Three-dimensional topology dataset of folded radar stratigraphy in northern Greenland

We present a dataset of reconstructed three-dimensional (3D) englacial stratigraphic horizons in northern Greenland. The data cover four different regions representing key ice-dynamic settings in Greenland: (i) the onset of Petermann Glacier, (ii) a region upstream of the 79° North Glacier (Nioghalvfjerdsbræ), near the northern Greenland ice divide, (iii) the onset of the Northeast Greenland Ice Stream (NEGIS) and (iv) a 700 km wide region extending across the central ice divide over the entire northern part of central Greenland. In this paper, we promote the advantages of a 3D perspective of deformed englacial stratigraphy and explain how 3D horizons provide an improved basis for interpreting and reconstructing the ice-dynamic history. The 3D horizons are provided in various formats to allow a wide range of applications and reproducibility of results

Three-dimensional topology dataset of folded radar stratigraphy in northern Greenland

We present a dataset of reconstructed three-dimensional (3D) englacial stratigraphic horizons in northern Greenland. The data cover four different regions representing key ice-dynamic settings in Greenland: (i) the onset of Petermann Glacier, (ii) a region upstream of the 79° North Glacier (Nioghalvfjerdsbræ), near the northern Greenland ice divide, (iii) the onset of the Northeast Greenland Ice Stream (NEGIS) and (iv) a 700 km wide region extending across the central ice divide over the entire northern part of central Greenland. In this paper, we promote the advantages of a 3D perspective of deformed englacial stratigraphy and explain how 3D horizons provide an improved basis for interpreting and reconstructing the ice-dynamic history. The 3D horizons are provided in various formats to allow a wide range of applications and reproducibility of results

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 days in co-culture has been established at a minute but standardized microsystem scale. Preformed human intestine and skin models have been integrated into the four-organ-chip on standard cell culture inserts at a size 100000-fold smaller than their human counterpart organs. A 3D-based spheroid, equivalent to ten liver lobules, mimics liver function. Finally, a barrier segregating the media flow through the organs from fluids excreted by the kidney has been generated by a polymeric membrane covered by a monolayer of human proximal tubule epithelial cells. A peristaltic on-chip micropump ensures pulsatile media flow interconnecting the four tissue culture compartments through microfluidic channels. A second microfluidic circuit ensures drainage of the fluid excreted through the kidney epithelial cell layer. This four-organ-chip system assures near to physiological fluid-to-tissue ratios. In-depth metabolic and gene analysis revealed the establishment of reproducible homeostasis among the co-cultures within two to four days, sustainable over at least 28 days independent of the individual human cell line or tissue donor background used for each organ equivalent. Lastly, 3D imaging two-photon microscopy visualised details of spatiotemporal segregation of the two microfluidic flows by proximal tubule epithelia. To our knowledge, this study is the first approach to establish a system for in vitro microfluidic ADME profiling and repeated dose systemic toxicity testing of drug candidates over 28 days.BMBF, 0315569, GO-Bio 3: Multi-Organ-Bioreaktoren für die prädiktive Substanztestung im Chipforma

A comprehensive in-vitro/in-vivo screening toolbox for the elucidation of glucose homeostasis modulating properties of plant extracts (from roots) and its bioactives

Plant extracts are increasingly recognized for their potential in modulating (postprandial) blood glucose levels. In this context, root extracts are of particular interest due to their high concentrations and often unique spectrum of plant bioactives. To identify new plant species with potential glucose-lowering activity, simple and robust methodologies are often required. For this narrative review, literature was sourced from scientific databases (primarily PubMed) in the period from June 2022 to January 2024. The regulatory targets of glucose homeostasis that could be modulated by bioactive plant compounds were used as search terms, either alone or in combination with the keyword “root extract”. As a result, we present a comprehensive methodological toolbox for studying the glucose homeostasis modulating properties of plant extracts and its constituents. The described assays encompass in-vitro investigations involving enzyme inhibition (α-amylase, α-glucosidase, dipeptidyl peptidase 4), assessment of sodium-dependent glucose transporter 1 activity, and evaluation of glucose transporter 4 translocation. Furthermore, we describe a patch-clamp technique to assess the impact of extracts on KATP channels. While validating in-vitro findings in living organisms is imperative, we introduce two screenable in-vivo models (the hen’s egg test and Drosophila melanogaster). Given that evaluation of the bioactivity of plant extracts in rodents and humans represents the current gold standard, we include approaches addressing this aspect. In summary, this review offers a systematic guide for screening plant extracts regarding their influence on key regulatory elements of glucose homeostasis, culminating in the assessment of their potential efficacy in-vivo. Moreover, application of the presented toolbox might contribute to further close the knowledge gap on the precise mechanisms of action of plant-derived compounds

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Geochemistry of Old Black Spruce Fen (OBS3 C3) peat core from Canada

Geochemistry data of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project

Calibrated ages of Old Black Spruce Fen (OBS3 C3) peat core from Canada

Calibrated ages of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project

Geochemistry of Sandhill Fen (SF4 C3) peat core from Canada

Geochemistry data of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project

Calibrated ages of Sandhill Fen (SF4 C3) peat core from Canada

Calibrated ages of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project

Age determination of Sandhill Fen (SF4 C3) peat core from Canada

14C and 210Pb age determination of a high-resolution peat core from the Past Global Changes - Carbon in Peat on EArth through Time (PAGES_C-PEAT) Project