Hepatitis C virus core, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection

<p>Abstract</p> <p>Background</p> <p>The viral genome of hepatitis C virus constitutes a 9.6-kb single-stranded positive-sense RNA which encodes altogether 11 viral proteins. In order to study the humoral immune responses against different HCV proteins in patients suffering from chronic HCV infection, we produced three structural (core, E1 and E2) and six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) in <it>Sf</it>9 insect cells by using the baculovirus expression system.</p> <p>Results</p> <p>The recombinant HCV core, E1, E2, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins were purified and used in Western blot analysis to determine antibody responses against individual HCV protein in 68 HCV RNA and antibody positive human sera that were obtained from patients suffering from genotype 1, 2, 3 or 4 infection. These sera were also analysed with INNO-LIA Score test for HCV antibodies against core, NS3, NS4AB and NS5A, and the results were similar to the ones obtained by Western blot method. Based on our Western blot analyses we found that the major immunogenic HCV antigens were the core, NS4B, NS3 and NS5A proteins which were recognized in 97%, 86%, 68% and 53% of patient sera, respectively. There were no major genotype specific differences in antibody responses to individual HCV proteins. A common feature within the studied sera was that all except two sera recognized the core protein in high titers, whereas none of the sera recognized NS2 protein and only three sera (from genotype 3) recognised NS5B.</p> <p>Conclusion</p> <p>The data shows significant variation in the specificity in humoral immunity in chronic HCV patients.</p

Requirements analysis document

This document details the purpose, features, and expected interfaces for the complete EXCELERATE WP9 (Use Case D: ELIXIR framework for secure archiving, dissemination and analysis of human access-controlled data). It outlines the tasks the system will perform, the constraints under which it operates, and how it reacts in certain circumstances. This document is intended for stakeholders, designers and developers as well as users of the system, and derives from a joint analysis carried out with these groups

Common ELIXIR Service for Researcher Authentication and Authorisation

Linden M, Prochazka M, Lappalainen I, et al. Common ELIXIR Service for Researcher Authentication and Authorisation. F1000Research. 2018;7: 1199.A common Authentication and Authorisation Infrastructure (AAI) that would allow single sign-on to services has been identified as a key enabler for European bioinformatics. ELIXIR AAI is an ELIXIR service portfolio for authenticating researchers to ELIXIR services and assisting these services on user privileges during research usage. It relieves the scientific service providers from managing the user identities and authorisation themselves, enables the researcher to have a single set of credentials to all ELIXIR services and supports meeting the requirements imposed by the data protection laws. ELIXIR AAI was launched in late 2016 and is part of the ELIXIR Compute platform portfolio. By the end of 2017 the number of users reached 1000, while the number of relying scientific services was 36. This paper presents the requirements and design of the ELIXIR AAI and the policies related to its use, and how it can be used for serving some example services, such as document management, social media, data discovery, human data access, cloud compute and training services

Annotation and curation of human genomic variations: an ELIXIR Implementation Study

Background: ELIXIR is an intergovernmental organization, primarily based around European countries, established to host life science resources, including databases, software tools, training material and cloud storage for the scientific community under a single infrastructure. Methods: In 2018, ELIXIR commissioned an international survey on the usage of databases and tools for annotating and curating human genomic variants with the aim of improving ELIXIR resources. The 27-question survey was made available on-line between September and December 2018 to rank the importance and explore the usage and limitations of a wide range of databases and tools for annotating and curating human genomic variants, including resources specific for next generation sequencing, research into mitochondria and protein structure. Results: Eighteen countries participated in the survey and a total of 92 questionnaires were collected and analysed. Most respondents (89%, n=82) were from academia or a research environment. 51% (n=47) of respondents gave answers on behalf of a small research group (10 people). The survey showed that the scientific community considers several resources supported by ELIXIR crucial or very important. Moreover, it showed that the work done by ELIXIR is greatly valued. In particular, most respondents acknowledged the importance of key features and benefits promoted by ELIXIR, such as the verified scientific quality and maintenance of ELIXIR-approved resources. Conclusions ELIXIR is a "one-stop-shop" that helps researchers identify the most suitable, robust and well-maintained bioinformatics resources for delivering their research tasks

SHANK3 conformation regulates direct actin binding and crosstalk with Rap1 signaling

Actin-rich cellular protrusions direct versatile biological processes from cancer cell invasion to dendritic spine development. The stability, morphology, and specific biological functions of these protrusions are regulated by crosstalk between three main signaling axes: integrins, actin regulators, and small guanosine triphosphatases (GTPases). SHANK3 is a multifunctional scaffold protein, interacting with several actin -binding proteins and a well-established autism risk gene. Recently, SHANK3 was demonstrated to sequester integrin-activating small GTPases Rap1 and R-Ras to inhibit integrin activity via its Shank/ProSAP N-terminal (SPN) domain. Here, we demonstrate that, in addition to scaffolding actin regulators and actin-binding proteins, SHANK3 interacts directly with actin through its SPN domain. Molecular simulations and targeted mutagenesis of the SPN-ankyrin repeat region (ARR) interface reveal that actin binding is inhibited by an intramolecular closed conformation of SHANK3, where the adjacent ARR domain covers the actin-binding interface of the SPN domain. Actin and Rap1 compete with each other for binding to SHANK3, and mutation of SHANK3, resulting in reduced actin binding, augments inhibition of Rap1-mediated integrin activity. This dynamic crosstalk has functional implications for cell morphology and integrin activity in cancer cells. In addition, SHANK3-actin interaction regulates dendritic spine morphology in neurons and autism-linked phenotypes in vivo.Peer reviewe

Genetic Diversity of the 2009 Pandemic Influenza A(H1N1) Viruses in Finland

Peer reviewe

Hepatiitti C -virusinfektioiden seuranta Suomessa vuosina 1995-2013

Hepatiitti C on yleisin Suomessa esiintyvistä hepatiiteista, ja se saadaan useimmiten suonensisisäisten huumeiden käytön seurauksena. Tartunta saadaan usein nuorena, infektio jää valtaosalla krooniseksi ja altistaa kantajansa vuosikymmenien kuluessa erilaisille maksasairauksille. Hepatiitti C -tartunnan saaneita voidaan kuitenkin hoitaa lääkkeillä ja suurin osa hoidetuista paranee. Tämä raportti on ensimmäinen kokonaisvaltainen selvitys hepatiitti C -virusinfektioista Suomessa. Siihen on koottu tietoa tartuntatautirekisterin hepatiitti C -tapauksista. Lisäksi esitetään arvioita hepatiitti C -tartuntojen esiintyvyydestä eri väestöryhmissä ja käsitellään hoitoa ja ennaltaehkäisyä. Raportti on tarkoitettu hepatiitti C -potilaita hoitaville, tartuntojen ehkäisytyötä tekeville ja muille asiasta kiinnostuneille