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51.
Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex 总被引:9,自引:0,他引:9
Newby LJ Streets AJ Zhao Y Harris PC Ward CJ Ong AC 《The Journal of biological chemistry》2002,277(23):20763-20773
The functions of the two proteins defective in autosomal dominant polycystic kidney disease, polycystin-1 and polycystin-2, have not been fully clarified, but it has been hypothesized that they may heterodimerize to form a "polycystin complex" involved in cell adhesion. In this paper, we demonstrate for the first time the existence of a native polycystin complex in mouse kidney tubular cells transgenic for PKD1, non-transgenic kidney cells, and normal adult human kidney. Polycystin-1 is heavily N-glycosylated, and several glycosylated forms of polycystin-1 differing in their sensitivity to endoglycosidase H (Endo H) were found; in contrast, native polycystin-2 was fully Endo H-sensitive. Using highly specific antibodies to both proteins, we show that polycystin-2 associates selectively with two species of full-length polycystin-1, one Endo H-sensitive and the other Endo H-resistant; importantly, the latter could be further enriched in plasma membrane fractions and co-immunoprecipitated with polycystin-2. Finally, a subpopulation of this complex co-localized to the lateral cell borders of PKD1 transgenic kidney cells. These results demonstrate that polycystin-1 and polycystin-2 interact in vivo to form a stable heterodimeric complex and suggest that disruption of this complex is likely to be of primary relevance to the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease. 相似文献
52.
Mutational activation of the gene for epidermal growth factor receptor (EGFR) is 1 of the main ways by which this receptor induces non-small cell lung cancers (NSCLC). Variant III EGFR (EGFRvIII) is a potential therapeutic target in NSCLC treatment because of the high frequency of deletion mutations in this protein. This study used noninvasive magnetic resonance imaging (MRI) to investigate the role of an EGFRvIII mutant in lung tumorigenesis and tumor maintenance as well as its response to the EGFR small molecule inhibitor erlotinib (Tarceva) on bitransgenic mice. Both spin-echo and gradient-echo sequences with and without cardiac and respiratory gating were performed to image the invasive mouse lung tumor driven by EGFRvIII mutation. Tumor volumes were measured based on 2-dimensional axial MRI; 3-dimensional rendering of the images were obtained to demonstrate the spatial location and distribution of the tumor in the lung. The MRI results indicated that the tumor driven by the EGFRvIII mutation was generated and maintained in the bitransgenic mice with the use of doxycycline. Tumor monitoring via MRI showed that Erlotinib can significantly inhibit the growth of tumor in vivo. MRI has the ability to image mouse lung tumor with different sequences focusing on tissue contrasts between tumor and surroundings. The MRI approaches in this work can be applied on other antitumor drug treatment evaluation in vivo when appropriate sequences are chosen. 相似文献
53.
E. V. Albert U. N. Kavai-ool T. A. Ezhova 《Russian Journal of Developmental Biology》2014,45(5):267-272
A constancy of stem cell pool in shoot apical meristem of Arabidopsis thaliana is provided by a genetic regulation system with negative feedback loop based on the interaction of the gene WUS, which maintains indeterminate state of cells, with CLV genes, which restrict the level of WUS expression and stem cell pool size. clv mutations lead to an increase in the pool of stem cells in the apical and floral meristems and wus mutation leads to the opposite effect. Mutation na (nana), like wus mutation, causes premature termination of shoot apical meristem function, although it does not affect the activity of the flower meristem. To elucidate the role of NA in the control of shoot apical meristem functioning, the interaction of NA with CLV genes were investigated. Additive phenotype of double mutants na clv1, na clv2-1, and na clv3-2 indicates that the NA gene makes an independent contribution to the functioning of the shoot apical meristem. It is assumed that the NA gene controls apical meristem cell proliferation during the transition to the reproductive phase of plant development, acting much later and independently of the genes WUS-CLV. 相似文献
54.
55.
Regulation of DOPA Decarboxylase Activity in Brain of Living Rat 总被引:3,自引:1,他引:3
Paul Cumming Hiroto Kuwabara Ariel Ase Albert Gjedde 《Journal of neurochemistry》1995,65(3):1381-1390
Abstract: To test the hypothesis that l -DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [3 H]DOPA. The unidirectional blood-brain clearance of [3 H]DOPA ( K D 1 ) was 0.049 ml g−1 min−1 . The relative DDC activity ( k D 3 ) was 0.26 min−1 in striatum, 0.04 min−1 in hypothalamus, and 0.02 min−1 in hippocampus. In striatum, 3,4-[3 H]dihydroxyphenylacetic acid ([3 H]DOPAC) was formed from [3 H]DA with a rate constant of 0.013 min−1 , [3 H]homovanillic acid ([3 H]HVA) was formed from [3 H]DOPAC at a rate constant of 0.020 min−1 , and [3 H]HVA was eliminated from brain at a rate constant of 0.037 min−1 . Together, these rate constants predicted the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA catabolism, substantially reduced the contrast between striatum and cortex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, k D 3 was reduced by 50% in striatum and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC activity is reduced in specific brain regions after monoamine oxidase inhibition. Thus, DDC activity may be a regulated step in the synthesis of DA. 相似文献
56.
Curtis J. Condon Su-Hua Chang Albert S. Feng 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,168(6):709-725
Summary Response characteristics of 130 single neurons in the superior olivary nucleus of the northern leopard frog (Rana pipiens pipiens) were examined to determine their selectivity to various behaviorally relevant temporal parameters [rise-fall time, duration, and amplitude modulation (AM) rate of acoustic signals. Response functions were constructed with respect to each of these variables. Neurons with different temporal firing patterns such as tonic, phasic or phasic-burst firing patterns, participated in time domain analysis in specific manners. Phasic neurons manifested preferences for signals with short rise-fall times, thus possessing low-pass response functions with respect to this stimulus parameter; conversely, tonic and phasic-burst units were non-selective and possessed all-pass response functions. A distinction between temporal firing patterns was also observed for duration coding. Whereas phasic units showed no change in the mean spike count with a change in stimulus duration (i.e., all-pass duration response functions), tonic and phasic-burst units gave higher mean spike counts with an increase in stimulus duration (i.e., primary-like high-pass response functions). Phasic units manifested greater response selectivity for AM rate than did tonic or phasic-burst units, and many phasic units were tuned to a narrow range of modulation rates (i.e., band-pass). The results suggest that SON neurons play an important role in the processing of complex acoustic patterns; they perform extensive computations on AM rate as well as other temporal parameters of complex sounds. Moreover, the response selectivities for rise-fall time, duration, and AM rate could often be shown to contribute to the differential responses to complex synthetic and natural sounds.Abbreviations
SON
superior olivary nucleus
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DMN
dorsal medullary nucleus
-
TS
torus semicircularis
-
FTC
frequency threshold curve
-
BF
best excitatory frequency
-
PAM
pulsatile amplitude modulation
-
SAM
sinusoidal amplitude modulation
-
SQAM
square-wave amplitude modulation
-
MTF
modulation transfer function
-
PSTH
peri-stimulus time histogram 相似文献
57.
Hillaire ML van Eijk M van Trierum SE van Riel D Saelens X Romijn RA Hemrika W Fouchier RA Kuiken T Osterhaus AD Haagsman HP Rimmelzwaan GF 《PloS one》2011,6(9):e25005
The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted. 相似文献
58.
59.
By sequence analysis of 96 randomly selected clones in a cDNA library of Xanthophyllomyces dendrorhous, ten novel, full-length clones encoding cytoplasmic ribosomal proteins (rp) were found. The deduced amino acid sequences showed significant homology to their counterparts from eukaryotic origin including mammals, fungi and plants. Some ribosmal protein encoding cDNAs appeared several times, but by Southern blot analysis it was shown they are encoded by a single copy gene. The nucleotide sequences of ten full length cDNAs were used to investigate the codon usage in X. dendrorhous. 相似文献
60.
We developed a general method, microarray-based genomic selection (MGS), capable of selecting and enriching targeted sequences from complex eukaryotic genomes without the repeat blocking steps necessary for bacterial artificial chromosome (BAC)-based genomic selection. We demonstrate that large human genomic regions, on the order of hundreds of kilobases, can be enriched and resequenced with resequencing arrays. MGS, when combined with a next-generation resequencing technology, can enable large-scale resequencing in single-investigator laboratories. 相似文献