3,100 research outputs found

    Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens

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    Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway

    The shear mode of multilayer graphene

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    The quest for materials capable of realizing the next generation of electronic and photonic devices continues to fuel research on the electronic, optical and vibrational properties of graphene. Few-layer graphene (FLG) flakes with less than ten layers each show a distinctive band structure. Thus, there is an increasing interest in the physics and applications of FLGs. Raman spectroscopy is one of the most useful and versatile tools to probe graphene samples. Here, we uncover the interlayer shear mode of FLGs, ranging from bilayer graphene (BLG) to bulk graphite, and suggest that the corresponding Raman peak measures the interlayer coupling. This peak scales from ~43 cm−1 in bulk graphite to ~31 cm−1 in BLG. Its low energy makes it sensitive to near-Dirac point quasiparticles. Similar shear modes are expected in all layered materials, providing a direct probe of interlayer interactions

    Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

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    Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included

    Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0

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    Using 58 million J/psi and 14 million psi' decays obtained by the BESII experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous measurements.Comment: 9 pages, 8 figures, RevTex

    First observation of psi(2S)-->K_S K_L

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    The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

    Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection

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    Severe pulmonary infection is a major threat to human health accompanied by substantial, which increases medical costs, prolonged inpatient requirements, and high mortality rates. New anti-microbial therapeutic strategies are urgently required to address with the emergence of antibiotic resistance and persistent bacterial infections. In this study, we show that constitutive expression of a native anti-microbial peptide hCAP-18/LL-37 (LL9 37) in transgenic mice aids in clearing Pseudomonas aeruginosa (PAO1), a major pathogen of clinical pulmonary infection. Orthotopic transplantation of adult mouse distal airway stem cells (DASCs), genetically engineered to express LL-37, into injured mouse lung foci enabled large scale incorporation of cells and long-term release of the host defense peptide, protecting the mice from bacterial pneumonia and hypoxemia. Further, adult human DASCs were isolated, expanded, and genetically engineered to demonstrate successful construction of an anti-infective artificial lung. Together, our stem cell-based gene delivery therapeutic platform proposes a new strategy for addressing recurrent pulmonary infections with, providing future translational opportunities

    A facile chemical conversion synthesis of Sb2S3 nanotubes and the visible light-driven photocatalytic activities

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    We report a simple chemical conversion and cation exchange technique to realize the synthesis of Sb2S3 nanotubes at a low temperature of 90°C. The successful chemical conversion from ZnS nanotubes to Sb2S3 ones benefits from the large difference in solubility between ZnS and Sb2S3. The as-grown Sb2S3 nanotubes have been transformed from a weak crystallization to a polycrystalline structure via successive annealing. In addition to the detailed structural, morphological, and optical investigation of the yielded Sb2S3 nanotubes before and after annealing, we have shown high photocatalytic activities of Sb2S3 nanotubes for methyl orange degradation under visible light irradiation. This approach offers an effective control of the composition and structure of Sb2S3 nanomaterials, facilitates the production at a relatively low reaction temperature without the need of organics, templates, or crystal seeds, and can be extended to the synthesis of hollow structures with various compositions and shapes for unique properties

    Activation of cGMP-Dependent Protein Kinase Stimulates Cardiac ATP-Sensitive Potassium Channels via a ROS/Calmodulin/CaMKII Signaling Cascade

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    ) channels, an ion channel critical for stress adaptation in the heart; however, the underlying mechanism remains largely unknown. The present study was designed to address this issue. channels was confirmed in intact ventricular cardiomyocytes, which was ROS- and CaMKII-dependent. Kinetically, PKG appeared to stimulate these channels by destabilizing the longest closed state while stabilizing the long open state and facilitating opening transitions. channels and contribute to cardiac protection against ischemia-reperfusion injury
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