University of Cologne

About: University of Cologne is a education organization based out in Cologne, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 32050 authors who have published 66350 publications receiving 2210092 citations. The organization is also known as: Universität zu Köln & Universitatis Coloniensis.

Cancer therapy shapes the fitness landscape of clonal hematopoiesis

Abstract: Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies. Environmental exposures shape patterns of selection for mutations in clonal hematopoiesis. Cancer therapies promote the growth of clones with mutations that are strongly enriched in treatment-related myeloid neoplasms.

Formation of Membrane-bound Ring Complexes by Prohibitins in Mitochondria

Abstract: Prohibitins comprise a remarkably conserved protein family in eukaryotic cells with proposed functions in cell cycle progression, senescence, apoptosis, and the regulation of mitochondrial activiti...

The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19.

Abstract: We propose an ordinal tool to measure the full spectrum of functional outcomes following COVID-19. This “Post-COVID-19 Functional Status (PCFS) Scale” can be used for tracking functional status over time as well as for research purposes.

Bone mineral content per muscle cross-sectional area as an index of the functional muscle-bone unit.

Abstract: Bone densitometric data often are difficult to interpret in children and adolescents because of large inter- and intraindividual variations in bone size. Here, we propose a functional approach to bone densitometry that addresses two questions: Is bone strength normally adapted to the largest physiological loads, that is, muscle force? Is muscle force adequate for body size? To implement this approach, forearm muscle cross-sectional area (CSA) and bone mineral content (BMC) of the radial diaphysis were measured in 349 healthy subjects from 6 to 19 years of age (183 girls), using peripheral quantitative computed tomography (pQCT). Reference data were established for height-dependent muscle CSA and for the variation with age in the BMC/muscle CSA ratio. These reference data were used to evaluate results from three pediatric patient groups: children who had sustained multiple fractures without adequate trauma (n = 11), children with preterminal chronic renal failure (n = 11), and renal transplant recipients (n = 15). In all three groups mean height, muscle CSA, and BMC were low for age, but muscle CSA was normal for height. In the multiple fracture group and in renal transplant recipients the BMC/muscle CSA ratio was decreased (p < 0.05), suggesting that bone strength was not adapted adequately to muscle force. In contrast, chronic renal failure patients had a normal BMC/muscle CSA ratio, suggesting that their musculoskeletal system was adapted normally to their (decreased) body size. This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques.

NUANCE, a giant protein connecting the nucleus and actin cytoskeleton.

Abstract: NUANCE (NUcleus and ActiN Connecting Element) was identified as a novel protein with an alpha-actinin-like actin-binding domain. A human 21.8 kb cDNA of NUANCE spreads over 373 kb on chromosome 14q22.1-q22.3. The cDNA sequence predicts a 796 kDa protein with an N-terminal actin-binding domain, a central coiled-coil rod domain and a predicted C-terminal transmembrane domain. High levels of NUANCE mRNA were detected in the kidney, liver, stomach, placenta, spleen, lymphatic nodes and peripheral blood lymphocytes. At the subcellular level NUANCE is present predominantly at the outer nuclear membrane and in the nucleoplasm. Domain analysis shows that the actin-binding domain binds to Factin in vitro and colocalizes with the actin cytoskeleton in vivo as a GFP-fusion protein. The C-terminal transmembrane domain is responsible for the targeting the nuclear envelope. Thus, NUANCE is the first alpha-actinin-related protein that has the potential to link the microfilament system with the nucleus.