Ectopic Noggin in a Population of Nfatc1 Lineage Endocardial Progenitors Induces Embryonic Lethality

The initial heart is composed of a myocardial tube lined by endocardial cells. The TGFβ superfamily is known to play an important role, as BMPs from the myocardium signal to the overlying endocardium to create an environment for EMT. Subsequently, BMP and TGFβ signaling pathways synergize to form primitive valves and regulate myocardial growth. In this study, we investigated the requirement of BMP activity by transgenic over-expression of extracellular BMP antagonist Noggin. Using Nfatc1Cre to drive lineage-restricted Noggin within the endocardium, we show that ectopic Noggin arrests cardiac development in E10.5-11 embryos, resulting in small hearts which beat poorly and die by E12.5. This is coupled with hypoplastic endocardial cushions, reduced trabeculation and fewer mature contractile fibrils in mutant hearts. Moreover, Nfatc1Cre -mediated diphtheria toxin fragment-A expression in the endocardium resulted in genetic ablation and a more severe phenotype with lethality at E11 and abnormal linear hearts. Molecular analysis demonstrated that endocardial Noggin resulted in a specific alteration of TGFβ/BMP-mediated signal transduction, in that, both Endoglin and ALK1 were downregulated in mutant endocardium. Combined, these results demonstrate the cell-autonomous requirement of the endocardial lineage and function of unaltered BMP levels in facilitating endothelium-cardiomyocyte cross-talk and promoting endocardial cushion formation

Decrease in hyperosmotic stress-induced corneal epithelial cell apoptosis by L-carnitine

Purpose: To characterize the osmoprotective properties of L-carnitine on human corneal epithelial cell volume and apoptosis during hyperosmotic stress. Methods: Human corneal limbal epithelial (HCLE) cells were exposed to culture medium at 300 mOsm (isotonic) or 500 mOsm (hyperosmotic) with or without L-carnitine (10 mM). Induction of apoptosis was detected by quantifying the proteolytic activity of caspase-8, caspase-9, and caspase-3/7 using caspase activity assays, the expression of tumor necrosis factor (TNF)-α with enzyme-linked immunosorbent assay, and annexin V/propidium iodide staining of HCLE cells evaluated with confocal microscopy and flow cytometry. Cell volume changes in response to hyperosmotic stress were analyzed using flow cytometry. Results: After the HCLE cells were exposed to hyperosmotic medium (500 mOsm), the percentage of shrunken cells and damaged/dead cells (stained positively for annexin V and/or propidium iodide) was six- and three-fold, respectively, higher than that under isotonic conditions (300 mOsm). This was paralleled by an increase in TNF-α concentration in media and caspase-8, -9, and -3/7 activities (six-, four-, ten-, and twelve-fold, respectively; all showing p\u3c0.001). Addi­tion of L-carnitine during hyperosmotic stress partly restored cell volume and significantly reduced the concentration of TNF-α released (p=0.005) and caspase-9 activity (p=0.0125). Addition of L-carnitine reduced the percentage of hyperosmolarity-induced damaged/dead cells to levels observed under isotonic conditions

W(h)ither Fossils? Studying Morphological Character Evolution in the Age of Molecular Sequences

A major challenge in the post-genomics era will be to integrate molecular sequence data from extant organisms with morphological data from fossil and extant taxa into a single, coherent picture of phylogenetic relationships; only then will these phylogenetic hypotheses be effectively applied to the study of morphological character evolution. At least two analytical approaches to solving this problem have been utilized: (1) simultaneous analysis of molecular sequence and morphological data with fossil taxa included as terminals in the analysis, and (2) the molecular scaffold approach, in which morphological data are analyzed over a molecular backbone (with constraints that force extant taxa into positions suggested by sequence data). The perceived obstacles to including fossil taxa directly in simultaneous analyses of morphological and molecular sequence data with extant taxa include: (1) that fossil taxa are missing the molecular sequence portion of the character data; (2) that morphological characters might be misleading due to convergence; and (3) character weighting, specifically how and whether to weight characters in the morphological partition relative to characters in the molecular sequence data partition. The molecular scaffold has been put forward as a potential solution to at least some of these problems. Using examples of simultaneous analyses from the literature, as well as new analyses of previously published morphological and molecular sequence data matrices for extant and fossil Chiroptera (bats), we argue that the simultaneous analysis approach is superior to the molecular scaffold approach, specifically addressing the problems to which the molecular scaffold has been suggested as a solution. Finally, the application of phylogenetic hypotheses including fossil taxa (whatever their derivation) to the study of morphological character evolution is discussed, with special emphasis on scenarios in which fossil taxa are likely to be most enlightening: (1) in determining the sequence of character evolution; (2) in determining the timing of character evolution; and (3) in making inferences about the presence or absence of characteristics in fossil taxa that may not be directly observable in the fossil record. Published By: Missouri Botanical Garde

Pressure Dependence of the Elastic Moduli in Aluminum Rich Al-Li Compounds

I have carried out numerical first principles calculations of the pressure dependence of the elastic moduli for several ordered structures in the Aluminum-Lithium system, specifically FCC Al, FCC and BCC Li, L1_2 Al_3Li, and an ordered FCC Al_7Li supercell. The calculations were performed using the full potential linear augmented plane wave method (LAPW) to calculate the total energy as a function of strain, after which the data was fit to a polynomial function of the strain to determine the modulus. A procedure for estimating the errors in this process is also given. The predicted equilibrium lattice parameters are slightly smaller than found experimentally, consistent with other LDA calculations. The computed elastic moduli are within approximately 10% of the experimentally measured moduli, provided the calculations are carried out at the experimental lattice constant. The LDA equilibrium shear modulus C11-C12 increases from 59.3 GPa in Al, to 76.0 GPa in Al_7Li, to 106.2 GPa in Al_3Li. The modulus C_44 increases from 38.4 GPa in Al to 46.1 GPa in Al_7Li, then falls to 40.7 GPa in Al_3Li. All of the calculated elastic moduli increase with pressure with the exception of BCC Li, which becomes elastically unstable at about 2 GPa, where C_11-C_12 vanishes.Comment: 17 pages (REVTEX) + 7 postscript figure

Inhomogeneous broadening of tunneling conductance in double quantum wells

The lineshape of the tunneling conductance in double quantum wells with a large-scale roughness of heterointerfaces is investigated. Large-scale variations of coupled energy levels and scattering due to the short-range potential are taken into account. The interplay between the inhomogeneous broadening, induced by the non-screened part of large-scale potential, and the homogeneous broadening due to the scattering by short-range potentials is considered. It is shown that the large inhomogeneous broadening can be strongly modified by nonlocal effects involved in the proposed mechanism of inhomogeneity. Related change of lineshape of the resonant tunneling conductance between Gaussian and Lorentzian peaks is described. The theoretical results agree quite well with experimental data.Comment: 11 pages, 5 figure

Structure and Magnetic Order in the NdFeAs(O,F) Superconductor System

The transition temperature Tc~26 K of the recently discovered superconductor LaFeAs(O,F) has been demonstrated to be extremely sensitive to the lanthanide ion, reaching 55 K for the Sm containing oxypnictides. Therefore, it is important to determine how the moment on the lanthanide affects the overall magnetism in these systems. Here we report a neutron diffraction study of the Nd oxypnictides. Long ranged antiferromagnetic order is apparent in NdFeAsO below 1.96 K. Rietveld refinement shows that both Fe and Nd magnetic ordering are required to describe the observed data with the staggered moment 1.55(4) Bohr magneton per Nd and 0.9(1) Bohr magneton per Fe at 0.3 K. The other structural properties such as the tetragonal-orthorhombic distortion are found to be very similar to those in LaFeAsO. Neither the magnetic ordering nor the structural distortion occur in the superconducting sample NdFeAsO0.80F0.20 at any temperatures down to 1.5 K.Comment: 4 pages, 5 figures, 1 table. Identical to v3, correct HTML front matter; Scientific data and conclusions the same as in v

Fermi-liquid behaviour of the low-density 2D hole gas in GaAs/AlGaAs heterostructure at large values of r_s

We examine the validity of the Fermi-liquid description of the dilute 2D hole gas in the crossover from 'metallic'-to-'insulating' behaviour of R(T).It has been established that, at r_s as large as 29, negative magnetoresistance does exist and is well described by weak localisation. The dephasing time extracted from the magnetoresistance is dominated by the T^2 -term due to Landau scattering in the clean limit. The effect of hole-hole interactions, however, is suppressed when compared with the theory for small r_s.Comment: 4 pages ReVTeX, 4 ps figure

Nonmonotonic Temperature-dependent Resistance in Low Density 2D Hole Gases

The low temperature longitudinal resistance-per-square Rxx(T) in ungated GaAs/AlGaAs quantum wells of high peak hole mobility 1.7x10^6 cm^2/Vs is metallic for 2D hole density p as low as 3.8x10^9 cm-2. The electronic contribution to the resistance, R_{el}(T), is a nonmonotonic function of T, exhibiting thermal activation, R_{el}(T) ~ exp{-E_a/kT}, for kT<<E_F and a heretofore unnoted decay R_{el}(T) ~ 1/T for k_T>EF. The form of R_{el}(T) is independent of density, indicating a fundamental relationship between the low and high T scattering mechanisms in the metallic state