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111.
Dourson M Maier A Meek B Renwick A Ohanian E Poirier K 《Biological trace element research》1998,66(1-3):453-463
Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This
observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of
fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data
as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data
on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for
interspecies differences and 10-fold for intraspecies differences) with data-derived values.
The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for
kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3-to 4-fold higher in rats than in humans
and data on dynamic differences—in order to modify the default value—are unavailable. A data-derived adjustment of 6-fold
(1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for
intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available
data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide
a stronger basis for replacement of default uncertainty factors for interspecies variation. 相似文献
112.
A parsimony analysis was performed on restriction sites at the Hba-ps4
pseudogene locus within one of four inversions associated with mouse t
haplotypes. The results suggest that all t haplotypes form a monophyletic
group and that the in (17)4 inversion originated before the radiation of
the Mus musculus species complex but after the divergence of the lineages
leading to M. spretus, M. abbotti, and M. hortulanus. A time frame based on
the evolutionary rate of mouse pseudogenes places the origin of this t
haplotype inversion at 1.5 Mya, or approximately 1.5 Myr after the origin
of the more proximal t complex inversion, in (17)2. The accumulated
evidence indicates that complete t haplotypes have been assembled in a
stepwise manner, with each of these inversions occurring on separate
chromosomal lineages and at different evolutionary times. In addition, the
evolutionary relationships of pseudogene sequences resulting from genetic
exchange between wild-type and t haplotype alleles were examined. Analysis
of sequences from the 5' and 3' sides of a putative site of recombination
resulted in cladograms with different topologies. The implications for
hypotheses concerning the evolutionary forces acting on t haplotypes and
their rapid propagation throughout worldwide populations of mice are
discussed.
相似文献
113.
114.
J Meek 《Stain technology》1978,53(3):131-135
Optic tecta of goldfish were coated with egg yolk and immersed for only one week in one of the following impregnation fluids: a) Solution A + B; A = 1 g K2Cr2O7 and 1 g HgCl2 boiled for 15 min in 85 ml distilled water and allowed to cool; B = 0.8 g K2Cr2O4 and 0.5 g KWO4 dissolved in 20 ml distilled water. b) Solution A + B two volumes diluted with boiled distilled water. c) Solution A + B four volumes diluted with boiled distilled water. Each tectum was immersed 6 hr in 100 ml distilled water containing 0.5 g LiOH and 15 g KNO3, washed 18 hr in 500 ml 0.2% acetic acid, dehydrated with ethanol, and embedded in low viscosity nitro cellulose. Sections were cut at 100 micron with a rotary microtome after clearing with cedarwood oil. Methods b) and c) have two advantages compared with method a), the original Golgi-Cox method. First, more cells are impregnated, especially in the layers extending 200-400 micron below the surface, and dendrites as well as unmyelinated axons are well impregnated. Second, myelin sheaths are impregnated and can be recognized by their peculiar chain-like appearance. The described Golgi-Cox modification offers an appropriate method to study the morphology of superficially located nervous tissue. 相似文献
115.
J. Meek 《Biotechnic & histochemistry》1978,53(3):131-135
Optic tecta of goldfish were coated with egg yolk and immersed for only one week in one of the following impregnation fluids: a) Solution A + B; A = 1 g K2Cr2O7 and 1 g HgCl2 boiled for 15 min in 85 ml distilled water and allowed to cool; B = 0.8 g K2Cr2O7 and 0.5 g KWO4 dissolved in 20 ml distilled water, b) Solution A + B two volumes diluted with boiled distilled water, c) Solution A + B four volumes diluted with boiled distilled water. Each tectum was immersed 6 hr in 100 ml distilled water containing 0.5 g LiOH and 15 g KNO3, washed 18 hr in 500 ml 0.2% acetic acid, dehydrated with ethanol, and embedded in low viscosity nitro cellulose. Sections were cut at 100 pm with a rotary microtome after clearing with cedarwood oil. Methods b) and c) have two advantages compared with method a), the original Golgi-Cox method. First, more cells are impregnated, especially in the layers extending 200-400 μm below the surface, and dendrites as well as unmyelinated axons are well impregnated. Second, myelin sheaths are impregnated and can be recognized by their peculiar chain-like appearance. The described Golgi-Cox modification offers an appropriate method to study the morphology of superficially located nervous tissue. 相似文献
116.
A L Fluharty Z Katona W E Meek K Frei A V Fowler 《Biochemical medicine and metabolic biology》1992,47(1):66-85
The activator protein for hydrolysis of cerebroside sulfate by arylsulfatase A was purified from pig kidney in high yield. This protein, also known as sphingolipid activator protein-1 and saposin-B, was particularly rich in pig kidney. Purification was achieved by a simple procedure involving homogenation and heat treatment followed by affinity, ion exchange, and gel filtration chromatographies. The final product was better than 90% pure by gel electrophoresis and HPLC. It was possible to sequence more than 60 amino acids from the N-terminus with only a few uncertain residues. The sequence differed from that predicted for the human protein by about 10%, with most amino acid variations being conservative. There appeared to be a residual glycosyl substituent on asparagine 21, but the sugar content was low and the protein failed to bind to concanavalin A. The cerebroside sulfate activator proved to be exceptionally resistant to denaturation or protease digestion. The apparent molecular mass was approximately 20,000 Da on preparative gel-filtration columns, but was variable when estimated by HPLC gel filtration. Values ranging from 30,000 to over 100,000 Da were observed in neutral buffers, while values around 15,000-16,000 Da were seen in acidic buffers such as those used for assay of the biological activity. This was further decreased to a putative subunit of 7000-8000 Da under severe denaturing conditions. Pig kidney is a convenient source for the large-scale preparation of this interesting protein which has heretofore been obtained from human sources. 相似文献
117.
Proteins of approximately 35, 55 and 65kDa were purified from cauliflower extracts by microcystin-Sepharose chromatography and identified by amino acid sequencing as plant forms of protein (serine/threonine) phosphatase 1 (PP1) catalytic subunit, PP5 and a regulatory A-subunit of PP2A, respectively. Peptides that corresponded both to the tetratricopeptide (TPR) repeat and catalytic domains of PP5 were identified. Similar to mammalian PP5,the casein phosphatase activity of plant PP5 was activated >10-fold by arachidonic acid, with half-maximal stimulation occurring at approximately 100 microM lipid. 相似文献
118.
Both V(D)J recombination and radioresistance require DNA-PK kinase activity, though minimal levels suffice for V(D)J recombination 总被引:6,自引:1,他引:5 下载免费PDF全文
DNA-dependent protein kinase (DNA-PK) is utilized in both DNA double-strand break repair (DSBR) and V(D)J recombination, but the mechanism by which this multiprotein complex participates in these processes is unknown. To evaluate the importance of DNA-PK-mediated protein phosphorylation in DSBR and V(D)J recombination, we assessed the effects of the phosphatidyl inositol 3-kinase inhibitor wortmannin on the repair of ionizing radiation-induced DNA double-strand breaks and V(D)J recombination in the V(D)J recombinase inducible B cell line HDR37. Wortmannin radiosensitized HDR37, but had no affect on V(D)J recombination despite a marked reduction in DNA-PK activity. On the other hand, studies with mammalian expression vectors for wild-type human DNA-PK catalytic subunit (DNA-PKcs) and a kinase domain mutant demonstrated that only the kinase active form of DNA-PKcs can reconstitute DSBR and V(D)J recombination in a DNA-PKcs-deficient cell line (Sf19), implying that DNA-PKcs kinase activity is essential for both DSBR and V(D)J recombination. These apparently contradictory results were reconciled by analyses of cell lines varying in their expression of recombinant wild-type human DNA-PKcs. These studies establish that minimal DNA-PKcs protein levels are sufficient to support V(D)J recombination, but insufficient to confer resistance to ionizing radiation. 相似文献
119.
DNA-PK is a protein complex that consists of a DNA-binding, regulatory subunit [Ku] and a larger ~465 kDa catalytic subunit [DNA-PKcs], a serine/threonine protein kinase. The kinase activity of DNA-PKcs resides between residues 3745 and 4013, a PI3 kinase domain. Another recognized domain within this large protein is a leucine zipper (LZ) motif or perhaps more appropriately designated a leucine rich region (LRR) that spans residues 1503–1602. Whereas, DNA-PK's kinase activity has been shown to be absolutely indispensable for its function in non-homologous end joining (NHEJ), little is known about the functional relevance of the LRR. Here we show that DNA-PKcs with point mutations in the LRR can only partially reverse the radiosensitive phenotype and V(D)J recombination deficits of DNA-PKcs deficient cells. Disruption of the LRR motif affects the ability to purify DNA-PKcs via its binding to DNA-cellulose, but does not affect its interaction with Ku or its catalytic activity. These data suggest that the LRR region of DNA-PKcs may contribute to its intrinsic DNA affinity, and moreover, that intrinsic DNA binding is important for optimal function of DNA-PKcs in repairing double strand breaks in living cells. 相似文献
120.
Sherman DL Tait S Melrose S Johnson R Zonta B Court FA Macklin WB Meek S Smith AJ Cottrell DF Brophy PJ 《Neuron》2005,48(5):737-742
Voltage-gated sodium channels are concentrated in myelinated nerves at the nodes of Ranvier flanked by paranodal axoglial junctions. Establishment of these essential nodal and paranodal domains is determined by myelin-forming glia, but the mechanisms are not clear. Here, we show that two isoforms of Neurofascin, Nfasc155 in glia and Nfasc186 in neurons, are required for the assembly of these specialized domains. In Neurofascin-null mice, neither paranodal adhesion junctions nor nodal complexes are formed. Transgenic expression of Nfasc155 in the myelinating glia of Nfasc-/- nerves rescues the axoglial adhesion complex by recruiting the axonal proteins Caspr and Contactin to the paranodes. However, in the absence of Nfasc186, sodium channels remain diffusely distributed along the axon. Our study shows that the two major Neurofascins play essential roles in assembling the nodal and paranodal domains of myelinated axons; therefore, they are essential for the transition to saltatory conduction in developing vertebrate nerves. 相似文献