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141.
Pitkänen L Tuomainen P Virkki L Tenkanen M 《International journal of biological macromolecules》2011,49(5):963-969
Two α-l-arabinofuranosidases with different substrate specificities were used to modify the arabinose-to-xylose ratio of cereal arabinoxylans: one enzyme (AXH-m) removed the l-arabinofuranosyl substituents from the monosubstituted xylopyranosyl residues and the other (AXH-d3) the (1 → 3)-linked l-arabinofuranosyl units from the disubstituted xylopyranosyl residue. In this study, we noticed that not only the arabinose-to-xylose ratio but also the position of the arabinofuranosyl substituents affects the water-solubility of arabinoxylans. The AXH-d3 treatment had no significant effect on the solution conformation of arabinoxylans, but the density of the arabinoxylan molecules decreased in DMSO solution after AXH-m modification. The possible heterogeneity of arabinoxylans complicated the interpretation of data describing the macromolecular properties of the enzymatically modified samples. 相似文献
142.
Srikanth Kotapati Leena Maddukuri Susith Wickramaratne Uthpala Seneviratne Melissa Goggin Matthew G. Pence Peter Villalta F. Peter Guengerich Lawrence Marnett Natalia Tretyakova 《The Journal of biological chemistry》2012,287(46):38800-38811
The 1,N6-(2-Hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N6-γ-HMHP-dA) adducts are formed upon bifunctional alkylation of adenine nucleobases in DNA by 1,2,3,4-diepoxybutane, the putative ultimate carcinogenic metabolite of 1,3-butadiene. The presence of a substituted 1,N6-propano group on 1,N6-γ-HMHP-dA is expected to block the Watson-Crick base pairing of the adducted adenine with thymine, potentially contributing to mutagenesis. In this study, the enzymology of replication past site-specific 1,N6-γ-HMHP-dA lesions in the presence of human DNA polymerases (hpols) β, η, κ, and ι and archebacterial polymerase Dpo4 was investigated. Run-on gel analysis with all four dNTPs revealed that hpol η, κ, and Dpo4 were able to copy the modified template. In contrast, hpol ι inserted a single base opposite 1,N6-γ-HMHP-dA but was unable to extend beyond the damaged site, and a complete replication block was observed with hpol β. Single nucleotide incorporation experiments indicated that although hpol η, κ, and Dpo4 incorporated the correct nucleotide (dTMP) opposite the lesion, dGMP and dAMP were inserted with a comparable frequency. HPLC-ESI-MS/MS analysis of primer extension products confirmed the ability of bypass polymerases to insert dTMP, dAMP, or dGMP opposite 1,N6-γ-HMHP-dA and detected large amounts of −1 and −2 deletion products. Taken together, these results indicate that hpol η and κ enzymes bypass 1,N6-γ-HMHP-dA lesions in an error-prone fashion, potentially contributing to A→T and A→C transversions and frameshift mutations observed in cells following treatment with 1,2,3,4-diepoxybutane. 相似文献
143.
Changes in the Above- and Below-ground Biomass and Nutrient Pools of Ground Vegetation After Clear-cutting of a Mixed Boreal Forest 总被引:3,自引:0,他引:3
Marjo Palviainen Leena Finér Hannu Mannerkoski Sirpa Piirainen Michael Starr 《Plant and Soil》2005,275(1-2):157-167
Ground vegetation may act as a sink for nutrients after clear-cutting and thus decrease leaching losses. Biomass and nutrient
(N, P, K, Ca) pools of ground vegetation (mosses, roots and above-ground parts of field layer) were determined one year before
and five years after clear-cutting of a Norway spruce (Picea abies (L.) H. Karst.) dominated boreal mixed forest stand in
eastern Finland (63°51′ N, 28°58′ E). Before clear-cutting the average biomass of ground vegetation was 5307 kg ha−1, with nutrient contents of 46.9 kg N ha−11, 4.1 kg P ha−11, 16.2 kg K ha−11 and 13.9 kg Ca ha−11. The biomass and nutrient pools decreased after clear-cutting being lowest in the second year, the biomass decreasing by
46–65% in the cut plots. The nutrient pools decreased as follows: N 54–72%, P 36–68%, K 51–71% and Ca 57–74%. The decrease
in ground vegetation nutrient uptake, and the observed reduced depth of rooting may decrease nutrient retention after clear-cutting
and decomposing dead ground vegetation is a potential source of leached nutrients. These negative effects of clear-cutting
on the nutrient binding capacity of ground vegetation was short-lived since the total biomass and nutrient pools returned
to pre-cutting levels or were even greater by the end of the 5-year study period. 相似文献
144.
Sarah Eddy Amit Ketkar Maroof K. Zafar Leena Maddukuri Jeong-Yun Choi Robert L. Eoff 《Nucleic acids research》2014,42(5):3272-3285
The Y-family DNA polymerase Rev1 is required for successful replication of G-quadruplex DNA (G4 DNA) in higher eukaryotes. Here we show that human Rev1 (hRev1) disrupts G4 DNA structures and prevents refolding in vitro. Nucleotidyl transfer by hRev1 is not necessary for mechanical unfolding to occur. hRev1 binds G4 DNA substrates with Kd,DNA values that are 4–15-fold lower than those of non-G4 DNA substrates. The pre-steady-state rate constant of deoxycytidine monophosphate (dCMP) insertion opposite the first tetrad-guanine by hRev1 is ∼56% as fast as that observed for non-G4 DNA substrates. Thus, hRev1 can promote fork progression by either dislodging tetrad guanines to unfold the G4 DNA, which could assist in extension by other DNA polymerases, or hRev1 can prevent refolding of G4 DNA structures. The hRev1 mechanism of action against G-quadruplexes helps explain why replication progress is impeded at G4 DNA sites in Rev1-deficient cells and illustrates another unique feature of this enzyme with important implications for genome maintenance. 相似文献
145.
Justin S. LaFountaine Leena Kumari Prasad Chris Brough Dave A. Miller James W. McGinity Robert O. WilliamsIII 《AAPS PharmSciTech》2016,17(1):120-132
Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output. 相似文献
146.
Emelia Zukowski Marco Sannella Jack Donato Rockhold Gabriella H. Kalantar Jingting Yu Sara SantaCruz-Calvo Madison K. Kuhn Nasun Hah Ling Ouyang Tzu-Wen Wang Lyanne Murphy Heather Marszalkowski Kaleigh Gibney Micah J. Drummond Elizabeth A. Proctor Hatice Hasturk Barbara S. Nikolajczyk Leena P. Bharath 《Aging cell》2023,22(11):e13996
Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production. 相似文献
147.
Amit Ketkar Lane Smith Callie Johnson Alyssa Richey Makayla Berry Jessica
H Hartman Leena Maddukuri Megan R Reed Julie E C Gunderson Justin W C Leung Robert L Eoff 《Nucleic acids research》2021,49(4):2065
We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication. 相似文献
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