Gi-Coupled GPCR Signaling Controls the Formation and Organization of Human Pluripotent Colonies

BACKGROUND:Reprogramming adult human somatic cells to create human induced pluripotent stem (hiPS) cell colonies involves a dramatic morphological and organizational transition. These colonies are morphologically indistinguishable from those of pluripotent human embryonic stem (hES) cells. G protein-coupled receptors (GPCRs) are required in diverse developmental processes, but their role in pluripotent colony morphology and organization is unknown. We tested the hypothesis that G(i)-coupled GPCR signaling contributes to the characteristic morphology and organization of human pluripotent colonies. METHODOLOGY/PRINCIPAL FINDINGS:Specific and irreversible inhibition of G(i)-coupled GPCR signaling by pertussis toxin markedly altered pluripotent colony morphology. Wild-type hES and hiPS cells formed monolayer colonies, but colonies treated with pertussis toxin retracted inward, adopting a dense, multi-layered conformation. The treated colonies were unable to reform after a scratch wound insult, whereas control colonies healed completely within 48 h. In contrast, activation of an alternative GPCR pathway, G(s)-coupled signaling, with cholera toxin did not affect colony morphology or the healing response. Pertussis toxin did not alter the proliferation, apoptosis or pluripotency of pluripotent stem cells. CONCLUSIONS/SIGNIFICANCE:Experiments with pertussis toxin suggest that G(i) signaling plays a critical role in the morphology and organization of pluripotent colonies. These results may be explained by a G(i)-mediated density-sensing mechanism that propels the cells radially outward. GPCRs are a promising target for modulating the formation and organization of hiPS and hES cell colonies and may be important for understanding somatic cell reprogramming and for engineering pluripotent stem cells for therapeutic applications

Shell Model Study of the Double Beta Decays of 76^{76}Ge, 82^{82}Se and 136^{136}Xe

The lifetimes for the double beta decays of $^{76}$Ge, $^{82}$Se and $^{136}$Xe are calculated using very large shell model spaces. The two neutrino matrix elements obtained are in good agreement with the present experimental data. For $<1$ eV we predict the following upper bounds to the half-lives for the neutrinoless mode: $T^{(0\nu)}_{1/2}(Ge) > 1.85\,10^{25} yr.$, $T^{(0\nu)}_{1/2}(Se) > 2.36\,10^{24} yr.$ and $T^{(0\nu)}_{1/2}(Xe) > 1.21\,10^{25} yr$. These results are the first from a new generation of Shell Model calculations reaching O(10$^{8}$) dimensions

A large Hilbert space QRPA and RQRPA calculation of neutrinoless double beta decay

A large Hilbert space is used for the calculation of the nuclear matrix elements governing the light neutrino mass mediated mode of neutrinoless double beta decay of Ge76, Mo100, Cd116, Te128 and Xe136 within the proton-neutron quasiparticle random phase approximation (pn-QRPA) and the renormalized QRPA with proton-neutron pairing (full-RQRPA) methods. We have found that the nuclear matrix elements obtained with the standard pn-QRPA for several nuclear transitions are extremely sensitive to the renormalization of the particle-particle component of the residual interaction of the nuclear hamiltonian. Therefore the standard pn-QRPA does not guarantee the necessary accuracy to allow us to extract a reliable limit on the effective neutrino mass. This behaviour, already known from the calculation of the two-neutrino double beta decay matrix elements, manifests itself in the neutrinoless double-beta decay but only if a large model space is used. The full-RQRPA, which takes into account proton-neutron pairing and considers the Pauli principle in an approximate way, offers a stable solution in the physically acceptable region of the particle-particle strength. In this way more accurate values on the effective neutrino mass have been deduced from the experimental lower limits of the half-lifes of neutrinoless double beta decay.Comment: 19 pages, RevTex, 1 Postscript figur

Neutrinoless Double Beta Decay within QRPA with Proton-Neutron Pairing

We have investigated the role of proton-neutron pairing in the context of the Quasiparticle Random Phase approximation formalism. This way the neutrinoless double beta decay matrix elements of the experimentally interesting A= 48, 76, 82, 96, 100, 116, 128, 130 and 136 systems have been calculated. We have found that the inclusion of proton-neutron pairing influences the neutrinoless double beta decay rates significantly, in all cases allowing for larger values of the expectation value of light neutrino masses. Using the best presently available experimental limits on the half life-time of neutrinoless double beta decay we have extracted the limits on lepton number violating parameters.Comment: 16 RevTex page

A New Class of Majoron-Emitting Double-Beta Decays

Motivated by the excess events that have recently been found near the endpoints of the double beta decay spectra of several elements, we re-examine models in which double beta decay can proceed through the neutrinoless emission of massless Nambu-Goldstone bosons (majorons). Noting that models proposed to date for this process must fine-tune either a scalar mass or a VEV to be less than 10 keV, we introduce a new kind of majoron which avoids this difficulty by carrying lepton number $L=-2$. We analyze in detail the requirements that models of both the conventional and our new type must satisfy if they are to account for the observed excess events. We find: (1) the electron sum-energy spectrum can be used to distinguish the two classes of models from one another; (2) the decay rate for the new models depends on different nuclear matrix elements than for ordinary majorons; and (3) all models require a (pseudo) Dirac neutrino, having a mass of a several hundred MeV, which mixes with $\nu_e$.Comment: 43 pages, 10 figures (included), [figure captions are now included

New results for the two neutrino double beta decay in deformed nuclei with angular momentum projected basis

Four nuclei which are proved to be $2\nu\beta\beta$ emitters ($^{76}$Ge, $^{82}$Se, $^{150}$Nd, $^{238}$U), and four suspected, due to the corresponding Q-values, to have this property ($^{148}$Nd, $^{154}$Sm, $^{160}$Gd, $^{232}$Th), were treated within a proton-neutron quasiparticle random phase approximation (pnQRPA) with a projected spherical single particle basis. The advantage of the present procedure over the ones using a deformed Woods Saxon or Nilsson single particle basis is that the actual pnQRPA states have a definite angular momentum while all the others provide states having only K as a good quantum number. The model Hamiltonian involves a mean field term yielding the projected single particle states, a pairing interaction for alike nucleons and a dipole-dipole proton-neutron interaction in both the particle-hole (ph) and particle-particle (pp) channels. The effect of nuclear deformation on the single beta strength distribution as well as on the double beta Gamow-Teller transition amplitude (M$_{{\rm GT}}$) is analyzed. The results are compared with the existent data and with the results from a different approach, in terms of the process half life T$_{1/2}$. The case of different deformations for mother and daughter nuclei is also presented.Comment: 45 pages, 13 figure

Additional Nucleon Current Contributions to Neutrinoless Double Beta Decay

We have examined the importance of momentum dependent induced nucleon currents such as weak-magnetism and pseudoscalar couplings to the amplitude of neutrinoless double beta decay in the mechanisms of light and heavy Majorana neutrino as well as in that of Majoron emission. Such effects are expected to occur in all nuclear models in the direction of reducing the light neutrino matrix elements by about 30%. To test this we have performed a calculation of the nuclear matrix elements of the experimentally interesting nuclei A = 76, 82, 96, 100, 116, 128, 130, 136 and 150 within the pn-RQRPA. We have found that indeed such corrections vary somewhat from nucleus to nucleus, but in all cases they are greater than 25 percent. In the case of heavy neutrino the effect is much larger (a factor of 3). Combining out results with the best presently available experimental limits on the half-life of the neutrinoless double beta decay we have extracted new limits on the effective neutrino mass (light and heavy) and the effective Majoron coupling constant.Comment: 31 pages, RevTex, 3 Postscript figures, submitted to Phys. Rev.

Limits on the Majorana neutrino mass in the 0.1 eV range

The Heidelberg-Moscow experiment gives the most stringent limit on the Majorana neutrino mass. After 24 kg yr of data with pulse shape measurements, we set a lower limit on the half-life of the neutrinoless double beta decay in 76Ge of T_1/2 > 5.7 * 10^{25} yr at 90% C.L., thus excluding an effective Majorana neutrino mass greater than 0.2 eV. This allows to set strong constraints on degenerate neutrino mass models.Comment: 6 pages (latex) including 3 postscript figures and 2 table

Constraining Almost Degenerate Three-Flavor Neutrinos

We discuss constraints on a scenario of almost degenerate three-flavor neutrinos imposed by the solar and the atmospheric neutrino anomalies, hot dark matter, and neutrinoless double $\beta$ decays. It is found that in the Majorana version of the model the region with relatively large $\theta_{13}$ is favored and a constraint on the CP violating phases is obtained.Comment: 19 pages (uses revtex), including 6 figures (uses epsf