共查询到20条相似文献,搜索用时 15 毫秒
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Lucien Rufener Nicola Bedoni Roland Baur Samantha Rey Dominique A. Glauser Jacques Bouvier Robin Beech Erwin Sigel Alessandro Puoti 《PLoS pathogens》2013,9(8)
Monepantel is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro-intestinal nematodes in sheep including those that are resistant to the classical anthelmintics. Previous studies have shown that the Caenorhabditis elegans acr-23 and the Haemonchus contortus Hco-mptl-1 genes may be prominent targets of monepantel. With this discovery it became possible to investigate the mode of action of monepantel in nematodes at the molecular level. In the present study, we show that a C. elegans mutant acr-23 strain is fully rescued by expressing the wild-type acr-23 gene. Moreover, we present a new mutant allele, and characterize acr-23 alleles genetically. We also show that acr-23 is expressed in body wall muscle cells, and provide therefore a possible explanation for the paralysis caused by monepantel. Furthermore, genetic evidence suggests that the chaperone RIC-3 is required for expression of full monepantel resistance. Finally, we present reconstitution of the C. elegans ACR-23 receptor in Xenopus laevis oocytes and provide direct evidence of its modulation by monepantel. Conversely, co-injection of the chaperone RIC-3 had no impact for channel reconstitution in X. laevis oocytes. These results reinforce the involvement of the ACR-23 family in the mode of action of monepantel and advance our understanding of this new class of anthelmintics. 相似文献
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Yuki Miyasaka Sari Suzuki Yasuhiro Ohshiba Kei Watanabe Yoshihiko Sagara Shumpei P. Yasuda Kunie Matsuoka Hiroshi Shitara Hiromichi Yonekawa Ryo Kominami Yoshiaki Kikkawa 《Experimental Animals》2013,62(4):333-346
The waltzer (v) mouse mutant harbors a mutation in Cadherin 23
(Cdh23) and is a model for Usher syndrome type 1D, which is
characterized by congenital deafness, vestibular dysfunction, and prepubertal onset of
progressive retinitis pigmentosa. In mice, functionally null Cdh23
mutations affect stereociliary morphogenesis and the polarity of both cochlear and
vestibular hair cells. In contrast, the murine Cdh23ahl
allele, which harbors a hypomorphic mutation, causes an increase in susceptibility to
age-related hearing loss in many inbred strains. We produced congenic mice by crossing
mice carrying the v niigata (Cdh23v-ngt) null
allele with mice carrying the hypomorphic Cdh23ahl allele on
the C57BL/6J background, and we then analyzed the animals’ balance and hearing phenotypes.
Although the
Cdh23v-ngt/ahl
compound heterozygous mice exhibited normal vestibular function, their hearing ability was
abnormal: the mice exhibited higher thresholds of auditory brainstem response (ABR) and
rapid age-dependent elevation of ABR thresholds compared with
Cdh23ahl/ahl
homozygous mice. We found that the stereocilia developed normally but were progressively
disrupted in
Cdh23v-ngt/ahl mice.
In hair cells, CDH23 localizes to the tip links of stereocilia, which are thought to gate
the mechanoelectrical transduction channels in hair cells. We hypothesize that the
reduction of Cdh23 gene dosage in
Cdh23v-ngt/ahl mice
leads to the degeneration of stereocilia, which consequently reduces tip link tension.
These findings indicate that CDH23 plays an important role in the maintenance of tip links
during the aging process. 相似文献
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Fokina AA Kuznetsova MA Repkova MN Venyaminova AG 《Nucleosides, nucleotides & nucleic acids》2004,23(6-7):1031-1035
A new strategy for engineering of catalytic two-component constructions based on 10-23 DNAzyme was proposed. The using of a combination of shortened DNAzyme with 2'-O-methyl oligomers as effectors significantly increased the catalytic activity of this DNAzyme. 相似文献
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《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1031-1035
A new strategy for engineering of catalytic two‐component constructions based on 10–23 DNAzyme was proposed. The using of a combination of shortened DNAzyme with 2′‐O‐methyl oligomers as effectors significantly increased the catalytic activity of this DNAzyme. 相似文献
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Partial trisomy 10q was observed in an eighteen year old girl with severe mental and physical retardation, microcephaly, a high forehead, microphthalmia, antimongoloid slants, low set ears and severely malformed extremities. A balanced translocation t(10q-;18q+), present in several family members, was identified by fluorescence and thermic denaturation techniques; the break points were 10q25 and 18q23. A comparison made with seven similar cases suggests a common, phenotypical appearance which may be of diagnostic value. 相似文献
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Two brothers trisomic for the distal two thirds of 10p are reported. Trisomy results from the malsegregation of a familial translocation rcp (10;18)(p13;q23) present in the father, a half-brother and the grand-father of the propositi. The phenotype is comparable to that of other 10p trisomic patients reported in the literature. 相似文献
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近20年间,DNA介导的生物传感器得到了快速的发展,DNA能够作为遗传信息重要载体的同时,其折叠成的空间构象也具有很多的功能。功能核酸的概念逐渐引入到了包括生物传感、生物成像、医疗在内的重要领域中。10-23脱氧核酶作为功能核酸的一种,是通过体外筛选技术得到的,Mg2+存在的条件下能够特异性识别并切割RNA,切割位点为RNA中的嘧啶与嘌呤间的磷酸二酯键。由于其独特的识别以及切割能力,10-23脱氧核酶介导的相关疾病治疗得到了广泛的应用,同时人们逐渐开始关注10-23脱氧核酶介导的生物传感器的搭建。对于10-23脱氧核酶的结构、性质、作用方式及改进修饰进行了介绍,并对10-23脱氧核酶介导的生物传感器的搭建及应用进行了综述,旨为人们在未来使用10-23脱氧核酶搭建新型快捷生物传感器奠定理论基础。 相似文献
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Joel A. Mathews David R. Gibb Bing-Hung Chen Peggy Scherle Daniel H. Conrad 《The Journal of biological chemistry》2010,285(48):37531-37541
The low affinity receptor for IgE, CD23, is the natural regulator of IgE synthesis, and understanding both the synthesis and the catabolism of CD23 are, thus, important issues. Membrane CD23 is cleaved by a disintegrin and metalloproteinase 10 (ADAM10) and this cleavage influences the ability of CD23 to regulate IgE. In contrast to the belief that cleavage is a cell surface event, endosomal neutralization with NH4Cl was found to dramatically reduce CD23 cleavage, suggesting that the majority of CD23 cleavage occurred subsequent to internalization in the endosomal pathway and not at the cell surface. In line with this, full-length CD23 was shown to be sorted in an ADAM10-dependent manner into exosomes. Greatly increased ADAM10-mediated CD23 cleavage was seen at endosomal pH. Additionally, the stalk region of CD23 was found to interact with ADAM10 and ADAM10 binding of CD23 was found to be protease independent. SPR analysis of the interaction indicated about a 10-fold increase in the Rmax at endosomal pH (pH 5.8) compared with pH 7.4, whereas the affinity of the interaction was not significantly changed. The Rmax change, combined with the increased cleavage at endosomal pH, indicates greater accessibility of the CD23 stalk region for ADAM10 at the lower pH. These results indicate a model where CD23 internalization results in ADAM10-dependent incorporation into exosomes, followed by partial cleavage of CD23 by ADAM10 prior to being released from the cell. The increased cleavage at endosomal pH also has implications for other ADAM10 substrates. 相似文献
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M A Enriquez-Guerra H Rivera M Moller H Castillo-Sanchez J M Cantu 《Journal de génétique humaine》1986,34(3-4):327-330
An infant deceased at 2 months of age was found to have a 46,XY,-10, +der(10),t (6;10) (q23;q26) mat karyotype. Since the clinical findings were similar to those of the trisomy 6qter syndrome, the present observation agrees with the assignment of the 6q23----qter segment as the pathogenetic determiner of this entity. 相似文献
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