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Paul L. Wood Tadimeti S. Rao Smriti Iyengar Thomas Lanthorn Joseph Monahan Alex Cordi Eric Sun Michael Vazquez Nancy Gray Patricia Contreras 《Neurochemical research》1990,15(2):217-230
Conclusions Current neurochemical studies of the NMDA receptor macromolecular complex are yielding new insights into the interactions of the subunits of this complex and the associated potential clinical benefits of selective modulation of these subnits. Such studies offer the great potential for a new generation of pharmacotherapies for a wide range of CNS disorders, including stroke, a condition for which there is currently no effective pharmacological treatment. However, it is essential to understand that the first generation products in this area may not be optimal pharmacotherapies, such that haracterization of possible receptor subtypes and understanding the molecular biology of the component proteins of the receptor complex will be crucial in the design of the optimal pharmacological modulators of the NMDA receptor complex.Special issue dedicated to Dr. Erminio Costa 相似文献
4.
In the Panamanian iceryine coccid Icerya zeteki
Cockerell (Family Margarodidae
Morrison) all females become hermaphroditic early in the first instar; occasional males arise from unfertilized eggs, but self-fertilization is assured by the protandry of the hermaphrodite. In the development of the ovotestis, initiation of the male phase is brought about by haploidization of those germ cells destined for spermatogenesis. In both Icerya zeteki and Icerya purchasi this gonial reduction results from the degeneration and elimination of one genome during prophase. Except for minor variations in the coiling cycle of spermatocytes, the chromosomes (n=2) of I. zeteki correspond closely to those of all other haplo-diploid iceryines known. The present status of the species Icerya zeteki
Cockerell is reviewed, and on both taxonomicand cytological grounds is judged to be uncertain.Supported in part by National Science Foundation Grant GB — 1922. 相似文献
5.
N-Methyl-D-Aspartate Recognition Site Ligands Modulate Activity at the Coupled Glycine Recognition Site 总被引:1,自引:1,他引:0
In synaptic plasma membranes from rat forebrain, the potencies of glycine recognition site agonists and antagonists for modulating [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding and for displacing strychnine-insensitive [3H]glycine binding are altered in the presence of N-methyl-D-aspartate (NMDA) recognition site ligands. The NMDA competitive antagonist, cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755), reduces [3H]glycine binding, and the reduction can be fully reversed by the NMDA recognition site agonist, L-glutamate. Scatchard analysis of [3H]glycine binding shows that in the presence of CGS 19755 there is no change in Bmax (8.81 vs. 8.79 pmol/mg of protein), but rather a decrease in the affinity of glycine (KD of 0.202 microM vs. 0.129 microM). Similar decreases in affinity are observed for the glycine site agonists, D-serine and 1-aminocyclopropane-1-carboxylate, in the presence of CGS 19755. In contrast, the affinity of glycine antagonists, 1-hydroxy-3-amino-2-pyrrolidone and 1-aminocyclobutane-1-carboxylate, at this [3H]glycine recognition site increases in the presence of CGS 19755. The functional consequence of this change in affinity was addressed using the modulation of [3H]TCP binding. In the presence of L-glutamate, the potency of glycine agonists for the stimulation of [3H]TCP binding increases, whereas the potency of glycine antagonists decreases. These data are consistent with NMDA recognition site ligands, through their interactions at the NMDA recognition site, modulating activity at the associated glycine recognition site. 相似文献
6.
WhileEscherichia coli is common as a commensal organism in the distal ileum and colon, the presence of colonization factors (CF) on pathogenic strains ofE. coli facilitates attachment of the organism to intestinal receptor molecules in a species- and tissue-specific fashion. After the initial adherence, colonization occurs, and the involvement of additional virulence determinants leads to illness. EnterotoxigenicE. coli (ETEC) is the most extensively studied of the five categories ofE. coli that cause diarrheal disease, and has the greatest impact on health worldwide. ETEC can be isolated from domestic animals and humans. The biochemistry, genetics, epidemiology, antigenic characteristics, and cell and receptor binding properties of ETEC have been extensively described. Another major category, enteropathogenicE. coli (EPEC), has virulence mechanisms, primarily effacement and cytoskeletal rearrangement of intestinal brush borders, that are distinct from ETEC. An EPEC CF receptor has been purified and characterized as a sialidated transmembrane glycoprotein complex directly attached to actin, thereby associating CF-binding with host-cell response. Three, additional categories ofE. coli diarrheal disease, their colonization factors and their host cell receptors are discussed. It appears that biofilms exist in the intestine in a manner similar to oral bacterial biofilms, and thatE. coli is part of these biofilms as both commensals and pathogens.Abbreviations CF
colonization factor
- CFA
Colonization Factor Antigen
- CS
coli-surface-associated antigen
- EAggEC
enteroaggregativeE. coli
- ECDD
E. coli diarrheal disease
- EHEC
enterohemorrhagicE. coli
- EIEC
enteroinvasiveE. coli
- EPEC
enteropathogenicE. coli
- ETEC
enterotoxigenicE. coli
- Gal
galactose
- GalNAc
N-acetyl galactosamine
- LT
heat-labile toxin
- NeuAc
N-acetyl neuraminic acid
- PCF
Putative colonization factor
- RBC
red blood cells
- SLT
Shiga-like toxin
- ST
heat-stable toxin 相似文献
7.
DNA sequences were determined for three to five alleles of the bride-of-
sevenless (boss) gene in each of four species of Drosophila. The product of
boss is a transmembrane receptor for a ligand coded by the sevenless gene
that triggers differentiation of the R7 photoreceptor cell in the compound
eye. Population parameters affecting the rate and pattern of molecular
evolution of boss were estimated from the multinomial configurations of
nucleotide polymorphisms of synonymous codons. The time of divergence
between D. melanogaster and D. simulans was estimated as approximately 1
Myr, that between D. teissieri and D. yakuba as approximately 0.75 Myr, and
that between the two pairs of sibling species as approximately 2 Myr. (The
boss genes themselves have estimated divergence times approximately 50%
greater than the species divergence times.) The effective size of the
species was estimated as approximately 5 x 10(6), and the average mutation
rate was estimated as 1-2 x 10(-9)/nucleotide/generation. The ratio of
amino acid polymorphisms within species to fixed differences between
species suggests that approximately 25% of all possible single-step amino
acid replacements in the boss gene product may be selectively neutral or
nearly neutral. The data also imply that random genetic drift has been
responsible for virtually all of the observed differences in the portion of
the boss gene analyzed among the four species.
相似文献
8.
Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene 总被引:8,自引:1,他引:7
We have analyzed the conserved regions of the gene coding for the
circumsporozoite protein (CSP) in 12 species of Plasmodium, the malaria
parasite. The closest evolutionary relative of P. falciparum, the agent of
malignant human malaria, is P. reichenowi, a chimpanzee parasite. This is
consistent with the hypothesis that P. falciparum is an ancient human
parasite, associated with humans since the divergence of the hominids from
their closest hominoid relatives. Three other human Plasmodium species are
each genetically indistinguishable from species parasitic to nonhuman
primates; that is, for the DNA sequences included in our analysis, the
differences between species are not greater than the differences between
strains of the human species. The human P. malariae is indistinguishable
from P. brasilianum, and P. vivax is indistinguishable from P. simium; P.
brasilianum and P. simium are parasitic to New World monkeys. The human P.
vivax-like is indistinguishable from P. simiovale, a parasite of Old World
macaques. We conjecture that P. malariae, P. vivax, and P. vivax-like are
evolutionarily recent human parasites, the first two at least acquired only
within the last several thousand years, and perhaps within the last few
hundred years, after the expansion of human populations in South America
following the European colonizations. We estimate the rate of evolution of
the conserved regions of the CSP gene as 2.46 x 10(-9) per site per year.
The divergence between the P. falciparum and P. reichenowi lineages is
accordingly dated 8.9 Myr ago. The divergence between the three lineages
leading to the human parasites is very ancient, about 100 Myr old between
P. malariae and P. vivax (and P. vivax-like) and about 165 Myr old between
P. falciparum and the other two.
相似文献
9.
Factors affecting the transformation of Escherichia coli strain chi1776 by pBR322 plasmid DNA. 总被引:41,自引:0,他引:41
The susceptibility of E. coli strain chi1776 to transformation by pBR322 plasmid DNA was examined and optimized. Maximum transformation to tetracycline (Tc) resistance was achieved when cells were harvested from L broth at 5.0--6.0 . 10(7) cfu/ml, followed by washing twice in cold 0.1 M NaCl + 5 mM MgCl2 + 5 mM Tris, pH 7.6. Cells grown in the presence of D-cycloserine (Cyc) rather than nalidixic acid (Nx) transformed markedly better. The presence of 5 mM Mg2+ ions in washing and CaCl2 solutions stimulated transformation about 2-fold. Optimal conditions for transformation included a pH range of 7.25-7.75 and a cell-to-DNA ratio of about 1.6 . 10(8) cfu/ng plasmid DNA. The frequency of transformation was highest when cells were exposed to 100 mM CaCl2 in 250 mM KCl + 5 mM MgCl2 + 5 mM Tris, pH 7.6, before mixing with DNA. A 60 min incubation period for cell + DNA mixtures held on ice produced the maximum number of Tcr transformants. In our hands, heat shocks at 37 degrees C or 42 degrees C for various times all decreased transformation to about one-half of optimal levels. Furthermore, the recovery of transformants was best when cell + DNA mixtures were plated on precooled (4 degrees C) Tc agar plates. The efficiency of plating was optimum when only 5 microliter of cell + DNA mixture was spread per plate, suggesting that non-viable background chi1776 cells on selective medium inhibited the recovery of transformants. It was also found that the presence of linear DNA molecules in cell + DNA mixtures markedly inhibited the transformation of chi1776 by pBR322 plasmid DNA. On the basis of these findings, a new procedure for the plasmid-specific transformation of E. coli chi1776 by pBR322 plasmid DNA is proposed. The use of this technique has allowed us to attain transformation frequencies in excess of 10(7) transformants/microgram pBR322 plasmid DNA. 相似文献
10.
Oligomeric forms of the membrane-bound acetylcholine receptor disclosed upon extraction of the M(r) 43,000 nonreceptor peptide 下载免费PDF全文
FJ Barrantes 《The Journal of cell biology》1982,92(1):60-68
Oligomeric forms of the acetylcholine receptor are directly visualized by electron microscopy in receptor-rich membranes from torpedo marmorata. The receptor structures are quantitatively correlated with the molecular species so far identified only after detergent solubilization, and further related to the polypeptide composition of the membranes and changes thereof. The structural identification is made possibly by the increased fragility of the membranes after extraction of nonreceptor peptides and their subsequent disruption upon drying onto hydrophilic carbon supports. Receptor particles in native membranes depleted of nonreceptor peptides appear as single units of 7-8 nm, and double and multiple aggregates thereof. Particle doublets having a main-axis diameter of 19 +/- 3 nm predominate in these membranes. Linear aggregates of particles similar to those observed in rotary replicas of quick-frozen fresh electrolytes (Heuser, J.E. and S. R. Salpeter. 1979, J. Cell Biol. 82: 150-173) are also present in the alkaline-extracted membranes. Chemical modifications of the thiol groups shift the distribution of structural species. Dithiothreitol reduction, which renders almost exclusively the 9S, monomeric receptor form, results in the observation of the 7-8 nm particle in isolated form. The proportion of doublets increases in membranes alkylated with N-ethylmaleimide. Treatment with 5,5’-dithiobis-(nitrobenzoic acid) increases the proportion of higher oligomeric species, and particle aggregates (n=oligo) predominate. The nonreceptor v-peptide (doublet of M(r) 43,000) appears to play a role in the receptor monomer-polymer equilibria. Receptor protein and v-peptide co-aggregate upon reduction and reoxidation of native membranes. In membranes protected ab initio with N- ethylmaleimide, only the receptor appears to self-aggregate. The v-peptide cannot be extracted from these alkylated membranes, though it is easily released from normal, subsequently alkylated or reduced membranes. A stabilization of the dimeric species by the nonreceptor v-peptide is suggested by these experiments. Monospecific antibodies against the v-peptide are used in conjunction with rhodamine- labeled anti-bodies in an indirect immunoflourescence assay to map the vectorial exposure of the v-peptide. When intact membranes, v-peptide depleted and “holey” native membranes (treated with 0.3 percent saponin) are compared, maximal labeling is obtained with the latter type of membranes, suggesting a predominantly cytoplasmic exposure of the antigenic determinants of the v-peptide in the membrane. The influence of the v-peptide in the thiol-dependent interconversions of the receptor protein and the putative topography of the peptide are analyzed in the light of the present results. 相似文献