GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes

Induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) have the potential to transform regenerative cardiac medicine and the modelling of cardiac disease. This is of particular importance in the context of diabetic cardiomyopathy where diabetic individuals exhibit reduced cardiac diastolic contractile performance in the absence of vascular disease, significantly contributing towards high cardiovascular morbidity. In this study, the capacity of iPSC-CM to act as a novel cellular model of cardiomyocytes was assessed. The diabetic phenotype is characterised by insulin resistance, therefore there was a specific focus upon metabolic parameters. Despite expressing crucial insulin signalling intermediates and relevant trafficking proteins, it was identified that iPSC-CM do not exhibit insulin-stimulated glucose uptake. iPSC-CM are spontaneously contractile however contraction mediated uptake was not found to mask any insulin response. The fundamental limitation identified in these cells was a critical lack of expression of the insulin sensitive glucose transporter GLUT4. Using comparative immunoblot analysis and the GLUT-selective inhibitor BAY-876 to quantify expression of these transporters, we show that iPSC-CM express high levels of GLUT1 and low levels of GLUT4 compared to primary cardiomyocytes and cultured adipocytes. Interventions to overcome this limitation were unsuccessful. We suggest that the utility of iPSC-CMs to study cardiac metabolic disorders may be limited by their apparent foetal-like phenotype

Lemur Biorhythms and Life History Evolution

Skeletal histology supports the hypothesis that primate life histories are regulated by a neuroendocrine rhythm, the Havers-Halberg Oscillation (HHO). Interestingly, subfossil lemurs are outliers in HHO scaling relationships that have been discovered for haplorhine primates and other mammals. We present new data to determine whether these species represent the general lemur or strepsirrhine condition and to inform models about neuroendocrine-mediated life history evolution. We gathered the largest sample to date of HHO data from histological sections of primate teeth (including the subfossil lemurs) to assess the relationship of these chronobiological measures with life history-related variables including body mass, brain size, age at first female reproduction, and activity level. For anthropoids, these variables show strong correlations with HHO conforming to predictions, though body mass and endocranial volume are strongly correlated with HHO periodicity in this group. However, lemurs (possibly excepting Daubentonia) do not follow this pattern and show markedly less variability in HHO periodicity and lower correlation coefficients and slopes. Moreover, body mass is uncorrelated, and brain size and activity levels are more strongly correlated with HHO periodicity in these animals. We argue that lemurs evolved this pattern due to selection for risk-averse life histories driven by the unpredictability of the environment in Madagascar. These results reinforce the idea that HHO influences life history evolution differently in response to specific ecological selection regimes

Prospects for detection of Υ(1D)→Υ(1S)ππ\Upsilon(1D) \to \Upsilon(1S) \pi \pi via Υ(3S)→Υ(1D)+X\Upsilon(3S) \to \Upsilon(1D) + X

At least one state in the first family of D-wave $b \bar b$ quarkonium levels has been discovered near the predicted mass of 10.16 GeV/$c^2$. This state is probably the one with J=2. This state and the ones with J=1 and J=3 may contribute a detectable amount to the decay $\Upsilon(1D) \to \Upsilon(1S) \pi \pi$, depending on the partial widths for these decays for which predictions vary considerably. The prospects for detection of the chain $\Upsilon(3S) \to \Upsilon(1D) + X \to \Upsilon \pi \pi + X$ are discussed.Comment: 4 pages, LaTeX, 1 figure, to be published in Phys. Rev. D, comment added after Eq. (2

Properties of the Strange Axial Mesons in the Relativized Quark Model

We studied properties of the strange axial mesons in the relativized quark model. We calculated the $K_1$ decay constant in the quark model and showed how it can be used to extract the $K_1 (^3P_1) - K_1 (^1P_1)$ mixing angle ($\theta_K$) from the weak decay $\tau \to K_1 \nu_\tau$. The ratio $BR(\tau \to \nu_\tau K_1 (1270))/BR(\tau\to \nu_\tau K_1(1400))$ is the most sensitive measurement and also the most reliable since the largest of the theoretical uncertainties factor out. However the current bounds extracted from the TPC/Two-Gamma collaboration measurements are rather weak: we typically obtain $-30^o \lesssim \theta_K \lesssim 50^o$ at 68\% C.L. We also calculated the strong OZI-allowed decays in the pseudoscalar emission model and the flux-tube breaking model and extracted a $^3P_1 - ^1P_1$ mixing angle of $\theta_K \simeq 45^o$. Our analysis also indicates that the heavy quark limit does not give a good description of the strange mesons.Comment: Revised version to be published in Phys. Rev. D. Minor changes. Latex file uses revtex version 3 and epsfig, 4 postcript figures are attached. The full postcript version with embedded figures is available at ftp://ftp.physics.carleton.ca/pub/theory/godfrey/ocipc9512.ps.

Fine structure splittings of excited P and D states in charmonium

It is shown that the fine structure splittings of the $2 ^3P_J$ and $3 ^3P_J$ excited states in charmonium are as large as those of the $1^3P_J$ state if the same $\alpha_s(\mu)\approx 0.36$ is used. The predicted mass $M(2 ^3P_0)=3.84$ GeV appears to be 120 MeV lower that the center of gravity of the $2 ^3P_J$ multiplet and lies below the $D\bar D^*$ threshold. Our value of $M(2 ^3P_0)$ is approximately 80 MeV lower than that from the paper by Godfrey and Isgur while the differences in the other masses are \la 20 MeV. Relativistic kinematics plays an important role in our analysis.Comment: 12 page

Magneto-infrared modes in InAs-AlSb-GaSb coupled quantum wells

We have studied a series of InAs/GaSb coupled quantum wells using magneto-infrared spectroscopy for high magnetic fields up to 33T within temperatures ranging from 4K to 45K in both Faraday and tilted field geometries. This type of coupled quantum wells consists of an electron layer in the InAs quantum well and a hole layer in the GaSb quantum well, forming the so-called two dimensional electron-hole bilayer system. Unlike the samples studied in the past, the hybridization of the electron and hole subbands in our samples is largely reduced by having narrower wells and an AlSb barrier layer interposed between the InAs and the GaSb quantum wells, rendering them weakly hybridized. Previous studies have revealed multiple absorption modes near the electron cyclotron resonance of the InAs layer in moderately and strongly hybridized samples, while only a single absorption mode was observed in the weakly hybridized samples. We have observed a pair of absorption modes occurring only at magnetic fields higher than 14T, which exhibited several interesting phenomena. Among which we found two unique types of behavior that distinguishes this work from the ones reported in the literature. This pair of modes is very robust against rising thermal excitations and increasing magnetic fields alligned parallel to the heterostructures. While the previous results were aptly explained by the antilevel crossing gap due to the hybridization of the electron and hole wavefunctions, i.e. conduction-valence Landau level mixing, the unique features reported in this paper cannot be explained within the same concept. The unusual properties found in this study and their connection to the known models for InAs/GaSb heterostructures will be disccused; in addition, several alternative ideas will be proposed in this paper and it appears that a spontaneous phase separation can account for most of the observed features

A Multi-Wavelength Study of the Jet, Lobes and Core of the Quasar PKS 2101-490

We present a detailed study of the X-ray, optical and radio emission from the jet, lobes and core of the quasar PKS 2101-490 as revealed by new Chandra, HST and ATCA images. We extract the radio to X-ray spectral energy distributions from seven regions of the 13 arcsecond jet, and model the jet X-ray emission in terms of Doppler beamed inverse Compton scattering of the cosmic microwave background (IC/CMB) for a jet in a state of equipartition between particle and magnetic field energy densities. This model implies that the jet remains highly relativistic hundreds of kpc from the nucleus, with a bulk Lorentz factor Gamma ~ 6 and magnetic field of order 30 microGauss. We detect an apparent radiative cooling break in the synchrotron spectrum of one of the jet knots, and are able to interpret this in terms of a standard one-zone continuous injection model, based on jet parameters derived from the IC/CMB model. However, we note apparent substructure in the bright optical knot in one of the HST bands. We confront the IC/CMB model with independent estimates of the jet power, and find that the IC/CMB model jet power is consistent with the independent estimates, provided that the minimum electron Lorentz factor gamma_min > 50, and the knots are significantly longer than the jet width, as implied by de-projection of the observed knot lengths.Comment: 16 pages, 10 figures, 6 table