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排序方式: 共有326条查询结果,搜索用时 15 毫秒
1.
A. Weber 《Cellular and molecular life sciences : CMLS》1948,4(10):394-395
Summary All sensory endings of the trigeminal nerve in the dura mater of the rat are formed by a small swelling, from which continues themetaterminal apparatus, fine filaments at the limit of visibility. Periodically the fine granules at the extremity of the filaments swell, whereas the fibrils themselves disappear, leaving a small, round, argentophil mass. Later the filaments reappear, then redeposit their debris, which persists for a time.Thus the metaterminal apparatus manifests cyclic variations, which recall the transitory existence of collaterals observed duringin vivo orin vitro development of nerve fibres. 相似文献
2.
J. -M. Weber 《Cellular and molecular life sciences : CMLS》1992,48(6):557-564
The study of metabolic fuel provision and its regulation has reached an exciting stage where specific molecular events can be correlated with parameters of the organism's ecology. This paper examines substrate supply pathways from storage sites to locomotory muscle mitochondria and discusses ecological implications of the limits for maximal flux through these pathways. The relative importance of the different oxidative fuels is shown to depend on aerobic capacity. Very aerobic, endurance-adapted animals such as long distance migrants favor the use of lipids and intramuscular fuels over carbohydrates and circulatory fuels. The hypothesis of functional co-adaptation between oxygen and metabolic fuel supply systems allows us to predict that the capacity of several biochemical processes should be scaled with maximal oxygen consumption. Key enzymes, transmembrane transporter proteins, glucose precursor supply and soluble fatty acid transport proteins must all be geared to support higher maximal glucose and fatty acid fluxes in aerobic than in sedentary species. 相似文献
3.
MSI and MSII made on ribosome in idling step of protein synthesis 总被引:56,自引:0,他引:56
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Vedrana Filić Maja Marinović Jan Faix Igor Weber 《Cellular and molecular life sciences : CMLS》2014,71(15):2775-2785
Proteins are typically categorized into protein families based on their domain organization. Yet, evolutionarily unrelated proteins can also be grouped together according to their common functional roles. Sequestering proteins constitute one such functional class, acting as macromolecular buffers and serving as an intracellular reservoir ready to release large quantities of bound proteins or other molecules upon appropriate stimulation. Another functional protein class comprises effector proteins, which constitute essential components of many intracellular signal transduction pathways. For instance, effectors of small GTP-hydrolases are activated upon binding a GTP-bound GTPase and thereupon participate in downstream interactions. Here we describe a member of the IQGAP family of scaffolding proteins, DGAP1 from Dictyostelium, which unifies the roles of an effector and a sequestrator in regard to the small GTPase Rac1. Unlike classical effectors, which bind their activators transiently leading to short-lived signaling complexes, interaction between DGAP1 and Rac1-GTP is stable and induces formation of a complex with actin-bundling proteins cortexillins at the back end of the cell. An oppositely localized Rac1 effector, the Scar/WAVE complex, promotes actin polymerization at the cell front. Competition between DGAP1 and Scar/WAVE for the common activator Rac1-GTP might provide the basis for the oscillatory re-polarization typically seen in randomly migrating Dictyostelium cells. We discuss the consequences of the dual roles exerted by DGAP1 and Rac1 in the regulation of cell motility and polarity, and propose that similar signaling mechanisms may be of general importance in regulating spatiotemporal dynamics of the actin cytoskeleton by small GTPases. 相似文献
6.
Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins 总被引:1,自引:0,他引:1
Brigitte M. E. Hayes Marilyn A. Anderson Ana Traven Nicole L. van der Weerden Mark R. Bleackley 《Cellular and molecular life sciences : CMLS》2014,71(14):2651-2666
Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules. 相似文献
7.
PTC124 targets genetic disorders caused by nonsense mutations 总被引:1,自引:0,他引:1
Welch EM Barton ER Zhuo J Tomizawa Y Friesen WJ Trifillis P Paushkin S Patel M Trotta CR Hwang S Wilde RG Karp G Takasugi J Chen G Jones S Ren H Moon YC Corson D Turpoff AA Campbell JA Conn MM Khan A Almstead NG Hedrick J Mollin A Risher N Weetall M Yeh S Branstrom AA Colacino JM Babiak J Ju WD Hirawat S Northcutt VJ Miller LL Spatrick P He F Kawana M Feng H Jacobson A Peltz SW Sweeney HL 《Nature》2007,447(7140):87-91
Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options. 相似文献
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International Consortium for Blood Pressure Genome-Wide Association Studies Ehret GB Munroe PB Rice KM Bochud M Johnson AD Chasman DI Smith AV Tobin MD Verwoert GC Hwang SJ Pihur V Vollenweider P O'Reilly PF Amin N Bragg-Gresham JL Teumer A Glazer NL Launer L Zhao JH Aulchenko Y Heath S Sõber S Parsa A Luan J Arora P Dehghan A Zhang F Lucas G Hicks AA Jackson AU Peden JF Tanaka T Wild SH Rudan I Igl W Milaneschi Y Parker AN Fava C Chambers JC Fox ER Kumari M Go MJ van der Harst P Kao WH 《Nature》2011,478(7367):103-109
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. 相似文献
10.
Kharchenko PV Alekseyenko AA Schwartz YB Minoda A Riddle NC Ernst J Sabo PJ Larschan E Gorchakov AA Gu T Linder-Basso D Plachetka A Shanower G Tolstorukov MY Luquette LJ Xi R Jung YL Park RW Bishop EP Canfield TK Sandstrom R Thurman RE MacAlpine DM Stamatoyannopoulos JA Kellis M Elgin SC Kuroda MI Pirrotta V Karpen GH Park PJ 《Nature》2011,471(7339):480-485
Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function. 相似文献