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31.
Rohit Surana Sakshi Sikka Wanpei Cai Eun Myoung Shin Sudha R. Warrier Hong Jie Gabriel Tan Frank Arfuso Simon A. Fox Arun M. Dharmarajan Alan Prem Kumar 《生物化学与生物物理学报:癌评论》2014
The Wnt (wingless-type) signaling pathway plays an important role in embryonic development, tissue homeostasis, and tumor progression becaluse of its effect on cell proliferation, migration, and differentiation. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by binding directly to Wnt ligands or to Frizzled receptors. In recent years, aberrant expression of SFRPs has been reported to be associated with numerous cancers. As gene expression of SFRP members is often lost through promoter hypermethylation, inhibition of methylation through the use of epigenetic modifying agents could renew the expression of SFRP members and further antagonize deleterious Wnt signaling. Several reports have described epigenetic silencing of these Wnt signaling antagonists in various human cancers, suggesting their possible role as tumor suppressors. SFRP family members thus come across as potential tools in combating Wnt-driven tumorigenesis. However, little is known about SFRP family members and their role in different cancers. This review comprehensively covers all the available information on the role of SFRP molecules in various human cancers. 相似文献
32.
Sunaina Zutshi Meenakshi Choudhary Naveen Bharat Malik Zainul Abdin Tasneem Fatma 《Journal of phycology》2008,44(4):889-896
Lead (Pb) is a heavy metal and a potentially hazardous environmental pollutant. In this study, the potential of lead to induce oxidative stress in biological systems was assessed using the cyanobacterium Hapalosiphon fontinalis‐339 as model test organism. The impact of lead toxicity on the cellular antioxidant system and the biochemical modulations that result in generation of antioxidant defense responses were also studied. To determine the effect of Pb toxicity, the test organism was grown in the presence of various concentrations (0.05, 0.10, 0.20, 0.40, 0.80, 1.0, 1.20, and 1.25 mg · L?1) of exogenous lead chloride (PbCl2), and its effects on growth were observed in terms of the change in chl content. There was a significant increase in metal uptake by the alga with a concomitant decrease in growth. Lead stress appeared to significantly up‐regulate the levels of stress‐related antioxidant enzymes—such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR)—while a decrease in catalase (CAT) levels was observed. In addition, the levels of nonenzymatic antioxidants, oxidized and total glutathione, were changed. Our results suggest the existence of a potent antioxidant defense machinery in H. fontinalis‐339 and this organism can be employed to monitor lead toxicity in the environment. 相似文献
33.
Priyanka Pandya Surendra Gattani Pankaj Jain Lokesh Khirwal Sanjay Surana 《AAPS PharmSciTech》2008,9(4):1247-1252
A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility,
dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility
and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer
hydroxypropyl methylcellulose (HPMC K3LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of
HPMC K3LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state
was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy,
and Fourier-transform infrared spectroscopy. In vitro–in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of
the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased
in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol
and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug
and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces
amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM. 相似文献
34.
In the budding yeast Saccharomyces cerevisiae, the DNA damage-induced G2 arrest requires the checkpoint control genes RAD9, RAD17, RAD24, MEC1, MEC2 and MEC3. These genes also prevent entry into mitosis of a temperature-sensitive mutant, cdc13, that accumulates chromosome damage at 37°?C. Here we show that a cdc13 mutant overexpressing Cdc20, a β-transducin homologue, no longer arrests in G2 at the restrictive temperature but instead undergoes nuclear division, exits mitosis and enters a subsequent division cycle, which suggests that the DNA damage-induced G2/M checkpoint control is not functional in these cells. This is consistent with our observation that overexpression of CDC20 in wild-type cells results in increased sensitivity to UV irradiation. Overproduction of Cdc20 does not influence the arrest phenotype of the cdc mutants whose cell cycle block is independent of RAD9-mediated checkpoint control. Therefore, we suggest that the DNA damage-induced checkpoint controls prevent mitosis by inhibiting the nuclear division pathway requiring CDC20 function. 相似文献
35.
Cdc42, a member of the Rho subfamily of small GTPases, is highly conserved in both sequence and function across eukaryotic species. In budding yeast, Cdc42 triggers polarized growth necessary for bud emergence via rearrangement of the actin cytoskeleton. It has been shown that the role of Cdc42 in bud emergence requires both Cdc28-Cln (G1) kinase and the passage through START. In this report, we show that Cdc42 also serves an essential function in the establishment of bud site prior to START by catalyzing the translocation of bud-site components such as Spa2 to the cell cortex. Our analysis of various conditional alleles of CDC42 suggests that these two functions (bud site establishment and bud emergence) are genetically separable. Surprisingly, the role of Cdc42 in the cortical localization of Spa2 appears to be independent of its well known GTP/GDP exchange factor Cdc24. We also provide evidence that this role of Cdc42 requires the function of the COPI coatomer complex. 相似文献
36.
Light‐Induced Degradation of Perovskite Solar Cells: The Influence of 4‐Tert‐Butyl Pyridine and Gold
João P. Bastos Ulrich W. Paetzold Robert Gehlhaar Weiming Qiu David Cheyns Supriya Surana Valentina Spampinato Tom Aernouts Jef Poortmans 《Liver Transplantation》2018,8(23)
Stability is one of the key challenges for industrial scale commercialization of perovskite solar cells. In this work, a degradation mechanism that depends on materials and bias conditions of the device during light‐soaking is proposed. The observed degradation is linked to the additive 4‐tert‐butyl pyridine (tBP), crucial to the hole transport layer of most perovskite solar cells, and gold. This conclusion is reached through the statistical analysis of multiple compositional profiles of light‐soaked and nonlight‐soaked devices and by selective replacement of material layers of the device. Moreover, the rate of the light‐induced degradation is enhanced by operation at forward bias, which is required for power generation. Thus, this work stresses the need for the development of transport layers that do not require tBP, and to replace gold to produce high‐performing devices that are also stable under operating conditions. 相似文献
37.
Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28.
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In eukaryotes, mitosis requires the activation of cdc2 kinase via association with cyclin B and dephosphorylation of the threonine 14 and tyrosine 15 residues. It is known that in the budding yeast Saccharomyces cerevisiae, a homologous kinase, Cdc28, mediates the progression through M phase, but it is not clear what specific mitotic function its activation by the dephosphorylation of an equivalent tyrosine (Tyr-19) serves. We report here that cells expressing cdc28-E19 (in which Tyr-19 is replaced by glutamic acid) perform Start-related functions, complete DNA synthesis, and exhibit high levels of Clb2-associated kinase activity but are unable to form bipolar spindles. The failure of these cells to form mitotic spindles is due to their inability to segregate duplicated spindle pole bodies (SPBs), a phenotype strikingly similar to that exhibited by a previously reported mutant defective in both kinesin-like motor proteins Cin8 and Kip1. We also find that the overexpression of SWE1, the budding-yeast homolog of wee1, also leads to a failure to segregate SPBs. These results imply that dephosphorylation of Tyr-19 is required for the segregation of SPBs. The requirement of Tyr-19 dephosphorylation for spindle assembly is also observed under conditions in which spindle formation is independent of mitosis, suggesting that the involvement of Cdc28/Clb kinase in SPB separation is direct. On the basis of these results, we propose that one of the roles of Tyr-19 dephosphorylation is to promote SPB separation. 相似文献
38.
Dephosphorylation of threonine 169 of Cdc28 is not required for exit from mitosis but may be necessary for start in Saccharomyces cerevisiae. 总被引:2,自引:0,他引:2
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Entry into mitosis requires activation of cdc2 kinase brought on by its association with cyclin B, phosphorylation of the conserved threonine (Thr-167 in Schizosaccharomyces pombe) in the T loop, and dephosphorylation of the tyrosine residue at position 15. Exit from mitosis, on the other hand, is induced by inactivation of cdc2 activity via cyclin destruction. It has been suggested that in addition to cyclin degradation, dephosphorylation of Thr-167 may also be required for exit from the M phase. Here we show that Saccharomyces cerevisiae cells expressing cdc28-E169 (a CDC28 allele in which the equivalent threonine, Thr-169, has been replaced by glutamic acid) are able to degrade mitotic cyclin Clb2, inactivate the Cdc28/Clb2 kinase, and disassemble the anaphase spindles, suggesting that they exit mitosis normally. The cdc28-E169 allele is active with respect to its mitotic functions, since it complements the mitosis-defective cdc28-1N allele. Whereas replacement of Thr-169 with serine affects neither Start nor the mitotic activity of Cdc28, replacement with glutamic acid or alanine renders Cdc28 inactive for Start-related functions. Coimmunoprecipitation experiments show that although Cdc28-E169 associates with mitotic cyclin Clb2, it fails to associate with the G1 cyclin Cln2. Thus, an unmodified threonine at position 169 in Cdc28 is important for interaction with G1 cyclins. We propose that in S. cerevisiae, dephosphorylation of Thr-169 is not required for exit from mitosis but may be necessary for commitment to the subsequent division cycle. 相似文献
39.
Flaviviral RNA-dependent RNA polymerases (RdRps) initiate replication of the single-stranded RNA genome in the absence of a primer. The template sequence 5′-CU-3′ at the 3′-end of the flaviviral genome is highly conserved. Surprisingly, flaviviral RdRps require high concentrations of the second incoming nucleotide GTP to catalyze de novo template-dependent RNA synthesis. We show that GTP stimulates de novo RNA synthesis by RdRp from Japanese encephalitis virus (jRdRp) also. Crystal structures of jRdRp complexed with GTP and ATP provide a basis for specific recognition of GTP. Comparison of the jRdRpGTP structure with other viral RdRp-GTP structures shows that GTP binds jRdRp in a novel conformation. Apo-jRdRp structure suggests that the conserved motif F of jRdRp occupies multiple conformations in absence of GTP. Motif F becomes ordered on GTP binding and occludes the nucleotide triphosphate entry tunnel. Mutational analysis of key residues that interact with GTP evinces that the jRdRpGTP structure represents a novel pre-initiation state. Also, binding studies show that GTP binding reduces affinity of RdRp for RNA, but the presence of the catalytic Mn2+ ion abolishes this inhibition. Collectively, these observations suggest that the observed pre-initiation state may serve as a checkpoint to prevent erroneous template-independent RNA synthesis by jRdRp during initiation. 相似文献
40.