Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study.

Background: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study.

Methods: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0.

Decoupling of a tight-fit transceiver phased array for human brain imaging at 9.4T: Loop overlapping rediscovered.

Purpose: To improve the decoupling of a transceiver human head phased array at ultra-high fields (UHF, ≥ 7T) and to optimize its transmit (Tx) and receive (Rx) performance, a single-row eight-element (1 × 8) tight-fit transceiver overlapped loop array was developed and constructed. Overlapping the loops increases the RF field penetration depth but can compromise decoupling by generating substantial mutual resistance.

Methods: Based on analytical modeling, we optimized the loop geometry and relative positioning to simultaneously minimize the resistive and inductive coupling and constructed a 9.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects.

Comprehensive Thermodynamic Profiling for the Binding of a G-Quadruplex Selective Indoloquinoline.

Binding of a positively charged indoloquinoline derivative to a G-quadruplex formed by the G-rich promoter element of the c-MYC oncogene was subjected to a rigorous isothermal calorimetric analysis. Binding of the indoloquinoline is primarily enthalpy-driven but is also promoted by a favorable entropy term. Both binding enthalpy ΔH° and binding entropy ΔS° exhibit a noticeable temperature dependence with almost complete enthalpy-entropy compensation as a result of a negative change in heat capacity ΔC°.

Preparation and In Vitro Characterization of Magnetized miR-modified Endothelial Cells.

To date, the available surgical and pharmacological treatments for cardiovascular diseases (CVD) are limited and often palliative. At the same time, gene and cell therapies are highly promising alternative approaches for CVD treatment. However, the broad clinical application of gene therapy is greatly limited by the lack of suitable gene delivery systems.

Prevalence of Fatty Liver Disease and Hepatic Iron Overload in a Northeastern German Population by Using Quantitative MR Imaging.

Purpose To quantify liver fat and liver iron content by measurement of confounder-corrected proton density fat fraction (PDFF) and R2* and to identify clinical associations for fatty liver disease and liver iron overload and their prevalence in a large-scale population-based study. Materials and Methods From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift-encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed.

Trait variation in response to varying winter temperatures, diversity patterns and signatures of selection along the latitudinal distribution of the widespread grassland plant .

Across Europe, genetic diversity can be expected to decline toward the North because of stochastic and selective effects which may imply diminished phenotypic variation and less potential for future genetic adaptations to environmental change. Understanding such latitudinal patterns can aid provenance selection for breeding or assisted migration approaches. In an experiment simulating different winter temperatures, we assessed quantitative trait variation, genetic diversity, and differentiation for natural populations of the grass originating from a large latitudinal gradient.

Discovery of novel substituted benzo-anellated 4-benzylamino pyrrolopyrimidines as dual EGFR and VEGFR2 inhibitors.

The quinazoline scaffold is the main part of many marketed EGFR inhibitors. Resistance developments against those inhibitors enforced the search for novel structural lead compounds. We developed novel benzo-anellated 4-benzylamine pyrrolopyrimidines with varied substitution patterns at both the molecular scaffold and the attached residue in the 4-position.

Insight into the evolution of microbial metabolism from the deep-branching bacterium, .

Anaerobic thermophiles inhabit relic environments that resemble the early Earth. However, the lineage of these modern organisms co-evolved with our planet. Hence, these organisms carry both ancestral and acquired genes and serve as models to reconstruct early metabolism.

Ergosterol Peroxide: A Mushroom-Derived Compound with Promising Biological Activities-A Review.

Ergosterol peroxide (EP; 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol) is a C28-sterol and a component of many medicinal mushrooms. Since its discovery nearly a century ago, many sources and biological effects of this compound have been described. Effects range from antimicrobial to cytotoxic to immunosuppressive and other activities.

Mortality is associated with inflammation, anemia, specific diseases and treatments, and molecular markers.

Lifespan is a complex trait, and longitudinal data for humans are naturally scarce. We report the results of Cox regression and Pearson correlation analyses using data of the Study of Health in Pomerania (SHIP), with mortality data of 1518 participants (113 of which died), over a time span of more than 10 years. We found that in the Cox regression model based on the Bayesian information criterion, apart from chronological age of the participant, six baseline variables were considerably associated with higher mortality rates: smoking, mean attachment loss (i.

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies.

Speciation in progress? A phylogeographic study among populations of Hemitrichia serpula (Myxomycetes).

Myxomycetes (plasmodial slime molds, Amoebozoa) are often perceived as widely distributed, confounding to the "everything is everywhere" hypothesis. To test if gene flow within these spore-dispersed protists is restricted by geographical barriers, we chose the widespread but morphologically unmistakable species Hemitrichia serpula for a phylogeographic study. Partial sequences from nuclear ribosomal RNA genes (SSU) revealed 40 ribotypes among 135 specimens, belonging to three major clades.

Discovery of novel heart rate-associated loci using the Exome Chip.

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation.

Genetic engineering of the branched fatty acid metabolic pathway of Bacillus subtilis for the overproduction of surfactin C isoform.

Surfactin, a lipopeptide produced by Bacillus subtilis, is one of the most powerful biosurfactants known. This molecule consists of a cyclic heptapeptide linked to a β-hydroxy fatty acid chain. The isomery and the length of the fatty acid (FA) chain are responsible for the surfactin's activities.

Effects on P3 of spreading targets and response prompts apart.

When key-press responses to targets have to be withheld until the presentation of response prompts, target-evoked P3 amplitudes are reduced and so is the P3 difference between rare and frequent targets (the oddball effect on P3). Recently we showed that this even applied when go-signals followed targets by 100ms. Here we aimed at replicating this result with more fine-grained temporal resolution in 100ms steps from 0ms to 500ms, and dissecting the P3 complex to stimulus- and response-related portions by applying residue iteration decomposition (RIDE).

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects.

Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging.

Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underestimated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL.

Tracing Effects of Fluorine Substitutions on G-Quadruplex Conformational Changes.

A human telomere sequence that folds into an intramolecular (3 + 1)-hybrid G-quadruplex was modified by the incorporation of 2'-fluoro-2'-deoxyriboguanosines (G) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a G-substituted (3 + 1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal.

Effects of extracts and compounds from Tricholoma populinum Lange on degranulation and IL-2/IL-8 secretion of immune cells.

Tricholoma populinum Lange is an edible basidiomycete from the family Tricholomataceae. Extracts, fractions, and different metabolites isolated from the fruiting bodies of this mushroom were tested for degranulation-inhibiting activities on RBL-2H3 cells (rat basophils). Dichloromethane extracts decreased degranulation significantly, as did a fraction after column chromatography.

Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis.

The function of articular cartilage as an avascular tissue is mainly served by collagen type II and proteoglycan molecules. Within this matrix homeostasis between production and breakdown of the matrix is exceptionally sensitive. The current study was conducted to identify regional differences in specific alterations in cartilage composition during the osteoarthritic process of the human knee joint.

Role of purinergic signaling in experimental pneumococcal meningitis.

Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7.

Symbiotic Interplay of Fungi, Algae, and Bacteria within the Lung Lichen Lobaria pulmonaria L. Hoffm. as Assessed by State-of-the-Art Metaproteomics.

Lichens are recognized by macroscopic structures formed by a heterotrophic fungus, the mycobiont, which hosts internal autotrophic photosynthetic algal and/or cyanobacterial partners, referred to as the photobiont. We analyzed the structure and functionality of the entire lung lichen Lobaria pulmonaria L. Hoffm.

Selective Targeting of G-Quadruplex Structures by a Benzothiazole-Based Binding Motif.

A benzothiazole derivative was identified as potent ligand for DNA G-quadruplex structures. Fluorescence titrations revealed selective binding to quadruplexes of different topologies including parallel, antiparallel, and (3+1) hybrid structures. The parallel c-MYC sequence was found to constitute the preferred target with dissociation constants in the micromolar range.