Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6   6   6 m liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light.

Glycolipid-dependent and lectin-driven transcytosis in mouse enterocytes.

Glycoproteins and glycolipids at the plasma membrane contribute to a range of functions from growth factor signaling to cell adhesion and migration. Glycoconjugates undergo endocytic trafficking. According to the glycolipid-lectin (GL-Lect) hypothesis, the construction of tubular endocytic pits is driven in a glycosphingolipid-dependent manner by sugar-binding proteins of the galectin family.

Functional dissection of the retrograde Shiga toxin trafficking inhibitor Retro-2.

The retrograde transport inhibitor Retro-2 has a protective effect on cells and in mice against Shiga-like toxins and ricin. Retro-2 causes toxin accumulation in early endosomes and relocalization of the Golgi SNARE protein syntaxin-5 to the endoplasmic reticulum. The molecular mechanisms by which this is achieved remain unknown.

Spatiotemporal control of interferon-induced JAK/STAT signalling and gene transcription by the retromer complex.

Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome.

Glycosylation-Dependent IFN-γR Partitioning in Lipid and Actin Nanodomains Is Critical for JAK Activation.

Understanding how membrane nanoscale organization controls transmembrane receptors signaling activity remains a challenge. We studied interferon-γ receptor (IFN-γR) signaling in fibroblasts from homozygous patients with a T168N mutation in IFNGR2. By adding a neo-N-glycan on IFN-γR2 subunit, this mutation blocks IFN-γ activity by unknown mechanisms.

Galectin-3 drives glycosphingolipid-dependent biogenesis of clathrin-independent carriers.

Several cell surface molecules including signalling receptors are internalized by clathrin-independent endocytosis. How this process is initiated, how cargo proteins are sorted and membranes are bent remains unknown. Here, we found that a carbohydrate-binding protein, galectin-3 (Gal3), triggered the glycosphingolipid (GSL)-dependent biogenesis of a morphologically distinct class of endocytic structures, termed clathrin-independent carriers (CLICs).

Rab12 localizes to Shiga toxin-induced plasma membrane invaginations and controls toxin transport.

Several exogenous and endogenous cargo proteins are internalized independently of clathrin, including the bacterial Shiga toxin. The mechanisms underlying early steps of clathrin-independent uptake remain largely unknown. In this study, we have designed a protocol to obtain gradient fractions containing Shiga toxin internalization intermediates.

SNAP-tag based proteomics approach for the study of the retrograde route.

Proteomics is a powerful technique for protein identification at large scales. A number of proteomics approaches have been developed to study the steady state composition of intracellular compartments. Here, we report a novel vectorial proteomics strategy to identify plasma membrane proteins that undergo retrograde transport to the trans-Golgi network (TGN).

Kava extracts: safety and risks including rare hepatotoxicity.

Kava is a perennial shrub native to some islands of the South Pacific and has been cultivated for centuries to prepare a psychoactive beverage from its rhizoma by means of extraction. Subsequently, kava extracts are commonly used as herbal anxiolytic drugs also in many other countries all over the world including European ones and the USA. Toxicological and clinical studies have shown that kava extracts are virtually devoid of toxic effects with the exception of rare hepatotoxic side effects reported in few patients.

Low-field MR arthrography of the shoulder joint: technique, indications, and clinical results.

In the age of cost containment and urgent reductions in health care expenditures, new options have to be explored to satisfy both diagnostic requirements and economic limitations. The introduction of low-field MR systems for assessment of joint disorders seemed to be an option for lower costs. The purpose of this article is to summarize available experiences with low-field MR arthrography of the glenohumeral joint with respect to image quality and diagnostic accuracy in detecting labral and rotator cuff lesions.

Differential therapy of constipation--a review.

Constipation is a common condition occurring with increasing frequency in advanced age. As a symptom, it is not always dealt with directly by the physician, but is often left to the care of nurses. Many patients rely on self-medication.

MR arthrography of the shoulder: comparison of low-field (0.2 T) vs high-field (1.5 T) imaging.

The objective of this study was to compare the image quality, sensitivity, specificity, and diagnostic accuracy of an open low-field MR system (0.2 T) with a standard high-field MR system (1.5 T) after arthrography of the shoulder.

[Phytogenic drugs in heart diseases exemplified by Crataegus].

According to the results, standardized extracts differ from other inotropic drugs used for treatment of chronic heart insufficiency. Crataegus extracts have positive inotropic, positive chronotropic, positive dromotropic but negative bathmotropic effects, increase coronary and myocardial perfusion, lower periphere resistance and has anti-arrhythmic and economizing effects. In randomized double-blind clinical trials, key surrogates for efficacy in chronic heart insufficiency were improved.

Studies on vitamin B12 status in the elderly--prophylactic and therapeutic consequences.

Because of the large liver stores (about 5 mg), low turnover rate (0.143%) and small daily requirement (3 micrograms), vitamin B12 deficiency does not occur under normal circumstances. This is not the case in individuals with chronic inflammatory or trophic changes at vitamin B12 absorption sites.

[The validity of radioimmunologic determination of bioavailability of beta-escin in horse chestnut extracts].

The bioavailability under steady state conditions of a standard, slow-release horse chestnut seed extract (HCSE)-containing product was compared with that of an analogous, fast-release test preparation (Noricaven novo) in a prospective, randomised, double-blind study in a double cross-over design. The serum concentration of beta-escin (CAS 6805-41-0) was measured by radioimmunoassay. In addition, the biopharmaceutical properties of the HCSEs present in the products were investigated, the amount and composition of the active ingredient, escin, being analysed with a validated HPLC method.

[Therapeutic trial, clinical research and therapeutic freedom--medical aspects].

In the history of medicine, the approach has changed from prevention to curative medicine- hand in hand with the availability of the pharmacologic findings. Prior to the era of a medicine based on natural science, drugs were found by an empirical trial- and error approach resulting in a steadily growing of drugs. With the upcoming natural sciences, medicine reached new levels in drug treatment by extensive and systematic research in experimental and clinical trials.

Subcutaneous implantation metastasis of a cholangiocarcinoma of the bile duct after percutaneous transhepatic biliary drainage (PTBD).

Percutaneous transhepatic biliary drainage (PTBD) is the basis for most biliary interventional procedures. We recently observed the occurrence of a subcutaneous implantation metastasis after PTBD in a patient with incurable cholangiocarcinoma. Although tumor cell seeding along the catheter tract is a very rare complication, we think that PTBD should be avoided when curative resection is planned.