排序方式: 共有22条查询结果,搜索用时 15 毫秒
1.
Don't judge species on their origins 总被引:1,自引:0,他引:1
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At the end of mitosis, daughter cells are separated from each other by cytokinesis. This process involves equal partitioning
and segregation of cytoplasm between the two cells. Despite years of study, the mechanism driving cytokinesis in animal cells
is not fully understood. Actin and myosin are major components of the contractile ring, the structure at the equator between
the dividing cells that provides the force necessary to constrict the cytoplasm. Despite this, there are also tantalizing
results suggesting that cytokinesis can occur in the absence of myosin. It is unclear what the roles are of the few other
contractile ring components identified to date. While it has been difficult to identify important proteins involved in cytokinesis,
it has been even more challenging to pinpoint the regulatory mechanisms that govern this vital process. Cytokinesis must be
precisely controlled both spatially and temporally; potential regulators of these parameters are just beginning to be identified.
This review discusses the recent progress in our understanding of cytokinesis in animal cells and the mechanisms that may
regulate it.
Received 24 August 1998; received after revision 9 October 1998; accepted 9 October 1998 相似文献
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Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector 总被引:24,自引:0,他引:24
Kay MA Manno CS Ragni MV Larson PJ Couto LB McClelland A Glader B Chew AJ Tai SJ Herzog RW Arruda V Johnson F Scallan C Skarsgard E Flake AW High KA 《Nature genetics》2000,24(3):257-261
Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease. 相似文献
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Pang SS Berry R Chen Z Kjer-Nielsen L Perugini MA King GF Wang C Chew SH La Gruta NL Williams NK Beddoe T Tiganis T Cowieson NP Godfrey DI Purcell AW Wilce MC McCluskey J Rossjohn J 《Nature》2010,467(7317):844-848
The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR β-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent αβ T-cell lineage differentiation. Whereas αβTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant α-chain (pre-Tα) that pairs with any TCR β-chain (TCRβ) following successful TCR β-gene rearrangement. Here we provide the basis of pre-Tα-TCRβ assembly and pre-TCR dimerization. The pre-Tα chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR α-chain; nevertheless, the mode of association between pre-Tα and TCRβ mirrored that mediated by the Cα-Cβ domains of the αβTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Tα domain to interact with the variable (V) β domain through residues that are highly conserved across the Vβ and joining (J) β gene families, thus mimicking the interactions at the core of the αβTCR's Vα-Vβ interface. Disruption of this pre-Tα-Vβ dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Tα chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR β-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Tα represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex. 相似文献
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The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells 总被引:45,自引:0,他引:45
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Vanessa Liang Milena Ullrich Hong Lam Yee Lian Chew Samuel Banister Xiaomin Song Thiri Zaw Michael Kassiou Jürgen Götz Hannah R. Nicholas 《Cellular and molecular life sciences : CMLS》2014,71(17):3339-3361
Protein misfolding and aggregation as a consequence of impaired protein homeostasis (proteostasis) not only characterizes numerous age-related diseases but also the aging process itself. Functionally related to the aging process are, among others, ribosomal proteins, suggesting an intimate link between proteostasis and aging. We determined by iTRAQ quantitative proteomic analysis in C. elegans how the proteome changes with age and in response to heat shock. Levels of ribosomal proteins and mitochondrial chaperones were decreased in aged animals, supporting the notion that proteostasis is altered during aging. Mitochondrial enzymes of the tricarboxylic acid cycle and the electron transport chain were also reduced, consistent with an age-associated energy impairment. Moreover, we observed an age-associated decline in the heat shock response. In order to determine how protein synthesis is altered in aging and in response to heat shock, we complemented our global analysis by determining the de novo proteome. For that, we established a novel method that enables both the visualization and identification of de novo synthesized proteins, by incorporating the non-canonical methionine analogue, azidohomoalanine (AHA), into the nascent polypeptides, followed by reacting the azide group of AHA by ‘click chemistry’ with an alkyne-labeled tag. Our analysis of AHA-tagged peptides demonstrated that the decreased abundance of, for example, ribosomal proteins in aged animals is not solely due to degradation but also reflects a relative decrease in their synthesis. Interestingly, although the net rate of protein synthesis is reduced in aged animals, our analyses indicate that the synthesis of certain proteins such as the vitellogenins increases with age. 相似文献
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(滚)法推拿形成运动狭窄粘弹性血管血液动力学 总被引:2,自引:0,他引:2
建立具有局部轴向运动狭窄的粘弹性血管中脉动血流模型,模拟研究中医扌衮法推拿的血液动力学机理.血液为牛顿流体,血流遵循线化Navier Stokes方程,血管壁为线性粘弹体,扌衮法推拿作用下血管形成轴向运动狭窄水平外力作用.求解得出血管内血液流速、流量以及管壁切应力.结果表明在扌衮法作用下,血管一个心动周期血液流量有明显变化,且随手法频率的加快以及作用力水平渗透系数增大而增大,随最大狭窄度的增大而减小;同时狭窄段内以及狭窄后部切应力随手法作用也明显变化.手法频率,血管最大狭窄度和作用力水平渗透系数,是中医扌衮法推拿的重要参数. 相似文献
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Chin K de Solorzano CO Knowles D Jones A Chou W Rodriguez EG Kuo WL Ljung BM Chew K Myambo K Miranda M Krig S Garbe J Stampfer M Yaswen P Gray JW Lockett SJ 《Nature genetics》2004,36(9):984-988
Transition through telomere crisis is thought to be a crucial event in the development of most breast carcinomas. Our goal in this study was to determine where this occurs in the context of histologically defined breast cancer progression. To this end, we assessed genome instability (using fluorescence in situ hybridization) and other features associated with telomere crisis in normal ductal epithelium, usual ductal hyperplasia, ductal carcinoma in situ and invasive cancer. We modeled this process in vitro by measuring these same features in human mammary epithelial cell cultures during ZNF217-mediated transition through telomere crisis and immortalization. Taken together, the data suggest that transition through telomere crisis and immortalization in breast cancer occurs during progression from usual ductal hyperplasia to ductal carcinoma in situ. 相似文献
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Oligohydramnios and cortisone-induced cleft palate in the mouse 总被引:2,自引:0,他引:2