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Cellular integrity in yeasts is ensured by a rigid cell wall whose synthesis is controlled by a MAP kinase signal transduction cascade. In Saccharomyces cerevisiae upstream regulatory components of this MAP kinase pathway involve a single protein kinase C, which is regulated in part by interaction with the small GTPase Rho1p. This small G protein is in turn rendered inactive (GDP-bound) or is activated (GTP-bound) by the influence of GTPase activating proteins (GAPs) and the GDP/GTP exchange factors (GEFs), respectively. We report here on the isolation of a gene from Kluyveromyces lactis, KlROM2, which encodes a member of the latter protein family. The nucleotide sequence contains an open reading frame of 1227 amino acids, with an overall identity of 57% to the Rom2 protein of S. cerevisiae. Four conserved sequence motifs could be identified: a RhoGEF domain, a DEP sequence, a CNH domain and a less conserved pleckstrin homology (PH) sequence. Klrom2 null mutants show a lethal phenotype, which indicates that the gene may encode the only functional GEF regulating the cellular integrity pathway in K. lactis. Conditional genomic expression of KlROM2 resulted in sensitivity towards caffeine and Calcofluor white as typical phenotypes of mutants defective in this pathway. Overexpression of KIROM2 from multicopy plasmids under the control of the ScGAL1 promoter severely impaired growth in both S. cerevisiae and in K. lactis. The fact that the lethal phenotype was not prevented in mpk1 deletion mutants indicates that growth inhibition is not simply caused by hyperactivation of the Pkc1p signal transduction pathway. 相似文献
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An efficient hardware implementation of the elliptic curve cryptographic processor over prime field,
Thirumalesu Kudithi Sakthivel R 《International Journal of Circuit Theory and Applications》2020,48(8):1256-1273
Elliptic curve cryptography (ECC) schemes are widely adopted for the digital signature applications due to their key sizes, hardware resources, and higher security per bit than Rivest-Shamir-Adleman (RSA). In this work, we proposed a new hardware architecture for elliptic curve scalar multiplication (ECSM) in Jacobian coordinates over prime field, . This is a combination of point doubling and point addition architecture, implemented using resource sharing concept to achieve high speed and low hardware resources, which is synthesized both in field-programmable gate array (FPGA) and application-specific integrated circuit (ASIC). The proposed ECSM takes 1.76 and 2.44 ms on Virtex-7 FPGA platform over 224-bit and 256-bit prime field, respectively. Similarly, ASIC (GF 40 nm complementary metal-oxide semiconductor [CMOS]) technology implementation provides energy efficient with a latency of 0.46 and 0.6 ms over prime field and , respectively. This design provides better area-delay product and high throughput value in both FPGA and ASIC when compared with other designs. 相似文献
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Mohammad Mojtaba Sadeghi Mohamed F. Salama Yusuf A. Hannun 《International journal of molecular sciences》2021,22(11)
Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC. 相似文献
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Tomohiro Itoh Kenji Ohguchi Chizuru Nakajima Masayoshi Oyama Munekazu Iinuma Yoshinori Nozawa Yukihiro Akao Masafumi Ito 《Food chemistry》2011
We found that two distinct flavonoid glycosides isolated from the peel of Japanese persimmon (Diospyros kaki Fuyu), isoquercitrin (Isq) and hyperin (Hyp), are capable of inhibiting antigen-stimulated degranulation in rat basophilic leukaemia RBL-2H3 cells. In order to elucidate the underlying mechanisms, we examined effects of Isq and Hyp on cellular responses induced by antigen stimulation. Treatment with both Isq and Hyp markedly inhibited antigen-stimulated elevation of intracellular free Ca2+ concentration and reactive oxygen species (ROS). Isq and Hyp did not affect NADPH oxidase (NOX) activity, but they possessed DPPH radical-scavenging activity similar to that of epigallocatechin gallate, a potent anti-oxidant, Finally, Isq and Hyp showed little or no effects on Ag-stimulated Syk activation or phosphorylation of signalling molecules. These results indicate that inhibition of antigen-stimulated degranulation by Isq and Hyp is mainly due to suppression of intracellular Ca2+ elevation, which is caused by direct scavenging of ROS that are generated by NOX. Our findings suggest that Isq and Hyp, isolated from the peel of persimmon, would be beneficial for alleviating symptoms of type I allergy. 相似文献
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cAMP pathway in podocytes 总被引:1,自引:0,他引:1
Podocytes possess receptors for a variety of hormones. The following receptors whose stimulation results in increased cAMP levels have been detected in podocytes: adrenergic beta(2) receptor, dopamine D(1) receptor, prostaglandin IP and EP(4) receptors, and parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor. Besides activating protein kinase A, increased levels of cAMP depolarize podocytes via opening of chloride channels. Relatively little is known about the impact of the cAMP pathway on podocyte function. Results obtained in a limited number of studies indicate that cAMP in podocytes may regulate cell morphology, actin assembly, and matrix production. In addition, cAMP seems to attenuate the action of hormones, which activate the Ca(2+)/protein kinase C pathway. Effects of the cAMP pathway on further aspects of podocyte biology, such as contractility, phosphorylation state of slit membrane-associated proteins, glomerular permeability, cell cycle control, and synthesis of reactive oxygen species can be anticipated from studies on other cell types and from studies on isolated glomeruli. In summary, the data available indicate that the cAMP pathway affects several aspects of podocyte biology in an overall glomerulo-protective manner. 相似文献
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Antidiabetic Activity of Ergosterol from Pleurotus Ostreatus in KK‐Ay Mice with Spontaneous Type 2 Diabetes Mellitus 下载免费PDF全文
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研究他莫昔芬(Tamoxifen,TAM)联合Y射线辐照对脑胶质瘤细胞PKCα蛋白表达的影响,初步探讨TAM降低辐射抗性的机制.采用Western-Blot法检测PKCα和G1期调控蛋白CylinD1的表达;碱性单细胞凝胶电泳法检测DNA链断裂.结果提示,TAM联合γ射线辐照可诱导PKCα蛋白和CyclinD1蛋白表达... 相似文献
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为设计后量子公钥密码,赵永哲等人提出了一种基于BMQ问题新的公钥方案。利用有限域上遍历矩阵的性质,从该方案公钥能够直接求出其等价私钥,从而破解了该HFEM公钥密码方案。 相似文献