Tryptophan hydroxylase-2-mediated serotonin biosynthesis suppresses cell reprogramming into pluripotent state

The monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has important functions both in the neural system and during embryonic development in mammals. In this study, we set out to investigate whether and how endogenous serotonin affects reprogramming to pluripotency. As serotonin is synthesized from tryptophan by the rate limiting enzymes tryptophan hydroxylase-1 and -2 (TPH1 and TPH2), we have assessed the reprogramming of TPH1- and/or TPH2-deficient mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs). The reprogramming of the double mutant MEFs showed a dramatic increase in the efficiency of iPSC generation. In contrast, ectopic expression of TPH2 alone or in conjunction with TPH1 reverted the rate of reprogramming of the double mutant MEFs to the wild-type level and besides, TPH2 overexpression significantly suppressed reprogramming of wild-type MEFs. Our data thus suggest a negative role of serotonin biosynthesis in the reprogramming of somatic cells to a pluripotent state

Transfer of synthetic human chromosome into human induced pluripotent stem cells for biomedical applications

Alphoid(tetO)-type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic diseases caused by the loss of a particular gene function. The alphoid(tetO)-HAC vector has been successfully transferred into murine embryonic stem cells (ESCs) and maintained stably as an independent chromosome during the proliferation and differentiation of these cells. Human ESCs and iPSCs have significant differences in culturing conditions and pluripotency state in comparison with the murine naïve-type ESCs and iPSCs. To date, transferring alphoid(tetO)-HAC vector into human iPSCs (hiPSCs) remains a challenging task. In this study, we performed the microcell-mediated chromosome transfer (MMCT) of alphoid(tetO)-HAC expressing the green fluorescent protein into newly generated hiPSCs. We used a recently modified MMCT method that employs an envelope protein of amphotropic murine leukemia virus as a targeting cell fusion agent. Our data provide evidence that a totally artificial vector, alphoid(tetO)-HAC, can be transferred and maintained in human iPSCs as an independent autonomous chromosome without affecting pluripotent properties of the cells. These data also open new perspectives for implementing alphoid(tetO)-HAC as a gene therapy tool in future biomedical applications

LATE PLEISTOCENE-HOLOCENE ENVIRONMENTAL AND CLIMATIC CHANGES IN THE BAIKAL REGION INFERRED FROM MULTI-PROXY LACUSTRINE RECORDS

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SUSY Resonances from UHE neutralinos in Neutrino Telescopes and in the Sky

In the Top-down scenarios, the decay of super-heavy particles (m~10^{12-16}GeV), situated in dark-matter halos not very far from our Galaxy, can explain the ultra-high-energy (UHE) cosmic-ray spectrum beyond the Griesen-Zatasepin-Kuzmin cut-off. In the MSSM, a major component of the UHE cosmic-ray flux at PeV-EeV energies could be given by the lightest neutralino \chi, that is the lightest stable supersymmetric particle. Then, the signal of UHE \chi's on earth might emerge over the interactions of a comparable neutrino component. We compute the event rates for the resonant production of "right" selectrons and "right" squarks in mSUGRA, when UHE neutralinos of energy larger than 10^5 GeV scatter off electrons and quarks in an earth-based detector like IceCube. When the resonant channel dominates in the total \chi-e,\chi-q scattering cross section, the only model parameters affecting the corresponding visible signal rates turn out to be the physical masses of the resonant right-scalar and of the lightest neutralino. We compare the expected number of supersymmetric events with the rates corresponding to the expected Glashow W resonance and to the continuum UHE \nu-N scattering for realistic power-law spectra. We find that the event rate in the leptonic selectron channel is particularly promising, and can reach a few tens for a one-year exposure in IceCube. Finally, we note that UHE neutralinos at much higher energies (up to hundreds ZeV) may produce sneutrino resonances by scattering off relic neutrinos in the Local Group hot dark halo. The consequent \tilde{\nu}-burst into hadronic final states could mimic Z-burst events, although with quite smaller conversion efficiency.Comment: 23 pages, 4 figures; one reference adde

Study of KS KL Coupled Decays and KL -Be Interactions with the CMD-2 Detector at VEPP-2M Collider

The integrated luminosity about 4000 inverse nanobarn of around phi meson mass ( 5 millions of phi mesons) has been collected with the CMD-2 detector at the VEPP-2M collider. A latest analysis of the KS KL coupled decays based on 30 % of available data is presented in this paper. The KS KL pairs from phi meson decays were reconstructed in the drift chamber when both kaons decayed into two charged particles. From a sample of 1423 coupled decays a selection of candidates to the CP violating KL into pi+ pi- decay was performed. CP violating decays were not identified because of the domination of events with a KL regenerating at the Be beam pipe into KS and a background from KL semileptonic decays. The regeneration cross section of 110 MeV/c KL mesons was found to be 53 +- 17 mb in agreement with theoretical expectations. The angular distribution of KS mesons after regeneration and the total cross section of KL for Be have been measured.Comment: 14 pages, 8 figure

Study of the radiative decay ϕ→ηγ\phi \to \eta \gamma with CMD-2 detector

Using the $1.9 pb^{-1}$ of data collected with the CMD-2 detector at VEPP-2M the decay mode $\phi \to \eta \gamma$, $\eta \to \pi^+\pi^-\pi^0$ has been studied. The obtained branching ratio is B($\phi \to \eta \gamma) = (1.18 \pm 0.03 \pm 0.06)$.Comment: 13 pages, 5 figures, LaTex2e, to be published in Phys. Lett.

Observation of KS0K_S^0 semileptonic decays with CMD-2 detector

The decay $K_S^0 \to \pi e \nu$ has been observed by the CMD-2 detector at the e^+e^- collider VEPP-2M at Novosibirsk. Of 6 million produced $K_L^0K_S^0$ pairs, $75 \pm 13$ events of the $K_S^0 \to \pi e \nu$ decay were selected. The corresponding branching ratio is $B(K_S^0 \to \pi e \nu)=(7.2 \pm 1.4)\times10^{-4}$. This result is consistent with the evaluation of $B(K_S^0 \to \pi e \nu)$ from the $K_L^0$ semileptonic rate and $K_S^0$ lifetime assuming $\Delta S=\Delta Q$ .Comment: 7 pages, 6 figures, LaTex2e. Submitted to Phys.Lett.

Measurement of omega meson parameters in pi^+pi^-pi^0 decay mode with CMD-2

About 11 200 e^+e^- -> omega -> pi^+pi^-pi^0 events selected in the center of mass energy range from 760 to 810 MeV were used for the measurement of the \omega meson parameters. The following results have been obtained: sigma _{0}=(1457 \pm 23 \pm 19)nb, m_{\omega}=(782.71 \pm 0.07 \pm 0.04) MeV/c^{2}, \Gamma_{\omega}=(8.68 \pm 0.23 \pm 0.10) MeV, \Gamma_{e^+e^-}\cdot Br (\omega -> pi^+pi^-pi^0)= (0.528 \pm 0.012 \pm 0.007) \cdot 10^{-3} MeV.Comment: 8 pages, 4 figure

Study of the process e+e- to pi+pi-pi+pi-pi0 with CMD-2 detector

The process e+e- to pi+ pi- pi+ pi- pi0 has been studied in the center of mass energy range 1280 -- 1380 MeV using 3.0 1/pb of data collected with the CMD-2 detector in Novosibirsk. Analysis shows that the cross section of the five pion production is dominated by the contributions of the eta pi+pi- and omega pi+pi- intermediate states.Comment: 8 pages, 3 figure. Submitted to Phys. Lett.

Towards the Theory of Cosmological Phase Transitions

We discuss recent progress (and controversies) in the theory of finite temperature phase transitions. This includes the structure of the effective potential at a finite temperature, the infrared problem in quantum statistics of gauge fields, the theory of formation of critical and subcritical bubbles and the theory of bubble wall propagation.Comment: 50 p