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101.
Complexation energies and acidities of 19 primary, secondary and tertiary amine-boranes were investigated using MP2/6-311+G(d,p) and B3LYP/6-311+G(d,p) methods. Gas phase acidities for free amines were also calculated. Acidity values for studied complexes range from 327.3 to 349.1 kcal mol?1 and the most acidic are the ones with direct connection between deprotonation center and a π-system. Results obtained by both computational methods are in good agreement with each other and with known experimental data. Addition of BH3 increases the acidity of amines by 30 to 50 kcal mol?1. This enhancement effect was compared to the respective effect witnessed in phosphine-boranes and traced back to changes of charge delocalization on nitrogen. A question about the structural stability of several deprotonated amine-borane anions in the gas phase was also raised. 相似文献
102.
I. Ahmad Mirza David L. Burk Bing Xiong Hiroaki Iwaki Yoshie Hasegawa Stephan Grosse Peter C. K. Lau Albert M. Berghuis 《PloS one》2013,8(3)
Cyclohexylamine oxidase (CHAO) is a flavoprotein first described in Brevibacterium oxydans strain IH-35A that carries out the initial step of the degradation of the industrial chemical cyclohexylamine to cyclohexanone. We have cloned and expressed in Escherichia coli the CHAO-encoding gene (chaA) from B. oxydans, purified CHAO and determined the structures of both the holoenzyme form of the enzyme and a product complex with cyclohexanone. CHAO is a 50 kDa monomer with a PHBH fold topology. It belongs to the flavin monooxygenase family of enzymes and exhibits high substrate specificity for alicyclic amines and sec-alkylamines. The overall structure is similar to that of other members of the flavin monooxygenase family, but lacks either of the C- or N-terminal extensions observed in these enzymes. Active site features of the flavin monooxygenase family are conserved in CHAO, including the characteristic aromatic cage. Differences in the orientations of residues of the CHAO aromatic cage result in a substrate-binding site that is more open than those of its structural relatives. Since CHAO has a buried hydrophobic active site with no obvious route for substrates and products, a random acceleration molecular dynamics simulation has been used to identify a potential egress route. The path identified includes an intermediate cavity and requires transient conformation changes in a shielding loop and a residue at the border of the substrate-binding cavity. These results provide a foundation for further studies with CHAO aimed at identifying features determining substrate specificity and for developing the biocatalytic potential of this enzyme. 相似文献
103.
The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4 总被引:1,自引:0,他引:1
104.
105.
Gus Koerbin Jillian R Tate Julie Ryan Graham RD Jones Ken A Sikaris David Kanowski Maxine Reed Janice Gill George Koumantakis Tina Yen Andrew St John Peter E Hickman Aaron Simpson Peter Graham 《The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists》2014,35(4):203-211
Harmonisation of reference intervals for routine general chemistry analytes has been a goal for many years. Analytical bias may prevent this harmonisation. To determine if analytical bias is present when comparing methods, the use of commutable samples, or samples that have the same properties as the clinical samples routinely analysed, should be used as reference samples to eliminate the possibility of matrix effect. The use of commutable samples has improved the identification of unacceptable analytical performance in the Netherlands and Spain. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has undertaken a pilot study using commutable samples in an attempt to determine not only country specific reference intervals but to make them comparable between countries. Australia and New Zealand, through the Australasian Association of Clinical Biochemists (AACB), have also undertaken an assessment of analytical bias using commutable samples and determined that of the 27 general chemistry analytes studied, 19 showed sufficiently small between method biases as to not prevent harmonisation of reference intervals. Application of evidence based approaches including the determination of analytical bias using commutable material is necessary when seeking to harmonise reference intervals. 相似文献
106.
BC Smith T McAndrew Z Chen A Harari DM Barris S Viswanathan AC Rodriguez P Castle R Herrero M Schiffman RD Burk 《PloS one》2012,7(7):e40425
Background
The rapidly expanding field of microbiome studies offers investigators a large choice of methods for each step in the process of determining the microorganisms in a sample. The human cervicovaginal microbiome affects female reproductive health, susceptibility to and natural history of many sexually transmitted infections, including human papillomavirus (HPV). At present, long-term behavior of the cervical microbiome in early sexual life is poorly understood.Methods
The V6 and V6–V9 regions of the 16S ribosomal RNA gene were amplified from DNA isolated from exfoliated cervical cells. Specimens from 10 women participating in the Natural History Study of HPV in Guanacaste, Costa Rica were sampled successively over a period of 5–7 years. We sequenced amplicons using 3 different platforms (Sanger, Roche 454, and Illumina HiSeq 2000) and analyzed sequences using pipelines based on 3 different classification algorithms (usearch, RDP Classifier, and pplacer).Results
Usearch and pplacer provided consistent microbiome classifications for all sequencing methods, whereas RDP Classifier deviated significantly when characterizing Illumina reads. Comparing across sequencing platforms indicated 7%–41% of the reads were reclassified, while comparing across software pipelines reclassified up to 32% of the reads. Variability in classification was shown not to be due to a difference in read lengths. Six cervical microbiome community types were observed and are characterized by a predominance of either G. vaginalis or Lactobacillus spp. Over the 5–7 year period, subjects displayed fluctuation between community types. A PERMANOVA analysis on pairwise Kantorovich-Rubinstein distances between the microbiota of all samples yielded an F-test ratio of 2.86 (p<0.01), indicating a significant difference comparing within and between subjects’ microbiota.Conclusions
Amplification and sequencing methods affected the characterization of the microbiome more than classification algorithms. Pplacer and usearch performed consistently with all sequencing methods. The analyses identified 6 community types consistent with those previously reported. The long-term behavior of the cervical microbiome indicated that fluctuations were subject dependent. 相似文献107.
Safaeian M Hildesheim A Gonzalez P Yu K Porras C Li Q Rodriguez AC Sherman ME Schiffman M Wacholder S Burk R Herrero R Burdette L Chanock SJ Wang SS 《PloS one》2012,7(4):e33619
Background
Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer.Methodology/Principal Findings
We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P trend<0.0001), and RPS19 rs2305809 (P trend=0.0007), respectively. Both SNPs were also associated with progression.Conclusions/Significance
These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis. 相似文献108.
Lucia F. C. Pedrosa Amy K. Motley Teri D. Stevenson Kristina E. Hill Raymond F. Burk 《Biological trace element research》2012,149(3):377-381
Whole-body selenium is regulated by excretion of the element. Reports of studies carried out using isotopic tracers have led to the conclusion that urinary selenium excretion is regulated by selenium intake but that fecal excretion is not. Because of the limitations of tracer studies, we measured urinary and fecal selenium excretion by mice with selenium intakes in the form of sodium selenite ranging from deficient to almost toxic. Tissue and whole-body selenium concentrations increased sharply between deficient and adequate selenium intakes, reflecting tissue accumulation of selenium in the form of selenoproteins. Once the requirement for selenium had been satisfied, a 31-fold further increase in intake resulted in less than doubling of tissue and whole-body selenium, demonstrating the effectiveness of selenium excretion by the mouse. Urinary selenium excretion increased with increases in dietary selenium intake. Fecal selenium excretion, which was 20 to 30?% of the selenium excreted in the physiological range, responded to moderately high selenium intake but did not increase further when selenium intake was increased to even higher levels. Thus, fecal selenium excretion contributes to regulation of whole-body selenium at physiological selenium intakes. The pattern of its response to the full spectrum of selenium intakes was different from the urinary excretion response, suggesting that the mechanisms of fecal and urinary routes of excretion are different. 相似文献
109.
Samuel A. Ramirez Michael Pablo Sean Burk Daniel J. Lew Timothy C. Elston 《PLoS computational biology》2021,17(7)
Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell membrane. The clusters assemble, disassemble, and move between different regions of the membrane before eventually forming a stable polarity site directed toward the pheromone source. Pathways that regulate clustering have been identified but the molecular mechanisms that regulate cluster mobility are not well understood. To gain insight into the contribution of chemical noise to cluster behavior we simulated clustering using the reaction-diffusion master equation (RDME) framework to account for molecular-level fluctuations. RDME simulations are a computationally efficient approximation, but their results can diverge from the underlying microscopic dynamics. We implemented novel concentration-dependent rate constants that improved the accuracy of RDME-based simulations, allowing us to efficiently investigate how cluster dynamics might be regulated. Molecular noise was effective in relocating clusters when the clusters contained low numbers of limiting polarity factors, and when Cdc42, the central polarity regulator, exhibited short dwell times at the polarity site. Cluster stabilization occurred when abundances or binding rates were altered to either lengthen dwell times or increase the number of polarity molecules in the cluster. We validated key results using full 3D particle-based simulations. Understanding the mechanisms cells use to regulate the dynamics of polarity clusters should provide insights into how cells dynamically track external directional cues. 相似文献
110.
Stephan DA Howell GR Teslovich TM Coffey AJ Smith L Bailey-Wilson JE Malechek L Gildea D Smith JR Gillanders EM Schleutker J Hu P Steingruber HE Dhami P Robbins CM Makalowska I Carpten JD Sood R Mumm S Reinbold R Bonner TI Baffoe-Bonnie A Bubendorf L Heiskanen M Kallioneimi OP Baxevanis AD Joseph SS Zucchi I Burk RD Isaacs W Ross MT Trent JM 《Genomics》2002,79(1):41-50