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Modest Contribution (modest + contribution)

Distribution by Scientific Domains

Life Sciences	50%

Selected Abstracts

MCMC-based linkage analysis for complex traits on general pedigrees: multipoint analysis with a two-locus model and a polygenic component

GENETIC EPIDEMIOLOGY, Issue 2 2007
Yun Ju Sung
Abstract We describe a new program lm_twoqtl, part of the MORGAN package, for parametric linkage analysis with a quantitative trait locus (QTL) model having one or two QTLs and a polygenic component, which models additional familial correlation from other unlinked QTLs. The program has no restriction on number of markers or complexity of pedigrees, facilitating use of more complex models with general pedigrees. This is the first available program that can handle a model with both two QTLs and a polygenic component. Competing programs use only simpler models: one QTL, one QTL plus a polygenic component, or variance components (VC). Use of simple models when they are incorrect, as for complex traits that are influenced by multiple genes, can bias estimates of QTL location or reduce power to detect linkage. We compute the likelihood with Markov Chain Monte Carlo (MCMC) realization of segregation indicators at the hypothesized QTL locations conditional on marker data, summation over phased multilocus genotypes of founders, and peeling of the polygenic component. Simulated examples, with various sized pedigrees, show that two-QTL analysis correctly identifies the location of both QTLs, even when they are closely linked, whereas other analyses, including the VC approach, fail to identify the location of QTLs with modest contribution. Our examples illustrate the advantage of parametric linkage analysis with two QTLs, which provides higher power for linkage detection and better localization than use of simpler models. Genet. Epidemiol. © 2006 Wiley-Liss, Inc. [source]

Synthesis and In Vitro Evaluation of 2-Aminoquinazolin-4(3H)-one-Based Inhibitors for tRNA-Guanine Transglycosylase (TGT)

HELVETICA CHIMICA ACTA, Issue 6 2004
Emmanuel
tRNA-Guanine transglycosylase (TGT) plays a key role in the post-transcriptional modification of tRNA. It has been linked with the pathogenicity of shigellae, the causative agents of bacillary dysentery (shigellosis). Here, we report structureactivity relationships (SARs) for a new series of 2-aminoquinazolin-4(3H)-one-based inhibitors of TGT, resulting from structure-based design (Fig.,2). Versatile synthetic protocols allow selective functionalization of the 2-aminoquinazolin-4(3H)-one core (Schemes,1,6) with H-bond-donor groups in position 6 (for H-bonding to the C=O group of Leu231) and lipophilic residues in position 8 for reaching into a shallow, newly discovered lipophilic pocket lined by Val282, Val45, and Leu68. The binding mode of several of these ligands in the active site of TGT was established by crystal structure analyses (Figs.,4 and 6). A dramatic S effect was observed, with the replacement of the S-atom in the (phenylsulfanyl)methyl residue in position 8 of inhibitor 1c (Ki=100,nM) by the O-atom (in 1h, Ki=5.6,,M) or CH2 (in 1i, Ki=3.6,,M), resulting in a massive loss of activity (Fig.,3). Crystal structure analysis showed that the lipophilic Me group points into a highly polar region of the active site encompassed by the side chains of Asp280 and Asp102 and collides directly (d(C,,,O)=3.1,Å) with one of the O-atoms of the carboxylate of Asp102. Similarly, lipophilic linkers departing from position 8 and orienting residues in the shallow hydrophobic pocket presumably encounter analogous unfavorable contacts, accounting for the modest contribution to the binding free enthalpy upon introduction of these residues. These findings provide a valuable starting point for future structure-based lead optimization cycles leading to TGT inhibitors with increased in vitro potency. [source]

Soil organic matter decline and compositional change associated with cereal cropping in southern Tanzania

LAND DEGRADATION AND DEVELOPMENT, Issue 1 2001
J. F. McDonagh
Abstract The spatial analogue method and 13C analytical techniques were used to reveal medium- to long-term changes in soil organic matter (SOM) in farmers' fields under maize in southern Tanzania. Aerial photography and detailed farmer interviews were used to relate land-use history to declines in SOM concentration and changes in composition. The research attempted to measure the rate of SOM decline and the extent to which farmers' residue management practice was allowing cereal residues to contribute to SOM. The combination of research methods employed in this study proved to be highly complementary. Results indicate that native SOM decreased by on average 50 per cent; after 25 years of cultivation. Under current residue management with cereal residues mostly grazed and burnt there is only a relatively modest contribution from cereal residues to SOM. When cereal residues are retained in the field it is likely they will contribute significantly to SOM but they are much less likely to build SOM in the medium to long term. The paper concludes that in many situations it is probably best for farmers to allow the majority of the residues to be eaten by cattle in these systems rather than attempt to build SOM or risk nitrogen immobilization in cropped fields. The greater importance of inputs of high-quality (e.g. legume) residues for nutrient supply in the short term is highlighted, in contrast to inputs of poor-quality (e.g. cereal) residues in an attempt to build SOM in the longer term. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Stable isotopic evidence for diet at the Imperial Roman coastal site of Velia (1st and 2nd Centuries AD) in Southern Italy

AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2009
Oliver E. Craig
Abstract Here we report on a stable isotope palaeodietary study of a Imperial Roman population interred near the port of Velia in Southern Italy during the 1st and 2nd centuries AD. Carbon and nitrogen stable isotope analyses were performed on collagen extracted from 117 adult humans as well as a range of fauna to reconstruct individual dietary histories. For the majority of individuals, we found that stable isotope data were consistent with a diet high in cereals, with relatively modest contributions of meat and only minor contributions of marine fish. However, substantial isotopic variation was found within the population, indicating that diets were not uniform. We suggest that a number of individuals, mainly but not exclusively males, had greater access to marine resources, especially high trophic level fish. However, the observed dietary variation did not correlate with burial type, number of grave goods, nor age at death. Also, individuals buried at the necropolis at Velia ate much less fish overall compared with the contemporaneous population from the necropolis of Portus at Isola Sacra, located on the coast close to Rome. Marine and riverine transport and commerce dominated the economy of Portus, and its people were in a position to supplement their own stocks of fish with imported goods in transit to Rome, whereas at Velia marine exploitation existed side-by-side with land-based economic activities. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source]