Das Forschungsdatenzentrum der Universität Hamburg

The more recent discussion of research data practices at relevant conferences, workshops and respective publications suggest substantially different foci of problems and solutions in managing data between scientific disciplines. There seems to be a particularly profound gap in natural science and humanities whereas social and life sciences are placed somewhere in between. Indeed data centers tailored to the specific needs of a single discipline (physics, chemistry, climate studies) are numerous in science and tend to be nearly absent for a specific humanities subject. While the former ask for and report solutions on scaling up (larger quantities of data can be run by the same application) and scaling out (larger quantities of data can use the same infrastructure), the latter are concerned with the heterogeneity of relatively small amounts of data (long-tail problem) and a divergence of agreed standards; something we may term as cross scaling. In either case, an efficiency problem has to be solved. On the one hand, huge amounts of data have to be handled within an acceptable time frame, on the other hand, many different applications with diverse functionalities have to be handled with an acceptable number of resources.  We would like to argue here that independent from the discipline either optimization problem should be addressed. Throughout the last decade, we have also observed that projects in science diversify and prefer individualized solutions which additionally hints at increasing data heterogeneity in natural science as well while, at the same time, some humanities projects produce petabytes of data. To show the necessity of a differentiated approach, the research data center of Universität Hamburg is offered as a case in point. The evolution of the center specialized in humanities projects to a research data center offering services for the whole university whereas other disciplinary data centers continue to exist side by side illustrates the entire range of tasks of data stewardship. It includes the continuous development of services while getting more and more involved in natural science projects as well as task sharing and communication with other data institutions. A core asset to understand the requirements of each discipline is a multidisciplinary team. Yet, the main organizing principle of the offered services centers around the stages of the data life cycle (1. data creation and deposit, 2. managing active data, 3. data repositories and archives, 4. data catalog and registries). The interdigitation of these stages is paramount in the long term strategy

DHODH inhibition modulates glucose metabolism and circulating GDF15, and improves metabolic balance

Dihydroorotate dehydrogenase (DHODH) is essential for the de novo synthesis of pyrimidine ribonucleotides, and as such, its inhibitors have been long used to treat autoimmune diseases and are in clinical trials for cancer and viral infections. Interestingly, DHODH is located in the inner mitochondrial membrane and contributes to provide ubiquinol to the respiratory chain. Thus, DHODH provides the link between nucleotide metabolism and mitochondrial function. Here we show that pharmacological inhibition of DHODH reduces mitochondrial respiration, promotes glycolysis, and enhances GLUT4 translocation to the cytoplasmic membrane and that by activating tumor suppressor p53, increases the expression of GDF15, a cytokine that reduces appetite and prolongs lifespan. In addition, similar to the antidiabetic drug metformin, we observed that in db/db mice, DHODH inhibitors elevate levels of circulating GDF15 and reduce food intake. Further analysis using this model for obesity-induced diabetes revealed that DHODH inhibitors delay pancreatic β cell death and improve metabolic balance.publishedVersio

Präsentation zum ZFDM und HCDS-Tag 2023

Die Folien der Präsentation zum gemeinsamen Tag vom Zentrum für nachhaltiges Forschungsdatenmanagement (ZFDM) und dem House of Computing and Data Science (HCDS), bei dem die Dienste und Angebote der beiden Einrichtungen an der Universität Hamburg vorgestellt wurden: Datenmanagementpläne (RDMO) Forschungsdatenrepositorium FUNDus! Sammlungsportal Arbeiten mit Daten, HCDS Forschungsinformationssytem Schulungsangebot

DHODH inhibition modulates glucose metabolism and circulating GDF15, and improves metabolic balance

Dihydroorotate dehydrogenase (DHODH) is essential for the de novo synthesis of pyrimidine ribonucleotides, and as such, its inhibitors have been long used to treat autoimmune diseases and are in clinical trials for cancer and viral infections. Interestingly, DHODH is located in the inner mitochondrial membrane and contributes to provide ubiquinol to the respiratory chain. Thus, DHODH provides the link between nucleotide metabolism and mitochondrial function. Here we show that pharmacological inhibition of DHODH reduces mitochondrial respiration, promotes glycolysis, and enhances GLUT4 translocation to the cytoplasmic membrane and that by activating tumor suppressor p53, increases the expression of GDF15, a cytokine that reduces appetite and prolongs lifespan. In addition, similar to the antidiabetic drug metformin, we observed that in db/db mice, DHODH inhibitors elevate levels of circulating GDF15 and reduce food intake. Further analysis using this model for obesity-induced diabetes revealed that DHODH inhibitors delay pancreatic β cell death and improve metabolic balance

Triggering of a Dll4–Notch1 loop impairs wound healing in diabetes

Diabetic foot ulcerations (DFUs) represent a major medical, social, and economic problem. Therapeutic options are restricted due to a poor understanding of the pathogenic mechanisms. The Notch pathway plays a pivotal role in cell differentiation, proliferation, and angiogenesis, processes that are profoundly disturbed in diabetic wounds. Notch signaling is activated upon interactions between membrane-bound Notch receptors (Notch 1-4) and ligands (Jagged 1-2 and Delta-like 1, 3, 4), resulting in cell-context-dependent outputs. Here, we report that Notch1 signaling is activated by hyperglycemia in diabetic skin and specifically impairs wound healing in diabetes. Local inhibition of Notch1 signaling in experimental wounds markedly improves healing exclusively in diabetic, but not in nondiabetic, animals. Mechanistically, high glucose levels activate a specific positive Delta-like 4 (Dll4)-Notch1 feedback loop. Using loss-of-function genetic approaches, we demonstrate that Notch1 inactivation in keratinocytes is sufficient to cancel the repressive effects of the Dll4-Notch1 loop on wound healing in diabetes, thus making Notch1 signaling an attractive locally therapeutic target for the treatment of DFUs

The mRNA expression of IGF-I, IGF-II and IGF-IR in the skin of liver-specific IGF-I deficient mice versus WT control animals with or without diabetes.

<p>The mRNA expression of IGF-I, IGF-II and IGF-IR in the skin of liver-specific IGF-I deficient mice versus WT control animals with or without diabetes.</p