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31.
Stem cells, including mesenchymal stem cells and pluripotent stem cells, are becoming an indispensable tool for various biomedical applications including drug discovery, disease modeling, and tissue engineering. Bioprocess engineering, targeting large scale production, provides a platform to generate a controlled microenvironment that could potentially recreate the stem cell niche to promote stem cell proliferation or lineage-specific differentiation. This survey aims at defining the characteristics of stem cell populations currently in use and the present-day limits in their applications for therapeutic purposes. Furthermore, a bioprocess engineering strategy based on bioreactors and 3-D cultures is discussed in order to achieve the improved stem cell yield, function, and safety required for production under current good manufacturing practices. 相似文献
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33.
Seasonal water quality of shallow and eutrophic Lake Pamvotis, Greece: implications for restoration 总被引:6,自引:2,他引:4
José R. Romero Iphigenia Kagalou Jörg Imberger Dimitra Hela Melina Kotti Aristides Bartzokas Triantafyllos Albanis Nicholaos Evmirides Spiros Karkabounas Joannis Papagiannis Amalia Bithava 《Hydrobiologia》2002,474(1-3):91-105
Lake Pamvotis is a moderately sized (22 km2) shallow (z
avg=4 m) lake with a polymictic stratification regime located in northwest Greece. The lake has undergone cultural eutrophication over the past 40 years and is currently eutrophic (annual averages of FRP=0.07 mg P l-1, TP=0.11 mg P l-1, NH4
+=0.25 mg N l-1, NO3
–=0.56 mg N l-1). FRP and NH4
+ levels are correlated to external loading from streams during the winter and spring, and to internal loading during multi-day periods of summer stratification. Algal blooms occurred in summer (July–August green algae, August–September blue-green algae), autumn (October blue-green algae and diatoms), and winter (February diatoms), but not in the spring (March–June). The phytoplankton underwent brief periods of N- and P-limitation, though persistent low transparency (secchi depth of 60–80 cm) also suggests periods of light limitation. Rotifers counts were highest from mid-summer to early autumn whereas copepods were high in the spring and cladocerans were low in the summer. Removal of industrial and sewage point sources a decade ago resulted in a decrease in FRP. A phosphorus mass balance identified further reductions in external loading from the predominately agricultural catchment will decrease FRP levels further. The commercial fishery and lake hatchery also provides opportunities to control algal biomass through biomanipulation measures. 相似文献
34.
Peleg AY Miyakis S Ward DV Earl AM Rubio A Cameron DR Pillai S Moellering RC Eliopoulos GM 《PloS one》2012,7(1):e28316
Background
Daptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus.Methods
Whole genome sequencing was performed on a unique collection of isogenic, clinical (21 strains) and laboratory (12 strains) derived strains that had been exposed to daptomycin and developed daptomycin-nonsusceptibility. Electron microscopy (EM) and lipid membrane studies were performed on selected isolates.Results
On average, six coding region mutations were observed across the genome in the clinical daptomycin exposed strains, whereas only two mutations on average were seen in the laboratory exposed pairs. All daptomycin-nonsusceptible strains had a mutation in a phospholipid biosynthesis gene. This included mutations in the previously described mprF gene, but also in other phospholipid biosynthesis genes, including cardiolipin synthase (cls2) and CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase (pgsA). EM and lipid membrane composition analyses on two clinical pairs showed that the daptomycin-nonsusceptible strains had a thicker cell wall and an increase in membrane lysyl-phosphatidylglycerol.Conclusion
Point mutations in genes coding for membrane phospholipids are associated with the development of reduced susceptibility to daptomycin in S. aureus. Mutations in cls2 and pgsA appear to be new genetic mechanisms affecting daptomycin susceptibility in S. aureus. 相似文献35.
36.
Sophia Letsiou Ying Lu Tzortzis Nomikos Smaragdi Antonopoulou Demosthenes Panagiotakos Christos Pitsavos Christodoulos Stefanadis Spiros A. Pergantis 《Proteomics》2010,10(19):3447-3457
In this study, a method, based on dual column affinity chromatography hyphenated to isotope dilution inductively coupled plasma–quadrupole MS, was developed for selenium determination in selenoprotein P, glutathione peroxidase, and selenoalbumin in human serum samples from a group of healthy volunteers (n=399). Method improvement was achieved using methanol‐enhanced isotope dilution which resulted in improved sensitivity and removal of isobaric interferences. Although no human serum reference materials are currently certified for their selenium species levels, method development was conducted using human serum reference material BCR 637 and 639 as their Se species content has been reported in the previous studies, and thus comparisons were possible. The mean selenium concentrations determined for the 399 healthy volunteer serum samples were 23±10 ng Se mL?1 for glutathione peroxidase, 49±15 ng Se mL?1 for selenoprotein P and 11±4 ng Se mL?1 for selenoalbumin. These values are found to be in close agreement with published values for a limited number of healthy volunteer samples, and to establish baseline Se levels in serum proteins for an apparently healthy group of individuals, thus allowing for subsequent comparisons with respective values determined for groups of individuals with selenium related health issues, as well as assist in the discovery of potential selenium biomarkers. Also, the relationship between Se serum protein levels and some anthropometric characteristics of the volunteer population were investigated. Additionally, further development of the analytical method used in this study was achieved by adding a size exclusion chromatography column after the two affinity columns via a switching valve. This allowed for the separation of small selenium‐containing molecules from glutathione peroxidase and thus enhanced the overall confidence in its identification. 相似文献
37.
Nathalie Bouloc Jonathan M. Large Magda Kosmopoulou Chongbo Sun Amir Faisal Mizio Matteucci Jóhannes Reynisson Nathan Brown Butrus Atrash Julian Blagg Edward McDonald Spiros Linardopoulos Richard Bayliss Vassilios Bavetsias 《Bioorganic & medicinal chemistry letters》2010,20(20):5988-5993
Co-crystallisation of the imidazo[1,2-a]pyrazine derivative 15 (3-chloro-N-(4-morpholinophenyl)-6-(pyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine) with Aurora-A provided an insight into the interactions of this class of compound with Aurora kinases. This led to the design and synthesis of potent Aurora-A inhibitors demonstrating up to 70-fold selectivity in cell-based Aurora kinase pharmacodynamic biomarker assays. 相似文献
38.
Spiros Liras Stanton F. McHardy Martin P. Allen Barb E. Segelstein Steven D. Heck Dianne K. Bryce Anne W. Schmidt Michelle Vanase-Frawley Ernesto Callegari Stafford McLean 《Bioorganic & medicinal chemistry letters》2010,20(2):503-507
The design and synthesis of novel opiates are reported. Based on the message-address principle a novel class of 4,4- and 3,3-biaryl piperidines was designed and synthesized. Biological evaluation confirmed that these compounds exhibit high affinity and selectivity for the delta opioid receptor. Key structure–activity relationships that influence affinity, selectivity, functional activity and clearance are reported. 相似文献
39.
Hui‐Su Kim Bo‐Young Lee Jeonghoon Han Chang‐Bum Jeong Dae‐Sik Hwang Min‐Chul Lee Hye‐Min Kang Duck‐Hyun Kim Hee‐Jin Kim Spiros Papakostas Steven A. J. Declerck Ik‐Young Choi Atsushi Hagiwara Heum Gi Park Jae‐Seong Lee 《Molecular ecology resources》2018,18(3):646-655
Monogononta is the most speciose class of rotifers, with more than 2,000 species. The monogonont genus Brachionus is widely distributed at a global scale, and a few of its species are commonly used as ecological and evolutionary models to address questions related to aquatic ecology, cryptic speciation, evolutionary ecology, the evolution of sex and ecotoxicology. With the importance of Brachionus species in many areas of research, it is remarkable that the genome has not been characterized. This study aims to address this lacuna by presenting, for the first time, the whole‐genome assembly of the freshwater species Brachionus calyciflorus. The total length of the assembled genome was 129.6 Mb, with 1,041 scaffolds. The N50 value was 786.6 kb, and the GC content was 24%. A total of 16,114 genes were annotated with repeat sequences, accounting for 21% of the assembled genome. This assembled genome may form a basis for future studies addressing key questions on the evolution of monogonont rotifers. It will also provide the necessary molecular resources to mechanistically investigate ecophysiological and ecotoxicological responses. 相似文献
40.
White TR Renzelman CM Rand AC Rezai T McEwen CM Gelev VM Turner RA Linington RG Leung SS Kalgutkar AS Bauman JN Zhang Y Liras S Price DA Mathiowetz AM Jacobson MP Lokey RS 《Nature chemical biology》2011,7(11):810-817
Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective, on-resin N-methylation of cyclic peptides to generate compounds with drug-like membrane permeability and oral bioavailability. The selectivity and degree of N-methylation of the cyclic peptide was dependent on backbone stereochemistry, suggesting that conformation dictates the regiochemistry of the N-methylation reaction. The permeabilities of the N-methyl variants were corroborated by computational studies on a 1,024-member virtual library of N-methyl cyclic peptides. One of the most permeable compounds, a cyclic hexapeptide (molecular mass = 755 Da) with three N-methyl groups, showed an oral bioavailability of 28% in rat. 相似文献