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目的:探究人髓细胞白血病基因-1(myeloid cell leukemia-1,Mcl-1)是否参与非小细胞肺癌对吉非替尼的耐药。方法:应用Western blot检测Mcl-1在吉非替尼敏感细胞PC-9和耐药细胞H1975表达差异;梯度浓度的吉非替尼作用于PC-9细胞后,Western blot实验检测B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)家族中抗凋亡蛋白的表达变化;应用Western blot实验检测Mcl-1在PC-9和H1975细胞内降解速度差异。结果:Mcl-1在PC-9细胞内的表达明显低于H1975细胞,差异有统计学意义(P0.05),并且随着吉非替尼作用浓度的升高,Mcl-1表达逐渐降低,而Bcl-2和Bcl-x L表达基本不变,并且PC-9细胞内Mcl-1降解更迅速,半衰期明显缩短。结论:非小细胞肺癌对吉非替尼耐药可能与Mcl-1的表达量上调,降解速度减慢,半衰期延长有关。  相似文献   
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By integrating next‐generation sequencing (NGS), bioinformatics, electron microscopy and conventional molecular biology tools, a new virus infecting kiwifruit vines has been identified and characterized. Being associated with double‐membrane‐bound bodies in infected tissues and having a genome composed of RNA segments, each one containing a single open reading frame in negative polarity, this virus shows the typical features of members of the genus Emaravirus. Five genomic RNA segments were identified. Additional molecular signatures in the viral RNAs and in the proteins they encode, together with data from phylogenetic analyses, support the proposal of creating a new species in the genus Emaravirus to classify the novel virus, which is tentatively named Actinidia chlorotic ringspot‐associated virus (AcCRaV). Bioassays showed that AcCRaV is mechanically transmissible to Nicotiana benthamiana plants which, in turn, may develop chlorotic spots and ringspots. Field surveys disclosed the presence of AcCRaV in four different species of kiwifruit vines in five different provinces of central and western China, and support the association of the novel virus with symptoms of leaf chlorotic ringspots in Actinidia. Data on the molecular features of small RNAs of 21–24 nucleotides, derived from AcCRaV RNAs targeted by host RNA silencing mechanisms, are also reported, and possible molecular pathways involved in their biogenesis are discussed.  相似文献   
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Jie Liu  Guoxian Yu  Yazhou Ren  Maozu Guo  Jun Wang 《Genomics》2019,111(5):1176-1182
Single nucleotide polymorphism (SNP) interactions can explain the missing heritability of common complex diseases. Many interaction detection methods have been proposed in genome-wide association studies, and they can be divided into two types: population-based and family-based. Compared with population-based methods, family-based methods are robust vs. population stratification. Several family-based methods have been proposed, among which Multifactor Dimensionality Reduction (MDR)-based methods are popular and powerful. However, current MDR-based methods suffer from heavy computational burden. Furthermore, they do not allow for main effect adjustment. In this work we develop a two-stage model-based MDR approach (TrioMDR) to detect multi-locus interaction in trio families (i.e., two parents and one affected child). TrioMDR combines the MDR framework with logistic regression models to check interactions, so TrioMDR can adjust main effects. In addition, unlike consuming permutation procedures used in traditional MDR-based methods, TrioMDR utilizes a simple semi-parameter P-values correction procedure to control type I error rate, this procedure only uses a few permutations to achieve the significance of a multi-locus model and significantly speeds up TrioMDR. We performed extensive experiments on simulated data to compare the type I error and power of TrioMDR under different scenarios. The results demonstrate that TrioMDR is fast and more powerful in general than some recently proposed methods for interaction detection in trios. The R codes of TrioMDR are available at: https://github.com/TrioMDR/TrioMDR.  相似文献   
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Sucrose non-fermenting (Snf1)-related kinase (SNRK) is a novel member of the AMP-activated protein kinase (AMPK) family and is involved in many metabolic processes. Here we report the crystal structure of an N-terminal SNRK fragment containing kinase and adjacent ubiquitin-associated (UBA) domains. This structure shows that the UBA domain binds between the N- and C-lobes of the kinase domain. The mode of UBA binding in SNRK largely resembles that in AMPK and brain specific kinase (BRSK), however, unique interactions play vital roles in stabilizing the KD-UBA interface of SNRK. We further propose a potential role of the UBA domain in the regulation of SNRK kinase activity. This study provides new insights into the structural diversities of the AMPK kinase family.  相似文献   
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Some social species exhibit high levels of fission–fusion dynamics (FFD) that improve foraging efficiency. In this study, we shed light on the way that FFD allows animal groups to cope with fluctuations in fruit availability. We explore the relative contribution of fruit availability and social factors like sex in determining association and proximity patterns in spider monkeys. We tested the influence of fruit availability and social factors on the association and proximity patterns using three-year data from a group of spider monkeys in the Yucatan Peninsula of Mexico. We identified subgroup members and estimated their Interindividual distances through instantaneous scan sampling. We evaluated fruit availability by monitoring the phenology of the 10 most important food tree species for spider monkeys in the study site. Social network analyses allowed us to evaluate association and proximity patterns in subgroups. We showed that association patterns vary between seasons, respond to changes in fruit availability, and are influenced by the sex of individuals, likely reflecting biological and behavioral differences between sexes and the interplay between ecological and social factors. In contrast, proximity patterns were minimally affected by changes in fruit availability, suggesting that social factors are more important than food availability in determining cohesion within subgroups.  相似文献   
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组蛋白乙酰化是表观遗传修饰的重要方式,主要受到组蛋白乙酰转移酶(histone acetyltransferases,HATs)和组蛋白去乙酰化酶(histone deacetylase,HDACs)催化.MYST是人类HATs的4大家族之一,包括MOF(males absent on the first),TIP60(tat interacting protein 60 kD),结合ORC1的组蛋白乙酰转移酶(histone acetyltransferase binding to ORC1,HBO1),单核细胞白血病锌指蛋白(monocytic leukemia zinc finger protein,MOZ)和MOZ相关蛋白(MOZ related factor,MORF)等,均具有典型的MYST结构域.MYST介导的乙酰化是重要的翻译后修饰,其催化底物包括组蛋白和非组蛋白,如组蛋白H3,H4,H2A,H2A突变体,以及许多参与DNA代谢、细胞增殖和发育调控的蛋白因子.MYST蛋白家族参与许多细胞的生理过程,本文主要综述其在调节基因转录、DNA损伤修复和肿瘤发生发展等方面的生物学功能.  相似文献   
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