Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice

Runt-related transcription factor 2 (Runx2)-deficient mice can be used to model congenital tooth agenesis in humans. Conversely, uterine sensitization-associated gene-1 (Usag-1)-deficient mice exhibit supernumerary tooth formation. Arrested tooth formation can be restored by crossing both knockout-mouse strains; however, it remains unclear whether topical inhibition of Usag-1 expression can enable the recovery of tooth formation in Runx2-deficient mice. Here, we tested whether inhibiting the topical expression of Usag-1 can reverse arrested tooth formation after Runx2 abrogation. The results showed that local application of Usag-1 Stealth small interfering RNA (siRNA) promoted tooth development following Runx2 siRNA-induced agenesis. Additionally, renal capsule transplantation of siRNA-loaded cationized, gelatin-treated mouse mandibles confirmed that cationized gelatin can serve as an effective drug-delivery system. We then performed renal capsule transplantation of wild-type and Runx2-knockout (KO) mouse mandibles, treated with Usag-1 siRNA, revealing that hindered tooth formation was rescued by Usag-1 knockdown. Furthermore, topically applied Usag-1 siRNA partially rescued arrested tooth development in Runx2-KO mice, demonstrating its potential for regenerating teeth in Runx2-deficient mice. Our findings have implications for developing topical treatments for congenital tooth agenesis

Simple Stratification of Hepatocellular Carcinoma Surveillance after Direct-acting Antiviral Therapy for Chronic Hepatitis C

Reports on surveillance systems useful for determining the risk of developing hepatocellular carcinoma （HCC） after direct-acting antiviral （DAA） treatment for hepatitis C have been published. Liver cirrhosis （LC） is a high-risk factor for HCC, but the evaluation frequency necessary for patients with chronic hepatitis （CH） remains unknown. Here, we aimed to identify how frequent CH patients should be evaluated for HCC, with particular emphasis on patients achieving a sustained virological response （SVR） with DAA treatment. Data were collected pre-treatment （Pre） and at the time of SVR for 141 patients with hepatitis C receiving DAA treatment. We defined LC by a platelet （PLT） count ≤10×104/µl, and CH was defined by a PLT count of ＞10×104/µl. The incidence of HCC in patients with CH after achieving SVR was retrospectively evaluated. In total, 128 patients （CH, n＝102; LC, n＝26） achieved SVR, and 13 developed HCC after SVR during the follow-up period （mean, 748 days）. Although fibrosis-4 （FIB-4） index, the presence of α-fetoprotein, and prothrombin time were significant risk factors for HCC in patients with CH in the univariate analysis, only the Pre-FIB-4 index was an independent predictive factor for HCC development in the multivariate analysis （p＝0.04）. An FIB-4 index ≥3 was a significant risk factor for HCC （p＝0.005）. The cumulative risk for HCC at 1000 days was 2.6％ and 24.2％ in the FIB-4 index ＜3 and FIB-4 index ≥3 groups, respectively （p＝0.004）. Frequent HCC examination is recommended for FIB-4 index ≥3 CH patients who obtain SVR after DAA treatment

Persistence of Cryoglobulinemia in Patients with Chronic Hepatitis C after Successful Treatment with Direct-acting Antivirals

Hepatitis C virus（HCV）infection can cause chronic liver disease; it has also been associated with lymphoproliferative disorders（LPDs）, such as cryoglobulinemia and B-cell non-Hodgkin’s lymphoma. Our previous studies suggested that cryoglobulinemia, high titer of rheumatoid factor（RF）, and hypocomplementemia are immunological markers of LPDs. In addition, recent therapies with direct-acting antivirals（DAAs）have achieved high rates of sustained virological response（SVR）in patients with chronic hepatitis C（CH-C）. This study analyzed the efficacy of DAA therapy in CH-C patients with cryoglobulinemia, and the association of biochemical and other immune markers for LPDs with persistence of cryoglobulinemia in patients after DAA therapy. Of 226 patients tested, 31（13.7％）had cryoglobulinemia prior to receiving DAAs, and these individuals showed lower complement 4 levels, decreased complement hemolytic activity, and higher IgM than patients without cryoglobulinemia. Of the 24 cryoglobulinemia-positive patients（83％）who could be followed for 24 weeks, 20 became cryoglobulinemia negative after the therapy. The remaining four patients retained the abnormal LPD markers, indicating the possibility of long-term LPD persistence even following successful eradication of HCV in CH-C patients. Thus, long-term follow-up is recommended to avoid exacerbation of extrahepatic manifestations as well as new events

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

Search for Higgs Boson Decaying to b-bbar and Produced in Association with W Bosons in p-pbar Collisions at sqrt{s}=1.96 TeV

We present a search for Higgs bosons decaying into b-bbar and produced in association with W bosons in p-pbar collisions at sqrt{s}=1.96 TeV. This search uses 320 pb-1 of the dataset accumulated by the upgraded Collider Detector at Fermilab. Events are selected that have a high-transverse momentum electron or muon, missing transverse energy, and two jets, one of which is consistent with a hadronization of a b quark. Both the number of events and the dijet mass distribution are consistent with standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching ratio for the Higgs boson or any new particle with similar decay kinematics. These upper limits range from 10 pb for mH=110 GeV/c2 to 3 pb for mH=150 GeV/c2.Comment: 7 pages, 3 figures; updated title to published versio

Search for Pair Production of Scalar Top Quarks Decaying to a tau Lepton and a b Quark in ppbar Collisions at sqrt{s}=1.96 TeV

We search for pair production of supersymmetric top quarks (~t_1), followed by R-parity violating decay ~t_1 -> tau b with a branching ratio beta, using 322 pb^-1 of ppbar collisions at sqrt{s}=1.96 TeV collected by the CDF II detector at Fermilab. Two candidate events pass our final selection criteria, consistent with the standard model expectation. We set upper limits on the cross section sigma(~t_1 ~tbar_1)*beta^2 as a function of the stop mass m(~t_1). Assuming beta=1, we set a 95% confidence level limit m(~t_1)>153 GeV/c^2. The limits are also applicable to the case of a third generation scalar leptoquark (LQ_3) decaying LQ_3 -> tau b.Comment: 7 pages, 2 eps figure

Search for Second-Generation Scalar Leptoquarks in ppˉ\bm{p \bar{p}} Collisions at s\sqrt{s}=1.96 TeV

Results on a search for pair production of second generation scalar leptoquark in $p \bar{p}$ collisions at $\sqrt{s}$=1.96 TeV are reported. The data analyzed were collected by the CDF detector during the 2002-2003 Tevatron Run II and correspond to an integrated luminosity of 198 pb$^{-1}$. Leptoquarks (LQ) are sought through their decay into (charged) leptons and quarks, with final state signatures represented by two muons and jets and one muon, large transverse missing energy and jets. We observe no evidence for $LQ$ production and derive 95% C.L. upper limits on the $LQ$ production cross sections as well as lower limits on their mass as a function of $\beta$, where $\beta$ is the branching fraction for $LQ \to \mu q$.Comment: 9 pages (3 author list) 5 figure

Observation of Bs-Bsbar Oscillations

We report the observation of Bs-Bsbar oscillations from a time-dependent measurement of the Bs-Bsbar oscillation frequency Delta ms. Using a data sample of 1 fb^-1 of p-pbar collisions at sqrt{s}=1.96 TeV collected with the CDF II detector at the Fermilab Tevatron, we find signals of 5600 fully reconstructed hadronic Bs decays, 3100 partially reconstructed hadronic Bs decays, and 61500 partially reconstructed semileptonic Bs decays. We measure the probability as a function of proper decay time that the Bs decays with the same, or opposite, flavor as the flavor at production, and we find a signal for Bs-Bsbar oscillations. The probability that random fluctuations could produce a comparable signal is 8 X 10^-8, which exceeds 5 sigma significance. We measure Delta ms = 17.77 +- 0.10 (stat) +- 0.07 (syst) ps^-1 and extract |Vtd/Vts| = 0.2060 +- 0.0007 (exp) + 0.0081 - 0.0060 (theor).Comment: 9 pages, 5 figures, submitted to Physical Review Letter