University of Göttingen

About: University of Göttingen is a education organization based out in Göttingen, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 43851 authors who have published 86318 publications receiving 3010295 citations. The organization is also known as: Georg-August-Universität Göttingen & Universität Göttingen.

Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms.

Abstract: Mutations in human presenilin (PS) genes cause aggressive forms of familial Alzheimer's disease. Presenilins are polytopic proteins that harbour the catalytic site of the gamma-secretase complex and cleave many type I transmembrane proteins including beta-amyloid precursor protein (APP), Notch and syndecan 3. Contradictory results have been published concerning whether PS mutations cause 'abnormal' gain or (partial) loss of function of gamma-secretase. To avoid the possibility that wild-type PS confounds the interpretation of the results, we used presenilin-deficient cells to analyse the effects of different clinical mutations on APP, Notch, syndecan 3 and N-cadherin substrate processing, and on gamma-secretase complex formation. A loss in APP and Notch substrate processing at epsilon and S3 cleavage sites was observed with all presenilin mutants, whereas APP processing at the gamma site was affected in variable ways. PS1-Delta9 and PS1-L166P mutations caused a reduction in beta-amyloid peptide Abeta40 production whereas PS1-G384A mutant significantly increased Abeta42. Interestingly PS2, a close homologue of PS1, appeared to be a less efficient producer of Abeta than PS1. Finally, subtle differences in gamma-secretase complex assembly were observed. Overall, our results indicate that the different mutations in PS affect gamma-secretase structure or function in multiple ways.

Osteolysis in alloarthroplasty of the hip. The role of ultra-high molecular weight polyethylene wear particles.

Abstract: Massive localized osteolysis around artificial joints has been seen more frequently in the past few years. It is still not generally accepted that ultra-high molecular weight polyethylene (UHMWPE) wear particles can induce massive bone resorption, even distant from the joint. This article describes a series of eight soft-top prostheses with large UHMWPE ball heads that contributed to the erosion of surrounding bone. Roentgenographically, all of the cases showed a marked loss of proximal cortical bone, more or less combined with osteolysis, which was distal to the femoral shaft and deep into the acetabulum. In two cases, remodeling and resorption transformed the bone into a tumorlike appearance. Tissue samples from areas of osteolysis as well as from the joint capsule were taken at revision surgery, processed for histology, examined microscopically, and evaluated semiquantitatively. The retrieved devices were also carefully inspected. Large amounts of UHMWPE wear debris were found not only in the joint capsule but also in layers of granulomatous tissue from the acetabulum and femur, whereas metal particles and fragmented polymethylmethacrylate were either completely absent or occurred only in very small amounts. The results of this study demonstrate that UHMWPE wear products alone can cause massive osteolysis by triggering foreign-body granuloma formation at the bone-cement interface; the bone cement may remain fixed in areas beyond the osteolytic transformation.

Seismic evidence for a rapidly rotating core in a lower-giant-branch star observed with kepler

Abstract: Rotation is expected to have an important influence on the structure and the evolution of stars. However, the mechanisms of angular momentum transport in stars remain theoretically uncertain and very complex to take into account in stellar models. To achieve a better understanding of these processes, we desperately need observational constraints on the internal rotation of stars, which until very recently was restricted to the Sun. In this paper, we report the detection of mixed modes—i.e., modes that behave both as g modes in the core and as p modes in the envelope—in the spectrum of the early red giant KIC 7341231, which was observed during one year with the Kepler spacecraft. By performing an analysis of the oscillation spectrum of the star, we show that its non-radial modes are clearly split by stellar rotation and we are able to determine precisely the rotational splittings of 18 modes. We then find a stellar model that reproduces very well the observed atmospheric and seismic properties of the star. We use this model to perform inversions of the internal rotation profile of the star, which enables us to show that the core of the star is rotating at least five times faster than the envelope. This will shed new light on the processes of transport of angular momentum in stars. In particular, this result can be used to place constraints on the angular momentum coupling between the core and the envelope of early red giants, which could help us discriminate between the theories that have been proposed over the last few decades.

Stromal biology and therapy in pancreatic cancer: a changing paradigm

Abstract: Pancreatic ductal adenocarcinoma (PDA) exhibits one of the poorest prognosis of all solid tumours and poses an unsolved problem in cancer medicine. Despite the recent success of two combination chemotherapies for palliative patients, the modest survival benefits are often traded against significant side effects and a compromised quality of life. Although the molecular events underlying the initiation and progression of PDA have been intensively studied and are increasingly understood, the reasons for the poor therapeutic response are hardly apprehended. One leading hypothesis over the last few years has been that the pronounced tumour microenvironment in PDA not only promotes carcinogenesis and tumour progression but also mediates therapeutic resistance. To this end, targeting of various stromal components and pathways was considered a promising strategy to biochemically and biophysically enhance therapeutic response. However, none of the efforts have yet led to efficacious and approved therapies in patients. Additionally, recent data have shown that tumour-associated fibroblasts may restrain rather than promote tumour growth, reinforcing the need to critically revisit the complexity and complicity of the tumour-stroma with translational implications for future therapy and clinical trial design.

Abiotic and biotic factors and their interactions as causes of oak decline in Central Europe

Abstract: Summary Incidences of oak decline have occurred repeatedly during the past three centuries as well as in the most recent decades. On the basis of historical records and dendrochronological measurements, oak decline in Central Europe has been attributed to the single or combined effects of climatic extremes (winter frost, summer drought), defoliating insects, and pathogenic fungi. Starting from a literature review, we discuss the possible roles of various abiotic (air pollution, nitrogen eutrophication, soil chemical stress, climatic extremes, site conditions) and biotic factors (insect defoliation, borer attack, infection by pathogenic fungi, microorganisms) that have been related to oak decline. On the basis of investigations on Quercus petraea and Quercus robur at three different levels (from experiments with young trees to monitoring on a supraregional scale), we suggest a conceptual model of the interaction of abiotic and biotic factors responsible for the onset of oak decline. This model should be valid for Central European oak stands at more acidic sites (soil pH (H2O) £ 4.2; on soils with higher pH, pathogenic Phytophthora species may contribute to oak decline). The combination of severe insect defoliation in at least two consecutive years with climatic extremes is the most significant complex of factors in the incidence of oak decline. Combined with defoliation, summer drought or winter ⁄ spring frost or both have to occur within the same year or in consecutive years to trigger major outbreaks of decline. Important additional stress factors are the following: (1) hydromorphic site conditions which, particularly in the case of Q. robur, render the trees more susceptible to drought stress as a result of an impairment of root growth in the subsoil; and (2), possibly, excess nitrogen which, in combination with drought stress, results in distinct decreases in the foliar concentrations of allelochemicals in Q. robur, thereby probably making the trees more susceptible to insect defoliation. Air pollution, soil chemical stress (including excess manganese), and nitrogen-induced nutritional imbalance do not seem to be important causal factors in the complex of oak decline. On the basis of the model, the appearance of the most recent oak decline in North-western Germany can be adequately explained.