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81.
Chacinska A Lind M Frazier AE Dudek J Meisinger C Geissler A Sickmann A Meyer HE Truscott KN Guiard B Pfanner N Rehling P 《Cell》2005,120(6):817-829
The presequence translocase of the inner mitochondrial membrane (TIM23 complex) operates at a central junction of protein import. It accepts preproteins from the outer membrane TOM complex and directs them to inner membrane insertion or, in cooperation with the presequence translocase-associated motor (PAM), to the matrix. Little is known of how the TIM23 complex coordinates these tasks. We have identified Tim21 (YGR033c) that interacts with the TOM complex. Tim21 is specific for a TIM23 form that cooperates with TOM and promotes inner membrane insertion. Protein translocation into the matrix requires a switch to a Tim21-free, PAM bound presequence translocase. Tim17 is crucial for the switch by performing two separable functions: promotion of inner membrane insertion and binding of Pam18 to form the functional TIM-PAM complex. Thus, the presequence translocase is not a static complex but switches between TOM tethering and PAM binding in a reaction cycle involving Tim21 and Tim17. 相似文献
82.
Frazier AE Dudek J Guiard B Voos W Li Y Lind M Meisinger C Geissler A Sickmann A Meyer HE Bilanchone V Cumsky MG Truscott KN Pfanner N Rehling P 《Nature structural & molecular biology》2004,11(3):226-233
Mitochondrial preproteins destined for the matrix are translocated by two channel-forming transport machineries, the translocase of the outer membrane and the presequence translocase of the inner membrane. The presequence translocase-associated protein import motor (PAM) contains four essential subunits: the matrix heat shock protein 70 (mtHsp70) and its three cochaperones Mge1, Tim44 and Pam18. Here we report that the PAM contains a fifth essential subunit, Pam16 (encoded by Saccharomyces cerevisiae YJL104W), which is selectively required for preprotein translocation into the matrix, but not for protein insertion into the inner membrane. Pam16 interacts with Pam18 and is needed for the association of Pam18 with the presequence translocase and for formation of a mtHsp70-Tim44 complex. Thus, Pam16 is a newly identified type of motor subunit and is required to promote a functional PAM reaction cycle, thereby driving preprotein import into the matrix. 相似文献
83.
We constructed a model of speciation from evolution in an ecosystem consisting of a limited amount of energy recources. The species possesses genetic information, which is inherited according to the rules of the Penna model of genetic evolution. The increase in the number of the individuals of each species depends on the quality of their genotypes and the available energy resources. The decrease in number of the individuals results from genetic death or maximum-age reaching by the individual. The amount of energy resources is represented by a solution of the differential logistic equation, where the growth rate of the amount of the energy resources has been modified to include the number of individuals from all species in the ecosystem under consideration. The fluctuating surrounding is modelled with the help of the function V(x, t) = 1/4 x4 + 1/2 b(t)x2, where x represents phenotype and the coefficient b(t) shows the cos(omega t) time dependence. The closer the value x of an individual to the minimum of V(x, t), the better adapted its genotype to the surrounding. We observed that the life span of the organisms strongly depends on the value of the frequency omega. It becomes shorter the more frequent the changes of the surrounding. However, there is a tendency for the species that have a higher value of the reproduction age aR to win the competition with the other species. Another observation is that small evolutionary changes of the inherited genetic information lead to spontaneous bursts of the evolutionary activity when many new species may appear in a short period. 相似文献
84.
Dudek SM Birukov KG Zhan X Garcia JG 《Biochemical and biophysical research communications》2002,298(4):511-519
Inflammatory mediators such as thrombin evoke increases in vascular permeability through activation of endothelial contractile mechanisms which involve increased levels of MLC phosphorylation catalyzed by Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK). We previously noted that the high molecular weight endothelial MLCK isoform (EC MLCK) is stably associated with a complex containing p60(src) and 80kDa cortactin, an actin-binding protein and known p60(src) target. In this study we have utilized in vitro binding assays to confirm specific interaction between EC MLCK and cortactin. Tyrosine phosphorylation of either EC MLCK (Y(464), Y(471)) or cortactin (Y(421), Y(466), and Y(482)) by p60(src) significantly increased this direct association. Site-specific antibody and peptide studies subsequently confirmed EC MLCK AA #972-979 and 1019-1025 as sites of cortactin interaction. EC MLCK-cortactin interaction in vitro failed to modulate MLCK enzymatic activity but appeared to inhibit EC MLCK binding to F-actin, while EC MLCK abolished cortactin-mediated augmentation of Arp2/3-stimulated actin polymerization. These data suggest that cortactin-EC MLCK interaction may be a novel determinant of endothelial cortical actin-based cytoskeletal rearrangement. 相似文献
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In this fifth issue of News from the Biological Stain Commission (BSC), under the heading of Regulatory Affairs, the BSC's International Affairs Committee provides more information from the meeting of the International Standards Organization ISO/TC 212 Committee that took place on June 2–4, 2008 at Vancouver, Canada. In addition, we give an update on the current situation regarding the supplies of hematoxylin. 相似文献
89.
RW Dapson 《Biotechnic & histochemistry》2013,88(3):95-100
One of the most sweeping changes in the dye industry since the advent of synthetic dyes grew out of the health risks associated with benzidine. Dyes made from benzidine and its derivatives were used around the world until adverse health effects become incontrovertible. Workers and family members of workers involved in production and use of benzidine-based dyes had a high incidence of bladder cancer. Following publication of several reports documenting this health hazard, dye makers in the USA, Europe, and Japan phased these dyes out of production in the 1970s. Government regulations lent legal support for these voluntary initiatives. Two strategies subsequently evolved to compensate: developed nations brought alternative substances to market while emerging countries increased production of carcinogenic dyes and sold them at discount prices around the world. Nearly all dye manufacturing now has moved away from nations whose costs of production and compliance rendered them unable to compete. The purpose of this brief review is to publicize the health risks associated with dyes made from benzidine and its congeners, and to alert all companies and end users handling these dyes for biomedical applications that composition of the product and lot-to-lot variability may be problematic because of the manufacturing and distribution practices of the countries where they are produced. 相似文献
90.
RW Dapson 《Biotechnic & histochemistry》2013,88(2):49-72
Staining of tissues by dyes is accomplished through various types of bonds, some of which have been poorly defined in traditional biological literature. Here, basic principles of bonding are reviewed to establish uniform terminology and definitions consistent with the field of chemistry. The concept of charge – its presence or absence, magnitude, extent of delocalization and potential for being displaced by outside forces – underlies all bonding phenomena. These same attributes influence solubility and resistance to extraction during dehydration of tissue sections. Covalent bonds involve shared electrons; they are very strong and essentially irreversible under conditions encountered during staining. Polar covalent bonds within dye molecules generate partial atomic charges that create the potential for hydrogen bonding. This is measured by the hydrogen bonding parameter (h), the number of groups bearing charges within the ranges ?0.15 to ?0.50 eV or +0.15 to +0.30 eV. The potential for ionic bonding is indicated by net charge (Z), while the strength of such bonds is a function of charge site geometry on both bonding partners. Charge delocalization owing to conjugation, electron influencing groups, and resonance creates soft charge sites in which the ionic charge is spread over a large volume. Poorly delocalized charges or point charges are hard (small in volume). Firm bonds result from hard-hard or soft-soft pairs. Hard-soft combinations are weak, readily displaced in competitive interactions, and disrupted by solvents. Coordinate bonds with certain metals are involved with mordant staining and metal chelation dyes. Three different van der Waals attractions comprise the remainder of bonding types, all involving dipoles: Keesom (dipole-dipole) forces, Debye (dipole-induced dipole) forces and London (induced dipole-induced dipole) forces. Potentials for engaging in any of these is quantified by measures of polarity (dipole moment, d), polarizability (crudely with π atoms describing the size of the conjugated system, or more directly with α), hydrophobicity (with the octanol-water partition coefficient, log P or the more convenient Hydrophobic Index, HI), and the number of halogen atoms (X). By using molecular modeling software, quantitative measures of bonding potential (bonding parameters) have been determined for over 400 dyes. 相似文献