• 【黏质塑料脂肪酸合成对于弓形虫的细胞器生物发生和寄生虫生存至关重要。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.0603391103 复制DOI
    作者列表:Mazumdar J,H Wilson E,Masek K,A Hunter C,Striepen B
    BACKGROUND & AIMS: :Apicomplexan parasites are the cause of numerous important human diseases including malaria and AIDS-associated opportunistic infections. Drug treatment for these diseases is not satisfactory and is threatened by resistance. The discovery of the apicoplast, a chloroplast-like organelle, presents drug targets unique to these parasites. The apicoplast-localized fatty acid synthesis (FAS II) pathway, a metabolic process fundamentally divergent from the analogous FAS I pathway in humans, represents one such target. However, the specific biological roles of apicoplast FAS II remain elusive. Furthermore, the parasite genome encodes additional and potentially redundant pathways for the synthesis of fatty acids. We have constructed a conditional null mutant of acyl carrier protein, a central component of the FAS II pathway in Toxoplasma gondii. Loss of FAS II severely compromises parasite growth in culture. We show FAS II to be required for the activation of pyruvate dehydrogenase, an important source of the metabolic precursor acetyl-CoA. Interestingly, acyl carrier protein knockout also leads to defects in apicoplast biogenesis and a consequent loss of the organelle. Most importantly, in vivo knockdown of apicoplast FAS II in a mouse model results in cure from a lethal challenge infection. In conclusion, our study demonstrates a direct link between apicoplast FAS II functions and parasite survival and pathogenesis. Our genetic model also offers a platform to dissect the integration of the apicoplast into parasite metabolism, especially its postulated interaction with the mitochondrion.
    背景与目标: 顶杆虫寄生虫是导致许多重要人类疾病的原因,包括疟疾和艾滋病相关的机会性感染。对这些疾病的药物治疗并不令人满意,并且受到耐药性的威胁。 apicoplast(一种叶绿体样细胞器)的发现提出了这些寄生虫特有的药物靶标。脂蛋白定位的脂肪酸合成(FAS II)途径(一种与人的类似FAS I途径基本不同的代谢过程)代表了这样一个目标。但是,apicoplast FAS II的具体生物学作用仍然难以捉摸。此外,寄生虫基因组编码用于脂肪酸合成的其他途径和潜在的冗余途径。我们已经构建了一个有条件的空缺突变体的酰基载体蛋白,这是弓形虫中FAS II途径的重要组成部分。 FAS II的丧失严重损害了培养物中寄生虫的生长。我们显示FAS II是激活丙酮酸脱氢酶所需的,丙酮酸脱氢酶是代谢前体乙酰辅酶A的重要来源。有趣的是,酰基载体蛋白的敲除也导致了无顶质生物发生中的缺陷和随之而来的细胞器的损失。最重要的是,在小鼠模型中体内敲除apicoplast FAS II可导致致命性攻击感染的治愈。总之,我们的研究表明了apicoplast FAS II功能与寄生虫生存和发病机制之间的直接联系。我们的遗传模型还提供了一个平台,可用于分析apicoplast整合到寄生虫代谢中,尤其是其与线粒体相互作用的假设。
  • 【肾上腺素不会损害人体中外源氨基酸的利用。】 复制标题 收藏 收藏
    DOI:10.1093/ajcn/65.6.1765 复制DOI
    作者列表:Schiefermeier M,Ratheiser KM,Zauner C,Roth E,Eichler HG,Matthews DE
    BACKGROUND & AIMS: The effect of epinephrine on leucine and phenylalanine kinetics was measured by using the stable isotope amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]-phenylalanine in the postabsorptive state and during the intravenous administration of a standard amino acid solution with respect to the amino acid load. Infusion of epinephrine (plasma concentrationapproximately 3600 pmol/L) decreased leucine and phenylalanine and increased ketoisocaproate plasma concentrations and increased the metabolic clearance rate of leucine and phenylalanine. Epinephrine neither influenced leucine or phenylalanine flux nor leucine oxidation or leucine net balance. Hyperaminoacidemia from amino acid infusion reduced endogenous leucine release and stimulated leucine oxidation and nonoxidative disposal of leucine, resulting in a dose-dependent increase in leucine net balance. Epinephrine did not influence any changes in amino acid kinetics during parenteral amino acid administration. Therefore, we conclude that epinephrine had no catabolic effects on amino acid metabolism and no negative effect on the utilization of a parenterally offered amino acid solution in healthy humans.

    背景与目标: 肾上腺素对亮氨酸和苯丙氨酸动力学的影响通过使用稳定的同位素氨基酸示踪剂L- [1-(13)C]亮氨酸和L- [苯基-2H5]-苯丙氨酸在吸收后的状态下和静脉内给予相对于氨基酸负载的标准氨基酸溶液。输注肾上腺素(血浆浓度约为3600 pmol / L)会降低亮氨酸和苯丙氨酸,增加酮异己酸血浆浓度,并增加亮氨酸和苯丙氨酸的代谢清除率。肾上腺素既不影响亮氨酸或苯丙氨酸通量,也不影响亮氨酸氧化或亮氨酸净平衡。来自氨基酸输注的高氨基酸血症减少了内源性亮氨酸的释放,并刺激了亮氨酸的氧化和亮氨酸的非氧化处置,从而导致了亮氨酸净平衡的剂量依赖性增加。肾上腺素不影响肠胃外氨基酸给药过程中氨基酸动力学的任何变化。因此,我们得出结论,肾上腺素对氨基酸的代谢没有分解代谢作用,对健康人肠胃外提供的氨基酸溶液的利用也没有负面影响。

  • 【分枝杆菌物种的组成型脂肪酸和酶谱。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Teng LJ,Liaw SJ,Hsueh PR,Fan JH,Luh KT,Ha SW
    BACKGROUND & AIMS: Sixty-one strains of Mycobacterium tuberculosis complex and 47 strains of nontuberculous mycobacteria were analyzed for fatty acids and enzyme profiles. Cellular fatty acids were extracted from bacteria, methylated and analyzed by gas liquid chromatography operated either manually (Perkin-Elmer) or by the automatic Microbial Identification System. The major cellular fatty acids in all mycobacterial species were C161. Tuberculostearic acid was found in all species with the exception of Mycobacterium gordonae. The fatty acids with a carbon-length longer than 20 could be detected only by conventional gas chromatography. Strains of M.

    tuberculosis had a high ratio of C260. For determination of branched-chain fatty acids, the MIS provided more definitive results. The data indicated that the fatty acid profiles could provide rapid species identification. The results of the enzyme profile analysis using API-ZYM strips showed 39 different patterns from 59 strains of M. tuberculosis, and 41 different patterns from 46 nontuberculous mycobacteria strains, suggesting that enzyme profiles can also be used for strain characterization within the same species.

    背景与目标: 分析了61株结核分枝杆菌复合体和47株非结核分枝杆菌的脂肪酸和酶谱。从细菌中提取细胞脂肪酸,进行甲基化,然后通过手动(Perkin-Elmer)或自动微生物鉴定系统操作的气相色谱法进行分析。所有分枝杆菌物种中的主要细胞脂肪酸均为C161。除戈登分枝杆菌外,所有物种中均发现了结核硬脂酸。碳长于20的脂肪酸只能通过常规气相色谱法检测到。结核分枝杆菌的菌株具有高的C 260比率。为了确定支链脂肪酸,MIS提供了更明确的结果。数据表明,脂肪酸谱可以提供快速的物种鉴定。使用API​​-ZYM试纸条进行酶谱分析的结果显示,来自59株结核分枝杆菌的39种不同模式和来自46株非结核分枝杆菌菌株的41种不同模式,表明酶谱也可用于同一物种内的菌株表征。

  • 【环氧二十碳三烯酸通过鸟嘌呤核苷酸结合蛋白激活冠状动脉平滑肌中的K通道。】 复制标题 收藏 收藏
    DOI:10.1161/01.res.80.6.877 复制DOI
    作者列表:Li PL,Campbell WB
    BACKGROUND & AIMS: Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the KCa channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the KCa channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also increased the KCa channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the pipette solution completely blocked the activation of the KCa channels induced by 11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.

    背景与目标: 环氧二十碳三烯酸(EET)是内皮细胞色素P450的花生四烯酸代谢产物。它们扩张冠状动脉,打开K通道,并使血管平滑肌超极化。但是,这些平滑肌动作的机制仍然未知。这项研究检查了EETs对小牛冠状动脉平滑肌细胞中大电导Ca(2)激活的K通道(KCa)的影响。在贴有细胞的膜片钳实验中,当以1,10和100 nmol / L的浓度添加时,11,12-EET使KCa通道的活性增加0.5至10倍。在由内而外的切膜模式下,除非将GTP(0.5 mmol / L)或GTP和ATP(1 mmol / L)添加到浴液中,否则11,12-EET对KCa通道的活性没有影响。在存在GTP和ATP的情况下,由内而外的贴片中11,12-EET的KCa通道活性的增加与细胞附着的贴片中的KCa通道活性的增加相当。通过添加GDP-β-S(100 mumol / L),阻止了由内而外的11,12-EET的这种作用。在外向斑块中,将GTP和ATP添加到移液器中时,11,12-EET也增加了KCa通道活性。在移液器中添加特异性抗Gsα抗体(100 nmol / L)完全阻断了11,12-EET诱导的KCa通道的激活。抗Gβγ或抗Giα抗体无效。我们得出的结论是11,12-EET通过Gs alpha介导的机制激活了KCa通道。这种机制有助于将EETs作为内皮源的超极化因子来使动脉平滑肌超极化和松弛。

  • 【发现烯基硼酸作为神经保护剂,可影响涉及阿尔茨海默氏病的多个生物学靶标。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2012.11.068 复制DOI
    作者列表:Jiménez-Aligaga K,Bermejo-Bescós P,Martín-Aragón S,Csákÿ AG
    BACKGROUND & AIMS: :Alkenylboronic acids have shown important biological activities that contribute to neuroprotection. We have determined their influence on the β-amyloid (βA) aggregation process, β-secretase and acethylcholinesterase activities on cell-free systems, on the redox and lipid peroxidation status, and on the vulnerability to apoptotic death in an APPswe neuroblastoma cell line, before and after hydrogen peroxide treatment. We have discovered that 2-arylvinylboronic acids and some of their esters possess a set of properties which makes them highly useful as neuroprotective agents affecting multiple biological targets involved in AD. These properties are not paralleled by the related 2-arylboronic acids.
    背景与目标: 烯基硼酸已显示出重要的生物活性,可促进神经保护作用。我们已经确定了它们对β-淀粉样蛋白(βA)聚集过程,β-分泌酶和乙酰胆碱酯酶活性对无细胞系统,氧化还原和脂质过氧化状态的影响,以及对APPswe神经母细胞瘤细胞株凋亡死亡的脆弱性的影响,过氧化氢处理前后。我们已经发现2-芳基乙烯基硼酸及其某些酯具有一组特性,这使得它们非常有用地用作影响涉及AD的多个生物学靶标的神经保护剂。这些性能是相关的2-芳基硼酸无法比拟的。
  • 【通过显微注射兴奋性氨基酸进一步介导中脑神经元介导猫的防御反应。】 复制标题 收藏 收藏
    DOI:10.1016/0304-3940(85)90261-7 复制DOI
    作者列表:Bandler R,Prineas S,McCulloch T
    BACKGROUND & AIMS: :Microinjections (0.05 microliter) of L-glutamic acid, L-aspartic acid and DL-homocysteic acid were made in the midbrain at the same sites from which a defence reaction had been elicited previously by electrical stimulation. It was found that injections made at sites within the midbrain periaqueductal grey region (PAG) consistently elicited the facio-vocal signs of the defence reaction, whereas injections made at sites in the tegmentum bordering the PAG did not. As injections of excitatory amino acids depolarize cell bodies but not axons, the results indicate that the midbrain PAG but not the adjacent tegmentum contains a population of neurones whose excitation elicits these reactions. Furthermore, the data suggested that such neurones may be located preferentially within the caudal half of the midbrain PAG.
    背景与目标: :在中脑的相同部位进行微量注射(0.05微升)的L-谷氨酸,L-天冬氨酸和DL-同型半胱氨酸,先前通过电刺激已引起防御反应。发现在中脑导水管周围灰色区域(PAG)内进行的注射始终会引起防御反应的面部声音迹象,而在与PAG相邻的睑板部位进行的注射则不然。随着注射兴奋性氨基酸使细胞体去极化而不是使轴突去极化,结果表明中脑PAG而不是相邻的盖骨包含了一群神经元,这些神经元的兴奋引发了这些反应。此外,数据表明此类神经元可能优先位于中脑PAG的尾半部。
  • 【豆浆抑制胆固醇诱导的炎症基因表达,并改善SD大鼠皮肤中的脂肪酸谱。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbrc.2012.10.074 复制DOI
    作者列表:Lee SM,Kim Y,Choi Hj,Choi J,Yi Y,Yoon S
    BACKGROUND & AIMS: :Recently, an elevation in skin cholesterol level has been implicated in skin inflammation. Given the potential therapeutic effects of soy on low grade inflammatory diseases, we hypothesized that a CHOL diet could promote an inflammatory response in skin and that soy milk (SM) or fermented soy milk (F.SM) could prevent this cholesterol-induced skin inflammation. To test this hypothesis, freeze-dried SM or F.SM was provided as a protein replacement for 20% of the casein in the diets of Sprague-Dawley (SD) rats. The animals were divided into the following groups: (1) control group (CTRL), AIN76A diet without cholesterol, (2) high cholesterol (CHOL) group, AIN76A with 1% (w/w) cholesterol, (3) SM group, CHOL diet with freeze-dried SM, and (4) F.SM group, CHOL diet with F.SM. In the CHOL group, the expression levels of pro-inflammatory genes, including IL-1β, IL-1α, iNOS, and COX-2, were elevated. In comparison, the SM and F.SM groups displayed the lowered expression of IL-1β, COX-2, F4/80, and Cd68, an increase of a n-3/n-6 ratio, and a reduction in the estimated desaturase activities of delta 5 desaturase (D5D) and steaoryl CoA desaturase (SCD-1). In particular, F.SM significantly increased the proportion of dihomo-γ-linolenic acid (DGLA) in skin fatty acid (FA) composition compared with the CHOL group. Here we present evidence that SM or F.SM could alleviate the inflammatory response in the skin that is triggered by excess dietary cholesterol by reducing the expression of pro-inflammatory genes. This response could be partly associated with a decreased in macrophages in skin and/or by modulation of the skin's FA composition.
    背景与目标: :最近,皮肤胆固醇水平升高与皮肤炎症有关。考虑到大豆对低度炎症性疾病的潜在治疗作用,我们假设CHOL饮食可以促进皮肤中的炎症反应,而豆浆(SM)或发酵豆浆(F.SM)可以预防这种胆固醇诱导的皮肤炎症。为了检验这一假设,提供了冷冻干燥的SM或F.SM作为Sprague-Dawley(SD)大鼠饮食中20%酪蛋白的蛋白质替代品。将动物分为以下几组:(1)对照组(CTRL),不含胆固醇的AIN76A饮食,(2)高胆固醇(CHOL)组,含1%(w / w)胆固醇的AIN76A,(3)SM组,冻干SM的CHOL饮食,和(4)F.SM组,F.SM的CHOL饮食。在CHOL组中,促炎基因包括IL-1β,IL-1α,iNOS和COX-2的表达水平升高。相比之下,SM和F.SM组显示出IL-1β,COX-2,F4 / 80和Cd68的表达降低,n-3 / n-6比例增加以及估计的去饱和酶降低δ5去饱和酶(D5D)和硬脂酰CoA去饱和酶(SCD-1)的活性。特别是,与CHOL组相比,F.SM显着增加了皮肤脂肪酸(FA)组合物中二高-γ-亚麻酸(DGLA)的比例。在这里,我们提供的证据表明,SM或F.SM可以通过减少促炎基因的表达来缓解皮肤中由过量饮食胆固醇触发的炎症反应。该反应可能部分与皮肤巨噬细胞减少和/或通过调节皮肤的FA成分有关。
  • 【线粒体转化和脂肪酸去饱和之间的泛素依赖性平衡调节线粒体融合。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms15832 复制DOI
    作者列表:Cavellini L,Meurisse J,Findinier J,Erpapazoglou Z,Belgareh-Touzé N,Weissman AM,Cohen MM
    BACKGROUND & AIMS: :Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and Rsp5 that modulates mitochondrial fusion. Ubp2 is an antagonist of Rsp5, which promotes synthesis of the fatty acids desaturase Ole1. We show that Ubp2 also counteracts Mdm30-mediated turnover of the yeast mitofusin Fzo1 and that Mdm30 targets Ubp2 for degradation thereby inducing Rsp5-mediated desaturation of fatty acids. Exogenous desaturated fatty acids inhibit Ubp2 degradation resulting in higher levels of Fzo1 and maintenance of efficient mitochondrial fusion. Our results demonstrate that the Mdm30-Ubp2-Rsp5 crosstalk regulates mitochondrial fusion by coordinating an intricate balance between Fzo1 turnover and the status of fatty acids saturation. This pathway may link outer membrane fusion to lipids homeostasis.
    背景与目标: 线粒体的完整性依赖于相邻外膜之间的同型融合,这种融合是由称为线粒体融合蛋白的大型GTP酶介导的。尽管如此,对这一过程的规制仍然难以捉摸。在这里,我们报道了泛素蛋白酶Ubp2与泛素连接酶Mdm30和Rsp5之间的串扰,该串扰调节线粒体融合。 Ubp2是Rsp5的拮抗剂,可促进脂肪酸去饱和酶Ole1的合成。我们表明,Ubp2还抵消了酵母Mofmin Fzo1的Mdm30介导的营业额,并且Mdm30靶向Ubp2降解,从而诱导了Rsp5介导的脂肪酸去饱和。外源性不饱和脂肪酸抑制Ubp2降解,导致Fzo1含量更高,并维持有效的线粒体融合。我们的结果表明,Mdm30-Ubp2-Rsp5串扰通过协调Fzo1周转率与脂肪酸饱和状态之间的复杂平衡来调节线粒体融合。该途径可能将外膜融合与脂质稳态联系起来。
  • 【1期或更高阶段的脂肪浸润显着损害了棘上修复的长期愈合。】 复制标题 收藏 收藏
    DOI:10.1016/j.jse.2017.03.024 复制DOI
    作者列表:Godenèche A,Elia F,Kempf JF,Nich C,Berhouet J,Saffarini M,Collin P,SOFCOT.
    BACKGROUND & AIMS: BACKGROUND:Fatty infiltration (FI) compromises outcomes of rotator cuff repairs. Most clinicians consider FI of the infraspinatus, whether it is torn or intact, because it is most rapidly affected. The purpose of this study was to report long-term outcomes of isolated supraspinatus repairs and to determine their associations with FI of the infraspinatus and supraspinatus. METHODS:The records of 182 patients who underwent repair of isolated supraspinatus tears and had preoperative magnetic resonance imaging were retrieved. Of these, 147 patients were evaluated at 10 years' follow-up using the Constant score and magnetic resonance imaging scans. RESULTS:Preoperative FI was greater in the supraspinatus (52% stage ≥1) than in the infraspinatus (29% stage ≥1). The 10-year Constant scores were influenced by FI of the supraspinatus (P = .006) but not of the infraspinatus (P = .422). Multivariable regression confirmed that Constant scores were significantly lower for female patients, repetitive work, and stage 1 and stage 2 FI of the supraspinatus in addition to open surgery. Retear rates (Sugaya types IV-V) were also influenced by FI of the supraspinatus (P = .001) but not of the infraspinatus (P = .979). Shoulders with supraspinatus FI at stages 0, 1, and 2 had retear rates of 10%, 22%, and 31%, respectively. Multivariable regression affirmed that the odds of retears are significantly increased by both stage 1 and stage 2 FI of the supraspinatus. CONCLUSIONS:The Constant scores and retear rates were significantly associated with FI of the torn supraspinatus (stage ≥1) but not of the intact infraspinatus. The authors recommend that rapid surgical intervention be considered, before accumulation of fat, especially for young, active patients.
    背景与目标: 背景:脂肪浸润(FI)损害了肩袖修复的效果。大多数临床医生都考虑到下鼻窦的FI,无论其是撕裂的还是完整的,因为它受到的影响最为迅速。这项研究的目的是报告孤立的上棘修复的长期结果,并确定它们与下脊柱和上棘的FI的关系。
    方法:检索182例行孤立性上睑上睑裂孔修复并术前进行磁共振成像的患者的病历。在其中的147位患者中,使用Constant评分和磁共振成像扫描在10年的随访中对其进行了评估。
    结果:术前FI在棘上肌(52%≥1)大于在鼻下肌(29%≥1)。 10年常数评分受脊柱上方FI的影响(P = .006),但不影响椎下肌的FI(P = .422)。多变量回归证实,除开放手术外,女性患者,重复性工作以及棘上肌第1期和第2期FI的恒定评分明显更低。退缩率(Sugaya IV-V型)也受棘上肌FI的影响(P = .001),而不受鞘下肌FI的影响(P = .979)。棘上棘FI在0、1和2期的肩后退率分别为10%,22%和31%。多变量回归证实,上棘的第1阶段和第2阶段FI均使后遗几率显着增加。
    结论:恒定评分和后退率与棘上棘(≥1期)的FI显着相关,而与完整的鼻下肌无关。作者建议在脂肪积聚之前考虑快速外科手术干预,尤其是对于年轻活跃的患者。
  • 【GFT投影NMR可有效鉴定核酸中的(1)H /(13)C糖自旋系统。】 复制标题 收藏 收藏
    DOI:10.1007/s10858-012-9687-5 复制DOI
    作者列表:Atreya HS,Sathyamoorthy B,Jaipuria G,Beaumont V,Varani G,Szyperski T
    BACKGROUND & AIMS: :A newly implemented G-matrix Fourier transform (GFT) (4,3)D HC(C)CH experiment is presented in conjunction with (4,3)D HCCH to efficiently identify (1)H/(13)C sugar spin systems in (13)C labeled nucleic acids. This experiment enables rapid collection of highly resolved relay 4D HC(C)CH spectral information, that is, shift correlations of (13)C-(1)H groups separated by two carbon bonds. For RNA, (4,3)D HC(C)CH takes advantage of the comparably favorable 1'- and 3'-CH signal dispersion for complete spin system identification including 5'-CH. The (4,3)D HC(C)CH/HCCH based strategy is exemplified for the 30-nucleotide 3'-untranslated region of the pre-mRNA of human U1A protein.
    背景与目标: :结合(4,3)D HCCH提出了新实施的G-矩阵傅里叶变换(GFT)(4,3)D HC(C)CH实验,以有效识别(1)H /(13)C糖自旋(13)C标记核酸中的系统。该实验能够快速收集高度解析的中继4D HC(C)CH光谱信息,即由两个碳键分隔的(13)C-(1)H基团的位移相关性。对于RNA,(4,3)D HC(C)CH利用相对有利的1'-和3'-CH信号分散度来完全识别包括5'-CH的自旋系统。基于(4,3)D HC(C)CH / HCCH的策略以人U1A蛋白前mRNA的30个核苷酸的3'非翻译区为例。
  • 【模型膜I中的荧光探针:二棕榈酰磷脂酰胆碱的单层和脂质体中的蒽酰基脂肪酸衍生物。】 复制标题 收藏 收藏
    DOI:10.1021/bi00643a034 复制DOI
    作者列表:Cadenhead DA,Kellner BM,Jacobson K,Papahadjopoulos D
    BACKGROUND & AIMS: A study of three fluorescent anthroyl probes has been carried out using pure and mixed monomolecular films with dipalmitoylphosphatidylcholine. In addition, fluorescence depolarization and differential scanning calorimetry data were obtained from dipalmitoylphosphatidylcholine vesicles with incorporated anthroyl probes. The three probes used were 2-(9-anthroyl)palmitic acid. 12-(9-anthroyl)stearic acid, and 16-(9-anthroyl)palmitic acid. The latter probe was synthesized for these studies. In monolayers the probes shifted the onset of the liquid-condensed/liquid-expanded monolayer phase transition with the extent of the shift decreasing in the order2-(9-anthroyl)palmitic acid greater than 12-(9-anthroyl)stearic acid greater than 16-(9-anthroyl)stearic acid. A corresponding decrease in the gel-liquid crystalline bilayer transition temperature (Tc) showed the same order of perturbation in both the fluorescence depolarization and differential scanning calorimetry data. Locating the anthroyl entity in the center of the bilayer would appear to provide a minimum perturbation.

    背景与目标: 使用带有二棕榈酰磷脂酰胆碱的纯的和混合的单分子膜对三种荧光蒽基探针进行了研究。此外,荧光二极化和差示扫描量热法数据是从二棕榈酰磷脂酰胆碱囊泡中掺入蒽酰基探针获得的。使用的三个探针是2-(9-蒽基)棕榈酸。 12-(9-蒽基)硬脂酸和16-(9-蒽基)棕榈酸。合成了后一种探针用于这些研究。在单层中,探针使液体缩合/液体膨胀的单层相变的开始发生位移,其移位程度以2-(9-蒽基)棕榈酸大于12-(9-蒽基)硬脂酸大于16-(9-蒽基)硬脂酸。凝胶-液晶双层转变温度(Tc)的相应降低在荧光去极化和差示扫描量热数据中都显示出相同程度的扰动。将蒽基实体位于双层的中心似乎可以提供最小的扰动。

  • 【脂肪酸氢过氧化物对解脂耶氏酵母的毒性:其膜流化作用的含义。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbamem.2007.05.016 复制DOI
    作者列表:Tran Thanh H,Beney L,Simonin H,Nguyen TX,Gervais P,Belin JM,Husson F
    BACKGROUND & AIMS: :Linoleic acid hydroperoxide (HPOD), substrate of hydroperoxide lyase, an enzyme of the lipoxygenase pathway, can be transformed into many aromatic compounds, the so-called "green notes". The presence of linoleic acid hydroperoxide in the culture medium of Yarrowia lipolytica, the yeast expressing the cloned hydroperoxide lyase of green bell pepper, undoubtedly exerted an inhibition on the growth and a toxic effect with 90% of yeast cells died after 120 min of exposition in 100 mM HPOD solution. The increase in cell membrane fluidity evaluated by measuring fluorescence generalized polarization with the increasing concentration of HPOD in the medium confirmed the fluidizing action of HPOD on yeast membrane. In addition, we determined by infrared spectroscopy measurement that this compound rapidly diffused into model phospholipids [1, 2-Dimyristoyl-D54-sn-Glycero-3-Phosphocholine (DMPC-D54)] bilayer, modifying their general physical state and their phase transition. In the presence of various concentrations of HPOD, the phase transition of DMPC-D54 occurred with an increase of both the corresponding wave number shift and the temperature range but the phase transition temperature was not modified. These results show that the toxic effects of HPOD on the yeast Yarrowia lipolytica may be initially linked to a strong interaction of this compound with the cell membrane phospholipids and components.
    背景与目标: :亚油酸氢过氧化物(HPOD),氢过氧化物裂解酶的底物,脂氧合酶途径的一种酶,可以转化为许多芳香族化合物,即所谓的“绿色香精”。表达克隆的青椒的氢氧化酵母的酵母耶氏酵母(Yarrowia lipolytica)培养基中亚油酸氢过氧化物的存在无疑对生长产生抑制作用,90%的酵母细胞在暴露120min后死亡的毒性作用。 100 mM HPOD解决方案。通过测量荧光广义极化随培养基中HPOD浓度的增加而评估的细胞膜流动性的增加证实了HPOD在酵母膜上的流化作用。此外,我们通过红外光谱测量确定该化合物迅速扩散到模型磷脂[1,2-Dimyristoyl-D54-sn-Glycero-3-Phosphocholine(DMPC-D54)]双层中,从而改变了它们的一般物理状态和相变。在各种浓度的HPOD存在下,DMPC-D54的相变会随着相应波数偏移和温度范围的增加而发生,但相变温度没有改变。这些结果表明,HPOD对酵母解脂耶氏酵母的毒性作用可能最初与该化合物与细胞膜磷脂和组分的强相互作用有关。
  • 【小鼠中脂肪酸结合蛋白的缺乏赋予了对实验性自身免疫性脑脊髓炎发展的保护。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.179.1.313 复制DOI
    作者列表:Reynolds JM,Liu Q,Brittingham KC,Liu Y,Gruenthal M,Gorgun CZ,Hotamisligil GS,Stout RD,Suttles J
    BACKGROUND & AIMS: :Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of experimental autoimmune encephalomyelitis to test the hypothesis that these FABPs impact adaptive immune responses and contribute to the pathogenesis of autoimmune disease. FABP-deficient mice exhibited a lower incidence of disease, reduced clinical symptoms of experimental autoimmune encephalomyelitis and dramatically lower levels of proinflammatory cytokine mRNA expression in CNS tissue as compared with wild-type mice. In vitro Ag recall responses of myelin oligodendrocyte glycoprotein 35-55-immunized FABP(-/-) mice showed reduced proliferation and impaired IFN-gamma production. Dendritic cells deficient for FABPs were found to be poor producers of proinflammatory cytokines and Ag presentation by FABP(-/-) dendritic cells did not promote proinflammatory T cell responses. This study reveals that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.
    背景与目标: :脂肪酸结合蛋白(FABP)充当多种疏水化合物的细胞内受体,使其在细胞质区室中扩散。最近的研究表明FABP同时调节代谢和炎症途径的能力。我们调查了脂肪细胞FABP和上皮FABP在实验性自身免疫性脑脊髓炎的发展中的作用,以检验以下假设:这些FABP影响适应性免疫反应并有助于自身免疫性疾病的发病机理。与野生型小鼠相比,FABP缺陷型小鼠表现出较低的疾病发病率,减少了实验性自身免疫性脑脊髓炎的临床症状,并且在CNS组织中的促炎细胞因子mRNA表达水平大大降低。髓鞘少突胶质细胞糖蛋白35-55免疫的FABP(-/-)小鼠的体外Ag召回反应显示出增殖减少和IFN-γ产生受损。发现缺乏FABP的树突状细胞是促炎性细胞因子的不良生产者,并且FABP(-/-)树突状细胞的Ag呈递并不促进促炎性T细胞应答。这项研究表明,FABPs对代谢-炎症途径的交叉调节有助于适应性免疫反应和随后的自身免疫炎症。
  • 【长寿侏儒小鼠:胆汁酸是长寿信号吗?】 复制标题 收藏 收藏
    DOI:10.1111/j.1474-9726.2007.00309.x 复制DOI
    作者列表:Gems D
    BACKGROUND & AIMS: :Pathways that control aging act via regulated biochemical processes, among which metabolism of xenobiotics (potentially harmful chemical agents encountered as environmental toxicants, for example, drugs, or produced internally) is one possible candidate. A new study of long-lived Ghrhr mutant mice reports that increased bile acid levels activate xenobiotic metabolism via the nuclear receptor, farnesoid X receptor. This increases resistance to xenobiotic stress, possibly contributing to longevity.
    背景与目标: :控制衰老的途径是通过受控的生化过程起作用的,其中异生素(作为环境毒物遇到的潜在有害化学剂,例如药物或内部产生)的代谢可能是一种候选方法。一项针对长寿Ghrhr突变小鼠的新研究报告,胆汁酸水平升高会通过核受体,法呢素X受体激活异种生物代谢。这增加了对异种生物胁迫的抵抗力,可能有助于延长寿命。
  • 【脂肪酸氧化途径作为胰岛素抵抗的治疗靶标。】 复制标题 收藏 收藏
    DOI:10.1517/14728222.10.5.749 复制DOI
    作者列表:Clapham JC,Storlien LH
    BACKGROUND & AIMS: :It is recognised that obesity is a major driver for insulin resistance and Type 2 diabetes in both adult and young members of diverse societies. Weight loss strategies involving diet, exercise and behaviour modification work only for the minority of highly motivated individuals, but fail completely in the vast majority; yet weight loss is associated with benefits in metabolic health. Why is it so difficult to maintain weight loss in the longer term? Here, the authors explore the possibility that energy partitioning, especially of lipids, plays a key role in both weight recidivism and, by association, insulin resistance. Drug targets that address key pathways important in this process, where progress in drug discovery is apparent, are discussed.
    背景与目标: :众所周知,肥胖是各种社会的成年和年轻成员中胰岛素抵抗和2型糖尿病的主要驱动力。涉及饮食,运动和行为改变的减肥策略仅对少数积极进取的人有效,但在绝大多数人中完全无效;减肥与代谢健康有关。为什么长期保持减肥如此困难?在这里,作者探索了能量分配(尤其是脂质)在体重减轻和胰岛素抵抗中起关键作用的可能性。讨论了解决在此过程中很重要的关键途径的药物靶标,在该过程中,药物发现有了明显的进展。

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