Aligning Biobanks and Data Integration Centers Efficiently (ABIDE_MI).

ABIDE_MI is a complementary funded 18 months project within the German Medical Informatics Initiative (MII), which aims to align IT infrastructures and regulatory/governance structures between biobanks/biobanking IT and the MII data integration centres (DIC) at German university hospitals. A major task in 2021 was the systematic collection of all documents describing rules, as well as proposal/contract templates for data and biosample use and access at each of the participating 24 university hospitals and their comparison with MII-wide consented data sharing principles, documents and governance structures. This comparison revealed large heterogeneity across the ABIDE_MI sites and further, redundant structures/regulations currently established at the German university hospitals. A second task was the design and stepwise development of an IT network infrastructure with central components (data and biosample query portal) and decentralized standardized FHIR servers to capture the standardized FHIR-based core data set modules (resources) defined within the MII working group "Interoperability". Subsequent steps in the project are the harmonization of the data and biosample sharing governance/regulation frameworks at each ABIDE_MI site, creating synergies for the research infrastructures at the German university hospitals and to link those resources to the German Portal for Medical Research Data and with the BBMRI-ERIC Directory and Negotiator tools.

Initial Characterization of Stressed Transgenic Mice With Cardiomyocyte-Specific Overexpression of Protein Phosphatase 2C.

As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated mice with cardiac-specific overexpression of PP2Cß (PP2C-TG) and compared them with littermate wild type mice (WT) serving as a control. Cardiac fibrosis was noted histologically in PP2C-TG. Collagen 1a, interleukin-6 and the natriuretic peptides ANP and BNP were augmented in PP2C-TG vs. WT (p < 0.05). Left atrial preparations from PP2C-TG were less resistant to hypoxia than atria from WT. PP2C-TG maintained cardiac function after the injection of lipopolysaccharide (LPS, a model of sepsis) and chronic isoproterenol treatment (a model of heart failure) better than WT. Crossbreeding of PP2C-TG mice with PP2A-TG mice (a genetic model of heart failure) resulted in double transgenic (DT) mice that exhibited a pronounced increase of heart weight in contrast to the mild hypertrophy noted in the mono-transgenic mice. The ejection fraction was reduced in PP2C-TG and in PP2A-TG mice compared with WT, but the reduction was the highest in DT compared with WT. PP2A enzyme activity was enhanced in PP2A-TG and DT mice compared with WT and PP2C-TG mice. In summary, cardiac overexpression of PP2Cß and co-overexpression of both the catalytic subunit of PP2A and PP2Cß were detrimental to cardiac function. PP2Cß overexpression made cardiac preparations less resistant to hypoxia than WT, leading to fibrosis, but PP2Cß overexpression led to better adaptation to some stressors, such as LPS or chronic ß-adrenergic stimulation. Hence, the effect of PP2Cß is context sensitive.