Recent advances in drug discovery for diabetic kidney disease

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area. Areas covered: The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review. Expert opinion: Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

Molecular mechanisms and cellular functions of cGAS-STING signalling

The cGAS–STING signalling axis, comprising the synthase for the second messenger cyclic GMP–AMP (cGAS) and the cyclic GMP–AMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated by endogenous DNA, including extranuclear chromatin resulting from genotoxic stress and DNA released from mitochondria, placing cGAS–STING as an important axis in autoimmunity, sterile inflammatory responses and cellular senescence. Initial models assumed that co-localization of cGAS and DNA in the cytosol defines the specificity of the pathway for non-self, but recent work revealed that cGAS is also present in the nucleus and at the plasma membrane, and such subcellular compartmentalization was linked to signalling specificity of cGAS. Further confounding the simple view of cGAS–STING signalling as a response mechanism to infectious agents, both cGAS and STING were shown to have additional functions, independent of interferon response. These involve non-catalytic roles of cGAS in regulating DNA repair and signalling via STING to NF-κB and MAPK as well as STING-mediated induction of autophagy and lysosome- dependent cell death. We have also learnt that cGAS dimers can multimerize and undergo liquid–liquid phase separation to form biomolecular condensates that could importantly regulate cGAS activation. Here, we review the molecular mechanisms and cellular functions underlying cGAS–STING activation and signalling, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved

Observation of the Decay B=> J/psi eta K and Search for X(3872)=> J/psi eta

We report the observation of the $B$ meson decay $B^\pm\to J/\psi \eta K^\pm$ and evidence for the decay $B^0\to J/\psi \eta K^0_S$, using {90} million $BBbar$ events collected at the \ensuremath{\Upsilon{(4S)}}\xspace resonance with the $BaBar$ detector at the PEP-II $e^+ e^-$ asymmetric-energy storage ring. We obtain branching fractions of $\cal{B}$$(B^\pm\to J/\psi \eta K^{\pm}$)=$(10.8\pm 2.3(\rm{stat.})\pm 2.4(\rm{syst.}))\times 10^{-5}$ and $\cal{B}$$(B^0\to J/\psi\eta K_{\rm{S}}^{0}$)=$(8.4\pm 2.6(\rm{stat.})\pm 2.7(\rm{syst.}))\times 10^{-5}$. We search for the new narrow mass state, the X(3872), recently reported by the Belle Collaboration, in the decay B^\pm\to X(3872)K^\pm, X(3872)\to \jpsi \eta and determine an upper limit of $\cal{B}$(B^\pm \to X(3872) K^\pm \to \jpsi \eta K^\pm) $<7.7\times 10^{-6}$ at 90% C.L.Comment: 7 pages and two figures, submitted to Phys. Rev. Lett

Measurement of the polar-angle distribution of leptons from W boson decay as a function of the W transverse momentum in proton-antiproton collisions at sqrt{s}=1.8 TeV

We present a measurement of the coefficient alpha_2 of the leptonic polar-angle distribution from W boson decays, as a function of the W transverse momentum. The measurement uses an 80+/-4 pb^{-1} sample of proton-antiproton collisions at sqrt{s}=1.8 TeV collected by the CDF detector and includes data from both the W->e+nu and W->mu+nu decay channels. We fit the W boson transverse mass distribution to a set of templates from a Monte Carlo event generator and detector simulation in several ranges of the W transverse momentum. The measurement agrees with the Standard Model expectation, whereby the ratio of longitudinally to transversely polarized W bosons, in the Collins-Soper W rest frame, increases with the W transverse momentum at a rate of approximately 15% per 10 GeV/c.Comment: 47 pages, 16 figures, submitted to Physical Review

Measurement of dσ/dyd\sigma/dy of Drell-Yan e+e−e^+e^- pairs in the ZZ Mass Region from ppˉp\bar{p} Collisions at s=1.96\sqrt{s}=1.96 TeV

Submitted to Phys. Letter BWe report on a CDF measurement of the total cross section and rapidity distribution, $d\sigma/dy$, for $q\bar{q}\to \gamma^{*}/Z\to e^{+}e^{-}$ events in the $Z$ boson mass region ($66M_{ee}We report on a CDF measurement of the total cross section and rapidity distribution, dσ/dy, for γ*/Z→e+e− events in the Z boson mass region (66<Mee<116 GeV/c2) produced in p pbar collisions at \sqrt{s}=1.96 TeV with 2.1 fb−1 of integrated luminosity. The measured cross section of 257±16 pb and dσ/dy distribution are compared with Next-to-Leading-Order (NLO) and Next-to-Next-to-Leading-Order (NNLO) QCD theory predictions with CTEQ and MRST/MSTW parton distribution functions (PDFs). There is good agreement between the experimental total cross section and dσ/dy measurements with theoretical calculations with the most recent NNLO PDFs.Peer reviewe

Measurement of the Top Pair Production Cross Section in the Dilepton Decay Channel in ppbar Collisions at sqrt s = 1.96 TeV

Submitted to Phys. Rev. DA measurement of the \ttbar production cross section in \ppbar collisions at $\sqrt{{\rm s}}$ = 1.96 TeV using events with two leptons, missing transverse energy, and jets is reported. The data were collected with the CDF II Detector. The result in a data sample corresponding to an integrated luminosity 2.8 fb$^{-1}$ is: \sigma_{\ttbar} = 6.27 $\pm$ 0.73(stat) $\pm$ 0.63(syst) $\pm$ 0.39(lum) pb. for an assumed top mass of 175 GeV/$c^{2}$.A measurement of the tt̅ production cross section in pp̅ collisions at √s=1.96  TeV using events with two leptons, missing transverse energy, and jets is reported. The data were collected with the CDF II detector. The result in a data sample corresponding to an integrated luminosity 2.8  fb-1 is σtt̅ =6.27±0.73(stat)±0.63(syst)±0.39(lum)  pb. for an assumed top mass of 175  GeV/c2.Peer reviewe