Cryptochromes

隐色素
  • 文章类型: Journal Article
    背景:根据一些研究,饮食可与CRY1基因多态性相互作用,可能与肥胖和心血管疾病(CVD)的风险有关。所以,这项研究调查了超重女性和肥胖女性中CRY1多态性和AHEI对心血管危险因素的交互作用.
    方法:这项横断面研究是对377名年龄在18-48岁(BMI≥25kg/m2)的超重和肥胖的伊朗妇女进行的。通过使用食物频率问卷(FFQ)评估147个项目的饮食摄入量。AHEI是根据以前的研究计算的。评估人体测量和生化测量,并使用生物电阻抗分析方法进行身体分析。通过限制性片段长度多态性(PCR-RFLP)方法对rs2287161进行基因分型。根据rs2287161基因型将对象分为三组。
    结果:我们的发现确定C等位基因的患病率为51.9%,G等位基因的患病率为48.0%。平均年龄和BMI分别为36.6±9.1岁和31±4kg/m2。在控制了混杂因素(BMI,年龄,总能量摄入,和身体活动),这项研究表明,CC基因型和坚持AHEI对高LDL的几率有显著的交互作用(OR=1.94,95%CI=1.24-3.05,交互作用的P=0.004),高血压(OR=1.80,95%CI=1.11~2.93,交互作用P=0.01)和高血糖(OR=1.56,95%CI=0.98~2.47,交互作用P=0.05)。
    结论:这项研究表明坚持AHEI可以降低高LDL的几率,高血压,rs2287161的CC基因型和高血糖。
    BACKGROUND: According to some studies, diet can be interaction with CRY1 polymorphism and may be related to obesity and the risk of cardiovascular diseases (CVD). So, this study examined the interaction between CRY1 polymorphism and AHEI on cardiovascular risk factors in overweight women and women with obesity.
    METHODS: This cross-sectional study was performed on 377 Iranian women with overweight and obesity aged 18-48(BMI ≥ 25 kg/m2). Dietary intake was evaluated by the use of a food frequency questionnaire (FFQ) with 147 items. The AHEI was calculated based on previous studies. Anthropometric and biochemical measurements were assessed and the bioelectrical impedance analysis method was used for body analysis. The rs2287161 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method. Objects were divided into three groups based on rs2287161 genotypes.
    RESULTS: Our findings determined that the prevalence of the C allele was 51.9% and the G allele was 48.0%. The mean age and BMI were 36.6 ± 9.1years and 31 ± 4 kg/m2 respectively. After controlling for confounders (BMI, age, total energy intake, and physical activity), this study demonstrated that there was a significant interaction between CC genotype and adherence to AHEI on odds of hyper LDL (OR = 1.94, 95% CI = 1.24-3.05, P for interaction = 0.004), hypertension (OR = 1.80, 95% CI = 1.11-2.93, P for interaction = 0.01) and hyperglycemia (OR = 1.56, 95% CI = 0.98-2.47, P for interaction = 0.05).
    CONCLUSIONS: This study indicated that adherence to AHEI can reduce the odds of hyper LDL, hypertension, and hyperglycemia in the CC genotype of rs2287161.
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  • 文章类型: Journal Article
    认为迁徙鸣鸟的磁罗盘感觉的生物物理机制依赖于位于鸟类眼中的隐色素蛋白中含黄素的自由基对的光化学反应。这一假设的结果是,地球磁场对反应产物量子产率的影响应该对同位素取代敏感,同位素取代会改变自由基中的超精细相互作用。在这份报告中,我们使用自旋动力学模拟来探索1H→2H的影响,12C→13C,和14N→15N同位素取代对隐色素4a作为磁性方向传感器的作用。得出两个主要结论。(1)黄素发色团的均匀氘代似乎是增强磁场效应各向异性并改变其对称性的最佳方法。(2)12个黄素碳中的3个的13C取代,特别是C4,C4a,和C8α,似乎是减弱各向异性的最佳方法。一旦光谱技术可用于测量定向蛋白质样品上的磁场效应,这些预测就应该深入了解控制磁灵敏度的因素。
    The biophysical mechanism of the magnetic compass sense of migratory songbirds is thought to rely on the photochemical reactions of flavin-containing radical pairs in cryptochrome proteins located in the birds\' eyes. A consequence of this hypothesis is that the effect of the Earth\'s magnetic field on the quantum yields of reaction products should be sensitive to isotopic substitutions that modify the hyperfine interactions in the radicals. In this report, we use spin dynamics simulations to explore the effects of 1H → 2H, 12C → 13C, and 14N → 15N isotopic substitutions on the functioning of cryptochrome 4a as a magnetic direction sensor. Two main conclusions emerge. (1) Uniform deuteration of the flavin chromophore appears to be the best way to boost the anisotropy of the magnetic field effect and to change its symmetry. (2) 13C substitution of three of the 12 flavin carbons, in particular C4, C4a, and C8α, seems to be the best recipe for attenuating the anisotropy. These predictions should give insight into the factors that control the magnetic sensitivity once spectroscopic techniques are available for measuring magnetic field effects on oriented protein samples.
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  • 文章类型: Journal Article
    A number of genome-wide association studies have investigated sleep phenotypes and disorders in humans. However, the contribution of genetic variation to sleep problems in Japanese populations has remained unclear. Sleep-onset problems are the most common symptom of insomnia. Here, we examined the relationship between single nucleotide polymorphisms (SNPs) of BMAL1 (ARNTL1), CLOCK, CRY1, CRY2, and PER2, which are genes involved in the clock mechanism, and sleep-onset problems in a Japanese general population. This study included 1,397 subjects aged ≥ 40 years who participated in an annual health check-up in Yamagata Prefecture. A total of 80 SNPs of 5 circadian clock genes were analyzed. Multivariate logistic regression analyses identified variant rs11113179 in CRY1 and variants rs1026071 and rs1562438 in BMAL1 as genetic risk factors for sleep induction disorder. These findings suggest that CRY1 and BMAL1 polymorphisms are related to sleep-onset problems in a Japanese general population. However, none of the SNPs remained significant at a stringent level of multiple correction.
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  • 文章类型: Journal Article
    Cell migration is a complex biophysical process which involves the coordination of molecular assemblies including integrin-dependent adhesions, signaling networks and force-generating cytoskeletal structures incorporating both actin polymerization and myosin activity. During the last decades, proteomic studies have generated impressive protein-protein interaction maps, although the subcellular location, duration, strength, sequence, and nature of these interactions are still concealed. In this chapter we describe how recent developments in superresolution microscopy (SRM) and single-protein tracking (SPT) start to unravel protein interactions and actions in subcellular molecular assemblies driving cell migration.
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  • 文章类型: Journal Article
    背景:转录因子(TF)是真核生物生长和发育的重要调节因子。碱性-螺旋-环-螺旋(bHLHs)是涉及几种关键调节功能的最重要的TFs家族之一。与隐色素相互作用的bHLH(CIB)和隐色素形成广泛的调节网络,以介导过多的途径。尽管bHLHs调节植物中的关键生物过程,关于菠萝bHLHs的信息仍未被探索。
    结果:这里,我们在菠萝基因组中鉴定出121个bHLH蛋白.鉴定的基因根据其基因ID的升序重命名,并通过系统发育分析分为18个亚组。我们发现bHLH基因在菠萝发育的不同器官和阶段都有表达。此外,通过AcCIB2在拟南芥中的异位表达和Atcib2突变体的互补,我们验证了AcCIB2参与光形态发生和非生物应激反应。
    结论:我们的发现表明AcCIB2在开花时间调节和非生物胁迫反应中起着重要作用。本研究提供了有关bHLH基因的最新知识的更多见解,并表明它们在菠萝发育过程中的各种生物过程中的潜在作用。
    BACKGROUND: Transcription factors (TFs) are essential regulators of growth and development in eukaryotes. Basic-helix-loop-helix (bHLHs) is one of the most significant TFs families involved in several critical regulatory functions. Cryptochrome-interacting bHLH (CIB) and cryptochromes form an extensive regulatory network to mediate a plethora of pathways. Although bHLHs regulate critical biological processes in plants, the information about pineapple bHLHs remains unexplored.
    RESULTS: Here, we identified a total of 121 bHLH proteins in the pineapple genome. The identified genes were renamed based on the ascending order of their gene ID and classified into 18 subgroups by phylogenetic analysis. We found that bHLH genes are expressed in different organs and stages of pineapple development. Furthermore, by the ectopic expression of AcCIB2 in Arabidopsis and complementation of Atcib2 mutant, we verified the involvement of AcCIB2 in photomorphogenesis and abiotic stress response.
    CONCLUSIONS: Our findings revealed that AcCIB2 plays an essential role in flowering time regulation and abiotic stress response. The present study provides additional insights into the current knowledge of bHLH genes and suggests their potential role in various biological processes during pineapple development.
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  • 文章类型: Journal Article
    真核发生,真核生物的起源,仍然知之甚少。在这里,我们展示了覆盖有关键生化特征图的详细的全王国系统发育分析如何提供有价值的线索。众所周知,光解酶/隐色素家族的蛋白质可以响应阳光的潜在有害影响修复DNA,并引起昼夜节律。来自多种原核生物和真核生物的光解酶/隐色素蛋白序列的系统发育分析指出了祖先细菌和祖先真核生物之间的许多水平基因转移事件。先前的实验研究已经表征了这些蛋白质中色氨酸残基的模式,这些模式对于光接收很重要,特别是色氨酸二元体,典型的色氨酸三合会,替代色氨酸三合会,色氨酸四分体和替代四分体。我们的结果表明,不同的三联体和四联体基序在生命王国中的传播伴随着推定的水平基因转移,并且与多种细菌对真核发生的贡献相一致。
    Eukaryogenesis, the origin of the eukaryotes, is still poorly understood. Herein, we show how a detailed all-kingdom phylogenetic analysis overlaid with a map of key biochemical features can provide valuable clues. The photolyase/cryptochrome family of proteins are well known to repair DNA in response to potentially harmful effects of sunlight and to entrain circadian rhythms. Phylogenetic analysis of photolyase/cryptochrome protein sequences from a wide range of prokaryotes and eukaryotes points to a number of horizontal gene transfer events between ancestral bacteria and ancestral eukaryotes. Previous experimental research has characterised patterns of tryptophan residues in these proteins that are important for photoreception, specifically a tryptophan dyad, a canonical tryptophan triad, an alternative tryptophan triad, a tryptophan tetrad and an alternative tetrad. Our results suggest that the spread of the different triad and tetrad motifs across the kingdoms of life accompanied the putative horizontal gene transfers and is consistent with multiple bacterial contributions to eukaryogenesis.
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  • 文章类型: Journal Article
    Photolyases (PL) and cryptochromes (CRY) are light-sensitive flavoproteins, respectively, involved in DNA repair and signal transduction. Their activation is triggered by an electron transfer process, which partially or fully reduces the photo-activated FAD cofactor. The full reduction additionally requires a proton transfer to the isoalloxazine ring. In plant CRY, an efficient proton transfer takes place within several μs, enabled by a conserved aspartate working as a proton donor, whereas in E. coli PL a proton transfer occurs in the 4 s timescale without any obvious proton donor, indicating the presence of a long-range proton transfer pathway. Unexpectedly, the insertion of an aspartate as a proton donor in a suitable position for proton transfer in E. coli PL does not initiate a transfer process similar to plant CRY, but even prevents the formation of a protonated FAD. In the present work, thanks to a combination of classical molecular dynamics and state-of-the-art DFTB3/MM simulations, we identify a proton transfer pathway from bulk to FAD in E. coli PL associated with a free energy profile in agreement with the experimental kinetics data. The free energy profiles of the proton transfer between aspartate and FAD show an inversion of the driving force between plant CRY and E. coli PL mutants. In the latter, the proton transfer from the aspartate is faster than in plant CRY but also thermodynamically disfavoured, in agreement with the experimental data. Our results further illustrate the fine tuning of the electrostatic FAD environment and the adaptability of the FAD pocket to ensure the divergent functions of the members of the PL-CRY family.
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  • 文章类型: Journal Article
    Background Metabolic syndrome (MetS) is a cluster of metabolic risk factors which increases the chances for future cardiovascular diseases, as well as diabetes. The underlying causes of MetS include overweight and obesity, physical inactivity and genetic factors. Our intension here was to focus in this study on the importance of the chronobiology, represented by melatonin (MT) and cryptochrome 2 (CRY2), in developing MetS and type 2 diabetes mellitus (T2DM). Thus, we aimed to compare MT and CRY2 plasma levels and correlate both biomarkers with adiposity, atherogenicity and hematological indices in MetS and T2DM cohorts. Methods In a cross-sectional study, 28 normoglycemic lean subjects (controls), 29 normoglycemic MetS subjects and 30 MetS (pre-diabetic/diabetic) were recruited. Results MT (pg/mL) was elevated significantly in MetS arm p-value < 0.05, whereas CRY2 levels (ng/mL) were markedly higher in both MetS groups (non-diabetic and pre-diabetic/diabetic) (all with p-value < 0.001). A reciprocal MT-CRY2 relationship was observed in the MetS (non-diabetic) group (p-value = 0.003). Of note in the total study population, both MT and CRY2 proportionally correlated with each of the following: atherogenicity index of plasma (AIP), waist circumference (WC) and systolic blood pressure (SBP) (all with p-value < 0.05) for MT and CRY2, respectively). Whereas MT correlated inversely with high-density lipoprotein-cholesterol (HDL-C) (p-value < 0.05). Additionally, CRY2 correlated directly with each of the following: diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein (LDL-C), hip circumference (HC), body adiposity index (BAI), weight-to-height (WHtR) ratio, mean platelet volume (MPV) and platelet/lymphocyte ratio (PLR) (p-value < 0.05). Conclusion These findings substantiate that both metabolic risk biomarkers can be prognostic tools and pharmacotherapeutic targets to slowdown the accelerated nature of T2DM.
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  • 文章类型: Journal Article
    Optogenetics allows precise, fast and reversible intervention in biological processes. Light-sheet microscopy allows observation of the full course of Drosophila embryonic development from egg to larva. Bringing the two approaches together allows unparalleled precision into the temporal regulation of signaling pathways and cellular processes in vivo. To develop this method, we investigated the regulation of canonical Wnt signaling during anterior-posterior patterning of the Drosophila embryonic epidermis. Cryptochrome 2 (CRY2) from Arabidopsis Thaliana was fused to mCherry fluorescent protein and Drosophila β-catenin to form an easy to visualize optogenetic switch. Blue light illumination caused oligomerization of the fusion protein and inhibited downstream Wnt signaling in vitro and in vivo. Temporal inactivation of β-catenin confirmed that Wnt signaling is required not only for Drosophila pattern formation, but also for maintenance later in development. We anticipate that this method will be easily extendable to other developmental signaling pathways and many other experimental systems.
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  • 文章类型: Journal Article
    Akt is commonly overexpressed and activated in cancer cells and plays a pivotal role in cell survival, protection, and chemoresistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anticancer drugs. Here we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic helix-loop-helix (CIB1), can regulate Akt-associated cell functions. By illuminating blue light to the cells stably transfected with PA-Akt probe, CRY2-Akt (a fusion protein of CRY2 and Akt) underwent a structural change and interacted with Myr-CIBN (myristoylated N-terminal portion of CIB1), anchoring it at the cell membrane. Western blot analysis revealed that S473 and T308 of the Akt of probe-Akt were sequentially phosphorylated by intermittent and continuous light illumination. Endogenous Akt and GSK-3β, one of the main downstream signals of Akt, were also phosphorylated, depending on light intensity. These facts indicate that photo-activation of probe-Akt can activate endogenous Akt and its downstream signals. The photo-activated Akt conferred protection against nutritional deprivation and H₂O₂ stresses to the cells significantly. Using the newly developed PA-Akt probe, endogenous Akt was activated easily, transiently, and repeatedly. This probe will be a unique tool in studying Akt-associated specific cellular functions in cancer cells and developing anticancer drugs.
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