Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae

We have used different mouse strains to examine in vivo and in vitro responses to the 18 kDa protein of Mycobacterium leprae, which appears to be strongly immunogenic in both mice and humans. B and T cell stimulatory epitopes recognised by different strains of mice have been mapped using overlapping peptides that span the entire 18 kDa protein. Previous work established that Immunization of mice with the 18 kDa protein results in specific antibody production to common B cell epitopes and immunization of mice with peptides containing these B cell epitopes resulted in the induction of specific IgG to only a limited subset of epitopes in each strain. Now we report that T cells purified from mice immunized with peptides that stimulate antibody production, proliferate in vitro when rechallenged. The proliferating T cells produce levels of IL-2 and IFN-γ, that indicate antigen-specific T helper type 1 cells are present in significant numbers. Thus, a comparison of in vivo and in vitro data suggests that T cells bearing the phenotype associated with potentially protective cell-mediated responses can be primed in vivo by epitopes on small peptides. Since T cells from both strains of mice are capable of responding to the immunogenic synthetic peptides in vitro, but give different responses to the same peptides in vivo, factors other than epltope structure appear to influence T cell subset activation. This may have important implications for diseases such as leprosy where a polarized T cell response appears to develop and for the development of synthetic subunit vaccine

Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts

Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson’s disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population. Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD. Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models. Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43). Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.publishedVersio

GBA and APOE Impact Cognitive Decline in Parkinson's Disease : A 10-Year Population-Based Study

Acknowledgments: We would like to thank all participants, study personnel from each study, and funders of individual studies and of PICC. We would like to thank Artur Wozniak and Adrian Martin from the University of Aberdeen, Data Management Department, for help in developing the PICC database. We acknowledge the contributions of members of the individual study groups as detailed below. Members of PICC Steering Group: Dr. Angus D. Macleod, Dr. Carl E. Counsell (Chair), University of Aberdeen, UK; Prof. Ole-Bjørn Tysnes, University of Bergen, Norway; Marta Camacho, Dr. Caroline WilliamsGray, University of Cambridge, UK; Dr. Rachael A. Lawson, Newcastle University, UK; Dr. Jodi Maple-Grødem, Prof. Guido Alves, Stavanger University Hospital, Norway; Prof. Lars Forgren, Umeå University, Sweden. CamPaIGN study: Roger A. Barker, Thomas Foltynie, Sarah L. Mason, Caroline H. Williams-Gray. ICICLE-PD Study: David Burn, Lynn Rochester, Alison J. Yarnall, Rachael A. Lawson, Gordon W. Duncan, Tien K. Khoo. NYPUM Study: Lars Forsgren, Jan Linder, Mona Edström, Jörgen Andersson, Linda Eriksson, David Bäckström, Gun-Marie Hariz, Magdalena Domellöf. ParkWest Study: ParkWest Principal investigators: Guido Alves (Norwegian Centre for Movement Disorders, Stavanger University Hospital) and Ole-Bjørn Tysnes (Haukeland University Hospital). Study personnel: Michaela Dreetz Gjerstad, Kenn Freddy Pedersen, Elin Bjelland Forsaa, Veslemøy Hamre Frantzen, Anita Laugaland, Jodi MapleGrødem, Johannes Lange, Karen Simonsen, Eldbjørg Fiske and Ingvild Dalen (Stavanger University Hospital); Bernd Müller, Geir Olve Skeie and Marit Renså (Haukeland University Hospital); Wenche Telstad, Aliaksei Labusau and Jane Kastet (Førde Hospital); Ineke HogenEsch, Marianne Kjerandsen and Liv Kari Håland (Haugesund Hospital); Karen Herlofson, Solgunn Ongre, and Siri Bruun (Sørlandet Hospital Arendal). PICNICS study: Roger A. Barker, Marta Camacho, Gemma Cummins, Jonathan R. Evans, David P. Breen, Ruwani S. Wijeyekoon, Caroline H. Williams-Gray. PINE Study: Medical: Carl E. Counsell, Kate S. M. Taylor, Robert Caslake, Angus D. Macleod, David J. M. McGhee, Diane Swallow; Research nurse/assistant: Joanne Gordon, Clare Harris, Ann Hayman, Nicola Johannesson, Hazel Forbes; Data management: Valerie Angus, Alasdair Finlayson, David Dawson, Katie Wilde, David Ritchie, Artur Wozniak; Statisticians: Neil Scott, Shona Fielding; Radiology: Prof. Alison Murray; Pathology: Ishbel Gall, Dr. James MacKenzie, Prof. Colin Smith; Secretarial: Aileen Sylvester, Susan Mitchell, Pam Rebecca, Ann Christie, and Diane McCosh. Funding agencies: This work was supported by the Research Council of Norway (287842). The CamPaIGN study has received funding from the Wellcome Trust, the Medical Research Council, the Patrick Berthoud Trust, and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The ICICLE-PD study was funded by Parkinson’s UK (J-0802, G-1301, G-1507) and supported by the Lockhart Parkinson’s Disease Research Fund, National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit and Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The NYPUM study was supported by grants from the Swedish Medical Research Council, Erling-Persson Foundation, the Swedish Brain Foundation (Hjärnfonden), Umeå University, Västerbotten County Council, King Gustaf V and Queen Victoria Freemason Foundation, Swedish Parkinson Foundation, Swedish Parkinson Research Foundation, Kempe Foundation, Swedish PD Association, the European Research Council, and the Knut and Alice Wallenberg Foundation. The Norwegian ParkWest study has received funding from the Research Council of Norway (177966), the Western Norway Regional Health Authority (911218), the Norwegian Parkinson’s Research Foundation, and Rebergs Legacy. The PICNICS study was funded by the Cure Parkinson’s Trust, the Van Geest Foundation, the Medical Research Council, Parkinson’s UK, and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The PINE study was funded by Parkinson’s UK (grant numbers G0502, G0914, and G1302), the Scottish Chief Scientist Office (CAF/12/05, PCL/17/10), Academy of Medical Sciences, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING. The PICC collaboration has been supported by The Chief Scientist Office of the Scottish Government (PCL/17/10), the Academy of Medical Sciences, Parkinson’s UK (initial collaborator meeting) and the Norwegian Association for Public Health. C.R.S.’s work was supported by NIH grants NINDS/NIA R01NS115144, U01NS095736, U01NS100603, and the American Parkinson Disease Association Center for Advanced Parkinson Research. This research was funded in whole, or in part by the UKRI Medical Research Council [MR/R007446/1]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

Sensory determinants of stated liking for vegetable names and actual liking for canned vegetables: A cross-country study among European adolescents.

Sensory properties are reported as one of the main factors hindering an appropriate vegetable intake by the young. In the present work the sensory determinants of likings for vegetables were explored in adolescents of four European countries (Denmark, n = 88; France, n = 206; Italy, n = 110 and United Kingdom, n = 93). A questionnaire was designed to study cross country differences in stated liking for and familiarity with a list of vegetables popular among European markets (between-vegetable approach). A within-vegetable comparison approach with actual tasting was used to analyze differences and similarities in liking for canned pea and sweet corn samples across the countries. A close positive relationship between stated liking and familiarity was found. Irrespective of the country, one group of highly liked vegetables (carrots, tomatoes, green salad) was identified, characterized by innately liked tastes (sweet, umami), delicate flavour and bright appealing colour. A second group of highly disliked vegetables consists of cauliflowers and broccoli, characterized by disliked sensations such as bitter taste and objectionable flavour. Internal Preference Maps from actual liking scores indicate that the generally disliked tastes (bitter, sour), are clearly correlated with a negative hedonic response for both peas and sweet corn. The hedonic valence of a generally well accepted taste such as salty and texture descriptors depends on the type of vegetable. Internal preference maps from actual liking data indicate that flavour and appearance descriptors of the distinct sensory properties of each type of vegetable positively affect liking, while the intensity of unusual flavours is related to sample disliking

Cognitive and Motor Decline in Dementia with Lewy Bodies and Parkinson's Disease Dementia

Funding Information: The University of Stavanger supported M.C.G. The CamPaIGN study has received funding from the Wellcome Trust, the Medical Research Council, the Patrick Berthoud Trust, and the NIHR Cambridge Biomedical Research Centre (BRC‐1215‐20014). The ICICLE‐PD study was funded by Parkinson's UK (J‐0802, G‐1301, G‐1507) and supported by the Lockhart Parkinson's Disease Research Fund, National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit and Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The PICNICS study was funded by the Cure Parkinson's Trust, the Van Geest Foundation, the Medical Research Council, Parkinson's UK, and the NIHR Cambridge Biomedical Research Centre (BRC‐1215‐20014). The NYPUM study was supported by grants from the Swedish Medical Research Council, Erling‐Persson Foundation, the Swedish Brain Foundation (Hjärnfonden), Umeå University, Västerbotten County Council, King Gustaf V and Queen Victoria Freemason Foundation, Swedish Parkinson Foundation, Swedish Parkinson Research Foundation, Kempe Foundation, Swedish PD Association, the European Research Council, and the Knut and Alice Wallenberg Foundation. The PINE study was funded by Parkinson's UK (grant numbers G0502, G0914, and G1302), the Scottish Chief Scientist Office (CAF/12/05, PCL/17/10), Academy of Medical Sciences, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING. The PARKWEST study was supported by the Research Council of Norway (grant# 177966), the Western Norway Regional Health Authority (grant# 911218 and # 911949), Reberg legacy and the Norwegian Parkinson's Research Foundation. The PICC collaboration has been supported by The Chief Scientist Office of the Scottish Government (PCL/17/10), the Academy of Medical Sciences, Parkinson's UK (initial collaborator meeting) and the Norwegian Association for Public Health. The DEMVEST Study was supported by the regional health authorities of Western Norway, Helse‐Vest (grant# 911973). Motol University Hospital's Czech Brain Aging Study was supported by the National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107)—Funded by the European Union—Next Generation EU and by Charles University grant PRIMUS 22/MED/011. The Sant Pau Initiative on Neurodegeration (SPIN) cohort was supported by the Fondo de Investigaciones Sanitario (FIS), Instituto de Salud Carlos III (PI14/01126, PI17/01019 and PI20/01473 to JF, PI13/01532 and PI16/01825 to RB, PI18/00335 to MCI, PI18/00435 and INT19/00016 to DA, PI17/01896 and AC19/00103to AL) and the CIBERNED program (Program 1, Alzheimer Disease to AL), jointly funded by Fondo Europeo de Desarrollo Regional, Unión Europea, “Una manera de hacer Europa”. It was also supported by the National Institutes of Health (NIA grants 1R01AG056850‐01A1; R21AG056974; and R01AG061566), by Generalitat de Catalunya (2017‐SGR‐547, SLT006/17/125, SLT006/17/119, SLT002/16/408) and “Marató TV3” foundation grants 20141210, 044412 and 20142610. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The sponsors were not involved in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. The authors declare that there are no conflicts of interest relevant to this work. Funding Sources and Conflicts of Interest:Peer reviewedPublisher PD

U-Shaped Relation between Plasma Oxytocin Levels and Behavior in the Trust Game

10.1371/journal.pone.0051095PLoS ONE712

ISPMD consensus on the management of premenstrual disorders

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration

Boundary-Scan in the ATCA standard

Larger systems today, like telephone and optical switches, are usually based on a multiboard architecture where a set of printed-circuit boards are connected to a backplane board. These systems are also equipped with Boundary-Scan to enable testing, however, the backplane in a multi-board system has a limited wiring capability, which makes the additional backplane Boundary-Scan wiring highly costly. The problem is to access the Boundary-Scan enabled boards with the Boundary-Scan controller located at a central board. In this MSc. thesis project we propose an approach suitable for the Advanced Telecommunication Computing Architecture (ATCA) standard where we make use of the existing Intelligent Platform Management Bus (IPMB) and expands its protocol for application of Boundary-Scan tests. We have also defined a command set as well as a test data format for storing embedded test data on the boards to support the remote execution of Boundary-Scan tests. For validation of the proposed approach we have developed demonstrator