Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis

Ankylosing spondylitis (AS) is a common and highly familial rheumatic disorder. The sibling recurrence risk ratio for the disease is 63 and heritability assessed in twins > 90%. Although MHC genes, including HLA-B27, contribute only 20-50% of the genetic risk for the disease, no non-MHC gene has yet been convincingly demonstrated to influence either susceptibility to the disease or its phenotypic expression. Previous linkage and association studies have suggested the presence of a susceptibility gene for AS close to, or within, the cytochrome P450 2D6 gene (CYP2D6, debrisoquine hydroxylase) located at chromosome 22q13.1. We performed a linkage study of chromosome 22 in 200 families with AS affected sibling-pairs. Association of alleles of the CYP2D6 gene was examined by both case-control and within-family means. For case-control studies, 617 unrelated individuals with AS (361 probands from sibling-pair and parent-case trio families and 256 unrelated non-familial sporadic cases) and 402 healthy ethnically matched controls were employed. For within-family association studies, 361 families including 161 parent-case trios and 200 affected sibling-pair families were employed. Homozygosity for poor metabolizer alleles was found to be associated with AS. Heterozygosity for the most frequent poor metabolizer allele (CYP2D6*4) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D6*4 alleles and AS was demonstrated. Weak linkage was also demonstrated between CYP2D6 and AS. We postulate that altered metabolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS.

Conformation-activity correlations for chemotactic tripeptide analogs incorporating dialkyl residues with linear and cyclic alkyl sidechains at position 2

Five stereochemically constrained analogs of the chemotactic tripeptide incorporating 1-aminocycloalkane-1-carboxylic acid (Ac(n)c) and alpha,alpha-dialkylglycines (Deg, diethylglycine; Dpg, n,n-dipropylglycine and Dbg, n,n-dibutylglycine) at position 2 have been synthesized. NMR studies of peptides For-Met-Xxx-Phe-OMe (Xxx = Ac(7)c, I; Ac(8)c, II; Deg, III; Dpg, IV and Dbg, V; For, formyl) establish that peptides with cycloalkyl residues, I and II, adopt folded beta-turn conformations in CDCl3 and (CD3)(2)SO. In contrast, analogs with linear alkyl sidechains, III-V, favour fully extended (C-5) conformations in solution. Peptides I-V exhibit high activity in inducing beta-glucosaminidase release from rabbit neutrophils, with ED(50) values ranging from 1.4-8.0 x 10(-11)M. In human neutrophils the Dxg peptides III-V have ED(50) values ranging from 2.3 x 10(-8) to 5.9 x 10(-10) M, with the activity order being V > IV > III. While peptides I-IV are less active than the parent. For-Met-Leu-Phe-OH, in stimulating histamine release from human basophils, the Dbg peptide V is appreciably more potent, suggesting its potential utility as a probe for formyl peptide receptors.

Structural correlations in GexSe1-x glasses - a neutron diffraction study

Neutron diffraction measurement is carried out on GexSe1-x glasses, where 0.1 less than or equal to x less than or equal to 0.4, in a Q interval of 0.55-13.8 Angstrom(-1). The first sharp diffraction peak (FSDP) in the structure factor, S(Q), shows a systematic increase in the intensity and shifts to a lower Q with increasing Ge concentration. The coherence length of FSDP increases with x and becomes maximum for 0.33 less than or equal to x less than or equal to 0.4. The Monte-Carlo method, due to Soper, is used to generate S(Q) and also the pair correlation function, g(r). The generated S(Q) is in agreement with the experimental data for all x. Analysis of the first four peaks in the total correlation function, T(r), shows that the short range order in GeSe2 glass is due to Ge(Se-1/2)(4) tetrahedra, in agreement with earlier reports. Se-rich glasses contain Se-chains which are cross-linked with Ge(Se-1/2)(4) tetrahedra. Ge-2(Se-1/2)(6) molecular units are the basic structural units in Ge-rich, x = 0.4, glass. For x = 0.2, 0.33 and 0.4 there is evidence for some of the tetrahedra being in an edge-shared configuration. The number of edge-shared tetrahedra in these glasses increase with increasing Ge content.

Dynamics of a dilute sheared inelastic fluid. II. The effect of correlations

The effect of correlations on the viscosity of a dilute sheared inelastic fluid is analyzed using the ring-kinetic equation for the two-particle correlation function. The leading-order contribution to the stress in an expansion in epsilon=(1-e)(1/2) is calculated, and it is shown that the leading-order viscosity is identical to that obtained from the Green-Kubo formula, provided the stress autocorrelation function in a sheared steady state is used in the Green-Kubo formula. A systemmatic extension of this to higher orders is also formulated, and the higher-order contributions to the stress from the ring-kinetic equation are determined in terms of the terms in the Chapman-Enskog solution for the Boltzmann equation. The series is resummed analytically to obtain a renormalized stress equation. The most dominant contributions to the two-particle correlation function are products of the eigenvectors of the conserved hydrodynamic modes of the two correlated particles. In Part I, it was shown that the long-time tails of the velocity autocorrelation function are not present in a sheared fluid. Using those results, we show that correlations do not cause a divergence in the transport coefficients; the viscosity is not divergent in two dimensions, and the Burnett coefficients are not divergent in three dimensions. The equations for three-particle and higher correlations are analyzed diagrammatically. It is found that the contributions due to the three-particle and higher correlation functions to the renormalized viscosity are smaller than those due to the two-particle distribution function in the limit epsilon -> 0. This implies that the most dominant correlation effects are due to the two-particle correlations.

Relationships between Patterns of Behaviour and Liveweight Gains of Feedlot Steers

There is considerable individual variation in the performance of feedlot cattle even when they are of the same genotype and sourced from the same property (Hasker et al., 1996). It is possible that behavioural differences between individuals may account for some of this variation. This paper reports the correlations between some behavioural patterns and average daily gain (ADG) of Brahman steers that were feedlot-fed for 100 days.

The credit risk(+) model with general sector correlations

We consider an enhancement of the credit risk+ model to incorporate correlations between sectors. We model the sector default rates as linear combinations of a common set of independent variables that represent macro-economic variables or risk factors. We also derive the formula for exact VaR contributions at the obligor level.

Genetic control of propagation traits in a single Corymbia torelliana x Corymbia variegata family

Genetic control of vegetative propagation traits was described for a second-generation, outbred, intersectional hybrid family (N = 208) derived from two species, Corymbia torelliana (F. Muell.) K.D. Hill & L.A.S. Johnson and Corymbia variegata (F. Muell.) K.D. Hill & L.A.S. Johnson, which contrast for propagation characteristics and in their capacity to develop lignotubers. Large phenotypic variances were evident for rooting and most other propagation traits, with significant proportions attributable to differences between clones (broad-sense heritabilities 0.2-0.5). Bare root assessment of rooting rate and root quality parameters tended to have the highest heritabilities, whereas rooting percentage based on root emergence from pots and shoot production were intermediate. Root biomass and root initiation had the lowest heritabilities. Strong favourable genetic correlations were found between rooting percentage and root quality traits such as root biomass, volume, and length. Lignotuber development on a seedling was associated with low rooting and a tendency to poor root quality in cuttings and was in accord with the persistence of species parent types due to gametic phase disequilibrium. On average, nodal cuttings rooted more frequently and with higher quality root systems, but significant cutting type x genotype interaction indicated that for some clones, higher rooting rates were obtained from tips. Low germination, survival of seedlings, and rooting rates suggested strong hybrid breakdown in this family.

Synthetic peptides as chemoattractants for bull spermatozoa structure activity correlations

The ability of various synthetic peptide analogs of. Formyl-Met-Leu-Phe to induce chemotaxis in bull sperm is compared using an inverted capillary assay. The formyl group is essential for chemotactic activity and corresponding t-butyloxycarbonyl tripeptides are inactive. Sequence analogs, Formyl-Met-Phe-Leu, Formyl-Leu-Met-Phe and Formyl-Leu-Phe-Met are active. Replacement of Met and Leu by Pro does not diminish activity. Formyl-Met-Leu-Phe-NH2 is active suggesting that electrostatic interactions involving the carboxyl group may be unimportant in receptor interactions. The studies establish the importance of an amino terminal formyl group and a sequence of at least three hydrophobic residues, for inducing sperm chemotaxis.

Crop and environmental attributes underpinning genotype by environment interaction in synthetic-derived bread wheat evaluated in Mexico and Australia

Synthetic backcrossed-derived bread wheats (SBWs) from CIMMYT were grown in the north-west of Mexico (CIANO) and sites across Australia during 3 seasons. A different set of lines was evaluated each season, as new materials became available from the CIMMYT crop enhancement program. Previously, we have evaluated both the performance of genotypes across environments and the genotype x environment interaction (G x E). The objective of this study was to interpret the G x E for yield in terms of crop attributes measured at individual sites and to identify the potential environmental drivers of this interaction. Groups of SBWs with consistent yield performance were identified, often comprising closely related lines. However, contrasting performance was also relatively common among sister lines or between a recurrent parent and its SBWs. Early flowering was a common feature among lines with broad adaptation and/or high yield in the northern Australian wheatbelt, while yields in the southern region did not show any association with the maturity type. Lines with high yields in the southern and northern regions had cooler canopies during flowering and early grain filling. Among the SBWs with Australian genetic backgrounds, lines best adapted to CIANO were tall (>100 cm), with a slightly higher ground cover. These lines also displayed a higher concentration of water-soluble carbohydrates in the stem at flowering, which was negatively correlated with stem number per unit area when evaluated in southern Australia (Horsham). Possible reasons for these patterns are discussed. Selection for yield at CIANO did not specifically identify the lines best adapted to northern Australia, although they were not the most poorly adapted either. In addition, groups of lines with specific adaptation to the south would not have been selected by choosing the highest yielding lines at CIANO. These findings suggest that selection at CIMMYT for Australian environments may be improved by either trait based selection or yield data combined with trait information. Flowering date, canopy temperature around flowering, tiller density, and water-soluble carbohydrate concentration in the stem at flowering seem likely candidates.

Developmental and physiological traits associated with high yield and stay-green phenotype in wheat

Water availability is a key limiting factor in wheat production in the northern grain belt of Australia. Varieties with improved adaptation to such conditions are actively sought. The CIMMYT wheat line SeriM82 has shown a significant yield advantage in multi-environment screening trials in this region. The objective of this study was to identify the physiological basis of the adaptive traits underpinning this advantage. Six detailed experiments were conducted to compare the growth, development, and yield of SeriM82 with that of the adapted cultivar, Hartog. The experiments were undertaken in field environments that represented the range of moisture availability conditions commonly encountered by winter crops grown on the deep Vertosol soils of this region. The yield of SeriM82 was 6-28% greater than that of Hartog, and SeriM82 exhibited a stay-green phenotype by maintaining green leaf area longer during the grain-filling period in all environments where yield was significantly greater than Hartog. However, where the availability of deep soil moisture was limited, SeriM82 failed to exhibit significantly greater yield or to express the stay-green phenotype. Thus, the stay-green phenotype was closely associated with the yield advantage of SeriM82. SeriM82 also exhibited higher mean grain mass than Hartog in all environments. It is suggested that small differences in water use before anthesis, or greater water extraction from depth after anthesis, could underlie the stay-green phenotype. The inability of SeriM82 to exhibit stay-green and higher yield where deep soil moisture was depleted indicates that extraction of deep soil moisture is important.

Heritability of reproductive traits and genetic correlations with growth in the black tiger prawn Penaeus monodon reared in tanks

Captive-reared broodstock of the black tiger prawn (Penaeus monodon) have exhibited poor reproductive performance limiting attempts to domesticate this species. The potential for improved reproductive performance was assessed by determining heritabilities of four measures of reproductive performance, their genetic correlations with each other and with growth rate and weight at age. Heritability estimates (h2 ± S.E.) obtained from √ (days to spawn), √ (egg number), √ (nauplii number) and arcsin √ (proportion hatched) were 0.47 ± 0.15, 0.41 ± 0.18, 0.27 ± 0.16, and 0.18 ± 0.16, respectively. Estimates of genetic correlations between reproductive traits and weight at age, or growth rate were less than 0.5 except for √ (egg number) and weight at 54 weeks (0.93 ± 0.19) and √ (egg number) and 16-54-week growth (0.63 ± 0.29).

Spatial correlations around a Kondo impurity

We present a method for calculating zero-frequency, spatially varying response and correlation functions around a magnetic impurity in metals. We illustrate the procedure which involves a combination of perturbative scaling and nonperturbative renormalization-group methods for the spin-(1/2) Kondo impurity. We explain the factorization of the temperature and spatial dependence of the Knight shift observed in NMR experiments.

Genetics of heifer performance in 'wet' and 'dry' seasons and their relationships with steer performance in two tropical beef genotypes.

The genetics of heifer performance in tropical 'wet' and 'dry' seasons, and relationships with steer performance, were studied in Brahman (BRAH) and Tropical Composite (TCOMP) (50% Bos indicus, African Sanga or other tropically adapted Bos taurus; 50% non-tropically adapted Bos taurus) cattle of northern Australia. Data were from 2159 heifers (1027 BRAH, 1132 TCOMP), representing 54 BRAH and 51 TCOMP sires. Heifers were assessed after post-weaning 'wet' (ENDWET) and 'dry' (ENDDRY) seasons. Steers were assessed post-weaning, at feedlot entry, over a 70-day feed test, and after similar to 120-day finishing. Measures studied in both heifers and steers were liveweight (LWT), scanned rump fat, rib fat and M. longissimus area (SEMA), body condition score (CS), hip height (HH), serum insulin-like growth factor-I concentration (IGF-I), and average daily gains (ADG). Additional steer measures were scanned intra-muscular fat%, flight time, and daily (DFI) and residual feed intake (RFI). Uni- and bivariate analyses were conducted for combined genotypes and for individual genotypes. Genotype means were predicted for a subset of data involving 34 BRAH and 26 TCOMP sires. A meta-analysis of genetic correlation estimates examined how these were related to the difference between measurement environments for specific traits. There were genotype differences at the level of means, variances and genetic correlations. BRAH heifers were significantly (P < 0.05) faster-growing in the 'wet' season, slower-growing in the 'dry' season, lighter at ENDDRY, and taller and fatter with greater CS and IGF-I at both ENDWET and ENDDRY. Heritabilities were generally in the 20 to 60% range for both genotypes. Phenotypic and genetic variances, and genetic correlations, were commonly lower for BRAH. Differences were often explained by the long period of tropical adaptation of B. indicus. Genetic correlations were high between corresponding measures at ENDWET and ENDDRY, positive between fat and muscle measures in TCOMP but negative in BRAH (mean of 13 estimates 0.50 and -0.19, respectively), and approximately zero between steer feedlot ADG and heifer ADG in BRAH. Numerous genetic correlations between heifers and steers differed substantially from unity, especially in BRAH, suggesting there may be scope to select differently in the sexes where that would aid the differing roles of heifers and steers in production. Genetic correlations declined as measurement environments became more different, the rates of decline (environment sensitivity) sometimes differing with genotype. Similar measures (LWT, HH and ADG; IGF-I at ENDWET in TCOMP) were genetically correlated with steer DFI in heifers as in steers. Heifer SEMA was genetically correlated with steer feedlot RFI in BRAH (0.75 +/- 0.27 at ENDWET, 0.66 +/- 0.24 at ENDDRY). Selection to reduce steer RFI would reduce SEMA in BRAH heifers but otherwise have only small effects on heifers before their first joining.

Genetics of heifer puberty in two tropical beef genotypes in northern Australia and associations with heifer- and steer-production traits

A total of 2115 heifers from two tropical genotypes (1007 Brahman and 1108 Tropical Composite) raised in four locations in northern Australia were ovarian-scanned every 4-6 weeks to determine the age at the first-observed corpus luteum (CL) and this was used to de. ne the age at puberty for each heifer. Other traits recorded at each time of ovarian scanning were liveweight, fat depths and body condition score. Reproductive tract size was measured close to the start of the first joining period. Results showed significant effects of location and birth month on the age at first CL and associated puberty traits. Genotypes did not differ significantly for the age or weight at first CL; however, Brahman were fatter at first CL and had a small reproductive tract size compared with that of Tropical Composite. Genetic analyses estimated the age at first CL to be moderately to highly heritable for Brahman (0.57) and Tropical Composite (0.52). The associated traits were also moderately heritable, except for reproductive tract size in Brahmans (0.03) and for Tropical Composite, the presence of an observed CL on the scanning day closest to the start of joining (0.07). Genetic correlations among puberty traits were mostly moderate to high and generally larger in magnitude for Brahman than for Tropical Composite. Genetic correlations between the age at CL and heifer- and steer-production traits showed important genotype differences. For Tropical Composite, the age at CL was negatively correlated with the heifer growth rate in their first postweaning wet season (-0.40) and carcass marbling score (-0.49), but was positively correlated with carcass P8 fat depth (0.43). For Brahman, the age at CL was moderately negatively genetically correlated with heifer measures of bodyweight, fatness, body condition score and IGF-I, in both their first postweaning wet and second dry seasons, but was positively correlated with the dry-season growth rate. For Brahman, genetic correlations between the age at CL and steer traits showed possible antagonisms with feedlot residual feed intake (-0.60) and meat colour (0.73). Selection can be used to change the heifer age at puberty in both genotypes, with few major antagonisms with steer- and heifer- production traits.