54 research outputs found
Catalytic mechanism of a C-C hydrolase enzyme: Evidence for a gem-diol intermediate, not an acyl enzyme
No full text2-Hydroxy-6-keto-nona-2,4-diene 1,9-dioic acid 5,6-hydrolase (MhpC) from Escherichia coli catalyses the hydrolytic cleavage of the extradiol ring fission product on the phenylpropionate catabolic pathway and is a member of the alpha/beta hydrolase family. The catalytic mechanism of this enzyme has previously been shown to proceed via initial ketonization of the dienol substrate (Henderson, I. M. J., and Bugg,T. D. H. (1997) Biochemistry 36, 12252-12258), followed by stereospecific fragmentation. Despite the implication of an active site serine residue in the alpha/beta hydrolase family, attempts to verify a putative acyl enzyme intermediate by radiochemical trapping methods using a C-14-labeled substrate yielded a stoichiometry of <1% covalent intermediate, which could be accounted for by nonenzymatic processes. In contrast, incorporation of 5-6% of two atoms of O-18 from (H2O)-O-18 into succinic acid was observed using the natural substrate, consistent with the reversible formation of a gem-diol intermediate. Furthermore, time-dependent incorporation of O-18 from (H2O)-O-18 into the carbonyl group of a nonhydrolysable analogue 4-keto-nona-1,9-dioic acid was observed in the presence of MhpC, consistent with enzyme-catalyzed attack of water at the ketone carbonyl. These results favor a catalytic mechanism involving base-catalyzed attack of water, rather than nucleophilic attack of an active site serine. The implication of this work is that the putative active site serine in this enzyme may have an alternative function, for example, as a base
Petrology and Geochemistry of Felsic Volcaniclastic Rocks along the Sherman Mine Road, Temagami Greenstone Belt, Strathy Township, Ontario
No full textTitle: Petrology and Geochemistry of Felsic Volcaniclastic Rocks along the Sherman Mine Road, Temagami Greenstone Belt, Strathy Township, Ontario, Author: Timothy C. Schwartz, Location: ThodeFelsic volcaniclastic rocks and intrusions along the Sherman Mine road, Temagami greenstone belt, were studied to determine if the petrological and chemical characteristics of these rocks indicate they are favourable hosts for volcanogenic massive sulphide deposits. Mapping of these felsic rocks was done at a scale of 1:5000 utilizing a 100 m spaced cut grid and pace and compass. Since outcrop is scarce and exposures are poor in this area, most correlation of the felsic horizons was done on the basis of trace and rare-earth element geochemistry. On the basis of the chemistry of the rocks, three distinct felsic horizons were defined. The quartz feldspar porphyries are FI type cacl-alkaline felsic intrusives with [La/Yb]n ratio from 16 to 29 and no Eu anomaly. The Link Lake and Sherman Gate horizons are FII type calc-alkaline volcaniclastic horizon with [La/Yb]n ratio from 5 to 7 and weak negative to positive Eu anomalies. The Upper and Lower Felsic horizons are FIIIa type tholeiitic rhyolite lava flows and valcaniclastics. These horizons have [La/Yb]n ratios from 1 to 3 and strong negative Eu anomalies from 0.16 to 0.42. Petrology and net transfer of material calculations indicate the Upper and Lower Felsic Horizons have been silicified, resulting in a net addition of Si and Al to these rocks. There is no distinct pattern of chemical changes which would indicate proximity to a single volcanogenic massive sulphide alteration pipe, however, an enrichment of the light rare-earth elements in the eastern section of the thesis area suggests this area maybe more
proximal to an alteration pipe, and thus a vent. Lithological characteristics of the eastern section of the thesis area also suggests it is more proximal to a vent than the western section. Pyrite clasts are present in several of the volcaniclastic units. While the presence of sulphide rich clasts can be an indicator of proximity to a volcanogenic massive sulphide deposit, the textural and chemical characteristics of these clasts indicate they originated from shale horizons in this area. For this reason, these clasts should not be used as an indicator of proximity to a volcanogenic massive sulphide deposit. Trace and rare-earth element classifications indicate both the Link Lake and Sherman Gate horizons, and Upper and Lower Felsic horizons are favourable host rocks for volcanogenic massive sulphide style mineralization while the quartz feldspar porphyries, such as the Milne vent and the City Dump vent, are not. Although the felsic volcanic packages are relatively thin, potential exploration targets would be the upper contact of the Upper Felsic horizon and the Link Lake and Sherman Gate horizons./ThesisMaster of Science (MS
Recent changes in the initiation liturgies: a comparative study
No full textIn this thesis the author examines the recent rites of initiation within the Orthodox, Roman Catholic, Church of England, and Methodist Churches. The object is two-fold: (l) to see whether there has been convergence in the recent liturgical practice and theological understanding of initiation; and (2)' to see the extent to which the rites of the present-day mark a deliberate return to the pool of symbolic actions and words that were current in the post-apostolic period (and maybe even earlier).From the witness of Scripture it is felt that no established practice was being set before us at that time, particularly as the primary role of Scripture is as a witness to Christ rather than as a manual of devotion. The establishing of normative procedures for initiation would seem to be a post-apostolic development which took distinctive eastern and western lines of development. The Orthodox Church continues to employ the ancient rites which extend back for over twelve hundred years, and its insistence on the unity of baptism, chrismation and eucharist in theological thought and administration is characteristic. The other denominations express in their recent rites the desire to return to an archetypal service, but at the same time wishing to maintain the validity of a fragmented initiation practice. The Church of England, .and Methodism which grew from it, show increasing use of ceremonial. Most of this had been removed from the Church of England's liturgy at the Reformation. Taking note of recent work by the World Council of Churches the author concludes that convergence in liturgy and theology, though incomplete, has taken place; and further, that faithful witness is borne to the practice and understanding of the early Church of the post-apostolic period. Some aspects may date from the New Testament times
A letter to the Reverend Nathaniel Whitaker, D.D [electronic resource] : Wherein some of his gross misrepresentations of Mr. Hart's doctrines in his dialogue, intitled, A brief examination, &c. and his false and injurious charges against him, contained in his appendix and postscript to his discourses on 2 Cor. 5. 19. lately reprinted at Salem, are detected, and justly censured. With remarks on sundry doctrines, tending to illustrate and confirm the truth, and expose the contrary errors taught by the doctor. By the author of that dialogue. [Four lines of Scripture texts].
No full textSignatures: [A]p4s B-Hp4s (H4 verso blank)Evans,Trumbull, J.H. Connecticut,Johnson, H.A. New London,Electronic reproduction.English Short Title Catalog,Reproduction of original from Library of Congress
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
Taxonomy, phylogeny and eco-biogeography of southern African white-eyes (Zosterops spp.) Aves: order Passeriformes, Family: Zosteropidae
No full textIncludes abstract.Includes bibliographical references (p. 193-216).The aim of this study was to incorporate all lines of evidence to establish the true taxonomy and phylogeny of southern African Zosterops. Character data sets used include plumage and morphometric measures, vocal characters and molecular (mitochondrial and nuclear) DNA sequences. A broad scale phylogeographic analysis was also performed to establish the evolutionary process driving the diversity observed among these birds
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
No full textApproaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
No full textObesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation
Interplay between network configurations and network governance mechanisms in supply networks a systematic literature review
No full textPurpose: This work systematically reviews the extant academic management literature on supply networks. It specifically examines how network configurations and network governance mechanisms influence each other in supply networks.
Design: 125 analytical and empirical studies were identified using an evidence-based approach to review the literature mainly published between 1985 and 2012.
Synthesis: Drawing on a multi-disciplinary theoretical foundation, this work develops an integrative framework to identify three distinct yet interdependent themes that characterize the study of supply networks: a) Network Configurations (structures and relationships); b) Network Governance Mechanisms (formal and informal); and c) The Interplay between Network Configurations and Network Governance Mechanisms.
Findings: Network configurations and network governance mechanisms mutually influence each other and cannot be considered in isolation. Formal and informal governance mechanisms provide better control when used as complements rather than as substitutes. The choice of governance mechanism depends on the nature of exchange; role of management; desired level of control; level of flexibility in formal contracts; and complementary role of formal and informal governance mechanism.
Research implications: This nascent field has thematic and methodological research opportunities for academics. Comparative network analysis using longitudinal case studies offers a rich area for further study.
Practical Implications: The complexity surrounding the conflicting roles of managers at the organisation and network levels poses a significant challenge during the development and implementation stage of strategic network policies.
Originality/value: This review reveals that formal and informal governance mechanisms provide better control when used as complements rather than as substitutes
Modeling of very low frequency motions during RIPEX
No full textNumerical computations are used to explain the presence of very low frequency motions (VLFs), with frequencies less than 0.004 Hz, in the rip current velocity signals observed during the Rip-current field Experiment (RIPEX) field experiment. Observations show that the VLF motions are most intense within the surfzone and then quickly taper off in the offshore direction. By comparing computed VLF intensity (URMS,vlf) distributions in both the cross-shore and alongshore direction with observations in a qualitative sense, the most important contributions to the VLF dynamics are established. VLF motions at neighboring rip-channels are seen to interact in the computations, with stronger surfzone intensity for increasing bathymetric variation. The intermittent forcing by spatially varying wave groups is essential in obtaining the correct URMS,vlf distribution in the cross-shore direction, suggesting this is the predominant mechanism responsible for the generation of the VLF motions observed during RIPEX. Computations also suggest that VLF motions can occasionally propagate offshore but are mostly confined to the surfzone corresponding to surfzone eddies. A quantitative comparison shows good correspondence between model computations and measurements of URMS,vlf with a model skill of O(0.7), with generally increased (decreased) URMS,vlf during mean low (high) water levels.Hydraulic EngineeringCivil Engineering and Geoscience
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