Positive association between serum silicon levels and bone mineral density in female rats following oral silicon supplementation with monomethylsilanetriol.

UNLABELLED: Observational (epidemiological) studies suggest the positive association between dietary silicon intake and bone mineral density may be mediated by circulating estradiol level. Here, we report the results of a silicon supplementation study in rats that strongly support these observations and suggest an interaction between silicon and estradiol. INTRODUCTION: Epidemiological studies report strong positive associations between dietary silicon (Si) intake and bone mineral density (BMD) in premenopausal women and indicate that the association may be mediated by estradiol. We have tested this possibility in a mixed-gender rodent intervention study. METHODS: Tissue samples were obtained from three groups of 20-week-old Sprague Dawley rats (five males and five females per group) that had been supplemented ad libitum for 90 days in their drinking water with (i) <0.1 mg Si/L (vehicle control), (ii) 115 mg Si/L (moderate dose) or (iii) 575 mg Si/L (high dose). All rats received conventional laboratory feed, whilst supplemental Si was in the form of monomethylsilanetriol, increasing dietary Si intakes by 18 and 99 %, for the moderate- and high-dose groups, respectively. RESULTS: Fasting serum and tissue Si concentrations were increased with Si supplementation (p < 0.05), regardless of gender. However, only for female rats was there (i) a trend for a dose-responsive increase in serum osteocalcin concentration with Si intervention and (ii) strong significant associations between serum Si concentrations and measures of bone quality (p < 0.01). Correlations were weaker or insignificant for tibia Si levels and absent for other serum or tibia elemental concentrations and bone quality measures. CONCLUSIONS: Our findings support the epidemiological observations that dietary Si positively impacts BMD in younger females, and this may be due to a Si-estradiol interaction. Moreover, these data suggest that the Si effect is mediated systemically, rather than through its incorporation into bone

The two-hour orbit of a binary millisecond X-ray pulsar

Typical radio pulsars are magnetized neutron stars that are born rapidly rotating and slow down as they age on time scales of 10 to 100 million years. However, millisecond radio pulsars spin very rapidly even though many are billions of years old. The most compelling explanation is that they have been "spun up" by the transfer of angular momentum during accretion of material from a companion star in so-called low-mass X-ray binary systems, LMXBs. (LMXBs consist of a neutron star or black hole accreting from a companion less than one solar mass.) The recent detection of coherent X-ray pulsations with a millisecond period from a suspected LMXB system appears to confirm this link. Here we report observations showing that the orbital period of this binary system is two hours, which establishes it as an LMXB. We also find an apparent modulation of the X-ray flux at the orbital period (at the two per cent level), with a broad minimum when the pulsar is behind this low-mass companion star. This system seems closely related to the "black widow" millisecond radio pulsars, which are evaporating their companions through irradiation. It may appear as an eclipsing radio pulsar during periods of X-ray quiescence.Comment: 4 pages with 1 figure. Style files included. Fig. 2 deleted and text revised. To appear in Nature. Press embargo until 18:00 GMT on 1998 July 2

Power grip, pinch grip, manual muscle testing or thenar atrophy - which should be assessed as a motor outcome after carpal tunnel decompression? A systematic review

<p>Abstract</p> <p>Background</p> <p>Objective assessment of motor function is frequently used to evaluate outcome after surgical treatment of carpal tunnel syndrome (CTS). However a range of outcome measures are used and there appears to be no consensus on which measure of motor function effectively captures change. The purpose of this systematic review was to identify the methods used to assess motor function in randomized controlled trials of surgical interventions for CTS. A secondary aim was to evaluate which instruments reflect clinical change and are psychometrically robust.</p> <p>Methods</p> <p>The bibliographic databases Medline, AMED and CINAHL were searched for randomized controlled trials of surgical interventions for CTS. Data on instruments used, methods of assessment and results of tests of motor function was extracted by two independent reviewers.</p> <p>Results</p> <p>Twenty-two studies were retrieved which included performance based assessments of motor function. Nineteen studies assessed power grip dynamometry, fourteen studies used both power and pinch grip dynamometry, eight used manual muscle testing and five assessed the presence or absence of thenar atrophy. Several studies used multiple tests of motor function. Two studies included both power and pinch strength and reported descriptive statistics enabling calculation of effect sizes to compare the relative responsiveness of grip and pinch strength within study samples. The study findings suggest that tip pinch is more responsive than lateral pinch or power grip up to 12 weeks following surgery for CTS.</p> <p>Conclusion</p> <p>Although used most frequently and known to be reliable, power and key pinch dynamometry are not the most valid or responsive tools for assessing motor outcome up to 12 weeks following surgery for CTS. Tip pinch dynamometry more specifically targets the thenar musculature and appears to be more responsive. Manual muscle testing, which in theory is most specific to the thenar musculature, may be more sensitive if assessed using a hand held dynamometer – the Rotterdam Intrinsic Handheld Myometer. However further research is needed to evaluate its reliability and responsiveness and establish the most efficient and psychometrically robust method of evaluating motor function following surgery for CTS.</p

Shock waves in strongly coupled plasmas

Shock waves are supersonic disturbances propagating in a fluid and giving rise to dissipation and drag. Weak shocks, i.e., those of small amplitude, can be well described within the hydrodynamic approximation. On the other hand, strong shocks are discontinuous within hydrodynamics and therefore probe the microscopics of the theory. In this paper we consider the case of the strongly coupled N=4 plasma whose microscopic description, applicable for scales smaller than the inverse temperature, is given in terms of gravity in an asymptotically $AdS_5$ space. In the gravity approximation, weak and strong shocks should be described by smooth metrics with no discontinuities. For weak shocks we find the dual metric in a derivative expansion and for strong shocks we use linearized gravity to find the exponential tail that determines the width of the shock. In particular we find that, when the velocity of the fluid relative to the shock approaches the speed of light $v\to 1$ the penetration depth $\ell$ scales as $\ell\sim (1-v^2)^{1/4}$. We compare the results with second order hydrodynamics and the Israel-Stewart approximation. Although they all agree in the hydrodynamic regime of weak shocks, we show that there is not even qualitative agreement for strong shocks. For the gravity side, the existence of shock waves implies that there are disturbances of constant shape propagating on the horizon of the dual black holes.Comment: 47 pages, 8 figures; v2:typos corrected, references adde

Localization of N=4 Superconformal Field Theory on S^1 x S^3 and Index

We provide the geometrical meaning of the ${\cal N}=4$ superconformal index. With this interpretation, the ${\cal N}=4$ superconformal index can be realized as the partition function on a Scherk-Schwarz deformed background. We apply the localization method in TQFT to compute the deformed partition function since the deformed action can be written as a $\delta_\epsilon$-exact form. The critical points of the deformed action turn out to be the space of flat connections which are, in fact, zero modes of the gauge field. The one-loop evaluation over the space of flat connections reduces to the matrix integral by which the ${\cal N}=4$ superconformal index is expressed.Comment: 42+1 pages, 2 figures, JHEP style: v1.2.3 minor corrections, v4 major revision, conclusions essentially unchanged, v5 published versio

Peripheral blood gene expression profiles in COPD subjects

To identify non-invasive gene expression markers for chronic obstructive pulmonary disease (COPD), we performed genome-wide expression profiling of peripheral blood samples from 12 subjects with significant airflow obstruction and an equal number of non-obstructed controls. RNA was isolated from Peripheral Blood Mononuclear Cells (PBMCs) and gene expression was assessed using Affymetrix U133 Plus 2.0 arrays.Tests for gene expression changes that discriminate between COPD cases (FEV1 80% predicted, FEV1/FVC > 0.7) were performed using Significance Analysis of Microarrays (SAM) and Bayesian Analysis of Differential Gene Expression (BADGE). Using either test at high stringency (SAM median FDR = 0 or BADGE p < 0.01) we identified differential expression for 45 known genes. Correlation of gene expression with lung function measurements (FEV1 & FEV1/FVC), using both Pearson and Spearman correlation coefficients (p < 0.05), identified a set of 86 genes. A total of 16 markers showed evidence of significant correlation (p < 0.05) with quantitative traits and differential expression between cases and controls. We further compared our peripheral gene expression markers with those we previously identified from lung tissue of the same cohort. Two genes, RP9and NAPE-PLD, were identified as decreased in COPD cases compared to controls in both lung tissue and blood. These results contribute to our understanding of gene expression changes in the peripheral blood of patients with COPD and may provide insight into potential mechanisms involved in the disease. © 2011 Bhattacharya et al; licensee BioMed Central Ltd

Cochlin, Intraocular Pressure Regulation and Mechanosensing

Fluid shear modulates many biological properties. How shear mechanosensing occurs in the extracellular matrix (ECM) and is transduced into cytoskeletal change remains unknown. Cochlin is an ECM protein of unknown function. Our investigation using a comprehensive spectrum of cutting-edge techniques has resulted in following major findings: (1) over-expression and down-regulation of cochlin increase and decrease intraocular pressure (IOP), respectively. The overexpression was achieved in DBA/2J-Gpnmb+/SjJ using lentiviral vectors, down-regulation was achieved in glaucomatous DBA/2J mice using targeted disruption (cochlin-null mice) and also using lentiviral vector mediated shRNA against cochlin coding region; (2) reintroduction of cochlin in cochlin-null mice increases IOP; (3) injection of exogenous cochlin also increased IOP; (4) increasing perfusion rates increased cochlin multimerization, which reduced the rate of cochlin proteolysis by trypsin and proteinase K; The cochlin multimerization in response to shear stress suggests its potential mechanosensing. Taken together with previous studies, we show cochlin is involved in regulation of intraocular pressure in DBA/2J potentially through mechanosensing of the shear stress

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Hydrodynamics from charged black branes

We extend the recent work on fluid-gravity correspondence to charged black-branes by determining the metric duals to arbitrary charged fluid configuration up to second order in the boundary derivative expansion. We also derive the energy-momentum tensor and the charge current for these configurations up to second order in the boundary derivative expansion. We find a new term in the charge current when there is a bulk Chern-Simons interaction thus resolving an earlier discrepancy between thermodynamics of charged rotating black holes and boundary hydrodynamics. We have also confirmed that all our expressions are covariant under boundary Weyl-transformations as expected.Comment: 0+ 31 Pages; v2: 0+33 pages, typos corrected and new sections (in appendix) added; v3:published versio