共查询到20条相似文献,搜索用时 0 毫秒
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H L Pahl 《European journal of biochemistry》2000,267(12):3395-3401
Polycythemia rubra vera (PV) is one of four diseases collectively called the myeloproliferative disorders (MPDs). Each disorder leads to an increased production of one or several hematopoietic cell lineages. MPDs arise from acquired mutations in a pluripotent hematopoietic stem cell. However, the molecular mechanisms leading to the development of these diseases are poorly understood. This review will summarize and evaluate recent advances in our understanding of one particular MPD, PV. 相似文献
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The Drosophila auditory system is presented as a powerful new genetic model system for understanding the molecular aspects of development and physiology of hearing organs. The fly's ear resides in the antenna, with Johnston's organ serving as the mechanoreceptor. New approaches using electrophysiology and laser vibrometry have provided useful tools to apply to the study of mutations that disrupt hearing. The fundamental developmental processes that generate the peripheral nervous system are fairly well understood, although specific variations of these processes for chordotonal organs (CHO) and especially for Johnston's organ require more scrutiny. In contrast, even the fundamental physiologic workings of mechanosensitive systems are still poorly understood, but rapid recent progress is beginning to shed light. The identification and analysis of mutations that affect auditory function are summarized here, and prospects for the role of the Drosophila auditory system in understanding both insect and vertebrate hearing are discussed. 相似文献
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Williams RS Boeckeler K Gräf R Müller-Taubenberger A Li Z Isberg RR Wessels D Soll DR Alexander H Alexander S 《Trends in molecular medicine》2006,12(9):415-424
The social amoeba Dictyostelium discoideum is increasingly being used as a simple model for the investigation of problems that are relevant to human health. This article focuses on several recent examples of Dictyostelium-based biomedical research, including the analysis of immune-cell disease and chemotaxis, centrosomal abnormalities and lissencephaly, bacterial intracellular pathogenesis, and mechanisms of neuroprotective and anti-cancer drug action. The combination of cellular, genetic and molecular biology techniques that are available in Dictyostelium often makes the analysis of these problems more amenable to study in this system than in mammalian cell culture. Findings that have been made in these areas using Dictyostelium have driven research in mammalian systems and have established Dictyostelium as a powerful model for human-disease analysis. 相似文献
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Residing beneath the phenotypic landscape of a plant are intricate and dynamic networks of genes and proteins. As evolution operates on phenotypes, we expect its forces to shape somehow these underlying molecular networks. In this review, we discuss progress being made to elucidate the nature of these forces and their impact on the composition and structure of molecular networks. We also outline current limitations and open questions facing the broader field of plant network analysis. 相似文献
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Albenne C Skov LK Tran V Gajhede M Monsan P Remaud-Siméon M André-Leroux G 《Proteins》2007,66(1):118-126
Amylosucrase from Neisseria polysaccharea (AS) is a transglucosidase from the glycoside-hydrolase family 13 that catalyzes the synthesis of an amylose-like polymer from sucrose, without any primer. Its affinity towards glycogen is particularly noteworthy since glycogen is the best D-glucosyl unit acceptor and the most efficient activator (98-fold k(cat) increase) known for this enzyme. Glycogen-enzyme interactions were modeled starting from the crystallographic AS: maltoheptaose complex, where two key oligosaccharide binding sites, OB1 and OB2, were identified. Two maltoheptaose molecules were connected by an alpha-1,6 branch by molecular modeling to mimic a glycogen branching. Among the various docking positions obtained, four models were chosen based on geometry and energy criteria. Robotics calculations enabled us to describe a back and forth motion of a hairpin loop of the AS specific B'-domain, a movement that assists the elongation of glycogen branches. Modeling data combined with site-directed mutagenesis experiments revealed that the OB2 surface site provides an anchoring platform at the enzyme surface to capture the polymer and direct the branches towards the OB1 acceptor site for elongation. On the basis of the data obtained, a semiprocessive glycogen elongation mechanism can be proposed. 相似文献
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Leonard TA Møller-Jensen J Löwe J 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2005,360(1455):523-535
Bacteria ensure the fidelity of genetic inheritance by the coordinated control of chromosome segregation and cell division. Here, we review the molecules and mechanisms that govern the correct subcellular positioning and rapid separation of newly replicated chromosomes and plasmids towards the cell poles and, significantly, the emergence of mitotic-like machineries capable of segregating plasmid DNA. We further describe surprising similarities between proteins involved in DNA partitioning (ParA/ParB) and control of cell division (MinD/MinE), suggesting a mechanism for intracellular positioning common to the two processes. Finally, we discuss the role that the bacterial cytoskeleton plays in DNA partitioning and the missing link between prokaryotes and eukaryotes that is bacterial mechano-chemical motor proteins. 相似文献
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Schilling AF Priemel M Timo Beil F Haberland M Holzmann T Catalá-Lehnen P Pogoda P Blicharski D Müldner C Löcherbach C Rueger JM Amling M 《Journal of musculoskeletal & neuronal interactions》2001,1(3):275-289
Our understanding of the biology of the skeleton, like that of virtually every other subject in biology, has been transformed by recent advances in human and mouse genetics. Among mammals, mice are the most promising animals for this experimental work. Because extensive genetic information exists, many mouse mutations are known, and cells from early mouse developmental stages are accessible, scientists have developed transgenic mice - mice in which a gene is introduced or ablated in the germ line. Thus far, we have analyzed more than 100 different transgenic and knock out models with various skeletal phenotypes, covering the major aspects of both skeletal development and skeletal maintenance. Based on these results we here present a first perspective on transgenic and gene knock out animals in skeletal research, including insights in signaling pathways controlling endochondral bone formation, in the regulation of osteoblast function, osteoclastic bone resorption and in bone tumorigenesis, as well as the central control of bone formation. The use of transgenic mice to dissect and analyze regulatory mechanisms in bone cell physiology and the pathogenesis of human bone diseases is an extremely powerful experimental tool. The data presented here demonstrate that the successful convergence of novel genetic approaches with the established and fundamental knowledge of bone biology has made a beginning. 相似文献
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《Biotechnology and bioengineering》2012,109(2):fmvi-fmvi
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Towards a functional understanding of good genes 总被引:1,自引:0,他引:1
The Hamilton & Zuk hypothesis (1982) underpins our understanding of the relationship between secondary sexual characters, parasites, and immunological function. However, despite the wealth of empirical studies that attempt to address issues raised by the Hamilton & Zuk hypothesis, there have been no overt attempts to identify the good genes that females select or how those good genes influence the host's immune system. Behavioural ecologists have generally viewed this aspect of immunity as a black box. In this review we propose candidate good genes in vertebrates, discuss their role in immune function and parasite resistance, and discuss several aspects of the assumptions that pervade studies of parasite mediated sexual selection in vertebrates. We also examine invertebrates (specifically insects) where our current knowledge of these systems suggests the patterns apparent in vertebrates are not underpinned by the same genetic mechanisms. 相似文献
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The changes in the contents of cyclic AMP, cyclic GMP, ATP, ADP, AMP and fructose-2,6-bisphosphate that occur in the mantle tissue of the mussel Mytilus galloprovincialis Lmk were analysed with regard to the annual gametogenic cycle. Throughout 2 years, the lowest contents of AMP, ADP and ATP were detected during late winter-spring, whereas the maximum appeared in the autumn months. During the second year, fructose-2,6-bisphosphate and cAMP showed a very similar behaviour. The levels of both compounds rose throughout the year until a maximum in September. Their behaviour was also similar to that observed during the first year, but displaced in time. Both in 1998 and in 1999, the highest level of cGMP was detected during the spring-summer months. The results obtained suggest that the glycolytic pathway, with regard to the breeding cycle, might be regulated by fructose-2,6-bisphosphate and cyclic AMP through the activation of 6-phosphofructo-1-kinase, which is the main regulating enzyme of the glycolysis in mantle of M. galloprovincialis. 相似文献
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Computer simulation has emerged as a powerful tool for studying the structural and functional properties of complex biological membranes. In the last few years, the use of recently developed simulation methodologies and current generation force fields has permitted novel applications of molecular dynamics simulations, which have enhanced our understanding of the different physical processes governing biomembrane structure and dynamics. This review focuses on frontier areas of research with important biomedical applications. We have paid special attention to polyunsaturated lipids, membrane proteins and ion channels, surfactant additives in membranes, and lipid–DNA gene transfer complexes. 相似文献
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Towards understanding the glycoprotein hormone receptors. 总被引:2,自引:0,他引:2
Lutropin (LH), follitropin (FSH) and thyrotropin (TSH), as well as choriogonadotropin (CG, which binds to the LH receptor) constitute the glycoprotein hormone family. Their 3 receptors have been cloned during the last few months. They belong to the large group of G-protein coupled membrane proteins, with their specific N-terminal domain likely to bind the hormone and the characteristic 7 membrane-spanning segments in their C-terminal moiety. The present review discusses the main results of amino acid sequence analysis performed on the glycoprotein hormone receptors. The putative extracellular head exhibits less than 45% homology over the 3 receptors, while approximately 70% residue conservation is found in the transmembrane moiety. Here only, limited sequence homologies (approximately 20%) can be found with other G-protein coupled receptors. The secondary structure predictions performed on the 3 receptors revealed that the polypeptide sequence predicted as ordered (either alpha-helix or beta-strand) were repeated evenly throughout the extracellular head with a period of approximately 25 amino acids. This analysis helped to define the intervening loops between this ordered stretches as potential candidates for bearing at least part of the binding site of the hormones. Some of the perspectives opened by the cloning of the receptors are described, like the production of the extracellular head of the porcine LH receptor in baculovirus-infected insect cells, and the exploration of the LH receptor's mechanism of functioning as a dimer. 相似文献
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Towards an understanding of the arginine-aspartate interaction. 总被引:1,自引:0,他引:1
We have made a comparison of the geometries of intra- and intermolecular arginine-aspartate interactions by extracting orientation information from protein co-ordinate data. The results show a pronounced difference, with both types of interaction preferring to form twin N-H . . . O = C hydrogen bonds, but involving different nitrogen atoms. In intramolecular interactions, the aspartate favours a "side on" geometry, forming hydrogen bonds with N epsilon and N eta 2; in the intermolecular case, however, "end on" contacts involving N eta 1 and N eta 2 of the arginine are preferred. We have used Distributed Multipole Analysis of the methylguanidinium-acetate system to model the electrostatic component of the arginine-aspartate ion pair interaction in vacuo. We find, in agreement with the experimental arginine-aspartate distribution, that side on and end on doubly N-H . . . O = C hydrogen-bonded configurations are clearly the most favourable, with the side on being marginally lower in energy. Thus, despite the many competing side-chain interactions in proteins, many arginine-aspartate pairs adopt one of the minimum electrostatic energy conformations, or one close to a minimum. Within each of the two regions (side on and end on) we find only a small energy gap between the "symmetric" doubly hydrogen-bonded and slightly displaced "staggered" structures, again in agreement with the crystal structure data. Further calculations of the total ab initio interaction energy show that this follows the electrostatic term in its orientational variation, this phenomenon of "electrostatic domination" being well known in hydrogen-bonded systems. The end on arginine nitrogen atoms are observed to be more surface-exposed than N epsilon, as demonstrated by their greater accessibilities over a large sample of proteins. This helps explain the side on and end on preferences of intra- and intermolecular interactions, respectively. We also note the effect of short sequence intervals, particularly i in equilibrium with i + 2 relationships, in forcing many intramolecular contacts to be side on. 相似文献
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Verkhivker GM Rejto PA Bouzida D Arthurs S Colson AB Freer ST Gehlhaar DK Larson V Luty BA Marrone T Rose PW 《Journal of molecular recognition : JMR》1999,12(6):371-389
The thermodynamic and kinetic aspects of molecular recognition for the methotrexate (MTX)-dihydrofolate reductase (DHFR) ligand-protein system are investigated by the binding energy landscape approach. The impact of 'hot' and 'cold' errors in ligand mutations on the thermodynamic stability of the native MTX-DHFR complex is analyzed, and relationships between the molecular recognition mechanism and the degree of ligand optimization are discussed. The nature and relative stability of intermediates and thermodynamic phases on the ligand-protein association pathway are studied, providing new insights into connections between protein folding and molecular recognition mechanisms, and cooperativity of ligand-protein binding. The results of kinetic docking simulations are rationalized based on the thermodynamic properties determined from equilibrium simulations and the shape of the underlying binding energy landscape. We show how evolutionary ligand selection for a receptor active site can produce well-optimized ligand-protein systems such as MTX-DHFR complex with the thermodynamically stable native structure and a direct transition mechanism of binding from unbound conformations to the unique native structure. 相似文献
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Towards understanding plant bioacoustics 总被引:2,自引:0,他引:2
Little is known about plant bioacoustics. Here, we present a rationale as to why the perception of sound and vibrations is likely to have also evolved in plants. We then explain how current evidence contributes to the view that plants may indeed benefit from mechanosensory mechanisms thus far unsuspected. 相似文献