Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans

Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay of gastric emptying.Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2).Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments.Results: Ex(9-39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation.Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic \textgreeka cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans

Abundance, horizontal and vertical distribution of the invasive ctenophore Mnemiopsis leidyi in the central Baltic Sea, November 2007

The distribution and abundance of the invasive ctenophore Mnemiopsis leidyi in the Bornholm Basin, an important spawning ground of several fish stocks, and in adjacent areas in the central Baltic Sea was studied in November 2007. The study showed that M. leidyi were relatively small (body length 18.6 ± 7.6 mm) and they were patchily distributed over a large part of the investigated area. Specimens were found on 68 and 59% of stations sampled with a Bongo net (n=39) and an Isaac-Kidd midwater trawl (n=51), respectively. Vertically, the highest densities of M. leidyi occurred at 40 to 60 m around the halocline. Horizontally, the highest abundances were found north and west of Bornholm, but relatively high densities were also observed in the Slupsk Furrow. The mean abundance was 1.58 ± 2.12 ind. m-2, the peak abundance was 8.92 ind. m-2, and the average and peak population density were 0.03 ± 0.05 and 0.28 ind. m-3, respectively. The abundances are low compared to densities recently observed in other areas of the Baltic region (e. g. Limfjorden, Åland Sea) and the estimated predation impact on zooplankton by M. leidyi was negligible in November 2007. However, because of the ctenophore’s wide distribution in the central Baltic Sea, its ability for rapid population growth, and its potential influence on fish stocks by competing for food and by preying on fish eggs and newly hatched larvae, close monitoring of the future development of M. leidyi in the Baltic Sea is strongly recommended

Orbital-dependent metamagnetic response in Sr4Ru3O10

We show that the metamagnetic transition in Sr$_4$Ru$_3$O$_{10}$ bifurcates into two transitions as the field is rotated away from the conducting planes. This two-step process comprises partial or total alignment of moments in ferromagnetic bands followed by an itinerant metamagnetic transition whose critical field increases with rotation. Evidence for itinerant metamagnetism is provided by the Shubnikov-de Hass effect which shows a non-trivial evolution of the geometry of the Fermi surface and an enhancement of the quasiparticles effective-mass across the transition. The metamagnetic response of Sr$_4$Ru$_3$O$_{10}$ is orbital-dependent and involves ferromagnetic and metamagnetic bands.Comment: Physical Review B (in press

DFT plus U study of the structures and properties of the actinide dioxides

The actinide oxides play a vital role in the nuclear fuel cycle. For systems where current experimental measurements are difficult, computational techniques provide a means of predicting their behaviour. However, to date no systematic methodology exists in the literature to calculate the properties of the series, due to the lack of experimental data and the computational complexity of the systems. Here, we present a systematic study where, within the DFT+U formulism, we have parametrized the most suitable Coulombic (U) and exchange (J) parameters for different functionals (LDA, PBE, PBE-Sol and AM05) to reproduce the experimental band-gap and lattice parameters for ThO2, UO2, NpO2, PuO2, AmO2 and CmO2. After successfully identifying the most suitable parameters for these actinide dioxides, we have used our model to describe the electronic structures of the different systems and determine the band structures, optical band-gaps and the Bulk moduli. In general, PBE-Sol provides the most accurate reproduction of the experimental properties, where available. We have employed diamagnetic order for ThO2, PuO2 and CmO2, transverse 3k antiferromagnetic order for UO2 and AmO2, and longitudinal 3k antiferromagnetic order for NpO2. The Fm m cubic symmetry is preserved for diamagnetic ThO2, PuO2 and CmO2 and longitudinal 3k NpO2. For UO2 and AmO2, the transverse 3k antiferromagnetic state results in Pa symmetry, in agreement with recent experimental findings. Although the electronic structure of ThO2 cannot be reproduced by DFT or DFT+U, for UO2, PuO2, NpO2, AmO2 and CmO2, the experimental properties are very well represented when U = 3.35 eV, 6.35 eV, 5.00 eV, 7.00 eV and 6.00 eV, respectively, with J = 0.00 eV, 0.00 eV, 0.75 eV, 0.50 eV and 0.00 eV, respectively

DFT+U study of the structures and properties of the actinide dioxides

The actinide oxides play a vital role in the nuclear fuel cycle. For systems where current experimental measurements are difficult, computational techniques provide a means of predicting their behaviour. However, to date no systematic methodology exists in the literature to calculate the properties of the series, due to the lack of experimental data and the computational complexity of the systems. Here, we present a systematic study where, within the DFT+U formulism, we have parametrized the most suitable Coulombic (U) and exchange (J) parameters for different functionals (LDA, PBE, PBE-Sol and AM05) to reproduce the experimental band-gap and lattice parameters for ThO2, UO2, NpO2, PuO2, AmO2 and CmO2. After successfully identifying the most suitable parameters for these actinide dioxides, we have used our model to describe the electronic structures of the different systems and determine the band structures, optical band-gaps and the Bulk moduli. In general, PBE-Sol provides the most accurate reproduction of the experimental properties, where available. We have employed diamagnetic order for ThO2, PuO2 and CmO2, transverse 3k antiferromagnetic order for UO2 and AmO2, and longitudinal 3k antiferromagnetic order for NpO2. The Fm m cubic symmetry is preserved for diamagnetic ThO2, PuO2 and CmO2 and longitudinal 3k NpO2. For UO2 and AmO2, the transverse 3k antiferromagnetic state results in Pa symmetry, in agreement with recent experimental findings. Although the electronic structure of ThO2 cannot be reproduced by DFT or DFT+U, for UO2, PuO2, NpO2, AmO2 and CmO2, the experimental properties are very well represented when U = 3.35 eV, 6.35 eV, 5.00 eV, 7.00 eV and 6.00 eV, respectively, with J = 0.00 eV, 0.00 eV, 0.75 eV, 0.50 eV and 0.00 eV, respectively

Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086–1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan–Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts