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101.
Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model. 相似文献
102.
V Timmerman E Nelis W Van Hul B W Nieuwenhuijsen K L Chen S Wang K Ben Othman B Cullen R J Leach C O Hanemann 《Nature genetics》1992,1(3):171-175
Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy. 相似文献
103.
104.
Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. 总被引:22,自引:0,他引:22
P Froguel M Vaxillaire F Sun G Velho H Zouali M O Butel S Lesage N Vionnet K Clément F Fougerousse 《Nature》1992,356(6365):162-164
Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM. 相似文献
105.
Flask-shaped microfossils are reported from bracts of a moss in Eocene-Oligocene amber from the northern Dominican Republic. These microfossils are identical with the thecae of certain living moss-dwelling rotifers in the genusHabrotrocha (Bdelloidea), which have previously been reported as fossils only from Holocene peat. What may be an egg and a rotifer body fossil are associated with these thecae and further support the identification of these fossils withHabrotrocha; the fossils are almost identical to extantH. angusticollis. The parthenogenetic bdelloid rotifers have a longer evolutionary history than was previously thought; habrotrochid rotifers seem to have persisted for 35 million years with very little change in morphology or ecological role. 相似文献
106.
Stable propagation of synchronous spiking in cortical neural networks 总被引:25,自引:0,他引:25
The classical view of neural coding has emphasized the importance of information carried by the rate at which neurons discharge action potentials. More recent proposals that information may be carried by precise spike timing have been challenged by the assumption that these neurons operate in a noisy fashion--presumably reflecting fluctuations in synaptic input and, thus, incapable of transmitting signals with millisecond fidelity. Here we show that precisely synchronized action potentials can propagate within a model of cortical network activity that recapitulates many of the features of biological systems. An attractor, yielding a stable spiking precision in the (sub)millisecond range, governs the dynamics of synchronization. Our results indicate that a combinatorial neural code, based on rapid associations of groups of neurons co-ordinating their activity at the single spike level, is possible within a cortical-like network. 相似文献
107.
108.
109.
Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana 总被引:21,自引:0,他引:21
Lin X Kaul S Rounsley S Shea TP Benito MI Town CD Fujii CY Mason T Bowman CL Barnstead M Feldblyum TV Buell CR Ketchum KA Lee J Ronning CM Koo HL Moffat KS Cronin LA Shen M Pai G Van Aken S Umayam L Tallon LJ Gill JE Adams MD Carrera AJ Creasy TH Goodman HM Somerville CR Copenhaver GP Preuss D Nierman WC White O Eisen JA Salzberg SL Fraser CM Venter JC 《Nature》1999,402(6763):761-768
Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2. 相似文献
110.
A structural change in the kinesin motor protein that drives motility 总被引:34,自引:0,他引:34
Rice S Lin AW Safer D Hart CL Naber N Carragher BO Cain SM Pechatnikova E Wilson-Kubalek EM Whittaker M Pate E Cooke R Taylor EW Milligan RA Vale RD 《Nature》1999,402(6763):778-784
Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer. 相似文献