Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy.

RAMPs (receptor activity-modifying proteins) serve as oligomeric modulators for numerous G-protein-coupled receptors, yet elucidating the physiological relevance of these interactions remains complex. Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null for canonical adrenomedullin/calcitonin receptor-like receptor signaling. We aimed to genetically rescue the Ramp2(-/-) lethality in order to further delineate the spatiotemporal requirements for RAMP2 function during development and thereby enable the elucidation of an expanded repertoire of RAMP2 functions with family B G-protein-coupled receptors in adult homeostasis. Endothelial-specific expression of Ramp2 under the VE-cadherin promoter resulted in the partial rescue of Ramp2(-/-) mice, demonstrating that endothelial expression of Ramp2 is necessary and sufficient for survival. The surviving Ramp2(-/-) Tg animals lived to adulthood and developed spontaneous hypotension and dilated cardiomyopathy, which was not observed in adult mice lacking calcitonin receptor-like receptor. Yet, the hearts of Ramp2(-/-) Tg animals displayed dysregulation of family B G-protein-coupled receptors, including parathyroid hormone and glucagon receptors, as well as their downstream signaling pathways. These data suggest a functional requirement for RAMP2 in the modulation of additional G-protein-coupled receptor pathways in vivo, which is critical for sustained cardiovascular homeostasis. The cardiovascular importance of RAMP2 extends beyond the endothelium and canonical adrenomedullin/calcitonin receptor-like receptor signaling, in which future studies could elucidate novel and pharmacologically tractable pathways for treating cardiovascular diseases

Heparin Reduces Neuroinflammation and Transsynaptic Neuronal Apoptosis in a Model of Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) can lead to disabling motor, cognitive, and neuropsychological abnormalities. Part of the secondary injury to cerebral tissues associated with SAH is attributable to the neuroinflammatory response induced by blood. Heparin is a pleiotropic compound that reduces inflammatory responses in conditions outside the central nervous system. Using a model of SAH devoid of global insult, we evaluated the effect of delayed intravenous (IV) infusion of heparin, at a dose that does not produce therapeutic anticoagulation, on neuroinflammation, myelin preservation, and apoptosis. Adult male rats underwent bilateral stereotactic injections of autologous blood (50 μL) into the subarachnoid space of the entorhinal cortex. The rats were implanted with mini-osmotic pumps that delivered either vehicle or unfractionated heparin (10 U/kg/h IV) beginning 12 h after SAH. No mechanical or hemorrhagic injury was observed in the hippocampus. In vehicle controls assessed at 48 h, SAH was associated with robust neuroinflammation in the adjacent cortex [neutrophils, activated phagocytic microglia, nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-1beta] and neurodegeneration (Fluoro-Jade C staining and loss of NeuN). In the hippocampus, a muted neuroinflammatory response was indicated by Iba1-positive, ED1-negative microglia exhibiting an activated morphology. The perforant pathway showed Fluoro-Jade C staining and demyelination, and granule cells of the dentate gyrus had pyknotic nuclei, labeled with Fluoro-Jade C and showed upregulation of cleaved caspase-3, consistent with transsynaptic apoptosis. Administration of heparin significantly reduced neuroinflammation, demyelination, and transsynaptic apoptosis. We conclude that delayed IV infusion of low-dose unfractionated heparin may attenuate adverse neuroinflammatory effects of SAH

Immune-Related Gene Expression in Two B-Complex Disparate Genetically Inbred Fayoumi Chicken Lines Following Eimeria maxima Infection

To investigate the influence of genetic differences in the MHC on susceptibility to avian coccidiosis, M5.1 and M15.2 B-haplotype-disparate Fayoumi chickens were orally infected with live Eimeria maxima oocysts, and BW gain, fecal oocyst production, and expression of 14 immune-related genes were determined as parameters of protective immunity. Weight loss was reduced and fecal parasite numbers were lower in birds of the M5.1 line compared with M15.2 line birds. Intestinal intraepithelial lymphocytes from M5.1 chickens expressed greater levels of transcripts encoding interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-8, IL-12, IL-15, IL-17A, inducible nitric oxide synthase, and lipopolysaccharide-induced tumor necrosis factor-α factor and lower levels of mRNA for IFN-α, IL-10, IL-17D, NK-lysin, and tumor necrosis factor superfamily 15 compared with the M15.2 line. In the spleen, E. maxima infection was associated with greater expression levels of IFN-γ, IL-15, and IL-8 and lower levels of IL-6, IL-17D, and IL-12 in M5.1 vs. M15.2 birds. These results suggest that genetic determinants within the chicken MHC influence resistance to E. maxima infection by controlling the local and systemic expression of immune-related cytokine and chemokine genes

Spin-Peierls transition in an anisotropic two-dimensional XY model

The two-dimensional Jordan-Wigner transformation is used to investigate the zero temperature spin-Peierls transition for an anisotropic two-dimensional XY model in adiabatic limit. The phase diagram between the dimerized (D) state and uniform (U) state is shown in the parameter space of dimensionless interchain coupling $h$ $(=J_{\perp}/J)$ and spin-lattice coupling $\eta$. It is found that the spin-lattice coupling $\eta$ must exceed some critical value $\eta_c$ in order to reach the D phase for any finite $h$. The dependence of $\eta_c$ on $h$ is given by $-1/\ln h$ for $h\to 0$ and the transition between U and D phase is of first-order for at least $h>10^{-3}$.Comment: 2 eps figures, considerable revisions were mad

Baryonic Response of Dense Holographic QCD

The response function of a homogeneous and dense hadronic system to a time-dependent (baryon) vector potential is discussed for holographic dense QCD (D4/D8 embedding) both in the confined and deconfined phases. Confined holographic QCD is an uncompressible and static baryonic insulator at large N_c and large \lambda, with a gapped vector spectrum and a massless pion. Deconfined holographic QCD is a diffusive conductor with restored chiral symmetry and a gapped transverse baryonic current. Similarly, dense D3/D7 is diffusive for any non-zero temperature at large N_c and large \lambda. At zero temperature dense D3/D7 exhibits a baryonic longitudinal visco-elastic mode with a first sound speed \lambda/\sqrt{3} and a small width due to a shear viscosity to baryon ratio \eta/n_B=\hbar/4. This mode is turned diffusive by arbitrarily small temperatures, a hallmark of holography.Comment: V2: 47 pages, 7 figures, references added, typos correcte

Real-time single-molecule imaging reveals a direct interaction between UvrC and UvrB on DNA tightropes

Nucleotide excision DNA repair is mechanistically conserved across all kingdoms of life. In prokaryotes, this multi-enzyme process requires six proteins: UvrA?D, DNA polymerase I and DNA ligase. To examine how UvrC locates the UvrB? DNA pre-incision complex at a site of damage, we have labeled UvrB and UvrC with different colored quantum dots and quantitatively observed their interactions with DNA tightropes under a variety of solution conditions using oblique angle fluorescence imaging. Alone, UvrC predominantly interacts statically with DNA at low salt. Surprisingly, however, UvrC and UvrB together in solution bind to form the previously unseen UvrBC complex on duplex DNA. This UvrBC complex is highly motile and engages in unbiased one-dimensional diffusion. To test whether UvrB makes direct contact with the DNA in the UvrBC?DNA complex, we investigated three UvrB mutants: Y96A, a b-hairpin deletion and D338N. These mutants affected the motile properties of the UvrBC complex, indicating that UvrB is in intimate contact with the DNA when bound to UvrC. Given the in vivo excess of UvrB and the abundance of UvrBC in our experiments, this newly identified complex is likely to be the predominant form of UvrC in the cell. © 2013 The Author(s)

The optimal approach of detecting stochastic gravitational wave from string cosmology using multiple detectors

String cosmology models predict a relic background of gravitational wave produced during the dilaton-driven inflation. It's spectrum is most likely to be detected by ground gravitational wave laser interferometers (IFOs), like LIGO, Virgo, GEO, as the energy density grows rapidly with frequency. We show the certain ranges of the parameters that underlying string cosmology model using two approaches, associated with 5% false alarm and 95% detection rate. The result presents that the approach of combining multiple pairs of IFOs is better than the approach of directly combining the outputs of multiple IFOs for LIGOH, LIGOL, Virgo and GEO.Comment: 4 pages, 4 figures, accepted for publication in Physics Letters

Conductivity and quasinormal modes in holographic theories

We show that in field theories with a holographic dual the retarded Green's function of a conserved current can be represented as a convergent sum over the quasinormal modes. We find that the zero-frequency conductivity is related to the sum over quasinormal modes and their high-frequency asymptotics via a sum rule. We derive the asymptotics of the quasinormal mode frequencies and their residues using the phase-integral (WKB) approach and provide analytic insight into the existing numerical observations concerning the asymptotic behavior of the spectral densities.Comment: 24 pages, 3 figure

Bulk spectral function sum rule in QCD-like theories with a holographic dual

We derive the sum rule for the spectral function of the stress-energy tensor in the bulk (uniform dilatation) channel in a general class of strongly coupled field theories. This class includes theories holographically dual to a theory of gravity coupled to a single scalar field, representing the operator of the scale anomaly. In the limit when the operator becomes marginal, the sum rule coincides with that in QCD. Using the holographic model, we verify explicitly the cancellation between large and small frequency contributions to the spectral integral required to satisfy the sum rule in such QCD-like theories.Comment: 16 pages, 2 figure

Transport Properties of the Quark-Gluon Plasma -- A Lattice QCD Perspective

Transport properties of a thermal medium determine how its conserved charge densities (for instance the electric charge, energy or momentum) evolve as a function of time and eventually relax back to their equilibrium values. Here the transport properties of the quark-gluon plasma are reviewed from a theoretical perspective. The latter play a key role in the description of heavy-ion collisions, and are an important ingredient in constraining particle production processes in the early universe. We place particular emphasis on lattice QCD calculations of conserved current correlators. These Euclidean correlators are related by an integral transform to spectral functions, whose small-frequency form determines the transport properties via Kubo formulae. The universal hydrodynamic predictions for the small-frequency pole structure of spectral functions are summarized. The viability of a quasiparticle description implies the presence of additional characteristic features in the spectral functions. These features are in stark contrast with the functional form that is found in strongly coupled plasmas via the gauge/gravity duality. A central goal is therefore to determine which of these dynamical regimes the quark-gluon plasma is qualitatively closer to as a function of temperature. We review the analysis of lattice correlators in relation to transport properties, and tentatively estimate what computational effort is required to make decisive progress in this field.Comment: 54 pages, 37 figures, review written for EPJA and APPN; one parag. added end of section 3.4, and one at the end of section 3.2.2; some Refs. added, and some other minor change