BBMRI-ERIC's contributions to research and knowledge exchange on COVID-19

During the COVID-19 pandemic, the European biobanking infrastructure is in a unique position to preserve valuable biological material complemented with detailed data for future research purposes. Biobanks can be either integrated into healthcare, where preservation of the biological material is a fork in clinical routine diagnostics and medical treatment processes or they can also host prospective cohorts or material related to clinical trials. The paper discussed objectives of BBMRI-ERIC, the European research infrastructure established to facilitate access to quality-defined biological materials and data for research purposes, with respect to the COVID-19 crisis: (a) to collect information on available European as well as non-European COVID-19-relevant biobanking resources in BBMRI-ERIC Directory and to facilitate access to these via BBMRI-ERIC Negotiator platform; (b) to help harmonizing guidelines on how data and biological material is to be collected to maximize utility for future research, including large-scale data processing in artificial intelligence, by participating in activities such as COVID-19 Host Genetics Initiative; (c) to minimize risks for all involved parties dealing with (potentially) infectious material by developing recommendations and guidelines; (d) to provide a European-wide platform of exchange in relation to ethical, legal, and societal issues (ELSI) specific to the collection of biological material and data during the COVID-19 pandemic

An MDA approach for developing Secure OLAP applications: metamodels and transformations

Decision makers query enterprise information stored in Data Warehouses (DW) by using tools (such as On-Line Analytical Processing (OLAP) tools) which employ specific views or cubes from the corporate DW or Data Marts, based on multidimensional modelling. Since the information managed is critical, security constraints have to be correctly established in order to avoid unauthorized access. In previous work we defined a Model-Driven based approach for developing a secure DW repository by following a relational approach. Nevertheless, it is also important to define security constraints in the metadata layer that connects the DW repository with the OLAP tools; that is, over the same multidimensional structures that end users manage. This paper incorporates a proposal for developing secure OLAP applications within our previous approach: it improves a UML profile for conceptual modelling; it defines a logical metamodel for OLAP applications; and it defines and implements transformations from conceptual to logical models, as well as from logical models to secure implementation in a specific OLAP tool (SQL Server Analysis Services).This research is part of the following projects: SIGMA-CC (TIN2012-36904), GEODAS-BC (TIN2012-37493-C01) and GEODAS-BI (TIN2012-37493-C03) funded by the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional FEDER. SERENIDAD (PEII11-037-7035) and MOTERO (PEII11- 0399-9449) funded by the Consejería de Educación, Ciencia y Cultura de la Junta de Comunidades de Castilla La Mancha, and Fondo Europeo de Desarrollo Regional FEDER

Impact of the pre-examination phase on multicenter metabolomic studies

The development of metabolomics in clinical applications has been limited by the lack of validation in large multicenter studies. Large population cohorts and their biobanks are a valuable resource for acquiring insights into molecular disease mechanisms. Nevertheless, most of their collections are not tailored for metabolomics and have been created without specific attention to the pre-analytical requirements for high-quality metabolome assessment. Thus, comparing samples obtained by different pre-analytical procedures remains a major challenge. Here, H-1 NMR-based analyses are used to demonstrate how human serum and plasma samples collected with different operating procedures within several large European cohort studies from the Biobanking and Biomolecular Resources Infrastructure - Large Prospective Cohorts (BBMRI-LPC) consortium can be easily revealed by supervised multivariate statistical analyses at the initial stages of the process, to avoid biases in the downstream analysis. The inter-biobank differences are discussed in terms of deviations from the validated CEN/TS 16945:2016 / ISO 23118:2021 norms. It clearly emerges that biobanks must adhere to the evidence-based guidelines in order to support wider-scale application of metabolomics in biomedicine, and that NMR spectroscopy is informative in comparing the quality of different sample sources in multi cohort/center studies.Peer reviewe

Metabolomic Fingerprints in Large Population Cohorts : Impact of Preanalytical Heterogeneity

Non peer reviewe

Tackling the translational challenges of multi-omics research in the realm of European personalised medicine : A workshop report

Personalised medicine (PM) presents a great opportunity to improve the future of individualised healthcare. Recent advances in -omics technologies have led to unprecedented efforts characterising the biology and molecular mechanisms that underlie the development and progression of a wide array of complex human diseases, supporting further development of PM. This article reflects the outcome of the 2021 EATRIS-Plus Multi-omics Stakeholder Group workshop organised to 1) outline a global overview of common promises and challenges that key European stakeholders are facing in the field of multi-omics research, 2) assess the potential of new technologies, such as artificial intelligence (AI), and 3) establish an initial dialogue between key initiatives in this space. Our focus is on the alignment of agendas of European initiatives in multi-omics research and the centrality of patients in designing solutions that have the potential to advance PM in long-term healthcare strategies.Peer reviewe

The role of caveolae in the function of cardiac myocotes

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Caveolae act as membrane reserves which limit mechanosensitive I(Cl,swell) channel activation during swelling in the rat ventricular myocyte.

BACKGROUND:Many ion channels are preferentially located in caveolae where compartmentalisation/scaffolding with signal transduction components regulates their activity. Channels that are mechanosensitive may be additionally dependent on caveolar control of the mechanical state of the membrane. Here we test which mechanism underlies caveolar-regulation of the mechanosensitive I(Cl,swell) channel in the adult cardiac myocyte. METHODOLOGY/PRINCIPAL FINDINGS:Rat ventricular myocytes were exposed to solution of 0.02 tonicity (T; until lysis), 0.64T for 10-15 min (swelling), and/or methyl-beta-cyclodextrin (MBCD; to disrupt caveolae). MBCD and 0.64T swelling reduced the number of caveolae visualised by electron microscopy by 75 and 50% respectively. MBCD stimulated translocation of caveolin 3 from caveolae-enriched buoyant membrane fractions, but both caveolin 1 and 3 remained in buoyant fractions after swelling. I(Cl,swell) inhibition in control cells decreased time to half-maximal volume (t(0.5,vol); 0.64T), consistent with a role for I(Cl,swell) in volume regulation. MBCD-treated cells showed reduced time to lysis (0.02T) and t(0.5,vol) (0.64T) compared with controls. The negative inotropic response to swelling (an index of I(Cl,swell) activation) was enhanced by MBCD. CONCLUSIONS/SIGNIFICANCE:These data show that disrupting caveolae removes essential membrane reserves, which speeds swelling in hyposmotic conditions, and thereby promotes activation of I(Cl,swell). They illustrate a general principle whereby caveolae as a membrane reserve limit increases in membrane tension during stretch/swelling thereby restricting mechanosensitive channel activation

Hyposmotic swelling does not cause translocation of Cav 1 or Cav 3 from caveolar membrane fractions.

<p>Ventricular myocytes were exposed to isotonic or hypotonic solutions for 15 min, then subject to Na₂CO₃ extraction and discontinuous sucrose density gradient fractionation. A. Mean data showing Cav 1 in each fraction normalised to the sum of Cav 1 in all fractions for each sample (<i>n</i> = 6 hearts). Representative immunoblots, with equal volume loading of fractions, is shown below. B. Mean data showing Cav 3 in each fraction with representative immunoblots below. In both isotonic and hypotonic conditions, Cav 1 and 3 were enriched in the buoyant lipid raft fractions (5,6) of the myocyte. Hyposmotic swelling had no effect on the location of either Cav isoform.</p

Time-course of myocyte swelling in response to 0.64T hypotonic solution.

<p>Myoycte volume was estimated from a video image of the cell, assuming the cell is an elliptical cylinder. Data are fitted with a logistic sigmoidal curve from which values of maximum cell volume and time to half-maximal volume were obtained. Mean±S.E.M. from <i>n</i> = 16 cells.</p