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Objectives: To evaluate the efficacy of ultrasound and contrast-enhanced ultrasound (CEUS) in disease activity assessment of Takayasu arteritis (TA) with carotid involvement. Methods: This is a cohort study of 115 patients of TA with carotid involvement. We investigated correlations between clinical data, sonographic features, and CEUS enhancement at the site most prominent lesion of each patient. Disease activity was assessed by the National Institute of Health Kerr criteria. Sonographic findings were compared with follow-up examinations. CEUS was repeated after a 3-7 months interval in 35 patients to evaluate change of CEUS enhancement after treatment. Results: Extensiveness of CEUS enhancement at most prominent carotid lesions had significant correlations with disease activity by the Kerr criteria (P < .001). The specificity of extensive enhancement for indicating active disease was 95%, while sensitivity was 67%. Patients with active disease showed greater arterial wall thickness and more prominent reduction of arterial wall thickness after treatment. Most of the patients (68%) with subsided active disease after treatment featured decrease of CEUS enhancement. Conclusions: Extensiveness of enhancement by CEUS and arterial wall thickness by ultrasonography may be useful markers for initial and follow-up assessment of disease activity of TA with common carotid artery involvement. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether in vitro induced erythromycin resistance facilitates the cross-resistance to the novel fluoroketolide, solithromycin, in Staphylococcus aureus. Four strains of methicillin-susceptible S. aureus strains S2, S3, S5 and S7 were successfully induced to establish erythromycin-resistant strains by continuous in vitro culture with erythromycin. Mutations at drug binding sites were shown to increase the minimal inhibitory concentrations for ketolides, including telithromycin and the novel compound solithromycin, but did not increase for lincosamides, chloramphenicols or oxazolidinones. In S2-, S5- and S7-derived strains, L22 protein mutations occurred first, resulting in a low level of cross-resistance to ketolides (≤4 μg/mL). The L4 protein mutations were dependent on the L22 protein, resulting in high-level cross-resistance to ketolides (≥8 μg/mL). In S3-derived strains, high levels of cross-resistance occurred concurrently in the 23S rRNA domains II/V and the L22 protein. Hence, long-term exposure of erythromycin results in resistance to ketolides in S. aureus through drug binding site mutations. These results demonstrate that since erythromycin has been used clinically for a long time, it is necessary to carefully evaluate the rewards and risks when prescribing solithromycin for the treatment of infectious diseases. [ABSTRACT FROM AUTHOR]

AIMS: The Notch1 signaling pathway is implicated in multiple inflammatory diseases. However, the role of Notch1 signaling in alcoholic steatohepatitis (ASH) has not been fully investigated. We aimed to determine whether Notch1-Nuclear factor-κB (NF-κB) signaling mediates oxidative stress-induced ASH. METHODS: In vitro, three cell lines were used: the HepG2 cells, HepG2 cells transfected with a control vector (Neo cells) and HepG2 cells transfected with a cytochrome P4502E1-expression vector (2E1 cells), which allows the cells to undergo oxidative stress in response to ethanol. All three cell lines were incubated with ethanol with/without Notch1 inhibitor treatment, oxidative stress marker, steatohepatitis marker and Notch1-NF-κB signaling were assessed. To further test Notch1-NF-κB signaling in vivo, rats were fed with ethanol, ethanol plus Notch1 inhibitor or an isocaloric diet for 8 weeks. Hepatitis, oxidative stress and Notch1-NF-κB activity in the liver were assessed to further verify the in vitro results. RESULTS: Ethanol was shown to induce oxidative stress and steatohepatitis with remarkably elevated Notch1-NF-κB expression in 2E1 cells rather than HepG2 and Neo cells. Notch1 inhibitor was non-toxic in the three cell lines and had a protective effect against markers of ASH. Similarly, chronic alcohol administration in vivo induced alcoholic hepatitis, oxidative stress and elevated Notch1-NF-κB expression in rats, while Notch1 inhibitor attenuated alcoholic liver injury. CONCLUSION: These findings provide direct in vitro and in vivo evidence that the oxidative stress-induced ASH is mediated by the Notch1-NF-κB signaling pathway, which can be effectively reversed by Notch1 inhibitor. [ABSTRACT FROM AUTHOR]

In this study, the protective efficacy of a novel recombinant bacille Calmette Géurin (BCG) strain (rBCG-AEI) expressing fusion protein the antigen 85B (Ag85B)- the 6-kDa early secreted antigen target (ESAT-6)-IFN-γ against Mycobacterium tuberculosis H37Rv in mice was evaluated. The immunogenicity study showed that rBCG-AEI could induce higher specific antibody titers and significantly increase cellular immune response than BCG, or rBCG-A strain (expressing Ag85B), or rBCG-AE strain (expressing fusion protein Ag85B-ESAT-6). The protective experiment demonstrated that rBCG-AEI could confer similar or even better protective efficacy against M. tuberculosis infection compared with others in organ bacterial loads, lung histopathology and net weight gain or loss. The results suggested that rBCG-AEI is a potential candidate for further study. [ABSTRACT FROM AUTHOR]

Reports the isolation of rho3[sup +], encoding a Rho family GTPase, as a high-copy suppressor of an exocyst mutant sec8-1 in Schizosaccharomyces pombe. Regulation of cell separation by Rho3p; Aspects of cytokinesis; Suppression of the temperature-sensitive growth phenotype observed in cells lacking Exo70p due to overproduction of Rho3p.

Shows that drc1/cps1, which encodes a 1,3-beta-glucan synthase, is essential for assembly of the division septum, but not for cell elongation and cell growth. Five steps in the cytokinesis in Schizosaccharomyces pombe; Description of temperature-sensitive mutation that prevents division septum assembly; Links between Drc1p and other cytokinesis regulators.

Plant long non-coding RNAs (lncRNAs) function in diverse biological processes, and lncRNA expression is under epigenetic regulation, including by cytosine DNA methylation. However, it remains unclear whether 5-methylcytosine (5mC) plays a similar role in different sequence contexts (CG, CHG, and CHH). In this study, we characterized and compared the profiles of genome-wide lncRNA profiles (including long intergenic non-coding RNAs [lincRNAs] and long noncoding natural antisense transcripts [lncNATs]) of a null mutant of the rice DNA methyltransferase 1, OsMET1-2 (designated OsMET1-2-/-) and its isogenic wild type (OsMET1-2+/+). The En/Spm transposable element (TE) family, which was heavily methylated in OsMET1-2+/+, was transcriptionally de-repressed in OsMET1-2/ due to genome-wide erasure of CG methylation, and this led to abundant production of specific lncRNAs. In addition, RdDM-mediated CHH hypermethylation was increased in the 50 -upstream genomic regions of lncRNAs in OsMET1-2-/-. The positive correlation between the expression of lincRNAs and that of their proximal protein-coding genes was also analyzed. Our study shows that CG methylation negatively regulates the TE-related expression of lncRNA and demonstrates that CHH methylation is also involved in the regulation of lncRNA expression. [ABSTRACT FROM AUTHOR]