Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

Measurement of the conductance of a hydrogen molecule

Recent years have shown steady progress in research towards molecular electronics [1,2], where molecules have been investigated as switches [3-5], diodes [6], and electronic mixers [7]. In much of the previous work a Scanning Tunnelling Microscope was employed to address an individual molecule. As this arrangement does not provide long-term stability, more recently metal-molecule-metal links have been made using break junction devices [8-10]. However, it has been difficult to establish unambiguously that a single molecule forms the contact [11]. Here, we show that a single H2 molecule can form a stable bridge between Pt electrodes. In contrast to results for other organic molecules, the bridge has a nearly perfect conductance of one quantum unit, carried by a single channel. The H2-bridge provides a simple test system and a fundamental step towards understanding transport properties of single-molecule devices.Comment: 6 pages, 4 figure

Awareness and use of intertrochanteric osteotomies in current clinical practice. An international survey

Current literature shows that intertrochanteric osteotomies can produce excellent results in selected hip disorders in specific groups of patients. However, it appears that this surgical option is considered an historical one that has no role to play in modern practice. In order to examine current awareness of and views on intertrochanteric osteotomies among international hip surgeons, an online survey was carried out. The survey consisted of a set of questions regarding current clinical practice and awareness of osteotomies. The second part of the survey consisted of five clinical cases and sought to elicit views on preoperative radiological investigations and preferred (surgical) treatments. The results of our survey showed that most of these experts believe that intertrochanteric osteotomies should still be performed in selected cases. Only 56% perform intertrochanteric osteotomies themselves and of those, only 11% perform more than five per year. The responses to the cases show that about 30–40% recommend intertrochanteric osteotomies in young symptomatic patients. This survey shows that the role of intertrochanteric osteotomies is declining in clinical practice

Coherent electron-phonon coupling and polaron-like transport in molecular wires

We present a technique to calculate the transport properties through one-dimensional models of molecular wires. The calculations include inelastic electron scattering due to electron-lattice interaction. The coupling between the electron and the lattice is crucial to determine the transport properties in one-dimensional systems subject to Peierls transition since it drives the transition itself. The electron-phonon coupling is treated as a quantum coherent process, in the sense that no random dephasing due to electron-phonon interactions is introduced in the scattering wave functions. We show that charge carrier injection, even in the tunneling regime, induces lattice distortions localized around the tunneling electron. The transport in the molecular wire is due to polaron-like propagation. We show typical examples of the lattice distortions induced by charge injection into the wire. In the tunneling regime, the electron transmission is strongly enhanced in comparison with the case of elastic scattering through the undistorted molecular wire. We also show that although lattice fluctuations modify the electron transmission through the wire, the modifications are qualitatively different from those obtained by the quantum electron-phonon inelastic scattering technique. Our results should hold in principle for other one-dimensional atomic-scale wires subject to Peierls transitions.Comment: 21 pages, 8 figures, accepted for publication in Phys. Rev. B (to appear march 2001