Extraction and complexation studies with 2,6-bis(5-(tert -butyl)-1 H -pyrazol-3-yl)pyridine in the presence of 2-bromohexanoic acid

To improve the understanding of the extraction chemistry of An(III) and Ln(III) with N-donor ligands 2,6-bis(5-(tert-butyl)-1H-pyrazol-3-yl)pyridine (C4-BPP) in the presence of 2-bromohexanoic acid was investigated

Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors

SIPEX-2: A study of sea-ice physical, biochemical and ecosystem processes off East Antarctica during spring 2012

This editorial introduces a suite of articles resulting from the second Sea Ice Physics and Ecosystems eXperiment(SIPEX-2) voyage by presenting some background information on the study areaandAntarcticsea-ice conditions,and summarising the key findings from the project.Using the Australian iceb reaker RV Aurora Australis, SIPEX-2 was conducted in the area between 115–125°E and 62–66°S off East Antarctica during September to November 2012. This region had been sampled during two previous experiments,i.e. ARISE in 2003 (Massom etal.,2006a) and SIPEX in 2007(Worbyetal.,2011a). The 2012 voyage combined traditional and newly developed sampling methods with satellite and other data to measure sea-ice physical properties and pro- cesses on large scales,which provided context for bio geochemical and ecological case studies. Thes pecific goals of the SIPEX-2 project were to:(i)measure the spatial variability in sea-ice and snow-cover properties over small-to regional-length scales;(ii) improve understanding of sea-ice kinematic processes;and(iii) advance knowledge of the links between sea-ice physical characteristics,sea-ice biogeochemical cycling and ice-associated food-web dynamics.Our field-based activities were designed to inform modelling approaches and to improve our capability to assess impacts of predicted changes in Antarctic sea ice on Southern Ocean biogeochemical cycles and ecosystem function

Biological therapy in Sjögren’s syndrome : outcomes and evaluation

Het syndroom van Sjögren is een chronische ziekte waarbij klieren ontstoken raken, vooral de speeksel- en traanklieren, met een droge mond en droge ogen als gevolg. Daarnaast kunnen de ontstekingen zich ook uiten in andere organen zoals de longen, nieren of bloedvaten. Bijna alle patiënten zijn chronische vermoeid. Na reumatoïde artritis is Sjögren de meest voorkomende systemische auto-immuunziekte. Ondanks het frequent voorkomen van deze ziekte is er relatief weinig aandacht voor en zijn de behandelopties gering. Door de komst van biologische ‘Disease Modifying Antireumatische Drugs’ (DMARDs) en de mogelijkheid om hier onderzoek mee te doen bij deze ziekte kan hierin verandering worden gebracht. Deze DMARDs richten zich op cellen en cytokinen die betrokken zijn bij de pathogenese van deze ziekte en worden beschouwd als veelbelovend. In dit proefschrift wordt het effect van het hebben van Sjögren op het dagelijks functioneren en arbeidsparticipatie onderzocht, wordt de werkzaamheid van twee biologische DMARDs (rituximab, abatacept) geëvalueerd en wordt het vermogen van de European League Against Rheumatism (EULAR) Syndroom van Sjögren Disease Activity index (ESSDAI) en de EULAR Sjögren Syndrome Patient Reported index (ESSPRI) om het effect van behandeling in primair SS te evalueren bestudeerd. De belangrijkste bevindingen van dit onderzoek zijn de grote impact van het hebben van Sjögren op kwaliteit van leven, werk en arbeidsongeschiktheid, de observatie dat ESSDAI en ESSPRI gevoelige instrumenten zijn voor het meten van veranderingen in ziekteactiviteit en de veelbelovende effectiviteit van rituximab en abatacept in de behandeling van het syndroom van Sjögren. Sjögren’s syndrome, the most common systemic autoimmune disease after rheumatoid arthritis, is characterized by chronic inflammation of the exocrine glands. The salivary and lacrimal glands are commonly affected, resulting in dry mouth and dry eyes. Extraglandular involvement can occur, and includes pulmonary disease, renal disease and vasculitis. Almost all patients suffer from chronic fatigue. Sjögren’s syndrome can be primary or secondary, the latter being associated with other autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Although there is currently no curative or causal treatment for Sjögren’s syndrome, various supportive and palliative treatment options are available. Biological disease-modifying antirheumatic drugs (DMARDs) have become available over the past decade. These DMARDs target cells and cytokines involved in the pathogenesis of Sjögren’s syndrome, and are considered promising therapies. In this thesis, the impact of having Sjögren’s syndrome on patients’ functioning and daily activity is investigated, the efficacy of 2 biological DMARDs (rituximab, abatacept) is assessed, and the ability of the European League against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjögren’s syndrome Patient Reported Index (ESSPRI) to monitor the effect of intervention treatment in primary Sjögren’s syndrome is studied. The key findings of the research presented in this thesis are the major impact of Sjögren’s syndrome on health-related quality of life, employment and disability in these individuals; the observation that ESSDAI and ESSPRI are sensitive instruments for measuring changes in disease activity and the promising efficacy of rituximab and abatacept in the treatment of primary Sjögren’s syndrome.