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1.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
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2.
Protection from quinidine or physostigmine against in vitro inhibition by sarin of acetylcholinesterase activity 总被引:3,自引:0,他引:3
We have studied the relative effectiveness of quinidine and physostigmine in protecting against the inhibition of acetylcholinesterase (AChE) by sarin, an organophosphate (OP) compound. The protective effects of these compounds were studied in vitro in both synaptosomal and soluble samples obtained from various regions of sarin-administered or control isolated, perfused canine brain. Although AChE activities in the sarin-administered brain were substantially lower than in the control brain, we observed regional differences in the AChE activity in both. The AChE in the control brain and the AChE remaining in sarin-administered brain had different susceptibilities to inhibition from OP compounds in vitro and, therefore, have different properties. Quinidine partially protected AChE from the inhibitory effects of sarin in vitro possibly by altering the sarin binding sites. Addition of sarin to physostigmine-treated control brain samples allowed partial recovery of the AChE activity. The protective effects of quinidine or physostigmine were lost when samples from sarin-administered brain were treated in vitro with these compounds and then again exposed to sarin. Therefore, both quinidine and physostigmine provided partial protection against the inhibitory effects of sarin in vitro if they were added prior to sarin. 相似文献
3.
Assignment of orthologous relationships among mammalian alpha-globin genes by examining flanking regions reveals a rapid rate of evolution 总被引:1,自引:0,他引:1
In order to study the relationships among mammalian alpha-globin genes, we
have determined the sequence of the 3' flanking region of the human alpha 1
globin gene and have made pairwise comparisons between sequenced
alpha-globin genes. The flanking regions were examined in detail because
sequence matches in these regions could be interpreted with the least
complication from the gene duplications and conversions that have occurred
frequently in mammalian alpha-like globin gene clusters. We found good
matches between the flanking regions of human alpha 1 and rabbit alpha 1,
human psi alpha 1 and goat I alpha, human alpha 2 and goat II alpha, and
horse alpha 1 and goat II alpha. These matches were used to align the
alpha-globin genes in gene clusters from different mammals. This alignment
shows that genes at equivalent positions in the gene clusters of different
mammals can be functional or nonfunctional, depending on whether they
corrected against a functional alpha-globin gene in recent evolutionary
history. The number of alpha-globin genes (including pseudogenes) appears
to differ among species, although highly divergent pseudogenes may not have
been detected in all species examined. Although matching sequences could be
found in interspecies comparisons of the flanking regions of alpha- globin
genes, these matches are not as extensive as those found in the flanking
regions of mammalian beta-like globin genes. This observation suggests that
the noncoding sequences in the mammalian alpha-globin gene clusters are
evolving at a faster rate than those in the beta-like globin gene clusters.
The proposed faster rate of evolution fits with the poor conservation of
the genetic linkage map around alpha-globin gene clusters when compared to
that of the beta-like globin gene clusters. Analysis of the 3' flanking
regions of alpha-globin genes has revealed a conserved sequence
approximately 100-150 bp 3' to the polyadenylation site; this sequence may
be involved in the expression or regulation of alpha-globin genes.
相似文献
4.
Characterization of the Blood-Brain Barrier: Protein Composition of the Capillary Endothelial Cell Membrane 总被引:7,自引:4,他引:3
Microvessels were isolated from canine cerebral cortex, and the composition of the endothelial cell membrane was investigated. Endothelial cell membranes were separated from the surrounding basement membrane, solubilized, and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis in 12% gels. Staining with Coomassie Blue revealed a characteristic banding pattern of at least 12 major proteins with apparent molecular weights between 14,000 and 250,000. When proteins from red blood cell ghosts were run simultaneously, no similarities were observed, except for proteins at apparent molecular weights of 43,000 (band 3) and 35,000 (band 4). These two proteins migrated exactly to the positions of the erythrocyte proteins actin and glyceraldehyde 3-phosphate dehydrogenase, respectively. Membrane glycoproteins in gels were also examined by the use of fluorescent lectins. Of the fluorescein isothiocyanate-conjugated (FITC) lectins tested, only FITC-concanavalin A had an affinity for any membrane components. Diazotized [125I]iodosulfanilic acid, a membrane-impermeable reagent, was used to label the internal (lumen) cell surface and the external (antilumen) cell surface. Autoradiography and determination of radioactivity levels in gel slices showed that several proteins were specifically labeled, and that major differences in radioactivity of proteins existed in internal and external labeling experiments. It is concluded that the protein composition of the luminal membrane is different from that of the antiluminal membrane. 相似文献
5.
Condensed tannins. Optically active diastereoisomers of (+)-mollisacacidin by epimerization 总被引:2,自引:2,他引:0
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1. (+)-Mollisacacidin [(+)-3′,4′,7-trihydroxy-2,3-trans-flavan-3,4-trans- diol] is converted by autoclaving into the optically active free phenolic 2,3-trans-3-4-cis (12% yield), 2,3-cis-3,4-trans (11%) and 2,3-cis-3,4-cis (2·8%) diastereoisomers through epimerization at C-2 and C-4. 2. The relative configurations of the epimeric forms were determined by nuclear-magnetic-resonance spectrometry and paper ionophoresis in comparison with synthetic reference compounds, and was confirmed by chemical interconversions. 3. From this a scheme of epimerization is inferred and their absolute configurations are assigned as (2R:3S:4S), (2S:3S:4R) and (2S:3S:4S) respectively from the known absolute configuration (2R:3S:4R) of (+)-mollisacacidin. 相似文献
6.
Muscarinic acetylcholine receptor regulates phosphatidylcholine phospholipase D in canine brain 总被引:10,自引:0,他引:10
The hydrolytic activity of phosphatidylcholine phospholipase D in the synaptosomes from canine brain was examined using a radiochemical assay with 1,2-dipalmitoyl-sn-glycerol-3-phosphoryl[3H]choline as the exogenous substrate. The involvement of G protein(s) in regulation of this enzyme was demonstrated by a 2- to 3-fold stimulation of the basal activity (4.81 +/- 0.44 nmol choline released/mg protein/h) with guanosine 5'-(3-O-thiol)triphosphate (GTP gamma S), guanyl-5'-yl-(beta, gamma-methylene)diphosphonate, aluminum fluoride, or cholera toxin. The stimulation of phospholipase D hydrolytic activity by GTP gamma S was inhibited by 2 mM guanosine 5'-(2-O-thiol)diphosphate. GTP gamma S at the maximum stimulatory concentration (10 microM) had an additive effect on the maximum cholera toxin stimulation of phospholipase D activity. However, the reverse was not true, thus indicating the possibility that more than one G protein may be involved. Furthermore, cholinergic agonists, including acetylcholine, carbachol, and muscarine, were able to increase the phospholipase D hydrolytic activity at low but not maximally stimulatory concentrations of guanine nucleotide. These cholinergic stimulations were antagonized by atropine, a muscarinic blocker. In addition, O-tetradecanoylphorbol 13-acetate, a protein kinase C activator, was able to stimulate the hydrolytic activity of phospholipase D more than 300% in the presence of 0.2 microM GTP gamma S. However, in the absence of GTP gamma S, stimulation was less than 60%. Our results not only indicate that the receptor-G protein-regulated phospholipase D may be directly responsible for the rapid accumulation of choline and phosphatidic acid in the central nervous system but also reveal that muscarinic acetylcholine receptor-G protein-regulated phospholipase D is a novel signal transduction process coupling the neuronal muscarinic receptor to cellular responses. 相似文献
7.
Summary Whole isolated ellipsoids (sheathed capillaries of Schweiger-Seidel) of the pig spleen were explanted in Medium 199 containing 20% fetal calf serum or horse serum respectively. Cultures were kept in a gas phase of 5% carbon dioxide in air at 37°C. After about 4 days in culture the outgrowth of two morphologically different cell types was apparent. Small cells of fusiform or stellate morphology disalayed high activity of acid phosphatase. N-acetyl--glucosaminidase and -glucuronidase activity were also detectable. Furthermore these cells were highly reactive for unspecific esterase and -glutamyl transpeptidase activity. Endogenous peroxidase activity was present in the cytoplasm and in the perinuclear space. Stellate cells therefore are thought of as ellipsoid macrophages. Additional observations reported are the expression of Fc-receptors on stellate cells. They triggered the phagocytosis of opsonized test particles. The second cell type showed fibroblastic morphology. The large well spread cells did exhibit low activities of acid phophatase and N-acetyl--glucosaminidase. The other enzyme activities examined were not detectable. The nature of these cells is not well understood at present. Most likely they are constituents of the framework of the ellipsoids. No transitions between stellate cells and fibroblastic cells were found. 相似文献
8.
Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro 总被引:5,自引:0,他引:5
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H Wille G Drewes J Biernat E M Mandelkow E Mandelkow 《The Journal of cell biology》1992,118(3):573-584
Recent evidence from several laboratories shows that the paired helical filaments of Alzheimer's disease brains consist mainly of the protein tau in an abnormally phosphorylated form, but the mode of assembly is not understood. Here we use EM to study several constructs derived from human brain tau and expressed in Escherichia coli. All constructs or tau isoforms are rodlike molecules with a high tendency to dimerize in an antiparallel fashion, as shown by antibody labeling and chemical crosslinking. The length of the rods is largely determined by the region of internal repeats that is also responsible for microtubule binding. One unit length of the repeat domain (three or four repeats) is around 22-25 nm, comparable to the cross-section of Alzheimer PHF cores. Constructs corresponding roughly to the repeat region of tau can form synthetic paired helical filaments resembling those from Alzheimer brain tissue. A similar self-assembly occurs with the chemically cross-linked dimers. In both cases there is no need for phosphorylation of the protein. 相似文献
9.
Gregory J. Crowther Heidi K. Hillesland Katelyn R. Keyloun Molly C. Reid Maria Jose Lafuente-Monasterio Sonja Ghidelli-Disse Stephen E. Leonard Panqing He Jackson C. Jones Mallory M. Krahn Jack S. Mo Kartheek S. Dasari Anna M. W. Fox Markus Boesche Majida El Bakkouri Kasey L. Rivas Didier Leroy Raymond Hui Gerard Drewes Dustin J. Maly Wesley C. Van Voorhis Kayode K. Ojo 《PloS one》2016,11(3)
In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds’ mechanisms of action—i.e., the specific molecular targets by which they kill the parasite—would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children’s Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible. 相似文献
10.