Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in lactococcus lactis

© 2016 John Wiley & Sons Ltd. The second messenger cyclic-di-adenosine monophosphate (c-di-AMP) plays important roles in growth, virulence, cell wall homeostasis, potassium transport and affects resistance to antibiotics, heat and osmotic stress. Most Firmicutes contain only one c-di-AMP synthesizing diadenylate cyclase (CdaA); however, little is known about signals and effectors controlling CdaA activity and c-di-AMP levels. In this study, a genetic screen was employed to identify components which affect the c-di-AMP level in Lactococcus. We characterized suppressor mutations that restored osmoresistance to spontaneous c-di-AMP phosphodiesterase gdpP mutants, which contain high c-di-AMP levels. Loss-of-function and gain-of-function mutations were identified in the cdaA and gdpP genes, respectively, which led to lower c-di-AMP levels. A mutation was also identified in the phosphoglucosamine mutase gene glmM, which is commonly located within the cdaA operon in bacteria. The glmM I154F mutation resulted in a lowering of the c-di-AMP level and a reduction in the key peptidoglycan precursor UDP-N-acetylglucosamine in L. lactis. C-di-AMP synthesis by CdaA was shown to be inhibited by GlmMI154F more than GlmM and GlmMI154F was found to bind more strongly to CdaA than GlmM. These findings identify GlmM as a c-di-AMP level modulating protein and provide a direct connection between c-di-AMP synthesis and peptidoglycan biosynthesis. c-di-AMP is an essential signalling molecule which affects peptidoglycan homeostasis and resistance against various stressors, however little is known regarding how the c-di-AMP level is regulated in the cell. Here we identify the peptidoglycan biosynthesis enzyme GlmM as a modulator of c-di-AMP synthesis through its regulation of diadenylate cyclase enzyme CdaA activity in Lactococcus lactis

Correlated EEMD and effective feature extraction for both periodic and irregular faults diagnosis in rotating machinery

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Intelligent fault diagnosis of complex machinery is crucial for industries to reduce the maintenance cost and to improve fault prediction performance. Acoustic signal is an ideal source for diagnosis because of its inherent characteristics in terms of being non-directional and insensitive to structural resonances. However, there are also two main drawbacks of acoustic signal, one of which is the low signal to noise ratio (SNR) caused by its high sensitivity and the other one is the low computational efficiency caused by the huge data size. These would decrease the performance of the fault diagnosis system. Therefore, it is significant to develop a proper feature extraction method to improve computational efficiency and performance in both periodic and irregular fault diagnosis. To enhance SNR of the acquired acoustic signal, the correlation coefficient (CC) method is employed to eliminate the redundant intrinsic mode functions (IMF), which comes from the decomposition procedure of pre-processing known as ensemble empirical mode decomposition (EEMD), because the higher the correlated coefficient of an IMF is, the more significant fault signatures it would contain, and the redundant IMF would compromise both the SNR and the computational cost performance. Singular value decomposition (SVD) and sample Entropy (SampEn) are subsequently used to extract the fault feature, by exploiting their sensitivities to irregular and periodic fault signals, respectively. In addition, the proposed feature extraction method using sparse Bayesian based pairwise coupled extreme learning machine (PC-SBELM) outperforms the existing pairwise-coupling probabilistic neural network (PC-PNN) and pairwise-coupling relevance vector machine (PC-RVM) by 1.8%and 2%, respectively, to achieve an accuracy of 93.9%. The experiments conducted on the periodic and irregular faults in the gears and bearings have demonstrated that the proposed hybrid fault diagnosis system is effective

Facile Synthesis of High Quality Graphene Nanoribbons

Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Antiproliferative activity of recombinant human interferon-λ2 expressed in stably transformed BmN cells

This study aimed at the generation of a stable transformed silkworm BmN cell line which can continuously express human interferon-λ2 (IFN-λ2) gene, and investigated the antiproliferative activity of this recombinant human IFN-λ2. Silkworm BmN cells were transfected with the recombinant vector pIZT/V5-His harboring the human IFN-λ2 gene. After the BmN cells were transfected with the pIZT/V5- His- hIFN-λ2 vector, the stably transformed BmN cells expressing hIFN-λ2 gene were selected using Zeocin. Following two months of screening, the transformed BmN cell line was obtained. Stable transformed BmN cell line can be maintained at a lower Zeocin concentration. The representing 26 kDa protein band of IFN-λ2 was detected by SDS-PAGE and Western blotting. The expression level of hIFN- λ2, determined by ELISA, was about 8.142 ng in 4 × 105 cells. The antiproliferative activity of hIFN-λ2 was determined by MTT assay. The 50% inhibitory concentrations (IC50) of the recombinant hIFN-λ2 on A549 (lung cancer cells), HL60 (acute promyelocytic leukemia cells), BEL-7402 (liver cancer cells) and M231 cells (breast cancer cells) were approximately 3.21, 2.84, 6.29 and 9.32 ng/ml, respectively. In summary, Human IFN-λ2 can be stably expressed in the transformed BmN cell line, and the expressed recombinant hIFN-λ2 demonstrated antiproliferative activity to tumor cells in vitro.Key words: Human interferon-λ2 protein, gene expression, antiproliferative activity

Experimental studies of e + e -→ some charmless processes containing K S0 at √s = 3.773 and 3.65 GeV

We measure the observed cross sections for the charmless processes e + e -→K S0 K - K - K + π ++ c.c., K S0 K - π + η+c.c., K S0 K - π + π + π - η+c.c., K S0 K - K - K + π + η+c.c., K S0 K - K - K + π + π 0+c.c., K S0 K - ρ ++c.c. and K S0 K - π + ρ 0+c.c. We also extract upper limits on the branching fractions for ψ(3770) decays into these final states at 90% C.L. Analyzed data samples correspond to 17.3 pb-1 and 6.5 pb-1 integrated luminosities registered, respectively, at √s = 3.773 and 3.65 GeV, with the BES-II detector at the BEPC collider. © 2009 Springer-Verlag / Società Italiana di Fisica.published_or_final_versionSpringer Open Choice, 21 Feb 201

Insights into biofilm dispersal regulation from the crystal structure of the PAS-GGDEF-EAL region of RbdA from Pseudomonas aeruginosa

© 2018 American Society for Microbiology. RbdA is a positive regulator of biofilm dispersal of Pseudomonas aeruginosa. Its cytoplasmic region (cRbdA) comprises an N-terminal Per-ARNT-Sim (PAS) domain followed by a diguanylate cyclase (GGDEF) domain and an EAL domain, whose phosphodiesterase activity is allosterically stimulated by GTP binding to the GGDEF domain. We report crystal structures of cRbdA and of two binary complexes: one with GTP/Mg 2+ bound to the GGDEF active site and one with the EAL domain bound to the c-di-GMP substrate. These structures unveil a 2-fold symmetric dimer stabilized by a closely packed N-terminal PAS domain and a noncanonical EAL dimer. The autoinhibitory switch is formed by an α-helix (S-helix) immediately N-terminal to the GGDEF domain that interacts with the EAL dimerization helix (α6-E) of the other EAL monomer and maintains the protein in a locked conformation. We propose that local conformational changes in cRbdA upon GTP binding lead to a structure with the PAS domain and S-helix shifted away from the GGDEF-EAL domains, as suggested by small-angle X-ray scattering (SAXS) experiments. Domain reorientation should be facilitated by the presence of an α-helical lever (H-helix) that tethers the GGDEF and EAL regions, allowing the EAL domain to rearrange into an active dimeric conformation

Search for ψ(3770)→ charmless final states involving η or π0 mesons

We search for ψ(3770) → π+π-η, K+K-η, pp̄η, ρ0π+π-η, K+K-π+π-η, pp̄π+π-η, pp̄K+K-η and pp̄K+K- π0 using data samples of 17.3 and 6.5 pb-1 integrated luminosities recorded at the center-of-mass energies of 3.773 and 3.65 GeV, respectively, by the BES-II detector operating at the BEPC collider. We obtain cross section measurements at both energies and upper limits on ψ(3770) decay branching fractions to the final states studied. © © Springer-Verlag / Società Italiana di Fisica 2010.published_or_final_versionSpringer Open Choice, 21 Feb 201

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women

Xin-Yu Liang,1,&ast; Li-yuan Mu,1,&ast; Lei Hu,2,&ast; Rui-ling She,1,&ast; Chen-yu Ma,1,&ast; Jun-han Feng,1,&ast; Zhi-yu Jiang,1 Zhao-xing Li,1 Xiu-quan Qu,1 Bai-qing Peng,1 Kai-nan Wu,1 Ling-quan Kong1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Information Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling-quan Kong, Department of Breast and Thyroid Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +8613101380893, Email [email protected]: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies.Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening.Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P< 0.001, 95% CI, 0.867– 0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P< 0.001, 95% CI, 0.632– 0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%).Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.Keywords: breast cancer, diabetes, HbA1c, prediabete