.; Lipschultz, B.; Dux, R.; Pütterich, T.; Viezzer, E.

    2013-01-01

    A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique

  8. Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, R. M.; Theiler, C.; Lipschultz, B. [MIT Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Dux, R.; Pütterich, T.; Viezzer, E. [Max-Planck-Institut für Plasmaphysik, EURATOM Association, Boltzmannstrasse 2, D-85748 Garching (Germany); Collaboration: Alcator C-Mod Team; ASDEX Upgrade Team

    2013-09-15

    A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique.

  9. Gravity Probe-B (GP-B) Mission and Tracking, Telemetry and Control Subsystem Overview

    Science.gov (United States)

    Kennedy, Paul; Bell, Joseph L. (Technical Monitor)

    2001-01-01

    The National Aeronautics and Space Administration's (NASA) Marshall Space Flight Center (MSFC) in Huntsville, Alabama will launch the Gravity Probe B (GP-B) space experiment in the Fall of 2002. The GP-B spacecraft was developed to prove Einstein's theory of General Relativity. This paper will provide an overview of the GPB mission and will discuss the design, and test of the spacecraft Tracking, Telemetry and Control (TT&C) subsystem which incorporates NASA's latest generation standard transponder for use with the NASA Tracking and Data Relay Satellite System (TDRSS).

  10. Patient knowledge and perception of antibiotics: A questionnaire survey in primary care

    DEFF Research Database (Denmark)

    Sydenham, Rikke Vognbjerg; Plejdrup Hansen, Malene; Bruun Lauridsen, Gitte

    2015-01-01

    of antibiotics. Objectives: This study aimed to study patient knowledge and perceptions of antibiotic treatment and to explore possible associations between patient gender, age, and educational level and accurate knowledge of antibiotics. Design/Methods: As part of an Audit Project Odense project a questionnaire...... survey was conducted during winter 2014. Patients aged ≥18 years consulting their GP with symptoms of ARI were requested to fill in a questionnaire on knowledge and perception of antibiotic treatment. Socio-demographic information was obtained. Results: 361 patients completed the questionnaire (response...... rate 64%). 75% recognized that antibiotics are effective against bacteria and not against virus. Overuse of antibiotics was acknowledged by 80% of respondents as an important factor in the development of resistant bacteria. Female gender was the only patient characteristic significantly associated...

  11. Mimicking protein-protein interactions through peptide-peptide interactions: HIV-1 gp120 and CXCR4

    Directory of Open Access Journals (Sweden)

    Andrea eGross

    2013-09-01

    Full Text Available We have recently designed a soluble synthetic peptide that functionally mimics the HIV-1 coreceptor CXCR4, which is a chemokine receptor that belongs to the family of seven-transmembrane GPCRs. This CXCR4 mimetic peptide, termed CX4-M1, presents the three extracellular loops (ECLs of the receptor. In binding assays involving recombinant proteins, as well as in cellular infection assays, CX4-M1 was found to selectively recognize gp120 from HIV-1 strains that use CXCR4 for cell entry (X4 tropic HIV-1. Furthermore, anti-HIV-1 antibodies modulate this interaction in a molecular mechanism related to that of their impact on the gp120-CXCR4 interaction. We could now show that the selectivity of CX4-M1 pertains not only to gp120 from X4 tropic HIV-1, but also to synthetic peptides presenting the V3 loops of these gp120 proteins. The V3 loop is thought to be an essential part of the coreceptor binding site of gp120 that contacts the second ECL of the coreceptor. We were able to experimentally confirm this notion in binding assays using substitution analogs of CX4-M1 and the V3 loop peptides, respectively, as well as in cellular infection assays. These results indicate that interactions of the HIV-1 Env with coreceptors can be mimicked by synthetic peptides, which may be useful to explore these interactions at the molecular level in more detail.

  12. Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

    Directory of Open Access Journals (Sweden)

    Cátia Teixeira

    Full Text Available HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules.

  13. Small-angle scattering from GP zones in Al–Cu alloy

    Indian Academy of Sciences (India)

    Administrator

    ficial aging, which are extensively used in commercial practice. It is well established ... Cu system shows the variety of metastable states follow- ing the sequence SSS .... the model for spinodal decomposition of GP 1 zones in. Al–Cu system ...

  14. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue, E-mail: lixue@imm.ac.cn; Hu, Jinping, E-mail: hujp@imm.ac.cn; Wang, Baolian, E-mail: wangbaolian@imm.ac.cn; Sheng, Li, E-mail: shengli@imm.ac.cn; Liu, Zhihao, E-mail: liuzhihao@imm.ac.cn; Yang, Shuang, E-mail: yangsh@imm.ac.cn; Li, Yan, E-mail: yanli@imm.ac.cn

    2014-03-01

    Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F{sub 1} [20(S)-GF{sub 1}] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC{sub 50} = 9.42 μM), followed by 18β-GA (IC{sub 50} = 21.78 μM), 20(S)-GF{sub 1} (IC{sub 50} = 76.08 μM) and DAG (IC{sub 50} = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K{sub m} and V{sub max} values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF{sub 1} exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC{sub 0−t} and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF{sub 1} and Rh{sub 1} at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18

  15. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

    International Nuclear Information System (INIS)

    Li, Xue; Hu, Jinping; Wang, Baolian; Sheng, Li; Liu, Zhihao; Yang, Shuang; Li, Yan

    2014-01-01

    Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F 1 [20(S)-GF 1 ] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC 50 = 9.42 μM), followed by 18β-GA (IC 50 = 21.78 μM), 20(S)-GF 1 (IC 50 = 76.08 μM) and DAG (IC 50 = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K m and V max values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF 1 exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC 0−t and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF 1 and Rh 1 at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18β-GA, DAG, and 20(S)-GF 1 significantly inhibited P-gp in vitro

  16. Re-Audit of the Contents of GP Referral letters to General Adult Community Psychiatrists.

    Science.gov (United States)

    Odelola, Catherine; Jabbar, Farid

    2017-09-01

    The quality of information provided by referring general practitioners to secondary care mental health services are crucial elements in the effective management of patients. In order to establish effective communication, both primary and secondary care health professionals should contribute to planning and organising this process taking into account their different opinions and views. Anonymous questionnaire was designed to collect information on items that GPs and psychiatrist rated as most important items in GP referral letters to psychiatrists. The questionnaires were sent out electronically. Each item was scored using a rating scale where 0 was least important and 10 was most important. Items that scored 8 and above were agreed by all as the most important items. 76 GP letters were audited using a devised checklist of the identified most important items. Data was collected and analysed using a devised data collection tool. A re-audit was done 6months later. A response rate of 70% was obtained for both psychiatrists and GPs. Reasons for referral were described in almost all GP referral letters (95%). Only 24% referral letters had details about current physical health which improved to 59%. Concerns about risk were described in only 47% of letters and treatment provided by GP in 50% of letters. These improved in 79% and 71% of letters respectively in the re-audit. The involvement of professionals in devising a standardised approach for referral letters has improved communication in this re-audit between GPs and Psychiatrists. This is evident in the improvement in key aspects of the referral letters: past medical history, past psychiatric history, current physical health, treatment provided by GP. Efficient communication between GPs and psychiatrists improves the quality of health care for patients.

  17. Increased Circulating Level of the Survival Factor GP88 (Progranulin in the Serum of Breast Cancer Patients When Compared to Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Katherine Rak Tkaczuk

    2011-01-01

    Full Text Available Introduction GP88 (PC-Cell Derived Growth Factor, progranulin is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC and healthy volunteers (HV. Methods An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay. Results Serum GP88 level was 28.7+ 5.8 ng/ml in HV and increased to 40.7+ 16.0 ng/ml ( P = 0.007 for stage 1-3 and 45.3 +23.3 ng/ml ( P = 0.0007 for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression. Conclusion These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.

  18. [Research progress on ebola virus glycoprotein].

    Science.gov (United States)

    Ding, Guo-Yong; Wang, Zhi-Yu; Gao, Lu; Jiang, Bao-Fa

    2013-03-01

    Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans and there are no effective therapeutic or prophylactic treatments available. The glycoprotein (GP) of EBOV is a transmembrane envelope protein known to play multiple functions including virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. GP is the primary target of protective immunity and the key target for developing neutralizing antibodies. In this paper, the research progress on genetic structure, pathogenesis and immunogenicity of EBOV GP in the last 5 years is reviewed.

  19. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site.

    Directory of Open Access Journals (Sweden)

    Barna Dey

    2009-05-01

    Full Text Available The human immunodeficiency virus type 1 (HIV-1 exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region.

  20. Antiviral Activity of HIV gp120 Targeting Bispecific T Cell Engager (BiTE®) Antibody Constructs.

    Science.gov (United States)

    Brozy, Johannes; Schlaepfer, Erika; Mueller, Christina K S; Rochat, Mary-Aude; Rampini, Silvana K; Myburgh, Renier; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A; Muenz, Markus; Speck, Roberto F

    2018-05-02

    Today's gold standard in HIV therapy is the combined antiretroviral therapy (cART). It requires strict adherence by patients and life-long medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency, but cannot cure patients. The bispecific T cell engaging (BiTE®) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. We here generated BiTE® antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1+2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ϵ scFv. These engineered human BiTE® antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in PBMCs as well as in macrophages co-cultured with autologous CD8+ T-cells, the most potent being the human CD4(1+2) BiTE® antibody construct and the CD4(1+2)L17b BiTE® antibody construct. The CD4(1+2) h BiTE® antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE® antibody constructs as well as the CD4(1+2)L17b BiTE® antibody construct did not. Thus, BiTE® antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential. Importance HIV is a chronic infection well controlled with the current cART. However, we lack cure of HIV, and the HIV pandemic goes on. Here we showed in vitro and ex vivo t hat a bispecific T-cell engaging (BiTE®) antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE® antibody constructs display efficient killing of gp120 expressing cells and inhibited replication in ex vivo

  1. The Ixodes scapularis Salivary Protein, Salp15, Prevents the Association of HIV-1 gp120 and CD4

    OpenAIRE

    Juncadella, Ignacio J.; Garg, Renu; Bates, Tonya C.; Olivera, Elias R.; Anguita, Juan

    2007-01-01

    Ixodes scapularis salivary protein, Salp15, inhibits CD4+ T cell activation by binding to the most-extracellular domains of the CD4 molecule, potentially overlapping with the gp120-binding region. We now show that Salp15 inhibits the interaction of gp120 and CD4. Furthermore, Salp15 prevents syncytia formation between HL2/3 (a stable HeLa cell line expressing the envelope protein) and CD4-expressing cells. Salp15 prevented gp120-CD4 interaction at least partially through its direct interactio...

  2. The EU as a Normative Power and the Research on External Perceptions: the Missing Link

    DEFF Research Database (Denmark)

    Larsen, Henrik

    2014-01-01

    perception offer some findings that are central for the NPE debate. This article’s argument is that the external perceptions literature points to a limited (if still identifiable) perception of the EU as a normative power depending on the geographical area. By comparison, the image of a powerful economic......In research on European foreign policy two important axes of debate have been running relatively independently of each other for more than a decade: the study of the European Union as a normative power (NPE) and the study of external perceptions of the EU. However, the studies of external...... actor is prevalent. The article raises the question of whether the thin and geographically varied character of the perceptions relating to the EU as a normative power justifies the general designation of NPE.Anew agenda focusing on geographical differences and interaction with other sources of power...

  3. Extracellular biosynthesis of silver nanoparticles using Bacillus sp. GP-23 and evaluation of their antifungal activity towards Fusarium oxysporum

    Science.gov (United States)

    Gopinath, V.; Velusamy, P.

    2013-04-01

    In last few decades nanoparticles have attracted and emerged as a field in biomedical research due to their incredible applications. The current research was focused on extracellular synthesis of silver nanoparticles (AgNPs) using cell free culture supernatant of strain GP-23. It was found that the strain GP-23 belonged to Bacillus species by 16S rRNA sequence analysis. Biosynthesis of AgNPs was achieved by addition of culture supernatant with aqueous silver nitrate solution, after 24 h it turned to brown color solution with a peak at 420 nm corresponding to the Plasmon absorbance of AgNPs by UV-Vis Spectroscopy. The nanoparticles were characterized by FTIR, XRD, HRTEM, EDX and AFM. The synthesized nanoparticles were found to be spherical in shape with size in the range of 7-21 nm. It was stable in aqueous solution for five months period of storage at room temperature under dark condition. The biosynthesized AgNPs exhibited strong antifungal activity against plant pathogenic fungus, Fusarium oxysporum at the concentration of 8 μg ml-1. The results suggest that the synthesized AgNPs act as an effective antifungal agent/fungicide.

  4. Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate

    DEFF Research Database (Denmark)

    Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume

    2013-01-01

    Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutr...

  5. What weekday? How acute? An analysis of reported planned and unplanned GP visits by older multi-morbid patients in the Patient Journey Record System database.

    Science.gov (United States)

    Surate Solaligue, David Emanuel; Hederman, Lucy; Martin, Carmel Mary

    2014-08-01

    . The PaJR project Care Guides advised patients to make unplanned visits in 6.3% of calls and advised planned GP visits in 2.5% of calls. Unplanned GP visits consistently indicated a significant change to worse health with planned visits presenting less acuity in this study of older multi-morbid patients in general practice, when monitored by regular calls at about every 3 days. The PaJR study actively prompted GP visits according to its algorithms. Assessing and predicting acuity in older multi-morbid patients appears to be a promising strategy to improve access to primary care, and thus to reducing avoidable hospital utilization. Further research is needed to investigate the topic on a wider scale. © 2014 John Wiley & Sons, Ltd.

  6. The process behind the expression of mdr-1/P-gp and mrp/MRP in human leukemia/lymphoma.

    Science.gov (United States)

    Hirose, Masao

    2009-04-01

    There is a controversy over the link between phenotypes of multidrug resistance (MDR) and clinical outcome in leukemia/lymphoma patients. This may be because the process behind the induction and loss of expression of genotypes and phenotypes by which MDR develops and the role of MDR in fresh cells of human leukemia/lymphoma are not clearly defined. P-glycoprotein (P-gp) increased and decreased along with mdr-1 expression in three cell lines out of five vincristine (VCR)-resistant cell lines. MRP appeared with increased mrp expression in the other two cell lines. After the drug was removed from the culture system, mdr-1/P-gp changed in parallel with the level of VCR resistance, although mrp and MRP did not. It was concluded that P-gp is directly derived from mdr-1 and that mdr-1/P-gp supports the VCR-resistance but mrp/MRP is not directly linked to the VCR-resistance. These results should contribute to a better understanding of MDR phenomenon in cancer.

  7. Reject analysis: A comparison of radiographer and radiologist perceptions of image quality

    International Nuclear Information System (INIS)

    Mount, J.

    2016-01-01

    This study explores the potential differences in perceptions of image quality between radiographers and radiologists in a large UK hospital and the subsequent impact this has on image rejection. Image rejection, while sometimes necessary, often leads to an increased radiation dose to the patient due to the need to repeat. Moreover, this translates into increased waiting times, departmental costs, and lower patient satisfaction. Adopting a mixed methods approach, this paper first seeks to quantify the differences in radiographer and radiologist perceptions and second establish the underlying causes of such differences through a quantitative and qualitative investigation respectively. Using a standardized psychometric scale of a GP lateral knee, the study reveals significant differences in the perceptions of quality and rejection rates between radiographers and radiologists driven by a conflict in the evaluation criteria used. The study has significant implications for improving departmental performance and proposes a potential solution for reducing reject rates and image repeats. - Highlights: • Significant differences are found to exist in perceptions of image quality. • Differences in perceptions of image quality directly influence reject rates. • Radiographers judge images on technical criteria. • Radiologists judge images on diagnostic criteria. • Results suggest better communication could reduce reject rates.

  8. Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Haiyan ZHENG

    2010-08-01

    Full Text Available Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1 The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05. The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05. (2 The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05, but not to age, gross type, histological type and lymph node metastasis (P > 0.05. The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05, but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05. CD8 expression was related to clinical stage (P < 0.05, but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05. The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3 There was positive correlation between gp

  9. Health risk behaviours of high school learners and their perceptions ...

    African Journals Online (AJOL)

    their interaction with their GP in dealing with these health risk behaviours. Results: The research .... It also assisted in the layout and phrasing of the final ... The Committee for Research on Human Subjects issued a clearance certificate number ...

  10. A combined AHP-GP model to allocate internal auditing time to ...

    African Journals Online (AJOL)

    Analytic hierarchy process, goal programming, internal audit, risk assessment. ..... Services area and are listed, together with their associated management ..... [2] Badri MA, 2001, A combined AHP-GP model for quality control systems, Interna-.

  11. Dentists' dietary perception and practice patterns in a dental practice-based research network.

    Directory of Open Access Journals (Sweden)

    Yoko Yokoyama

    Full Text Available Dental caries are largely preventable, and epidemiological evidence for a relationship between diet and oral health is abundant. To date, however, dentists' perceptions about the role of diet and dentists' practice patterns regarding diet counseling have not been clarified.THE PURPOSES OF THIS STUDY WERE TO: (1 examine discordance between dentists' perception of the importance of diet in caries treatment planning and their actual provision of diet counseling to patients, and (2 identify dentists' characteristics associated with their provision of diet counseling.The study used a cross-sectional study design consisting of a questionnaire survey in Japan.The study queried dentists working in outpatient dental practices who were affiliated with the Dental Practice-Based Research Network Japan (JDPBRN, which aims to allow dentists to investigate research questions and share experiences and expertise (n = 282.Dentists were asked about their perceptions on the importance of diet and their practice patterns regarding diet counseling, as well as patient, practice, and dentist background data.The majority of participants (n = 116, 63% recognized that diet is "more important" to oral health. However, among participants who think diet is "more important" (n = 116, only 48% (n = 56 provide diet counseling to more than 20% of their patients. Multiple logistic regression analysis suggested that several variables were associated with providing diet counseling; dentist gender, practice busyness, percentage of patients interested in caries prevention, caries risk assessment, and percentage of patients who receive blood pressure screening.Some discordance exists between dentists' perception of the importance of diet in caries treatment planning and their actual practice pattern regarding diet counseling to patients. Reducing this discordance may require additional dentist education, including nutritional and systemic disease concepts; patient

  12. Conceptualising GP teachers' knowledge: a pedagogical content knowledge perspective.

    Science.gov (United States)

    Cantillon, Peter; de Grave, Willem

    2012-05-01

    Most teacher development initiatives focus on enhancing knowledge of teaching (pedagogy), whilst largely ignoring other important features of teacher knowledge such as subject matter knowledge and awareness of the learning context. Furthermore, teachers' ability to learn from faculty development interventions is limited by their existing (often implicit) pedagogical knowledge and beliefs. Pedagogical content knowledge (PCK) represents a model of teacher knowledge incorporating what they know about subject matter, pedagogy and context. PCK can be used to explore teachers' prior knowledge and to structure faculty development programmes so that they take account of a broader range of teachers' knowledge. We set out to examine the application of a PCK model in a general practice education setting. This study is part of a larger study that employed a mixed method approach (concept mapping, phenomenological interviews and video-stimulated recall) to explore features of GP teachers' subject matter knowledge, pedagogical knowledge and knowledge of the learning environment in the context of a general practice tutorial. This paper presents data on GP teachers' pedagogical and context knowledge. There was considerable overlap between different GP teachers' knowledge and beliefs about learners and the clinical learning environment (i.e. knowledge of context). The teachers' beliefs about learners were largely based on assumptions derived from their own student experiences. There were stark differences, however, between teachers in terms of pedagogical knowledge, particularly in terms of their teaching orientations (i.e. transmission or facilitation orientation) and this was manifest in their teaching behaviours. PCK represents a useful model for conceptualising clinical teacher prior knowledge in three domains, namely subject matter, learning context and pedagogy. It can and should be used as a simple guiding framework by faculty developers to inform the design and delivery of

  13. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

    Directory of Open Access Journals (Sweden)

    Natalia Brzozowska

    2016-05-01

    Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

  14. The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.

    Science.gov (United States)

    Lu, Lin; Dong, Haixia; Liu, Guixiang; Yuan, Bin; Li, Yizhao; Liu, Huaxiang

    2014-11-01

    Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

  15. Dual-phase 99mTc-MIBI imaging and the expressions of P-gp, GST-π, and MRP1 in hyperparathyroidism.

    Science.gov (United States)

    Xue, Jianjun; Liu, Yan; Yang, Danrong; Yu, Yan; Geng, Qianqian; Ji, Ting; Yang, Lulu; Wang, Qi; Wang, Yuanbo; Lu, Xueni; Yang, Aimin

    2017-10-01

    The aim of this study was to further elucidate the mechanisms of dual-phase technetium-99m methoxyisobutylisonitrile (Tc-MIBI) parathyroid imaging by exploring the association between early uptake results (EUR), delayed uptake results (DUR), and the retention index (RI) in dual-phase Tc-MIBI parathyroid imaging and P glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and glutathione S-transferase-π (GST-π) expression in hyperparathyroidism (HPT). Preoperative dual-phase (early and delayed) Tc-MIBI imaging was performed on 74 patients undergoing parathyroidectomy for HPT. EUR, DUR, and RI were calculated. P-gp, MRP1, and GST-π expressions were assessed using immunohistochemistry in resected tissue from HPT and control patients. The association between P-gp, MRP1, and GST-π expressions and EUR, DUR, and RI in HPT was evaluated. The positive rate of dual-phase T c-MIBI imaging was 91.89% (68/74) and the false-negative rate was 8.11% (6/74). P-gp and GST-π expressions were higher in tissues resected from control compared with HPT patients (47.37 and 81.5%, P<0.05); there was no difference in MRP1. EUR were associated with P-gp and GST-π expressions, and DUR were associated with MRP1 expression. There was a significant difference in MRP1 expression between RI greater than or equal to 0 and RI less than 0. There was no relationship between the sensitivity of dual-phase Tc-MIBI imaging and P-gp, MRP1, and GST-π expressions in resected parathyroid tissue. The six false-negative HPT cases consisted of three P-gp (-)/MRP1 (-) tissues, three P-gp (-)/GST-π (-) tissues, and four MRP1 (-)/GST-π (-) tissues. As P-gp and GST-π expressions were higher in tissues resected from control compared with HPT patients, Tc-MIBI may wash out faster from normal parathyroid tissue surrounding the lesion compared with the lesion itself, facilitating detection.

  16. Epidemiology and resistance patterns in urinary pathogens from long-term care facilities and GP populations.

    LENUS (Irish Health Repository)

    Brabazon, E D

    2012-06-01

    Urinary tract infections (UTIs) are a major source of antimicrobial prescribing in the clinical setting and a potential reservoir for the emergence of resistant organisms. Although studies have been published on resistance rates for urinary pathogens from both hospital and general practitioner (GP) settings, there is little information from Long-Term Care Facilities (LTCFs) in Ireland. This study aimed to document the epidemiology and resistance rates in urinary isolates, in the LTCF and GP setting, from samples submitted to a typical microbiology laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary isolates from GPs, identified from patients 65 years and over, with cytology suggestive of infection. E. coil was the most common causative organism identified. There were significantly higher levels of resistance to ampicillin, co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and piperacillin\\/tazobactam in the LTCF population compared to the GP population (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v- 4% respectively). Isolates with resistance mechanisms to beta-lactams, were identified in both populations. Results presented in this paper demonstrate significant differences between resistance rates in LTCF and GP populations which suggest that there are implications for empiric antimicrobial prescribing for UTIs in the LTCF setting.

  17. Immersive Virtual Environment Technology to Supplement Environmental Perception, Preference and Behavior Research: A Review with Applications.

    Science.gov (United States)

    Smith, Jordan W

    2015-09-11

    Immersive virtual environment (IVE) technology offers a wide range of potential benefits to research focused on understanding how individuals perceive and respond to built and natural environments. In an effort to broaden awareness and use of IVE technology in perception, preference and behavior research, this review paper describes how IVE technology can be used to complement more traditional methods commonly applied in public health research. The paper also describes a relatively simple workflow for creating and displaying 360° virtual environments of built and natural settings and presents two freely-available and customizable applications that scientists from a variety of disciplines, including public health, can use to advance their research into human preferences, perceptions and behaviors related to built and natural settings.

  18. A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics

    DEFF Research Database (Denmark)

    Saaby, Lasse; Brodin, Birger

    2017-01-01

    Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties...... and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may...... mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate...

  19. HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway.

    Science.gov (United States)

    Wang, Yongdi; Liao, Jinxu; Tang, Shao-Jun; Shu, Jianhong; Zhang, Wenping

    2017-06-01

    HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway. We demonstrated that activation of the pathway by Wnt3a upregulated BDNF expression. In contrast, inhibition of the Wnt/β-catenin pathway by either DKK1 or IWR-1 attenuated BDNF upregulation induced by gp120 or Wnt3a. These findings collectively suggest that gp120 stimulates BDNF expression in BV2 cells via the Wnt/β-catenin signaling pathway.

  20. Perceptions of physiotherapists towards research: a mixed methods study.

    Science.gov (United States)

    Janssen, J; Hale, L; Mirfin-Veitch, B; Harland, T

    2016-06-01

    To explore the perceptions of physiotherapists towards the use of and participation in research. Concurrent mixed methods research, combining in-depth interviews with three questionnaires (demographics, Edmonton Research Orientation Survey, visual analogue scales for confidence and motivation to participate in research). One physiotherapy department in a rehabilitation hospital, consisting of seven specialised areas. Twenty-five subjects {four men and 21 women, mean age 38 [standard deviation (SD) 11] years} who had been registered as a physiotherapist for a mean period of 15 (SD 10) years participated in this study. They were registered with the New Zealand Board of Physiotherapy, held a current practising certificate, and were working as a physiotherapist or physiotherapy/allied health manager at the hospital. The primary outcome measure was in-depth interviews and the secondary outcome measures were the three questionnaires. Physiotherapists were generally positive towards research, but struggled with the concept of research, the available literature and the time to commit to research. Individual confidence and orientation towards research seemed to influence how these barriers were perceived. This study showed that physiotherapists struggle to implement research in their daily practice and become involved in research. Changing physiotherapists' conceptions of research, making it more accessible and providing dedicated research time could facilitate increased involvement in the physiotherapy profession. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  1. Integrity of the marriage and family therapy research literature: perceptions and recommendations.

    Science.gov (United States)

    Brock, Gregory W; Whiting, Jason B; Matern, Brianne; Fife, Stephen T

    2009-04-01

    Reports of falsification, fabrication, plagiarism, and other violations of research integrity across the sciences are on the increase. Joining with other disciplines to actively protect the integrity of the marriage and family therapy (MFT) research literature is of utmost importance to both the discipline and the future of the profession. To inform the issues raised, results are presented of an informal survey among MFT clinical members on their perceptions about the literature together with their preferences for how best to protect its integrity. This article initiates an important discussion about the honesty of MFT research.

  2. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

    Science.gov (United States)

    Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

    2011-02-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition

    NARCIS (Netherlands)

    Goudsmit, J.; Boucher, C. A.; Meloen, R. H.; Epstein, L. G.; Smit, L.; van der Hoek, L.; Bakker, M.

    1988-01-01

    PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino

  4. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  5. High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis.

    Science.gov (United States)

    Weiss, Eric R; Alter, Galit; Ogembo, Javier Gordon; Henderson, Jennifer L; Tabak, Barbara; Bakiş, Yasin; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Luzuriaga, Katherine

    2017-01-01

    The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM. Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a

  6. State of the Science in Heart Failure Symptom Perception Research: An Integrative Review.

    Science.gov (United States)

    Lee, Solim; Riegel, Barbara

    Heart failure (HF) is a common condition requiring self-care to maintain physical stability, prevent hospitalization, and improve quality of life. Symptom perception, a domain of HF self-care newly added to the Situation-Specific Theory of HF Self-Care, is defined as a comprehensive process of monitoring and recognizing physical sensations and interpreting and labeling the meaning of the sensations. The purpose of this integrative review was to describe the research conducted on HF symptom perception to further understanding of this new concept. A literature search was conducted using 8 databases. The search term of HF was combined with symptom, plus symptom perception subconcepts of monitoring, somatic awareness, detection, recognition, interpretation, and appraisal. Only peer-reviewed original articles published in English with full-text availability were included. No historical limits were imposed. Study subjects were adults. Twenty-one studies met the inclusion criteria. Each study was categorized into either symptom monitoring or symptom recognition and interpretation. Although daily weighing and HF-related symptom-monitoring behaviors were insufficient in HF patients, use of a symptom diary improved HF self-care, symptom distress and functional class, and decreased mortality, hospital stay, and medical costs. Most HF patients had trouble recognizing an exacerbation of symptoms. Aging, comorbid conditions, and gradual symptom progression made it difficult to recognize and correctly interpret a symptom exacerbation. Living with others, higher education, higher uncertainty, shorter symptom duration, worse functional class, and an increased number of previous hospitalizations were positively associated with symptom recognition. Existing research fails to capture all of the elements in the theoretical definition of symptom perception.

  7. Speeding up IA mechanically-steered multistatic radar scheduling with GP-GPUs

    CSIR Research Space (South Africa)

    Focke, RW

    2016-07-01

    Full Text Available In this paper, the authors investigate speeding up the execution time of Interval Algebra (IA) mechanically-steered multistatic and multisite radar scheduling using a general-purpose graphical processing unit (GP-GPU). Multistatic/multisite radar...

  8. Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

    Science.gov (United States)

    Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

    2008-01-01

    Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. PMID:9862627

  9. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    International Nuclear Information System (INIS)

    Roche, Julien; Louis, John M.; Aniana, Annie; Ghirlando, Rodolfo; Bax, Ad

    2015-01-01

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion

  10. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  11. Basket Option Pricing Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-08-01

    We introduce a basket option pricing problem arisen in financial mathematics. We discretized the problem based on the alternating direction implicit (ADI) method and parallel cyclic reduction is applied to solve the set of tridiagonal matrices generated by the ADI method. To reduce the computational time of the problem, a general purpose graphics processing units (GP-GPU) environment is considered. Numerical results confirm the convergence and efficiency of the proposed method. © 2010 IEEE.

  12. P-gp expression levels in the erythrocytes of brown trout: a new tool for aquatic sentinel biomarker development.

    Science.gov (United States)

    Valton, Emeline; Wawrzyniak, Ivan; Amblard, Christian; Combourieu, Bruno; Bayle, Marie-Laure; Desmolles, François; Kwiatkowski, Fabrice; Penault-Llorca, Frédérique; Bamdad, Mahchid

    2017-09-01

    P-glycoprotein (P-gp) is a ubiquitous membrane detoxification pump involved in cellular defence against xenobiotics. Blood is a hub for the trade and transport of physiological molecules and xenobiotics. Our recent studies have highlighted the expression of a 140-kDa P-gp in brown trout erythrocytes in primary cell culture and its dose-dependent response to Benzo[a]pyrene pollutant. The purpose of this study was focused on using P-gp expression in brown trout erythrocytes as a biomarker for detecting the degree of river pollution. abcb1 gene and P-gp expression level were analysed by reverse transcriptase-PCR and Western blot, in the erythrocytes of brown trouts. The latter were collected in upstream and downstream of four rivers in which 17 polycyclic aromatic hydrocarbons and 348 varieties of pesticides micro-residues were analysed by liquid chromatography and mass spectrometry. The abcb1 gene and the 140-kDa P-gp were not expressed in trout erythrocytes from uncontaminated river. In contrast, they are clearly expressed in contaminated rivers, in correlation with the river pollution degree and the nature of the pollutants. This biological tool may offer considerable advantages since it provides an effective response to the increasing need for an early biomarker.

  13. Anti-coagulation effect of Fc fragment against anti-β2-GP1 antibodies in mouse models with APS.

    Science.gov (United States)

    Xie, Weidong; Zhang, Yaou; Bu, Cunya; Sun, Shijing; Hu, Shaoliang; Cai, Guoping

    2011-01-01

    Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.

    Directory of Open Access Journals (Sweden)

    Lijun Chao

    Full Text Available The HIV-1 envelope glycoprotein (Env gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521 of the human POB1 (the partner of RalBP1, designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR of gp41, and to the six-helix bundle (6-HB formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.

  15. The Bacteriophage lambdaDNA packaging enzyme: Identification of four structural domains of the gpNu1 subunit using limited proteolysis

    Directory of Open Access Journals (Sweden)

    PAMELA ARAYA

    2001-01-01

    Full Text Available Lambda DNA terminase, the enzyme that cleaves virion-length chromosomes from multigenomic concatemers and packages them into the bacteriophage head, is composed of two subunits, gpNu1 and gpA. Direct determination of the structure of gpNu1, the smaller subunit, has not been possible because of its insolubility in aqueous solutions. Therefore, to identify smaller and potentially water-soluble domains of gpNu1, we analyzed the nature of the products obtained by limited digestion of the protein with several proteases. The gpNu1 subunit was obtained from E.coli cells transfected with the plasmid pH6-Nu1 that overproduces the protein. Incubation of gpNu1 solubized in 2.5 M guanidinium chloride with chymotrypsin resulted in the formation of at least eight discrete protein bands, while treatment with endoproteinase glu-C and bromelain yielded three and one major bands, respectively. The peptides generated by digestion with the various proteases were separated by two-dimensional gel electrophoresis and transferred to Immobilon membranes. Amino acid sequencing of the peptides allowed for the precise assignment of their N-terminal amino acid, while their estimated molecular weights permitted the identification of their C-terminal ends. The results reveal that in the presence of 2.5 M guanidinium chloride, gpNu1 is partially folded in at least four distinct structural domains that correspond to functional domains as determined by previously reported genetic experiments. This information is key to design new plasmids to overproduce these domains for further structural analysis.

  16. Small-angle scattering from GP zones in Al–Cu alloy

    Indian Academy of Sciences (India)

    ... and smallangle scattering experiments were carried on the powdered samples as a function of time during artificial aging. Small-angle scattering data were analysed, and evidence has been obtained for the occurrence of spinodal decomposition as the mechanism responsible in the early stages of formation of GP zones.

  17. Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology

    Directory of Open Access Journals (Sweden)

    Harty Ronald N

    2006-05-01

    Full Text Available Abstract Recently we described a role for Ebola virus proteins, NP, GP, and VP35 in enhancement of VP40 VLP budding. To explore the possibility that VLP structure was altered by co-expression of EBOV proteins leading to the observed enhancement of VP40 VLP budding, we performed density gradient analysis as well as electron microscopy studies. Our data suggest that VP40 is the major determinant of VLP morphology, as co-expression of NP, GP and VP35 did not significantly change VLP density, length, and diameter. Ultra-structural changes were noted in the core of the VLPs when NP was co-expressed with VP40. Overall, these findings indicate that major changes in morphology of VP40 VLPs were likely not responsible for enhanced budding of VP40 VLPs in the presence of GP, NP and/or VP35.

  18. Observing the temperature dependent transition of the GP2 peptide using terahertz spectroscopy.

    Directory of Open Access Journals (Sweden)

    Yiwen Sun

    Full Text Available The GP2 peptide is derived from the Human Epidermal growth factor Receptor 2 (HER2/nue, a marker protein for breast cancer present in saliva. In this paper we study the temperature dependent behavior of hydrated GP2 at terahertz frequencies and find that the peptide undergoes a dynamic transition between 200 and 220 K. By fitting suitable molecular models to the frequency response we determine the molecular processes involved above and below the transition temperature (T(D. In particular, we show that below T(D the dynamic transition is dominated by a simple harmonic vibration with a slow and temperature dependent relaxation time constant and that above T(D, the dynamic behavior is governed by two oscillators, one of which has a fast and temperature independent relaxation time constant and the other of which is a heavily damped oscillator with a slow and temperature dependent time constant. Furthermore a red shifting of the characteristic frequency of the damped oscillator was observed, confirming the presence of a non-harmonic vibration potential. Our measurements and modeling of GP2 highlight the unique capabilities of THz spectroscopy for protein characterization.

  19. Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice.

    Science.gov (United States)

    Piccinelli, Ana Claudia; Morato, Priscila Neder; Dos Santos Barbosa, Marcelo; Croda, Julio; Sampson, Jared; Kong, Xiangpeng; Konkiewitz, Elisabete Castelon; Ziff, Edward B; Amaya-Farfan, Jaime; Kassuya, Cândida Aparecida Leite

    2017-04-01

    We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection. These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. Copyright © 2016. Published by Elsevier Inc.

  20. Computational study of HIV gp120 as a target for polyanionic entry inhibitors: Exploiting the V3 loop region.

    Directory of Open Access Journals (Sweden)

    Louis R Hollingsworth

    Full Text Available Multiple approaches are being utilized to develop therapeutics to treat HIV infection. One approach is designed to inhibit entry of HIV into host cells, with a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have been shown to be effective in inhibiting HIV entry, with a mechanism involving electrostatic interactions with the V3 loop of gp120 being proposed. In this study, we applied computational methods to elucidate molecular interactions between the repeat unit of the precisely alternating polyanion, Poly(4,4'-stilbenedicarboxylate-alt-maleic acid (DCSti-alt-MA and the V3 loop of gp120 from strains of HIV against which these polyanions were previously tested (IIIb, BaL, 92UG037, JR-CSF as well as two strains for which gp120 crystal structures are available (YU2, 2B4C. Homology modeling was used to create models of the gp120 proteins. Using monomers of the gp120 protein, we applied extensive molecular dynamics simulations to obtain dominant morphologies that represent a variety of open-closed states of the V3 loop to examine the interaction of 112 ligands of the repeating units of DCSti-alt-MA docked to the V3 loop and surrounding residues. Using the distance between the V1/V2 and V3 loops of gp120 as a metric, we revealed through MD simulations that gp120 from the lab-adapted strains (BaL and IIIb, which are more susceptible to inhibition by DCSti-alt-MA, clearly transitioned to the closed state in one replicate of each simulation set, whereas none of the replicates from the Tier II strains (92UG037 and JR-CSF did so. Docking repeat unit microspecies to the gp120 protein before and after MD simulation enabled identification of residues that were key for binding. Notably, only a few residues were found to be important for docking both before and after MD simulation as a result of the conformational heterogeneity provided by the simulations. Consideration of the residues that were consistently involved in interactions

  1. Council tax valuation bands and contacts with a GP out-of-hours service.

    Science.gov (United States)

    Beale, Norman; Taylor, Gordon; Gwynne, Mark; Peart, Carole

    2006-04-01

    UK GPs are no longer responsible for the organisation of out-of-hours care for their patients, but resources remains capitation-based. This cross-sectional study tests whether council tax valuation bands can predict the demand for such services. All out-of-hours contacts made by patients in North Wiltshire over 4 months were classified by council tax band; frequencies compared with official population statistics. Council tax band predicts out-of-hours GP workload irrespective of age and sex: the more modest the home, the higher the GP contact rate. It may prove more difficult to sustain out-of-hours services in deprived parts of the UK.

  2. Public perception of mental health in Iraq

    Directory of Open Access Journals (Sweden)

    Al-Hasoon Saad

    2010-10-01

    Full Text Available Abstract Background People who suffer from mental illness, the professionals who treat them, and indeed the actual concept of mental illness are all stigmatised in public perception and often receive very negative publicity. This paper looks at Iraq, which has a population of 30 million who are mainly Moslem. Mental health services and professionals have historically been sparse in Iraq with 1 psychiatrist per 300,000 before 2003 falling to 1 per million until recently and 1 primary care centre (40 Healthcare Workers including 4 General Practitioners to 35,000 population, compared with 1 GP per 1700 population in the UK. Methods We aimed to assess public attitudes and perceptions to mental illness. Participants were asked to complete a questionnaire (additional file 1, which was designed specifically for Iraqi contexts and was made available in 2 languages. The survey was carried out in 500 participants' homes across 2 districts of Baghdad. Additional file 1 Public Perception of Mental Illness Questionnaire. Click here for file Results The response rate of the survey was 86.4%. The paper shows respondents views on the aetiology of mental illness, perceptions of people with mental illness and attitudes towards care and treatment of people with mental illness. Conclusions This survey of public attitudes towards mental illness in Iraq has shown that community opinion about the aetiology of mental illness is broadly compatible with scientific evidence, but understanding of the nature of mental illness, its implications for social participation and management remains negative in general.

  3. Assessment of reliability of Greulich and Pyle (gp) method for ...

    African Journals Online (AJOL)

    Background: Greulich and Pyle standards are the most widely used age estimation standards all over the world. The applicability of the Greulich and Pyle standards to populations which differ from their reference population is often questioned. This study aimed to assess the reliability of Greulich and Pyle (GP) method for ...

  4. A RESEARCH ON CORPORATE SOCIAL RESPONSIBILITY PERCEPTIONS OF MARITIME FACULTY STUDENTS

    OpenAIRE

    KAYA ÖZBAĞ, Gönül

    2017-01-01

    Corporate Social Responsibility(CSR) concept has attracted considerable interest in recent years byresearchers and practitioners. Due to an increased awareness of theneed for CSR this study examines corporate social responsibility perceptions ofmaritime faculty students (MFS).  MFSwere chosen for this research since these students are usually employed by aninternational organization and have diffuculties in interpreting ethical issuesin a business context because of...

  5. Chinese Teaching English as a Foreign Language (TEFL) Academics' Perceptions about Research in a Transitional Culture

    Science.gov (United States)

    Bai, Li; Millwater, Jan; Hudson, Peter

    2012-01-01

    Research capacity building has become a prominent theme in higher education institutions in China and across the world. However, Chinese Teaching English as a Foreign Language academics' research output has been quite limited. In order to build their research capacity, it is necessary to understand their perceptions about research. This case study…

  6. Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors

    Directory of Open Access Journals (Sweden)

    Jacqueline Ameri

    2017-04-01

    Full Text Available Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2 as a specific cell surface marker for isolating pancreatic endoderm cells (PECs from differentiated hESCs and human fetal pancreas. Isolated GP2+ PECs efficiently differentiated into glucose responsive insulin-producing cells in vitro. We found that in vitro PEC proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK inhibitors CDKN1A and CDKN2A. However, we identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2+ PECs. Altogether, our results contribute tools and concepts toward the isolation and use of PECs as a source for the safe production of hPSC-derived β cells.

  7. The major surface glycoprotein (gp63) from Leishmania major and Leishmania donovani cleaves CD4 molecules on human T cells

    DEFF Research Database (Denmark)

    Hey, A S; Theander, T G; Hviid, L

    1994-01-01

    The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4......-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against other surface markers present on human T-cells--CD2, CD3, CD5......, CD8, CD11A, CD25, CD45RO, CD45RA, CD58, TCR-alpha, TCR-gamma, and HLA DQ--was not inhibited by gp63. These data suggest that gp63, both in its purified form and in the form anchored to the parasite membrane, cleaves CD4 on human T cells. The cleavage of CD4 by the protease might play a role...

  8. Some recent research findings on the social dynamics of environmental risk perception

    International Nuclear Information System (INIS)

    Horlick-Jones, T.; Marchi, B. de; Del Zotto, M.; Pellizzoni, L.; Ungaro, D.; Prades Lopez, A.; Diaz Hidalgo, M.; Pidgeon, N.; Sime, J.

    1998-01-01

    Full text of publication follows: key themes: social dynamics of public risk perception; trust, tolerability, and risk management; discourses of environmental risk; implications for risk communication and environmental valuation; application of mixed qualitative/quantitative methods in risk perception research. This paper presents some of the key findings of a two-year comparative European study (the PRISP Project) on public perception of risks associated with industrial sites in the UK, Italy and Spain. The project utilised a mixed-method approach (comprising community ethnography, semi-structured interviews, questionnaire survey and focus groups), within a Grounded Theory framework, to examine the social dynamics of risk comprehension, tolerability and politics in settings adjacent to a range of industrial facilities. These often complex industrial zones present a portfolio of 'acute' and 'chronic' risks including hazards associated with sites regulated by the European Union COMAH Directive. Our findings have important implications for the regulation of both major accident hazard and pollution risks, risk communication programmes, industrial risk management practices and for the methodological basis of health and safety and environmental valuation techniques. (authors)

  9. Traditional Chinese medicine research in the post-genomic era: good practice, priorities, challenges and opportunities.

    Science.gov (United States)

    Uzuner, Halil; Bauer, Rudolf; Fan, Tai-Ping; Guo, De-An; Dias, Alberto; El-Nezami, Hani; Efferth, Thomas; Williamson, Elizabeth M; Heinrich, Michael; Robinson, Nicola; Hylands, Peter J; Hendry, Bruce M; Cheng, Yung-Chi; Xu, Qihe

    2012-04-10

    GP-TCM is the 1st EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. This paper aims to summarise the objectives, structure and activities of the consortium and introduces the position of the consortium regarding good practice, priorities, challenges and opportunities in TCM research. Serving as the introductory paper for the GP-TCM Journal of Ethnopharmacology special issue, this paper describes the roadmap of this special issue and reports how the main outputs of the ten GP-TCM work packages are integrated, and have led to consortium-wide conclusions. Literature studies, opinion polls and discussions among consortium members and stakeholders. By January 2012, through 3 years of team building, the GP-TCM consortium had grown into a large collaborative network involving ∼200 scientists from 24 countries and 107 institutions. Consortium members had worked closely to address good practice issues related to various aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of this Journal of Ethnopharmacology special issue, leading to state-of-the-art reports, guidelines and consensus on the application of omics technologies in TCM research. In addition, through an online survey open to GP-TCM members and non-members, we polled opinions on grand priorities, challenges and opportunities in TCM research. Based on the poll, although consortium members and non-members had diverse opinions on the major challenges in the field, both groups agreed that high-quality efficacy/effectiveness and mechanistic studies are grand priorities and that the TCM legacy in general and its management of chronic diseases in particular represent grand opportunities. Consortium members cast their votes of confidence in omics and systems biology approaches to TCM research and believed that quality and pharmacovigilance of TCM products are not only grand priorities, but also grand challenges. Non-members, however, gave priority

  10. Features of Perception of Modern Russian Political Leaders in University Students (A Psychosemantic Research

    Directory of Open Access Journals (Sweden)

    Sobkin V.S.

    2015-09-01

    Full Text Available The paper presents outcomes of a research on features of perception of modern Russian political leaders in young people. A technique of multidimensional semantic differential was employed: the subjects were asked to assess 15 objects (political leaders, 'my ideal', 'ideal leader', 'antipathetic person' and 'Myself' according to 33 personality traits using a seven-point scale. The outcomes suggest that the structure of the students' perception of political leaders is quite simple and is based on three modalities: 'morality', 'power' and 'intelligence'. Comparing these outcomes with the research data obtained in 2004 using the same technique allowed the authors to conclude that the students do not assess modern political leaders according to the moral qualities of the latter, but rather perceive them through the qualities of power associated with social manipulation.

  11. A loudspeaker-based room auralization system for auditory perception research

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Favrot, Sylvain Emmanuel

    2009-01-01

    Most research on basic auditory function has been conducted in anechoic or almost anechoic environments. The knowledge derived from these experiments cannot directly be transferred to reverberant environments. In order to investigate the auditory signal processing of reverberant sounds....... This system provides a flexible research platform for conducting auditory experiments with normal-hearing, hearing-impaired, and aided hearing-impaired listeners in a fully controlled and realistic environment. This includes measures of basic auditory function (e.g., signal detection, distance perception......) and measures of speech intelligibility. A battery of objective tests (e.g., reverberation time, clarity, interaural correlation coefficient) and subjective tests (e.g., speech reception thresholds) is presented that demonstrates the applicability of the LoRA system....

  12. A competency based selection procedure for Dutch postgraduate GP training: a pilot study on validity and reliability.

    Science.gov (United States)

    Vermeulen, Margit I; Tromp, Fred; Zuithoff, Nicolaas P A; Pieters, Ron H M; Damoiseaux, Roger A M J; Kuyvenhoven, Marijke M

    2014-12-01

    Abstract Background: Historically, semi-structured interviews (SSI) have been the core of the Dutch selection for postgraduate general practice (GP) training. This paper describes a pilot study on a newly designed competency-based selection procedure that assesses whether candidates have the competencies that are required to complete GP training. The objective was to explore reliability and validity aspects of the instruments developed. The new selection procedure comprising the National GP Knowledge Test (LHK), a situational judgement tests (SJT), a patterned behaviour descriptive interview (PBDI) and a simulated encounter (SIM) was piloted alongside the current procedure. Forty-seven candidates volunteered in both procedures. Admission decision was based on the results of the current procedure. Study participants did hardly differ from the other candidates. The mean scores of the candidates on the LHK and SJT were 21.9 % (SD 8.7) and 83.8% (SD 3.1), respectively. The mean self-reported competency scores (PBDI) were higher than the observed competencies (SIM): 3.7(SD 0.5) and 2.9(SD 0.6), respectively. Content-related competencies showed low correlations with one another when measured with different instruments, whereas more diverse competencies measured by a single instrument showed strong to moderate correlations. Moreover, a moderate correlation between LHK and SJT was found. The internal consistencies (intraclass correlation, ICC) of LHK and SJT were poor while the ICC of PBDI and SIM showed acceptable levels of reliability. Findings on content validity and reliability of these new instruments are promising to realize a competency based procedure. Further development of the instruments and research on predictive validity should be pursued.

  13. GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

    Directory of Open Access Journals (Sweden)

    Sabnis Gauri

    2011-06-01

    Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

  14. [Characteristics of beneficiaries of a GP-centred health care contract in Germany].

    Science.gov (United States)

    Freund, Tobias; Szecsenyi, Joachim; Ose, Dominik

    2010-11-01

    Since 2004, primary care in Germany has increasingly been provided in special general practitioner (GP)-centred health care contracts (HZV). To date there is limited evidence about the characteristics of their beneficiaries regarding morbidity burden and health care utilization. We analysed insurance claims data from all beneficiaries of the "Allgemeine Ortskrankenkasse (AOK) Baden-Württemberg" listed in 10 general practices that contracted in a special GP-centred health care contract (HZV). We compared beneficiaries enrolled in the HZV with those who were not enrolled in the contract. Comparisons included the number of hospital admissions in 2007-2008 and the Charlson comorbidity index. Insurance claims data of 6,026 beneficiaries were available for analysis. In the third quarter of 2009, 51% (3,066) of the beneficiaries were enrolled in the HZV. They were significantly older (mean 61 years [SD 18 years] vs. 49 years [SD 22 years]; p contract tended to be older and suffered from a higher morbidity burden when compared with beneficiaries of the same health care fund who were not enrolled in the contract. Besides, beneficiaries of the contract had higher numbers of hospital admissions during the two year period before enrolment. These findings have substantial implications for individualized care management approaches that may be offered to beneficiaries of GP-centred health care contracts.

  15. Leading US nano-scientists' perceptions about media coverage and the public communication of scientific research findings

    Science.gov (United States)

    Corley, Elizabeth A.; Kim, Youngjae; Scheufele, Dietram A.

    2011-12-01

    Despite the significant increase in the use of nanotechnology in academic research and commercial products over the past decade, there have been few studies that have explored scientists' perceptions and attitudes about the technology. In this article, we use survey data from the leading U.S. nano-scientists to explore their perceptions about two issues: the public communication of research findings and media coverage of nanotechnology, which serves as one relatively rapid outlet for public communication. We find that leading U.S. nano-scientists do see an important connection between the public communication of research findings and public attitudes about science. Also, there is a connection between the scientists' perceptions about media coverage and their views on the timing of public communication; scientists with positive attitudes about the media are more likely to support immediate public communication of research findings, while others believe that communication should take place only after research findings have been published through a peer-review process. We also demonstrate that journalists might have a more challenging time getting scientists to talk with them about nanotechnology news stories because nano-scientists tend to view media coverage of nanotechnology as less credible and less accurate than general science media coverage. We conclude that leading U.S. nano-scientists do feel a sense of responsibility for communicating their research findings to the public, but attitudes about the timing and the pathway of that communication vary across the group.

  16. Leading US nano-scientists’ perceptions about media coverage and the public communication of scientific research findings

    International Nuclear Information System (INIS)

    Corley, Elizabeth A.; Kim, Youngjae; Scheufele, Dietram A.

    2011-01-01

    Despite the significant increase in the use of nanotechnology in academic research and commercial products over the past decade, there have been few studies that have explored scientists’ perceptions and attitudes about the technology. In this article, we use survey data from the leading U.S. nano-scientists to explore their perceptions about two issues: the public communication of research findings and media coverage of nanotechnology, which serves as one relatively rapid outlet for public communication. We find that leading U.S. nano-scientists do see an important connection between the public communication of research findings and public attitudes about science. Also, there is a connection between the scientists’ perceptions about media coverage and their views on the timing of public communication; scientists with positive attitudes about the media are more likely to support immediate public communication of research findings, while others believe that communication should take place only after research findings have been published through a peer-review process. We also demonstrate that journalists might have a more challenging time getting scientists to talk with them about nanotechnology news stories because nano-scientists tend to view media coverage of nanotechnology as less credible and less accurate than general science media coverage. We conclude that leading U.S. nano-scientists do feel a sense of responsibility for communicating their research findings to the public, but attitudes about the timing and the pathway of that communication vary across the group.

  17. Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail

    Directory of Open Access Journals (Sweden)

    Takeo eKuwata

    2013-05-01

    Full Text Available The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1 infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of nonhuman primates with simian immunodeficiency virus (SIV is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7900-fold, 1000-fold, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody.

  18. PARTAKE survey of public knowledge and perceptions of clinical research in India.

    Directory of Open Access Journals (Sweden)

    Tal Burt

    Full Text Available BACKGROUND: A public that is an informed partner in clinical research is important for ethical, methodological, and operational reasons. There are indications that the public is unaware or misinformed, and not sufficiently engaged in clinical research but studies on the topic are lacking. PARTAKE - Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment is a program aimed at increasing public awareness and partnership in clinical research. The PARTAKE Survey is a component of the program. OBJECTIVE: To study public knowledge and perceptions of clinical research. METHODS: A 40-item questionnaire combining multiple-choice and open-ended questions was administered to 175 English- or Hindi-speaking individuals in 8 public locations representing various socioeconomic strata in New Delhi, India. RESULTS: Interviewees were 18-84 old (mean: 39.6, SD ± 16.6, 23.6% female, 68.6% employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and 58.9% expressed willingness to participate in clinical research. The following perceptions were reported (% true/% false/% not aware: 'research benefits society' (94.1%/3.5%/2.3%, 'the government protects against unethical clinical research' (56.7%/26.3%/16.9%, 'research hospitals provide better care' (67.2%/8.7%/23.9%, 'confidentiality is adequately protected' (54.1%/12.3%/33.5%, 'participation in research is voluntary' (85.3%/5.8%/8.7%; 'participants treated like 'guinea pigs'' (20.7%/53.2%/26.0%, and 'compensation for participation is adequate' (24.7%/12.9%/62.3%. CONCLUSIONS: Results suggest the Indian public is aware of some key features of clinical research (e.g., purpose, value, voluntary nature of participation, and supports clinical research in general but is unaware of other key features (e.g., compensation, confidentiality, protection of human participants and exhibits some distrust in the conduct and reporting of clinical trials. Larger, cross

  19. A study of role expansion: a new GP role in cardiology care

    Science.gov (United States)

    2014-01-01

    Background The National Health Service is reconfiguring health care services in order to meet the increasing challenge of providing care for people with long-term conditions and to reduce the demand on specialised outpatient hospital services by enhancing primary care. A review of cardiology referrals to specialised care and the literature on referral management inspired the development of a new GP role in Cardiology. This new extended role was developed to enable GPs to diagnose and manage patients with mild to moderate heart failure or atrial fibrillation and to use a range of diagnostics effectively in primary care. This entailed GPs participating in a four-session short course with on-going clinical supervision. The new role was piloted in a small number of GP practices in one county in England for four months. This study explores the impact of piloting the Extended Cardiology role on the GP’s role, patients’ experience, service delivery and quality. Methods A mixed methods approach was employed including semi-structured interviews with GPs, a patient experience survey, a quality review of case notes, and analysis on activity and referral data. Results The participating GPs perceived the extended GP role as a professional development opportunity that had the potential to reduce healthcare utilisation and costs, through a reduction in referrals, whilst meeting the patient’s wishes for the provision of care closer to home. Patient experience of the new GP service was positive. The standard of clinical practice was judged acceptable. There was a fall in referrals during the study period. Conclusion This new role in cardiology was broadly welcomed as a model of care by the participating GPs and by patients, because of the potential to improve the quality of care for patients in primary care and reduce costs. As this was a pilot study further development and continuing evaluation of the model is recommended. PMID:24885826

  20. User Fees in General Practice: Willingness to Pay and Potential Substitution Patterns-Results from a Danish GP Patient Survey.

    Science.gov (United States)

    Kronborg, Christian; Pedersen, Line Bjørnskov; Fournaise, Anders; Kronborg, Christel Nøhr

    2017-10-01

    Increases in public expenditures to general practitioner (GP) services and specialist care have spurred debate over whether to implement user fees for healthcare services such as GP consultations in Denmark. The objective of this study was to examine Danish patients' attitudes towards user fees and their willingness to pay (WTP) for a consultation, and to investigate how user charges may impact patients' behaviour. A questionnaire survey was conducted in a GP clinic. A total of 343 individual persons answered the questionnaire. One hundred and seventy (50%) persons were not willing to pay for a consultation. Among patients reporting positive WTP values, the mean WTP was 137 (standard deviation 140) Danish kroner (DKK). Patients who were 65 years old or older were more likely to be willing to pay for a GP consultation than patients under the age of 65 years. Furthermore, patients with a personal annual income of more than 200,000 DKK were more likely to be willing to pay for a consultation than other income groups. With respect to patients with a positive WTP value, their own assessment of the seriousness of the consultation and their self-assessed health influenced the amount they would be willing to pay. Finally, we observed a stated willingness to substitute GP consultations with alternatives that are free of charge. About half of the patients with an appointment for a GP consultation are willing to pay for the consultation. User charges may potentially influence the patients' behaviour. ClinicalTrials.gov NCT01784731.

  1. Generation of X-CGD cells for vector evaluation from healthy donor CD34+ HSCs by shRNA-mediated knock down of gp91phox

    Directory of Open Access Journals (Sweden)

    Christian Brendel

    2014-01-01

    Full Text Available Innovative approaches for the treatment of rare inherited diseases are hampered by limited availability of patient derived samples for preclinical research. This also applies for the evaluation of novel vector systems for the gene therapy of monogenic hematological diseases like X-linked chronic granulomatous disease (X-CGD, a severe primary immunodeficiency caused by mutations in the gp91phox subunit of the phagocytic NADPH oxidase. Since current gene therapy protocols involve ex vivo gene modification of autologous CD34+ hematopoietic stem cells (HSC, the ideal preclinical model should simulate faithfully this procedure. However, the low availability of patient-derived CD34+ cells limits the feasibility of this approach. Here, we describe a straightforward experimental strategy that circumvents this limitation. The knock down of gp91phox expression upon lentiviral delivery of shRNAs into CD34+ cells from healthy donors generates sufficient amounts of X-CGD CD34+ cells which subsequently can be used for the evaluation of novel gene therapeutic strategies using a codon-optimized gp91phox transgene. We have used this strategy to test the potential of a novel gene therapy vector for X-CGD.

  2. Are patients’ preferences regarding the place of treatment heard and addressed at the point of referral: an exploratory study based on observations of GP-patient consultations

    Science.gov (United States)

    2013-01-01

    Background Today, in several north-western European countries, patients are encouraged to choose, actively, a healthcare provider. However, patients often visit the provider that is recommended by their general practitioner (GP). The introduction of patient choice requires GPs to support patients to be involved, actively, in the choice of a healthcare provider. We aim to investigate whether policy on patient choice is reflected in practice, i.e. what the role of the patient is in their choices of healthcare providers at the point of referral and to what extent GPs’ and patients’ healthcare paths influence the role that patients play in the referral decision. Methods In 2007–2008, we videotaped Dutch GP-patient consultations. For this study, we selected, at random, 72 videotaped consultations between 72 patients and 39 GPs in which the patient was referred to a healthcare provider. These were analysed using an observation protocol developed by the researchers. Results The majority of the patients had little or no input into the choice of a healthcare provider at the point of referral by their GP. Their GPs did not support them in actively choosing a provider and the patients often agreed with the provider that the GP proposed. Patients who were referred for diagnostic purposes seem to have had even less input into their choice of a provider than patients who were referred for treatment. Conclusions We found that the GP chooses a healthcare provider on behalf of the patient in most consultations, even though policy on patient choice expects from patients that they choose, actively, a provider. On the one hand, this could indicate that the policy needs adjustments. On the other hand, adjustments may be needed to practice. For instance, GPs could help patients to make an active choice of provider. However, certain patients prefer to let their GP decide as their agent. Even then, GPs need to know patients’ preferences, because in a principal-agent relationship

  3. Are patients' preferences regarding the place of treatment heard and addressed at the point of referral: an exploratory study based on observations of GP-patient consultations.

    Science.gov (United States)

    Victoor, Aafke; Noordman, Janneke; Sonderkamp, Johan A; Delnoij, Diana M J; Friele, Roland D; van Dulmen, Sandra; Rademakers, Jany J D J M

    2013-12-10

    Today, in several north-western European countries, patients are encouraged to choose, actively, a healthcare provider. However, patients often visit the provider that is recommended by their general practitioner (GP). The introduction of patient choice requires GPs to support patients to be involved, actively, in the choice of a healthcare provider. We aim to investigate whether policy on patient choice is reflected in practice, i.e. what the role of the patient is in their choices of healthcare providers at the point of referral and to what extent GPs' and patients' healthcare paths influence the role that patients play in the referral decision. In 2007-2008, we videotaped Dutch GP-patient consultations. For this study, we selected, at random, 72 videotaped consultations between 72 patients and 39 GPs in which the patient was referred to a healthcare provider. These were analysed using an observation protocol developed by the researchers. The majority of the patients had little or no input into the choice of a healthcare provider at the point of referral by their GP. Their GPs did not support them in actively choosing a provider and the patients often agreed with the provider that the GP proposed. Patients who were referred for diagnostic purposes seem to have had even less input into their choice of a provider than patients who were referred for treatment. We found that the GP chooses a healthcare provider on behalf of the patient in most consultations, even though policy on patient choice expects from patients that they choose, actively, a provider. On the one hand, this could indicate that the policy needs adjustments. On the other hand, adjustments may be needed to practice. For instance, GPs could help patients to make an active choice of provider. However, certain patients prefer to let their GP decide as their agent. Even then, GPs need to know patients' preferences, because in a principal-agent relationship, it is necessary that the agent is fully

  4. Delivery of siRNA silencing P-gp in peptide-functionalized nanoparticles causes efflux modulation at the blood-brain barrier

    DEFF Research Database (Denmark)

    Gomes, Maria João; Kennedy, Patrick J; Martins, Susana

    2017-01-01

    AIM: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood-brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). MATERIALS & METHODS: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression...

  5. PARTAKE Survey of Public Knowledge and Perceptions of Clinical Research in India

    Science.gov (United States)

    Burt, Tal; Dhillon, Savita; Sharma, Pooja; Khan, Danish; MV, Deepa; Alam, Sazid; Jain, Sarika; Alapati, Bhavana; Mittal, Sanjay; Singh, Padam

    2013-01-01

    Background A public that is an informed partner in clinical research is important for ethical, methodological, and operational reasons. There are indications that the public is unaware or misinformed, and not sufficiently engaged in clinical research but studies on the topic are lacking. PARTAKE – Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment is a program aimed at increasing public awareness and partnership in clinical research. The PARTAKE Survey is a component of the program. Objective To study public knowledge and perceptions of clinical research. Methods A 40-item questionnaire combining multiple-choice and open-ended questions was administered to 175 English- or Hindi-speaking individuals in 8 public locations representing various socioeconomic strata in New Delhi, India. Results Interviewees were 18–84 old (mean: 39.6, SD±16.6), 23.6% female, 68.6% employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and 58.9% expressed willingness to participate in clinical research. The following perceptions were reported (% true/% false/% not aware): ‘research benefits society’ (94.1%/3.5%/2.3%), ‘the government protects against unethical clinical research’ (56.7%/26.3%/16.9%), ‘research hospitals provide better care’ (67.2%/8.7%/23.9%), ‘confidentiality is adequately protected’ (54.1%/12.3%/33.5%), ‘participation in research is voluntary’ (85.3%/5.8%/8.7%); ‘participants treated like ‘guinea pigs’’ (20.7%/53.2%/26.0%), and ‘compensation for participation is adequate’ (24.7%/12.9%/62.3%). Conclusions Results suggest the Indian public is aware of some key features of clinical research (e.g., purpose, value, voluntary nature of participation), and supports clinical research in general but is unaware of other key features (e.g., compensation, confidentiality, protection of human participants) and exhibits some distrust in the conduct and reporting of clinical trials

  6. Australian general practitioner perceptions of the detection and screening of at-risk drinking, and the role of the AUDIT-C: a qualitative study.

    Science.gov (United States)

    Tam, Chun Wah Michael; Zwar, Nicholas; Markham, Roslyn

    2013-08-20

    At-risk drinking is common in Australia. Validated screening tools such as the AUDIT-C have been promoted to general practitioners (GPs), but appear rarely used and detection of at-risk drinking in primary care remains low. We sought to describe Australian GP perceptions of the detection and screening of at-risk drinking; to understand their low uptake of alcohol screening questionnaires, and in particular, their attitude to the adoption of the AUDIT-C. Semi-structured focus group interviews of four groups of GPs and GP trainees were conducted in metropolitan Sydney between August and October 2011. Audio recordings were transcribed and analysed using grounded theory methodology. We identified four main themes: there was consensus that detecting at-risk drinking is important but difficult to do, social and cultural attitudes to alcohol consumption affect willingness to ask questions about its use, the dynamics of patient-doctor interactions are important, and alcohol screening questionnaires lack practical utility. Analysis suggests that the conceptual barriers to detecting at-risk drinking were: community stigma and stereotypes of "problem drinking", GP perceptions of unreliable patient alcohol use histories, and the perceived threat to the patient-doctor relationship. This small exploratory study found that the practice of, and barriers to, detecting at-risk drinking appear to be inextricably linked to the sociocultural beliefs surrounding alcohol use. Screening questionnaires such as the AUDIT-C are not designed to address these issues. In the current context, it is unlikely that approaches that focus on the use of these tools will be effective at improving detection of at-risk drinking by GPs.

  7. Structural improvement of unliganded simian immunodeficiency virus gp120 core by normal-mode-based X-ray crystallographic refinement

    International Nuclear Information System (INIS)

    Chen, Xiaorui; Lu, Mingyang; Poon, Billy K.; Wang, Qinghua; Ma, Jianpeng

    2009-01-01

    The structural model of the unliganded and fully glycosylated simian immunodeficiency virus gp120 core determined to 4.0 Å resolution was substantially improved using a recently developed normal-mode-based anisotropic B-factor refinement method. The envelope protein gp120/gp41 of simian and human immunodeficiency viruses plays a critical role in viral entry into host cells. However, the extraordinarily high structural flexibility and heavy glycosylation of the protein have presented enormous difficulties in the pursuit of high-resolution structural investigation of some of its conformational states. An unliganded and fully glycosylated gp120 core structure was recently determined to 4.0 Å resolution. The rather low data-to-parameter ratio limited refinement efforts in the original structure determination. In this work, refinement of this gp120 core structure was carried out using a normal-mode-based refinement method that has been shown in previous studies to be effective in improving models of a supramolecular complex at 3.42 Å resolution and of a membrane protein at 3.2 Å resolution. By using only the first four nonzero lowest-frequency normal modes to construct the anisotropic thermal parameters, combined with manual adjustments and standard positional refinement using REFMAC5, the structural model of the gp120 core was significantly improved in many aspects, including substantial decreases in R factors, better fitting of several flexible regions in electron-density maps, the addition of five new sugar rings at four glycan chains and an excellent correlation of the B-factor distribution with known structural flexibility. These results further underscore the effectiveness of this normal-mode-based method in improving models of protein and nonprotein components in low-resolution X-ray structures

  8. Gender and personal breastfeeding experience of rural GP registrars in Australia--a qualitative study of their effect on breastfeeding attitudes and knowledge.

    Science.gov (United States)

    Brodribb, W E; Jackson, C; Fallon, A B; Hegney, D

    2007-01-01

    While most doctors believe they have a major role to play in breastfeeding promotion, and consider it worthwhile taking time to assist women to continue to breastfeed, it appears that gender and personal breastfeeding experience affect their attitude and confidence concerning breastfeeding issues. As doctors practicing in rural and regional areas may be expected to provide a greater degree of assistance and support for breastfeeding women, their views on these topics are of particular interest. This article reports the results of qualitative interviews with eight GP registrars from rural and regional Australia, and their views about the influence gender and personal experience have on their ability to assist breastfeeding women. The study is part of a larger project investigating the breastfeeding skills and knowledge of GP registrars as a basis for designing a tailored educational breastfeeding resource. This project uses mixed methods and triangulation of data. Semi-structured, one-on-one interviews were conducted with eight GP registrars from southern Queensland, Australia. The participants were chosen so that there were eight unique combinations of age ( or =34), gender (male or female) and breastfeeding experience (self or spouse had breastfed/had not breastfed) to ensure diversity of responses and increase the transferability of results. Demographics were collected from each participant, as well as information about: their attitudes to breastfeeding and to counselling breastfeeding women; their perception of breastfeeding knowledge needs and their confidence assisting breastfeeding women; and prior training about breastfeeding. Transcripts of the recorded interviews were returned to the participants for verification before analysis. Emergent themes were identified both within and between interviews following content analysis. Four male and four female registrars with a mean age of 35 years (range 28-43 years) were recruited. Two participants of each gender

  9. Development of out-of-hours primary care by general practitioners (GPs) in The Netherlands: from small-call rotations to large-scale GP cooperatives.

    Science.gov (United States)

    van Uden, Caro J T; Giesen, Paul H J; Metsemakers, Job F M; Grol, Richard P T M

    2006-09-01

    Over the last 10 years, care outside office hours by primary care physicians in The Netherlands has experienced a radical change. While Dutch general practitioners (GPs) formerly performed these services in small-call rotations, care is nowadays delivered by large-scale GP cooperatives. We searched the literature for relevant studies on the effect of the out-of-hours care reorganization in The Netherlands. We identified research that included before- and afterintervention studies, descriptive studies, and surveys. These studies focused on the consequences of reorganizing several aspects of out-of-hours care, such as patient and GP satisfaction, patient characteristics, utilization of care, and costs. Various studies showed that the reorganization has successfully addressed many of the critical issues that Dutch GPs were confronted with delivering these services. GPs' job satisfaction has increased, and patients seem to be satisfied with current out-of-hours care. Several aspects of out-of-hours care are discussed, such as telephone triage, self referrals, and future expectations, which should receive extra attention by researchers and health policy makers in the near future.

  10. Participation in environmental health research by placenta donation - a perception study

    DEFF Research Database (Denmark)

    Lind, Uffe; Mose, Tina; Knudsen, Lisbeth E

    2007-01-01

    background information but no follow up. METHODS: Nineteen semi-structured qualitative interviews were conducted with participants in the placenta perfusion study after donation of placenta. Observation studies were made of recruitment sessions. RESULTS: The interviewed participants are generally in favour......, but trust is something which needs to be created through "trust-work". Face-to-face interaction, written information material and informed consent forms play important parts in creating trusting relationships in medical research. CONCLUSION: Medical research ethics do not only amount to specific types......BACKGROUND: Much environmental health research depends on human volunteers participating with biological samples. The perception study explores why and how people participate in a placenta perfusion study in Copenhagen. The participation implies donation of the placenta after birth and some...

  11. Value of combined detection of serum AFP and GP73 in early diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    GAO Haifeng

    2014-07-01

    Full Text Available ObjectiveTo investigate the value of combined detection of serum alpha-fetoprotein (AFP and Golgi protein-73 (GP73 in the diagnosis of hepatocellular carcinoma (HCC and to provide a basis for early diagnosis and differential diagnosis of HCC. MethodsA total of 408 patients hospitalized in Baoji Central Hospital from June 2012 to May 2013, as well as healthy persons who had normal test results in physical examination, were included in the study, and their specimens were collected. These patients were classified into HCC group (n=142, chronic hepatitis group (n=156, and liver cirrhosis group (n=110. Serum levels of AFP and GP73 in the three groups were measured by electrochemiluminescence immunoassay and double-antibody sandwich enzyme-linked immunosorbent assay, respectively. Comparison of test results between groups was made by analysis of variance, and comparison of rates was made by chi-square test. The sensitivity and specificity of the two indicators for the diagnosis of HCC were calculated using MedCalc statistical software. ResultsThe HCC group had significantly higher serum AFP and GP73 levels than the liver cirrhosis group and chronic hepatitis group (P<0.05; the liver cirrhosis group had significantly higher serum AFP and GP73 levels than the chronic hepatitis group (P<0.05. The sensitivity and specificity of the two indicators for the diagnosis of HCC were 95.8% and 98.6%, respectively, showing significant differences compared with those of each indicator alone (P<0.05. ConclusionCombined detection of serum AFP and GP73 has high diagnostic value and clinical significance for HCC, and they can be used as indicators for early diagnosis and differential diagnosis of HCC.

  12. Beyond the Law: A Review of Knowledge, Attitudes and Perceptions in ADA Employment Research

    Directory of Open Access Journals (Sweden)

    Robert Gould

    2015-09-01

    Full Text Available The Americans with Disabilities Act (ADA, 1990 is the cornerstone of civil rights policy for people with disabilities. Although enforced through the justice system, the legacy of the ADA transcends well beyond its legal ramifications. The policy’s framework and the rhetoric of Disability Rights suggest both an embrace of the spirit and the letter of the law, or promulgating both legislative and cultural change to ensure that the rights of people with disabilities are met.  In attempting to understand how and if such change has happened, researchers have gathered extensive evidence since 1990.  Much of this research evidence, however, remains fragmented, under-utilized, and at times inconclusive.  This article presents the results of a rapid evidence review of a sample of such research that is crucial to understand the ADA’s progress.  The study examines evidence about the ADA’s influence on knowledge, attitudes and perceptions about employment of people with disabilities. The research illustrates the importance of moving beyond the law to incorporate changes in knowledge about the law, perceptions of employability, and workplace culture.

  13. What is social about social perception research?

    Directory of Open Access Journals (Sweden)

    Christoph eTeufel

    2013-01-01

    Full Text Available A growing consensus in social cognitive neuroscience holds that large portions of the primate visual brain are dedicated to the processing of social information, i.e., to those aspects of stimuli that are usually encountered in social interactions such as others’ facial expressions, actions and symbols. Yet, studies of social perception have mostly employed simple pictorial representations of conspecifics. These stimuli are social only in the restricted sense that they physically resemble objects with which the observer would typically interact. In an equally important sense, however, these stimuli might be regarded as ‘non-social’: the observer knows that they are viewing pictures and might therefore not attribute current mental states to the stimuli or might do so in a qualitatively different way than in a real social interaction. Recent studies have demonstrated the importance of such higher-order conceptualisation of the stimulus for social perceptual processing. Here, we assess the similarity between the various types of stimuli used in the laboratory and object classes encountered in real social interactions. We distinguish two different levels at which experimental stimuli can match social stimuli as encountered in everyday social settings: (i the extent to which a stimulus’ physical properties resemble those typically encountered in social interactions and (ii the higher-level conceptualisation of the stimulus as indicating another person’s mental states. We illustrate the significance of this distinction for social perception research and report new empirical evidence further highlighting the importance of mental state attribution for perceptual processing. Finally, we discuss the potential of this approach to inform studies of clinical conditions such as autism.

  14. In silico analysis of HIV-1 Env-gp120 reveals structural bases for viral adaptation in growth-restrictive cells

    Directory of Open Access Journals (Sweden)

    Masaru eYokoyama

    2016-02-01

    Full Text Available Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1 envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co-receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness.

  15. [Evaluation of special GP-centered health care contracts in Germany by the participating GPs. present situation and future perspectives].

    Science.gov (United States)

    Klingenberg, Anja; Broge, Björn; Herholz, Harald; Szecsenyi, Joachim; Ose, Dominik

    2010-02-01

    In 2004, German statutory health care funds were given the possibility to offer their insured a special general practitioner-( GP-)centered health care contract (HZV), since 2007 they are obliged to do so. The aim of these contracts is to strengthen the role of the GP as a coordinator in the health care system. Until now, the evidence regarding the GPs' view on these contracts is poor. A written survey was conducted in Hesse in order to learn how the participating GPs evaluate the regional HZV. In Apri 2008, a questionnaire was developed, tested and mailed to 2,815 GPs who were participating in the GP-centered health care contract at that time. All analyses where conducted with SPSS (version 15.0). A total of 686 questionnaires were returned (response rate 24.4%). Altogether, the GPs' feedback ranged from great approval to clear disapproval of the contract. However, 70.0% of the survey's participants evaluated the HZV in general to be positive, 60.1% felt it strengthens their role as a GP. Quality circles on good prescribing and GP-specific education, obligatory parts of the HZV, were evaluated to be especially positive (70.3% and 69.4%, respectively). Positive effects were also seen concerning coordination of care (53.3%) and cooperation with patients (36.3%). Improvements concerning cooperation with specialists and hospitals were reported less often (24.9% and 13.0%, respectively). Workload because of additional administration for the HZV was criticized. In future, special GP-centered health care contracts should focus on improvement of cooperation between GPs and other caregivers. Workload for additional administration should be reduced.

  16. How do trained raters take context factors into account when assessing GP trainee communication performance? An exploratory, qualitative study.

    Science.gov (United States)

    Essers, Geurt; Dielissen, Patrick; van Weel, Chris; van der Vleuten, Cees; van Dulmen, Sandra; Kramer, Anneke

    2015-03-01

    Communication assessment in real-life consultations is a complex task. Generic assessment instruments help but may also have disadvantages. The generic nature of the skills being assessed does not provide indications for context-specific behaviour required in practice situations; context influences are mostly taken into account implicitly. Our research questions are: 1. What factors do trained raters observe when rating workplace communication? 2. How do they take context factors into account when rating communication performance with a generic rating instrument? Nineteen general practitioners (GPs), trained in communication assessment with a generic rating instrument (the MAAS-Global), participated in a think-aloud protocol reflecting concurrent thought processes while assessing videotaped real-life consultations. They were subsequently interviewed to answer questions explicitly asking them to comment on the influence of predefined contextual factors on the assessment process. Results from both data sources were analysed. We used a grounded theory approach to untangle the influence of context factors on GP communication and on communication assessment. Both from the think-aloud procedure and from the interviews we identified various context factors influencing communication, which were categorised into doctor-related (17), patient-related (13), consultation-related (18), and education-related factors (18). Participants had different views and practices on how to incorporate context factors into the GP(-trainee) communication assessment. Raters acknowledge that context factors may affect communication in GP consultations, but struggle with how to take contextual influences into account when assessing communication performance in an educational context. To assess practice situations, raters need extra guidance on how to handle specific contextual factors.

  17. "Mentoring Is Sharing the Excitement of Discovery": Faculty Perceptions of Undergraduate Research Mentoring

    Science.gov (United States)

    Vandermaas-Peeler, Maureen; Miller, Paul C.; Peeples, Tim

    2015-01-01

    Although an increasing number of studies have examined students' participation in undergraduate research (UR), little is known about faculty perceptions of mentoring in this context. The purpose of this exploratory study was to investigate four aspects of mentoring UR, including how faculty define high-quality UR mentoring and operationalize it in…

  18. Molecular docking guided structure based design of symmetrical N,N'-disubstituted urea/thiourea as HIV-1 gp120-CD4 binding inhibitors.

    Science.gov (United States)

    Sivan, Sree Kanth; Vangala, Radhika; Manga, Vijjulatha

    2013-08-01

    Induced fit molecular docking studies were performed on BMS-806 derivatives reported as small molecule inhibitors of HIV-1 gp120-CD4 binding. Comprehensive study of protein-ligand interactions guided in identification and design of novel symmetrical N,N'-disubstituted urea and thiourea as HIV-1 gp120-CD4 binding inhibitors. These molecules were synthesized in aqueous medium using microwave irradiation. Synthesized molecules were screened for their inhibitory ability by HIV-1 gp120-CD4 capture enzyme-linked immunosorbent assay (ELISA). Designed compounds were found to inhibit HIV-1 gp120-CD4 binding in micromolar (0.013-0.247 μM) concentrations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. A study into the effectiveness of unqualified GP assistants.

    Science.gov (United States)

    Philip, Marilyn; Turnbull, Betty

    This article aims to address the potential shortfall in care provision offered by general practitioners (GPs) resulting from pending retirement and the retention and recruitment crisis. An educational module was developed that offered both theory and practise to unqualified general practice assistants. The module content was determined following discussion with local GPs. A small qualitative study of six students was carried out to review efficacy of participants in their new role. Using a grounded theory approach, participant and supervisor views of course content and delivery, role preparation diversity were analysed and compared. Tape-recorded interviews were conducted and analysis carried out employing the constant comparative method. Data were coded and emergent themes categorized. Overall, participants agreed that the module had strengthened their knowledge, added new skills, heightened their job satisfaction, added significant diversity to their role and enhanced their employability potential. Five participants communicated that they were more confident in performing clinical skills and advising health improvement techniques. Supervisors also reported that participants displayed a more competent and professional approach to health care, which was complementary to the role of the GP and practice nurse. Ultimately this allowed both GP and practice nurse to focus on dealing with chronic illness targets, as required in the new directive (Scottish Executive, 2004).

  20. Fitting the elementary rate constants of the P-gp transporter network in the hMDR1-MDCK confluent cell monolayer using a particle swarm algorithm.

    Directory of Open Access Journals (Sweden)

    Deep Agnani

    Full Text Available P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the

  1. Biodegradation waste of the stations service by Rhodococcus erythropolis ohp-al-gp

    International Nuclear Information System (INIS)

    Pucci, Oscar Hector; Acuna, Adrian Javier; Pucci, Graciela Natalia

    2013-01-01

    The strain Rhodococcus erythropolis ohp-al-gp was isolated from turbine oil contaminated soil from northern Santa Cruz province, Argentina. Because of its potential in bioremediation, the aim was to know the abilities for degradation of pure compounds and mixtures of hydrocarbons, as well as degradation in the presence and absence of diesel nitrogen measured by gas chromatography. The strain possesses the ability to use diesel, kerosene, lubricating oil, pristane, hexane, heptane, octane, pentadecane and hexadecane. R. erythropolis ohp-al-gp has excellent potential for bioremediation of hydrocarbons, which are conflictive as lubricating oils, their potential use in removing mud from washing engines or gas stations would be its most important application. The degradation rate in optimal culture conditions, gives it an additional advantage. It also has a low degradation in the absence of nitrogen, a frequent limiting factor in Patagonian soils.

  2. Flash Flood Risk Perception in an Italian Alpine Region. From Research into Adaptive Strategies.

    Science.gov (United States)

    Scolobig, A.; de Marchi, B.; Borga, M.

    2009-04-01

    Flash floods are characterised by short lead times and high levels of uncertainty. Adaptive strategies to face them need to take into account not only the physical characteristics of the hydro-geological phenomena, but also peoples' risk perceptions, attitudes and behaviours in case of an emergency. It is quite obvious that a precondition for an effective adaptation, e.g. in the case of a warning, is the awareness of being endangered. At the same time the perceptions of those at risk and their likely actions inform hazard warning strategies and recovery programmes following such events. Usually low risk awareness or "wrong perceptions" of the residents are considered among the causes of an inadequate preparedness or response to flash floods as well as a symptom of a scarce self-protection culture. In this paper we will focus on flood risk perception and on how research on this topic may contribute to design adaptive strategies and give inputs to flood policy decisions. We will report on a flood risk perception study of the population residing in four villages in an Italian Alpine Region (Trentino Alto-Adige), carried out between October 2005 and January 2006. A total of 400 standardised questionnaires were submitted to local residents by face to face interviews. The surveys were preceded by focus groups with officers from agencies in charge of flood risk management and semi-structured and in-depth interviews with policy, scientific and technical experts. Survey results indicated that people are not so worried about hydro-geological phenomena, and think that their community is more endangered than themselves. The knowledge of the territory and danger sources, the unpredictability of flash floods and the feeling of safety induced by structural devices are the main elements which make the difference in shaping residents' perceptions. The study also demonstrated a widespread lack of adoption of preparatory measures among residents, together with a general low

  3. Working as a locum GP: their professional role in organizational context.

    NARCIS (Netherlands)

    Batenburg, R.; Hassel, D. van; Velden, L. van der

    2012-01-01

    Context: The workforce of General Practitioners (GPs) in the Netherlands is closely monitored and planned to ensure their pivotal role in primary care and the Dutch health care system. While the majority of GPs have their own practice or are employed by other GP practices or health community

  4. Key Stakeholders' Perceptions of Motivators for Research Participation Among Individuals Who Are Incarcerated.

    Science.gov (United States)

    Hanson, Bridget L; Faulkner, Sherilyn A; Brems, Christiane; Corey, Staci L; Eldridge, Gloria D; Johnson, Mark E

    2015-10-01

    Understanding motivations of research participants is crucial for developing ethical research protocols, especially for research with vulnerable populations. Through interviews with 92 institutional review board members, prison administrators, research ethicists, and researchers, we explored key stakeholders' perceptions of what motivates incarcerated individuals to participate in research. Primary motivators identified were a desire to contribute to society, gaining knowledge and health care, acquiring incentives, and obtaining social support. The potential for undue influence or coercion were also identified as motivators. These results highlight the need for careful analysis of what motivates incarcerated individuals to participate in research as part of developing or reviewing ethically permissible and responsible research protocols. Future research should expand this line of inquiry to directly include perspectives of incarcerated individuals. © The Author(s) 2015.

  5. Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41 Protein.

    Science.gov (United States)

    Murphy, R Elliot; Samal, Alexandra B; Vlach, Jiri; Saad, Jamil S

    2017-11-07

    The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an unknown structure. It plays important roles in HIV-1 replication such as mediating envelope (Env) intracellular trafficking and incorporation into assembling virions, mechanisms of which are poorly understood. Here, we present the solution structure of gp41CT in a micellar environment and characterize its interaction with the membrane. We show that the N-terminal 45 residues are unstructured and not associated with the membrane. However, the C-terminal 105 residues form three membrane-bound amphipathic α helices with distinctive structural features such as variable degree of membrane penetration, hydrophobic and basic surfaces, clusters of aromatic residues, and a network of cation-π interactions. This work fills a major gap by providing the structure of the last segment of HIV-1 Env, which will provide insights into the mechanisms of Gag-mediated Env incorporation as well as the overall Env mobility and conformation on the virion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Role perceptions of nurse clinical research coordinators

    Directory of Open Access Journals (Sweden)

    Jones CT

    2013-09-01

    Full Text Available Carolynn Thomas Jones, Lynda L Wilson School of Nursing, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Nursing roles in clinical research have evolved in the last 3 decades and include diverse responsibilities and job titles. Nurse clinical research coordinators’ (NCRCs roles include study planning, implementation, participant recruitment and retention, assessment of participants’ responses to clinical protocols, data management, and evaluation. The purpose of this study was to examine NCRCs’ perceptions of 59 specific clinical research activities that have been proposed as a taxonomy of NCRC activities. Participants were asked to check whether each of the 59 activities is being performed, and whether those activities should be performed, by NCRCs. The sample included 61 NCRCs who were attending the annual meeting of the International Association of Clinical Research Nurses. The percentage of respondents who indicated that the 59 activities are being performed by NCRCs at their sites ranged from 55%–98.4%. The percentage of respondents who indicated that the 59 activities should be performed by NCRCs ranged from 61.7%–88.5%. There were eight activities that fewer than 70% of the respondents reported should be performed by NCRCs. Chi-square analyses were conducted to determine whether there was a difference in the distribution of responses to the “are performed” versus “should be performed” responses for each of the 59 activities. There were significant differences in the distributions for 49 of the activities. The percentage of nurses responding “are performed” was higher than the percentage of responses to the “should be performed” items for 41 of these 49 activities. Findings suggest that further research is needed to validate the extent to which the taxonomy of clinical research nurse (CRN roles is a valid reflection of the actual practice of NCRCs, and also to explore reasons for the

  7. Perceptions of mental illness among Muslim general practitioners in South Africa.

    Science.gov (United States)

    Mohamed-Kaloo, Zaakiyah; Laher, Sumaya

    2014-03-26

    Mental health literacy on the part of medical practitioners is an important component of mental healthcare. General practitioners (GPs) are typically the first doctors consulted by a person who is ill. Exploration of their perceptions regarding mental illness, aetiological issues and treatment is important. To investigate perceptions of mental illness in a sample of ten South African Muslim GPs (five male, five female) in the Lenasia area (Johannesburg, South Africa). Using a qualitative approach, semi-structured interviews were conducted with each GP. The questionnaire encompassed 37 questions relating to the context in which the GPs practised, perceptions of mental illness, understanding of religion and culture, and treatment of mental illness (including aspects of spiritual illness). Thematic content analysis was used to analyse the data. Six dominant themes were identified, namely GPs' understanding of mental illness and its causation; stigma, secrecy and somatisation; the beneficial effects of religion in mental illnesses; perceptions of spiritual illnesses; collaboration with traditional healers; and collaboration with psychiatrists and psychologists. Greater awareness regarding the stigmatisation of mental illness is needed. Furthermore, it is important that healthcare professionals have an understanding of religious and cultural taxonomies of illness as well as the use of traditional healing as a mode of treatment. Participants identified a need for increased collaboration between healthcare professionals, including traditional healers.

  8. Differences in cell morphometry, cell wall topography and gp70 expression correlate with the virulence of Sporothrix brasiliensis clinical isolates.

    Directory of Open Access Journals (Sweden)

    Rafaela A Castro

    Full Text Available Sporotrichosis is a chronic infectious disease affecting both humans and animals. For many years, this subcutaneous mycosis had been attributed to a single etiological agent; however, it is now known that this taxon consists of a complex of at least four pathogenic species, including Sporothrix schenckii and Sporothrix brasiliensis. Gp70 was previously shown to be an important antigen and adhesin expressed on the fungal cell surface and may have a key role in immunomodulation and host response. The aim of this work was to study the virulence, morphometry, cell surface topology and gp70 expression of clinical isolates of S. brasiliensis compared with two reference strains of S. schenckii. Several clinical isolates related to severe human cases or associated with the Brazilian zoonotic outbreak of sporotrichosis were genotyped and clustered as S. brasiliensis. Interestingly, in a murine subcutaneous model of sporotrichosis, these isolates showed a higher virulence profile compared with S. schenckii. A single S. brasiliensis isolate from an HIV-positive patient not only showed lower virulence but also presented differences in cell morphometry, cell wall topography and abundant gp70 expression compared with the virulent isolates. In contrast, the highly virulent S. brasiliensis isolates showed reduced levels of cell wall gp70. These observations were confirmed by the topographical location of the gp70 antigen using immunoelectromicroscopy in both species. In addition, the gp70 molecule was sequenced and identified using mass spectrometry, and the sequenced peptides were aligned into predicted proteins using Blastp with the S. schenckii and S. brasiliensis genomes.

  9. Applying the Trigger Review Method after a brief educational intervention: potential for teaching and improving safety in GP specialty training?

    Science.gov (United States)

    McKay, John; de Wet, Carl; Kelly, Moya; Bowie, Paul

    2013-08-30

    The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be tested. Current TRM training utilizes a workplace face-to-face session by a GP expert, which is not feasible. A less costly, more sustainable educational intervention is necessary to build capability at scale. We aimed to determine the feasibility and impact of TRM and a related training intervention in GP training. We recruited 25 west of Scotland GP trainees to attend a 2-hour TRM workshop. Trainees then applied TRM to 25 clinical records and returned findings within 4-weeks. A follow-up feedback workshop was held. 21/25 trainees (84%) completed the task. 520 records yielded 80 undetected PSIs (15.4%). 36/80 were judged potentially preventable (45%) with 35/80 classified as causing moderate to severe harm (44%). Trainees described a range of potential learning and improvement plans. Training was positively received and appeared to be successful given these findings. TRM was valued as a safety improvement tool by most participants. This small study provides further evidence of TRM utility and how to teach it pragmatically. TRM is of potential value in GP patient safety curriculum delivery and preparing trainees for future safety improvement expectations.

  10. Medical students' and GP registrars' accommodation needs in the rural community: insight from a Victorian study.

    Science.gov (United States)

    Han, Gil-Soo; Wearne, Ben; O'Meara, Peter; McGrail, Matthew; Chesters, Janice

    2003-01-01

    Medical education in Australia is currently entering a new era, including support for the significant extension of medical students and general practitioner (GP) registrars' training programs in rural communities. This commitment to rural medical student and general practitioner recruitment and retention has made the provision of accommodation in rural communities a vital issue. This study has found that approximately half of all medical students on placement with rural GPs are currently accommodated with their GP supervisor or with other practice staff. This is a burden for many GPs and when the anticipated increase in the frequency and length of rural placements occurs what is currently a burden will become unsustainable. The changing gender and cultural demographics of medical students and rural general practitioners will also contribute to stresses on this accommodation system. It is important to have a systematic approach towards more appropriate and sustainable models of accommodation for both medical students and GP registrars.

  11. Activation of melatonin receptor (MT1/2) promotes P-gp transporter in methamphetamine-induced toxicity on primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Jumnongprakhon, Pichaya; Sivasinprasasn, Sivanan; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2017-06-01

    Melatonin has been known as a neuroprotective agent for the central nervous system (CNS) and the blood-brain barrier (BBB), which is the primary structure that comes into contact with several neurotoxins including methamphetamine (METH). Previous studies have reported that the activation of melatonin receptors (MT1/2) by melatonin could protect against METH-induced toxicity in brain endothelial cells via several mechanisms. However, its effects on the P-glycoprotein (P-gp) transporter, the active efflux pump involved in cell homeostasis, are still unclear. Thus, this study investigated the role of melatonin and its receptors on the METH-impaired P-gp transporter in primary rat brain microvascular endothelial cells (BMVECs). The results showed that METH impaired the function of the P-gp transporter, significantly decreasing the efflux of Rho123 and P-gp expression, which caused a significant increase in the intracellular accumulation of Rho123, and these responses were reversed by the interaction of melatonin with its receptors. Blockade of the P-gp transporter by verapamil caused oxidative stress, apoptosis, and cell integrity impairment after METH treatment, and these effects could be reversed by melatonin. Our results, together with previous findings, suggest that the interaction of melatonin with its receptors protects against the effects of the METH-impaired P-gp transporter and that the protective role in METH-induced toxicity was at least partially mediated by the regulation of the P-gp transporter. Thus, melatonin and its receptors (MT1/2) are essential for protecting against BBB impairment caused by METH. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A complete solution for GP-B's gyroscopic precession by retarded gravitational theory

    Science.gov (United States)

    Tang, Keyun

    Mainstream physicists generally believe that Mercury’s Perihelion precession and GP-B’ gyroscopic precession are two of the strongest evidences supporting Einstein’ curved spacetime and general relativity. However, most classical literatures and textbooks (e.g. Ohanain: Gravitation and Spacetime) paint an incorrect picture of Mercury’s orbit anomaly, namely Mercury’s perihelion precessed 43 arc-seconds per century; a correct picture should be that Mercury rotated 43 arc-seconds per century more than along Newtonian theoretical orbit. The essence of Le Verrier’s and Newcomb’s observation and analysis is that the angular speed of Mercury is slightly faster than the Newtonian theoretical value. The complete explanation to Mercury’s orbit anomaly should include two factors, perihelion precession is one of two factors, in addition, the change of orbital radius will also cause a change of angular speed, which is another component of Mercury's orbital anomaly. If Schwarzschild metric is correct, then the solution of the Schwarzschild orbit equation must contain three non-ignorable items. The first corresponds to Newtonian ellipse; the second is a nonlinear perturbation with increasing amplitude, which causes the precession of orbit perihelion; this is just one part of the angular speed anomaly of Mercury; the third part is a linear perturbation, corresponding to a similar figure of the Newton's ellipse, but with a minimal radius; this makes no contribution to the perihelion precession of the Schwarzschild orbit, but makes the Schwarzschild orbital radius slightly smaller, leading to a slight increase in Mercury’s angular speed. All classical literatures of general relativity ignored this last factor, which is a gross oversight. If you correctly take all three factors into consideration, the final result is that the difference between the angles rotated along Schwarzschild’s orbit and the angle rotated along Newton’s orbit for one hundred years should

  13. Perception of risk from radiation

    International Nuclear Information System (INIS)

    Slovic, P.

    1996-01-01

    Perceptions of risk from radiation have been studied systematically for about 20 years. This paper summarises the key findings and conclusions from this research with regard to the nature of risk perceptions, the impacts of these perceptions, and the need for communication about radiological hazards. Perhaps the most important generalisation from research in this area is that there is no uniform or consistent perception of radiation risks. Public perception and acceptance is determined by the context in which the radiation is used -and the very different reactions to different uses provide insight into the nature of perception and the determinants of acceptable risk. (author)

  14. General Practitioner (GP) trainees' experience of a '1-h protected supervision model' given during psychiatry placements in the United Kingdom.

    Science.gov (United States)

    Thomas, Gareth; McNeill, Helen

    2018-01-05

    Background A '1-hour protected supervision model' is well established for Psychiatry trainees. This model is also extended to GP trainees who are on placement in psychiatry. To explore the experiences of the '1-hour protected supervision model' for GP trainees in psychiatry placements in the UK. Methods Using a mixed methods approach, an anonymous online questionnaire was sent to GP trainees in the North West of England who had completed a placement in Psychiatry between February and August 2015. Results Discussing clinical cases whilst using the e-portfolio was the most useful learning event in this model. Patient care can potentially improve if a positive relationship develops between trainee/supervisor, which is impacted by the knowledge of this model at the start of the placement. Trainees found that clinical pressures were impacting on the occurrence of supervision. Conclusion The model works best when both GP trainees and their supervisors understand the model. The most frequently used and educationally beneficial aspect for GP trainees in psychiatry is the exploration of clinical cases using the learning portfolio as an educational tool. For effective delivery of this model of supervision, organisations must reflect on the balance between service delivery and allowing the supervisor and trainee adequate time for it to occur.

  15. Bone age assessment in Hispanic children: digital hand atlas compared with the Greulich and Pyle (G&P) atlas

    Science.gov (United States)

    Fernandez, James Reza; Zhang, Aifeng; Vachon, Linda; Tsao, Sinchai

    2008-03-01

    Bone age assessment is most commonly performed with the use of the Greulich and Pyle (G&P) book atlas, which was developed in the 1950s. The population of theUnited States is not as homogenous as the Caucasian population in the Greulich and Pyle in the 1950s, especially in the Los Angeles, California area. A digital hand atlas (DHA) based on 1,390 hand images of children of different racial backgrounds (Caucasian, African American, Hispanic, and Asian) aged 0-18 years was collected from Children's Hospital Los Angeles. Statistical analysis discovered significant discrepancies exist between Hispanic and the G&P atlas standard. To validate the usage of DHA as a clinical standard, diagnostic radiologists performed reads on Hispanic pediatric hand and wrist computed radiography images using either the G&P pediatric radiographic atlas or the Children's Hospital Los Angeles Digital Hand Atlas (DHA) as reference. The order in which the atlas is used (G&P followed by DHA or vice versa) for each image was prepared before actual reading begins. Statistical analysis of the results was then performed to determine if a discrepancy exists between the two readings.

  16. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

    Directory of Open Access Journals (Sweden)

    Mayumi Oakland

    2013-01-01

    Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

  17. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Directory of Open Access Journals (Sweden)

    Beuy Joob

    2014-12-01

    Full Text Available The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present. Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus. The in-depth analysis of the viral protein to find the binding site, active pocket is needed. Here, the authors analyzed the envelope glycoprotein GP2 from Ebola virus. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus was done. According to this assessment, 7 active pockets with varied druggability could be identified.

  18. Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations.

    Directory of Open Access Journals (Sweden)

    Siriwat Akapirat

    Full Text Available Sexual transmission is the principal driver of the human immunodeficiency virus (HIV pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080 efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2 previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE and Case A2 (subtype B in cervico-vaginal mucus (CVM, seminal plasma (SP and rectal secretions (RS from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively, followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11-17 fold and SP (2 fold two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS, gp70V1V2 92TH023 (CVM, SP, and Case A2 (CVM correlated with plasma IgG levels (p<0.001. Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA in anogenital secretions will help determine their role in preventing mucosal HIV acquisition.

  19. Recruitment and retention of rural general practitioners: a marketing approach reveals new possibilities.

    Science.gov (United States)

    Hemphill, Elizabeth; Dunn, Steve; Barich, Hayley; Infante, Rebecca

    2007-12-01

    This paper repositions the challenge of attracting and retaining rural GPs in a marketing context as a new focus for future research and policy development. Case study with mixed design of surveys of GPs and medical students and depth interviews with GPs, medical students, regional-division administrators and GP recruitment agents. GP recruitment and retention in the Limestone Coast region of South Australia. Twenty-seven Limestone Coast (LC) GPs; random sample of medical students from Adelaide University, Adelaide University Rural Health Society and Flinders University; snowball sampling two adjacent rural regions (20 GPs); and administrators from LC and adjacent regions and GP recruitment agencies in Adelaide. Drawing from marketing theory, creative suggestion of 'promotion of the practice and not the region' offers a means of GP recruitment and retention for structured succession planning for rural general practices. Structural attempts to broaden the GP market with overseas recruitment have done little for improving full-time equivalent GP levels. Market segmentation and market orientation offer a new emphasis on value exchange between the corporation (the practice), customer (GPs) and competition (all practices) to influence future mobility. A marketing orientation to the GP challenge emphasises individual's perceptions of value, GP expectations and practice offerings. Failure to acknowledge benefits of this marketing approach means that solutions such as those developed in the Limestone Coast region are unlikely. Research is now required to define GP satisfaction and value for long-term viability of general practices.

  20. Systematic Protein-Protein Docking and Molecular Dynamics Studies of HIV-1 gp120 and CD4: Insights for New Drug Development

    Directory of Open Access Journals (Sweden)

    M. Rizman-Idid

    2011-12-01

    Full Text Available Background and the purpose of the study: The interactions between HIV-1 gp120 and mutated CD4 proteins were investigated in order to identify a lead structure for therapy based on competitive blocking of the HIV binding receptor for human T-cells. Crystal structures of HIV gp120-CD4 complexes reveal a close interaction of the virus receptor with CD4 Phe43, which is embedded in a pocket of the virus protein.Methods: This study applies computer simulations to determine the best binding of amino acid 43 CD4 mutants to HIV gp120. Besides natural CD4, three mutants carrying alternate aromatic residues His, Trp and Tyr at position 43 were investigated. Several docking programs were applied on isolated proteins based on selected crystal structures of gp120-CD4 complexes, as well as a 5 ns molecular dynamics study on the protein complexes. The initial structures were minimized in Gromacs to avoid crystal packing effects, and then subjected to docking experiments using AutoDock4, FireDock, ClusPro and ZDock. In molecular dynamics, the Gibbs free binding energy was calculated for the gp120-CD4 complexes. The docking outputs were analyzed on energy within the respective docking software.Results and conclusion: Visualization and hydrogen bonding analysis were performed using the Swiss-PdbViewer. Strong binding to HIV gp120 can be achieved with an extended aromatic group (Trp. However, the sterical demand of the interaction affects the binding kinetics. In conclusion, a ligand for an efficient blocking of HIV gp120 should involve an extended but conformational flexible aromatic group, i.e. a biphenyl. A docking study on biphenylalanine-43 confirms this expectation

  1. Research and Assessment of Learning Environments through Photoelicitation: Graduate Student Perceptions of Electronics Manufacturing in India

    Science.gov (United States)

    Berdanier, Catherine G. P.; Cox, Monica F.

    2015-01-01

    This research studies the positive and negative perceptions of graduate students from the United States studying issues of sustainable electronics and electronics manufacturing in India as part of a National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT) curriculum. The purpose of this paper is to discuss the…

  2. Gp85 genetic diversity of avian leukosis virus subgroup J among different individual chickens from a native flock.

    Science.gov (United States)

    Li, Yang; Fu, Jiayuan; Cui, Shuai; Meng, Fanfeng; Cui, Zhizhong; Fan, Jianhua; Chang, Shuang; Zhao, Peng

    2017-05-01

    To compare the genetic diversity and quasispecies evolution of avian leukosis virus (ALV) among different individuals, 5 chickens, raised in Shandong Provice of China, were randomly selected from a local chicken flock associated with serious tumor cases. Blood samples were collected and inoculated into chicken embryo fibroblast and DF-1 cell lines for virus isolation and identification, respectively, of Marek's disease virus (MDV), reticuloendotheliosis virus (REV), and ALV. Five strains of ALV subgroup J (ALV-J) were identified, and the gp85 gene from each strain was amplified and cloned. For each strain, about 20 positive clones of gp85 gene were selected for sequence analyses and the variability of the quasispecies of the 5 strains was compared. The results showed that the nuclear acid length of gp85 gene of 5 ALV-J isolates is 921 bp, 921 bp, 924 bp, 918 bp, and 912 bp respectively, and amino acid homologies of different gp85 clones from the 5 ALV-J strains were 99.3 to 100%, 99.3 to 100%, 99.4 to 100%, 98.4 to 100%, 99.0 to 100%, respectively. The proportions of dominant quasispecies were 65.0%, 85.0%, 85.0%, 50.0%, 84.2%, respectively, and homology of the gp85 among these dominant quasispecies was 89.2 to 92.5%. These data demonstrated the composition of the ALV-J quasispecies varied among infected individuals even within the same flock, and the dominant quasispecies continued to evolve both for their proportion and gene mutation. © 2016 Poultry Science Association Inc.

  3. Proteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6.

    Science.gov (United States)

    Weekes, Michael P; Antrobus, Robin; Talbot, Suzanne; Hör, Simon; Simecek, Nikol; Smith, Duncan L; Bloor, Stuart; Randow, Felix; Lehner, Paul J

    2012-03-02

    The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.

  4. Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex

    International Nuclear Information System (INIS)

    Onischenko, Evgeny A.; Crafoord, Ellinor; Hallberg, Einar

    2007-01-01

    The nuclear pore complexes (NPCs) reversibly disassemble and reassemble during mitosis. Disassembly of the NPC is accompanied by phosphorylation of many nucleoporins although the function of this is not clear. It was previously shown that in the transmembrane nucleoporin gp210 a single serine residue at position 1880 is specifically phosphorylated during mitosis. Using amino acid substitution combined with live cell imaging, time-lapse microscopy and FRAP, we investigated the role of serine 1880 in binding of gp210 to the NPC in vivo. An alanine substitution mutant (S1880A) was significantly more dynamic at the NPC compared to the wild-type protein, suggesting that serine 1880 is important for binding of gp210 to the NPC. Moreover a glutamate substitution (S1880E) closely mimicking phosphorylated serine specifically interfered with incorporation of gp210 into the NPC and compromised its post-mitotic recruitment to the nuclear envelope of daughter nuclei. Our findings are consistent with the idea that mitotic phosphorylation acts to dissociate gp210 from the structural elements of the NPC

  5. Binding of HIV-1 gp120 to DC-SIGN promotes ASK-1-dependent activation-induced apoptosis of human dendritic cells.

    Directory of Open Access Journals (Sweden)

    Yongxiong Chen

    2013-01-01

    Full Text Available During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC, including DC-SIGN⁺ cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN⁺ blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV⁺ serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN⁺ DC that were isolated directly from HIV-1⁺ individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential

  6. Membrane proximal external region of gp41 from HIV-1 strains HXB2 and JRFL has different sensitivity to alanine mutation

    Science.gov (United States)

    Yi, Hyun Ah; Diaz-Rohrer, Barbara; Saminathan, Priyanka; Jacobs, Amy

    2015-01-01

    The transmembrane subunit (gp41) of the HIV envelope protein complex (Env) mediates the viral fusion step of HIV entry. The membrane-proximal external region (MPER), one of the functional domains of gp41, has been the focus of a great deal of research because it is a target for neutralizing antibodies. In this study, we examined 23 amino acid residues in MPER (660-683) in both a CXCR4 co-receptor utilizing strain (HXB2) and a CCR5 utilizing strain (JRFL) by alanine scanning mutagenesis. Despite the high degree of gp41 sequence conservation, the effects of alanine mutation in the MPER were different between the two strains. Most mutations in HXB2 had fusogenicity and protein expression levels not less than 50% of wild type in the case of cell-cell fusion. However, about thirty percent of the mutants in HXB2 showed a severe defect in fusogenicity in viral entry. Mutations in the MPER of strain JRFL had more dramatic effects than HXB2 in cell-cell fusion and viral entry. The fact that there are large differences in the effects of mutation between two strains suggests the potential for MPER interaction with non-conserved sequences such as the fusion peptide and/or other NHR domains as well as potential long-range structural effects on the conformational changes that occur with the Env complex during membrane fusion. PMID:25649507

  7. Degradation of 1,2-Dibromoethane by Mycobacterium sp. Strain GP1

    NARCIS (Netherlands)

    Poelarends, Gerrit J.; van Hylckama Vlieg, Johannes; Marchesi, Julian R.; Freitas dos Santos, Luisa M.; Janssen, Dick B.

    The newly isolated bacterial strain GP1 can utilize 1,2-dibromoethane as the sole carbon and energy source. On the basis of 16S rRNA gene sequence analysis, the organism was identified as a member of the subgroup which contains the fast-growing mycobacteria, The first step in 1,2-dibromoethane

  8. Introducing the Geneva Multimodal expression corpus for experimental research on emotion perception.

    Science.gov (United States)

    Bänziger, Tanja; Mortillaro, Marcello; Scherer, Klaus R

    2012-10-01

    Research on the perception of emotional expressions in faces and voices is exploding in psychology, the neurosciences, and affective computing. This article provides an overview of some of the major emotion expression (EE) corpora currently available for empirical research and introduces a new, dynamic, multimodal corpus of emotion expressions, the Geneva Multimodal Emotion Portrayals Core Set (GEMEP-CS). The design features of the corpus are outlined and justified, and detailed validation data for the core set selection are presented and discussed. Finally, an associated database with microcoded facial, vocal, and body action elements, as well as observer ratings, is introduced.

  9. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  10. The Effects of Employee’s Perceptions of Organizational Justice and Organizational Trust on Organizational Commitment: A Research on a Public Organization

    Directory of Open Access Journals (Sweden)

    Hakan CANDAN

    2014-12-01

    Full Text Available In this study, it is aimed to present the senses of employees about organizational justice, organizational trust and organizational commitment; and also to research the effects of organizational justice and organizational trust perceptions on organizational commitment. In this context, 260 questionnaires that obtained from registry and cadastre employees and determined appropriate for study is analyzed. Analyses are done by using SPSS 16.0 program and the consequences are consistent with national and international literature. Hypothesizes within the research are tested with correlation and regression analyses. According the consequences, distributional justice perception effects three sub-dimension of organizational commitment (affective, continuity, and normative positively, transactional justice perception has positive effects on only affective commitment and continuity commitment; procedural justice perception has no effect on sub-dimensions of organizational commitment. The other findings are perceptions of trust on manager and trust on organization that are two sub-dimensions of organizational trust; has positive effects on all dimensions of organizational commitment

  11. Radio Research in Spain - Characteristics, Perceptions and Impressions from the Scientific Community

    Directory of Open Access Journals (Sweden)

    Teresa Piñeiro Otero

    2017-11-01

    Full Text Available Research in communication has recently gained relevance, leading to the development of a significant and specialised corpus of studies. Along these lines, this work focuses on radio studies from the perspective of the scientific community – an innovative approach in the framework of communication meta-research. Starting with the outcomes of an initial survey, an in-depth study was then conducted to focus on the importance, themes and quality of radio research. We looked into the 31 most important authors of contributions published in scientific journals (1980-2013 to understand their perceptions and impressions about Spanish research. This study helped confirm that radio research is still a minority and individual endeavour. The respondents explained that this is due to limited support from research and academic institutions. In any case, radio researchers find the object of their study to be relevant, influential and well rooted, even if the topics and approaches are permeable to the context where the studies take place.

  12. Leishmania mexicana Gp63 cDNA Using Gene Gun Induced Higher Immunity to L. mexicana Infection Compared to Soluble Leishmania Antigen in BALB/C

    Science.gov (United States)

    Rezvan, H; Rees, R; Ali, SA

    2011-01-01

    Background Leishmaniasis is a worldwide disease prevalent in tropical and sub tropical countries. Many attempts have been made and different strategies have been approached to develop a potent vaccine against Leishmania. DNA immunisation is a method, which is shown to be effective in Leishmania vaccination. Leishmania Soluble Antigen (SLA) has also recently been used Leishmania vaccination. Methods The immunity generated by SLA and L. mexicana gp63 cDNA was compared in groups of 6 mice, which were statistically analysed by student t- test with the P-value of 0.05. SLA was administered by two different methods; intramuscular injection and injection of dendritic cells (DCs) loaded with SLA. L. mexicana gp63 cDNA was administered by the gene gun. Results Immunisation of BALB/c mice with L. mexicana gp63 resulted in high levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity, which were accompanied with protection induced by the immunisation against L. mexicana infection. In contrast, administration of SLA, produced a mixed Th1/Th2-type immune responses as well as a high level of CTL activity but did not protect mice from the infection. Conclusion The results indicate higher protection by DNA immunisation using L. mexicana gp63 cDNA compared to SLA, which is accompanied by a high level of Th1 immune response. However, the CTL activity does not necessarily correlate with the protection induced by the vaccine. Also, gene gun immunisation is a potential approach in Leishmania vaccination. These findings would be helpful in opening new windows in Leishmania vaccine research. PMID:22347315

  13. Binding of HIV-1 gp41-directed neutralizing and non-neutralizing fragment antibody binding domain (Fab and single chain variable fragment (ScFv antibodies to the ectodomain of gp41 in the pre-hairpin and six-helix bundle conformations.

    Directory of Open Access Journals (Sweden)

    John M Louis

    Full Text Available We previously reported a series of antibodies, in fragment antigen binding domain (Fab formats, selected from a human non-immune phage library, directed against the internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41. Broadly neutralizing antibodies from that series bind to both the fully exposed N-HR trimer, representing the pre-hairpin intermediate state of gp41, and to partially-exposed N-HR helices within the context of the gp41 six-helix bundle. While the affinities of the Fabs for pre-hairpin intermediate mimetics vary by only 2 to 20-fold between neutralizing and non-neutralizing antibodies, differences in inhibition of viral entry exceed three orders of magnitude. Here we compare the binding of neutralizing (8066 and non-neutralizing (8062 antibodies, differing in only four positions within the CDR-H2 binding loop, in Fab and single chain variable fragment (ScFv formats, to several pre-hairpin intermediate and six-helix bundle constructs of gp41. Residues 56 and 58 of the mini-antibodies are shown to be crucial for neutralization activity. There is a large differential (≥ 150-fold in binding affinity between neutralizing and non-neutralizing antibodies to the six-helix bundle of gp41 and binding to the six-helix bundle does not involve displacement of the outer C-terminal helices of the bundle. The binding stoichiometry is one six-helix bundle to one Fab or three ScFvs. We postulate that neutralization by the 8066 antibody is achieved by binding to a continuum of states along the fusion pathway from the pre-hairpin intermediate all the way to the formation of the six-helix bundle, but prior to irreversible fusion between viral and cellular membranes.

  14. Effect of the delegation of GP-home visits on the development of the number of patients in an ambulatory healthcare centre in Germany

    Science.gov (United States)

    2012-01-01

    Background The AGnES-concept (AGnES: GP-supporting, community-based, e-health-assisted, systemic intervention) was developed to support general practitioners (GPs) in undersupplied regions. The project aims to delegate GP-home visits to qualified AGnES-practice assistants, to increase the number of patients for whom medical care can be provided. This paper focuses on the effect of delegating GP-home visits on the total number of patients treated. First, the theoretical number of additional patients treated by delegating home visits to AGnES-practice assistants was calculated. Second, actual changes in the number of patients in participating GP-practices were analyzed. Methods The calculation of the theoretical increase in the number of patients was based on project data, data which were provided by the Association of Statutory Health Insurance Physicians, or which came from the literature. Setting of the project was an ambulatory healthcare centre in the rural county Oberspreewald-Lausitz in the Federal State of Brandenburg, which employed six GPs, four of which participated in the AGnES project. The analysis of changes in the number of patients in the participating GP-practices was based on the practices’ reimbursement data. Results The calculated mean capacity of AGnES-practice assistants was 1376.5 home visits/year. GPs perform on average 1200 home visits/year. Since home visits with an urgent medical reason cannot be delegated, we included only half the capacity of the AGnES-practice assistants in the analysis (corresponding to a 20 hour-work week). Considering all parameters in the calculation model, 360.1 GP-working hours/year can be saved. These GP-hours could be used to treat 170 additional patients/quarter year. In the four participating GP-practices the number of patients increased on average by 133 patients/quarter year during the project period, which corresponds to 78% of the theoretically possible number of patients. Conclusions The empirical

  15. Effect of the delegation of GP-home visits on the development of the number of patients in an ambulatory healthcare centre in Germany

    Directory of Open Access Journals (Sweden)

    van den Berg Neeltje

    2012-10-01

    Full Text Available Abstract Background The AGnES-concept (AGnES: GP-supporting, community-based, e-health-assisted, systemic intervention was developed to support general practitioners (GPs in undersupplied regions. The project aims to delegate GP-home visits to qualified AGnES-practice assistants, to increase the number of patients for whom medical care can be provided. This paper focuses on the effect of delegating GP-home visits on the total number of patients treated. First, the theoretical number of additional patients treated by delegating home visits to AGnES-practice assistants was calculated. Second, actual changes in the number of patients in participating GP-practices were analyzed. Methods The calculation of the theoretical increase in the number of patients was based on project data, data which were provided by the Association of Statutory Health Insurance Physicians, or which came from the literature. Setting of the project was an ambulatory healthcare centre in the rural county Oberspreewald-Lausitz in the Federal State of Brandenburg, which employed six GPs, four of which participated in the AGnES project. The analysis of changes in the number of patients in the participating GP-practices was based on the practices’ reimbursement data. Results The calculated mean capacity of AGnES-practice assistants was 1376.5 home visits/year. GPs perform on average 1200 home visits/year. Since home visits with an urgent medical reason cannot be delegated, we included only half the capacity of the AGnES-practice assistants in the analysis (corresponding to a 20 hour-work week. Considering all parameters in the calculation model, 360.1 GP-working hours/year can be saved. These GP-hours could be used to treat 170 additional patients/quarter year. In the four participating GP-practices the number of patients increased on average by 133 patients/quarter year during the project period, which corresponds to 78% of the theoretically possible number of patients

  16. Pseudotyping Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV): F Proteins from Group II NPVs are functionally analogous to AcMNPV GP64

    NARCIS (Netherlands)

    Lung, O.; Westenberg, M.; Vlak, J.M.; Zuidema, D.; Blissard, G.W.

    2002-01-01

    GP64, the major envelope glycoprotein of budded virions of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), is involved in viral attachment, mediates membrane fusion during virus entry, and is required for efficient virion budding. Thus, GP64 is essential for viral

  17. P-gp and MRP1 Expression in Parathyroid Tumors Related to Histology, Weight and Tc-99m-Sestamibi Imaging Results

    NARCIS (Netherlands)

    Jorna, F. H.; Hollema, H.; Hendrikse, H. N.; Bart, J.; Brouwers, A. H.; Plukker, J. T. M.

    Objective: P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are membrane efflux pumps that may have a role in the kinetics of Tc-99m-sestamibi (MIBI) in parathyroid tumors. P-gp and MRP1 expression in parathyroid tumors was studied and related to histology, weight and pre- and

  18. Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340

    DEFF Research Database (Denmark)

    Ligtenberg, T J; Bikker, F J; Groenink, J

    2001-01-01

    bound in a similar way to Streptococcus mutans and surfactant protein-D. Histochemically, the distribution of gp-340 in the submandibular salivary glands was identical with the agglutinin distribution, as shown in a previous paper [Takano, Bogert, Malamud, Lally and Hand (1991) Anat. Rec. 230, 307......-318]. We conclude that agglutinin is identical with gp-340, and that this molecule interacts with S. mutans and surfactant protein-D....

  19. Perception, awareness and practice of research-oriented medical education among undergraduate students of a medical college in Kolkata, West Bengal.

    Science.gov (United States)

    Chatterjee, Subhankar; Adhikari, Anjan; Haldar, Dibakar; Biswas, Payel

    2016-01-01

    The addition of research-oriented medical education (ROME) to the existing curriculum could promote logical thinking, rapid literature search and a better understanding of research methodology. Creation of research temperament could lead to innovations in healthcare. We assessed the perception, awareness and practice of ROME among undergraduate students. We conducted a cross-sectional survey among 234 students of R.G. Kar Medical College, Kolkata selected by the simple random sampling technique. Data were collected using a pre-designed, pre-tested, validated questionnaire by direct interviews. The mean (SD) perception score was 44.2 (5.03). Students from outside West Bengal (p=0.05), women (p=0.03) and students whose parents were doctors (p=0.01) had significantly higher scores. Students in the second and fourth semesters had a better perception than those in the sixth and eighth semesters. Awareness of research fellowships granted to undergraduate students such as the Indian Council of Medical Research-Short-term studentship (ICMR-STS) was low among the second semester students (13.9%), but more than half (59.3%) of the students in the eighth semester were aware (difference across semesters, pAwareness about journals, conferences and 'research bodies promoting student research' was low. Students in the senior semesters spent more time on research (6th semester 72.2% and 8th semester 88.9%) than those in the junior semesters (2nd: 66.7% and 4th: 77.8%; difference across semesters, p=0.03). About 3% of students participated in extracurricular research and/or had presented work at a conference. There is a good perception about the need for research but a lack of awareness of the why and how, as well as hardly any practice of ROME among medical students of this medical college.

  20. VSVΔG/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection.

    Science.gov (United States)

    Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

    2015-02-01

    Members of the species Zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. The VSVΔG/EBOV GP vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (NHP) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and NHPs from a lethal challenge of Ebola virus (EBOV). EBOV infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, suggesting a vital role for the innate immune system to control the infection before cells of the adaptive immune system can assume control. Natural killer (NK) cells are the predominant cell of the innate immune response, which has been shown to expand with VSVΔG/EBOV GP treatment. In the current study, an in vivo mouse model of the VSVΔG/EBOV GP post-exposure treatment was used for a mouse adapted (MA)-EBOV infection, to determine the putative VSVΔG/EBOV GP-induced protective mechanism of NK cells. NK depletion studies demonstrated that mice with NK cells survive longer in a MA-EBOV infection, which is further enhanced with VSVΔG/EBOV GP treatment. NK cell mediated cytotoxicity and IFN-γ secretion was significantly higher with VSVΔG/EBOV GP treatment. Cell mediated cytotoxicity assays and perforin knockout mice experiments suggest that there are perforin-dependent and -independent mechanisms involved. Together, these data suggest that NK cells play an important role in VSVΔG/EBOV GP-induced protection of EBOV by increasing NK cytotoxicity, and IFN-γ secretion.

  1. Positive evolution of the glycoprotein (GP) gene is related to transmission of the Ebola virus.

    Science.gov (United States)

    Jing, Y X; Wang, L N; Wu, X M; Song, C X

    2016-03-28

    Ebola hemorrhagic fever is a fatal disease caused by the negative-strand RNA of the Ebola virus. A high-intensity outbreak of this fever was reported in West Africa last year; however, there is currently no definitive treatment strategy available for this disease. In this study, we analyzed the molecular evolutionary history and attempted to determine the positive selection sites in the Ebola genes using multiple-genomic sequences of the various Ebola virus subtypes, in order to gain greater clarity into the evolution of the virus and its various subtypes. Only the glycoprotein (GP) gene was positively selected among the 8 Ebola genes, with the other genes remaining in the purification stage. The positive selection sites in the GP gene were identified by a random-site model; these sites were found to be located in the mucin-like region, which is associated with transmembrane protein binding. Additionally, different branches of the phylogenetic tree displayed different positive sites, which in turn was responsible for differences in the cell adhesion ability of the virus. In conclusion, the pattern of positive sites in the GP gene is associated with the epidemiology and prevalence of Ebola in different areas.

  2. Physics Faculty Perceptions of Research-based Assessment

    Science.gov (United States)

    Sayre, Eleanor

    2016-03-01

    When research-based resources are well aligned with the perceived needs of faculty, faculty members will more readily take them up. We used phenomenographic interviews of ordinary physics faculty and department chairs to identify four families of issues that faculty have around research-based assessments (RBAs). First, many faculty are interested in using RBAs, but need help with the practicalities of administering RBAs: how to find them, which ones there are, and how to administer them. Second, at the same time, many faculty think that RBAs are limited and don't measure many of the things they care about, or aren't applicable in their classes. They want assessments to measure skills, perceptions, and specific concepts. Third, many faculty want to turn to communities of other faculty and experts to help them interpret their assessment results and suggest other ways to do assessment. They want to better understand their assessment results by comparing to others and interacting with faculty from other schools to learn about how they do assessment. Fourth, many faculty consider their courses in the broader contexts of accountability and their departments. They want help with assessment in these broader contexts. We also discuss how faculty members' roles in their departments and institutions influence their perceived wants and needs around assessment. Supported by NSF DUE-1256354, DUE-1256354, DUE-1347821, DUE-1347728.

  3. Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric protein-based DNA and VLP vaccines.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14 in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy.

  4. Thymic and lymph node mesenchymal subsets can be derived from PDGFRα/β+Gp38+CD34+ICAM1- vascular adventitial precursors

    DEFF Research Database (Denmark)

    Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger

    While discrete Gp38- and Gp38+ mesenchymal populations have previously been described in the lymph nodes (LNs) and in the thymus the putative relationship between LN and thymic mesenchymal cells remains unclear. Here, using transcriptome profiling as well as phenotypic and localization studies we...

  5. An optimized D2Q37 Lattice Boltzmann code on GP-GPUs

    NARCIS (Netherlands)

    Biferale, L.; Mantovani, F.; Pivanti, M.; Pozzati, F.; Sbragaglia, M.; Scagliarini, Andrea; Schifano, S.F.; Toschi, F.

    2013-01-01

    We describe the implementation of a thermal compressible Lattice Boltzmann algorithm on an NVIDIA Tesla C2050 system based on the Fermi GP-GPU. We consider two different versions, including and not including reactive effects. We describe the overall organization of the algorithm and give details on

  6. Research of Executives' Perceptions in Companies and Organizations on the Importance of Mentoring in the Frame of In-House Education and Training

    Science.gov (United States)

    Fragoulis, Iosif; Valkanos, Efthymios; Voula, Florou

    2011-01-01

    The purpose of the present paper is to present the outcomes of a research on the executives' perceptions in companies and organizations on the importance of mentoring in the frame of in-house education and training. The paper researches the perceptions of people who work for companies and organizations as far as their participation in mentoring…

  7. Parallelized Local Volatility Estimation Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-01-01

    We introduce an inverse problem for the local volatility model in option pricing. We solve the problem using the Levenberg-Marquardt algorithm and use the notion of the Fréchet derivative when calculating the Jacobian matrix. We analyze the existence of the Fréchet derivative and its numerical computation. To reduce the computational time of the inverse problem, a GP-GPU environment is considered for parallel computation. Numerical results confirm the validity and efficiency of the proposed method. ©2010 IEEE.

  8. Application of interferon modulators to overcome partial resistance of human ovarian cancers to VSV-GP oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Catherine Dold

    2016-01-01

    Full Text Available Previously, we described an oncolytic vesicular stomatitis virus variant pseudotyped with the nonneurotropic glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, which was highly effective in glioblastoma. Here, we tested its potency for the treatment of ovarian cancer, a leading cause of death from gynecological malignancies. Effective oncolytic activity of VSV-GP could be demonstrated in ovarian cancer cell lines and xenografts in mice; however, remission was temporary in most mice. Analysis of the innate immune response revealed that ovarian cancer cell lines were able to respond to and produce type I interferon, inducing an antiviral state upon virus infection. This is in stark contrast to published data for other cancer cell lines, which were mostly found to be interferon incompetent. We showed that in vitro this antiviral state could be reverted by combining VSV-GP with the JAK1/2-inhibitor ruxolitinib. In addition, for the first time, we report the in vivo enhancement of oncolytic virus treatment by ruxolitinib, both in subcutaneous as well as in orthotopic xenograft mouse models, without causing significant additional toxicity. In conclusion, VSV-GP has the potential to be a potent and safe oncolytic virus to treat ovarian cancer, especially when combined with an inhibitor of the interferon response.

  9. Defamation on facebook: Isparta V Richter 2013 6 SA 529 (GP ...

    African Journals Online (AJOL)

    In this case discussion, a brief overview is given of the few cases already reported, but in the main the case of Isparta v Richter 2013 6 SA 4529 (GP) is discussed. In this case a South African court for the first time awarded damages to the plaintiff for defamatory comments made on Facebook. The questions that confronted ...

  10. Diagnostic value of Joint Detection of GP73 and AFP-L3 in Primary Hepatic Carcinoma with Low Concentration of AFP

    Directory of Open Access Journals (Sweden)

    Lei CAI

    2015-03-01

    Full Text Available Objective: To explore the applicative value of serum Golgi protein (GP73 and alpha-proteinvariant (AFP-L3 in the diagnosis of patients with primary hepatic carcinoma (PHC. Methods:Totally 110 patients were enrolled, including 60 PHC patients with low concentration of AFP ((1.1-108.0 μg/L and 50 patients with non-PHC digestive system diseases (20 cases of patients with chronic hepatitis, 15 patients with liver cirrhosis, 4 patients with bile duct cancer, 4 patients with gastric cancer, 4 patients with rectal cancer and 3 patients with colon cancer. In addition, 42 healthy people were selected as control group. GP73 was detected by enzyme-linked immunosorbent assay (ELISA trace centrifugal column method was adopted for separation of AFP-L3. Luo's chemiluminescence method was used to determine the total content of AFP and AFP-L3 in eluent for calculating the ratio of AFP-L3/ AFP. Results: The levels of serum GP73 and AFP-L3(% in PHC group were significantly higher than the other 2 groups (P<0.01 and the level of serum GP73 and AFP-L3 (% in Non-PHC group were higher than those in healthy group (P<0.01. ROC analysis showed that the area under ROC curve of single GP73 and AFP-L3(% in diagnosis of PHC and non-PHC were 0.887 and 0.860, respectively. Additionally, the ROC analysis also showed that critical value of GP73 and AFP-L3 for the diagnosis of HPC were 83.78 μg/L and 13.87%, respectively. The sensitivity of joint detection of serum GP73 or AFP-L3 was higher than detection of them alone (90.0 vs. 71.7 and 60.0, P<0.05 but the specificity was similar between single detection and joint detection (P>0.05. The positive predictive value and negative predictive value of joint detection of them was higher than single detections of them and there was significant differences in negative predictive value (P<0.05 but no difference in positive predictive value (P>0.05. The overall response rate of joint detection of GP73 and AFP-L3 was higher

  11. Participation in environmental health research by placenta donation - a perception study.

    Science.gov (United States)

    Lind, Uffe; Mose, Tina; Knudsen, Lisbeth E

    2007-11-22

    Much environmental health research depends on human volunteers participating with biological samples. The perception study explores why and how people participate in a placenta perfusion study in Copenhagen. The participation implies donation of the placenta after birth and some background information but no follow up. Nineteen semi-structured qualitative interviews were conducted with participants in the placenta perfusion study after donation of placenta. Observation studies were made of recruitment sessions. The interviewed participants are generally in favour of medical research. They participated in the placenta perfusion study due to a belief that societal progress follows medical research. They also felt that participating was a way of giving something back to the Danish health care system. The participants have trust in medical science and scientists, but trust is something which needs to be created through "trust-work". Face-to-face interaction, written information material and informed consent forms play important parts in creating trusting relationships in medical research. Medical research ethics do not only amount to specific types of written information material but should also be seen as a number of trust making performances involving researchers as well as research participants.

  12. Determination of the minimal fusion peptide of bovine leukemia virus gp30

    International Nuclear Information System (INIS)

    Lorin, Aurelien; Lins, Laurence; Stroobant, Vincent; Brasseur, Robert; Charloteaux, Benoit

    2007-01-01

    In this study, we determined the minimal N-terminal fusion peptide of the gp30 of the bovine leukemia virus on the basis of the tilted peptide theory. We first used molecular modelling to predict that the gp30 minimal fusion peptide corresponds to the 15 first residues. Liposome lipid-mixing and leakage assays confirmed that the 15-residue long peptide induces fusion in vitro and that it is the shortest peptide inducing optimal fusion since longer peptides destabilize liposomes to the same extent but not shorter ones. The 15-residue long peptide can thus be considered as the minimal fusion peptide. The effect of mutations reported in the literature was also investigated. Interestingly, mutations related to glycoproteins unable to induce syncytia in cell-cell fusion assays correspond to peptides predicted as non-tilted. The relationship between obliquity and fusogenicity was also confirmed in vitro for one tilted and one non-tilted mutant peptide

  13. Mechanisms of Percept-Percept and Image-Percept Integration in Vision: Behavioral and Electrophysiological Evidence

    Science.gov (United States)

    Dalvit, Silvia; Eimer, Martin

    2011-01-01

    Previous research has shown that the detection of a visual target can be guided not only by the temporal integration of two percepts, but also by integrating a percept and an image held in working memory. Behavioral and event-related brain potential (ERP) measures were obtained in a target detection task that required temporal integration of 2…

  14. Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model.

    Directory of Open Access Journals (Sweden)

    Atefeh Razazan

    Full Text Available One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE containing monophosphoryl lipid A (MPL adjuvant (DMPC-DMPG-DOPE-MPL-Gp2. BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation.

  15. Research on Language of Perception Still-Life as a Visual Aphorism

    Directory of Open Access Journals (Sweden)

    Anatolij P. Suprun

    2011-01-01

    Full Text Available This article describes a categorical structure of perception of still-life painting. Analysis is done on the system of visual opposition elements in still-life. A still-life is considered a "perceptual statement about the world", and a "visual aphorism" The research is based on such methods as: semantic spaces constructing and their transformation at introduction of additional elements in still-lifes. It also gives full analysis of an interpretation of complex images and understanding of types of still-life as a visual hermeneutics.

  16. GP140/CDCPI in the Development of Prostate Cancer Metastasis

    Science.gov (United States)

    2013-09-01

    localization of Gp140 to the plasma membrane of prostate epithelial cells is decreased or lost in PIN, invasive and metastatic prostate cancers when...Matrigel (BD Biosciences, Franklin Lakes, NJ) at 2000 cells per well. Spheroid structures were extracted and expanded in regu- lar tissue culture, and...cell surface (Figure 2A). Some surface-negative cells express E-cadherin in the cytoplasm. Cells were cultured in Matrigel, and spheroid structures

  17. Managerialism and the British GP: the GP as manager and as managed.

    Science.gov (United States)

    Warwicker, T

    1998-01-01

    The focus of the paper is on the relationship between General Practitioners (GPs) and central government. This relationship dates from the introduction of national health insurance in the UK. From the outset it had an impact on GPs' medical role, their professional status and income. The structure created in 1911 meant that GPs operated as franchisees and, notwithstanding Labour's policy objective of creating a salaried service, this role continued, effectively unchanged, after the creation of the National Health Service (NHS) in 1948. General practice was also the poor relation in contrast to hospital medicine, a feature intensified by the priorities of the NHS. These forces meant that GPs had a dual role: that of clinician and gatekeeper to specialist hospital services, a role in which they exercised substantial clinical freedom: and running a small business, a feature which was exaggerated by the absence of grant aid to improve premises prior to the Family Doctor Charter of 1965. This structural relationship has been progressively transformed by changes in the 1980s and 1990s. On the one hand the emphasis on cost control has seen central government attempting to combine a financial with a clinical gate-keeping keeping role. The crucial change in this respect is the creation of GP fundholding which, in turn, could be seen to have implications for the subordinate status of GPs within the medical profession. However, this has been combined with trends to greater measures of control over GPs. Of central importance in this respect were the changes introduced by the 1990 GP contract. The contract involved an attempt to substantially reduce clinical autonomy by building in much more detailed contractual duties with respect, for example, to health promotion activities. This was combined with the use of financial incentives to reach, for example, immunization targets. Control over clinical autonomy has also involved constraints over prescribing and the shift from Family

  18. A RESEARCH ON THE EFFECT OF ORGANIZATIONAL CLIMATE ON PERCEPTION OF SUPPORT FOR INNOVATION

    Directory of Open Access Journals (Sweden)

    GÖNÜL KAYA ÖZBAĞ

    2013-06-01

    Full Text Available The management of organizational climate is fairly important in terms of improving innovation in organizations. For that reason, the aim of this study is to investigate the effects of organizational climate dimensions (organizational encouragement, supervisory support, team support, otonomy, participation flexibility and communication on perception of support for innovation. Here the aim is trying to help administrators by determining the factors that increase or prevent innovation. Data obtained from 86 enterprises that are operating in Kocaeli is used in order to analyze the relationships among variables. After factor analysis, data is tested through correlation analysis and regression analysis. The findings of research indicate that organizational climate dimensions affect perception of support for innovation.

  19. Construction and immunogenicity of replication-competent adenovirus 5 host range mutant recombinants expressing HIV-1 gp160 of SF162 and TV1 strains.

    Science.gov (United States)

    Hidajat, Rachmat; Kuate, Seraphin; Venzon, David; Kalyanaraman, Vaniambadi; Kalisz, Irene; Treece, James; Lian, Ying; Barnett, Susan W; Robert-Guroff, Marjorie

    2010-05-21

    An HIV Env immunogen capable of eliciting broad immunity is critical for a successful vaccine. We constructed and characterized adenovirus 5 host range mutant (Ad5hr) recombinants encoding HIV(SF162) gp160 (subtype B) and HIV(TV1) gp160 (subtype C). Immunization of mice with one or both induced cellular immunity to subtype B and C peptides by ELISpot, and antibody responses with high binding titers to HIV Env of subtypes A, B, C, and E. Notably, Ad5hr-HIV(TV1) gp160 induced better cellular immunity than Ad5hr-HIV(SF162) gp160, either alone or following co-administration. Thus, the TV1 Env recombinant alone may be sufficient for eliciting immune responses against both subtype B and C envelopes. Further studies of Ad5hr-HIV(TV1) gp160 in rhesus macaques will evaluate the suitability of this insert for a future phase I clinical trial using a replication-competent Ad4 vector. Published by Elsevier Ltd.

  20. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    Energy Technology Data Exchange (ETDEWEB)

    Du, Yijun [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan (China); Pattnaik, Asit K. [School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900 (United States); Song, Cheng [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Yoo, Dongwan, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Gang, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing (China)

    2012-03-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  1. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    International Nuclear Information System (INIS)

    Du, Yijun; Pattnaik, Asit K.; Song, Cheng; Yoo, Dongwan; Li, Gang

    2012-01-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide–anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  2. Interpersonal amplification of risk? Citizen discussions and their impact on perceptions of risks and benefits of a biological research facility.

    Science.gov (United States)

    Binder, Andrew R; Scheufele, Dietram A; Brossard, Dominique; Gunther, Albert C

    2011-02-01

    Much risk communication research has demonstrated how mass media can influence individual risk perceptions, but lacks a comprehensive conceptual understanding of another key channel of communication: interpersonal discussion. Using the social amplification of risk as a theoretical framework, we consider the potential for discussions to function as amplification stations. We explore this possibility using data from a public opinion survey of residents living in potential locations for a new biological research facility in the United States. Controlling for a variety of key information variables, our results show that two dimensions of discussion-frequency and valence-have impacts on residents' perceptions of the facility's benefits and its risks. We also explore the possibility that an individual's overall attitude moderates the effect of discussion on their perceptions of risks and benefits. Our results demonstrate the potential for discussions to operate as amplifiers or attenuators of perceptions of both risks and benefits. © 2010 Society for Risk Analysis.

  3. Interview and recollection-based research with child disaster survivors: Participation-related changes in emotion and perceptions of participation

    Science.gov (United States)

    Hambrick, Erin P.; O’Connor, Bridget M.; Vernberg, Eric M.

    2015-01-01

    Objective Research suggests that some types of trauma research can be conducted safely with children ages 10 and older. The aim of this project was to learn more about potential risks or benefits of conducting research with younger children or with child disaster survivors, specifically about research that includes children providing trauma recollections. Method Fifty 8- to 12-year-old children who experienced a devastating tornado participated in an in-person interview that included both individual and joint (mother-child) recollections of their tornado experiences one year following exposure. These 50 children also rated three emotions at three timepoints and rated their perceptions (e.g., benefit and regret) of research post-participation. Children (N = 28) also participated in phone surveys three months later to assess persistent participation-related emotions and perceptions. Results Child reported emotions worsened from pre- to during participation; however, reports of emotions returned to pre-participation levels post-participation and remained so at the 3-month follow-up. Sixty-four percent of children reported at least some participation benefit and no participation regret immediately post-participation, as did 89.3% at the 3-month follow-up. Four percent of children reported some participation regret (no benefit) post-participation, and 0% three months later. No children requested to stop participating, and none required post-research connection with crisis services. Posttraumatic stress symptom severity, tornado exposure, and age were largely unrelated to child-reported emotions and perceptions of research. Conclusions Results indicate that carefully planned and executed disaster-related research that includes children providing recollections research can be conducted with preadolescents with little risk and some benefit. PMID:26390107

  4. Differences in Perceptions of Patient Safety Culture between Charge and Noncharge Nurses: Implications for Effectiveness Outcomes Research

    Directory of Open Access Journals (Sweden)

    Deleise Wilson

    2012-01-01

    Full Text Available The implementation of evidence-based practice guidelines can be influenced by nurses’ perceptions of the organizational safety culture. Shift-by-shift management of each nursing unit is designated to a subset of staff nurses (charge nurses, whom are often recruited as champions for change. The findings indicate that compared to charge nurses, noncharge nurses were more positive about overall perceptions of safety (=.05 and teamwork (<.05. Among charge nurses, significant differences were observed based on the number of years’ experience in charge: perception of teamwork within units [(3,365=3.52, <.01]; overall perceptions of safety, [(3,365=4.20, <.05]; safety grade for work area [(3,360=2.61, <.05]; number of events reported within the last month [(3,362=3.49, <.05]. These findings provide important insights to organizational contextual factors that may impact effectiveness outcomes research in the future.

  5. Sickness certification for common mental disorders and GP return-to-work advice.

    Science.gov (United States)

    Gabbay, Mark; Shiels, Chris; Hillage, Jim

    2016-09-01

    Aim To report the types and duration of sickness certification for different common mental disorders (CMDs) and the prevalence of GP advice aimed at returning the patient to work. In the United Kingdom, common mental health problems, such and depression and stress, have become the main reasons for patients requesting a sickness certificate to abstain from usual employment. Increasing attention is being paid to mental health and its impact on employability and work capacity in all parts of the welfare system. However, relatively little is known about the extent to which different mental health diagnoses impact upon sickness certification outcomes, and how the GP has used the new fit note (introduced in 2010) to support a return to work for patients with mental health diagnoses. Sickness certification data was collected from 68 UK-based general practices for a period of 12 months. Findings The study found a large part of all sickness absence certified by GPs was due to CMDs (29% of all sickness absence episodes). Females, younger patients and those living in deprived areas were more likely to receive a fit note for a CMD (compared with one for a physical health problem). The highest proportion of CMD fit notes were issued for 'stress'. However, sickness certification for depression contributed nearly half of all weeks certified for mental health problems. Only 7% of CMD fit notes included any 'may be fit' advice from the GP, with type of advice varying by mental health diagnostic category. Patients living in the most socially deprived neighbourhoods were less likely to receive 'may be fit' advice on their CMD fit notes.

  6. Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

    Science.gov (United States)

    Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

    2011-01-01

    Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

  7. Characteristics and career intentions of Scottish rural and urban GP registrars: cause for concern?

    Science.gov (United States)

    Ross, S; Gillies, J C

    1999-01-01

    To investigate the differences between the characteristics and career intentions of GP registrars in urban and rural areas, and to make recommendations to reduce a potential work force crisis in rural practice. Postal survey. All general practices in Scotland. In February 1996, 40/196 (20%) of urban and 45/150 (30%) of rural GP registrar places available in Scotland, were vacant (chi 2 = 4.22, df = 1, p = 0.02). Postal questionnaires were sent to all 261 GP registrars in post. Of 235 respondents (90%), the majority wished to remain in general practice (63% of urban and 53% of rural registrars), but only 22% of urban and 18% of rural registrars intended to apply for principal posts immediately after training. Fewer urban (8%) than rural registrars (21%) stated an intention to go abroad to work after training. Rural registrars tended to want to work in rural areas, and vice versa. Part-time and job-sharing were attractive employment options for both groups, and more flexible career structures were favoured by over 80%. Though much more attention has been paid to recruitment in inner cities, the findings from this study suggest that in Scotland difficulties in finding principals may occur first in rural areas. As general practitioners have an extended role in rural areas, including that of emergency care, shortages could have a serious impact on patient care.

  8. Identification of an N-linked glycan in the V1-loop of HIV-1 gp120 influencing neutralization by anti-V3 antibodies and soluble CD4

    DEFF Research Database (Denmark)

    Gram, G J; Hemming, A; Bolmstedt, A

    1994-01-01

    Glycosylation is necessary for HIV-1 gp120 to attain a functional conformation, and individual N-linked glycans of gp120 are important, but not essential, for replication of HIV-1 in cell culture. We have constructed a mutant HIV-1 infectious clone lacking a signal for N-linked glycosylation...... in the V1-loop of HIV-1 gp120. Lack of an N-linked glycan was verified by a mobility enhancement of mutant gp120 in SDS-gel electrophoresis. The mutated virus showed no differences in either gp120 content per infectious unit or infectivity, indicating that the N-linked glycan was neither essential nor...... affecting viral infectivity in cell culture. We found that the mutated virus lacking an N-linked glycan in the V1-loop of gp120 was more resistant to neutralization by monoclonal antibodies to the V3-loop and neutralization by soluble recombinant CD4 (sCD4). Both viruses were equally well neutralized by Con...

  9. Association between general practice characteristics and use of out-of-hours GP cooperatives.

    Science.gov (United States)

    Smits, Marleen; Peters, Yvonne; Broers, Sanne; Keizer, Ellen; Wensing, Michel; Giesen, Paul

    2015-05-01

    The use of out-of-hours healthcare services for non-urgent health problems is believed to be related to the organisation of daytime primary care but insight into underlying mechanisms is limited. Our objective was to examine the association between daytime general practice characteristics and the use of out-of-hours care GP cooperatives. A cross-sectional observational study in 100 general practices in the Netherlands, connected to five GP cooperatives. In each GP cooperative, we took a purposeful sample of the 10 general practices with the highest use of out-of-hours care and the 10 practices with the lowest use. Practice and population characteristics were obtained by questionnaires, interviews, data extraction from patient registration systems and telephone accessibility measurements. To examine which aspects of practice organisation were associated with patients' use of out-of-hours care, we performed logistic regression analyses (low versus high out-of-hours care use), correcting for population characteristics. The mean out-of-hours care use in the high use group of general practices was 1.8 times higher than in the low use group. Day time primary care practices with more young children and foreigners in their patient populations and with a shorter distance to the GP cooperative had higher out-of-hours primary care use. In addition, longer telephone waiting times and lower personal availability for palliative patients in daily practice were associated with higher use of out-of-hours care. Moreover, out-of-hours care use was higher when practices performed more diagnostic tests and therapeutic procedures and had more assistant employment hours per 1000 patients. Several other aspects of practice management showed some non-significant trends: high utilising general practices tended to have longer waiting times for non-urgent appointments, lower availability of a telephone consulting hour, lower availability for consultations after 5 p.m., and less frequent

  10. An Electrically Tight In Vitro Blood-Brain Barrier Model Displays Net Brain-to-Blood Efflux of Substrates for the ABC Transporters, P-gp, Bcrp and Mrp-1

    DEFF Research Database (Denmark)

    Helms, Hans Christian; Hersom, Maria; Kuhlmann, Louise Borella

    2014-01-01

    Efflux transporters of the ATP-binding cassette superfamily including breast cancer resistance protein (Bcrp/Abcg2), P-glycoprotein (P-gp/Abcb1) and multidrug resistance-associated proteins (Mrp's/Abcc's) are expressed in the blood-brain barrier (BBB). The aim of this study was to investigate......, zosuquidar, reversan and MK 571 alone or in combinations. Digoxin was mainly transported via P-gp, estrone-3-sulphate via Bcrp and Mrp's and etoposide via P-gp and Mrp's. The expression of P-gp, Bcrp and Mrp-1 was confirmed using immunocytochemistry. The findings indicate that P-gp, Bcrp and at least one...... isoform of Mrp are functionally expressed in our bovine/rat co-culture model and that the model is suitable for investigations of small molecule transport....

  11. Development of a Survey Instrument to Measure TEFL Academics' Perceptions about, Individual and Workplace Characteristics for Conducting Research

    Science.gov (United States)

    Bai, Li; Hudson, Peter; Millwater, Jan; Tones, Megan

    2013-01-01

    A 30-item survey was devised to determine Chinese TEFL (Teaching English as a Foreign Language) academics' potential for conducting research. A five-part Likert scale was used to gather data from 182 academics on four factors: (1) perceptions on teaching-research nexus, (2) personal perspectives for conducting research, (3) predispositions for…

  12. Antibiotics in Dutch general practice: nationwide electronic GP database and national reimbursement rates.

    NARCIS (Netherlands)

    Akkerman, A.E.; Kuyvenhoven, M.M.; Verheij, T.J.M.; Dijk, L. van

    2008-01-01

    PURPOSE: In order to assess whether different databases generate information which can be reliable compared with each other, this study aimed to assess to which degree prescribing rates for systemic antibiotics from a nationwide electronic general practitioner (GP) database correspond with national

  13. Inquiring Sport and Physical Activity students’ perceptions using metaphors as research tools

    OpenAIRE

    Martínez Ruiz, María Ángeles; Ávalos Ramos, María Alejandra; Merma Molina, Gladys

    2017-01-01

    The aim of this study is to analyse the metaphorical expressions designed by Science of Sport and Physical Activity university students, as a tool of inquiring two research questions: their perceptions of their physical education teachers, and the meaning physical activity has in students’ personal life. 51 students from the University of Alicante have participated in the study. Qualitative data analysis software AQUAD 6 was used for data processing. The results obtained from the analysis of ...

  14. Supply and demand in physician markets: a panel data analysis of GP services in Australia.

    Science.gov (United States)

    McRae, Ian; Butler, James R G

    2014-09-01

    To understand the trends in any physician services market it is necessary to understand the nature of both supply and demand, but few studies have jointly examined supply and demand in these markets. This study uses aggregate panel data on general practitioner (GP) services at the Statistical Local Area level in Australia spanning eight years to estimate supply and demand equations for GP services. The structural equations of the model are estimated separately using population-weighted fixed effects panel modelling with the two stage least squares formulation of the generalised method of moments approach (GMM (2SLS)). The estimated price elasticity of demand of [Formula: see text] is comparable with other studies. The direct impact of GP density on demand, while significant, proves almost immaterial in the context of near vertical supply curves. Supply changes are therefore due to shifts in the position of the curves, partly determined by a time trend. The model is validated by comparing post-panel model predictions with actual market outcomes over a period of three years and is found to provide surprisingly accurate projections over a period of significant policy change. The study confirms the need to jointly consider supply and demand in exploring the behaviour of physician services markets.

  15. Multifunctional PLGA Nanobubbles as Theranostic Agents: Combining Doxorubicin and P-gp siRNA Co-Delivery Into Human Breast Cancer Cells and Ultrasound Cellular Imaging.

    Science.gov (United States)

    Yang, Hong; Deng, Liwei; Li, Tingting; Shen, Xue; Yan, Jie; Zuo, Liangming; Wu, Chunhui; Liu, Yiyao

    2015-12-01

    Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. One of the effective approaches to overcome MDR is to use nanoparticle-mediated the gene silence of chemotherapeutic export proteins by RNA interference to increase drug accumulation in drug resistant cancer cells. In this work, a new co-delivery system, DOX-PLGA/PEI/P-gp shRNA nanobubbles (NBs) around 327 nm, to overcome doxorubicin (DOX) resistance in MCF-7 human breast cancer was designed and developed. Positively charged polyethylenimine (PEI) were modified onto the surface of DOX-PLGA NBs through DCC/NHS crosslinking, and could efficiently condense P-gp shRNA into DOX-PLGA/PEI NBs at vector/shRNA weight ratios of 70:1 and above. An in vitro release profile demonstrated an efficient DOX release (more than 80%) from DOX-PLGA/PEI NBs at pH 4.4, suggesting a pH-responsive drug release for the multifunctionalized NBs. Cellular experimental results further showed that DOX-PLGA/PEI/P-gp shRNA NBs could facilitate cellular uptake of DOX into cells and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The IC50 of DOX-PLGA NBs against MCF-7/ADR cells was 2-fold lower than that of free DOX. The increased cellular uptake and nuclear accumulation of DOX delivered by DOX-PLGA/PEI/P-gp shRNA NBs in MCF-7/ADR cells was confirmed by fluorescence microscopy and fluorescence spectrophotometry, and might be owning to the down-regulation of P-gp and reduced the efflux of DOX. The cellular uptake mechanism of DOX-PLGA/PEI/P-gp shRNA NBs indicated that the macropinocytosis was one of the pathways for the uptake of NBs by MCF-7/ADR cells, which was also an energy-dependent process. Furthermore, the in vitro cellular ultrasound imaging suggested that the employment of the DOX-PLGA/PEI/P-gp shRNA NBs could efficiently enhance ultrasound imaging of cancer cells. These results demonstrated

  16. Motivation for career choice and job satisfaction of GP trainees and newly qualified GPs across Europe: a seven countries cross-sectional survey.

    Science.gov (United States)

    Roos, Marco; Watson, Jessica; Wensing, Michel; Peters-Klimm, Frank

    2014-07-01

    Recruitment to general practice is a major concern in many countries. Cross-national exploration of motivation for career choice and career satisfaction could help inform workforce planning. Our aim was to explore motivation for career choice and job satisfaction of GP trainees and newly qualified GPs (NQGP) across seven European countries. We surveyed GP trainees and recently qualified GPs in the Czech Republic, Denmark, Germany, Italy, Norway, Portugal and the United Kingdom using a web-based questionnaire. The number of individuals who responded was 3722 (2533 GP trainees; 1189 NQGP). The most frequently cited reasons for choosing GP were 'compatibility with family life' (59.5%), 'challenging medically broad discipline' (58.9%), 'individual approach to people' (40.1%), 'holistic approach' (37.8%) and 'autonomy and independence' (30.4%). Despite differences in workload, work-life balance and earnings, overall job satisfaction was high, with over 80% saying that they would choose to be a doctor again; of these 78.4% would choose to be a GP again. In our sample reasons for choosing general practice as a career were strongly positive, with compatibility with family life the most frequently cited reason overall. This has implications for workforce planning. Further qualitative studies are needed to explore issues raised in more detail.

  17. Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

    Science.gov (United States)

    Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

    2017-07-20

    Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

  18. HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes.

    Science.gov (United States)

    Louboutin, Jean-Pierre; Agrawal, Lokesh; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

    2009-06-01

    Toxicity of HIV-1 envelope glycoprotein (gp120) for substantia nigra (SN) neurons may contribute to the Parkinsonian manifestations often seen in HIV-1-associated dementia (HAD). We studied the neurotoxicity of gp120 for dopaminergic neurons and potential neuroprotection by antioxidant gene delivery. Rats were injected stereotaxically into their caudate-putamen (CP); CP and (substantia nigra) SN neuron loss was quantified. The area of neuron loss extended several millimeters from the injection site, approximately 35% of the CP area. SN neurons, outside of this area of direct neurotoxicity, were also severely affected. Dopaminergic SN neurons (expressing tyrosine hydroxylase, TH, in the SN and dopamine transporter, DAT, in the CP) were mostly affected: intra-CP gp120 caused approximately 50% DAT+ SN neuron loss. Prior intra-CP gene delivery of Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) protected SN neurons from intra-CP gp120. Thus, SN dopaminergic neurons are highly sensitive to HIV-1 gp120-induced neurotoxicity, and antioxidant gene delivery, even at a distance, is protective.

  19. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    NARCIS (Netherlands)

    de Jong-Potjer, L. C.; Elsinga, J.; le Cessie, S.; van der Pal-de Bruin, K. M.; Neven, A. Knuistingh; Buitendijk, S. E.; Assendelft, W. J. J.

    2006-01-01

    BACKGROUND: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. METHODS: Randomised trial of usual care versus

  20. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    NARCIS (Netherlands)

    Jong-Potjer, L.C. de; Elsinga, J.; Cessie, S. le; Pal-de Bruin, K.M. van der; Knuistingh Neven, A.; Buitendijk, S.E.; Assendelft, W.J.J.

    2006-01-01

    Background: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods: Randomised trial of usual care versus

  1. Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers

    Directory of Open Access Journals (Sweden)

    Charles D. Morris

    2017-02-01

    Full Text Available Broadly neutralizing antibodies (bNAbs have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively. Trimeric scaffolds were also identified to stabilize the MPER-containing BG505 gp140.681 trimer in a native-like conformation. Following structural and antigenic evaluation, a subset of scaffold and trimer antigens was selected for immunization in BALB/c mice. Serum binding revealed distinct patterns of antibody responses to these two bNAb targets presented in different structural contexts. For example, the N332 nanoparticles elicited glycan epitope-specific antibody responses that could also recognize the native trimer, while a scaffolded BG505 gp140.681 trimer generated a stronger and more rapid antibody response to the trimer apex than its parent gp140.664 trimer. Furthermore, next-generation sequencing (NGS of mouse splenic B cells revealed expansion of antibody lineages with long heavy-chain complementarity-determining region 3 (HCDR3 loops upon activation by MPER scaffolds, in contrast to the steady repertoires primed by N332 nanoparticles and a soluble gp140.664 trimer. These findings will facilitate the future development of a coherent vaccination strategy that combines both epitope-focused and trimer-based approaches.

  2. Work-family balance by women GP specialist trainees in Slovenia: a qualitative study.

    Science.gov (United States)

    Petek, Davorina; Gajsek, Tadeja; Petek Ster, Marija

    2016-01-28

    Women physicians face many challenges while balancing their many roles: doctor, specialist trainee, mother and partner. The most opportune biological time for a woman to start a family coincides with a great deal of demands and requirements at work. In this study we explored the options and capabilities of women GP specialist trainees in coordinating their family and career. This is a phenomenological qualitative research. Ten GP specialist trainees from urban and rural areas were chosen by the purposive sampling technique, and semi-structured in-depth interviews were conducted, recorded, transcribed and analysed by using thematic analysis process. Open coding and the book of codes were formed. Finally, we performed the process of code reduction by identifying the themes, which were compared, interpreted and organised in the highest analytical units--categories. One hundred fifty-five codes were identified in the analysis, which were grouped together into eleven themes. The identified themes are: types, causes and consequences of burdens, work as pleasure and positive attitude toward self, priorities, planning and help, and understanding of superiors, disburdening and changing in specialisation. The themes were grouped into four large categories: burdens, empowerment, coordination and needs for improvement. Women specialist trainees encounter intense burdens at work and home due to numerous demands and requirements during their specialisation training. In addition, there is also the issue of the work-family conflict. There are many consequences regarding burden and strain; however, burnout stands out the most. In contrast, reconciliation of work and family life and needs can be successful. The key element is empowerment of women doctors. The foremost necessary systemic solution is the reinforcement of general practitioners in primary health care and their understanding of the specialisation training scheme with more flexible possibilities for time adaptations of

  3. PERCEPTION OF MODES OF PUBLIC TRANSPORT COMPARED TO TRAVEL BEHAVIOUR OF URBAN INHABITANTS IN LIGHT OF MARKETING RESEARCH

    Directory of Open Access Journals (Sweden)

    Katarzyna HEBEL

    2016-09-01

    Full Text Available The study introduces the notion of “travel behaviour” among urban inhabitants, as well as highlighting its most common determinants, one of which is the perception of public transport. The study includes a comparative analysis of the link between passenger perceptions of the main modes of public transport in relation to the actual mode of transport chosen to complete a certain journey, based on market research results collected within a given city.

  4. Induction of a protein-targeted catalytic response in autoimmune prone mice: antibody-mediated cleavage of HIV-1 glycoprotein GP120.

    Science.gov (United States)

    Ponomarenko, Natalia A; Vorobiev, Ivan I; Alexandrova, Elena S; Reshetnyak, Andrew V; Telegin, Georgy B; Khaidukov, Sergey V; Avalle, Bérangère; Karavanov, Alexander; Morse, Herbert C; Thomas, Daniel; Friboulet, Alain; Gabibov, Alexander G

    2006-01-10

    We have induced a polyclonal IgG that degrades the HIV-1 surface antigen, glycoprotein gp120, by taking advantage of the susceptibility of SJL mice to a peptide-induced autoimmune disorder, experimental autoimmune encephalomyelitis (EAE). Specific pathogen-free SJL mice were immunized with structural fragments of gp120, fused in-frame with encephalitogenic peptide MBP(85-101). It has resulted in a pronounced disease-associated immune response against antigens. A dramatic increase of gp120 degradation level by purified polyclonal IgG from immunized versus nonimmunized mice has been demonstrated by a newly developed fluorescence-based assay. This activity was inhibited by anti-mouse immunoglobulin antibodies as well as by Ser- and His-reactive covalent inhibitors. A dominant proteolysis site in recombinant gp120 incubated with purified polyclonal IgG from immunized mice was shown by SDS-PAGE. The SELDI-based mass spectrometry revealed that these antibodies exhibited significant specificity toward the Pro484-Leu485 peptide bond. The sequence surrounding this site is present in nearly half of the HIV-I variants. This novel strategy can be generalized for creating a catalytic vaccine against viral pathogens.

  5. Modification on ursodeoxycholic acid (UDCA) scaffold. discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1).

    Science.gov (United States)

    Sepe, Valentina; Renga, Barbara; Festa, Carmen; D'Amore, Claudio; Masullo, Dario; Cipriani, Sabrina; Di Leva, Francesco Saverio; Monti, Maria Chiara; Novellino, Ettore; Limongelli, Vittorio; Zampella, Angela; Fiorucci, Stefano

    2014-09-25

    Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3α,7β-dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of pro-glucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.

  6. Comb-like amphiphilic polypeptide-based copolymer nanomicelles for co-delivery of doxorubicin and P-gp siRNA into MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Suo, Aili, E-mail: ailisuo@mail.xjtu.edu.cn [Department of Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710061 (China); Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Zhang, Yaping; Liu, Rongrong; Xu, Weijun [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Wang, Hejing [Department of Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710061 (China)

    2016-05-01

    A comb-like amphiphilic copolymer methoxypolyethylene glycol-graft-poly(L-lysine)-block-poly(L-phenylalanine) (mPEG-g-PLL-b-Phe) was successfully synthesized. To synthesize mPEG-g-PLL-b-Phe, diblock copolymer PLL-b-Phe was first synthesized by successive ring-opening polymerization of α-amino acid N-carboxyanhydrides followed by the removal of benzyloxycarbonyl protecting groups, and then mPEG was grafted onto PLL-b-Phe by reductive amination via Schiff's base formation. The chemical structures of the copolymers were identified by {sup 1}H NMR. mPEG-g-PLL-b-Phe copolymer had a critical micelle concentration of 6.0 mg/L and could self-assemble in an aqueous solution into multicompartment nanomicelles with a mean diameter of approximately 78 nm. The nanomicelles could encapsulate doxorubicin (DOX) through hydrophobic and π–π stacking interactions between DOX molecules and Phe blocks and simultaneously complex P-gp siRNA with cationic PLL blocks via electrostatic interactions. The DOX/P-gp siRNA-loaded nanomicelles showed spherical morphology, possessed narrow particle size distribution and had a mean particle size of 120 nm. The DOX/P-gp siRNA-loaded nanomicelles exhibited pH-responsive release behaviors and displayed accelerated release under acidic conditions. The DOX/P-gp siRNA-loaded nanomicelles were efficiently internalized into MCF-7 cells, and DOX released could successfully reach nuclei. In vitro cytotoxicity assay demonstrated that the DOX/P-gp siRNA-loaded nanomicelles showed a much higher cytotoxicity in MCF-7 cells than DOX-loaded nanomicelles due to their synergistic killing effect and that the blank nanomicelles had good biocompatibility. Thus, the novel comb-like mPEG-g-PLL-b-Phe nanomicelles could be a promising vehicle for co-delivery of chemotherapeutic drug and genetic material. - Highlights: • Comb-like amphiphilic copolymer mPEG-g-PLL-b-Phe was successfully synthesized. • Polypeptide-based copolymer could self-assemble into

  7. Cloning and Characterization of the Genes Encoding the Murine Homologues of the Human Melanoma Antigens MART1 and gp100

    Science.gov (United States)

    Zhai, Yifan; Yang, James C.; Spiess, Paul; Nishimura, Michael I.; Overwijk, Willem W.; Roberts, Bruce; Restifo, Nicholas P.; Rosenberg, Steven A.

    2008-01-01

    The recent identification of genes encoding melanoma-associated antigens has opened new possibilities for the development of cancer vaccines designed to cause the rejection of established tumors. To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp 100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library. The open reading frames of murine MART1 and gp 100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins. Comparison of the DNA sequences of the murine MART1 genes, derived from normal melanocytes, the immortalized nontumorgenic melanocyte line Melan-a and the B16 melanoma, showed all to be identical. Northern and Western blot analyses confirmed that both genes encoded products that were melanocyte lineage proteins. Mice immunized with murine MART1 or gp 100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma. In contrast, immunization of mice with human gp 100 using recombinant adenoviruses elicited T cells specific for hgp100, but these T cells also cross reacted with B16 tumor in vitro and induced significant but weak protection against B16 challenge. Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hep100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma. These results may suggest that immunization with heterologous tumor antigen, rather than self, may be more effective as an immunotherapeutic reagent in designing antigen-specific cancer vaccines. PMID:9101410

  8. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro

    DEFF Research Database (Denmark)

    Niemeier, A; Willnow, T; Dieplinger, H

    1999-01-01

    for both LRP and megalin/gp330 were compared with regard to their ability to bind, internalize, and degrade dioctadecyltetramethylindocarbocyanine perchlorate (DiI)-fluorescence-labeled Lp(a) as well as equimolar amounts of 125I-labeled Lp(a) and LDL. Uptake and degradation of radiolabeled Lp...

  9. Organizational Justice Perception According to Generations

    Directory of Open Access Journals (Sweden)

    Zeki YÜKSEKBİLGİLİ

    2015-12-01

    Full Text Available Although there are many different researches on the subject of organizational justice, there is no research on organizational justice perception according to generations. In this study, the research subject is defined if there is a difference on the perception of organizational justice between x and y generations. After a conduct of 430 surveys the Organizational Justice Scale is used. As a result, it is proved that there is no significant difference between the organizational justice perceptions according to generations

  10. Aspects of public opinion research in risk perception studies covering the nuclear field

    Energy Technology Data Exchange (ETDEWEB)

    Tanimoto, Katia Suemi; Hiromoto, Goro, E-mail: ktanimoto@ipen.b, E-mail: hiromoto@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    A project for site selection and construction of a national radioactive waste repository is underway at the Comissao Nacional de Energia Nuclear. Public acceptance is determinant to the deployment of an undertaking of this size. A major concern regarding the use of nuclear energy are the problems related to safe management of the radioactive waste. For effective communication between decision makers and the public, a mutual understanding of views, as well as attitudes towards risk, is needed. The use of opinions polls is necessary in order to achieve it. This work aims to point out the major aspects to be approached by an opinion poll for the study of risk perception on the candidate regions for repository construction. A risk perception research model is presented, to be applied to the case of radioactive waste disposal, along with theoretical support to the organization and implementation of its structure. (author)

  11. Aspects of public opinion research in risk perception studies covering the nuclear field

    International Nuclear Information System (INIS)

    Tanimoto, Katia Suemi; Hiromoto, Goro

    2011-01-01

    A project for site selection and construction of a national radioactive waste repository is underway at the Comissao Nacional de Energia Nuclear. Public acceptance is determinant to the deployment of an undertaking of this size. A major concern regarding the use of nuclear energy are the problems related to safe management of the radioactive waste. For effective communication between decision makers and the public, a mutual understanding of views, as well as attitudes towards risk, is needed. The use of opinions polls is necessary in order to achieve it. This work aims to point out the major aspects to be approached by an opinion poll for the study of risk perception on the candidate regions for repository construction. A risk perception research model is presented, to be applied to the case of radioactive waste disposal, along with theoretical support to the organization and implementation of its structure. (author)

  12. Correlation of serum GP73, SOD and GPC3 contents with cell proliferation and angiogenesis in liver cancer lesion

    Directory of Open Access Journals (Sweden)

    Hua Xin

    2017-11-01

    Full Text Available Objective: To study the correlation of serum GP73, SOD and GPC3 contents with cell proliferation and angiogenesis in liver cancer lesion. Methods: Patients who were diagnosed with primary liver cancer in Jianghan Oilfield General Hospital between June 2014 and February 2017 were selected as liver cancer group, and healthy subjects who received physical examination in Jianghan Oilfield General Hospital during the same period were selected as control group. Serum was collected from two groups of subjects to determine the contents of GP73, SOD and GPC3; liver cancer lesion and adjacent lesion were collected from liver cancer group to determine the expression of cell proliferation molecules and angiogenesis molecules. Results: Serum GP73 and GPC3 levels of liver cancer group were obviously higher than those of control group while SOD content was obviously lower than that of control group; DNMT3B, STC2, SIRT6, LETM1, EphB4, SULT2B1, HIF-1α, VEGF, Ang-2, HGF and TGF-β1 protein expression levels in liver cancer lesion of liver cancer group were significantly higher than those in adjacent lesion; DNMT3B, STC2, SIRT6, LETM1, EphB4, SULT2B1, HIF-1α, VEGF, Ang-2, HGF and TGF-β1 protein expression levels in liver cancer lesion of liver cancer group were positively correlated with serum GP73 and GPC3 levels, and negatively correlated with serum SOD level. Conclusion: The changes of GP73, SOD and GPC3 levels in the serum of patients with liver cancer are closely related to the cell proliferation and angiogenesis in liver cancer lesion.

  13. Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*2402

    Directory of Open Access Journals (Sweden)

    Baba Toshiyuki

    2010-09-01

    Full Text Available Abstract Background The tumor associated antigen (TAA gp100 was one of the first identified and has been used in clinical trials to treat melanoma patients. However, the gp100 epitope peptide restricted to HLA-A*2402 has not been extensively examined clinically due to the ethnic variations. Since it is the most common HLA Class I allele in the Japanese population, we performed a phase I clinical trial of cancer vaccination using the HLA-A*2402 gp100 peptide to treat patients with metastatic melanoma. Methods The phase I clinical protocol to test a HLA-A*2402 gp100 peptide-based cancer vaccine was designed to evaluate safety as the primary endpoint and was approved by The University of Tokyo Institutional Review Board. Information related to the immunologic and antitumor responses were also collected as secondary endpoints. Patients that were HLA-A*2402 positive with stage IV melanoma were enrolled according to the criteria set by the protocol and immunized with a vaccine consisting of epitope peptide (VYFFLPDHL, gp100-in4 emulsified with incomplete Freund's adjuvant (IFA for the total of 4 times with two week intervals. Prior to each vaccination, peripheral blood mononuclear cells (PBMCs were separated from the blood and stored at -80°C. The stored PBMCs were thawed and examined for the frequency of the peptide specific T lymphocytes by IFN-γ- ELISPOT and MHC-Dextramer assays. Results No related adverse events greater than grade I were observed in the six patients enrolled in this study. No clinical responses were observed in the enrolled patients although vitiligo was observed after the vaccination in two patients. Promotion of peptide specific immune responses was observed in four patients with ELISPOT assay. Furthermore, a significant increase of CD8+ gp100-in4+ CTLs was observed in all patients using the MHC-Dextramer assay. Cytotoxic T lymphocytes (CTLs clones specific to gp100-in4 were successfully established from the PBMC of some

  14. Platelet GP II b/III a inhibitors in neurointervention therapeutics

    International Nuclear Information System (INIS)

    Wang Kuizhong; Huang Qinghai; Liu Jianmin

    2007-01-01

    The platelet glucoprotein (GP) II b/III a inhibitors prossess inhibiting platelet aggregation effectly. As new drugs of antiplatelet, they are different in mechanism with action, application and dosage between the II b/III a inhibitors and other tradional antiplatelet drugs such as aspirin or clopidogrel. In familiar with the pharmacologic action and clinical application of II b/III a inhibitors is important for endovascular interventional radiology, especially with important significance for obtaining high quality neuro-endovascular stenting in the perioperative period. (authors)

  15. Acceptability and perceived barriers and facilitators to creating a national research register to enable 'direct to patient' enrolment into research: the Scottish Health Research Register (SHARE).

    Science.gov (United States)

    Grant, Aileen; Ure, Jenny; Nicolson, Donald J; Hanley, Janet; Sheikh, Aziz; McKinstry, Brian; Sullivan, Frank

    2013-10-18

    Difficulties with recruitment pose a major, increasingly recognised challenge to the viability of research. We sought to explore whether a register of volunteers interested in research participation, with data linkage to electronic health records to identify suitable research participants, would prove acceptable to healthcare staff, patients and researchers. We undertook a qualitative study in which a maximum variation sampling approach was adopted. Focus groups and interviews were conducted with patients, general practitioners (GP), practice managers and health service researchers in two Scottish health boards. Analysis was primarily thematic to identify a range of issues and concerns for all stakeholder groups. The concept of a national research register was, in general, acceptable to all stakeholder groups and was widely regarded as beneficial for research and for society. Patients, however, highlighted a number of conditions which should be met in the design of a register to expedite confidence and facilitate recruitment. They also gave their perceptions on how a register should operate and be promoted, favouring a range of media. GPs and practice managers were primarily concerned with the security and confidentiality of patient data and the impact a register may have on their workload. Researchers were supportive of the initiative seeing advantages in more rapid access to a wider pool of patients. They did raise concerns that GPs may be able to block access to personal patient data held in general practice clinical systems and that the register may not be representative of the whole population. This work suggests that patients, healthcare staff and researchers have a favourable view of the potential benefits of a national register to identify people who are potentially eligible and willing to participate in health related research. It has highlighted a number of issues for the developers to incorporate in the design of research registers.

  16. The assessment of genetic risk of breast cancer : a set of GP guidelines

    NARCIS (Netherlands)

    de Bock, GH; Vlieland, TPMV; Hageman, GCHA; Oosterwijk, JC; Springer, MP; Kievit, J

    Background. Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to

  17. Protective Effect of Vitamin D3 and Gp63 Conjugated with Tetanus Toxoid on Outcome of Cutaneous Leishmaniasis Lesions in Balb/C Mice

    Directory of Open Access Journals (Sweden)

    S Soudi

    2006-01-01

    Full Text Available Introduction: GP63 is a major surface protease of Leishmania promastigotes that plays an important role in its virulance. As GP63 on its own can not develop an effective protection against leishmaniasis, the goal of this study was to evaluate the protective effect of GP63 conjugated with tetanus toxoid (TT and Vitamin D3 in susceptible BALB/c mice against cutaneous leishmaniasis. Methods: This study was a basic-applied experimental study performed in Tarbiat Modarres University from September 2002 to April 2005. Cloned virulant Leishmania (L. major [MRHO / IR / 75 / ER] strain was cultured and 5109 cells were harvested. GP63 Molecule was purified and conjugated with TT and conjugated molecule was used for immunization of 8 groups of female BALB/c mice. Results: Results showed that the group of mice receiving conjugated molecule with Vitamin D3 had significant differences from other groups regarding lesion progression (P0.05. The culture of spleen cells showed that the disease did not become systemic in this group. Conclusion: Conjugation of GP63 with TT strengthens cell immunity and its use along with vitamin D3 provokes macrophages activity. This basis can be used for production of an appropriate preparation for protection against Leishmaniasis.

  18. Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340.

    Science.gov (United States)

    Prakobphol, A; Xu, F; Hoang, V M; Larsson, T; Bergstrom, J; Johansson, I; Frängsmyr, L; Holmskov, U; Leffler, H; Nilsson, C; Borén, T; Wright, J R; Strömberg, N; Fisher, S J

    2000-12-22

    Salivary agglutinin is a high molecular mass component of human saliva that binds Streptococcus mutans, an oral bacterium implicated in dental caries. To study its protein sequence, we isolated the agglutinin from human parotid saliva. After trypsin digestion, a portion was analyzed by matrix-assisted laser/desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gave the molecular mass of 14 unique peptides. The remainder of the digest was subjected to high performance liquid chromatography, and the separated peptides were analyzed by MALDI-TOF/post-source decay; the spectra gave the sequences of five peptides. The molecular mass and peptide sequence information showed that salivary agglutinin peptides were identical to sequences in lung (lavage) gp-340, a member of the scavenger receptor cysteine-rich protein family. Immunoblotting with antibodies that specifically recognized either lung gp-340 or the agglutinin confirmed that the salivary agglutinin was gp-340. Immunoblotting with an antibody specific to the sialyl Le(x) carbohydrate epitope detected expression on the salivary but not the lung glycoprotein, possible evidence of different glycoforms. The salivary agglutinin also interacted with Helicobacter pylori, implicated in gastritis and peptic ulcer disease, Streptococcus agalactiae, implicated in neonatal meningitis, and several oral commensal streptococci. These results identify the salivary agglutinin as gp-340 and suggest it binds bacteria that are important determinants of either the oral ecology or systemic diseases.

  19. Students' Perception of a Flipped Classroom Approach to Facilitating Online Project-Based Learning in Marketing Research Courses

    Science.gov (United States)

    Shih, Wen-Ling; Tsai, Chun-Yen

    2017-01-01

    This study investigated students' perception of a flipped classroom approach to facilitating online project-based learning (FC-OPBL) in a marketing research course at a technical university. This combined strategy was aimed at improving teaching quality and learning efficiency. Sixty-seven students taking a marketing research course were surveyed.…

  20. VERTIGO AS AN ENT DISEASE : GENERAL PHYSICIAN AND THE COMMON MAN’S PERCEPTION

    Directory of Open Access Journals (Sweden)

    Sumit

    2015-08-01

    Full Text Available BACKGROUND : To study consciousness amongst General Physicians and common people, on their perception of Vertigo related to ENT disease. METHODS : Study was conducted in two different places of Eastern India from 2006 to 2015 . The patients with complaints of vertigo attending Otorhinolaryngologists at the first instance or by GP referral were studied . General Physicians also underwent a survey through a questionnaire. RESULTS : From the last 9 years of data , we find a defin ite increment in the number of vertigo patients at our OPD along with an increase in consciousness amongst the general physicians, though majority of doctors still don't think Vertigo to be predominantly an ENT disease

  1. Consumption of the Culture: Insights into the Research of the Perception of the Art

    Directory of Open Access Journals (Sweden)

    Eugenija Krukauskienė

    2015-10-01

    Full Text Available The main definitions of the culture consuption – research possibilities of the perception of art, including artistic products, creators of art, consumers of art, and the wider society are studied in this article. The analysis of how consumers use art, what meanings it elicits in their minds, and how it eventually penetrates into the general society, how it is mediated by these individuals and is affected by their attitudes and values, their social location is made analysed in this article. Art has a special function to provide the aesthetic experience. The perception of art is analysed by the data of Institute for Social Research in two levels: cognitive and emotional. The young people with bigger cultural capital perceive art in an aesthetic way and like elaborate art. Globalization has made Hollywood production more popular artifact throughout the world and it is production is the source of images for the young peoples. The mass media, like cinema, has created a new reality, hyperreality, which comprises constructing of images and modelling the everyday life of respondents – this is discussed in the article.

  2. Mucoadhesive properties and interaction with P-glycoprotein (P-gp) of thiolated-chitosans and -glycol chitosans and corresponding parent polymers: a comparative study.

    Science.gov (United States)

    Trapani, Adriana; Palazzo, Claudio; Contino, Marialessandra; Perrone, Maria Grazia; Cioffi, Nicola; Ditaranto, Nicoletta; Colabufo, Nicola Antonio; Conese, Massimo; Trapani, Giuseppe; Puglisi, Giovanni

    2014-03-10

    The aim of the present work was to compare the mucoadhesive and efflux pump P-glycoprotein (P-gp) interacting properties of chitosan (CS)- and glycolchitosan (GCS)-based thiomers and corresponding unmodified parent polymers. For this purpose, the glycol chitosan-N-acetyl-cysteine (GCS-NAC) and glycol chitosan-glutathione (GCS-GSH) thiomers were prepared under simple and mild conditions. Their mucoadhesive characteristics were studied by turbidimetric and zeta potential measurements. The P-gp interacting properties were evaluated measuring the effects of thiolated- and unmodified-polymers on the bidirectional transport (BA/AB) of rhodamine-123 across Caco-2 cells as well as in the calcein-AM and ATPase activity assays. Although all the thiomers and unmodified polymers showed optimal-excellent mucoadhesive properties, the best mucoadhesive performances have been obtained by CS and CS-based thiomers. Moreover, it was found that the pretreatment of Caco-2 cell monolayer with GCS-NAC or GCS restores Rho-123 cell entrance by inhibiting P-gp activity. Hence, GCS-NAC and GCS may constitute new biomaterials useful for improving the bioavailability of P-gp substrates.

  3. Stakeholder Perceptions of Risk in Construction

    Science.gov (United States)

    Zhao, Dong; McCoy, Andrew P.; Kleiner, Brian M.; Mills, Thomas H.; Lingard, Helen

    2015-01-01

    Safety management in construction is an integral effort and its success requires inputs from all stakeholders across design and construction phases. Effective risk mitigation relies on the concordance of all stakeholders’ risk perceptions. Many researchers have noticed the discordance of risk perceptions among critical stakeholders in safe construction work, however few have provided quantifiable evidence describing them. In an effort to fill this perception gap, this research performs an experiment that investigates stakeholder perceptions of risk in construction. Data analysis confirms the existence of such discordance, and indicates a trend in risk likelihood estimation. With risk perceptions from low to high, the stakeholders are architects, contractors/safety professionals, and engineers. Including prior studies, results also suggest that designers have improved their knowledge in building construction safety, but compared to builders they present more difficultly in reaching a consensus of perception. Findings of this research are intended to be used by risk management and decision makers to reassess stakeholders’ varying judgments when considering injury prevention and hazard assessment. PMID:26441481

  4. Addressing the crisis of GP recruitment and retention: a systematic review.

    Science.gov (United States)

    Marchand, Catherine; Peckham, Stephen

    2017-04-01

    The numbers of GPs and training places in general practice are declining, and retaining GPs in their practices is an increasing problem. To identify evidence on different approaches to retention and recruitment of GPs, such as intrinsic versus extrinsic motivational determinants. Synthesis of qualitative and quantitative research using seven electronic databases from 1990 onwards (Medline, Embase, Cochrane Library, Health Management Information Consortium [HMIC], Cumulative Index to Nursing and Allied Health Literature (Cinahl), PsycINFO, and the Turning Research Into Practice [TRIP] database). A qualitative approach to reviewing the literature on recruitment and retention of GPs was used. The studies included were English-language studies from Organisation for Economic Cooperation and Development countries. The titles and abstracts of 138 articles were reviewed and analysed by the research team. Some of the most important determinants to increase recruitment in primary care were early exposure to primary care practice, the fit between skills and attributes, and a significant experience in a primary care setting. Factors that seemed to influence retention were subspecialisation and portfolio careers, and job satisfaction. The most important determinants of recruitment and retention were intrinsic and idiosyncratic factors, such as recognition, rather than extrinsic factors, such as income. Although the published evidence relating to GP recruitment and retention is limited, and most focused on attracting GPs to rural areas, the authors found that there are clear overlaps between strategies to increase recruitment and retention. Indeed, the most influential factors are idiosyncratic and intrinsic to the individuals. © British Journal of General Practice 2017.

  5. Perceptions of Faculty toward Integrating Technology in Undergraduate Higher Education Traditional Classrooms at Research-Focused Regional Universities in South Texas

    Science.gov (United States)

    Shipman, Cheri Deann

    2017-01-01

    This qualitative study examined the perceptions of faculty members who use technology in undergraduate higher education traditional classrooms in research-focused regional universities in South Texas. Faculty members at research-focused regional universities are expected to divide time judiciously into three major areas: research, service, and…

  6. The Significance of Benefit Perceptions for the Ethics of HIV Research Involving Adolescents in Kenya.

    Science.gov (United States)

    Rennie, Stuart; Groves, Allison K; Hallfors, Denise Dion; Iritani, Bonita J; Odongo, Fredrick S; Luseno, Winnie K

    2017-10-01

    Assessment of benefits is traditionally regarded as crucial to the ethical evaluation of research involving human participants. We conducted focus group discussions (FGDs) with health and other professionals engaged with adolescents, caregivers/parents, and adolescents in Siaya County, Kenya, to solicit opinions about appropriate ways of conducting HIV research with adolescents. Our data revealed that many focus group participants have a profoundly positive conception of participation in health research, including studies conferring seemingly few benefits. In this article, we identify and analyze five different but interrelated types of benefits as perceived by Kenyan adolescent and adult stakeholders in HIV research, and discuss their ethical significance. Our findings suggest that future empirical and conceptual research should concentrate on factors that may trigger researcher obligations to improve benefit perceptions among research participants.

  7. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

    Directory of Open Access Journals (Sweden)

    Hammond Robert R

    2004-05-01

    Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

  8. Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

    Directory of Open Access Journals (Sweden)

    Gavin Churchyard

    Full Text Available The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM, SAAVI MVA-C (2.9 x 109 pfu IM and Novartis V2-deleted subtype C gp140 (100 mcg with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa.Participants at three South African sites were randomized (1:1:1:1 to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P; concurrent MVA/gp140 (MP/MP; DNA prime, sequential MVA boost (D/D/M/M; DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP or placebo. Peak HIV specific humoral and cellular responses were measured.184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens.The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen.ClinicalTrials.gov NCT01418235.

  9. Ninety-five- and 25-kDa fragments of the human immunodeficiency virus envelope glycoprotein gp120 bind to the CD4 receptor

    International Nuclear Information System (INIS)

    Nygren, A.; Bergman, T.; Matthews, T.; Joernvall, H.; Wigzell, H.

    1988-01-01

    Iodine-125-labeled gp120 (120-kDa envelope glycoprotein) from the BH10 isolate of human immunodeficiency virus is cleaved to a limited extend with the glutamate-specific protease from Staphylococcus aureus. After disulfide bond reduction, fragments with approximate molecular masses of 95, 60, 50, and 25 kDa are produced. Tests for binding to CD4-positive cells show that only two fragments, the 95- and 25- kDa peptides, are observed in cleavage products that retain the selective binding capacity of gp120. Radiosequence analysis of the fragments after sodium dodecyl sulfate/polyacrylamide gel electrophoresis and electroblotting demonstrates that the 95-kDa fragment lacks the N-terminal region of gp120 and starts at position 143 of the mature envelope protein. The 50-kDa fragment starts at the same position. The 25-kDa binding fragment was similarly deduced to be generated as a small fragment from a cleavage site in the C-terminal part of gp120. The identifications of these fragments demonstrate that radiosequence analysis utilizing 125 I-labeled tyrosine residues can function as a useful and reliable method for small-scale determination of cleavage sites in proteins. Combined, the data suggest domain-like subdivisions of gp120, define at least two intervening segments especially sensitive to proteolytic cleavage, and demonstrate the presence of a functional region for receptor binding in the C-terminal part of the molecule

  10. Canadian University Professors’Perceptions of the Challenges and Sup-port to Engage in Research

    Institute of Scientific and Technical Information of China (English)

    SHI Hui

    2013-01-01

    Research has been an important responsibility for university professors. Although there has been an increased demand for research, few studies have been conducted directly with university professors to obtain their perceptions of the challenges the in⁃creased focus on research have presented. This study employed a qualitative methodology to inquire into the change of work life bought about by the increased demand for research, and the strategies professors have adopted to balance their teaching, research and service. It also inquired into the barriers to conducting research, and effective support strategies. Some barriers and support identified in this study were in accordance with what previous studies have identified. Perhaps because the professors interviewed were all tenured, they noted that the increased demand for research had not significantly changed their work life. Strategies they used to help them meet the demands for research included, but were not limited to, integrating their teaching and research, and col⁃laborating with others on research projects. Barriers to research included bureaucratic constraints, newness to research, lack of time, and lack of funding.

  11. Functional cloning of a gp100-reactive T-cell receptor from vitiligo patient skin

    NARCIS (Netherlands)

    Klarquist, Jared; Eby, Jonathan M.; Henning, Steven W.; Li, Mingli; Wainwright, Derek A.; Westerhof, Wiete; Luiten, Rosalie M.; Nishimura, Michael I.; Le Poole, I. Caroline

    2016-01-01

    We isolated gp100-reactive T cells from perilesional skin of a patient with progressive vitiligo with superior reactivity toward melanoma cells compared with tumor-infiltrating lymphocytes 1520, a melanoma-derived T-cell line reactive with the same cognate peptide. After dimer enrichment and limited

  12. Does an in-house internist at a GP practice result in reduced referrals to hospital-based specialist care?

    Science.gov (United States)

    Quanjel, Tessa C C; Winkens, Anne; Spreeuwenberg, Marieke D; Struijs, Jeroen N; Winkens, Ron A G; Baan, Caroline A; Ruwaard, Dirk

    2018-03-01

    Consistent evidence on the effects of specialist services in the primary care setting is lacking. Therefore, this study evaluated the effects of an in-house internist at a GP practice on the number of referrals to specialist care in the hospital setting. Additionally, the involved GPs and internist were asked to share their experiences with the intervention. A retrospective interrupted times series study. Two multidisciplinary general practitioner (GP) practices. An internist provided in-house patient consultations in two GP practices and participated in the multidisciplinary meetings. The referral data extracted from the electronic medical record system of the GP practices, including all referral letters from the GPs to specialist care in the hospital setting. The number of referrals to internal medicine in the hospital setting. This study used an autoregressive integrated moving average model to estimate the effect of the intervention taking account of a time trend and autocorrelation among the observations, comparing the pre-intervention period with the intervention period. It was found that the referrals to internal medicine did not statistically significant decrease during the intervention period. This small explorative study did not find any clues to support that an in-house internist at a primary care setting results in a decrease of referrals to internal medicine in the hospital setting. Key Points An in-house internist at a primary care setting did not result in a significant decrease of referrals to specialist care in the hospital setting. The GPs and internist experience a learning-effect, i.e. an increase of knowledge about internal medicine issues.

  13. Crystal Structure of Bacteriophage SPP1 Distal Tail Protein (gp19.1)

    Science.gov (United States)

    Veesler, David; Robin, Gautier; Lichière, Julie; Auzat, Isabelle; Tavares, Paulo; Bron, Patrick; Campanacci, Valérie; Cambillau, Christian

    2010-01-01

    Siphophage SPP1 infects the Gram-positive bacterium Bacillus subtilis using its long non-contractile tail and tail-tip. Electron microscopy (EM) previously allowed a low resolution assignment of most orf products belonging to these regions. We report here the structure of the SPP1 distal tail protein (Dit, gp19.1). The combination of x-ray crystallography, EM, and light scattering established that Dit is a back-to-back dimer of hexamers. However, Dit fitting in the virion EM maps was only possible with a hexamer located between the tail-tube and the tail-tip. Structure comparison revealed high similarity between Dit and a central component of lactophage baseplates. Sequence similarity search expanded its relatedness to several phage proteins, suggesting that Dit is a docking platform for the tail adsorption apparatus in Siphoviridae infecting Gram-positive bacteria and that its architecture is a paradigm for these hub proteins. Dit structural similarity extends also to non-contractile and contractile phage tail proteins (gpVN and XkdM) as well as to components of the bacterial type 6 secretion system, supporting an evolutionary connection between all these devices. PMID:20843802

  14. Research progress of functional magnetic resonance imaging in cross-modal activation of visual cortex during tactile perception

    International Nuclear Information System (INIS)

    Zhan Jie; Gong Honghan

    2013-01-01

    An increasing amount of neuroimaging studies recently demonstrated activation of visual cortex in both blind and sighted participants when performing a variety of tactile tasks such as Braille reading and tactile object recognition, which indicates that visual cortex not only receives visual information, but may participate in tactile perception. To address these cross-modal changes of visual cortex and the neurophysiological mechanisms, many researchers conducted explosive studies using functional magnetic resonance imaging (fMRI) and have made some achievements. This review focuses on cross-modal activation of visual cortex and the underlying mechanisms during tactile perception in both blind and sighted individuals. (authors)

  15. A perceptual channel for information transfer over kilometer distances Historical perspective and recent research. [extrasensory perception

    Science.gov (United States)

    Puthoff, H. E.; Targ, R.

    1976-01-01

    For more than 100 years, scientists have attempted to determine the truth or falsity of claims for the existence of a perceptual channel whereby certain individuals are able to perceive and describe remote data not presented to any known sense. This paper presents an outline of the history of scientific inquiry into such so-called paranormal perception and surveys the current state of the art in parapsychological research in the United States and abroad. The nature of this perceptual channel is examined in a series of experiments carried out in the Electronics and Bioengineering Laboratory of Stanford Research Institute. The perceptual modality most extensively investigated is the ability of both experienced subjects and inexperienced volunteers to view, by innate mental processes, remote geographical or technical targets including buildings, roads, and laboratory apparatus. The accumulated data indicate that the phenomenon is not a sensitive function of distance, and Faraday cage shielding does not in any apparent way degrade the quality and accuracy of perception. On the basis of this research, some areas of physics are suggested from which a description or explanation of the phenomenon could be forthcoming.

  16. Food quality and safety: Consumer perception and demand

    DEFF Research Database (Denmark)

    Grunert, Klaus G.

    2005-01-01

    choice and consumer demand, addressing questions of price perception and the validity of willingness-to-pay measurements. It is concluded that food quality and safety are central issues in today's food economics, though many research questions remain to be addressed. Udgivelsesdato: SEP 1......Research on consumer quality perception is reviewed using the Total Food Quality Model as a structuring device. The relationship between food safety and quality is addressed, and is discussed in the context of research on consumer risk perception. Quality and safety perception is linked to food...

  17. Food quality and safety: Consumer perception and demand

    DEFF Research Database (Denmark)

    Grunert, Klaus G.

    2005-01-01

    Research on consumer quality perception is reviewed using the Total Food Quality Model as a structuring device. The relationship between food safety and quality is addressed, and is discussed in the context of research on consumer risk perception. Quality and safety perception is linked to food...... choice and consumer demand, addressing questions of price perception and the validity of willingness-to-pay measurements. It is concluded that food quality and safety are central issues in today's food economics, though many research questions remain to be addressed. Udgivelsesdato: SEP 1...

  18. Identification of an N-linked glycan in the V1-loop of HIV-1 gp120 influencing neutralization by anti-V3 antibodies and soluble CD4

    DEFF Research Database (Denmark)

    Gram, G J; Hemming, A; Bolmstedt, A

    1994-01-01

    affecting viral infectivity in cell culture. We found that the mutated virus lacking an N-linked glycan in the V1-loop of gp120 was more resistant to neutralization by monoclonal antibodies to the V3-loop and neutralization by soluble recombinant CD4 (sCD4). Both viruses were equally well neutralized by Con...... in the V1-loop of HIV-1 gp120. Lack of an N-linked glycan was verified by a mobility enhancement of mutant gp120 in SDS-gel electrophoresis. The mutated virus showed no differences in either gp120 content per infectious unit or infectivity, indicating that the N-linked glycan was neither essential nor...

  19. A tool to assess sex-gender when selecting health research projects.

    Science.gov (United States)

    Tomás, Concepción; Yago, Teresa; Eguiluz, Mercedes; Samitier, M A Luisa; Oliveros, Teresa; Palacios, Gemma

    2015-04-01

    To validate the questionnaire "Gender Perspective in Health Research" (GPIHR) to assess the inclusion of gender perspective in research projects. Validation study in two stages. Feasibility was analysed in the first, and reliability, internal consistence and validity in the second. Aragón Institute of Health Science, Aragón, Spain. GPIHR was applied to 118 research projects funded in national and international competitive tenders from 2003 to 2012. Analysis of inter- and intra-observer reliability with Kappa index and internal consistency with Cronbach's alpha. Content validity analysed through literature review and construct validity with an exploratory factor analysis. Validated GPIHR has 10 questions: 3 in the introduction, 1 for objectives, 3 for methodology and 3 for research purpose. Average time of application was 13min Inter-observer reliability (Kappa) varied between 0.35 and 0.94 and intra-observer between 0.40 and 0.94. Theoretical construct is supported in the literature. Factor analysis identifies three levels of GP inclusion: "difference by sex", "gender sensitive" and "feminist research" with an internal consistency of 0.64, 0.87 and 0.81, respectively, which explain 74.78% of variance. GPIHR questionnaire is a valid tool to assess GP and useful for those researchers who would like to include GP in their projects. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. Applying the trigger review method after a brief educational intervention: potential for teaching and improving safety in GP specialty training?

    OpenAIRE

    McKay, John; de Wet, Carl; Kelly, Moya; Bowie, Paul

    2013-01-01

    Background:\\ud The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be teste...