Circadian Clocks

昼夜节律时钟
  • 文章类型: Journal Article
    快速的发展和方法上的分歧阻碍了对科学知识如何积累的研究,整合和转移到公共领域。我们的工作建议使用维基百科,在线百科全书,作为当代科学的史学来源。我们选择了备受瞩目的基因编辑领域作为我们的测试案例,对CRISPR上的英文维基百科文章进行历史分析。使用混合方法方法,我们对CRISPR文章的文本进行了定性和定量分析,部分和参考文献,还有50篇附属文章。这些,我们发现,记录了CRISPR领域从基础科学发现到具有广泛社会和文化意义的生物技术革命的成熟。我们开发了自动化工具来支持此类研究,并证明了其在其他两个科学领域的适用性-冠状病毒和生物钟。我们的方法利用维基百科作为数字和免费档案,表明它可以记录知识的逐步增长以及科学研究积累并转化为公共话语的方式。以这种方式使用维基百科补充并克服了当代历史的一些问题,并且还可以增强现有的文献计量学研究。
    Rapid developments and methodological divides hinder the study of how scientific knowledge accumulates, consolidates and transfers to the public sphere. Our work proposes using Wikipedia, the online encyclopedia, as a historiographical source for contemporary science. We chose the high-profile field of gene editing as our test case, performing a historical analysis of the English-language Wikipedia articles on CRISPR. Using a mixed-method approach, we qualitatively and quantitatively analyzed the CRISPR article\'s text, sections and references, alongside 50 affiliated articles. These, we found, documented the CRISPR field\'s maturation from a fundamental scientific discovery to a biotechnological revolution with vast social and cultural implications. We developed automated tools to support such research and demonstrated its applicability to two other scientific fields-coronavirus and circadian clocks. Our method utilizes Wikipedia as a digital and free archive, showing it can document the incremental growth of knowledge and the manner scientific research accumulates and translates into public discourse. Using Wikipedia in this manner compliments and overcomes some issues with contemporary histories and can also augment existing bibliometric research.
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  • 文章类型: Journal Article
    背景:这项研究的目的是调查轮换夜班工作的关联,时钟,MTNR1A,钢铁工人MTNR1B基因多态性及其与2型糖尿病的相互作用。
    方法:在唐山唐钢公司进行了病例对照研究,中国。病例组和对照组的样本量分别为251和451。逻辑回归,采用对数线性模型和广义多因子维数(GMDR)方法研究昼夜节律基因之间的相互作用,褪黑素受体基因和旋转夜班对钢铁工人2型糖尿病的影响。由于相互作用(RERI)和可归因比例(AP)的相对超额风险用于评估加性相互作用。
    结果:旋转夜班工作,当前班次状态,夜班时间,校正混杂因素后,平均夜班频率与2型糖尿病风险增加相关.发现MTNR1B中的Rs1387153变体与2型糖尿病的风险增加有关,在MTNR1A基因rs2119882位点之间没有发现,CLOCK基因rs1801260位点与2型糖尿病的风险。MTNR1B基因rs1387153位点(RERI=0.98,(95%CI,0.40-1.55);AP=0.60,(95%CI,0.07-1.12))改变了轮换夜班工作与2型糖尿病风险之间的关联。MTNR1A基因rs2119882位点和CLOCK基因rs1801260位点的交互作用与2型糖尿病风险相关(RERI=1.07,(95%CI,0.23-1.91);AP=0.77,(95%CI,0.36-1.17))。基于GMDR方法的MTNR1A-MTNR1B-CLOCK旋转夜班工作模型的复杂相互作用可能会增加2型糖尿病的风险(P=0.011)。
    结论:轮班工作和MTNR1B中的rs1387153变异与钢铁工人患2型糖尿病的风险增加相关。MTNR1A-MTNR1B-CLOCK旋转夜班工作的复杂相互作用可能会增加2型糖尿病的风险。
    BACKGROUND: The purpose of this study is to investigate the association of rotating night shift work, CLOCK, MTNR1A, MTNR1B genes polymorphisms and their interactions with type 2 diabetes among steelworkers.
    METHODS: A case-control study was conducted in the Tangsteel company in Tangshan, China. The sample sizes of the case group and control group were 251 and 451, respectively. The logistic regression, log-linear model and generalized multifactor dimensionality (GMDR) method were used to investigate the interaction between circadian clock gene, melatonin receptor genes and rotating night shift work on type 2 diabetes among steelworkers. Relative excess risk due to interaction (RERI) and attributable proportions (AP) were used to evaluate additive interactions.
    RESULTS: Rotating night shift work, current shift status, duration of night shifts, and average frequency of night shifts were associated with an increased risk of type 2 diabetes after adjustment for confounders. Rs1387153 variants in MTNR1B was found to be associated with an increased risk of type 2 diabetes, which was not found between MTNR1A gene rs2119882 locus, CLOCK gene rs1801260 locus and the risk of type 2 diabetes. The association between rotating night shift work and risk of type 2 diabetes appeared to be modified by MTNR1B gene rs1387153 locus (RERI = 0.98, (95% CI, 0.40-1.55); AP = 0.60, (95% CI, 0.07-1.12)). The interaction between MTNR1A gene rs2119882 locus and CLOCK gene rs1801260 locus was associated with the risk of type 2 diabetes (RERI = 1.07, (95% CI, 0.23-1.91); AP = 0.77, (95% CI, 0.36-1.17)). The complex interaction of the MTNR1A-MTNR1B-CLOCK-rotating night shift work model based on the GMDR methods may increase the risk of type 2 diabetes (P = 0.011).
    CONCLUSIONS: Rotating night shift work and rs1387153 variants in MTNR1B were associated with an increased risk of type 2 diabetes among steelworkers. The complex interaction of MTNR1A-MTNR1B-CLOCK-rotating night shift work may increase the risk of type 2 diabetes.
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  • 文章类型: Journal Article
    Our purpose is to investigate the impact of circadian and melatonin pathway genes as well as their interactions with night-shift work (NSW) on breast cancer risk in Korean women. Information about NSW and other covariates was collected using a structured questionnaire and twenty-two polymorphisms in 11 genes were analyzed in a hospital-based case-control study with 941 cases of breast cancer and 959 controls. In analysis of the main effects of each single nucleotide polymorphisms(SNPs), variants in CLOCK rs11133373 was associated with breast cancer risk even after false discovery rate (FDR) correction (Odd Ratios (OR) = 1.38 (95% Confident Interval (CI) 1.14-1.69) in CG and CC compared to GG genotype. Analysis of MTNR1A rs2119882 demonstrated a decreased risk of breast cancer in CC compared to TT (p-FDR = 0.043). A correlation between NSW and breast cancer interaction was found in two loci. NSW increased risk of breast cancer in women who carried the heterozygote genotype of CRY2 rs2292912 (OR = 1.98, 95% CI = 1.14-3.44) or carried at least one minor allele of RORA rs1482057 (OR = 2.20, 95% CI = 1.10-4.37). Our study results support a putative role for several loci of circadian genes and genes of melatonin biosynthesis and their interaction, and the gene interactions with NSW in the development of breast cancer.
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  • 文章类型: Journal Article
    The circadian clock is entrained to light by the intrinsically photosensitive retinal ganglion cells. Loss of these cells in glaucoma, an eye disease with loss of retinal ganglion cells as its key feature, might thus result in a change in chronotype. We aimed to compare the chronotype between glaucoma patients and healthy subjects.
    We sent the Munich ChronoType Questionnaire to 221 glaucoma patients (response rate 81%); controls (primary control group) were primarily their spouses. After exclusion of shift workers and participants who woke-up due to an alarm clock on days off, 159 glaucoma patients (88 early, 21 moderate, 23 severe) and 163 controls remained. We calculated chronotype as the mid-sleep on days off, corrected for workweek accumulated sleep debt (MSFsc). We compared means and variances between groups using Welch\'s tests and F-tests, respectively. A secondary control group was recruited from participants in a citizen-science project (n = 17073) who completed an online questionnaire. A resampling method was applied to enable an age- and gender- matched comparison with the glaucoma patients.
    Compared to the primary control group, glaucoma did not affect the mean MSFsc (controls 3:47; early, moderate, and severe glaucoma 3:40, 3:45, and 3:33, respectively [P = 0.62]). Chronotype variability seemed to increase with increasing disease severity (severe glaucoma versus controls: P = 0.023). The mean MSFsc of the secondary control group was 3:50 (95% confidence interval 3:48 to 3:52); significantly later than that of the glaucoma patients (3:40; P = 0.024). Mean MSFsc did not differ significantly between the control groups (P = 0.42).
    No clear changes were found in the chronotype as determined by sleep phase in patients with glaucoma, especially not in early and moderate glaucoma. In severe glaucoma, chronotype variability seems to increase, possibly alongside a small advancement.
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  • 文章类型: Journal Article
    While research has shown that scientists use Wikipedia and that scientific content on Wikipedia ramifies back into scientific literature, many questions remain on how the two sides interact and through what paradigm this dynamic may be best understood. Using the circadian clock field as a case study, we discuss this scientific field\'s representation on Wikipedia. We traced the changes made to the articles for \"Circadian clock\" and \"Circadian rhythm\" and reviewed the debates that informed them over a span of a decade, using Wikipedia\'s native and third-party tools. Specifically, we focused on how groundbreaking research pertaining to the function of biological oscillators was integrated into the articles to reflect a wider paradigmatic shift within the field. We also identified the articles\' main editors to detail the dynamic collective editorial process that took place during a time that saw the field undergo a fundamental change. We discuss the different concerns the academic community has with Wikipedia-specifically regarding its content and its contributors-to ask whether the online encyclopedia\'s open model is inherently at odds with scientific culture or whether the model could reflect science or even expand on its core values and practices such as peer review and the idea of communicating science.
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  • 文章类型: Journal Article
    昼夜节律时钟通过精确基因表达程序的协调编排来驱动各种生物过程中的日常振荡。全局表达谱分析实验表明,转录组和蛋白质组的很大一部分处于昼夜节律控制之下,历史上人们认为这种输出节律依赖于这些基因的节律转录。最近的全基因组研究,然而,挑战了这种长期持有的观点,并指出了转录后调节在信使RNA(mRNA)水平驱动振荡的主要贡献,而其他人则强调了广泛的时钟平移调节,无论mRNA的节奏。有各种基因的例子,在一天中均匀转录,但表现出节律的mRNA水平,以及扁平的mRNA,随着蛋白质水平的波动,这种观察在很大程度上被认为是由每个步骤的独立监管产生的。因此,这些研究消除了任何联系,或耦合,这可能存在于基因表达的不同步骤之间,以及它们中的任何一个可能对后续步骤产生的影响。这里,我们认为,由于生物学和技术原因,在确定基因表达的每个不同阶段在调节输出分子节律中的相对贡献方面,陪审团仍然没有定论。此外,我们建议通过各种耦合机制,基因转录(即使是明显的心律失常)可能在决定基因表达振荡方面发挥了比目前估计的重要作用,调节下游步骤的节奏。此外,我们认为真核基因组在全基因组范围内调节每日RNA聚合酶II(RNAPII)募集和组蛋白修饰,为全球新生转录奠定基础,但是组织特异性机制在时钟控制下本地指定不同的过程。
    Circadian clocks drive daily oscillations in a variety of biological processes through the coordinate orchestration of precise gene expression programs. Global expression profiling experiments have suggested that a significant fraction of the transcriptome and proteome is under circadian control, and such output rhythms have historically been assumed to rely on the rhythmic transcription of these genes. Recent genome-wide studies, however, have challenged this long-held view and pointed to a major contribution of posttranscriptional regulation in driving oscillations at the messenger RNA (mRNA) level, while others have highlighted extensive clock translational regulation, regardless of mRNA rhythms. There are various examples of genes that are uniformly transcribed throughout the day but that exhibit rhythmic mRNA levels, and of flat mRNAs, with oscillating protein levels, and such observations have largely been considered to result from independent regulation at each step. These studies have thereby obviated any connections, or coupling, that might exist between the different steps of gene expression and the impact that any of them could have on subsequent ones. Here, we argue that due to both biological and technical reasons, the jury is still out on the determination of the relative contributions of each of the different stages of gene expression in regulating output molecular rhythms. In addition, we propose that through a variety of coupling mechanisms, gene transcription (even when apparently arrhythmic) might play a much relevant role in determining oscillations in gene expression than currently estimated, regulating rhythms at downstream steps. Furthermore, we posit that eukaryotic genomes regulate daily RNA polymerase II (RNAPII) recruitment and histone modifications genome-wide, setting the stage for global nascent transcription, but that tissue-specific mechanisms locally specify the different processes under clock control.
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