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101.
Brooksbank C Camon E Harris MA Magrane M Martin MJ Mulder N O'Donovan C Parkinson H Tuli MA Apweiler R Birney E Brazma A Henrick K Lopez R Stoesser G Stoehr P Cameron G 《Nucleic acids research》2003,31(1):43-50
As the amount of biological data grows, so does the need for biologists to store and access this information in central repositories in a free and unambiguous manner. The European Bioinformatics Institute (EBI) hosts six core databases, which store information on DNA sequences (EMBL-Bank), protein sequences (SWISS-PROT and TrEMBL), protein structure (MSD), whole genomes (Ensembl) and gene expression (ArrayExpress). But just as a cell would be useless if it couldn't transcribe DNA or translate RNA, our resources would be compromised if each existed in isolation. We have therefore developed a range of tools that not only facilitate the deposition and retrieval of biological information, but also allow users to carry out searches that reflect the interconnectedness of biological information. The EBI's databases and tools are all available on our website at www.ebi.ac.uk. 相似文献
102.
Kuhn R Pagano A Stoehr N Vranesic I Flor PJ Lingenhöhl K Spooren W Gentsch C Vassout A Pilc A Gasparini F 《Amino acids》2002,23(1-3):207-211
Summary. There is a need to identify subtype-specific ligands for mGlu receptors to elucidate the potential of these receptors for
the treatment of nervous system disorders. To date, most mGlu receptor antagonists are amino acid-like compounds acting as
competitive antagonists at the glutamate binding site located in the large extracellular N-terminal domain.
We have characterized novel subtype-selective mGlu5 receptor antagonists which are structurally unrelated to competitive mGlu receptor ligands. Using a series of chimeric receptors
and point mutations we demonstrate that these antagonists act as inverse agonists with a novel allosteric binding site in
the seven-transmembrane domain. Recent studies in animal models implicate mGlu5 receptors as a potentially important therapeutic target particularly for the treatment of pain and anxiety.
Received July 2, 2001 Accepted August 6, 2001 Published online September 10, 2002 相似文献
103.
Human neutrophils permeabilized with digitonin respond with lysosomal enzyme release when exposed to micromolar levels of free calcium 总被引:3,自引:0,他引:3
We have recently reported that human neutrophils can be permeabilized with the cholesterol complexing agent saponin and that these cells can be induced to secrete the granule enzyme lysozyme in response to micromolar levels of free calcium. We now report that digitonin can be used in place of saponin and that it has several advantages. Permeabilization of human neutrophils was accomplished with 10 micrograms/ml digitonin in a high potassium medium. Normally impermeant solutes such as [14C]sucrose and inulin [14C]carboxylic acid gained access to one half of the intracellular water space marked with [3H]H2O. Between 30 and 100% of the cytoplasmic enzyme, lactate dehydrogenase, leaked from the intracellular space. The permeabilization process and calcium-triggered granule secretion were critically dependent upon temperature, time and digitonin concentration. Permeabilized neutrophils secreted beta-glucuronidase, lysozyme and vitamin B-12 binding-protein, constituents of both azurophil and specific granules, when exposed to micromolar levels of free calcium. Release of specific granule constituents appeared to be more sensitive to free calcium than release from azurophil granules. Although the amount of permeabilization varied considerably with each batch of cells, release of these granule markers was a consistent finding. Release of granule markers was accompanied by resealing of the cells to high-molecular-weight (Mr greater than 5000) solutes. Electron microscopic evidence also suggested that granule and plasma membranes were intact following digitonin treatment and that fusion of these membranes occurred in response to calcium. These results suggest that elevation of intracellular free-calcium levels is a sufficient condition for lysosomal enzyme release. 相似文献
104.
Inositol Trisphosphate Mobilizes Intracellular Calcium in Permeabilized Adrenal Chromaffin Cells 总被引:10,自引:8,他引:2
Sally J. Stoehr James E. Smolen Ronald W. Holz Bernard W. Agranoff† 《Journal of neurochemistry》1986,46(2):637-640
Using permeabilized chromaffin cells and the fluorescent probe Quin 2 (an indicator of free Ca2+), we found that inositol trisphosphate (IP3) specifically triggered an immediate and dose-dependent release of Ca2+ from intracellular stores. Desensitization of the response was observed at nonsaturating concentrations of inositol trisphosphate and resequestration of Ca2+ was not observed. While representing only a small fraction of the total cellular Ca2+, the amount released by IP3 could significantly raise cytosolic Ca2+ and may account for muscarinic effects on Ca2+ metabolism in chromaffin cells. 相似文献
105.
Micromolar concentrations of free calcium provoke secretion of lysozyme from human neutrophils permeabilized with saponin 总被引:7,自引:0,他引:7
Permeabilization of human neutrophils has been accomplished by using saponin, a cholesterol complexing agent, permitting experimental manipulation of the intracellular milieu. Access of ordinarily impermeable solutes, such as [14C]-inulin or [14C]-sucrose, to the water space of the cells was considered the main criterion for permeabilization. Other criteria were substantial (50 to 80%) release of cytoplasmic lactate dehydrogenase and permeability to trypan blue. Successful permeabilization did not cause substantial release of the granule enzymes lysozyme or beta-glucuronidase. Washing the neutrophils, to remove soluble saponin and released cytoplasmic contents, and resuspension did not alter their permeabilized character. By supplementing the medium with CaCl2, thereby obtaining free Ca2+ concentrations of 1.5 X 10(-7) M to 10(-4) M, it was possible to stimulate lysozyme secretion from washed or unwashed permeabilized neutrophils. A total of 20 to 30% of the total cellular lysozyme was released during an incubation of 5 min at 37 degrees C. Secretion was inversely related to cell concentration. No beta-glucuronidase was secreted under these conditions and no response was obtained by using unpermeabilized cells. Thus, permeabilized neutrophils respond to increases in free Ca2+ alone, without resorting to conventional secretagogues. This system also permits the manipulation of intracellular constituents important for stimulus-response coupling. 相似文献
106.
Butterflies are regularly used as model systems for understanding the role of coloration in communication because of their highly variable and conspicuous phenotypes. Most research showing a role for color in communication has focused on aspects of brightness or hue of entire wings or large color patches. However, evidence is accumulating that butterflies sometimes use smaller wing pattern elements in communication. Here we provide evidence that both male and female cabbage white butterflies (Pieris rapae L.) discriminate among conspecifics on the basis of the number of small but conspicuous black wing spots of the dorsal forewing. Male butterflies were more interactive with model butterflies with two spots, which resemble female butterflies, than with model butterflies with only one spot, which resemble male butterflies. Female butterflies showed the opposite response, being more interactive with male-like (one-spot) models than with female-like (two-spot) models. Some of our experiments were conducted with an electronic device designed to create a realistic and controlled fluttering behavior of the models. We describe the design and function of this device and provide evidence that it increased butterfly responses compared to a non-fluttering model. This device could prove useful for others addressing questions of communication in butterflies or other flying insects. 相似文献
107.
We describe the upper portion of the bill sheath (rhinotheca) of the kākāpō (Strigops habroptilus) from three adult female specimens. The external buccal surface of the rhinotheca is deeply concave with a prominent palatal stop and hardened chevrons creating a ‘milling apparatus’ that the kākāpō uses to grind food. The palatal stop presents a working face of 40–50?mm2. The internal surface of the rhinotheca mirrors the overlying premaxilla and provides a distinct thickened abutment consistent with resistance against the increased workload of the mandibles (gnathotheca) due to the kākāpō’s fibrous diet and chewing style. Along the midline, the rhinotheca at the abutment is up to 5.6?mm thick, compared with as thin as 2.1?mm elsewhere on the midline. The closely related Nestor parrots have less developed palatal stops, chevrons and abutments on their rhinothecas consistent with their lower preference for fibrous plant material. The form of the rhinotheca agrees with the kākāpō’s feeding ecology as a generalist herbivore that grinds locally available fibrous material to assist digestion. 相似文献
108.
Molecular evolution modeled as a fractal Poisson process in agreement with mammalian sequence comparisons 总被引:1,自引:1,他引:0
The fractal doubly stochastic Poisson process (FDSPP) model of molecular
evolution, like other doubly stochastic Poisson models, agrees with the
high estimates for the index of dispersion found from sequence comparisons.
Unlike certain previous models, the FDSPP also predicts a positive
geometric correlation between the index of dispersion and the mean number
of substitutions. Such a relationship is statistically proven herein using
comparisons between 49 mammalian genes. There is no characteristic rate
associated with molecular evolution according to this model, but there is a
scaling relationship in rates according to a fractal dimension of
evolution. The FDSPP is a suitable replacement for the homogeneous Poisson
process in tests of the lineage dependence of rates and in estimating
confidence intervals for divergence times. As opposed to other fractal
models, this model can be interpreted in terms of Darwinian selection and
drift.
相似文献
109.
A novel nuclear inhibitor I-92 regulates DNA binding activity of octamer binding protein p92 during the cell cycle. 总被引:2,自引:1,他引:1
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Nuclear DNA binding protein p92 is a sequence specific octamer binding protein with identical molecular weight as the ubiquitous octamer binding protein Oct-1. It binds to octamer related sequences from the enhancer of human papillomavirus type 18. The activity and intracellular distribution of p92 is regulated by extracellular signals. In serum starved Hela-fibroblast hybrid cells p92 is localized to the cytosol. Serum stimulation leads to nuclear import of p92. In fractions of asynchronously growing cells, which were separated according to cell cycle phases into G1, S, and G2 populations by centrifugal elutriation, p92 DNA binding is confined to S phase. In binding site blots however, p92 DNA binding activity is also present in G1 and G2. In G1 and G2 DNA binding activity of p92 is masked by a novel nuclear inhibitor I-92. The cyclic association of p92 with its inhibitor I-92 provides a new mechanism of regulating S phase dependent activity of a sequence specific DNA binding protein. 相似文献
110.
An algorithm that allows rapid searching of nucleic acid sequencesbased on pregenerated index files is described. The programsand index files for searching the entire EMBL nucleotide sequencecollection are being distributed on the EMBL Data Library'sCDROM. 相似文献