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1.
Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling 总被引:5,自引:0,他引:5
The formation of cranial bone requires the differentiation of osteoblasts from undifferentiated mesenchymal cells. The balance between osteoblast recruitment, proliferation, differentiation and apoptosis in sutures between cranial bones is essential for calvarial bone formation. The mechanisms that control human osteoblasts during normal calvarial bone formation and premature suture ossification (craniosynostosis) begin to be understood. Our studies of the human calvaria osteoblast phenotype and calvarial bone formation showed that premature fusion of the sutures in non-syndromic and syndromic (Apert syndrome) craniosynostoses results from precocious osteoblast differentiation. We showed that Fibroblast Growth Factor-2 (FGF-2), FGF receptor-2 (FGFR-2) and Bone Morphogenetic Protein-2 (BMP-2), three essential factors involved in skeletal development, regulate the proliferation, differentiation and apoptosis in human calvaria osteoblasts. Mechanisms that induce the differentiated osteoblast phenotype have also been identified in human calvaria osteoblasts. We demonstrated the implication of molecules (N-cadherin, Il-1) and signaling pathways (src, PKC) by which these local factors modulate human calvaria osteoblast differentiation and apoptosis. The identification of these essential signaling molecules provides new insights into the pathways controlling the differentiated osteoblast phenotype, and leads to a more comprehensive view in the mechanisms that control normal and premature cranial ossification in humans. 相似文献
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Merce AL Landaluze JS Mangrich AS Szpoganicz B Sierakowski MR 《Bioresource technology》2001,76(1):29-37
The main interest in the biopolymer arabinogalactan is that it is edible. Complementing its high protein percentage, when complexed to essential metal ions, widens the use in food and pharmacology industries and technologies. The binding constants of Co2+, Cu2+, Mn2+ and Ni2+ with arabinogalactan, extracted from the leaves of Pereskia aculeata from Brazil were determined by potentiometric titrations and also the speciation according to pH values. The complexed species proposed by potentiometric titrations and the unique complexing ability of galacturonic acid groups towards Cu2+ and Ni2+ in the tridimensional web structure of arabinogalactan were confirmed by IR and EPR spectroscopies. The thermal stability of the complexed species also varied with the metal ion employed in the complexation when compared to the biopolymer alone. These complexes are new sources of additives for the food and pharmacology industries and carriers of essential metal ions to animal and vegetal biochemistry. 相似文献
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Sever S 《Developmental cell》2003,5(4):530-532
Clathrin and the adaptor protein complex (AP-2) constitute the major coat components of clathrin-coated vesicles. In the September issues of the Journal of Cell Biology and the Journal of Biological Chemistry, three reports reveal that AP-2, while essential for internalization of transferrin, is not essential for internalization of EGF. These novel data suggest the intriguing possibility that the major role of AP-2 is in cargo recruitment, and not in assembly of functionally active clathrin-coated pits. 相似文献
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Kim Fortun 《Dialectical Anthropology》2010,34(1):77-86
The global chemical industry has a rich history of investment in campaigns to educate the public about what it does. Beginning
in the 1930s, first Dupont then the industry overall promised “Better Living Through Chemistry.” In the 1990s, the industry
promoted its own environmentalism. The 2005 launch of the American Chemistry Council’s essential2life campaign was yet another
update. This essay examines the shifting logics of chemical industry public education campaigns, focusing particularly on
the disavowals of the essential2life campaign. The essay also raises questions about forms of collective deliberation—among
scientists, among activists and within industry—that reduce vulnerability to what Kirsch and Benson call “corporate oxymorons,”
facilitating critical awareness of ways vested interests shape articulations of history and knowledge. 相似文献
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Synaptotagmin C2A loop 2 mediates Ca2+-dependent SNARE interactions essential for Ca2+-triggered vesicle exocytosis 总被引:1,自引:1,他引:0
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Lynch KL Gerona RR Larsen EC Marcia RF Mitchell JC Martin TF 《Molecular biology of the cell》2007,18(12):4957-4968
Synaptotagmins contain tandem C2 domains and function as Ca(2+) sensors for vesicle exocytosis but the mechanism for coupling Ca(2+) rises to membrane fusion remains undefined. Synaptotagmins bind SNAREs, essential components of the membrane fusion machinery, but the role of these interactions in Ca(2+)-triggered vesicle exocytosis has not been directly assessed. We identified sites on synaptotagmin-1 that mediate Ca(2+)-dependent SNAP25 binding by zero-length cross-linking. Mutation of these sites in C2A and C2B eliminated Ca(2+)-dependent synaptotagmin-1 binding to SNAREs without affecting Ca(2+)-dependent membrane binding. The mutants failed to confer Ca(2+) regulation on SNARE-dependent liposome fusion and failed to restore Ca(2+)-triggered vesicle exocytosis in synaptotagmin-deficient PC12 cells. The results provide direct evidence that Ca(2+)-dependent SNARE binding by synaptotagmin is essential for Ca(2+)-triggered vesicle exocytosis and that Ca(2+)-dependent membrane binding by itself is insufficient to trigger fusion. A structure-based model of the SNARE-binding surface of C2A provided a new view of how Ca(2+)-dependent SNARE and membrane binding occur simultaneously. 相似文献
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Bacteriophage T4 RNA ligase 2 (Rnl2) exemplifies a polynucleotide ligase family that includes the trypanosome RNA-editing ligases and putative RNA ligases encoded by eukaryotic viruses and archaea. Here we analyzed 12 individual amino acids of Rnl2 that were identified by alanine scanning as essential for strand joining. We determined structure-activity relationships via conservative substitutions and examined mutational effects on the isolated steps of ligase adenylylation and phosphodiester bond formation. The essential residues of Rnl2 are located within conserved motifs that define a superfamily of nucleotidyl transferases that act via enzyme-(lysyl-N)-NMP intermediates. Our mutagenesis results underscore a shared active site architecture in Rnl2-like ligases, DNA ligases, and mRNA capping enzymes. They also highlight two essential signature residues, Glu(34) and Asn(40), that flank the active site lysine nucleophile (Lys(35)) and are unique to the Rnl2-like ligase family. 相似文献
9.
Montell C 《Current biology : CB》2003,13(20):R799-R801
TRPM6 and TRPM7 are distinct from all other ion channels in that they are composed of linked channel and protein kinase domains. Recent studies demonstrate that these 'chanzymes' are essential for Mg(2+) homeostasis, which is critical for human health and cell viability. 相似文献
10.
芹菜子的超临界CO2流体萃取物的化学成分研究 总被引:10,自引:0,他引:10
本文采用GC和GC-MS技术,就芹菜子的超临界CO2流体萃取法(SFE-CO2)精油和水汽蒸馏法(SD)精油的化学组成作了对比研究。结果表明,SD法精油的主要成分为单萜烯烃类物质,而SFE-CO2法精油为苯并呋喃酮类化合物。共有32种化合物被鉴定,其中两种为首次在芹子油中被发现。 相似文献
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Xiaoming Yang Patricia A. Wood William J. M. Hrushesky 《The Journal of biological chemistry》2010,285(5):3030-3034
Timeless (Tim), a core circadian clock gene in Drosophila, is retained in mammals but has no apparent mammalian circadian clock function. Mammalian TIM is essential for ATR-dependent Chk1 activation and S-phase arrest. We report that TIM is likewise essential for ATM-dependent Chk2-mediated signaling of doxorubicin-induced DNA double strand breaks. TIM depletion attenuates doxorubicin-induced G2/M cell cycle arrest and sensitizes cancer cells to doxorubicin-induced cytotoxicity. TIM is, thereby, a potential novel anticancer drug target whose inhibition may enhance the therapeutic cytotoxicity of agents that activate DNA damage pathways as part of their mechanism. 相似文献
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Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis 总被引:15,自引:0,他引:15
Tanaka T Hosoi F Yamaguchi-Iwai Y Nakamura H Masutani H Ueda S Nishiyama A Takeda S Wada H Spyrou G Yodoi J 《The EMBO journal》2002,21(7):1695-1703
Thioredoxin-2 (Trx-2) is a mitochondria-specific member of the thioredoxin superfamily. Mitochondria have a crucial role in the signal transduction for apoptosis. To investigate the biological significance of Trx-2, we cloned chicken TRX-2 cDNA and generated clones of the conditional Trx-2-deficient cells using chicken B-cell line, DT40. Here we show that TRX-2 is an essential gene and that Trx-2-deficient cells undergo apoptosis upon repression of the TRX-2 transgene, showing an accumulation of intracellular reactive oxygen species (ROS). Cytochrome c is released from mitochondria, while caspase-9 and caspase-3, but not caspase-8, are activated upon inhibition of the TRX-2 transgene. In addition, Trx-2 and cytochrome c are co-immunoprecipitated in an in vitro assay. These results suggest that mitochondrial Trx-2 is essential for cell viability, playing a crucial role in the scavenging ROS in mitochondria and regulating the mitochondrial apoptosis signaling pathway. 相似文献
13.
Shan Jiang Ronald L. Chandler Douglas P. Mortlock 《Biochemical and biophysical research communications》2010,392(2):124-128
The level of bone morphogenetic protein 2 (BMP2) profoundly influences essential cell behaviors such as proliferation, differentiation, apoptosis, and migration. The spatial and temporal pattern of BMP2 synthesis, particular in diverse embryonic cells, is highly varied and dynamic. We have identified GC-rich sequences within the BMP2 promoter region that strongly repress gene expression. These elements block the activity of a highly conserved, osteoblast enhancer in response to FGF2 treatment. Both positive and negative gene regulatory elements control BMP2 synthesis. Detecting and mapping the repressive motifs is essential because they impede the identification of developmentally regulated enhancers necessary for normal BMP2 patterns and concentration. 相似文献
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采用正交实验设计,对肾叶天胡荽(Hydrocotyle wigordi Maxim.)精油超临界CO2萃取条件进行了优化,并用GC—MS分析技术对精油的化学成分进行了鉴定,初步探讨了肾叶天胡荽精油对小菜蛾2龄幼虫的触杀活性。结果表明,肾叶天胡荽精油超临界CO2萃取的最佳条件为萃取压力35MPa、萃取温度50℃、解析压力5MPa、解析温度40℃、萃取时间75min、CO2流量34—36L·h^-1,精油得率最高可达5.32%。从精油中共鉴定出19种成分,总相对含量达到89.266%,主要成分为邻苯二甲酸二辛酯(64.302%)。用超临界CO2萃取技术提取的肾叶天胡荽精油对小菜蛾2龄幼虫有一定的触杀作用,20g·L^-1精油对小菜蛾2龄幼虫的24h校正死亡率高达90.00%。 相似文献
15.
Osteoclasts are hematopoietic lineage derived-multinucleated cells that resorb bone. Their activity in balance with that of osteoblast is essential for bone homeostasis. Receptor activator of NF-κB ligand (RANKL) is known as an essential cytokine for the osteoclastogenesis, and c-Jun signaling in cooperation with NFAT family is crucial for RANKL-regulated osteoclastogenesis. We show here that schlafen2 (Slfn2), a member of a new family of growth regulatory genes involved in thymocyte development, is critical for osteoclastogenesis. RANKL selectively induces Slfn2 expression in osteoclast precursors via Rac1 signaling pathway. Targeted inhibition of Slfn2 by small interfering RNAs (siRNAs) markedly inhibits the formation of osteoclasts by diminishing the activation of c-Jun and the expression of c-Jun and NFATc1. In contrast, the overexpression of Slfn2 markedly increased phosphorylation and transactivation of c-Jun by RANKL. Together, these results indicate that Slfn2 has an essential role in osteoclastogenesis, functioning upstream of c-Jun and NFATc1. 相似文献
16.
Maize endosperm ADP-glucose pyrophosphorylase SHRUNKEN2 and BRITTLE2 subunit interactions 总被引:4,自引:0,他引:4
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ADP-glucose pyrophosphorylase (AGP) represents a key regulatory step in polysaccharide synthesis in organisms ranging from bacteria to plants. Higher plant AGPs are complex in nature and are heterotetramers consisting of two similar but distinct subunits. How the subunits are assembled into enzymatically active polymers is not yet understood. Here, we address this issue by using naturally occurring null mutants of the Shrunken2 (Sh2) and Brittle2 (Bt2) loci of maize as well as the yeast two-hybrid expression system. In the absence of the maize endosperm large AGP subunit (SH2), the BT2 subunit remains as a monomer in the developing endosperm. In contrast, the SH2 protein, in the absence of BT2, is found in a complex of 100 kD. A direct interaction between SH2 and BT2 was proven when they were both expressed in yeast. Several motifs are essential for SH2:BT2 interaction because truncations removing the N or C terminus of either subunit eliminate SH2:BT2 interactions. Analysis of subunit interaction mutants (sim) also identified motifs essential for protein interactions. 相似文献
17.
The response of P2X(2) receptors to submaximal concentrations of ATP is potentiated by low levels of extracellular zinc. Histidines 120 and 213 have previously been shown to be essential in binding zinc across an intersubunit binding site. We tested the flexibility of the zinc-binding site by making mutations that had the effect of shifting the two essential histidines up to 13 residues upstream or downstream from their original positions and then testing the ability of the mutated receptors to respond to zinc. Using this method, we were able to explore potential orientations of the two regions relative to one another. Our data are consistent with a moderately flexible zinc-binding site and inconsistent with parallel and anti-parallel orientations of the regions surrounding histidines 120 and 213. 相似文献
18.
Complementation of the Essential Peptidoglycan Transpeptidase Function of Penicillin-Binding Protein 2 (PBP2) by the Drug Resistance Protein PBP2A in Staphylococcus aureus 总被引:8,自引:0,他引:8
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Mariana G. Pinho Srgio R. Filipe Hermínia de Lencastre Alexander Tomasz 《Journal of bacteriology》2001,183(22):6525-6531
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猪链球菌2型溶血素的化学修饰 总被引:6,自引:1,他引:6
用DTT、H2O2、DEPC、EDC、NAI、NBS、PCMB、2,3Diacetyl和SA 等9种化学修饰剂,处理猪链球菌2型江苏分离株提纯的溶血素,研究其分子中氨基酸侧链基团与其溶血活性的关系。结果表明,巯基、氨基、羧基和酪氨酸残基等与其溶血活性无关,而色氨酸、组氨酸和精氨酸的化学修饰引起溶血活性的大幅度下降,二硫键的化学修饰引起溶血活性的大幅度增强。显示色氨酸、组氨酸和精氨酸残基是该溶血素的活性必需基团,二硫键的断裂可引起其活性增强。 相似文献