Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans?

The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is a strong association between insulin resistance and lipid accumulation — and, in particular, lipotoxic fatty acid metabolites — in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing insulin-stimulated glucose uptake. Reduced fat-oxidation capacity appears to cause such lipid accumulation and, over the past few years, many studies have concluded that decreased mitochondrial oxidative phosphorylation could be the initiating cause of lipid deposition and the development of insulin resistance. The aim of this review is to summarize the latest findings regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance in humans. At present, there are too few studies to definitively conclude that, in this context, mitochondria are functionally impaired (dysfunction in the respiratory chain). Indeed, insulin resistance could also be related to a decrease in the number of mitochondria or to a combination of this and mitochondrial dysfunction. Finally, we also consider whether or not these aberrations could be the cause of the development of the disease or whether mitochondrial dysfunction may simply be the consequence of an insulin-resistant state

Thyroxine Therapy in Euthyroid Patients Does Not Affect Body Composition or Muscular Function

OBJECTIVE:The main objective of the study was to evaluate the effects of small increments in thyroxine (T4) levels following levothyroxine (L-T4) administration on the body composition of women patients. The secondary objective was to assess the effect of the therapy on energy expenditure and muscular function. METHODS: The prospective, randomized study consisted of a 12-month follow-up of 37 women with thyroid nodules. The patients were divided into two groups for comparison, one treated with L-T4 (20 women) and the other untreated (17 women). L-T4 dose was individually adjusted to obtain a serum thyroid-stimulating hormone in the lower portion of the normal range. Multiple tests, including bioelectrical impedance analysis, dual-energy X-ray absorptiometry, air displacement plethysmography, measurement of waist circumference, and skinfold anthropometry, were used to investigate the muscular, fat, and water compartments; energy expenditure and muscular function were assessed by cycle ergometry. RESULTS: There were no significant differences in body composition, heart rate, energy metabolism, or muscular function between the group of women treated with L-T4 and the untreated group. CONCLUSION: The controlled increase of circulating T4 does not appear to modify the body composition or muscular function in women patients

Mode regularization of the susy sphaleron and kink: zero modes and discrete gauge symmetry

To obtain the one-loop corrections to the mass of a kink by mode regularization, one may take one-half the result for the mass of a widely separated kink-antikink (or sphaleron) system, where the two bosonic zero modes count as two degrees of freedom, but the two fermionic zero modes as only one degree of freedom in the sums over modes. For a single kink, there is one bosonic zero mode degree of freedom, but it is necessary to average over four sets of fermionic boundary conditions in order (i) to preserve the fermionic Z$_2$ gauge invariance $\psi \to -\psi$, (ii) to satisfy the basic principle of mode regularization that the boundary conditions in the trivial and the kink sector should be the same, (iii) in order that the energy stored at the boundaries cancels and (iv) to avoid obtaining a finite, uniformly distributed energy which would violate cluster decomposition. The average number of fermionic zero-energy degrees of freedom in the presence of the kink is then indeed 1/2. For boundary conditions leading to only one fermionic zero-energy solution, the Z$_2$ gauge invariance identifies two seemingly distinct `vacua' as the same physical ground state, and the single fermionic zero-energy solution does not correspond to a degree of freedom. Other boundary conditions lead to two spatially separated $\omega \sim 0$ solutions, corresponding to one (spatially delocalized) degree of freedom. This nonlocality is consistent with the principle of cluster decomposition for correlators of observables.Comment: 32 pages, 5 figure

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

The GLAST Background Model

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil