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  • 文章类型: Journal Article
    Aneuploidy causes birth defects and miscarriages, occurs in nearly all cancers and is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein (Rp) gene mutations are also eliminated, by cell competition with normal cells. Because Rp genes are spread across the genome, their copy number is a potential marker for aneuploidy. We found that elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. Segmentally aneuploid cells derived from targeted chromosome excisions were eliminated by the RpS12-Xrp1 cell competition pathway if they differed from neighboring cells in Rp gene dose, whereas cells with normal doses of the Rp and eIF2γ genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in Rp gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.
    Aneuploid cells emerge when cellular division goes awry and a cell ends up with the wrong number of chromosomes, the tiny genetic structures carrying the instructions that control life’s processes. Aneuploidy can lead to fatal conditions during development, and to cancer in an adult organism. A safety mechanism may exist that helps the body to detect and remove these cells. Yet, exactly this happens is still poorly understood: in particular, it is unclear how cells manage to ‘count’ their chromosomes. One way they could do so is through the ribosomes, the molecular ‘factories’ that create the building blocks required for life. In a cell, every chromosome carries genes that code for the proteins (known as Rps) forming ribosomes. Aneuploidy will alter the number of Rp genes, and in turn the amount and type of Rps the cell produces, so that ribosomes and the genes for Rps could act as a ‘readout’ of aneuploidy. Ji et al set out to test this theory in fruit flies. The first experiment used a genetic manipulation technique called site-specific recombination to remove parts of chromosomes from cells in the developing eye and wing. Cells which retained all their Rp genes survived, while those that were missing some usually died – but only when the surrounding cells were normal. In this situation, healthy cells eliminated their damaged neighbours through a process known as cell competition. A second experiment, using radiation as an alternative method of damaging chromosomes, also gave similar results. The work by Ji et al. reveals how the body can detect and eliminate aneuploid cells, potentially before they can cause harm. If the same mechanism applies in humans, boosting cell competition may, one day, helps to combat diseases like cancer.
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  • 文章类型: Journal Article
    The biogenesis of ribosomes is a finely regulated multistep process linked to cell proliferation and growth-processes which require a high rate of protein synthesis. One of the master regulators of ribosome biogenesis is Myc, a well-known proto-oncogene that has an important role in ribosomal function and in the regulation of protein synthesis. The relationship between Myc and the ribosomes was first highlighted in Drosophila, where Myc\'s role in controlling Pol-I, II and III was evidenced by both microarrays data, and by the ability of Myc to control growth (mass), and cellular and animal size. Moreover, Myc can induce cell competition, a physiological mechanism through which cells with greater fitness grow better and thereby prevail over less competitive cells, which are actively eliminated by apoptosis. Myc-induced cell competition was shown to regulate both vertebrate development and tumor promotion; however, how these functions are linked to Myc\'s control of ribosome biogenesis, protein synthesis and growth is not clear yet. In this review, we will discuss the major pathways that link Myc to ribosomal biogenesis, also in light of its function in cell competition, and how these mechanisms may reflect its role in favoring tumor promotion.
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  • 文章类型: Journal Article
    Clinical MRI protocols are time-consuming; hence, new faster techniques are needed. One new fast multicontrast MRI technique, called echo planar image mix (EPIMix) (including contrasts T1 -FLAIR, T2 -weighted, diffusion-weighted images [DWI], apparent diffusion coefficient [ADC], T2 *-weighted, and T2 -FLAIR images) needs to be tested.
    To assess if EPIMix has comparable diagnostic performance as routine clinical brain MRI.
    Prospective.
    A consecutive series of 103 patients\' brain MRI (January 2018 to May 2018).
    1.5 T or 3T. EPIMix and routine clinical protocol (clinical MRI included all or some of the contrasts T1 -FLAIR, T2 -weighted, DWI, T2 *-weighted, T2 -FLAIR, 3D-FSE).
    Two neuroradiologists assessed EPIMix and clinical scans and categorized the images as abnormal or normal and described diagnosis, artifacts, diagnostic confidence image quality, and comparison of imaging time.
    Pivot tables with diagnostic performance calculated by receiver operating characteristics (ROC) and the area under curve (AUC). Disease categorization and image quality measures were evaluated. The study protocol is published at ClinicalTrials.gov NCT03338270.
    After exclusion of 21 patients, 82 patients had a routine clinical MRI with comparable contrasts to EPIMix and were evaluated. The diagnostic performance to categorize a full brain MRI investigation as abnormal or normal was comparable between EPIMix (AUC 0.99 (95% confidence interval [CI] 0.97-1.00) and 0.99 (95% CI 0.97-1.00)) and routine clinical MRI (n = 82). Sensitivity was 95% (95% CI 88-95) and 93% (95% CI 86-98), and specificity 100% (95% CI 97-100) and 100% (95% CI 90-100). Disease categorization was congruent between EPIMix and clinical routine MRI in 90% (reader 2) and 93% (reader 1). Image quality was generally rated lower for EPIMix (P < 0.001). Imaging time was 78 seconds for EPIMix and for the same contrasts 12 minutes 29 seconds for conventional 3T MRI.
    EPIMix has comparable diagnostic performance (disease identification and categorization) for most patients investigated in clinical routine. Level of Evidence 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1824-1833.
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  • 文章类型: Journal Article
    术语“细胞竞争”已被用于描述这样的现象,即特定细胞在组织生长期间只有当更具竞争性的细胞可用于替换它们时才被消除。多个例子暗示p53在哺乳动物细胞竞争中的差异活性,但尚未发现p53在果蝇中具有相同的作用,细胞竞争现象首先被认识到。最近的研究表明,果蝇细胞携带核糖体蛋白(Rp)基因突变,通过与野生型细胞的细胞竞争而被淘汰,激活p53靶基因,Xrp1。在DiamondBlackfan贫血中,人类Rp突变体激活p53本身,通过核仁应激途径。这些结果表明哺乳动物和果蝇Rp突变体之间存在联系,翻译,细胞竞争
    The term cell competition has been used to describe the phenomenon whereby particular cells can be eliminated during tissue growth only when more competitive cells are available to replace them. Multiple examples implicate differential activity of p53 in cell competition in mammals, but p53 has not been found to have the same role in Drosophila, where the phenomenon of cell competition was first recognized. Recent studies now show that Drosophila cells harboring mutations in Ribosomal protein (Rp) genes, which are eliminated by cell competition with wild type cells, activate a p53 target gene, Xrp1. In Diamond Blackfan Anemia, human Rp mutants activate p53 itself, through a nucleolar stress pathway. These results suggest a link between mammalian and Drosophila Rp mutants, translation, and cell competition.
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  • 文章类型: Journal Article
    Time estimation helps allocating time to different tasks and to plan behavioural sequences. It may also be relevant to animal welfare if it enables animals assessing the duration of a negative situation. Here, we investigated the ability of dry sows to estimate short and long time periods. We used a variant of the peak-interval procedure and the choice between 2 resources of different quality and replenishment rates to assess time periods in the order of minutes and days, respectively. In the minute-experiment, the sows were trained to expect an interruption while feeding at the end of an interval. Heart rate and heart rate variability slightly and continuously increased and decreased, respectively, towards the end of that interval. In the day-experiment, lasting about 60days, the sows were increasingly more likely to open the door to a high food reward on the correct day when this food reward was presented every fifth day. We conclude that the sows learnt to estimate time intervals of 5days after lengthy training but did not accurately learn intervals in the range of minutes. Therefore, they might re-visit replenishing resources after several days, but may not base short-term decisions solely on the passing of time.
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  • 文章类型: Journal Article
    A conventional view of development is that cells cooperate to build an organism. However, based on studies of Drosophila, it has been known for years that viable cells can be eliminated by their neighbours through a process termed cell competition. New studies in mammals have revealed that this process is universal and that many factors and mechanisms are conserved. During cell competition, cells with lower translation rates or those with lower levels of proteins involved in signal transduction, polarity and cellular growth can survive in a homogenous environment but are killed when surrounded by cells of higher fitness. Here, we discuss recent advances in the field as well as the mechanistic steps involved in this phenomenon, which have shed light on how and why cell competition exists in developing and adult organisms.
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  • 文章类型: Journal Article
    通过使用为观赏鱼中的Xiphophorus和Poeciliareticulata开发的微卫星(SSR)标记应用回交和testcross策略,构建了初步的连锁图。MollyPoeciliasp.具有18个SSR基因座的连锁图谱由四个连锁群组成,其图谱大小为516.1cM。以随机方式测试了基因型和表型之间的关联,发现背鳍长度的QTL与连锁群2上的基因座Msb069连锁。巧合的是,基因座Msb069也被报道为推定的同源引物对,其中包含SSR重复基序,该基序编码hSMP-1,这是一个性别决定基因座。背鳍长度,特别是在Poecilialatipinna的雄性中,是求偶显示过程中的重要特征。因此,我们推测背鳍长度和推定的hSMP-1基因与男性性特征非常接近。
    A preliminary linkage map was constructed by applying backcross and testcross strategy using microsatellite (SSR) markers developed for Xiphophorus and Poecilia reticulata in ornamental fish, molly Poecilia sp. The linkage map having 18 SSR loci consisted of four linkage groups that spanned a map size of 516.1cM. Association between genotypes and phenotypes was tested in a random fashion and QTL for dorsal fin length was found to be linked to locus Msb069 on linkage group 2. Coincidentally, locus Msb069 was also reported as putative homologue primer pairs containing SSRs repeat motif which encoded hSMP-1, a sex determining locus. Dorsal fin length particularly in males of Poecilia latipinna is an important feature during courtship display. Therefore, we speculate that both dorsal fin length and putative hSMP-1 gene formed a close proximity to male sexual characteristics.
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  • 文章类型: Journal Article
    己糖激酶家族包括己糖激酶I,II,III和IV,催化葡萄糖的磷酸化产生葡萄糖6-磷酸。己糖激酶IV,也被称为葡萄糖激酶,只有含有两个己糖激酶结构域的其他类型的己糖激酶的一半大小。尽管己糖激酶的研究取得了巨大的进展,葡萄糖激酶和其他己糖激酶之间的进化关系仍然不确定,导致脊椎动物己糖激酶出现的分子过程仍然存在争议。在这里,我们清楚地证明了在文昌鱼中存在单个己糖激酶样基因,Bjhk,显示组织特异性表达模式,在肝盲肠中表达最丰富,睾丸和卵巢。系统发育和同种学分析均表明BjHK是脊椎动物己糖激酶IV的原型,即葡萄糖激酶。我们还首次发现重组BjHK显示出类似脊椎动物己糖激酶I的功能性酶活性,II,III和IV。此外,在肝盲肠中检测到天然的葡萄糖激酶活性。最后,葡萄糖激酶活性在肝盲肠明显减少,而通过喂食却大大增加了。总之,这些表明Bjhk代表了葡萄糖激酶的原型,脊椎动物己糖激酶基因家族是通过基因复制进化而来的,肝盲肠在控制文昌鱼的葡萄糖稳态中起作用,支持肝盲肠是与肝脏同源的组织的观点。
    Hexokinase family includes hexokinases I, II, III and IV, that catalyze the phosphorylation of glucose to produce glucose 6-phosphate. Hexokinase IV, also known as glucokinase, is only half size of the other types of hexokinases that contain two hexokinase domains. Despite the enormous progress in the study of hexokinases, the evolutionary relationship between glucokinase and other hexokinases is still uncertain, and the molecular processes leading to the emergence of hexokinases in vertebrates remain controversial. Here we clearly demonstrated the presence of a single hexokinase-like gene in the amphioxus Branchiostoma japonicum, Bjhk, which shows a tissue-specific expression pattern, with the most abundant expression in the hepatic caecum, testis and ovary. The phylogenetic and synteny analyses both reveal that BjHK is the archetype of vertebrate hexokinases IV, i.e. glucokinases. We also found for the first time that recombinant BjHK showed functional enzyme activity resembling vertebrate hexokinases I, II, III and IV. In addition, a native glucokinase activity was detected in the hepatic caecum. Finally, glucokinase activity in the hepatic caecum was markedly reduced by fasting, whereas it was considerably increased by feeding. Altogether, these suggest that Bjhk represents the archetype of glucokinases, from which vertebrate hexokinase gene family was evolved by gene duplication, and that the hepatic caecum plays a role in the control of glucose homeostasis in amphioxus, in favor of the notion that the hepatic caecum is a tissue homologous to liver.
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  • 文章类型: Journal Article
    对非洲企鹅(Spheniscusdemersus)的完整线粒体基因组进行了测序。通过下一代测序和引物步移对分子进行测序。基因组的长度为17,346bp。与迄今为止报道的另外两个企鹅基因组的线粒体DNA进行了比较;小蓝企鹅(Eudyptulaminor)和Rockhopper企鹅(Eudypteschrysocome)。该分析使得鉴定常见的企鹅线粒体DNA特征成为可能。S.demersusmtDNA基因组非常相似,在组成和长度上都对E.chrysocome和E.minor基因组。非洲企鹅线粒体基因组的基因含量是典型的脊椎动物,所有三种企鹅都具有最初在鸡中鉴定的标准基因顺序。Demersus的控制区位于tRNA-Glu和tRNA-Phe之间,所有三种企鹅都包含两组相似的重复序列,在控制区的3'末端具有不同的拷贝数,考虑大小差异。这是非洲企鹅线粒体基因组完整核苷酸序列的首次报道,S、Demersus。这些结果随后可用于为企鹅系统发育研究提供信息,并深入了解基因组的进化。
    The complete mitochondrial genome of the African Penguin (Spheniscus demersus) was sequenced. The molecule was sequenced via next generation sequencing and primer walking. The size of the genome is 17,346 bp in length. Comparison with the mitochondrial DNA of two other penguin genomes that have so far been reported was conducted namely; Little blue penguin (Eudyptula minor) and the Rockhopper penguin (Eudyptes chrysocome). This analysis made it possible to identify common penguin mitochondrial DNA characteristics. The S. demersus mtDNA genome is very similar, both in composition and length to both the E. chrysocome and E. minor genomes. The gene content of the African penguin mitochondrial genome is typical of vertebrates and all three penguin species have the standard gene order originally identified in the chicken. The control region for S. demersus is located between tRNA-Glu and tRNA-Phe and all three species of penguins contain two sets of similar repeats with varying copy numbers towards the 3\' end of the control region, accounting for the size variance. This is the first report of the complete nucleotide sequence for the mitochondrial genome of the African penguin, S. demersus. These results can be subsequently used to provide information for penguin phylogenetic studies and insights into the evolution of genomes.
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  • 文章类型: Journal Article
    同种异体移植物炎症因子-1(AIF-1)是与炎症反应相关的关键因素之一。在本研究中,通过EST(表达序列标签)分析和RACE(cDNA末端的快速扩增)方法,从扇贝扇贝(命名为CfAIF-1)中鉴定了AIF-1的全长cDNA。CfAIF-1的cDNA由58bp的5末端非翻译区(UTR)组成,607bp的3-UTR,带有poly(A)尾巴,和468bp的开放阅读框(ORF),编码155个氨基酸的多肽,推定分子量为17.8kDa。在CfAIF-1的推导氨基酸序列中存在EF手Ca(2)结合基序,该基序在其他AIF-1s中保守。与脊椎动物相比,CfAIF-1与无脊椎动物具有更紧密的系统发育关系。CfAIF-1的mRNA转录本在肝胰腺中主要表达,血细胞和内收肌。在扇贝本体发育期间,在从卵到囊胚的早期发育阶段,CfAIF-1mRNA表达水平较低,然后从胃吸虫到晚期veliger幼虫显着增加(P<0.05)。此外,成年扇贝血细胞CfAIF-1mRNA表达水平在LPS后12-48h显著上调,PGN和polyI:C刺激(P<0.01),但葡聚糖刺激后没有检测到明显的波动。此外,在6h(P<0.05)和12h(P<0.01)时,细菌anguillarum的攻击显着诱导了血细胞中CfAIF-1的mRNA表达。所有这些结果共同表明,CfAIF-1可能参与了个体发育过程中的免疫反应,并有助于防御扇贝中的微生物感染。
    The allograft inflammatory factor-1 (AIF-1) is one of the key factors associated with inflammatory response. In the present study, the full-length cDNA of AIF-1 was identified from Zhikong scallop Chlamys farreri (named as CfAIF-1) by EST (expressed sequence tag) analysis and RACE (rapid-amplification of cDNA ends) approaches. The cDNA of CfAIF-1 consisted of a 5-terminal untranslated region (UTR) of 58 bp, a 3-UTR of 607 bp with a poly (A) tail, and an open reading frame (ORF) of 468 bp encoding a polypeptide of 155 amino acids with the putative molecular mass of 17.8 kDa. There was an EF hand Ca(2+)-binding motif in the deduced amino acid sequence of CfAIF-1 which was conserved in other AIF-1s. CfAIF-1 shared closer phylogenetic relationship with invertebrate counterparts than vertebrate. The mRNA transcripts of CfAIF-1 were dominantly expressed in hepatopancreas, hemocytes and adductor. During scallop ontogenesis, the CfAIF-1 mRNA was expressed at a low level at early developmental stages from eggs to blastula, and then increased significantly from gastruta to late veliger larvae (P<0.05). Moreover, the mRNA expression levels of CfAIF-1 in the hemocytes of adult scallop were significantly up-regulated during 12-48 h after LPS, PGN and poly I:C stimulation (P<0.01), but there was no significant fluctuation detected after glucan stimulation. Furthermore, the challenge of bacteria Vibrio anguillarum remarkably induced the mRNA expression of CfAIF-1 in hemocytes at 6h (P<0.05) and 12h (P<0.01). All these results collectively indicated that CfAIF-1 might be involved in the immune response during the ontogenesis and contribute to the defense against microbe infection in scallops.
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