Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects

The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.Deirdre O’Donovan, Christine Feinle-Bisset, Judith Wishart and Michael Horowit

Random matrix approach in search for weak signals immersed in background noise

We present new, original and alternative method for searching signals coded in noisy data. The method is based on the properties of random matrix eigenvalue spectra. First, we describe general ideas and support them with results of numerical simulations for basic periodic signals immersed in artificial stochastic noise. Then, the main effort is put to examine the strength of a new method in investigation of data content taken from the real astrophysical NAUTILUS detector, searching for the presence of gravitational waves. Our method discovers some previously unknown problems with data aggregation in this experiment. We provide also the results of new method applied to the entire respond signal from ground based detectors in future experimental activities with reduced background noise level. We indicate good performance of our method what makes it a positive predictor for further applications in many areas.Comment: 15 pages, 16 figure

Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs in preclinical research have highlighted several potential novel therapies for SMA, increasing the need for robust and sensitive clinical trial platforms for evaluating their effectiveness in human patient cohorts. Given that most clinical trials for SMA are likely to involve young children, there is a need for validated molecular biomarkers to assist with monitoring disease progression and establishing the effectiveness of therapies being tested. Proteomics technologies have recently been highlighted as a potentially powerful tool for such biomarker discovery. METHODS: We utilized label-free proteomics to identify individual proteins in pathologically-affected skeletal muscle from SMA mice that report directly on disease status. Quantitative fluorescent western blotting was then used to assess whether protein biomarkers were robustly changed in muscle, skin and blood from another mouse model of SMA, as well as in a small cohort of human SMA patient muscle biopsies. RESULTS: By comparing the protein composition of skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle proteome at a late-symptomatic time-point we identified increased expression of both Calreticulin and GRP75/Mortalin as robust indicators of disease progression in SMA mice. We report that these protein biomarkers were consistently modified in different mouse models of SMA, as well as across multiple skeletal muscles, and were also measurable in skin biopsies. Furthermore, Calreticulin and GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients. CONCLUSIONS: We conclude that label-free proteomics technology provides a powerful platform for biomarker identification in SMA, revealing Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting on disease progression in samples of muscle and skin

Simulation of primordial object formation

We have included the chemical rate network responsible for the formation of molecular Hydrogen in the N-body hydrodynamic code, Hydra, in order to study the formation of the first cosmological at redshifts between 10 and 50. We have tested our implementation of the chemical and cooling processes by comparing N-body top hat simulations with theoretical predictions from a semi-analytic model and found them to be in good agreement. We find that post-virialization properties are insensitive to the initial abundance of molecular hydrogen. Our main objective was to determine the minimum mass ($M_{SG}(z)$) of perturbations that could become self gravitating (a prerequisite for star formation), and the redshift at which this occurred. We have developed a robust indicator for detecting the presence of a self-gravitating cloud in our simulations and find that we can do so with a baryonic particle mass-resolution of 40 solar masses. We have performed cosmological simulations of primordial objects and find that the object's mass and redshift at which they become self gravitating agree well with the $M_{SG}(z)$ results from the top hat simulations. Once a critical molecular hydrogen fractional abundance of about 0.0005 has formed in an object, the cooling time drops below the dynamical time at the centre of the cloud and the gas free falls in the dark matter potential wells, becoming self gravitating a dynamical time later.Comment: 45 pages, 17 figures, submitted to Ap

FUSE observations of G226-29: First detection of the H_2 quasi-molecular satellite at 1150A

We present new FUV observations of the pulsating DA white dwarf G226-29 obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE). This ZZ Ceti star is the brightest one of its class and the coolest white dwarf observed by FUSE. We report the first detection of the broad quasi-molecular collision-induced satellite of Ly-beta at 1150 A, an absorption feature that is due to transitions which take place during close collisions of hydrogen atoms. The physical interpretation of this feature is based on recent progress of the line broadening theory of the far wing of Ly-beta. This predicted feature had never been observed before, even in laboratory spectra.Comment: Accepted for publication in ApJ Letters; 6 pages, 3 figure

Spectral Density of Sparse Sample Covariance Matrices

Applying the replica method of statistical mechanics, we evaluate the eigenvalue density of the large random matrix (sample covariance matrix) of the form $J = A^{\rm T} A$, where $A$ is an $M \times N$ real sparse random matrix. The difference from a dense random matrix is the most significant in the tail region of the spectrum. We compare the results of several approximation schemes, focusing on the behavior in the tail region.Comment: 22 pages, 4 figures, minor corrections mad