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Many proteins that can assemble into higher order structures termed amyloids can also concentrate into cytoplasmic inclusions via liquid–liquid phase separation. Here, we study the assembly of human Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1), an amyloidogenic protein of the Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP) protein superfamily, into cytosolic inclusions in Saccharomyces cerevisiae. Overexpression of GAPR-1-GFP results in the formation GAPR-1 oligomers and fluorescent inclusions in yeast cytosol. These cytosolic inclusions are dynamic and reversible organelles that gradually increase during time of overexpression and decrease after promoter shut-off. Inclusion formation is, however, a regulated process that is influenced by factors other than protein expression levels. We identified N-myristoylation of GAPR-1 as an important determinant at early stages of inclusion formation. In addition, mutations in the conserved metal-binding site (His54 and His103) enhanced inclusion formation, suggesting that these residues prevent uncontrolled protein sequestration. In agreement with this, we find that addition of Zn2+ metal ions enhances inclusion formation. Furthermore, Zn2+ reduces GAPR-1 protein degradation, which indicates stabilization of GAPR-1 in inclusions. We propose that the properties underlying both the amyloidogenic properties and the reversible sequestration of GAPR-1 into inclusions play a role in the biological function of GAPR-1 and other CAP family members.  相似文献   
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One of the major properties of the semi-synthetic minimal cell, as a model for early living cells, is the ability to self-reproduce itself, and the reproduction of the boundary layer or vesicle compartment is part of this process. A minimal bio-molecular mechanism based on the activity of one single enzyme, the FAS-B (Fatty Acid Synthase) Type I enzyme from Brevibacterium ammoniagenes, is encapsulated in 1-palmitoyl-2oleoyl-sn-glycero-3-phosphatidylcholine (POPC) liposomes to control lipid synthesis. Consequently molecules of palmitic acid released from the FAS catalysis, within the internal lumen, move toward the membrane compartment and become incorporated into the phospholipid bilayer. As a result the vesicle membranes change in lipid composition and liposome growth can be monitored. Here we report the first experiments showing vesicles growth by catalysis of one enzyme only that produces cell boundary from within. This is the prototype of the simplest autopoietic minimal cell.  相似文献   
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The therapeutic application of siRNA suffers from poor bioavailability caused by rapid degradation and elimination. The covalent attachment of PEG is a universal concept to increase molecular size and enhance the pharmacokinetic properties of biomacromolecules. We devised a facile approach for attachment of PEG molecules with a defined molecular weight, and successful purification of the resulting conjugates. We directly conjugated structurally defined PEG chains with twelve ethylene glycol units to the 3′-terminal hydroxyl group of both sense and antisense strands via an aminoalkyl linker. The conjugates were easily purified by HPLC and successful PEGylation and molecule integrity were confirmed by ESI-MS. The evaluation of in vitro gene knockdown of two different targets in MCF-7 breast cancer cells showed stable pharmacologic activity when combined with a standard transfection reagent. Sense strand PEGylation even increased the silencing potency of a CRCX4-siRNA which had modest activity in its wild-type form. The results indicate that PEG chains at the 3′-terminus of both strands of siRNA are well tolerated by the RNAi effector. The attachment of short, chemically defined PEG chains is a feasible approach to improve the pharmacokinetic properties of siRNA, and can be combined with other targeted and untargeted delivery vehicles.  相似文献   
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Summary Genetic effects for varietal value are defined at the level of the population of k-parent synthetic varieties. A simple expression for the total variance among synthetics arises directly from these definitions. A general expression for the covariance among related synthetics is given. Genetic effects are also defined in a completely general way so as to allow for any system of testing and used to derive an expression for the genetic advance in recurrent selection for varietal value. Covariances between relatives evaluated in the system of testing and in varietal combination are introduced, allowing a direct expression of the genetic advance in varietal development when parents are selected either individually or in groups. Some general implications for plant breeding are outlined.Dedicated to Professor F.W. Schnell on the occasion of his 65th birthday  相似文献   
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Many larvae from wild-caught female Glossina palpalis palpalis R.-D. treated topically with dieldrin or sumicidin or sumithrin or permethrin failed to pupariate and many larvae from mothers treated with sumicidin or sumithrin or neopynamin formed small or malformed puparia which failed to eclode. Puparia produced soon after maternal handling often did not emerge and many produced by flies starved more than 3 days also did not emerge. Very many puparia from dieldrin-treated mothers failed to emerge and non-emergence was common for puparia from flies treated with endosulfan or sumithrin or deltamethrin. Non-emerging puparia were produced soon after pyrethroid-treatment, probably due to effects on larval integumentand muscles, but were produced later after organochlorine-treatment, due to ingestion of insecticide by larvae while in utero.
Résumé Les expériences ont porté sur des femelles sauvages de Glossina palpalis palpalis R.D. capturées dans la nature. Les comparaisons ont porté sur l'état et les performances de lots de pupes provenant de mouches non-traitées et de larves mûres traitées localement avec de l'acétone (témoin) ou avec 14 insecticides différents.Toutes les larves témoin se sont nymphosées, mais le taux d'échec augmentait avec la diéldrine, la sumicidine, la sumithrine et la permethrine. Les pupes anormales (petites ou déformées) étaient plus nombreuses dans le lot témoin que dans le lot non-traité, et les fréquences étaient plus élevées que chez le témoin avec la sumidicine, la sumithrine et la néopynamine.Seulement 3 mouches sont issues de 107 pupes anormales; il n'y a eu aucune éclosion pour 28% des pupes du lot témoin contre 15% pour le lot non-traité. Pour le témoin le taux d'émergence était faible dans les pupes formées le premier jour (jour du traitement), par suite de la manipulation maternelle; il n'a pas augmenté jours 2 et 3, mais a diminué par la suite à cause du jeûne in utero. Les doses élevées de tous les insecticides réduisent plus les émergences que les doses faibles. Les organophosphates et le propoxur ne limitent pas les émergences, mais elles sont réduites par l'endosulfane, la sumithrine et la deltaméthrine, et très fortement par la diéldrine. Les pupes stériles ont été surtout formées dès le traitement aux pyréthroïdes (jour 1); et surtout plus tard (jours 2 et 3) lors des traitements aux organochlorés. L'ingestion par la larve in utero de grandes quantités d'insecticides pendant les 3 jours précédant la parturition était la principale cause de mortalité, et aussi de la forte tolérance aux organochlorés des femelles prégnantes. Les effets de pyréthroïdes sur l'activité musculaire réduisent aussi les émergences.Aucune mouche ne s'est alimentée après les traitements.
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8.
Sera from three chimpanzees infected with a primary lymphadenopathy-associated virus (LAV-1) or human T-lymphotropic virus type III (HTLV-IIIB) passage, from two chimpanzees infected with blood from the primary infected chimpanzees, and from one chimpanzee infected with blood from a secondary passage animal all bound the peptides 3B and 3B/RF, sharing the sequence IQRGPGR, with equally high titers. Pepscan analysis confirmed the amino acids Q, R, G, P, and G as irreplaceable in order to retain antigenicity.  相似文献   
9.
本文利用青蛙(Rana nigromaculata Hallowell)蝌蚪红细胞微核试验,作为检测城镇污水诱变活性的一种新的监测技术。在16d生活污水处理的实验中,青蛙蝌蚪红细胞微核细胞率2d后就呈现统计上的显著增加,并随处理时间的延长而增高,第12d达到最大值。在不同浓度混合污水处理实验中,蝌蚪红细胞微核细胞率呈现明显的剂量依赖性增加。上述实验证明城镇生活污水和混合污水都具有较强的诱变活性。作者从遗传毒理学的角度评价了湖北黄州综合生物塘系统对污水诱变活性的净化效能。城镇混合污水经综合生物塘各级塘处理,蝌蚪微核细胞率逐级下降,由进水的7.54‰下降到最后出水的1.52‰,接近对照(1.07‰)水平。其中综合生物塘的藻菌单元比水生植物单元对污水诱变活性具有更强的净化效力。本文提出污水“诱变指数”可作为综合生物塘一项功能评价指标。  相似文献   
10.
我们将三种乙型肝炎表面抗原的合成肽段在联结载体或不接载体的情况下,分别制备成4种免疫原对兔子进行了免疫。大部分兔子都产生了抗肽抗体。其中抗P_(122-48)(auw)与抗P_(122-148)(adw)都能与天然HBsAg反应,而抗P_(122-148)(adw)的抗HBs活力比文献报道的都高,通过结构分析表明:含有天然蛋白上免疫显性区域的免疫原是合成疫苗的理想选者。  相似文献   
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