BACKGROUND & AIMS: :Bacteria utilize quorum-sensing systems to modulate environmental stress responses. The quorum-sensing system of Streptococcus mutans is mediated by the competence-stimulating peptide (CSP), whose precursor is encoded by the comC gene. A comC mutant of strain GS5 exhibited enhanced antimicrobial sensitivity to a wide variety of different agents. Since the addition of exogenous CSP did not complement this phenotype, it was determined that the increased tetracycline, penicillin, and triclosan sensitivities resulted from repression of the putative bacteriocin immunity protein gene, bip, which is located immediately upstream from comC. We further demonstrated that the inactivation of bip or smbG, another bacteriocin immunity protein gene present within the smb operon in S. mutans GS5, affected sensitivity to a variety of antimicrobial agents. Furthermore, both the bip and smbG genes were upregulated in the presence of low concentrations of antibiotics and were induced during biofilm formation relative to in planktonic cells. These results suggest, for the first time, that the antimicrobial sensitivity of a bacterium can be modulated by some of the putative bacteriocin immunity proteins expressed by the organism. The implications of these observations for the evolution of bacteriocin immunity protein genes as well as for potential new chemotherapeutic strategies are discussed.

背景与目标： ：细菌利用群体感应系统来调节环境应激反应。变异链球菌的群体感应系统由能力刺激肽（CSP）介导，其前体由comC基因编码。菌株GS5的comC突变体对多种不同的药物表现出增强的抗菌敏感性。由于外源CSP的添加不能补充该表型，因此确定增加的四环素，青霉素和三氯生敏感性是由推定的细菌素免疫蛋白基因bip抑制而来的，该基因位于comC的上游。我们进一步证明了bip或smbG（变形链球菌GS5的smb操纵子内存在的另一种细菌素免疫蛋白基因）的失活影响了对多种抗菌剂的敏感性。此外，在低浓度抗生素存在下，bip和smbG基因均被上调，并且在生物膜形成过程中相对于浮游细胞被诱导。这些结果首次表明，细菌的抗菌敏感性可以由生物体表达的某些假定的细菌素免疫蛋白来调节。讨论了这些观察结果对细菌素免疫蛋白基因的进化以及潜在的新化学治疗策略的影响。

BACKGROUND & AIMS: Matrix ligands are agents for isolating proteins out of dilute crudes by coprecipitating proteins. The ligands have a strong anion sulfonate head which initiates binding to proteins having a positive net charge, ZH+ approximately 5-20. Initial binding tightens protein conformation and starts to squeeze water from conformationally motile proteins. The tails are stackable hydrophobic organic groups, azoaromatic dyes which draw protein-ligand complexes together. Proteins coprecipitate as guests, in the ligand host matrix. In addition to stacking, ligand tails displace water because of their bulk, and lower the average dielectric constant near charged groups, which reinforces the electrostatic component of binding. Matrix ligands protect proteins, scavenge them from dilute crudes (0.01-0.1 per cent protein), and densify coprecipitates. Detergent ions in low concentrations, 10(-4)-10(-5) M also sometimes serve as coprecipitating agents, entangling their tails but probably not stacking. Divalent metal ions, Zn++, sometimes are useful auxiliary agents. Preparative scaleability from crudes is demonstrated starting from 100-200 g of raw peanuts and raw pineapple to coprecipitate a lectin and bromelain enzyme respectively in 1-2 h with 80-90 per cent activity yields. Ligands are released from coprecipitates by shifting the pH and trapping the ligands with exchange resins. Protein conformation tightening in solution is seen by viscosity measurements.

背景与目标： 基质配体是通过共沉淀蛋白质从稀原油中分离蛋白质的试剂。配体具有很强的阴离子磺酸根头，可与具有正净电荷（ZH约为5-20）的蛋白质结合。初始结合会拉紧蛋白质构象，并开始从构象运动的蛋白质中挤出水。尾部是可堆叠的疏水有机基团，偶氮芳香族染料，可将蛋白质-配体复合物吸引在一起。蛋白质作为客体在配体宿主基质中共沉淀。除了堆积之外，配体尾部还因为其体积而置换了水，并降低了带电基团附近的平均介电常数，从而增强了结合的静电成分。基质配体可以保护蛋白质，从稀原油中清除蛋白质（蛋白质含量为0.01-0.1％），并浓缩共沉淀物。低浓度10（-4）-10（-5）M的去污剂离子有时还充当共沉淀剂，缠住它们的尾巴，但可能不会堆积。二价金属离子Zn有时是有用的辅助剂。从100-200 g的粗花生和菠萝开始，可在1-2小时内分别沉淀出凝集素和菠萝蛋白酶，具有80-90％的活性收率，证明了从原油可制备的可扩展性。通过改变pH值并用交换树脂捕获配体，从共沉淀物中释放出配体。通过粘度测量可以看出溶液中的蛋白质构象变紧。

BACKGROUND & AIMS: :Several cAMP-elevating agents such as cholera toxin (CT), forskolin and 3-isobutyl-1-methylxanthine (IBMX) exhibited weak mitogenic activity on bovine undifferentiated mammary epithelial cells in three-dimensional collagen culture. CT and IBMX strongly synergized with epidermal growth factor (EGF), insulin-like growth factor I (IGF-I) or both, but not with 10% fetal calf serum (FCS). Permeable cAMP analogs also synergized with IGF-I. Other hormones such as ovine prolactin, bovine growth hormone, estrogen or progesterone were not mitogenic and not synergistic with EGF, IGF-I, CT and FCS. Pertussis toxin (PT) reduced the DNA synthesis in cells cultured in the basal medium and attenuated 40-90% of the mitogenic activity stimulated by 10% FCS. PT inhibition of DNA synthesis was accompanied by ADP-ribosylation of 40 kDa and 41 kDa membrane proteins. The 41 kDa protein cross-reacted with antibodies that recognize the Gi-protein of the adenylate cyclase system, indicating the involvement of the latter in the mitogenic process. The nature of the second protein remains unknown. The present results suggest that the mitogenesis of normal mammary epithelial cells which is stimulated by IGF-I, EGF and other factors found in FCS is mediated through both cAMP-dependent and independent pathways. These pathways include PT-sensitive GTP-binding proteins.

背景与目标： ：几种cAMP增强剂，例如霍乱毒素（CT），毛喉素和3-异丁基-1-甲基黄嘌呤（IBMX）在三维胶原蛋白培养物中对牛未分化乳腺上皮细胞显示出弱的促有丝分裂活性。 CT和IBMX与表皮生长因子（EGF），胰岛素样生长因子I（IGF-I）或两者均具有强效协同作用，但与10％的胎牛血清（FCS）没有协同作用。渗透性cAMP类似物也与IGF-I协同作用。其他激素，例如绵羊催乳激素，牛生长激素，雌激素或孕激素，没有促有丝分裂作用，也不与EGF，IGF-I，CT和FCS协同作用。百日咳毒素（PT）减少了在基础培养基中培养的细胞中的DNA合成，并减弱了10％FCS刺激的有丝分裂活性的40-90％。 PT对DNA合成的抑制作用伴随着40 kDa和41 kDa膜蛋白的ADP-核糖基化。 41 kDa蛋白与识别腺苷酸环化酶系统的Gi蛋白的抗体发生交叉反应，表明后者参与了促有丝分裂过程。第二种蛋白质的性质仍然未知。目前的结果表明，通过IGF-I，EGF和FCS中发现的其他因素刺激的正常乳腺上皮细胞的有丝分裂是通过cAMP依赖性和独立途径介导的。这些途径包括PT敏感的GTP结合蛋白。

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。