Amiloride reduces portal hypertension in rat liver cirrhosis

Objective This study aimed to investigate the effect of amiloride on portal hypertension. Amiloride is known to inhibit Na(+)/H(+) exchangers on activated hepatic stellate cells. Methods Liver cirrhosis in rats was induced by bile duct ligation (BDL) or thioacetamide (TAA) administration. The effects of zymosan for Kupffer cell (KC) activation or a thromboxane (TX) analogue (U46619) were tested in isolated perfused livers of cirrhotic rats and in vivo. Downstream mechanisms were investigated using Rho kinase inhibitor (Y-27632) or amiloride. Acute and chronic effects of amiloride and canrenoate on portal pressure were compared in perfused livers and in vivo. TXB(2) efflux was measured by ELISA. The phosphorylation state of moesin (p-moesin) as an indicator of Rho kinase activity and expression of the thromboxane synthase were assessed by western blot analyses. The activity of hepatic stellate cells was analysed by western blot and staining for alpha-smooth muscle actin (alpha-SMA). Results In BDL rats, KC activation via zymosan increased portal pressure. This was attenuated by the Rho kinase inhibitor Y-27632. Increased thromboxane efflux following zymosan infusion remained unaltered by Y-27632. The infusion of amiloride attenuated zymosan- and U46619-induced increases in portal perfusion pressure. In vivo, direct administration of amiloride, but not of canrenoate, lowered portal pressure. In TAA and BDL rats, treatment with amiloride for 3 days reduced basal portal pressure and KC-induced increases in portal pressure whereas canrenoate had no effect. In livers of amiloride-treated animals, the phosphorylation state of moesin and the number of alpha-SMA positive cells were reduced. Conclusions Amiloride lowers portal pressure in rat liver cirrhosis by inhibition of intrahepatic vasocontraction. Therefore, patients with cirrhosis and portal hypertension may benefit from amiloride therapy

The Discovery of an Embedded Cluster of High-Mass Stars Near SGR 1900+14

Deep I-band imaging to approximately I = 26.5 of the soft gamma-ray repeater SGR 1900+14 region has revealed a compact cluster of massive stars located only a few arcseconds from the fading radio source thought to be the location of the SGR (Frail, Kulkarni, & Bloom 1999). This cluster was previously hidden in the glare of the pair of M5 supergiant stars (whose light was removed by PSF subtraction) proposed by Vrba et al. (1996) as likely associated with the SGR 1900+14. The cluster has at least 13 members within a cluster radius of approximately 0.6 pc, based on an estimated distance of 12-15 kpc. It is remarkably similar to a cluster found associated with SGR 1806-20 (Fuchs et al. 1999). That similar clusters have now been found at or near the positions of the two best-studied SGRs suggests that young neutron stars, thought to be responsible for the SGR phenomenon, have their origins in proximate compact clusters of massive stars.Comment: 5 pages, 3 figures, accepted Astrophysical Journal Letter

Longitudinal Recordings Reveal Transient Increase of Alpha/Low-Beta Power in the Subthalamic Nucleus Associated With the Onset of Parkinsonian Rest Tremor

Functional magnetic resonance imaging studies suggest that different subcortico-cortical circuits control different aspects of Parkinsonian rest tremor. The basal ganglia were proposed to drive tremor onset, and the cerebellum was suggested to be responsible for tremor maintenance (“dimmer-switch” hypothesis). Although several electrophysiological correlates of tremor have been described, it is currently unclear whether any of these is specific to tremor onset or maintenance. In this study, we present data from a single patient measured repeatedly within 2 years after implantation of a deep brain stimulation (DBS) system capable of recording brain activity from the target. Local field potentials (LFPs) from the subthalamic nucleus and the scalp electroencephalogram were recorded 1 week, 3 months, 6 months, 1 year, and 2 years after surgery. Importantly, the patient suffered from severe rest tremor of the lower limbs, which could be interrupted voluntarily by repositioning the feet. This provided the unique opportunity to record many tremor onsets in succession. We found that tremor onset and tremor maintenance were characterized by distinct modulations of subthalamic oscillations. Alpha/low-beta power increased transiently immediately after tremor onset. In contrast, beta power was continuously suppressed during tremor maintenance. Tremor maintenance was additionally associated with subthalamic and cortical power increases around individual tremor frequency. To our knowledge, this is the first evidence of distinct subthalamic LFP modulations in tremor onset and tremor maintenance. Our observations suggest the existence of an acceleration signal for Parkinsonian rest tremor in the basal ganglia, in line with the “dimmer-switch” hypothesis

A direct relationship between oscillatory subthalamic nucleus-cortex coupling and rest tremor in Parkinson's disease

Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems

Sugar maple (Acer saccharum March.) growth is influenced by close conspecifics and skid trait proximity following selection harvest

In this study, we quantified the effects of local neighbourhood competition, light availability, and proximity to skid trails on the growth of sugar maple (Acer saccharum Marsh.) trees following selection harvest. We hypothesized that growth would increase with decreasing competition and increasing light availability, but that proximity to skid trails would negatively affect growth. A total of 300 sugar maples were sampled 10 years after selection harvesting in 18 stands in Témiscamingue (Québec, Canada). Detailed tree and skid trail maps were obtained in one 0.4 ha plot per stand. Square-root transformed radial growth data were fitted to a linear mixed model that included tree diameter, crown position, a neighbourhood competition index, light availability (estimated using the SORTIE light model), and distance to the nearest skid trail as explanatory variables. We considered various distance-dependent or -independent indices based on neighbourhood radii ranging from 6 to 12 m. The competition index that provided the best fit to the data was a distance-dependent index computed in a 6 m search radius, but a\ud distance-independent version of the competition index provided an almost equivalent fit to data. Models corresponding to all combinations of main effects were fit to data using maximum likelihood, and weighted averages of parameter estimates were obtained usingmultimodel inference. All predictors had\ud an influence on growth, with the exception of light. Radial growth decreased with increasing tree diameter, level of competition and proximity to skid trails, and varied among crown positions with trees in suppressed and intermediate positions having lower growth rates than codominants and dominants. Our results indicate that in selection managed stands, the radial growth of sugarmaple trees depends on\ud competition from close (6 m) conspecific neighbours, and is still affected by proximity to skid trails 10 years after harvesting. Such results underscore the importance of minimizing the extent of skid trail networks by careful pre-harvest planning of trail layout. We also conclude that the impact of heterogeneity among individual-tree neighbourhoods, such as those resulting from alternative spatial patterns of harvest, can usefully be integrated into models of post-harvest tree growth

Structure factor of polymers interacting via a short range repulsive potential: application to hairy wormlike micelles

We use the Random Phase Approximation (RPA) to compute the structure factor, S(q), of a solution of chains interacting through a soft and short range repulsive potential V. Above a threshold polymer concentration, whose magnitude is essentially controlled by the range of the potential, S(q) exhibits a peak whose position depends on the concentration. We take advantage of the close analogy between polymers and wormlike micelles and apply our model, using a Gaussian function for V, to quantitatively analyze experimental small angle neutron scattering profiles of semi-dilute solutions of hairy wormlike micelles. These samples, which consist in surfactant self-assembled flexible cylinders decorated by amphiphilic copolymer, provide indeed an appropriate experimental model system to study the structure of sterically interacting polymer solutions

Effect of school based physical activity programme (KISS) on fitness and adiposity in primary schoolchildren: cluster randomised controlled trial

Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren

The Structure of Operators in Effective Particle-Conserving Models

For many-particle systems defined on lattices we investigate the global structure of effective Hamiltonians and observables obtained by means of a suitable basis transformation. We study transformations which lead to effective Hamiltonians conserving the number of excitations. The same transformation must be used to obtain effective observables. The analysis of the structure shows that effective operators give rise to a simple and intuitive perspective on the initial problem. The systematic calculation of n-particle irreducible quantities becomes possible constituting a significant progress. Details how to implement the approach perturbatively for a large class of systems are presented.Comment: 12 pages, 1 figure, accepted by J. Phys. A: Math. Ge

GluA4-Targeted AAV Vectors Deliver Genes Selectively to Interneurons while Relying on the AAV Receptor for Entry

Selective gene delivery into subtypes of interneurons remains an important challenge in vector development. Adeno-associated virus (AAV) vector particles are especially promising for intracerebral injections. For cell entry, AAV2 particles are supposed to attach to heparan-sulfate proteoglycans (HSPGs) followed by endocytosis via the AAV receptor (AAVR). Here, we assessed engineered AAV particles deficient in HSPG attachment but competent in recognizing the glutamate receptor 4 (GluA4, also known as GluRD or GRIA4) through a displayed GluA4-specific DARPin (designed ankyrin repeat protein). When injected into the mouse brain, histological evaluation revealed that in various regions, more than 90% of the transduced cells were interneurons, mainly of the parvalbumin-positive subtype. Although part of the selectivity was mediated by the DARPin, the chosen spleen focus-forming virus (SFFV) promoter had contributed as well. Further analysis revealed that the DARPin mediated selective attachment to GluA4-positive cells, whereas gene delivery required expression of AAVR. Our data suggest that cell selectivity of AAV particles can be modified rationally and efficiently through DARPins, but expression of the AAV entry receptor remains essential