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41.
Yael David Tamar Ziv Arie Admon Ami Navon 《The Journal of biological chemistry》2010,285(12):8595-8604
The ubiquitin-proteasome pathway plays a crucial role in many cellular processes by degrading substrates tagged by polyubiquitin chains, linked mostly through lysine 48 of ubiquitin. Although polymerization of ubiquitin via its six other lysine residues exists in vivo as part of various physiological pathways, the molecular mechanisms that determine the type of polyubiquitin chains remained largely unknown. We undertook a systematic, in vitro, approach to evaluate the role of E2 enzymes in determining the topology of polyubiquitin. Because this study was performed in the absence of an E3 enzyme, our data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines, depending on the specific E2 utilized. Moreover, our findings are in complete agreement with prior analyses of lysine preference assigned to certain E2s in the context of E3 (in vitro and in vivo). Finally, our findings support the rising notion that the functional unit of E2 is a dimer. To our knowledge, this is the first systematic indication for the involvement of E2 enzymes in specifying polyubiquitin chain assembly. 相似文献
42.
Introduction
The Microbicides Development Programme evaluated the safety and effectiveness of 0.5% and 2% PRO2000/5 microbicide gels in reducing the risk of vaginally acquired HIV. In February 2008 the Independent Data Monitoring Committee recommended that evaluation of 2% PRO2000/5 gel be discontinued due to futility. The Africa Centre site systematically collected participant responses to this discontinuation.Methods
Clinic and field staff completed field reports using ethnographic participant observation techniques. In-depth-interviews and focus group discussions were conducted with participants discontinued from 2% gel. A total of 72 field reports, 12 in-depth-interviews and 3 focus groups with 250 women were completed for this analysis. Retention of discontinued participants was also analysed. Qualitative data was analysed using NVivo 2 and quantitative data using STATA 10.0.Results
Participants responded initially with fear that discontinuation was due to harm, followed by acceptance after effective messaging, and finally with disappointment. Participants reported that their initial fear was exacerbated by being contacted and advised to visit the clinic for information about the closure. Operational changes were subsequently made to the contact procedures. By incorporating feedback from participants, messages were continuously revised to ensure that information was comprehensible and misconceptions were addressed quickly thereby enabling participants to accept the discontinuation. Participants were disappointed that 2% PRO2000/5 was being excluded as a HIV prevention option, but also that they would no longer have access to gel that improved their sexual relationships with their partners and assisted condom negotiations. In total 238 women were discontinued from gel and 185 (78%) went on to complete their scheduled follow-up period.Discussion
The use of qualitative social science techniques allowed the site team to amend operational procedures and messaging throughout the discontinuation period. This proved instrumental in ensuring that the discontinuation was successfully completed in a manner that was both understandable and acceptable to participants.Trial registration
Current Controlled Trials. ISRCTN64716212. 相似文献43.
Shilman Florin Brand Yael Brand Arnon Hedvat Ilan Hovav Ran 《Plant Molecular Biology Reporter》2011,29(1):232-241
The stearoyl–acyl carrier protein (ACP) desaturase (SAD) is a nuclear-encoded, plastid-localized soluble desaturase that catalyzes the conversion of stearoyl-ACP to oleoyl-ACP and plays a key role in the determination of the properties of the majority of cellular glycerolipids. Sad genes from a variety of plant species have been cloned and characterized. However, in peanut (Arachis hypogaea), an important edible and oilseed crop, these genes have not yet been characterized. By searching peanut expressed sequence tag (EST) and parallel sequencing (454) libraries, we have identified three members of the ahSad gene family. Among them, only one gene, ahSad3, was exclusively expressed during seed development and in a manner fully corresponding to oil accumulation. Both ahSad3 homeologous genes (ahSad3A and ahSad3B) were recovered from the allotetraploid peanut, and their mRNA expression levels were characterized. The open reading frames for ahSad3A and ahSad3B are 98% identical and consist of 1,158 bp, encoding a 386-full-amino-acid protein, with one intron in the coding sequence. Comparisons of the sequences of these two homeologous genes revealed seven single-nucleotide polymorphisms and one triplet insertion in the coding region. Southern blot analysis indicated that there are only two copies of the ahSad3 gene in the peanut genome. Homeolog-specific gene expression analysis showed that both ahSad3 homeologs are expressed in developing seeds, but gene expression is significantly biased toward the B genome. Our results point to ahSad3 as a possible target gene for manipulation of fatty acid saturation in A. hypogaea. 相似文献
44.
45.
Many of the targets of structural genomics will be proteins with little or no structural similarity to those currently in the database. Therefore, novel function prediction methods that do not rely on sequence or fold similarity to other known proteins are needed. We present an automated approach to predict nucleic-acid-binding (NA-binding) proteins, specifically DNA-binding proteins. The method is based on characterizing the structural and sequence properties of large, positively charged electrostatic patches on DNA-binding protein surfaces, which typically coincide with the DNA-binding-sites. Using an ensemble of features extracted from these electrostatic patches, we predict DNA-binding proteins with high accuracy. We show that our method does not rely on sequence or structure homology and is capable of predicting proteins of novel-binding motifs and protein structures solved in an unbound state. Our method can also distinguish NA-binding proteins from other proteins that have similar, large positive electrostatic patches on their surfaces, but that do not bind nucleic acids. 相似文献
46.
47.
When larvae of Tribolium castaneum were reared on diets deficient in thiamine, pyridoxine or riboflavin mortality was high and the rate of development was slow. The few surviving larvae did attain the same final stage as larvae developing on an all-vitamin control. On diets deficient in nicotinic acid, calcium pantothenate or choline chloride all aspects of development were impaired and no pupation occurred. The negative effects of folic acid deficiency were more pronounced in the pupal stage than in the larval instars. The dietary deficiency of folic acid, choline chloride or thiamine, had no apparent effect on adult fecundity, and a dietary deficiency of any one of the seven vitamins assayed did not adversely affect egg fertility.
Résumé Une mortalité importante a été constatée chez des larves de Tribolium castaneum élevées sur des régimes déficitaires en thiamine, pyridoxine et riboflavine. Le développement a été ralenti d'une façon considérable, mais les larves qui ont survécu sont arrivées au même stade final que les larves témoins nourries avec toutes les vitamines. Tous les autres régimes alimentaires ont été moins adéquates que celui contenant un supplément de levure. L'effet de l'absence de l'acide nicotinique, du pantothenate de calcium ou bien du chlorure de choline a été encore plus net, car les larves ne se sont pas nymphosées. Cet effet prononcé de l'insuffisance du chlorure de choline contraste avec la réaction de Tribolium confusum à l'absence de chlorure de choline dans le régime alimentaire.Le développement larvaire a été peu affecté par l'absence de l'acide folique. Mais, durant la nymphose, les effets négatifs se manifestent davantage encore. L'absence de pyridoxine, riboflavine, acide nicotinique ou pantothenate du calcium a réduit d'une façon importante le taux initial de la fécondité des adultes de T. castaneum. L'absence de l'acide folique, chlorure de choline ou thiamine n'a pas été marquée par un effet semblable. La fertilité des ufs n'a pas été affectée par le manque d'une vitamine quelconque.Ces résultats indiquent que le chlorure de choline et la thiamine sont nécessaires pour le développement larvaire, mais qu'elles sont peu importantes pour la vitalité des adultes. Les réserves en certaines vitamines essentielles chez les nymphes suffisent donc aux exigences des adultes, au moins pendant quelques mois après leur éclosion.相似文献
48.
49.
The complex pathway of tetrapyrrole biosynthesis can be dissected into five sections: the pathways that produce 5-aminolevulinate (the C-4 and the C-5 pathways), the steps that transform ALA to uroporphyrinogen III, which are ubiquitous in the biosynthesis of all tetrapyrroles, and the three branches producing specialized end products. These end products include corrins and siroheme, chlorophylls and hemes and linear tetrapyrroles. These branches have been subjects of recent reviews. This review concentrates on the early steps leading up to uroporphyrinogen III formation which have been investigated intensively in recent years in animals, in plants, and in a wide range of bacteria.Abbreviations ALA
5-aminolevulinic acid
- ALAS
5-aminolevulinic acid synthase
- GR
glutamyl-tRNA reductase
- GSA
glutamate-1-semialdehyde
- GSAT
glutamate-1-semialdehyde aminotransferase
- HMB
hydroxymethylbilane
- PBG
porphobilinogen
- PBGD
porphobilinogen deaminase
- PBGS
porphobilinogen synthase
- URO
uroporphyrin
- URO'gen
uroporphyrinogen
- US
uroporphyrinogen III synthase 相似文献
50.