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131.
This study first reports the absorption kinetics of GST-TatdMt, a recombinant Tat protein possessing potent anti-obesity activity, in rats after nasal, s.c., and p.o. administration. GST-TatdMt was over-expressed in E. coli, purified, and radioiodinated using the IODO-GEN method. The radioiodinated 125I-GST-TatdMt was administered to rats by nasal, s.c., and oral routes at doses of 7.3 microg (420.7 nCi), 146.5 microg (8413.8 nCi), and 146.5 microg (8413.8 nCi), respectively. For the determination of absolute bioavailability, 125I-GST-TatdMt was also given to rats by i.v. injection (73.2 microg, 4206.9 nCi). Following administration by extravascular routes, the systemic absorption of radioactivity was prolonged, with Cmax being attained within 4.2-8.0 h. The absolute bioavailability calculated as dose-normalized AUC(extravascular)/AUC(i.v.) was 98.0, 75.8, and 87.1% after nasal, s.c., and oral administration, respectively. The majority of administered radioactivity was excreted in urine (57.5-64.7%), with fecal excretion being less (2.5-12.7%). The distribution of 125I-GST-TatdMt to various tissues was also determined at 4 and 72 h after s.c. injection. The findings of this study suggest that this protein may be absorbed into the systemic circulation when given by extravascular administration. 相似文献
132.
Analysis of gene-trap Ds rice populations in Korea 总被引:1,自引:0,他引:1
Park SH Jun NS Kim CM Oh TY Huang J Xuan YH Park SJ Je BI Piao HL Park SH Cha YS Ahn BO Ji HS Lee MC Suh SC Nam MH Eun MY Yi G Yun DW Han CD 《Plant molecular biology》2007,65(4):373-384
Insertional mutagen-mediated gene tagging populations have been essential resources for analyzing the function of plant genes.
In rice, maize transposable elements have been successfully utilized to produce transposant populations. However, many generations
and substantial field space are required to obtain a sufficiently sized transposant population. In rice, the japonica and
indica subspecies are phenotypically and genetically divergent. Here, callus cultures with seeds carrying Ac and Ds were used to produce 89,700 lines of Dongjin, a japonica cultivar, and 6,200 lines of MGRI079, whose genome is composed of
a mixture of the genetic backgrounds of japonica and indica. Of the more than 3,000 lines examined, 67% had Ds elements. Among the Ds-carrying lines, 81% of Dongjin and 63% of MGRI079 contained transposed Ds, with an average of around 2.0 copies. By examining more than 15,000 lines, it was found that 12% expressed the reporter
gene GUS during the early-seedling stage. GUS was expressed in root hairs and crown root initials at estimated frequencies
of 0.78% and 0.34%, respectively. The 5,271 analyzed Ds loci were found to be randomly distributed over all of the rice chromosomes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Sung Han Park, Nam Soo Jun, Chul Min Kim are contributed equally to this paper 相似文献
133.
Shin DJ Kim E Park SB Jang WC Bae Y Han J Jang Y Joung B Lee MH Kim SS Huang H Chahine M Yoon SK 《Life sciences》2007,80(8):716-724
Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit (Na(v)1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in tsA201 cells, and the sodium currents (I(Na)) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Na(v)1.5/W1191X) co-transfected with the beta(1)-subunit in tsA201 cells resulted in a loss of function of Na(v)1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Na(v)1.5 activation and fast inactivation kinetics, the Na(v)1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in I(Na). No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel. 相似文献
134.
Park SH Kim CM Je BI Park SH Park SJ Piao HL Xuan YH Choe MS Satoh K Kikuchi S Lee KH Cha YS Ahn BO Ji HS Yun DW Lee MC Suh SC Eun MY Han CD 《Planta》2007,227(1):1-12
OSH6 (Oryza sativa Homeobox6) is an ortholog of lg3 (Liguleless3) in maize. We generated a novel allele, termed OSH6-Ds, by inserting a defective Ds element into the third exon of OSH6, which resulted in a truncated OSH6 mRNA. The truncated mRNA was expressed ectopically in leaf tissues and encoded the N-terminal region of OSH6, which includes
the KNOX1 and partial KNOX2 subdomains. This recessive mutant showed outgrowth of bracts or produced leaves at the basal node
of the panicle. These phenotypes distinguished it from the OSH6 transgene whose ectopic expression led to a “blade to sheath transformation” phenotype at the midrib region of leaves, similar
to that seen in dominant Lg3 mutants. Expression of a similar truncated OSH6 cDNA from the 35S promoter (35S::ΔOSH6) confirmed that the ectopic expression of this product was responsible for the aberrant bract development. These data suggest
that OSH6-Ds interferes with a developmental mechanism involved in bract differentiation, especially at the basal nodes of panicles.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
135.
136.
Oral administration of high molecular mass poly-gamma-glutamate induces NK cell-mediated antitumor immunity 总被引:1,自引:0,他引:1
Kim TW Lee TY Bae HC Hahm JH Kim YH Park C Kang TH Kim CJ Sung MH Poo H 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(2):775-780
We analyzed the in vivo tumor regression activity of high molecular mass poly-gamma-glutamate (gamma-PGA) from Bacillus subtilis sups. chungkookjang. C57BL/6 mice were orally administered 10-, 100-, or 2000-kDa gamma-PGA or beta-glucan (positive control), and antitumor immunity was examined. Our results revealed higher levels of NK cell-mediated cytotoxicity and IFN-gamma secretion in mice treated with higher molecular mass gamma-PGA (2000 kDa) vs those treated with lower molecular mass gamma-PGA (10 or 100 kDa) or beta-glucan. We then examined the effect of oral administration of 10- or 2000-kDa gamma-PGA on protection against B16 tumor challenge in C57BL/6 mice. Mice receiving high molecular mass gamma-PGA (2000 kDa) showed significantly smaller tumor sizes following challenge with the MHC class I-down-regulated tumor cell lines, B16 and TC-1 P3 (A15), but not with TC-1 cells, which have normal MHC class I expression. Lastly, we found that gamma-PGA-induced antitumor effect was decreased by in vivo depletion of NK cells using mAb PK136 or anti-asialo GM1 Ab, and that was completely blocked in NK cell-deficient B6 beige mice or IFN-gamma knockout mice. Taken together, we demonstrated that oral administration of high molecular mass gamma-PGA (2000 kDa) generated significant NK cell-mediated antitumor activity in mice bearing MHC class I-deficient tumors. 相似文献
137.
Tumor necrosis factor-alpha (TNFα)-blocking therapy, using biologic TNFα antagonists, has been approved for the treatment of several diseases including rheumatoid arthritis, psoriasis and Crohn's disease. There have been few detailed studies of binding characterizations for the complex formation by TNFα and clinically relevant antagonists, particularly Infliximab (Remicade®) and Etanercept (Enbrel®). Here we characterized the binding stoichiometry and size of soluble TNFα–antagonist complexes and identified energetically important binding sites on TNFα for the three antagonists, Etanercept, Infliximab, and the recently developed humanized TNFα neutralizing monoclonal antibody, YHB1411-2. Size-exclusion chromatography and dynamic light scattering analyses revealed that the three antagonists formed distinct thermodynamically stable TNFα–antagonist complexes that exhibited differences in their size and composition. Energetically important binding residues on TNFα were identified for each antagonist by a sequence of experiments that consisted of competition binding assays, fragmentations, loop mutations, and single-point mutations using yeast surface-displayed TNFα, which was further confirmed for solubly purified TNFα mutants by surface plasmon resonance technique. Analyses of the binding geometry based on binding site location, spatial constraints, and valency satisfaction allowed us to interpret the thermodynamically stable complexes as follows: one molecule of Etanercept and one molecule of trimeric TNFα (Etanercept1––TNFα1), Infliximab6–TNFα3, and YHB1411–24-TNFα2. The distinct features of the soluble antagonist–TNFα complex formation among the antagonists may give further insights into their different neutralizing mechanisms and pharmacokinetic profiles. 相似文献
138.
Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons 总被引:1,自引:0,他引:1
The Rap family of small GTPases is implicated in the mechanisms of synaptic plasticity, particularly synaptic depression. Here we studied the role of Rap in neuronal morphogenesis and synaptic transmission in cultured neurons. Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused decreased length and complexity of both axonal and dendritic branches. In addition, Rap2 caused loss of dendritic spines and spiny synapses, and an increase in filopodia-like protrusions and shaft synapses. These Rap2 morphological effects were absent in aspiny interneurons. In contrast, constitutively active Rap1 had no significant effect on axon or dendrite morphology. Dominant-negative Rap mutants increased dendrite length, indicating that endogenous Rap restrains dendritic outgrowth. The amplitude and frequency of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-mediated miniature excitatory postsynaptic currents (mEPSCs) decreased in hippocampal neurons transfected with active Rap1 or Rap2, associated with reduced surface and total levels of AMPA receptor subunit GluR2. Finally, increasing synaptic activity with GABA(A) receptor antagonists counteracted Rap2's inhibitory effect on dendrite growth, and masked the effects of Rap1 and Rap2 on AMPA-mediated mEPSCs. Rap1 and Rap2 thus have overlapping but distinct actions that potentially link the inhibition of synaptic transmission with the retraction of axons and dendrites. 相似文献
139.
Chai JY Park JH Guk SM Kim JL Kim HJ Kim WH Shin EH Klein TA Kim HC Chong ST Song JW Baek LJ 《The Korean journal of parasitology》2007,45(2):153-156
The small intestines of 6 species of rodents and 1 species of insectivore were examined seasonally for Plagiorchis muris infection in 3 different localities in northern Gyeonggi-do (Province), near the demilitarized zone (DMZ). A total of 1,496 animals, including 1,366 Apodemus agrarius, 54 Crocidura lasiura (insectivore), 32 Mus musculus, 28 Micronytus fortis, 9 Eothenomys regulus, 6 Micronys minutus, and 3 Cricetulus triton, were live-trapped at Yeoncheon-gun (n = 351), Paju-shi (804) and Pocheon-gun (343) at 3-mo intervals from December 2004 to September 2005. A total of 1,647 P. muris were collected from 72 (5.3%) A. agrarius. The infection rate was the highest in Pocheon-gun (8.2%), followed by Yeoncheon-gun (5.0%) and Paju-shi (4.2%). A higher infection rate was observed in A. agrarius captured during September (19.4%) than those captured during December (3.0%), June (2.6%), or April (0%). However, the worm burden was the highest in June (av. 32.1/animal), followed by September (24.7), December (4.0), and April (0). None of the other animal species were found infected with P. muris. The results reveal that A. agrarius is a natural definitive host for P. muris, and infection rates and worm burdens vary seasonally and geographically. 相似文献
140.