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排序方式: 共有273条查询结果,搜索用时 46 毫秒
171.
MN Khan SK Sharma LM Filkins ME Pichichero 《Microbes and infection / Institut Pasteur》2012,14(12):1102-1110
Streptococcus pneumoniae (pneumococci) adhere to human nasopharyngeal (NP) epithelial cells as a first step in colonization and adherence of pneumococci to lung epithelia may be required to establish pneumonia. We sought to determine if PcpA can serve as an adhesin to human NP (D562) and lung (A549) epithelial cells and whether PcpA mediated adherence can be inhibited by human anti-PcpA antibodies. A PcpA isogenic mutant was constructed in a pneumococcal TIGR4 background. When the mutant and wild type strains were compared for their adherence to D562 and A549 cell lines, a reduction in adherence by the mutant was observed (p = 0.0001 for both cell types). PcpA was ectopically expressed on the surface of minimally-adherent heterologous host Escherichia coli resulting in augmented adherence to D562 (p = 0.002) and A549 (p = 0.015) cells. Total IgG was purified from a pool of 6 human sera having high IgG titers of anti-pneumococcal proteins. The purified IgG reduced TIGR4 adherence to D562 cells but we determined that this effect was largely due to bacterial cell aggregation as determined by flow cytometry and confocal microscopy. Fab fragments were prepared from pooled IgG sera. Inhibition of TIGR4 adherence to D562 cells was observed using the Fab fragments without causing bacterial aggregation (p = 0.0001). Depletion of PcpA-specific Fab fragments resulted in an increase in adherence of TIGR4 to D562 cells (p = 0.028). We conclude that PcpA can mediate adherence of pneumococci to human NP and lung epithelial cells and PcpA mediated adherence can be inhibited by human anti-PcpA antibodies. 相似文献
172.
Parmar JH Bhartiya S Venkatesh KV 《Journal of industrial microbiology & biotechnology》2012,39(6):927-941
Yeast metabolism under hyperosmotic stress conditions was quantified using elementary mode analysis to obtain insights into the metabolic status of the cell. The fluxes of elementary modes were determined as solutions to a linear program that used the stoichiometry of the elementary modes as constraints. The analysis demonstrated that distinctly different sets of elementary modes operate under normal and hyperosmotic conditions. During the adaptation phase, elementary modes that only produce glycerol are active, while elementary modes that yield biomass, ethanol, and glycerol become active after the adaptive phase. The flux distribution in the metabolic network, calculated using the fluxes in the elementary modes, was employed to obtain the flux ratio at key nodes. At the glucose 6-phosphate (G6P) node, 25% of the carbon influx was diverted towards the pentose phosphate pathway under normal growth conditions, while only 0.3% of the carbon flux was diverted towards the pentose phosphate pathway during growth at 1?M NaCl, indicating that cell growth is arrested under hyperosmotic conditions. Further, objective functions were used in the linear program to obtain optimal solution spaces corresponding to the different accumulation rates. The analysis demonstrated that while biomass formation was optimal under normal growth conditions, glycerol synthesis was closer to optimal during adaptation to osmotic shock. 相似文献
173.
Maninder Minu Ananda Thangadurai Sharad Ramesh Wakode Shyam Sundar Agrawal Balasubramanian Narasimhan 《Bioorganic & medicinal chemistry letters》2009,19(11):2960-2964
Antimicrobial activity of synthesized 2,3-disubstituted-3,3a,4,5,6,7-hexahydro-2H-indazole derivatives indicated that 3-(4-chlorophenyl)-2-(4-nitrophenylsulfonyl)-3,3a,4,5,6,7-hexahydro-2H-indazole (6) and 3-(4-fluorophenyl)-2-(4-nitrophenylsulfonyl)-3,3a,4,5,6,7-hexahydro-2H-indazole (20) were the most active compounds. Further, the results of QSAR studies indicated the importance of topological parameters 2χ and 2χv in defining the antimicrobial activity of hexahydroindazoles. 相似文献
174.
Xiaoyun Zhu Donald Young Brian J. Watson Zhikui Wang Jerry Rolia Sharad Singhal Bret McKee Chris Hyser Daniel Gmach Robert Gardner Tom Christian Ludmila Cherkasova 《Cluster computing》2009,12(1):45-57
Recent advances in hardware and software virtualization offer unprecedented management capabilities for the mapping of virtual
resources to physical resources. It is highly desirable to further create a “service hosting abstraction” that allows application
owners to focus on service level objectives (SLOs) for their applications. This calls for a resource management solution that
achieves the SLOs for many applications in response to changing data center conditions and hides the complexity from both
application owners and data center operators. In this paper, we describe an automated capacity and workload management system
that integrates multiple resource controllers at three different scopes and time scales. Simulation and experimental results
confirm that such an integrated solution ensures efficient and effective use of data center resources while reducing service
level violations for high priority applications.
相似文献
Ludmila CherkasovaEmail: |
175.
In search for novel antidepressants, a series of 2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylthio)-N-(substituted phenyl)acetamides was synthesized and screened for potential antidepressant activity by tail suspension test (TST) in mice. Number of synthesized compounds exhibited impressive antidepressant activity, measured in terms of percentage decrease in immobility duration (%DID). QSAR analysis was also undertaken which correlated three parameters FOSA, PISA, and glob with biological activity. 相似文献
176.
Hong Lin Dennis S. Yamashita Jin Zeng Ren Xie Sharad Verma Juan I. Luengo Nelson Rhodes Shuyun Zhang Kimberly A. Robell Anthony E. Choudhry Zhihong Lai Rakesh Kumar Elisabeth A. Minthorn Kristin K. Brown Dirk A. Heerding 《Bioorganic & medicinal chemistry letters》2010,20(2):679-683
A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3β phosphorylation in a BT474 tumor xenograft model in mice. 相似文献
177.
Lei Wang Sharad C.Paudyal Yuchen Kang Mikito Owa Feng-Xia Liang Alexander Spektor Holger Knaut Irma Sánchez Brian D.Dynlacht 《Cell research》2022,(2):190-209
Cytoskeletal networks play an important role in regulating nuclear morphology and ciliogenesis.However,the role of microtubule (MT) post-translational modificat... 相似文献
178.
Adekar SP Takahashi T Jones RM Al-Saleem FH Ancharski DM Root MJ Kapadnis BP Simpson LL Dessain SK 《PloS one》2008,3(8):e3023
Background
Botulinum neurotoxins (BoNT) are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC), a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.Methods and Findings
We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A). The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro.Conclusions
An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components of an antibody antidote for BoNT exposure. 相似文献179.
Microsomal cytochrome P450 family 1 enzymes has great importance in the bioactivation of mutagens. P450 catalyzed reactions
involve a wide range of substrates, and this versatality is reflected in a structural diversity, evident in the active sites
of available P450 structures. This structure offers a template to study further structure-function relationships of alternative
substrates and other cytochrome P450 family 1 members. In this paper, we document a homology model of CYP P450 1A1 from Homo
sapiens, developed on the basis of template crystal structure of human microsomal P450 1a2 in complex with inhibitor (PDB
Id: 2HI4). Homology modeling is performed at the programs, both in the commercial and public realms. We tried to explore CYP1A1
as a potential target for anticancer chemotherapy. To gain an insight into the binding of ligands with enzyme, protein-ligand
complex was developed by including information about the known ligand as spatial restraints and optimizing the mutual interactions
between the ligand and the binding site. Active site characterization and the study for involvement of specific aminoacids
in binding with ligand, facilitates structure based inhibitor design. This study should prove useful in the design and development
of potential novel anticancer agents.
Figure The refined structure of homology model of CYP1A1 相似文献
180.
Rastogi S Imai M Sharov VG Mishra S Sabbah HN 《American journal of physiology. Heart and circulatory physiology》2008,295(6):H2475-H2482
In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-alpha (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) approximately 25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 microg/kg, n=7) or to no therapy (HF, n=7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1alpha, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1alpha and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia. 相似文献