13 research outputs found

    Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

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    Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

    Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

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    BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

    Genomic investigations of unexplained acute hepatitis in children

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    Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

    Development of an artificial insemination protocol in llamas using cooled semen

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    The objective of this study was to design an AI protocol using cooled semen to obtain pregnancies in the llama. Each raw ejaculate was subdivided into four aliquots which were extended 1:1 with: (1) 11% lactose-egg yolk (L-EY), (2) Tris-citrate-fructose-egg yolk (T-F-EY), (3) PBS-llama serum (S-PBS) and (4) skim milk-glucose (K). Each sample reached 5°C in 2.5h and remained at that temperature during 24h. Percentages of the semen variables (motility, live spermatozoa) in ejaculates and samples cooled with L-EY were significantly greater than those obtained when cooling with the other extenders; therefore this extender was used (1:1) for all inseminations. Females were randomly divided into four groups (A-D) according to insemination protocol. Group A: females were inseminated with a fixed dose of 12×10 6 live spermatozoa kept at 37°C. Group B: females were inseminated with a fixed dose of 12×10 6 live spermatozoa, cooled to 5°C and kept for 24h. Group C: females were inseminated with the whole ejaculate (variable doses), cooled to 5°C and kept for 24h. These groups (A-C) were inseminated between 22 and 24h after induction of ovulation. Group D: females were inseminated with the whole ejaculate (variable doses), cooled to 5°C, kept for 24h and AI was carried out within 2h after ovulation. Pregnancy rates were 75%, 0%, 0% and 23% for groups A, B, C and D respectively. These results indicate that it is possible to obtain llama pregnancies with AI using cooled semen and that the success of the technique would depend on the proximity to ovulation.Fil: Giuliano, Susana María. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; ArgentinaFil: Chaves, María Graciela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; ArgentinaFil: Trasorras, Virginia Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; ArgentinaFil: Gambarotta, Mariana. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Neild, Debora Margarita. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; ArgentinaFil: Director, Ariel. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Pinto, Marcelo R.. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; ArgentinaFil: Miragaya, Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; Argentin

    Shifting paradigms in human resource management while striving for service excellence in the tourism industry

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    Globalization has led the tourism industry to undergo radical changes, with an ideological shift toward embracing the customer-centric approach and discarding the traditional focus on profits. Tourism organizations need to fulfill the demands and expectations of customers by training staff to maintain service excellence. A strategic approach must ensure employees are engaged, recognized, innovative, trustworthy, and loyal, exhibiting innovation and enhanced performance. This conceptual study explores the paradigm shifts in tourism human-resource management, and highlights a strategic approach of integrating operational and cultural elements for achieving service excellence. The proposed Operational Integration and Cultural Integration (OICI) elucidates effective management of human resources to achieve service excellence. It highlights that the customers' power to choose has increased, as the quality of the overall experience is wholly based on perception and acts as a main differentiator in the competitive world. Hence there is a need for constantly innovative ways to enhance services' effectiveness through efficient utilization of human resources (employees). To achieve high performance and service excellence, organizations must constantly encourage and inspire their employees, and acknowledge their contribution. The OICI model's implementation can achieve organizational goals and lead to satisfied, delighted, and loyal customers

    From retail innovation and image to loyalty: moderating effects of product type

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    This study aims to analyse value-satisfaction-loyalty relationships in retailing by examining the contribution of image and innovation and understanding value as a multidimensional construct. Furthermore, to identify possible differences in these relationships the moderating effect of the type of product marketed in the store is examined. On a sample of 820 customers from four types of stores, SEM methodology and multigroup analysis were applied. The results confirm that image has more influence than innovation on the dimensions of value and that entertainment and excellence are the main antecedents of satisfaction. Some relationships have also been found in which the type of product marketed in the store has a moderating effect
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