The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H\u3csub\u3e2\u3c/sub\u3e0\u3csub\u3e2\u3c/sub\u3e and plays an integral role in insulin signal transduction

Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H2O2 generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action

Wearable activity sensors and early pain after total joint arthroplasty.

A prospective observational cohort of 20 primary total hip arthroplasty (n = 12) and total knee arthroplasty (n = 8) patients (mean age: 63 ± 6 years) was passively monitored with a consumer-level wearable activity sensor before and 6 weeks after surgery. Patients were clustered by minimal change or decreased activity using sensor data. Decreased postoperative activity was associated with greater pain reduction (-5.5 vs -2.0, P = .03). All patients surpassed minimal clinical benefit thresholds of total joint arthroplasty (TJA) (Hip Disability and Osteoarthritis Score Junior 30.5 vs 20.8, P = .23; Knee Injury and Osteoarthritis Outcome Score Junior 23.3 vs 18.2, P = .77) within 6 weeks. Patients who objectively "take it easy" after TJA may experience less pain with no difference in early subjective outcome. Remote, passive analysis of outpatient wearable sensor data may permit real-time detection of early problems after TJA

Direct relationship between levels of TNF-α expression and endothelial dysfunction in reperfusion injury

We previously found that myocardial ischemia/ reperfusion (I/R) initiates expression of tumor necrosis factor-α (TNF) leading to coronary endothelial dysfunction. However, it is not clear whether there is a direct relationship between levels of TNF expression and endothelial dysfunction in reperfusion injury. We studied levels of TNF expression by using different transgenic animals expressing varying amounts of TNF in I/R. We crossed TNF overexpression (TNF++/++) with TNF knockout (TNF-/-) mice; thus we have a heterozygote population of mice with the expression of TNF "in between" the TNF-/- and TNF++/++ mice. Mouse hearts were subjected to 30 min of global ischemia followed by 90 min of reperfusion and their vasoactivity before and after I/R was examined in wild type (WT), TNF-/-, TNF++/++ and TNF heterozygote (TNF -/++, cross between TNF-/- and TNF++/++) mice. In heterozygote TNF-/++ mice with intermediate cardiac-specific expression of TNF, acetyl-choline-induced or flow-induced endothelial-dependent vasodilation following I/R was between TNF++/++ and TNF-/- following I/R. Neutralizing antibodies to TNF administered immediately before the onset of reperfusion-preserved endothelial-dependent dilation following I/R in WT, TNF-/++ and TNF++/++ mice. In WT, TNF -/++ and TNF++/++ mice, I/R-induced endothelial dysfunction was progressively lessened by administration of free-radical scavenger TEMPOL immediately before initiating reperfusion. During I/R, production of superoxide (O2-) was greatest in TNF ++/++ mice as compared to WT, TNF-/++ and TNF -/- mice. Following I/R, arginase mRNA expression was elevated in the WT, substantially elevated in the TNF-/++ and TNF ++/++mice and not affected in the TNF-/- mice. These results suggest that the level of TNF expression determines arginase expression in endothelial cells during myocardial I/R, which is one of the mechanisms by which TNF compromises coronary endothelial function in reperfusion injury

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy

Clinical estrogen receptor (ER) testing for breast cancer is limited in predicting response to endocrine therapy (ET). In this phase 2 clinical trial, authors demonstrate that the responsiveness to ET can be predicted by use of PET/CT with 21-[18F]fluorofuranylnorprogesterone (FFNP) to detect the change in tumor progesterone receptor (PgR) levels after a one-day estradiol challenge

Analyticity and Integrabiity in the Chiral Potts Model

We study the perturbation theory for the general non-integrable chiral Potts model depending on two chiral angles and a strength parameter and show how the analyticity of the ground state energy and correlation functions dramatically increases when the angles and the strength parameter satisfy the integrability condition. We further specialize to the superintegrable case and verify that a sum rule is obeyed.Comment: 31 pages in harvmac including 9 tables, several misprints eliminate

Synthesis and controlled growth of osmium nanoparticles by electron irradiation

YesWe have synthesised osmium nanoparticles of defined size (1.5–50 nm) on a B- and S-doped turbostratic graphitic structure by electron-beam irradiation of an organometallic osmium complex encapsulated in self-spreading polymer micelles, and characterised them by transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and atomic force microscopy (AFM) on the same grid. Oxidation of the osmium nanoparticles after exposure to air was detected by X-ray photoelectron spectroscopy (XPS).We thank the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the University of Warwick (Grant No. RD14102 to NPEB), the ERC (Grant No. 247450 to PJS), and the EPSRC (EP/F034210/1 to PJS). L.M.A.P., J.L., and G.C. acknowledge financial support from the EU through the ERC Consolidator Grant “VISUAL-MS”

Fast synthesis of platinum nanopetals and nanospheres for highly-sensitive non-enzymatic detection of glucose and selective sensing of ions

Novel methods to obtain Pt nanostructured electrodes have raised particular interest due to their high performance in electrochemistry. Several nanostructuration methods proposed in the literature use costly and bulky equipment or are time-consuming due to the numerous steps they involve. Here, Pt nanostructures were produced for the first time by one-step template-free electrodeposition on Pt bare electrodes. The change in size and shape of the nanostructures is proven to be dependent on the deposition parameters and on the ratio between sulphuric acid and chloride-complexes (i.e., hexachloroplatinate or tetrachloroplatinate). To further improve the electrochemical properties of electrodes, depositions of Pt nanostructures on previously synthesised Pt nanostructures are also performed. The electroactive surface areas exhibit a two order of magnitude improvement when Pt nanostructures with the smallest size are used. All the biosensors based on Pt nanostructures and immobilised glucose oxidase display higher sensitivity as compared to bare Pt electrodes. Pt nanostructures retained an excellent electrocatalytic activity towards the direct oxidation of glucose. Finally, the nanodeposits were proven to be an excellent solid contact for ion measurements, significantly improving the time-stability of the potential. The use of these new nanostructured coatings in electrochemical sensors opens new perspectives for multipanel monitoring of human metabolism

Star Formation Rates from [C II] 158 μm and Mid-infrared Emission Lines for Starbursts and Active Galactic Nuclei

A summary is presented for 130 galaxies observed with the Herschel Photodetector Array Camera and Spectrometer instrument to measure fluxes for the [C II] 158 μm emission line. Sources cover a wide range of active galactic nucleus to starburst classifications, as derived from polycyclic aromatic hydrocarbon strength measured with the Spitzer Infrared Spectrograph. Redshifts from [C II] and line to continuum strengths (equivalent width (EW) of [C II]) are given for the full sample, which includes 18 new [C II] flux measures. Calibration of L([C II)]) as a star formation rate (SFR) indicator is determined by comparing [C II] luminosities with mid-infrared [Ne II] and [Ne III] emission line luminosities; this gives the same result as determining SFR using bolometric luminosities of reradiating dust from starbursts: log SFR = log L([C II)]) - 7.0, for SFR in M ⊙ yr-1 and L([C II]) in L ⊙. We conclude that L([C II]) can be used to measure SFR in any source to a precision of ~50%, even if total source luminosities are dominated by an active galactic nucleus (AGN) component. The line to continuum ratio at 158 μm, EW([C II]), is not significantly greater for starbursts (median EW([C II]) = 1.0 μm) compared to composites and AGNs (median EW([C II]) = 0.7 μm), showing that the far-infrared continuum at 158 μm scales with [C II] regardless of classification. This indicates that the continuum at 158 μm also arises primarily from the starburst component within any source, giving log SFR = log νL ν(158 μm) - 42.8 for SFR in M ⊙ yr-1 and νL ν(158 μm) in erg s-1

A multinuclear 1H, 13C and 11B solid-state MAS NMR study of 16- and 18-electron organometallic ruthenium and osmium carborane complexes

YesThe first 1H, 13C, 31P and 11B solid state MAS NMR studies of electron- deficient carborane-containing ruthenium and osmium complexes [Ru/Os(p-cym)(1,2-dicarba-closo-dodecaborane-1,2- dithiolate)] are reported. The MAS NMR data from these 16-electron complexes are compared to those of free carborane-ligand and an 18-electron triphenylphosphine ruthenium adduct, and reveal clear spectral differences between 16- and 18-electron organometallic carborane systems in the solid state.We thank the Swiss National Science Foundation (grant no. PA00P2-145308 to NPEB), the ERC (grant no. 247450 to PJS), EPSRC (grant no. EP/F034210/1) and EC COST Action CM1105 for support. JVH thanks EPSRC and the University of Warwick for partial funding of the solid state NMR infrastructure at Warwick, and acknowledges additional support obtained through Birmingham Science City: Innovative Uses for Advanced Materials in the Modern World (West Midlands Centre for Advanced Materials Project 2), with support from Advantage West Midlands (AWM) and partial funding by the European Regional Development Fund (ERDF)