Effect of GnRH and its antagonist (Antarelix) on LH release from cultured bovine anterior pituitary cells

In the following investigations, the LH secretion of cells from pituitaries in heifers on days 16-18 of their oestrous cycle (n = 14) was analysed. Cells were dissociated with trypsin and collagenase and maintained in a static culture system. For the estimation of LH release, the cells were incubated with various concentrations of mammalian GnRH (Lutrelef) for 6h. To determine the action of Antarelix (GnRH antagonist), the cells were preincubated for 1 h with concentrations of 10-5 or 10-4 M Antarelix followed by 10-6 M GnRH coincubation for a further 6h. At the end of each incubation, the medium was collected for LH analysis. Parallel, intracellular LH was qualitatively detected by immunocytochemistry. Changes in the intensity of LH staining within the cells in dependence of different GnRH concentrations were not observed, but a significant increase LH secretion in pituitary cells was measured at 10-6 M GnRH. Antarelix had no effect on basal LH secretion at concentrations of 10-4 and 10-5 M. After coincubation of pituitary cells with Antarelix and GnRH, Antarelix blocked the GnRH-stimulated LH secretion with a maximal effect of 10-4 M, but the staining of immunoreactive intracellular LH was detected at approximately the same level compared to the pituitary cells treated with exogenous GnRH alone. These data demonstrate that Antarelix is effective in influencing the GnRH-stimulated LH secretion of pituitary cells in vitro. After administration of Antarelix in vivo, the GnRH-stimulated LH secretion of cultured pituitary cells was not inhibited

Continued glacial retreat linked to changing macronutrient supply along the West Antarctic Peninsula

At the West Antarctic Peninsula (WAP), continued atmospheric and oceanic warming is causing significant physical and biogeochemical changes to glaciers and the marine environment. We compare sediment sources and drivers of macronutrient distributions at two bays along the WAP during austral summer 2020, using radioactive radium and stable oxygen isotopes to trace sedimentary influences and quantify different freshwater inputs. In the Ryder Bay, where the Sheldon Glacier is marine-terminating, radium activities at the sediment-water interface indicate considerable benthic mixing. Using radium isotope activity gradients to resolve radium and macronutrient fluxes, we find buoyant meltwater proximal to the glacier drives vigorous mixing of sediment and entrainment of macronutrient deep waters, on the order of 2.0 × 105 mol d− 1 for nitrate. Conversely, in the Marian Cove, where the Fourcade Glacier terminates on land, low salinities and oxygen isotopes indicate a meltwater-rich surface layer <1 m thick and rich in sediment, and strong vertical mixing to the seafloor. A continued shift to land-terminating glaciers along the WAP may have a significant impact upon nutrient and sediment supply to the euphotic zone, with impacts upon primary productivity and carbon uptake efficiency. The future of primary production, carbon uptake, and food web dynamics is therefore linked to glacier retreat dy�namics in the many fjords along the WAP

Can information affect sensory perceptions? Evidence from a survey on Italian organic food consumers

This paper aims to investigate the influence of information on consumers’ preferences and sensory perceptions of organic food using a sample of 301 Italian organic food consumers. Consumers stated their preferences for “core organic” attributes, labels and information on food products and performed blind and informed tests on strawberry yoghurts and cookies. Data were analysed using descriptive analysis, Mann-Whitney U tests and Wilcoxon signed-rank test. Results revealed that consumers appreciate “core organic” attributes, like artisanal production and variability of sensory attributes. Comparing blind and informed tests, results showed that information affects the overall liking of products and consumers’ perception of product-specific sensory attributes. However, the influence of information on sensory perceptions depends on the product category, sensory attributes and the type of information provided

a randomized, placebo-controlled phase II AIO trial with serum biomarker program

Background As a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response. Methods This double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively. Results Overall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70–1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50–1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed. Conclusions Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti- angiogenic RTK inhibitors are warranted. Trial registration This study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland- Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009

When and How to Provide Feedback and Instructions to Athletes?—How Sport Psychology and Pedagogy Insights Can Improve Coaching Interventions to Enhance Self-Regulation in Training

In specialist sports coaching, the type and manner of augmented information that the coach chooses to use in communicating and training with individual athletes can have a significant impact on skill development and performance. Informed by insights from psychology, pedagogy, and sport science, this position paper presents a practitioner-based approach in response to the overarching question: When, why, and how could coaches provide information to athletes during coaching interventions? In an ecological dynamics rationale, practice is seen as a search for functional performance solutions, and augmented feedback is outlined as instructional constraints to guide athletes’ self-regulation of action in practice. Using the exemplar of team sports, we present a Skill Training Communication Model for practical application in the context of the role of a specialist coach, using a constraints-led approach (CLA). Further based on principles of a non-linear pedagogy and using the recently introduced Periodization of Skill Training (PoST) framework, the proposed model aims to support practitioners’ understanding of the pedagogical constraints of feedback and instruction during practice. In detail, the PoST framework’s three skill development and training stages work to (1) directly impact constraint manipulations in practice designs and (2) indirectly affect coaches’ choices of external (coach-induced) information. In turn, these guide practitioners on how and when to apply different verbal instruction methodologies and aim to support the design of effective skill learning environments. Finally, several practical guidelines in regard to sports coaches’ feedback and instruction processes are proposed

Bacteria-responsive multilayer coatings comprising polycationic nanospheres for bacteria biofilm prevention on urinary catheters

This work reports on the development of infection-preventive coatings on silicone urinary catheters that contain in their structure and release on demand antibacterial polycationic nanospheres. Polycationic aminocellulose conjugate was first sonochemically processed into nanospheres to improve its antibacterial potential compared to the bulk conjugate in solution (ACSol). Afterwards the processed aminocellulose nanospheres (ACNSs) were combined with the hyaluronic acid (HA) polyanion to build a layer-by-layer construct on silicone surfaces. Although the coating deposition was more effective when HA was coupled with ACSol than with ACNSs, the ACNSs-based coatings were thicker and displayed smoother surfaces due to the embedment of intact nanospheres. The antibacterial effect of the ACNSs multilayers was by 40 % higher compared to the ACSol coatings. This fact was further translated into more effective prevention of Pseudomonas aeruginosa biofilm formation. The coatings were stable in absence of bacteria, whereas their disassembling occurred gradually during incubation with Pseudomonas aeruginosa, and thus eradicate the biofilm upon release of antibacterial agents. Only 5 bilayers of HA/ACNSs were sufficient to prevent the biofilm formation, in contrast to the 10 bilayers of ACSol required to achieve the same effect. The antibiofilm efficiency of (HA/ACNSs)10 multilayer construct built on a Foley catheter was additionally validated under dynamic conditions using a model of catheterized bladder in which the biofilm was grown during seven days.M.M.F. acknowledges the support of the European Commissionunder the Marie Curie Intra-European Fellowship (IEF) Program (Grant Agreement ‘‘NanoQuench” FP7-331416)

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Climatically sensitive transfer of iron to maritime Antarctic ecosystems by surface runoff

Iron supplied by glacial weathering results in pronounced hotspots of biological production in an otherwise iron-limited Southern Ocean Ecosystem. However, glacial iron inputs are thought to be dominated by icebergs. Here we show that surface runoff from three island groups of the maritime Antarctic exports more filterable (<0.45 μm) iron (6–81 kg km−2 a−1) than icebergs (0.0–1.2 kg km−2 a−1). Glacier-fed streams also export more acid-soluble iron (27.0–18,500 kg km−2 a−1) associated with suspended sediment than icebergs (0–241 kg km−2 a−1). Significant fluxes of filterable and sediment-derived iron (1–10 Gg a−1 and 100–1,000 Gg a−1, respectively) are therefore likely to be delivered by runoff from the Antarctic continent. Although estuarine removal processes will greatly reduce their availability to coastal ecosystems, our results clearly indicate that riverine iron fluxes need to be accounted for as the volume of Antarctic melt increases in response to 21st century climate change

Chimpanzee (Pan troglodytes) Precentral Corticospinal System Asymmetry and Handedness: A Diffusion Magnetic Resonance Imaging Study

Most humans are right handed, and most humans exhibit left-right asymmetries of the precentral corticospinal system. Recent studies indicate that chimpanzees also show a population-level right-handed bias, although it is less strong than in humans.We used in vivo diffusion-weighted and T1-weighted magnetic resonance imaging (MRI) to study the relationship between the corticospinal tract (CST) and handedness in 36 adult female chimpanzees. Chimpanzees exhibited a hemispheric bias in fractional anisotropy (FA, left>right) and mean diffusivity (MD, right>left) of the CST, and the left CST was centered more posteriorly than the right. Handedness correlated with central sulcus depth, but not with FA or MD.These anatomical results are qualitatively similar to those reported in humans, despite the differences in handedness. The existence of a left>right FA, right>left MD bias in the corticospinal tract that does not correlate with handedness, a result also reported in some human studies, suggests that at least some of the structural asymmetries of the corticospinal system are not exclusively related to laterality of hand preference

Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels

Alternative splicing creates several Nav1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Nav1.5 splice variants have been discovered. Four of them, namely Nav1.5a, Nav1.5c, Nav1.5d, and Nav1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Nav1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNav1.5, hNav1.5a, and hNav1.5c. In contrast, the hNav1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNav1.5e, the neonatal variant of hNav1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNav1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNav1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies