BACKGROUND & AIMS: :Histone methylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity. Enzymes that directly remove methyl marks from histones have recently been identified, revealing a new level of plasticity within this epigenetic modification system. Here we analyse the evolutionary relationship between Jumonji C (JmjC)-domain-containing proteins and discuss their cellular functions in relation to their potential enzymatic activities.

背景与目标： ：组蛋白甲基化在调节基因表达中起重要作用，并形成表观遗传记忆系统的一部分，该系统调节细胞命运和特性。最近已鉴定出可直接从组蛋白中去除甲基标记的酶，从而揭示了该表观遗传修饰系统中可塑性的新水平。在这里，我们分析Jumonji C（JmjC）域包含蛋白质之间的进化关系，并讨论其潜在的酶活性与其细胞功能。

BACKGROUND & AIMS: :Cellular iron homeostasis is maintained by iron and heme transport proteins that work in concert with ferrireductases, ferroxidases, and chaperones to direct the movement of iron into, within, and out of cells. Systemic iron homeostasis is regulated by the liver-derived peptide hormone, hepcidin. The interface between cellular and systemic iron homeostasis is readily observed in the highly dynamic iron handling of four main cell types: duodenal enterocytes, erythrocyte precursors, macrophages, and hepatocytes. This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease.

背景与目标： ：铁和血红素转运蛋白与铁还原酶，铁氧化酶和伴侣蛋白协同作用，维持细胞内铁稳态，从而指导铁进入，进入和离开细胞的运动。系统性铁稳态由肝脏衍生的肽激素hepcidin调节。在铁的四种主要细胞类型的高动态铁处理中，很容易观察到细胞与全身铁稳态之间的界面：十二指肠肠上皮细胞，红细胞前体，巨噬细胞和肝细胞。这篇综述概述了这些细胞类型如何处理铁，着重介绍了铁和血红素转运蛋白如何在健康和疾病中介导体内铁的交换和分布。

BACKGROUND & AIMS: :Establishment of anterior-posterior polarity in the Caenorhabditis elegans zygote requires two different processes: mechanical activity of the actin-myosin cortex and biochemical activity of partitioning-defective (PAR) proteins. Here we analyze how PARs regulate the behavior of the cortical motor protein nonmuscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate the Rho GTPase CDC-42, which in turn regulates the actin-myosin cortex. We find that PAR-3 and PAR-6 concentrate CDC-42-dependent NMY-2 in the anterior cortex, whereas PAR-2 inhibits CDC-42-dependent NMY-2 in the posterior domain by inhibiting PAR-3 and PAR-6. In addition, we find that PAR-1 and PAR-3 are necessary for inhibiting movement of NMY-2 across the cortex. PAR-1 protects NMY-2 from being moved across the cortex by forces likely originating in the cytoplasm. Meanwhile, PAR-3 stabilizes NMY-2 against PAR-2 and PAR-6 dynamics on the cortex. We find that PAR signaling fulfills two roles: localizing NMY-2 to the anterior cortex and preventing displacement of the polarized cortical actin-myosin network.

背景与目标： 秀丽隐杆线虫合子前后极性的建立需要两个不同的过程：肌动蛋白-肌球蛋白皮层的机械活性和分区缺陷（PAR）蛋白的生化活性。在这里，我们分析了PARs如何调节皮质运动蛋白非肌肉肌球蛋白（NMY-2）的行为，以补充最近的研究，即研究PARs如何调节Rho GTPase CDC-42，后者又调节肌动蛋白-肌球蛋白皮质。我们发现PAR-3和PAR-6在前皮质集中CDC-42依赖性NMY-2，而PAR-2通过抑制PAR-3和PAR-6抑制CDC-42依赖性NMY-2在后皮质。此外，我们发现PAR-1和PAR-3对于抑制NMY-2跨皮质运动是必需的。 PAR-1保护NMY-2免受可能源自细胞质的力穿过皮质移动。同时，PAR-3使NMY-2抵抗皮层上的PAR-2和PAR-6动态。我们发现，PAR信号传导起着两个作用：将NMY-2定位在前皮质，并防止极化皮质肌动蛋白-肌球蛋白网络的移位。

BACKGROUND & AIMS: :Among the three major food crops (rice, wheat and maize), wheat is unique in accumulating gluten proteins in its grains. Of these proteins, the high and low molecular weight glutenin subunits (HMW-GSs and LMW-GSs) form glutenin macropolymers that are vital for the diverse end-uses of wheat grains. In this work, we developed a new series of deletion mutants lacking one or two of the three Glu-1 loci (Glu-A1, -B1 and -D1) specifying HMW-GSs. Comparative analysis of single and double deletion mutants reinforced the suggestion that Glu-D1 (encoding the HMW-GSs 1Dx2 and 1Dy12) has the largest effects on the parameters related to gluten and dough functionalities and breadmaking quality. Consistent with this suggestion, the deletion mutants lacking Glu-D1 or its combination with Glu-A1 or Glu-B1 generally exhibited strong decreases in functional glutenin macropolymers (FGMPs) and in the incorporation of HMW-GSs and LMW-GSs into FGMPs. Further examination of two knockout mutants missing 1Dx2 or 1Dy12 showed that 1Dx2 was clearly more effective than 1Dy12 in promoting FGMPs by enabling the incorporation of more HMW-GSs and LMW-GSs into FGMPs. The new insight obtained and the mutants developed by us may aid further research on the control of wheat end-use quality by glutenin proteins.

背景与目标： ：在三种主要的粮食作物（大米，小麦和玉米）中，小麦在谷物中积累面筋蛋白方面是独特的。在这些蛋白质中，高分子量和低分子量的谷蛋白亚基（HMW-GS和LMW-GS）形成了谷蛋白大分子聚合物，对小麦籽粒的各种最终用途至关重要。在这项工作中，我们开发了一系列新的缺失突变体，它们缺少指定HMW-GS的三个Glu-1位点（Glu-A1，-B1和-D1）中的一个或两个。对单缺失和双缺失突变体的比较分析进一步表明，Glu-D1（编码HMW-GSs 1Dx2和1Dy12）对与面筋和面团功能以及面包制作质量相关的参数影响最大。与此建议一致，缺少Glu-D1或其与Glu-A1或Glu-B1结合的缺失突变体通常在功能性谷蛋白大分子（FGMP）以及将HMW-GS和LMW-GS掺入FGMP中表现出强烈的下降。对缺失1Dx2或1Dy12的两个敲除突变体的进一步检查表明，通过使更多的HMW-GS和LMW-GS掺入FGMP，1Dx2在促进FGMP方面明显比1Dy12更有效。我们获得的新见识和我们开发的突变体可能有助于通过谷蛋白的蛋白质控制小麦最终用途质量的进一步研究。

BACKGROUND & AIMS: :Plant leaves are a crucial organ associated closely with chloroplast development, photosynthesis rate and crop productivity. In this study, a white fine stripe leaf 1 (wfsl1) mutant was isolated and characterized from the japonica rice Zhonghua11 (ZH11) after ethyl methanesulfonate mutagenesis. The wfsl1 displayed white fine stripe leaves since tillering stage and abnormal chloroplast structure. Map-based cloning and Bioinformatic analysis indicated that WFSL1 on chromosome 1 contains an "A" to "T" substitution in protein coding region, and encodes a putative metal-dependent phosphohydrolase with HD domain at the N-terminus. WFSL1 was targeted to the chloroplasts and had higher expression in mature leaves and sheaths. RNA-seq analysis revealed that chloroplast development and photosynthesis genes were significantly affected in wfsl1 plants. Levels of WFSL1 and chloroplast encoded proteins were decreased in wfsl1 mutants via western blot analysis. Compared with WT, wfsl1 exhibits lower Chl content and defective in biogenesis of chloroplast ribosomes, which resulted in reduced grain yield. Taken together, our results show that WFSL1 is critical for chloroplast development, ribosome biogenesis, and light energy utilization, finally affects grain yield.

背景与目标： 植物叶片是与叶绿体发育，光合作用速率和农作物生产力密切相关的重要器官。在本研究中，从甲磺酸乙酯诱变后的粳稻中华11（ZH11）中分离并鉴定了白色细条叶1（wfsl1）突变体。分f期和叶绿体结构异常后，wfsl1呈白色细条状叶片。基于图谱的克隆和生物信息学分析表明，染色体1上的WFSL1在蛋白质编码区中包含“ A”至“ T”取代，并在N端编码具有HD结构域的推定的金属依赖性磷酸水解酶。 WFSL1靶向叶绿体，并在成熟的叶和鞘中具有较高的表达。 RNA-seq分析显示，wfsl1植物的叶绿体发育和光合作用基因受到显着影响。通过Western blot分析，wfsl1突变体中WFSL1和叶绿体编码蛋白的水平降低。与野生型相比，wfsl1的Chl含量较低，叶绿体核糖体的生物发生缺陷，从而导致谷物产量下降。综上所述，我们的结果表明WFSL1对叶绿体发育，核糖体生物发生和光能利用至关重要，最终影响谷物产量。

BACKGROUND & AIMS: :Detergent-resistant membranes (DRMs) represent specialized membrane domains resistant to detergent extraction, which may serve to segregate proteins in a specific environment in order to improve their function. Segregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs) in DRMs has been shown to be involved in their sorting to the apical membrane in polarized epithelial cells. Nonetheless, we have shown that both apical and basolateral GPI-APs associate with DRMs. In this report we investigated the lipid composition of DRMs associated with an apical and a basolateral GPI-AP. We found that apical and basolateral DRMs contain the same lipid species although in different ratios. This specific lipid ratio is maintained after mixing the cells before lysis indicating that DRMs maintain their identity after Triton extraction.

背景与目标： ：抗洗涤剂膜（DRMs）代表对去污剂萃取有抗性的特殊膜结构域，可用于在特定环境中分离蛋白质以改善其功能。研究表明，DRM中糖基磷脂酰肌醇锚定蛋白（GPI-AP）的分离与其在极化上皮细胞的顶膜中的分选有关。尽管如此，我们已经表明，根尖和基底外侧的GPI-AP均与DRM相关。在本报告中，我们研究了与根尖和基底外侧GPI-AP相关的DRM的脂质成分。我们发现顶端和基底外侧DRM包含相同的脂质种类，尽管比率不同。在裂解之前混合细胞后，该特定脂质比率得以维持，这表明DRM在Triton提取后仍保持其身份。

BACKGROUND & AIMS: :In Saccharomyces cerevisiae, diploid yeast cells follow a bipolar budding program, which depends on the two transmembrane glycoproteins Bud8p and Bud9p that potentially act as cortical tags to mark the cell poles. Here, we have performed systematic structure-function analyses of Bud8p and Bud9p to identify functional domains. We find that polar transport of Bud8p and Bud9p does not depend on N-terminal sequences but instead on sequences in the median part of the proteins and on the C-terminal parts that contain the transmembrane domains. We show that the guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange factor Bud5p, which is essential for bud site selection and physically interacts with Bud8p, also interacts with Bud9p. Regions of Bud8p and Bud9p predicted to reside in the extracellular space are likely to confer interaction with the N-terminal region of Bud5p, implicating indirect interactions between the cortical tags and the GDP/GTP exchange factor. Finally, we have identified regions of Bud8p and Bud9p that are required for interaction with the cortical tag protein Rax1p. In summary, our study suggests that Bud8p and Bud9p carry distinct domains for delivery of the proteins to the cell poles, for interaction with the general budding machinery and for association with other cortical tag proteins.

背景与目标： 在酿酒酵母中，二倍体酵母细胞遵循双极芽接程序，该程序取决于两个跨膜糖蛋白Bud8p和Bud9p，它们可能充当皮质标签来标记细胞极。在这里，我们进行了Bud8p和Bud9p的系统结构-功能分析，以识别功能域。我们发现Bud8p和Bud9p的极性转运不依赖于N末端序列，而是依赖于蛋白质中间部分的序列以及包含跨膜结构域的C末端部分。我们表明，鸟苷二磷酸（GDP）/鸟苷三磷酸（GTP）交换因子Bud5p，这对于芽位点选择至关重要，并且与Bud8p物理相互作用，也与Bud9p相互作用。预计驻留在细胞外空间中的Bud8p和Bud9p区域可能会赋予与Bud5p的N端区域相互作用，这暗示皮层标签与GDP / GTP交换因子之间存在间接相互作用。最后，我们确定了与皮质标签蛋白Rax1p相互作用所需的Bud8p和Bud9p区域。总而言之，我们的研究表明Bud8p和Bud9p携带不同的结构域，用于将蛋白质递送至细胞极，与一般的出芽机制相互作用以及与其他皮质标签蛋白结合。

BACKGROUND & AIMS: :The gene encoding a single-chain, ribosome-inactivating protein (SCRIP) was cloned from bitter melon (Momordica charantia L.) leaves infected with the fungus, Sphaerotheca fuliginea, by RT-PCR. The ORF was 861 bp. The ribosome-inactivating protein was expressed in E. coli and, when purified, it inhibited the growth of Fusarium solani [corrected] Northern blot analysis revealed that RIP transcripts rapidly accumulated in leaves 1-day post inoculation with Sphaerotheca fuliginea and reached a peak at 3 d. The expression pattern of RIP induced by methyl jasmonate and salicylic acid were different from that of pathogen-induced expression. Mechanical wounding, silver nitrate and osmotic stress stimulated only a slight accumulation of RIP transcripts. Abscisic acid also induced transcription of RIPs. The signal compounds, ethylene and okadaic acid, induced a moderate accumulation of RIP transcripts.

背景与目标： ：通过RT-PCR从感染了真菌Sphaerotheca fuliginea的苦瓜（Momordica charantia L.）叶片中克隆了编码单链核糖体失活蛋白（SCRIP）的基因。 ORF为861bp。核糖体失活蛋白在大肠杆菌中表达，纯化后抑制了茄镰刀菌的生长。 3天茉莉酸甲酯和水杨酸诱导的RIP表达模式与病原体诱导的表达模式不同。机械伤，硝酸银和渗透胁迫仅刺激了RIP转录物的少量积累。脱落酸还诱导RIP的转录。信号化合物，乙烯和冈田酸，诱导了RIP转录产物的适度积累。

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）充当各种疏水性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。髓磷脂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。

BACKGROUND & AIMS: :Type III protein secretion systems, which are organelles with the capacity to deliver bacterial proteins into host cells, have been adapted to deliver heterologous antigens for vaccine development. A limitation of these antigen delivery systems is that some proteins are not amenable to secretion through this pathway. We show here that proteins from the simian and human immunodeficiency viruses that are not permissive for secretion through a Salmonella enterica serovar Typhimurium type III secretion system can be modified to travel this secretion pathway by introduction of discrete mutations. Proteins optimized for secretion were presented more efficiently via the major histocompatibility complex class I pathway and were able to induce a better immune response.

背景与目标： ：III型蛋白质分泌系统具有细胞器的能力，能够将细菌蛋白质传递到宿主细胞中，已经适应于传递异源抗原用于疫苗开发。这些抗原递送系统的局限性是某些蛋白质不适合通过该途径分泌。我们在这里表明，猿猴和人类免疫缺陷病毒不允许通过沙门氏菌肠炎血清型鼠伤寒III型分泌系统分泌的蛋白质可以通过引入离散突变而被修饰为通过这种分泌途径。通过主要的组织相容性复合体I类途径可以更有效地表达针对分泌优化的蛋白质，并且能够诱导更好的免疫反应。

BACKGROUND & AIMS: :Some peptide hormones are associated with specific, high-affinity plasma proteins. The major binding protein (BP) for growth hormone (GH) in humans is a circulating fragment of the GH membrane receptor, consisting of the hydrophilic, extracellular portion of that transmembrane glycoprotein. The circulating levels of GH-BP mirror the levels of GH receptors. There are 4 well-characterized insulin-like growth factor (IGF)-BPs. One IGF-binding component in plasma is a fragment of the extracellular portion of the IGF-II/mannose-6-phosphate receptor, analogous to the GH-BP. The 3 other cloned IGF-BPs form a homologous family of proteins with differences in structure, glycosylation and hormonal control that suggest differences in function. The GH- and IGF-BPs play a major role in the metabolism and biological action of these peptide hormones.

背景与目标： ：某些肽激素与特定的高亲和力血浆蛋白有关。人类生长激素（GH）的主要结合蛋白（BP）是GH膜受体的循环片段，由该跨膜糖蛋白的亲水性细胞外部分组成。 GH-BP的循环水平反映了GH受体的水平。有4个特征明确的胰岛素样生长因子（IGF）-BP。血浆中一种IGF结合成分是类似于GH-BP的IGF-II /甘露糖6-磷酸受体的细胞外部分的片段。其他3个克隆的IGF-BPs形成同源的蛋白质家族，其结构，糖基化和激素控制方面存在差异，提示其功能存在差异。 GH-和IGF-BP在这些肽激素的代谢和生物学作用中起主要作用。

BACKGROUND & AIMS: :The intricate problems associated with the delivery and various unnecessary in vivo transitions of proteins and drugs needs to be tackled soon to be able to exploit the myriad of putative therapeutics created by the biotechnology boom. Nanomedicine is one of the most promising applications of nanotechnology in the field of medicine. It has been defined as the monitoring, repair, construction and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. These nanostructured medicines will eventually turn the world of drug delivery upside down. PEGylation (i.e. the attachment of polyethylene glycol to proteins and drugs) is an upcoming methodology for drug development and it has the potential to revolutionise medicine by drastically improving the pharmacokinetic and pharmacodynamic properties of the administered drug. This article provides a total strategy for improving the therapeutic efficacy of various biotechnological products in drug delivery. This article also presents an extensive analysis of most of the PEGylated proteins, peptides and drugs, together with extensive clinical data. Nanomedicines and PEGylation, the latest offshoots of nanotechnology will definitely pave a way in the field of drug delivery where targeted delivery, formulation, in vivo stability and retention are the major challenges.

背景与目标： ：与蛋白质和药物的输送以及各种不必要的体内不必要的转换有关的复杂问题需要尽快解决，以便能够利用生物技术繁荣带来的无数推定疗法。纳米医学是纳米技术在医学领域最有前途的应用之一。它已被定义为使用工程化的纳米器件和纳米结构在分子水平上监测，修复，构建和控制人类生物系统。这些纳米结构药物最终将颠覆药物输送的世界。聚乙二醇化（即聚乙二醇与蛋白质和药物的结合）是药物开发的一种新方法，它具有通过彻底改善所给药药物的药代动力学和药效学性质来革新药物的潜力。本文提供了用于提高各种生物技术产品在药物输送中的治疗功效的总体策略。本文还对大多数PEG化的蛋白质，肽和药物进行了广泛的分析，并提供了广泛的临床数据。纳米药物和聚乙二醇化是纳米技术的最新分支，这无疑将在药物递送领域铺平道路，其中靶向递送，制剂，体内稳定性和保留性是主要挑战。

BACKGROUND & AIMS: :There is now considerable evidence that the insulin-like growth factors (IGFs) play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP-1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP-1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP-1 levels correlated with FF-volume (r = 0.58, P less than 0.001) and with paired serum levels (r = 0.63, P less than 0.001). In post-LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP-1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF-binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.

背景与目标： ：现在有大量证据表明胰岛素样生长因子（IGF）在人卵巢中起重要作用。最近也已经很明显，IGF的生理活性受到许多特异性结合蛋白（IGFBP）的调节。为了理解IGF在卵巢生理中的作用，将需要表征这些IGFBP的存在和功能。作为对此的第一步，我们通过Western配体印迹研究了各种结合蛋白的存在，并测量了19种正常人从未刺激的优势和同类卵泡中获得的卵泡液（FF）中其中一种IGFBP-1的水平。女性和8例多囊性卵巢癌患者和1例多囊性卵巢癌患者。在正常女性中，优势卵泡中的IGFBP-1水平与匹配的血清水平相似，但在同龄卵泡中则显着降低。 IGFBP-1水平与FF量（r = 0.58，P小于0.001）和成对的血清水平（r = 0.63，P小于0.001）相关。在LH激增后的主要卵泡中，这种与血清水平的关系不再成立，在9名受试者中，有3名的FF水平高于血清。因此，正常人FF中的IGFBP-1似乎部分来自循环，但在较大的发育中的优势卵泡中有额外的局部产生。 Western配体印迹显示FF中有5种IGF结合蛋白与血清中鉴定的蛋白平行运行，这表明先前在血清中鉴定出的IGFBP种类也可能存在于FF中。如在血清中，对应于大（150kDa）结合复合物组分的位置上的两个条带是主要形式，在大多数FF样品中，它们甚至比随附的血清样品中更为突出。这与先前的淋巴研究相反，后者表明150kDa的复合物主要保留在循环系统中。 FF样本之间的所有三个小型IGFBP甚至在一个个体中都存在很大差异。每个IGFBP均独立于其他IGFBP而变化。我们的结果表明，FF中至少存在4个离散的IGFBP，提示每个子可能在卵巢内独立产生。

BACKGROUND & AIMS: BACKGROUND:The overproduction of recombinant proteins in host cells often leads to their misfolding and aggregation. Previous attempts to increase the solubility of recombinant proteins by co-overproduction of individual chaperones were only partially successful. We now assessed the effects of combined overproduction of the functionally cooperating chaperone network of the E. coli cytosol on the solubility of recombinant proteins. RESULTS:A two-step procedure was found to show the strongest enhancement of solubility. In a first step, the four chaperone systems GroEL/GroES, DnaK/DnaJ/GrpE, ClpB and the small HSPs IbpA/IbpB, were coordinately co-overproduced with recombinant proteins to optimize de novo folding. In a second step, protein biosynthesis was inhibited to permit chaperone mediated refolding of misfolded and aggregated proteins in vivo. This novel strategy increased the solubility of 70% of 64 different heterologous proteins tested up to 42-fold. CONCLUSION:The engineered E. coli strains and the two-step procedure presented here led to a remarkable increase in the solubility of a various recombinant proteins and should be applicable to a wide range of target proteins produced in biotechnology.

背景与目标： 背景：重组蛋白在宿主细胞中的过度产生通常会导致其错误折叠和聚集。通过共同过量生产单个分子伴侣来增加重组蛋白的溶解度的先前尝试仅部分成功。现在，我们评估了大肠杆菌细胞溶胶功能上协同的伴侣网络的联合过量生产对重组蛋白溶解性的影响。
结果：发现两步法显示出最强的溶解度增强。第一步，将四个分子伴侣系统GroEL / GroES，DnaK / DnaJ / GrpE，ClpB和小的HSP IbpA / IbpB与重组蛋白协同过量生产，以优化从头折叠。在第二步骤中，抑制蛋白质生物合成以允许伴侣蛋白介导的体内错误折叠和聚集的蛋白质的重新折叠。这种新颖的策略将64种不同异源蛋白质中70％的溶解度提高了42倍。
结论：这里提出的工程化大肠杆菌菌株和两步法导致各种重组蛋白的溶解度显着提高，应适用于生物技术中生产的多种靶蛋白。

BACKGROUND & AIMS: :Hepatocellular carcinoma (HCC) is a common malignancy and the main cause of mortality in patients with chronic liver diseases. This study reports the inhibitory effect of boron on HCC induced in rats by administering thioacetamide (TAA) (0.03%) in drinking water for 400days. Boron (4mg/kg body weight) was administered orally after induction of carcinoma. Treatment was continued for 122days, and cell proliferation, histology and biochemistry of treated and control group of rats were studied. Proliferating cell nuclear antigen (PCNA), and [(3)H]-thymidine incorporation, which increased in rats exposed to carcinogen, significantly decreased after boron treatment. PCNA index decreased from 80 in HCC rats to 32 after boron treatment. In the control group, it was 20. Boron caused a dose-dependent decrease in carcinogen-induced [(3)H]-thymidine uptake by the rat hepatocyte. It could partially reverse the activity of selected biochemical indicators of hepatic damage, oxidative stress, selenium and serum retinol, which are depleted in liver cancer, and improved overall health of animal. The study implicates the elevated levels of mammalian molybdenum Fe-S containing flavin hydroxylases, which increase the free radical production and oxidative stress, consequently causing increased hepatic cell proliferation in HCC, and reports boron to ameliorate these changes in liver cancer.

背景与目标： ：肝细胞癌（HCC）是一种常见的恶性肿瘤，是慢性肝病患者死亡的主要原因。这项研究报告了硼通过在饮用水中施用400天的硫代乙酰胺（TAA）（0.03％）对大鼠肝癌的抑制作用。诱发癌症后口服硼（4mg / kg体重）。持续治疗122天，并研究了处理组和对照组的细胞增殖，组织学和生化。硼处理后，在暴露于致癌物的大鼠中增加的增殖细胞核抗原（PCNA）和[（3）H]-胸苷的掺入显着降低。硼处理后，PCNA指数从HCC大鼠的80下降到32。对照组为20。硼导致致癌物诱导的大鼠肝细胞摄取[（3）H]-胸苷的剂量依赖性降低。它可以部分逆转肝癌中耗竭的肝损伤，氧化应激，硒和血清视黄醇等生化指标的选定活性，并改善动物的整体健康状况。这项研究暗示了含有黄素羟化酶的哺乳动物钼铁硫水平的升高，从而增加了自由基的产生和氧化应激，从而导致肝癌肝细胞增殖的增加，并报道了硼改善了肝癌的这些变化。