Traces of a prehistoric and potentially tsunamigenic mass movement in the sediments of Lake Thun (Switzerland).

Mass movements constitute major natural hazards in the Alpine realm. When triggered on slopes adjacent to lakes, these mass movements can generate tsunami-like waves that may cause additional damage along the shore. For hazard assessment, knowledge about the occurrence, the trigger and the geomechanical and hydrogeological mechanisms of these mass movements is necessary. For reconstructing mass movements that occurred in or adjacent to lakes, the lakes's sedimentary record can be used as an archive. Here, we present a prehistorical mass-movement event, of which the traces were found in an alpine lake, Lake Thun, in central Switzerland. The mass movement is identified by large blocks on the bathymetric map, a chaotic to transparent facies on the reflection seismic profiles, and by a mixture of deformed lake sediments and sandy organic-rich layers in the sediment-core record. The event is dated at 2642-2407 cal year BP. With an estimated volume of ~ 20 × 106 m3 it might have generated a wave with an initial amplitude of > 30 m. In addition to this prehistorical event, two younger deposits were identified in the sedimentary record. One could be dated at 1523-1361 cal year BP and thus can be potentially related to an event in 598/599 AD documented in historical reports. The youngest deposit is dated at 304-151 cal year BP (1646-1799 AD) and is interpreted to be related to the artificial Kander river deviation into Lake Thun (1714 AD). Supplementary Information The online version contains supplementary material available at 10.1186/s00015-022-00405-0

Macrophage cholesterol efflux correlates with lipoprotein subclass distribution and risk of obstructive coronary artery disease in patients undergoing coronary angiography

<p>Abstract</p> <p>Background</p> <p>Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in142 normolipidemic subjects undergoing coronary angiography.</p> <p>Methods</p> <p>Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography.</p> <p>Results</p> <p>Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concntration of larger and triglyceride rich particles (VLDL, chylomicrons). Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02).</p> <p>Conclusion</p> <p>Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.</p

Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma

Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies

Pro-angiogenic Activity Discriminates Human Adipose-Derived Stromal Cells From Retinal Pericytes: Considerations for Cell-Based Therapy of Diabetic Retinopathy

Diabetic retinopathy (DR) is a frequent diabetes-associated complication. Pericyte dropout can cause increased vascular permeability and contribute to vascular occlusion. Adipose-derived stromal cells (ASC) have been suggested to replace pericytes and restore microvascular support as potential therapy of DR. In models of DR, ASC not only generated a cytoprotective and reparative environment by the secretion of trophic factors but also engrafted and integrated into the retina in a pericyte-like fashion. The aim of this study was to compare the pro-angiogenic features of human ASC and human retinal microvascular pericytes (HRMVPC) in vitro. The proliferation and the expression of ASC and HRMVPC markers were compared. Adhesion to high glucose-conditioned endothelial extracellular matrix, mimicking the diabetic microenvironment, was measured. The angiogenesis-promoting features of both cell types and their conditioned media on human retinal endothelial cells (EC) were assessed. To identify a molecular basis for the observed differences, gene expression profiling was performed using whole-genome microarrays, and data were validated using PCR arrays and flow cytometry. Based on multiplex cytokine results, functional studies on selected growth factors were performed to assess their role in angiogenic support. Despite a distinct heterogeneity in ASC and HRMVPC cultures with an overlap of expressed markers, ASC differed functionally from HRMVPC. Most importantly, the pro-angiogenic activity was solely featured by ASC, whereas HRMVPC actively suppressed vascular network formation. HRMVPC, in contrast to ASC, showed impaired adhesion and proliferation on the high glucose-conditioned endothelial extracellular matrix. These data were supported by gene expression profiles with differentially expressed genes. The vessel-stabilizing factors were more highly expressed in HRMVPC, and the angiogenesis-promoting factors were more highly expressed in ASC. The vascular endothelial growth factor receptor-2 inhibition efficiently abolished the ASC angiogenic supportive capacities, whereas the addition of angiopoietin-1 and angiopoietin-2 did not alter these effects. Our results clearly show that ASC are pro-angiogenic, whereas HRMVPC are marked by anti-angiogenic/EC-stabilizing features. These data support ASC as pericyte replacement in DR but also suggest a careful risk-to-benefit analysis to take full advantage of the ASC therapeutic features

Pro-angiogenic Activity Discriminates Human Adipose-Derived Stromal Cells From Retinal Pericytes: Considerations for Cell-Based Therapy of Diabetic Retinopathy

Diabetic retinopathy (DR) is a frequent diabetes-associated complication. Pericyte dropout can cause increased vascular permeability and contribute to vascular occlusion. Adipose-derived stromal cells (ASC) have been suggested to replace pericytes and restore microvascular support as potential therapy of DR. In models of DR, ASC not only generated a cytoprotective and reparative environment by the secretion of trophic factors but also engrafted and integrated into the retina in a pericyte-like fashion. The aim of this study was to compare the pro-angiogenic features of human ASC and human retinal microvascular pericytes (HRMVPC) in vitro. The proliferation and the expression of ASC and HRMVPC markers were compared. Adhesion to high glucose-conditioned endothelial extracellular matrix, mimicking the diabetic microenvironment, was measured. The angiogenesis-promoting features of both cell types and their conditioned media on human retinal endothelial cells (EC) were assessed. To identify a molecular basis for the observed differences, gene expression profiling was performed using whole-genome microarrays, and data were validated using PCR arrays and flow cytometry. Based on multiplex cytokine results, functional studies on selected growth factors were performed to assess their role in angiogenic support. Despite a distinct heterogeneity in ASC and HRMVPC cultures with an overlap of expressed markers, ASC differed functionally from HRMVPC. Most importantly, the pro-angiogenic activity was solely featured by ASC, whereas HRMVPC actively suppressed vascular network formation. HRMVPC, in contrast to ASC, showed impaired adhesion and proliferation on the high glucose-conditioned endothelial extracellular matrix. These data were supported by gene expression profiles with differentially expressed genes. The vessel-stabilizing factors were more highly expressed in HRMVPC, and the angiogenesis-promoting factors were more highly expressed in ASC. The vascular endothelial growth factor receptor-2 inhibition efficiently abolished the ASC angiogenic supportive capacities, whereas the addition of angiopoietin-1 and angiopoietin-2 did not alter these effects. Our results clearly show that ASC are pro-angiogenic, whereas HRMVPC are marked by anti-angiogenic/EC-stabilizing features. These data support ASC as pericyte replacement in DR but also suggest a careful risk-to-benefit analysis to take full advantage of the ASC therapeutic features

Crossroads between contrastive linguistics, translation studies and machine translation: TC3-II

Contrastive Linguistics (CL), Translation Studies (TS) and Machine Translation (MT) have common grounds: They all work at the crossroad where two or more languages meet. Despite their inherent relatedness, methodological exchange between the three disciplines is rare. This special issue touches upon areas where the three fields converge. It results directly from a workshop at the 2011 German Association for Language Technology and Computational Linguistics (GSCL) conference in Hamburg where researchers from the three fields presented and discussed their interdisciplinary work. While the studies contained in this volume draw from a wide variety of objectives and methods, and various areas of overlaps between CL, TS and MT are addressed, the volume is by no means exhaustive with regard to this topic. Further cross-fertilisation is not only desirable, but almost mandatory in order to tackle future tasks and endeavours, and this volume is committed to bringing these three fields even closer together

Crossroads between contrastive linguistics, translation studies and machine translation: TC3-II

Contrastive Linguistics (CL), Translation Studies (TS) and Machine Translation (MT) have common grounds: They all work at the crossroad where two or more languages meet. Despite their inherent relatedness, methodological exchange between the three disciplines is rare. This special issue touches upon areas where the three fields converge. It results directly from a workshop at the 2011 German Association for Language Technology and Computational Linguistics (GSCL) conference in Hamburg where researchers from the three fields presented and discussed their interdisciplinary work. While the studies contained in this volume draw from a wide variety of objectives and methods, and various areas of overlaps between CL, TS and MT are addressed, the volume is by no means exhaustive with regard to this topic. Further cross-fertilisation is not only desirable, but almost mandatory in order to tackle future tasks and endeavours, and this volume is committed to bringing these three fields even closer together

Crossroads between contrastive linguistics, translation studies and machine translation: TC3-II

Contrastive Linguistics (CL), Translation Studies (TS) and Machine Translation (MT) have common grounds: They all work at the crossroad where two or more languages meet. Despite their inherent relatedness, methodological exchange between the three disciplines is rare. This special issue touches upon areas where the three fields converge. It results directly from a workshop at the 2011 German Association for Language Technology and Computational Linguistics (GSCL) conference in Hamburg where researchers from the three fields presented and discussed their interdisciplinary work. While the studies contained in this volume draw from a wide variety of objectives and methods, and various areas of overlaps between CL, TS and MT are addressed, the volume is by no means exhaustive with regard to this topic. Further cross-fertilisation is not only desirable, but almost mandatory in order to tackle future tasks and endeavours, and this volume is committed to bringing these three fields even closer together

Crossroads between contrastive linguistics, translation studies and machine translation: TC3-II

Contrastive Linguistics (CL), Translation Studies (TS) and Machine Translation (MT) have common grounds: They all work at the crossroad where two or more languages meet. Despite their inherent relatedness, methodological exchange between the three disciplines is rare. This special issue touches upon areas where the three fields converge. It results directly from a workshop at the 2011 German Association for Language Technology and Computational Linguistics (GSCL) conference in Hamburg where researchers from the three fields presented and discussed their interdisciplinary work. While the studies contained in this volume draw from a wide variety of objectives and methods, and various areas of overlaps between CL, TS and MT are addressed, the volume is by no means exhaustive with regard to this topic. Further cross-fertilisation is not only desirable, but almost mandatory in order to tackle future tasks and endeavours, and this volume is committed to bringing these three fields even closer together