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61.
Phuti E. Makgotlho Gabriella Marincola Daniel Sch?fer Qian Liu Taeok Bae Tobias Geiger Elizabeth Wasserman Christiane Wolz Wilma Ziebuhr Bhanu Sinha 《PloS one》2013,8(8)
The Staphylococcus aureus regulatory saePQRS system controls the expression of numerous virulence factors, including extracellular adherence protein (Eap), which amongst others facilitates invasion of host cells. The saePQRS operon codes for 4 proteins: the histidine kinase SaeS, the response regulator SaeR, the lipoprotein SaeP and the transmembrane protein SaeQ. S. aureus strain Newman has a single amino acid substitution in the transmembrane domain of SaeS (L18P) which results in constitutive kinase activity. SDS was shown to be one of the signals interfering with SaeS activity leading to inhibition of the sae target gene eap in strains with SaeSL but causing activation in strains containing SaeSP. Here, we analyzed the possible involvement of the SaeP protein and saePQ region in SDS-mediated sae/eap expression. We found that SaePQ is not needed for SDS-mediated SaeS signaling. Furthermore, we could show that SaeS activity is closely linked to the expression of Eap and the capacity to invade host cells in a number of clinical isolates. This suggests that SaeS activity might be directly modulated by structurally non-complex environmental signals, as SDS, which possibly altering its kinase/phosphatase activity. 相似文献
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63.
Jihye Han Joonbeom Bae Chang-Yong Choi Sang-Pil Choi Hyung-Sik Kang Eun-Kyeong Jo 《Autophagy》2016,12(12):2326-2343
Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl?/? mice show more severe symptoms than do wild-type (Axl+/+) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation. 相似文献
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Tapan Kumar Mohanta Nibedita Mohanta Pratap Parida Sujogya Kumar Panda Lakshmi Narayanan Ponpandian Hanhong Bae 《PloS one》2016,11(2)
The mitogen-activated protein kinase (MAPK) is characterized by the presence of the T-E-Y, T-D-Y, and T-G-Y motifs in its activation loop region and plays a significant role in regulating diverse cellular responses in eukaryotic organisms. Availability of large-scale genome data in the fungal kingdom encouraged us to identify and analyse the fungal MAPK gene family consisting of 173 fungal species. The analysis of the MAPK gene family resulted in the discovery of several novel activation loop motifs (T-T-Y, T-I-Y, T-N-Y, T-H-Y, T-S-Y, K-G-Y, T-Q-Y, S-E-Y and S-D-Y) in fungal MAPKs. The phylogenetic analysis suggests that fungal MAPKs are non-polymorphic, had evolved from their common ancestors around 1500 million years ago, and are distantly related to plant MAPKs. We are the first to report the presence of nine novel activation loop motifs in fungal MAPKs. The specificity of the activation loop motif plays a significant role in controlling different growth and stress related pathways in fungi. Hence, the presences of these nine novel activation loop motifs in fungi are of special interest. 相似文献
66.
Propelled by the increasing availability of large-scale high-quality data, advanced data modeling and analysis techniques are enabling many novel and significant scientific understanding of a wide range of complex social, natural, and technological systems. These developments also provide opportunities for studying cultural systems and phenomena—which can be said to refer to all products of human creativity and way of life. An important characteristic of a cultural product is that it does not exist in isolation from others, but forms an intricate web of connections on many levels. In the creation and dissemination of cultural products and artworks in particular, collaboration and communication of ideas play an essential role, which can be captured in the heterogeneous network of the creators and practitioners of art. In this paper we propose novel methods to analyze and uncover meaningful patterns from such a network using the network of western classical musicians constructed from a large-scale comprehensive Compact Disc recordings data. We characterize the complex patterns in the network landscape of collaboration between musicians across multiple scales ranging from the macroscopic to the mesoscopic and microscopic that represent the diversity of cultural styles and the individuality of the artists. 相似文献
67.
PIEZO1 is a mechanosensitive eukaryotic cation-selective channel that rapidly inactivates in a voltage-dependent manner. We previously showed that a fluorescent protein could be encoded within the hPIEZO1 sequence without loss of function. In this work, we split the channel into two at this site and asked if coexpression would produce a functional channel or whether gating and permeation might be contained in either segment. The split protein was expressed in two segments by a bicistronic plasmid where the first segment spanned residues 1 to 1591, and the second segment spanned 1592 to 2521. When the “split protein” is coexpressed, the parts associate to form a normal channel. We measured the whole-cell, cell-attached and outside-out patch currents in transfected HEK293 cells. Indentation produced whole-cell currents monotonic with the stimulus. Single channel recordings showed voltage-dependent inactivation. The Boltzmann activation curve for outside-out patches had a slope of 8.6/mmHg vs 8.1 for wild type, and a small leftward shift in the midpoint (32 mmHg vs 41 mmHg). The association of the two channel domains was confirmed by FRET measurements of mCherry on the N-terminus and EGFP on the C-terminus. Neither of the individual protein segments produced current when expressed alone. 相似文献
68.
Daniel C. Ilut Alexander E. Lipka Namhee Jeong Dong Nyuk Bae Dong Hyun Kim Ji Hong Kim Neelam Redekar Kiwoung Yang Won Park Sung-Taeg Kang Namshin Kim Jung-Kyung Moon M. A. Saghai Maroof Michael A. Gore Soon-Chun Jeong 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2016,129(3):453-468
69.
Jong Bae Seo Seung-Ryoung Jung Bertil Hille Duk-Su Koh 《Cell biology and toxicology》2016,32(3):229-247
Extracellular adenosine-5′-triphosphate (ATP) regulates cell death and survival of neighboring cells. The detailed effects are diverse depending on cell types and extracellular ATP concentration. We addressed the effect of ATP on ethanol-induced cytotoxicity in epithelial cells, the cell type that experiences the highest concentrations of alcohol. Using pancreatic duct epithelial cells (PDEC), we found that a micromolar range of ATP reverses all intracellular toxicity mechanisms triggered by exceptionally high doses of ethanol and, thus, improves cell viability dramatically. Out of the many purinergic receptors expressed in PDEC, the P2Y1 receptor was identified to mediate the protective effect, based on pharmacological and siRNA assays. Activation of P2Y1 receptors increased intracellular cyclic adenosine monophosphate (cAMP). The protective effect of ATP was mimicked by forskolin and 8-Br-cAMP but inhibited by a protein kinase A (PKA) inhibitor, H-89. Finally, ATP reverted leakiness of PDEC monolayers induced by ethanol and helped to maintain epithelial integrity. We suggest that purinergic receptors reduce extreme alcohol-induced cell damage via the cAMP signal pathway in PDEC and some other types of cells. 相似文献
70.
随着全球建造业向数字化全面转型,建筑信息模型(BIM)的教学将是未来几年风景园林设计与实施的重要主题。介绍了风景园林专业BIM的教学方法和数字化竖向设计及其应用在BIM场地设计项目中的重要性。数字化竖向设计是实现BIM的途径。风景园林教育必须在其教学中讲解BIM建模方法和过程。 相似文献