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21.
In our study of the biosynthesis of D-desosamine in Streptomyces venezuelae, we have cloned and sequenced the entire desosamine biosynthetic cluster. The deduced product of one of the genes, desR, in this cluster shows high sequence homology to beta-glucosidases, which catalyze the hydrolysis of the glycosidic linkages, a function not required for the biosynthesis of desosamine. Disruption of the desR gene led to the accumulation of glucosylated methymycin/neomethymycin products, all of which are biologically inactive. It is thus conceivable that methymycin/neomethymycin may be produced as inert diglycosides, and the DesR protein is responsible for transforming these antibiotics from their dormant to their active forms. This hypothesis is supported by the fact that the translated desR gene has a leader sequence characteristic of secretory proteins, allowing it to be transported through the cell membrane and hydrolyze the modified antibiotics extracellularly to activate them. Expression of desR and biochemical characterization of the purified protein confirmed the catalytic function of this enzyme as a beta-glycosidase capable of catalyzing the hydrolysis of glucosylated methymycin/neomethymycin produced by S. venezuelae. These results provide strong evidence substantiating glycosylation/deglycosylation as a likely self-resistance mechanism of S. venezuelae. However, further experiments have suggested that such a glycosylation/deglycosylation is only a secondary self-defense mechanism in S. venezuelae, whereas modification of 23S rRNA, which is the target site for methymycin and its derivatives, by PikR1 and PikR2 is a primary self-resistance mechanism. Considering that postsynthetic glycosylation is an effective means to control the biological activity of macrolide antibiotics, the availability of macrolide glycosidases, which can be used for the activation of newly formed antibiotics that have been deliberately deactivated by engineered glycosyltransferases, may be a valuable part of an overall strategy for the development of novel antibiotics using the combinatorial biosynthetic approach. 相似文献
22.
Brennan NM Ward AC Beresford TP Fox PF Goodfellow M Cogan TM 《Applied and environmental microbiology》2002,68(2):820-830
The bacteria on the surface of a farmhouse smear-ripened cheese at four stages of ripening (4, 16, 23, and 37 days) from inoculated (i.e., deliberately inoculated with Brevibacterium linens BL2) and noninoculated (not deliberately inoculated with B. linens BL2) cheese were investigated. The results show that, contrary to accepted belief, B. linens is not a significant member of the surface flora of smear cheese and no microbial succession of species occurred during the ripening of the cheeses. Of 400 isolates made, 390 were lactate-utilizing coryneforms and 10 were coagulase-negative Staphylococcus spp. A detailed analysis of the coryneforms was undertaken using phenotypic analysis, molecular fingerprinting, chemotaxonomic techniques, and 16S rRNA gene sequencing. DNA banding profiles (ramdom amplified polymorphic DNA [RAPD]-PCR) of all the coryneform isolates showed large numbers of clusters. However, pulsed-field gel electrophoresis (PFGE) of the isolates from the cheeses showed that all isolates within a cluster and in many contiguous clusters were the same. The inoculated and noninoculated cheeses were dominated by single clones of novel species of Corynebacterium casei (50.2% of isolates), Corynebacterium mooreparkense (26% of isolates), and Microbacterium gubbeenense (12.8% of isolates). In addition, five of the isolates from the inoculated cheese were Corynebacterium flavescens. Thirty-seven strains were not identified but many had similar PFGE patterns, indicating that they were the same species. C. mooreparkense and C. casei grew at pH values below 4.9 in the presence of 8% NaCl, while M. gubbeenense did not grow below pH 5.8 in the presence of 5 to 10% NaCl. B. linens BL2 was not recovered from the inoculated cheese because it was inhibited by all the Staphylococcus isolates and many of the coryneforms. It was concluded that within a particular batch of cheese there was significant bacterial diversity in the microflora on the surface. 相似文献
23.
Identification of murine germinal center B cell subsets defined by the expression of surface isotypes and differentiation antigens 总被引:9,自引:0,他引:9
Shinall SM Gonzalez-Fernandez M Noelle RJ Waldschmidt TJ 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(11):5729-5738
Germinal centers (GCs) are inducible lymphoid microenvironments that support the generation of memory B cells, affinity maturation, and isotype switching. Previously, phenotypic transitions following in vivo B cell activation have been exploited to discriminate GC from non-GC B cells in the mouse and to delineate as many as seven distinct human peripheral B cell subsets. To better understand the differentiative processes occurring within murine GCs, we sought to identify subpopulations of GC B cells corresponding to discrete stages of GC B cell ontogeny. We performed multiparameter flow-cytometric analyses of GC B cells at consecutive time points following immunization of BALB/c mice with SRBC. We resolved the murine GC compartment into subsets based on the differential expression of activation markers, surface Ig isotypes, and differentiation Ags. Class-switched and nonswitched GC B cells emerged contemporaneously, and their relative frequencies remained nearly constant throughout the GC reaction, perhaps reflecting the establishment of a steady state. A significant percentage of the nonswitched B cells with a GC phenotype exhibited surface markers associated with naive B cells, including CD23, surface IgD, and high levels of CD38 consistent with either prolonged recruitment into the GC reaction or protracted expression of these markers during differentiation within the GC. Expression of the activation marker BLA-1 was dynamic over time, with all GC B cells being positive early after immunization, followed by progressive loss as the GC reaction matured into the second and third week. Implications of these results concerning GC evolution are discussed. 相似文献
24.
Functional Interactions between Yeast Mitochondrial Ribosomes and mRNA 5′ Untranslated Leaders 下载免费PDF全文
Noelle S. Green-Willms Thomas D. Fox Maria C. Costanzo 《Molecular and cellular biology》1998,18(4):1826-1834
Translation of mitochondrial mRNAs in Saccharomyces cerevisiae depends on mRNA-specific translational activators that recognize the 5′ untranslated leaders (5′-UTLs) of their target mRNAs. We have identified mutations in two new nuclear genes that suppress translation defects due to certain alterations in the 5′-UTLs of both the COX2 and COX3 mRNAs, indicating a general function in translational activation. One gene, MRP21, encodes a protein with a domain related to the bacterial ribosomal protein S21 and to unidentified proteins of several animals. The other gene, MRP51, encodes a novel protein whose only known homolog is encoded by an unidentified gene in S. kluyveri. Deletion of either MRP21 or MRP51 completely blocked mitochondrial gene expression. Submitochondrial fractionation showed that both Mrp21p and Mrp51p cosediment with the mitochondrial ribosomal small subunit. The suppressor mutations are missense substitutions, and those affecting Mrp21p alter the region homologous to E. coli S21, which is known to interact with mRNAs. Interactions of the suppressor mutations with leaky mitochondrial initiation codon mutations strongly suggest that the suppressors do not generally increase translational efficiency, since some alleles that strongly suppress 5′-UTL mutations fail to suppress initiation codon mutations. We propose that mitochondrial ribosomes themselves recognize a common feature of mRNA 5′-UTLs which, in conjunction with mRNA-specific translational activation, is required for organellar translation initiation. 相似文献
25.
Noelle A. Benzekri Jacques Sambou Binetou Diaw El Hadji Ibrahima Sall Fatima Sall Alassane Niang Selly Ba Ndèye Fatou Ngom Guèye Mouhamadou Ba?la Diallo Stephen E. Hawes Moussa Seydi Geoffrey S. Gottlieb 《PloS one》2015,10(11)
Background
Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes.Methods
We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review.Results
One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01).Conclusions
Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population. 相似文献26.
27.
28.
Amel Dudakovic Emily T. Camilleri Fuhua Xu Scott M. Riester Meghan E. McGee-Lawrence Elizabeth W. Bradley Christopher R. Paradise Eric A. Lewallen Roman Thaler David R. Deyle A. Noelle Larson David G. Lewallen Allan B. Dietz Gary S. Stein Martin A. Montecino Jennifer J. Westendorf Andre J. van Wijnen 《The Journal of biological chemistry》2015,290(46):27604-27617
Epigenetic control of gene expression is critical for normal fetal development. However, chromatin-related mechanisms that activate bone-specific programs during osteogenesis have remained underexplored. Therefore, we investigated the expression profiles of a large cohort of epigenetic regulators (>300) during osteogenic differentiation of human mesenchymal cells derived from the stromal vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated during osteoblastic differentiation of AMSCs. Chemical inhibitor and siRNA knockdown studies show that EZH2, a histone methyltransferase that catalyzes trimethylation of histone 3 lysine 27 (H3K27me3), suppresses osteogenic differentiation. Blocking EZH2 activity promotes osteoblast differentiation and suppresses adipogenic differentiation of AMSCs. High throughput RNA sequence (mRNASeq) analysis reveals that EZH2 inhibition stimulates cell cycle inhibitory proteins and enhances the production of extracellular matrix proteins. Conditional genetic loss of Ezh2 in uncommitted mesenchymal cells (Prrx1-Cre) results in multiple defects in skeletal patterning and bone formation, including shortened forelimbs, craniosynostosis, and clinodactyly. Histological analysis and mRNASeq profiling suggest that these effects are attributable to growth plate abnormalities and premature cranial suture closure because of precocious maturation of osteoblasts. We conclude that the epigenetic activity of EZH2 is required for skeletal patterning and development, but EZH2 expression declines during terminal osteoblast differentiation and matrix production. 相似文献
29.
Karen E. Sears Allison K. Bormet Alexander Rockwell Lisa E. Powers Lisa Noelle Cooper Matthew B. Wheeler 《Evolution & development》2011,13(6):533-541
Digit reduction has occurred in parallel in many mammalian lineages. However, despite this pattern's prevalence, the developmental mechanisms underlying mammalian digit reduction remain controversial. We therefore undertook a study of digit development in the pig (Sus scrofa), a mammal with reduced first, second, and fifth digits. Our results indicate that from its earliest formation, the pig limb bud is significantly narrower than that of the model pentadactyl mammal, mouse. Furthermore, the cartilage condensations of the pig's reduced digits are noticeably smaller than those of their nonreduced counterparts from the time of their formation. In addition, growth rates of pig digits are comparable, as are the patterns of cell death in developing pig and mouse limbs. Taken together, results suggest that pig's first, second, and fifth digits are primarily reduced through evolutionary modifications in the early developmental patterning of their limbs. Results of this study, coupled with those from study of limb development in other mammals, suggest that although major developmental reorganizations (e.g., complete digit or limb loss) during early limb development may be selected against, it may be common for more subtle evolutionary modifications in limb development (e.g., changes in relative digit size) to occur at this time. 相似文献
30.
Roess AA Monroe BP Kinzoni EA Gallagher S Ibata SR Badinga N Molouania TM Mabola FS Mombouli JV Carroll DS MacNeil A Benzekri NA Moses C Damon IK Reynolds MG 《PLoS neglected tropical diseases》2011,5(10):e1356