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91.
Cell culture media supplementation of infrequently used sugars for the targeted shifting of protein glycosylation profiles 下载免费PDF全文
Patrick Hossler Christopher Racicot Christopher Chumsae Sean McDermott Keith Cochran 《Biotechnology progress》2017,33(2):511-522
Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized. These sugars are particularly interesting because they can be utilized by cells in culture in distinct ways. In the present work it has been found that many infrequently used sugars, and the corresponding cellular response towards them as substrates, led to differences in the protein N‐glycosylation profile of a recombinant glycoprotein. The selective media supplementation of raffinose, trehalose, turanose, palatinose, melezitose, psicose, lactose, lactulose, and mannose were found to be capable of redirecting N‐glycan oligosaccharide profiles. Despite this shifting of protein glycosylation, there were no other adverse changes in culture performance, including both cell growth and cellular productivity over a wide range of supplemented sugar concentrations. The approach presented highlights a potential means towards both the targeted shifting of protein glycosylation profiles and ensuring recombinant protein comparability, which up to this point in time has remained under‐appreciated for these under‐utilized compounds. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:511–522, 2017 相似文献
92.
Melanie Brügger Thomas Dmoulins G. Tuba Barut Beatrice Zumkehr Blandina I. Oliveira Esteves Kemal Mehinagic Quentin Haas Aline Schgler Marie-Anne Rameix-Welti Jean-Franois Elouët Ueli Moehrlen Thomas M. Marti Ralph A. Schmid Artur Summerfield Horst Posthaus Nicolas Ruggli Sean R. R. Hall Marco P. Alves 《PLoS pathogens》2021,17(7)
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94.
Larson RA Dai D Hosack VT Tan Y Bolken TC Hruby DE Amberg SM 《Journal of virology》2008,82(21):10768-10775
Several arenaviruses, including Lassa virus (LASV), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. The LASV envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. A benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. Subsequent lead optimization for antiviral activity identified a modified structure, ST-193, with a 50% inhibitory concentration (IC(50)) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes generated with other arenavirus envelopes as well, including the remaining four commonly associated with hemorrhagic fever (IC(50)s for Junín, Machupo, Guanarito, and Sabiá were in the 0.2 to 12 nM range) but exhibited no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 microM. Determinants of ST-193 sensitivity were mapped through a combination of LASV-LCMV domain-swapping experiments, genetic selection of viral variants, and site-directed mutagenesis. Taken together, these studies demonstrate that sensitivity to ST-193 is dictated by a segment of about 30 amino acids within the GP2 subunit. This region includes the carboxy-terminal region of the ectodomain and the predicted transmembrane domain of the envelope protein, revealing a novel antiviral target within the arenavirus envelope GP. 相似文献
95.
Young JM Endicott RM Parghi SS Walker M Kidd JM Trask BJ 《American journal of human genetics》2008,83(2):228-242
As much as a quarter of the human genome has been reported to vary in copy number between individuals, including regions containing about half of the members of the olfactory receptor (OR) gene family. We have undertaken a detailed study of copy-number variation of ORs to elucidate the selective and mechanistic forces acting on this gene family and the true impact of copy-number variation on human OR repertoires. We argue that the properties of copy-number variants (CNVs) and other sets of large genomic regions violate the assumptions of statistical methods that are commonly used in the assessment of gene enrichment. Using more appropriate methods, we provide evidence that OR enrichment in CNVs is not due to positive selection but is because of OR preponderance in segmentally duplicated regions, which are known to be frequently copy-number variable, and because purifying selection against CNVs is lower in OR-containing regions than in regions containing essential genes. We also combine multiplex ligation-dependent probe amplification (MLPA) and PCR to assay the copy numbers of 37 candidate CNV ORs in a panel of ~50 human individuals. We confirm copy-number variation of 18 ORs but find no variation in this human-diversity panel for 16 other ORs, highlighting the caveat that reported intervals often overrepresent true CNVs. The copy-number variation we describe is likely to underpin significant variation in olfactory abilities among human individuals. Finally, we show that both homology-based and homology-independent processes have played a recent role in remodeling the OR family. 相似文献
96.
Stem cells and niches: mechanisms that promote stem cell maintenance throughout life 总被引:2,自引:0,他引:2
Niches are local tissue microenvironments that maintain and regulate stem cells. Long-predicted from mammalian studies, these structures have recently been characterized within several invertebrate tissues using methods that reliably identify individual stem cells and their functional requirements. Although similar single-cell resolution has usually not been achieved in mammalian tissues, principles likely to govern the behavior of niches in diverse organisms are emerging. Considerable progress has been made in elucidating how the microenvironment promotes stem cell maintenance. Mechanisms of stem cell maintenance are key to the regulation of homeostasis and likely contribute to aging and tumorigenesis when altered during adulthood. 相似文献
97.
A road map for molecular ecology 总被引:1,自引:0,他引:1
Rose L. Andrew Louis Bernatchez Aurélie Bonin C. Alex. Buerkle Bryan C. Carstens Brent C. Emerson Dany Garant Tatiana Giraud Nolan C. Kane Sean M. Rogers Jon Slate Harry Smith Victoria L. Sork Graham N. Stone Timothy H. Vines Lisette Waits Alex Widmer Loren H. Rieseberg 《Molecular ecology》2013,22(10):2605-2626
The discipline of molecular ecology has undergone enormous changes since the journal bearing its name was launched approximately two decades ago. The field has seen great strides in analytical methods development, made groundbreaking discoveries and experienced a revolution in genotyping technology. Here, we provide brief perspectives on the main subdisciplines of molecular ecology, describe key questions and goals, discuss common challenges, predict future research directions and suggest research priorities for the next 20 years. 相似文献
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99.
Cultural or tool use behaviours are typically conducted in social or food procurement contexts where the individual interacts with conspecifics, heterospecifics or environmental features. We report on postcoital penis cleaning in chimpanzees, an activity that does not fit this pattern. In penis cleaning, leaves are employed as 'napkins' to wipe clean the penis after sex. Alternatively, the same cleaning motion can be done without leaves, simply using the fingers. Not all chimpanzee communities studied across Africa clean their penes and, where documented, the behaviour is rare. By contrast, we identify postcoital penis cleaning in Budongo Forest, Uganda, as customary and corroborate penis cleaning as another cultural trait in chimpanzees, one that is specific to only a subset of the eastern subspecies of chimpanzee (Pan troglodytes schweinfurthii). 相似文献
100.
Sean C. Brooks 《Inorganica chimica acta》2006,359(14):4635-4638
The synthesis, electrochemistry, spectroscopy and electrogenerated chemiluminescence (ECL) of five bis-bipyridine ruthenium(II) complexes containing acetylacetonate complexes are reported. More specifically, (bpy)2Ru(BA)2(PF6) (bpy = 2,2′-bipyridine; BA = benzoylacetonate), (bpy)2Ru(TTFA)(PF6) (TTFA = thenoyltrifluoroacetonate), (bpy)2Ru(TFPB)(PF6) (TFPB = 4,4,4-trifluoro-1-phenyl-1,3-butanedionate), (bpy)2Ru(TFPD)(PF6) (TFPD = 1,1,1-trifluoro-2-4-pentanedionate), and (bpy)2Ru(DBM)(PF6) (DBM = dibenzoylmethide) display UV-Vis, photoluminescence, electrochemical and ECL properties characteristic of ruthenium bipyridyl complexes. All complexes display absorptions in the UV and visible regions of the spectra, with visible absorptions ranging from 350 to 700 nm, typical of metal-to-ligand charge transfer (MLCT) transitions. Photoluminescence emission maxima are also characteristic of MLCT transitions with wavelength maxima from 575 to 600 nm depending on the nature of the acetylacetonate ligand. ECL efficiencies for the complexes (?ecl ∼ 0.013-0.051) are much lower than a standard (?ecl = 1) with electron-withdrawing substituents resulting in lower efficiencies. 相似文献