Exploring possible links between Quaternary aggradation in the Upper Rhine Graben and the glaciation history of northern Switzerland

The Quaternary filling of the Upper Rhine Graben is an excellent archive to reconstruct sediment dynamics in response to climate change, in particular related to past glaciations of the Swiss Alpine Foreland. Here, a sediment sequence recovered by drilling for exploration purposes near Kronau is investigated, using a combination of sedimentological logging, provenance studies (heavy minerals and clast petrography), and luminescence dating. Several phases of coarse sediment aggradation are identified that possibly correlate to Marine Isotope Stages (MIS) 12 (478-424 ka), 10 (374-337 ka), 8 (300-243 ka), 6 (191-130 ka) and/or 4 (71-57 ka), and 2 (29-14 ka). Several of these phases have previously also been reported from cores recovered in the major Quaternary depo-centre near Heidelberg. This suggests that the observed coarse aggradation in the Upper Rhine Graben can be assigned to various glaciations in northern Switzerland: Mohlin (MIS 12), Habsburg (MIS 10 or 8), Beringen (MIS 6), an unnamed glacial advance during MIS 4, and Birrfeld (MIS 2). However, due to the limited data available, this hypothesis and the suggested correlations require further confirmation by applying the approach presented here to further cores from the Upper Rhine Graben.</p

ChIP-Chip Designs to Interrogate the Genome of Xenopus Embryos for Transcription Factor Binding and Epigenetic Regulation

Chromatin immunoprecipitation combined with genome tile path microarrays or deep sequencing can be used to study genome-wide epigenetic profiles and the transcription factor binding repertoire. Although well studied in a variety of cell lines, these genome-wide profiles have so far been little explored in vertebrate embryos. genome. In particular, a whole-genome microarray design was used to identify active promoters by close proximity to histone H3 lysine 4 trimethylation. A second microarray design features these experimentally derived promoter regions in addition to currently annotated 5′ ends of genes. These regions truly represent promoters as shown by binding of TBP, a key transcription initiation factor. embryos

The influence of long distance running on sonographic joint and tendon pathology: results from a prospective study with marathon runners

Background: The impact of physical exercise on joints and tendons is still a matter of debate. The aim of this study was to investigate with ultrasound the acute effects of extreme physical exercise on knee and ankle joints and their surrounding structures in trained athletes. Methods: Participants of the Munich marathon were examined by arthrosonography before and after long distance running. Ultrasound assessment included grey scale and power Doppler examination of the knee and talocrural joints with surrounding tendons. Findings consistent with joint effusion, tendon and/or entheseal pathologies were documented. In addition to the ultrasound evaluation, information on training habits and past or present arthralgia or joint swelling was gathered. Results: One Hundred Five runners completed both the pre- and post-excercise ultrasound assessments (baseline and follow-up), resulting in the sonographic evaluation of 420 knee and talocrural joints. At baseline, 105 knee (50) and 38 talocrural joints (18.1) showed effusions, compared to 100 knee (47.6) and 33 talocrural joints (15.7 %) at follow-up. The differences were not significant (p > 0.05 each). Effusion size did not correlate with the timepoint of ultrasound assessment and was independent of covariates such as gender, age or running distance. Hypervascularity of the patellar tendon was detected in 21 cases (10.0 %) at follow-up in contrast to one at baseline (p < 0.001). This observation was more frequent in male than in female participants (p < 0.05). Conclusions: Acute physical stress is significantly associated with hypervascularity of the patellar tendon. No significant changes of synovial effusion were detected in knee and talocrural joints

HCV Causes Chronic Endoplasmic Reticulum Stress Leading to Adaptation and Interference with the Unfolded Protein Response

BACKGROUND: The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells to adapt by attenuation of UPR activation. Hepatitis C virus (HCV), a major human pathogen, was shown to cause ER stress, however it is unclear whether HCV induces chronic ER stress, and if so whether adaptation mechanisms are initiated. We wanted to characterize the kinetics of HCV-induced ER stress during infection and assess adaptation mechanisms and their significance. METHODS AND FINDINGS: The HuH7.5.1 cellular system and HCV-transgenic (HCV-Tg) mice were used to characterize HCV-induced ER stress/UPR pathway activation and adaptation. HCV induced a wave of acute ER stress peaking 2-5 days post-infection, which rapidly subsided thereafter. UPR pathways were activated including IRE1 and EIF2α phosphorylation, ATF6 cleavage and XBP-1 splicing. Downstream target genes including GADD34, ERdj4, p58ipk, ATF3 and ATF4 were upregulated. CHOP, a UPR regulated protein was activated and translocated to the nucleus. Remarkably, UPR activity did not return to baseline but remained elevated for up to 14 days post infection suggesting that chronic ER stress is induced. At this time, cells adapted to ER stress and were less responsive to further drug-induced ER stress. Similar results were obtained in HCV-Tg mice. Suppression of HCV by Interferon-α 2a treatment, restored UPR responsiveness to ER stress tolerant cells. CONCLUSIONS: Our study shows, for the first time, that HCV induces adaptation to chronic ER stress which was reversed upon viral suppression. These finding represent a novel viral mechanism to manipulate cellular response pathways

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029

Spectra of a shallow sea-unmixing for class identification and monitoring of coastal waters

Ocean colour-based monitoring of water masses is a promising alternative to monitoring concentrations in heterogeneous coastal seas. Fuzzy methods, such as spectral unmixing, are especially well suited for recognition of water masses from their remote sensing reflectances. However, such models have not yet been applied for water classification and monitoring. In this study, a fully constrained endmember model with simulated endmembers was developed for water class identification in the shallow Wadden Sea and adjacent German Bight. Its performance was examined on in situ measured reflectances and on MERIS satellite data. Water classification by means of unmixing reflectance spectra proved to be successful. When the endmember model was applied to MERIS data, it was able to visualise well-known spatial, tidal, seasonal, and wind-related variations in optical properties in the heterogeneous Wadden Sea. Analyses show that the method is insensitive to small changes in endmembers. Therefore, it can be applied in similar coastal areas. For use in open ocean situations or coastal or inland waters with other specific inherent optical properties, re-simulation of the endmember spectra with local optical properties is required. However, such an adaptation requires only a limited number of local in situ measurements