Calcium-independent inhibitory G-protein signaling induces persistent presynaptic muting of hippocampal synapses

Adaptive forms of synaptic plasticity that reduce excitatory synaptic transmission in response to prolonged increases in neuronal activity may prevent runaway positive feedback in neuronal circuits. In hippocampal neurons, for example, glutamatergic presynaptic terminals are selectively silenced, creating mute synapses, after periods of increased neuronal activity or sustained depolarization. Previous work suggests that cAMP-dependent and proteasome-dependent mechanisms participate in silencing induction by depolarization, but upstream activators are unknown. We, therefore, tested the role of calcium and G-protein signaling in silencing induction in cultured hippocampal neurons. We found that silencing induction by depolarization was not dependent on rises in intracellular calcium, from either extracellular or intracellular sources. Silencing was, however, pertussis toxin sensitive, which suggests that inhibitory G-proteins are recruited. Surprisingly, blocking four common inhibitory G-protein-coupled receptors (GPCRs) (adenosine A(1) receptors, GABA(B) receptors, metabotropic glutamate receptors, and CB(1) cannabinoid receptors) and one ionotropic receptor with metabotropic properties (kainate receptors) failed to prevent depolarization-induced silencing. Activating a subset of these GPCRs (A(1) and GABA(B)) with agonist application induced silencing, however, which supports the hypothesis that G-protein activation is a critical step in silencing. Overall, our results suggest that depolarization activates silencing through an atypical GPCR or through receptor-independent G-protein activation. GPCR agonist-induced silencing exhibited dependence on the ubiquitin-proteasome system, as was shown previously for depolarization-induced silencing, implicating the degradation of vital synaptic proteins in silencing by GPCR activation. These data suggest that presynaptic muting in hippocampal neurons uses a G-protein-dependent but calcium-independent mechanism to depress presynaptic vesicle release

Early Social Stress Promotes Inflammation and Disease Risk in Rhesus Monkeys.

Early social stress has potent lifelong health effects. We examined the association of early stress in the attachment relationship (low maternal sensitivity, low MS), lower maternal social hierarchy rank, and greater frequency of group-level social conflict, with biomarkers of inflammatory stress response in plasma (IL-8, MCP-1 and CRP collected two hours after temporary separation from mothers and social groups) and risk for developing a common macaques disease outcome (infectious colitis) in 170 socially-housed rhesus monkeys. We controlled for gene-environment correlations by comparing cross-fostered subjects with infants reared by their biological mothers. Low MS predicted higher levels of pro-inflammatory cytokines and proteins at 3-4 months of age (F(3, 162) = 3.508, p = 0.002, partial eta2 = 0.061) and higher lifetime risk for developing colitis for up to twelve years of age (chi square = 5.919, p = 0.026). Lower maternal social rank (F (3, 162) = 3.789, p = 0.012, partial eta2 = 0.06) and higher rates of social conflict (F (3, 162) = 4.264, p = 0.006, partial eta2 = 0.074) each also predicted greater inflammation in infancy, but not lifetime colitis risk (both p > 0.05). The effects of low MS, lower social rank, and higher social conflict were significant in infants reared by biological mothers and cross-fostered infants, suggesting that our results did not arise from gene-environment correlations, but environmental stressors alone. We conclude that several types of early social stress confer risk for inflammation in infancy, but that stress in the mother-infant relationship may confer the longest-term risk for adverse health outcomes

Quintessential Kination and Leptogenesis

Thermal leptogenesis induced by the CP-violating decay of a right-handed neutrino (RHN) is discussed in the background of quintessential kination, i.e., in a cosmological model where the energy density of the early Universe is assumed to be dominated by the kinetic term of a quintessence field during some epoch of its evolution. This assumption may lead to very different observational consequences compared to the case of a standard cosmology where the energy density of the Universe is dominated by radiation. We show that, depending on the choice of the temperature T_r above which kination dominates over radiation, any situation between the strong and the super--weak wash--out regime are equally viable for leptogenesis, even with the RHN Yukawa coupling fixed to provide the observed atmospheric neutrino mass scale ~ 0.05 eV. For M< T_r < M/100, i.e., when kination stops to dominate at a time which is not much later than when leptogenesis takes place, the efficiency of the process, defined as the ratio between the produced lepton asymmetry and the amount of CP violation in the RHN decay, can be larger than in the standard scenario of radiation domination. This possibility is limited to the case when the neutrino mass scale is larger than about 0.01 eV. The super--weak wash--out regime is obtained for T_r << M/100, and includes the case when T_r is close to the nucleosynthesis temperature ~ 1 MeV. Irrespective of T_r, we always find a sufficient window above the electroweak temperature T ~ 100 GeV for the sphaleron transition to thermalize, so that the lepton asymmetry can always be converted to the observed baryon asymmetry.Comment: 13 pages, 8 figure

Molecular dissection of the mechanism by which EWS/FLI expression compromises actin cytoskeletal integrity and cell adhesion in Ewing sarcoma.

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised

Tensor coupling effects on spin symmetry in anti-Lambda spectrum of hypernuclei

The effects of $\bar\Lambda\bar\Lambda\omega$-tensor coupling on the spin symmetry of $\bar{\Lambda}$ spectra in $\bar{\Lambda}$-nucleus systems have been studied with the relativistic mean-field theory. Taking $^{12}$C+$\bar{\Lambda}$ as an example, it is found that the tensor coupling enlarges the spin-orbit splittings of $\bar\Lambda$ by an order of magnitude although its effects on the wave functions of $\bar{\Lambda}$ are negligible. Similar conclusions has been observed in $\bar{\Lambda}$-nucleus of different mass regions, including $^{16}$O+$\bar{\Lambda}$, $^{40}$Ca+$\bar{\Lambda}$ and $^{208}$Pb+$\bar{\Lambda}$. It indicates that the spin symmetry in anti-lambda-nucleus systems is still good irrespective of the tensor coupling.Comment: 12 pages, 3 figures

Breakdown of the lattice polaron picture in La0.7Ca0.3MnO3 single crystals

When heated through the magnetic transition at Tc, La0.7Ca0.3MnO3 changes from a band metal to a polaronic insulator. The Hall constant R_H, through its activated behavior and sign anomaly, provides key evidence for polaronic behavior. We use R_H and the Hall mobility to demonstrate the breakdown of the polaron phase. Above 1.4Tc, the polaron picture holds in detail, while below, the activation energies of both R_H and the mobility deviate strongly from their polaronic values. These changes reflect the presence of metallic, ferromagnetic fluctuations, in the volume of which the Hall effect develops additional contributions tied to quantal phases.Comment: 11 pages, 3 figures, final version to appear in Phys. Rev. B Rapi

On Lattice Computations of K+ --> pi+ pi0 Decay at m_K =2m_pi

We use one-loop chiral perturbation theory to compare potential lattice computations of the K+ --> pi+ pi0 decay amplitude at m_K=2m_pi with the experimental value. We find that the combined one-loop effect due to this unphysical pion to kaon mass ratio and typical finite volume effects is still of order minus 20-30%, and appears to dominate the effects from quenching.Comment: 4 pages, revte

TeV Scale Seesaw and a flavorful Z' at the LHC

Small neutrino masses and their large mixing angles can be generated at the TeV scale by augmenting the Standard Model with an additional generation dependent, anomaly-free U(1)_{nu} symmetry, in the presence of three right-handed neutrinos. The Z' gauge boson associated with the breaking of the U(1)_{nu} symmetry can be produced at the LHC. The flavorful nature of the Z' can be established by measuring its non-universal couplings to the charged leptons as determined by the lepton's U(1)_{nu} charges, which also govern the neutrino flavor structure. While the LHC has the potential of discovering the Z' up to M_{Z'} = 4.5 TeV with 100 fb^(-1) data at the center of mass energy sqrt{s} = 14 TeV, to establish the flavorful nature of the Z' requires much higher integrated luminosity. For our bench mark parameters that are consistent with neutrino oscillation data, at sqrt{s} = 14 TeV, a 5 sigma distinction between the dielectron and dimuon channels for M_{Z'} = 3 TeV requires 500 fb^(-1) of data. We find that the forward backward asymmetry distributions can also be useful in distinguishing the dielectron and dimuon channels in the low invariant mass and transverse momentum regions.Comment: 9 pages, 13 figures; v2: version to appear in Phys. Rev.

Quantum Fluctuations of Radiation Pressure

Quantum fluctuations of electromagnetic radiation pressure are discussed. We use an approach based on the quantum stress tensor to calculate the fluctuations in velocity and position of a mirror subjected to electromagnetic radiation. Our approach reveals that radiation pressure fluctuations are due to a cross term between vacuum and state dependent terms in a stress tensor operator product. Thus observation of these fluctuations would entail experimental confirmation of this cross term. We first analyze the pressure fluctuations on a single, perfectly reflecting mirror, and then study the case of an interferometer. This involves a study of the effects of multiple bounces in one arm, as well as the correlations of the pressure fluctuations between arms of the interferometer. In all cases, our results are consistent with those previously obtained by Caves using different mehods.Comment: 23 pages, 3 figures, RevTe