NF-κB Induction of the SUMO Protease SENP2: A Negative Feedback Loop to Attenuate Cell Survival Response to Genotoxic Stress

Activation of NF-κB, pivotal for immunity and oncogenesis, is tightly controlled by multiple feedback mechanisms. In response to DNA damage, SUMOylation of NEMO (NF-κB essential modulator) is critical for NF-κB activation, however SUMO proteases and feedback mechanisms involved remain unknown. Here we show that among the six known SENPs (Sentrin/SUMO-specific proteases) only SENP2 can efficiently associate with NEMO, deSUMOylate NEMO and inhibit NF-κB activation induced by DNA damage. We further show that NF-κB induces SENP2 (and SENP1) transcription selectively in response to genotoxic stimuli, which involves ATM (ataxia telangiectasia mutated)-dependent histone methylation of SENP2 promoter κB regions and NF-κB recruitment. SENP2-null cells display biphasic NEMO SUMOylation and activation of IKK and NF-κB, and higher resistance to DNA damage-induced cell death. Our study establishes a self-attenuating feedback mechanism selective to DNA damage induced signaling to limit NF-κB-dependent cell survival responses

Bulk-sensitive photoemission spectroscopy of A_2FeMoO_6 double perovskites (A=Sr, Ba)

Electronic structures of Sr_2FeMoO_6 (SFMO) and Ba_2FeMoO_6 (BFMO) double perovskites have been investigated using the Fe 2p->3d resonant photoemission spectroscopy (PES) and the Cooper minimum in the Mo 4d photoionization cross section. The states close to the Fermi level are found to have strongly mixed Mo-Fe t_{2g} character, suggesting that the Fe valence is far from pure 3+. The Fe 2p_{3/2} XAS spectra indicate the mixed-valent Fe^{3+}-Fe^{2+} configurations, and the larger Fe^{2+} component for BFMO than for SFMO, suggesting a kind of double exchange interaction. The valence-band PES spectra reveal good agreement with the LSDA+U calculation.Comment: 4 pages, 3 figure

Role of calcineurin in Porphyromonas gingivalis-induced myocardial cell hypertrophy and apoptosis

Background and objective: Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) increased cardiomyocyte hypertrophy and apoptosis whereas Actinobaeillus actinomycetemcomitans and Prevotella intermedia had no effects. The purpose of this study is to clarify the role of calcineurin signaling pathway in P. gingivalis-induced H9c2 myocardial cell hypertrophy and apoptosis. Methods: DNA fragmentation, nuclear condensation, cellular morphology, calcineurin protein, Bcl2- associated death promoter (Bad) and nuclear factor of activated T cell (NFAT)-3 protein products in cultured H9c2 myocardial cell were measured by agarose gel electrophoresis, DAPI, immunofluorescence, and Western blotting following P. gingivalis and/or pre-administration of CsA (calcineurin inhibitors cyclosporin A). Results: P. gingivalis not only increased calcineurin protein, NFAT-3 protein products and cellular hypertrophy, but also increased DNA fragmentation, nuclear condensation and Bad protein products in H9c2 cells. The increased cellular sizes, DNA fragmentation, nuclear condensation, and Bad of H9c2 cells treated with P. gingivalis were all significantly reduced after pre-administration of CsA. Conclusion: Our findings suggest that the activity of calcineurin signal pathway may be initiated by P. gingivalis and further lead to cell hypertrophy and death in culture H9c2 myocardial cells

Local fluctuations in quantum critical metals

We show that spatially local, yet low-energy, fluctuations can play an essential role in the physics of strongly correlated electron systems tuned to a quantum critical point. A detailed microscopic analysis of the Kondo lattice model is carried out within an extended dynamical mean-field approach. The correlation functions for the lattice model are calculated through a self-consistent Bose-Fermi Kondo problem, in which a local moment is coupled both to a fermionic bath and to a bosonic bath (a fluctuating magnetic field). A renormalization-group treatment of this impurity problem--perturbative in $\epsilon=1-\gamma$, where $\gamma$ is an exponent characterizing the spectrum of the bosonic bath--shows that competition between the two couplings can drive the local-moment fluctuations critical. As a result, two distinct types of quantum critical point emerge in the Kondo lattice, one being of the usual spin-density-wave type, the other ``locally critical.'' Near the locally critical point, the dynamical spin susceptibility exhibits $\omega/T$ scaling with a fractional exponent. While the spin-density-wave critical point is Gaussian, the locally critical point is an interacting fixed point at which long-wavelength and spatially local critical modes coexist. A Ginzburg-Landau description for the locally critical point is discussed. It is argued that these results are robust, that local criticality provides a natural description of the quantum critical behavior seen in a number of heavy-fermion metals, and that this picture may also be relevant to other strongly correlated metals.Comment: 20 pages, 12 figures; typos in figure 3 and in the main text corrected, version as publishe

Measurement of Cosmic-ray Muon-induced Spallation Neutrons in the Aberdeen Tunnel Underground Laboratory

AbstractMuon-induced neutrons are one of the major backgrounds to various underground experiments, such as dark matter searches, low-energy neutrino oscillation experiments and neutrino-less double beta-decay experiments. Previous experiments on the underground production rate of muon-induced neutrons were mostly carried out either at shallow sites or at very deep sites. The Aberdeen Tunnel experiment aims to measure the neutron production rate at a moderate depth of 611 meters water equivalent. Our apparatus comprises of six layers of plastic-scintillator hodoscopes for tracking the incident cosmic-ray muons, and 760 L of gadolinium-doped liquid-scintillator for both neutron production and detection targets. In this paper, we describe the design and the performance of the apparatus. The preliminary result on the measurement of neutron production rate is also presented

Protons in near earth orbit

The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is parameterized by a power law. Below the geomagnetic cutoff a substantial second spectrum was observed concentrated at equatorial latitudes with a flux ~ 70 m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure

Search for antihelium in cosmic rays

The Alpha Magnetic Spectrometer (AMS) was flown on the space shuttle Discovery during flight STS-91 in a 51.7 degree orbit at altitudes between 320 and 390 km. A total of 2.86 * 10^6 helium nuclei were observed in the rigidity range 1 to 140 GV. No antihelium nuclei were detected at any rigidity. An upper limit on the flux ratio of antihelium to helium of < 1.1 * 10^-6 is obtained.Comment: 18 pages, Latex, 9 .eps figure

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

Search for Third Generation Vector Leptoquarks in p anti-p Collisions at sqrt(s) = 1.96 TeV

We describe a search for a third generation vector leptoquark (VLQ3) that decays to a b quark and tau lepton using the CDF II detector and 322 pb^(-1) of integrated luminosity from the Fermilab Tevatron. Vector leptoquarks have been proposed in many extensions of the standard model (SM). Observing a number of events in agreement with SM expectations, assuming Yang-Mills (minimal) couplings, we obtain the most stringent upper limit on the VLQ3 pair production cross section of 344 fb (493 fb) and lower limit on the VLQ3 mass of 317 GeV/c^2 (251 GeV/c^2) at 95% C.L.Comment: 7 pages, 2 figures, submitted to PR