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201.
Nan Zhang Semiramis Ayral-Kaloustian Thai Nguyen Richard Hernandez Judy Lucas Carolyn Discafani Carl Beyer 《Bioorganic & medicinal chemistry》2009,17(1):111-118
The synthesis and SAR of a series of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents are described. This series of 2-heteroarylpyrimidines was developed by modifying a series of anti-tumor [1,2,4]triazolo[1,5-a]pyrimidines and 2-cyanoaminopyrimidines we reported earlier. For the 2-heteroaryl group, the best activity is obtained when the heteroaryl group has a nitrogen atom at the ortho-position to the pyrimidyl core. The structure–activity relationship for the rest of the molecule in this 2-heteroarylpyrimidine series mimics that of the [1,2,4]triazolo[1,5-a]pyrimidine series. Like triazolopyrimidines and 2-cyanoaminopyrimidines, the 2-heteroarylpyrimidines retain the capability to overcome multidrug resistance due to Pgp. Mechanism of action studies showed that the lead compounds behaved in the same manner as triazolopyrimidines and 2-cyanoaminopyrimidines. The lead compounds in this series are more potent than the corresponding triazolopyrimidines in vitro and in vivo. Compound 21 (PTI-868) showed tumor growth inhibition in several nude mouse xenograft models, and was selected to advance to preclinical development. 相似文献
202.
Thai Nho Dinh Keisuke Nagahisa Katsunori Yoshikawa Takashi Hirasawa Chikara Furusawa Hiroshi Shimizu 《Bioprocess and biosystems engineering》2009,32(5):681-688
In industrial process, yeast cells are exposed to ethanol stress that affects the cell growth and the productivity. Thus,
investigating the intracellular state of yeast cells under high ethanol concentration is important. In this study, using DNA
microarray analysis, we performed comprehensive expression profiling of two strains of Saccharomyces cerevisiae, i.e., the ethanol-adapted strain that shows active growth under the ethanol stress condition and its parental strain used
as the control. By comparing the expression profiles of these two strains under the ethanol stress condition, we found that
the genes related to ribosomal proteins were highly up-regulated in the ethanol-adapted strain. Further, genes related to
ATP synthesis in mitochondria were suggested to be important for growth under ethanol stress. We expect that the results will
provide a better understanding of ethanol tolerance of yeast.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
203.
Luu Thai Danh Paul Truong Raffaella Mammucari Tam Tran Neil Foster 《International journal of phytoremediation》2009,11(8):664-691
Glasshouse and field studies showed that Vetiver grass can produce high biomass (>100t/tha?1 year?1) and highly tolerate extreme climatic variation such as prolonged drought, flood, submergence and temperatures (?15°–55°C), soils high in acidity and alkalinity (pH 3.3–9.5), high levels of Al (85% saturation percentage), Mn (578 mg kg?1), soil salinity (ECse 47.5 dS m?1), sodicity (ESP 48%), and a wide range of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, Se, and Zn). Vetiver can accumulate heavy metals, particularly lead (shoot 0.4% and root 1%) and zinc (shoot and root 1%). The majority of heavy metals are accumulated in roots thus suitable for phytostabilization, and for phytoextraction with addition of chelating agents. Vetiver can also absorb and promote biodegradation of organic wastes (2,4,6-trinitroluene, phenol, ethidium bromide, benzo[a]pyrene, atrazine). Although Vetiver is not as effective as some other species in heavy metal accumulation, very few plants in the literature have a wide range of tolerance to extremely adverse conditions of climate and growing medium (soil, sand, and tailings) combined into one plant as vetiver. All these special characteristics make vetiver a choice plant for phytoremediation of heavy metals and organic wastes. 相似文献
204.
Nguyen TX Yen MR Barabote RD Saier MH 《Journal of molecular microbiology and biotechnology》2006,11(6):345-360
We report bioinformatic analyses of the largest superfamily of integral membrane permeases of the bacterial phosphotransferase system (PTS), the Enzyme IIC constituents of the Glc superfamily. Phylogenetic analyses reveal that this superfamily consists of five equally distant families, the Glucose (Glc), beta-Glucoside (Bgl), Fructose (Fru), Mannitol (Mtl) and Lactose (Lac) families. Average hydropathy, amphipathicity and similarity plots were generated for these five families as well as for the entire superfamily. Charged residue distribution was analyzed, and the most conserved sequence motif, common to all five families, was identified. The results show that the members of all five families exhibit similar average hydropathy plots with regions of average amphipathicity and relative conservation also being similar. Evidence is presented suggesting that the Glucitol (Gut) family of Enzyme IIC constituents is a distant member of the Glc superfamily. Based on our analyses we offer a topological model that resembles, but differs in detail from the two previously proposed models. 相似文献
205.
Nguyen TX Alegre ER Kelley ST 《Journal of molecular microbiology and biotechnology》2006,11(6):291-301
Bacterial porin proteins allow for the selective movement of hydrophilic solutes through the outer membrane of Gram-negative bacteria. The purpose of this study was to clarify the evolutionary relationships among the Type 1 general bacterial porins (GBPs), a porin protein subfamily that includes outer membrane proteins ompC and ompF among others. Specifically, we investigated the potential utility of phylogenetic analysis for refining poorly annotated or mis-annotated protein sequences in databases, and for characterizing new functionally distinct groups of porin proteins. Preliminary phylogenetic analysis of sequences obtained from GenBank indicated that many of these sequences were incompletely or even incorrectly annotated. Using a well-curated set of porins classified via comparative genomics, we applied recently developed bayesian phylogenetic methods for protein sequence analysis to determine the relationships among the Type 1 GBPs. Our analysis found that the major GBP classes (ompC, phoE, nmpC and ompN) formed strongly supported monophyletic groups, with the exception of ompF, which split into two distinct clades. The relationships of the GBP groups to one another had less statistical support, except for the relationships of ompC and ompN sequences, which were strongly supported as sister groups. A phylogenetic analysis comparing the relationships of the GenBank GBP sequences to the correctly annotated set of GBPs identified a large number of previously unclassified and mis-annotated GBPs. Given these promising results, we developed a tree-parsing algorithm for automated phylogenetic annotation and tested it with GenBank sequences. Our algorithm was able to automatically classify 30 unidentified and 15 mis-annotated GBPs out of 78 sequences. Altogether, our results support the potential for phylogenomics to increase the accuracy of sequence annotations. 相似文献
206.
207.
Ted D. Center Paul D. Pratt Philip W. Tipping Min B. Rayamajhi Thai K. Van Susan A. Wineriter F. Allen Dray Jr. Matthew Purcell 《Biological Control》2006,39(3):363-374
Invasion of native plant communities by the Australian paperbark tree (“melaleuca”), Melaleuca quinquenervia, complicates restoration of the Florida Everglades. Biological control, within the context of a comprehensive management program, offers a means to suppress regeneration of melaleuca after removal of existing trees and a mechanism to forestall reinvasion. To meet this need, a biological control program commenced in 1997 upon the release of an Australian weevil (Oxyops vitiosa [Pascoe] [Coleoptera: Curculionidae]). Release of a second biological control agent, the melaleuca psyllid (Boreioglycaspis melaleucae Moore), followed in February 2002 at field sites containing mixed age-class melaleuca stands or coppicing stumps. Each site was inoculated with 7000–10,000 adult psyllids, with one exception where 2000 nymphs were released on seedlings the following December. Psyllid populations established everywhere irrespective of colony source, site conditions, or the quantity released, although numbers released and, to a lesser degree, colony age influenced the numbers of colonies produced. Quantity included in the release was the major determinant of the resultant number of colonies, although the duration of their tenure in quarantine culture may have also influenced this. One site, comprised mainly of coppicing stumps, contained 3.3 million psyllids per ha within 3 months after release. Less than 1% of the coppices at a similar site harbored psyllid colonies 2 months after release (May 2002), but this rose to 75% in October then to 100% by December. The census population exceeded 715,000 adults and nearly 11 million nymphs by late January 2003. Psyllid populations dispersed 2.2–10.0 km/year, with the slower rates in dense, continuous melaleuca stands and faster rates in fragmented stands. Over 1 million psyllids had been redistributed to 100 locations as of December 2005. This species now occurs throughout much of the range of melaleuca in south Florida due to natural range expansion as well as anthropogenic dissemination. 相似文献
208.
Jinghe Huang Patrick Burke Yue Yang Katherine Seiss Jill Beamon Thai Cung Ildiko Toth Florencia Pereyra Mathias Lichterfeld Xu G. Yu 《Journal of virology》2010,84(20):10784-10791
Dendritic cells represent a specialized class of professional antigen-presenting cells that are responsible for priming and maintaining antigen-specific effector cell responses and regulating immune activation by cytokine secretion. In HIV-1 infection, myeloid dendritic cells are highly dysfunctional, but mechanisms contributing to their functional alterations are not well defined. Here, we show that soluble molecules of the nonclassical major histocompatibility complex class Ib (MHC-Ib) antigen HLA-G are highly upregulated in the plasma during progressive HIV-1 infection, while levels of membrane-bound HLA-G surface expression on dendritic cells, monocytes, and T cells only slightly differ among HIV-1 progressors, HIV-1 elite controllers, and HIV-1-negative persons. These elevated levels of soluble HLA-G in progressive HIV-1 infection likely result from increased secretion of intracellularly stored HLA-G molecules in monocytes and dendritic cells and contribute to a functional disarray of dendritic cells by inhibiting their antigen-presenting properties, while simultaneously enhancing their secretion of proinflammatory cytokines. Interestingly, we observed that these immunoregulatory effects of soluble HLA-G were mainly mediated by interactions with the myelomonocytic HLA class I receptor leukocyte immunoglobulin-like receptor B2 (LILRB2; ILT4), while binding of soluble HLA-G to its alternative high-affinity receptor, LILRB1 (ILT2), appeared to be less relevant for its immunomodulatory functions on dendritic cells. Overall, these results demonstrate a critical role for soluble HLA-G in modulating the functional characteristics of professional antigen-presenting cells in progressive HIV-1 infection and suggest that soluble HLA-G might represent a possible target for immunotherapeutic interventions in HIV-1-infected persons.The hallmark of HIV-1-associated immune deficiency is a progressive decline of T-cell immunity; however, HIV-1 infection also involves dysfunction of multiple other components of the innate and adaptive immune systems, including B cells (25, 28), NK cells (22), and NK T (NKT) cells (30). Perhaps most importantly, HIV-1 infection leads to functional deficiencies of myeloid dendritic cells (mDC) (2, 8, 10), which as professional antigen-presenting cells have critical roles in priming and maintaining adaptive and innate effector cell responses and in regulating immune activation (4). In progressive HIV-1 infection, myeloid dendritic cells show an activated phenotype, with upregulation of costimulatory molecules and maturation markers (2, 6), but their functional antigen-presenting properties are poor (7), which may be responsible for the dysfunctional properties of antigen-specific T- and B-cell responses during HIV-1 infection. In addition, mDC in progressive HIV-1 infection seem to secrete higher levels of proinflammatory cytokines (2) and by this mechanism may contribute to generalized activation and exhaustion of the immune system, two events that play important roles in the pathogenesis of HIV-1 infection (9). The molecular pathways that contribute to dendritic cell dysfunction in HIV-1 infection, however, are unclear, but their understanding holds promise for a targeted manipulation of dendritic cells for immunotherapeutic interventions.HLA-G represents a nonclassical major histocompatibility complex class Ib (MHC-Ib) antigen, which, in comparison to classical HLA class I molecules, has limited functions for antigen presentation and restriction of T-cell immune responses but important immunoregulatory properties during various infectious, inflammatory, and malignant diseases (5). Unlike expression of classical HLA class I molecules, expression of HLA-G is mostly limited to fetal trophoblastic tissues (15), but ectopic expression of HLA-G on T cells (11), monocytes, and dendritic cells (3) has been documented in a variety of pathological conditions, including HIV-1 infection (16, 19). Moreover, it is well recognized that alternative splicing of HLA-G can lead to soluble isoforms which cause systemic immunoregulatory effects in the absence of localized tissue expression. The highest-affinity receptors for HLA-G include leukocyte immunoglobulin-like receptor B1 (LILRB1; ILT2) and LILRB2 (ILT4), two members of the LILR family, as well as the NK cell receptor KIR2DL4. By interacting with such receptors, HLA-G can induce a variety of immunomodulatory effects, including inhibition of antigen-specific T-cell (17) and NK cell responses (27). How HLA-G changes the functional profile of dendritic cells during chronic viral diseases such as HIV-1 infection remains unknown.In the present study, we analyzed immunomodulatory effects of HLA-G in individuals with different rates of HIV-1 disease progression. Our studies show that soluble HLA-G in the plasma, but not membrane-bound HLA-G expression on leukocytes, is strikingly upregulated during progressive HIV-1 infection. This soluble HLA-G critically contributes to the functional deficiencies of myeloid dendritic cells by interacting with ILT4 (LILRB2), while interactions with its other high-affinity receptor, ILT2, seem to be less relevant. Overall, these data show that binding interactions between ILT4 and soluble HLA-G play a key role in mediating dendritic cell dysfunction in progressive HIV-1 infection and might represent a possible target for immunotherapeutic interventions in HIV-1 infection. 相似文献
209.
Sharma P Tran T Stelmack GL McNeill K Gosens R Mutawe MM Unruh H Gerthoffer WT Halayko AJ 《American journal of physiology. Lung cellular and molecular physiology》2008,294(1):L57-L68
Airway smooth muscle (ASM) cells may contribute to asthma pathogenesis through their capacity to switch between a synthetic/proliferative and a contractile phenotype. The multimeric dystrophin-glycoprotein complex (DGC) spans the sarcolemma, linking the actin cytoskeleton and extracellular matrix. The DGC is expressed in smooth muscle tissue, but its functional role is not fully established. We tested whether contractile phenotype maturation of human ASM is associated with accumulation of DGC proteins. We compared subconfluent, serum-fed cultures and confluent cultures subjected to serum deprivation, which express a contractile phenotype. Western blotting confirmed that beta-dystroglycan, beta-, delta-, and epsilon-sarcoglycan, and dystrophin abundance increased six- to eightfold in association with smooth muscle myosin heavy chain (smMHC) and calponin accumulation during 4-day serum deprivation. Immunocytochemistry showed that the accumulation of DGC subunits was specifically localized to a subset of cells that exhibit robust staining for smMHC. Laminin competing peptide (YIGSR, 1 microM) and phosphatidylinositol 3-kinase (PI3K) inhibitors (20 microM LY-294002 or 100 nM wortmannin) abrogated the accumulation of smMHC, calponin, and DGC proteins. These studies demonstrate that the accumulation of DGC is an integral feature for phenotype maturation of human ASM cells. This provides a strong rationale for future studies investigating the role of the DGC in ASM smooth muscle physiology in health and disease. 相似文献
210.