Wdr1 and cofilin are necessary mediators of immune-cell-specific apoptosis triggered by Tecfidera.

Despite the emerging importance of reactive electrophilic drugs, deconvolution of their principal targets remains difficult. The lack of genetic tractability/interventions and reliance on secondary validation using other non-specific compounds frequently complicate the earmarking of individual binders as functionally- or phenotypically-sufficient pathway regulators. Using a redox-targeting approach to interrogate how on-target binding of pleiotropic electrophiles translates to a phenotypic output in vivo, we here systematically track the molecular components attributable to innate immune cell toxicity of the electrophilic-drug dimethyl fumarate (Tecfidera®). In a process largely independent of canonical Keap1/Nrf2-signaling, Keap1-specific modification triggers mitochondrial-targeted neutrophil/macrophage apoptosis. On-target Keap1-ligand-engagement is accompanied by dissociation of Wdr1 from Keap1 and subsequent coordination with cofilin, intercepting Bax. This phagocytic-specific cell-killing program is recapitulated by whole-animal administration of dimethyl fumarate, where individual depletions of the players identified above robustly suppress apoptosis

Novel family- and genus-specific DNA markers in Mugilidae

In this study, we identified novel family- and genus-specific DNA markers in Mugilidae fish. Genomic DNA was isolated from the blood of fish of 15 families and eighty (80) random primers were used for random amplified polymorphic DNA (RAPD) fingerprinting. When the primer OPAV04 was employed, a novel specific PCR product was observed in the Mugilidae family. In addition, another novel specific PCR product was also observed in the Liza genus while using primer OPAV10. Sequencing analysis revealed that the novel family- and genus-specific DNA fragments were 857 and 419 bp, respectively, and no similar sequences were found in GenBank. Two primers sets were designed based on the family- and genus-specific sequences to confirm the RAPD results and the 571 and 187 bp predicted bands were successfully amplified by PCR. Intriguingly, these two novel specific DNA markers were also effectively used for terrestrial and aquatic animal discrimination. Therefore, the novel family- and genus-specific DNA markers identified in this study can be used as an effective tool for rapid and accurate determination of the Mugilidae family and Liza genus, and even for cross-species identification

Narrow width of a glueball decay into two mesons

The widths of a glueball decay to two pions or kaons are analyzed in the pQCD framework. Our results show that the glueball ground state has small branching ratio for two-meson decay mode, which is around $10^{-2}$. The predicted values are consistent with the data of $\xi\to\pi\pi, KK$ if $\xi$ particle is a $2^{++}$ glueball. Applicability of pQCD to the glueball decay and comparison with $\chi_{cJ}$ decay are also discussed.Comment: 12 pages, revtex, 2 ps figure

Large non-Gaussianity from two-component hybrid inflation

We study the generation of non-Gaussianity in models of hybrid inflation with two inflaton fields, (2-brid inflation). We analyse the region in the parameter and the initial condition space where a large non-Gaussianity may be generated during slow-roll inflation which is generally characterised by a large f_NL, tau_NL and a small g_NL. For certain parameter values we can satisfy tau_NL>>f_NL^2. The bispectrum is of the local type but may have a significant scale dependence. We show that the loop corrections to the power spectrum and bispectrum are suppressed during inflation, if one assume that the fields follow a classical background trajectory. We also include the effect of the waterfall field, which can lead to a significant change in the observables after the waterfall field is destabilised, depending on the couplings between the waterfall and inflaton fields.Comment: 16 pages, 6 figures; v2: comments and references added, typos corrected, matches published versio

Diagnosing the Clumpy Protoplanetary Disk of the UXor Type Young Star GM Cephei

UX Orionis stars (UXors) are Herbig Ae/Be or T Tauri stars exhibiting sporadic occultation of stellar light by circumstellar dust. GM\,Cephei is such a UXor in the young ($\sim4$~Myr) open cluster Trumpler\,37, showing prominent infrared excess, emission-line spectra, and flare activity. Our photometric monitoring (2008--2018) detects (1)~an $\sim$3.43~day period, likely arising from rotational modulation by surface starspots, (2)~sporadic brightening on time scales of days due to accretion, (3)~irregular minor flux drops due to circumstellar dust extinction, and (4)~major flux drops, each lasting for a couple of months with a recurrence time, though not exactly periodic, of about two years. The star experiences normal reddening by large grains, i.e., redder when dimmer, but exhibits an unusual "blueing" phenomenon in that the star turns blue near brightness minima. The maximum extinction during relatively short (lasting $\leq 50$~days) events, is proportional to the duration, a consequence of varying clump sizes. For longer events, the extinction is independent of duration, suggestive of a transverse string distribution of clumps. Polarization monitoring indicates an optical polarization varying $\sim3\%$--8$\%$, with the level anticorrelated with the slow brightness change. Temporal variation of the unpolarized and polarized light sets constraints on the size and orbital distance of the circumstellar clumps in the interplay with the young star and scattering envelope. These transiting clumps are edge-on manifestations of the ring- or spiral-like structures found recently in young stars with imaging in infrared of scattered light, or in submillimeter of thermalized dust emission.Comment: 20 pages, 9 figure

Pseuduscalar Heavy Quarkonium Decays With Both Relativistic and QCD Radiative Corrections

We estimate the decay rates of $\eta_c\rightarrow 2\gamma$, $\eta_c'\rightarrow 2\gamma$, and $J/\psi\rightarrow e^+ e^-$, $\psi^\prime\rightarrow e^+e^-$, by taking into account both relativistic and QCD radiative corrections. The decay amplitudes are derived in the Bethe-Salpeter formalism. The Bethe-Salpeter equation with a QCD-inspired interquark potential are used to calculate the wave functions and decay widths for these $c\bar{c}$ states. We find that the relativistic correction to the ratio $R\equiv \Gamma (\eta_c \rightarrow 2\gamma)/ \Gamma (J/ \psi \rightarrow e^+ e^-)$ is negative and tends to compensate the positive contribution from the QCD radiative correction. Our estimate gives $\Gamma(\eta_c \rightarrow 2\gamma)=(6-7) ~keV$ and $\Gamma(\eta_c^\prime \rightarrow 2\gamma)=2 ~keV$, which are smaller than their nonrelativistic values. The hadronic widths $\Gamma(\eta_c \rightarrow 2g)=(17-23) ~MeV$ and $\Gamma(\eta_c^\prime \rightarrow 2g)=(5-7)~MeV$ are then indicated accordingly to the first order QCD radiative correction, if $\alpha_s(m_c)=0.26-0.29$. The decay widths for $b\bar b$ states are also estimated. We show that when making the assmption that the quarks are on their mass shells our expressions for the decay widths will become identical with that in the NRQCD theory to the next to leading order of $v^2$ and $\alpha_s$.Comment: 14 pages LaTex (2 figures included

Possible retardation effects of quark confinement on the meson spectrum

The reduced Bethe-Salpeter equation with scalar confinement and vector gluon exchange is applied to quark-antiquark bound states. The so called intrinsic flaw of Salpeter equation with static scalar confinement is investigated. The notorious problem of narrow level spacings is found to be remedied by taking into consideration the retardation effect of scalar confinement. Good fit for the mass spectrum of both heavy and light quarkomium states is then obtained.Comment: 14 pages in LaTex for

Semileptonic decays of Bs1B_{s1}, Bs2∗B_{s2}^*, Bs0B_{s0} and Bs1′B_{s1}'

Stimulated by recent observations of the excited bottom-strange mesons $B_{s1}$ and $B_{s2}^*$, we calculate the semileptonic decays $B_{s0}, B_{s1}^{\prime}, B_{s1}, B_{s2}^*\to [D_s(1968), D_{s}^*(2112), D_{sJ}(2317), D_{sJ}(2460)]\ell\bar{\nu}$, which is relevant for the exploration of the potential of searching these semileptonic decays in experiment.Comment: 11 pages, 3 figures, 9 tables. More discussion added, some descriptions changed. The version to appear in EPJ

The synthesized 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) promoted G2/M arrest through inhibition of CDK1 and induced apoptosis through the mitochondrial-dependent pathway in CT-26 murine colorectal adenocarcinoma cells

In this study, we investigated the effects of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) on cell viability, cell cycle arrest and apoptosis in CT-26 murine colorectal adenocarcinoma cells. For determining cell viability, the MTT assay was used. CHM-1 promoted G2/M arrest by PI staining and flow cytometric analysis. Apoptotic cells were evaluated by DAPI staining. We used CDK1 kinase assay, Western blot analysis and caspase activity assays for examining the CDK1 activity and proteins correlated with apoptosis and cell cycle arrest. The in vivo anti-tumor effects of CHM-1-P were evaluated in BALB/c mice inoculated with CT-26 cells orthotopic model. CHM-1 induced CT-26 cell viability inhibition and morphologic changes in a dose-dependent and time-dependent manner and the approximate IC(50) was 742.36 nM. CHM-1 induced significant G2/M arrest and apoptosis in CT-26 cells. CHM-1 inhibited the CDK1 activity and decreased CDK1, Cyclin A, Cyclin B protein levels. CHM-1 induced apoptosis in CT-26 cells and promoted increasing of cytosolic cytochrome c, AIF, Bax, BAD, cleavage of pro-caspase-9, and -3. The significant reduction of caspase-9 and -3 activity and increasing the viable CT-26 cells after pretreated with caspase-9 and -3 inhibitor indicated that CHM-1-induced apoptosis was mainly mediated a mitochondria-dependent pathway. CHM-1-P improved mice survival rate, and enlargement of the spleen and liver metastasis were significantly reduced in groups treated with either 10 mg/kg and 30 mg/kg of CHM-1-P and 5-FU in comparison to these of CT-26/BALB/c mice. Taken together, CHM-1 acted against colorectal adenocarcinoma cells in vitro via G2/M arrest and apoptosis, and CHM-1-P inhibited tumor growth in vivo

Anomalous Pseudoscalar-Photon Vertex In and Out of Equilibrium

The anomalous pseudoscalar-photon vertex is studied in real time in and out of equilibrium in a constituent quark model. The goal is to understand the in-medium modifications of this vertex, exploring the possibility of enhanced isospin breaking by electromagnetic effects as well as the formation of neutral pion condensates in a rapid chiral phase transition in peripheral, ultrarelativistic heavy-ion collisions. In equilibrium the effective vertex is afflicted by infrared and collinear singularities that require hard thermal loop (HTL) and width corrections of the quark propagator. The resummed effective equilibrium vertex vanishes near the chiral transition in the chiral limit. In a strongly out of equilibrium chiral phase transition we find that the chiral condensate drastically modifies the quark propagators and the effective vertex. The ensuing dynamics for the neutral pion results in a potential enhancement of isospin breaking and the formation of $\pi^0$ condensates. While the anomaly equation and the axial Ward identity are not modified by the medium in or out of equilibrium, the effective real-time pseudoscalar-photon vertex is sensitive to low energy physics.Comment: Revised version to appear in Phys. Rev. D. 42 pages, 4 figures, uses Revte