Bayesian Inference for Retrospective Population Genetics Models Using Markov Chain Monte Carlo Methods

Genetics, the science of heredity and variation in living organisms, has a central role in medicine, in breeding crops and livestock, and in studying fundamental topics of biological sciences such as evolution and cell functioning. Currently the field of genetics is under a rapid development because of the recent advances in technologies by which molecular data can be obtained from living organisms. In order that most information from such data can be extracted, the analyses need to be carried out using statistical models that are tailored to take account of the particular genetic processes. In this thesis we formulate and analyze Bayesian models for genetic marker data of contemporary individuals. The major focus is on the modeling of the unobserved recent ancestry of the sampled individuals (say, for tens of generations or so), which is carried out by using explicit probabilistic reconstructions of the pedigree structures accompanied by the gene flows at the marker loci. For such a recent history, the recombination process is the major genetic force that shapes the genomes of the individuals, and it is included in the model by assuming that the recombination fractions between the adjacent markers are known. The posterior distribution of the unobserved history of the individuals is studied conditionally on the observed marker data by using a Markov chain Monte Carlo algorithm (MCMC). The example analyses consider estimation of the population structure, relatedness structure (both at the level of whole genomes as well as at each marker separately), and haplotype configurations. For situations where the pedigree structure is partially known, an algorithm to create an initial state for the MCMC algorithm is given. Furthermore, the thesis includes an extension of the model for the recent genetic history to situations where also a quantitative phenotype has been measured from the contemporary individuals. In that case the goal is to identify positions on the genome that affect the observed phenotypic values. This task is carried out within the Bayesian framework, where the number and the relative effects of the quantitative trait loci are treated as random variables whose posterior distribution is studied conditionally on the observed genetic and phenotypic data. In addition, the thesis contains an extension of a widely-used haplotyping method, the PHASE algorithm, to settings where genetic material from several individuals has been pooled together, and the allele frequencies of each pool are determined in a single genotyping.

Extremely Low Microsatellite Diversity but Distinct Population Structure in a Long-Lived Threatened Species, the Australian Lungfish Neoceratodus forsteri (Dipnoi)

The Australian lungfish is a unique living representative of an ancient dipnoan lineage, listed as ‘vulnerable’ to extinction under Australia’s Environment Protection and Biodiversity Conservation Act 1999. Historical accounts indicate this species occurred naturally in two adjacent river systems in Australia, the Burnett and Mary. Current day populations in other rivers are thought to have arisen by translocation from these source populations. Early genetic work detected very little variation and so had limited power to answer questions relevant for management including how genetic variation is partitioned within and among sub-populations. In this study, we use newly developed microsatellite markers to examine samples from the Burnett and Mary Rivers, as well as from two populations thought to be of translocated origin, Brisbane and North Pine. We test whether there is significant genetic structure among and within river drainages; assign putatively translocated populations to potential source populations; and estimate effective population sizes. Eleven polymorphic microsatellite loci genotyped in 218 individuals gave an average within-population heterozygosity of 0.39 which is low relative to other threatened taxa and for freshwater fishes in general. Based on F_ST values (average over loci = 0.11) and STRUCTURE analyses, we identify three distinct populations in the natural range, one in the Burnett and two distinct populations in the Mary. These analyses also support the hypothesis that the Mary River is the likely source of translocated populations in the Brisbane and North Pine rivers, which agrees with historical published records of a translocation event giving rise to these populations. We were unable to obtain bounded estimates of effective population size, as we have too few genotype combinations, although point estimates were low, ranging from 29 - 129. We recommend that, in order to preserve any local adaptation in the three distinct populations that they be managed separately.

Optimising initial population density, growth time and nitrogen nutrition for assessing resistance of wheat cultivars to root-lesion nematode (Pratylenchus thornei)

Pratylenchus thornei is a major pathogen of wheat in Australia. Two glasshouse experiments with four wheat cultivars that had different final populations (Pf) of P. thornei in the field were used to optimise conditions for assessing resistance. With different initial populations (Pi) ranging up to 5250 P. thornei/kg soil, Pf of P. thornei increased to 16 weeks after sowing, and then decreased at 20 weeks in some cultivar x Pi combinations. The population dynamics of P. thornei up to 16 weeks were best described by a modified exponential equation P f (t) = aP i e kt where P f (t) is the final population density at time t, P i is the initial population density, a is the proportion of P i that initiates population development, and k is the intrinsic rate of increase of the population. The cultivar GS50a had very low k values at Pi of 5250 and 1050 indicating its resistance, Suneca and Potam had high k values indicating susceptibility, whereas intolerant Gatcher had a low value at the higher Pi and a high value at the lower Pi. Nitrate fertiliser increased plant growth and Pf values of susceptible cultivars, but in unplanted soil it decreased Pf. Nematicide (aldicarb 5 mg/kg soil) killed P. thornei more effectively in planted than in unplanted soil and increased plant growth particularly in the presence of N fertiliser. In both experiments, the wheat cultivars Suneca and Potam were more susceptible than the cultivar GS50a reflecting field results. The method chosen to discriminate wheat cultivars was to assess Pf after growth for 16 weeks in soil with Pi ~1050–5250 P. thornei/kg soil and fertilised with 200 mg NO3–N/kg soil.

Integrating pest population models with biophysical crop models to better represent the farming system

Farming systems frameworks such as the Agricultural Production Systems simulator (APSIM) represent fluxes through the soil, plant and atmosphere of the system well, but do not generally consider the biotic constraints that function within the system. We designed a method that allowed population models built in DYMEX to interact with APSIM. The simulator engine component of the DYMEX population-modelling platform was wrapped within an APSIM module allowing it to get and set variable values in other APSIM models running in the simulation. A rust model developed in DYMEX is used to demonstrate how the developing rust population reduces the crop's green leaf area. The success of the linking process is seen in the interaction of the two models and how changes in rust population on the crop's leaves feedback to the APSIM crop modifying the growth and development of the crop's leaf area. This linking of population models to simulate pest populations and biophysical models to simulate crop growth and development increases the complexity of the simulation, but provides a tool to investigate biotic constraints within farming systems and further moves APSIM towards being an agro-ecological framework.

The study of genetic diversity and population structure of the Korean fleshy shrimp, Fenneropenaeus chinensis, using newly developed microsatellite markers

The fleshy shrimp, Fenneropenaeus chinensis, is the family of Penaeidae and one of the most economically important marine culture species in Korea. However, its genetic characteristics have never been studied. In this study, a total of 240 wild F. chinensis individuals were collected from four locations as follows: Narodo (NRD, n = 60), Beopseongpo (BSP, n = 60), Chaesukpo (CSP, n = 60), and Cheonsuman (CSM, n = 60). Genetic variability and the relationships among four wild F. chinensis populations were analyzed using 13 newly developed microsatellite loci. Relatively high levels of genetic variability (mean allelic richness = 16.87; mean heterozygosity = 0.845) were found among localities. Among the 52 population loci, 13 showed significant deviation from the Hardy–Weinberg equilibrium. Neighbor-joining, principal coordinate, and molecular variance analyses revealed the presence of three subpopulations (NRD, CSM, BSP and CSP), which was consistent with clustering based on genetic distance. The mean observed heterozygosity values of the NRD, CSM, BSP, and CSP populations were 0.724, 0.821, 0.814, and 0.785 over all loci, respectively. These genetic variability and differentiation results of the four wild populations can be applied for future genetic improvement using selective breeding and to design suitable management guidelines for Korean F. chinensis culture.

Synthesis of Azo Coupled Crown Ethers Containing Transition Metal and other Chromophoric Environments and Their Ion Complexation Properties

The crown ethers, 2,3-benzo-1,4,7,10,13-pentaoxa-cyclopentadeca-2-ene and 2,3, ll,12-dibenzo-l,4,7,10,13,16-hexaoxscyclooctadeca-2,11-diene are incorporated into H,N'-ethylenebis(acetylacetoneimino) nickel(II) and copper(II), phenol, and β-naphthol by diazo coupling reactions. The selective nature of the coupling reaction has-been demonstrated by the isolation of both asymmetric mono- and symmetric bis(glyoxalarylcrownhydrazoneimino) metal(II) complexes. An interesting binuclear complex containing two intramolecularly rearranged (glyoxal-hydrazonearylimino) metal(II) groups joined by 18-crown-6 result8 when bis(arenediazonium)-18-crown-6 is coupled with the metal(I1) Schiff bases. The substituted ethers form cationic salts with NaClO4, KCNS, NH4CNS, 14g(CNS)2 and Ca(CNS)2. All the synthesised ethers exhibit ion selectivity sequence as K+ > Na+ and Ca2+ > Mg2+.

A Convenient Route for the Synthesis of Complex Metal Oxides Employing Solid-Solution Precursors

Synthesis of complex metal oxides by the thermal decomposition of solid-solution precursors (formed by isomorphous compounds of component metals) has been investigated since the method enables mixing of cations on an atomic scale and drastically reduces diffusion distances to a few angstroms. Several interesting oxides such as Ca2Fe03,5C, aCoz04,C a2C0205a, nd Ca,FeCo05 have been prepared by this technique starting from carbonate solid solutions of the type Ca,-,Fe,C03, Cal-,Co,C03, and Ca,-,,M,M'yC03 (M, M' = Mn, Fe, Co). The method has been extended to oxalate solid-solution precursors, and the possibility of making use of other kinds of precursor solid solutions is indicated.

Amide-catalysed isomerisation of 5,6-dihydroisoquinolines: a novel synthesis of 1,2-dihydroisoquinolines

Knoevenagel condensation of 2-acylcyclohexanones or 2-ethoxycarbonylcyclohexanone with either cyanoacetamide or malononitrile followed by silver salt alkylation gave the 5,6,7,8-tetrahydroisoquinolines (3a–i). Chromic acid oxidation of the 5,6,7,8-tetrahydroisoquinolines (3a–i) to the corresponding tetralones (4a–i) followed by sodium borohydride reduction and p-toluenesulphonic acid-catalysed dehydration of the resulting alcohols (5a–i) gave the 5,6-dihydroisoquinolines (6a–i). Reaction of 5,6-dihydroisoquinolines (6a–g) with potassium amide in liquid ammonia gave a mixture of the 1,3-dihydroisoquinolines (7a–g) and the isoquinolines (8a–g). The C-1 unsubstituted 1,2-dihydroisoquinoline (7c) was found to be very unstable. In the case of the 5,6-dihydroisoquinolines (6h and 6i), reaction of potassium amide in liquid ammonia resulted in a mixture of 1-aminoisoquinoline (9) and the isoquinolines (8h and 8i). All the above compounds have been characterised by spectral data. A probable pathway for the formation of the 1,2-dihydroisoquinolines (7a–g) and the isoquinolines (8a–i) is suggested.

Role of heme in the synthesis of cytochrome c oxidase in Neurospora crassa

The role of heme in the synthesis of cytochrome c oxidase has been investigated in the mold Neurospora crassa. Iron-deficient cultures of the mold have low levels of cytochrome oxidase and delta-aminolevulinate dehydratase, the latter being the rate-limiting enzyme of the heme-biosynthetic pathway in this organism. Addition of iron to the iron-deficient cultures results in an immediate increase in the levels of delta-aminolevulinate dehydratase followed by an increase in the rate of heme synthesis and cytochrome oxidase levels. The rate of precursor labeling of the mitochondrial subunits of cytochrome oxidase is decreased preferentially under conditions of iron deficiency and addition of iron corrects this picture. Exogenous hemin addition which prevents iron-mediated induction of delta-aminolevulinate dehydratase also inhibits the increase in the activity of cytochrome oxidase and the enhanced precursor labeling of the mitochondrial subunits of cytochrome oxidase. Protein synthesis on mitoribosomes measured in vivo and in vitro is decreased under conditions of heme deficiency. Hemin addition in vitro to mitochondrial lysates prepared from heme-deficient mycelia restores a near normal rate of protein synthesis. It is concluded that heme is required for the optimal rate of translation on mitoribosomes.

Aromatic amines and their derivatives. Part 3. The synthesis and crystal structure of 4,4-NN-tetramethyl-NN-dinitroso-2,2-methylenedianiline

The synthesis of 4,4,N,N-tetramethyl-NN-dinitroso-2,2-methylenedianiline (1) by the route p-MeC6H4NH2+ HCHO + OH–(p-MeC6H4NMe)2CH2(7b); (7b)+ acid at 70 °C 4,N-dimethyl-6-(N-methyl-p-toluidinomethyl)aniline (4b); (4b)+ acid at 130 °C 4,4,NN-tetramethyl-2,2-methylenedianiline (3b); (3b)+ HNO2(1), is described. Aspects of the 1H n.m.r. spectra of the above and related compounds are discussed. A crystal-structure analysis of compound (1) shows one of the N-nitroso-groups to be disordered with the endo-form being in preponderance (4 : 1) over the exo-form. The other N-nitroso-group is exclusively exo in the solid state. There is little or no resonance between the benzene ring and the nitroso-group attached to the ring, the two groups being almost perpendicular to each other. In one of the N-nitroso-groups, the nitrogen atom deviates significantly from the plane of the benzene ring to which it is attached. Both amide nitrogen atoms show some pyramidal character.

Interactions of aromatic mannosyl disulfide derivatives with Concanavalin A: synthesis, thermodynamic and NMR spectroscopy studies

α-d-Mannopyranosyl units were attached to an aromatic scaffold through disulfide linkages to obtain mono- to trivalent glycosylated ligands for lectin binding studies. Isothermal titration calorimetric (ITC) measurements indicated that binding affinities of these derivatives to Concanavalin A (Con A) were comparable to or slightly higher than that of methyl α-d-mannopyranoside (Ka values in the range of 104 M−1). The stoichiometries of the lectin-ligand complexes were in agreement with the formal valencies (1–3) of the respective ligands indicating cross-linking in interactions with the di- and trivalent derivatives. Multivalency effects could not, however, be observed with the latter. These ligands were shown to bind to the carbohydrate binding site of Con A using saturation transfer difference (STD) NMR competition experiments.

Macromolecular synthesis in mycobacteriophage I3 infected cells

DNA-, RNA- and protein synthesis have been studied inMycobacterium smegmatis cells infected with phage 13. The macromolecular synthesis continued until the end of latent period. Early RNA and protein synthesis were necessary prior to the commencement of DNA replication. The infecting phage DNA sedimented as larger than unit length of genome, after initiation of DNA synthesis. Although the host DNA was not degraded, 90 percent of the RNA synthesized after phage infection hybridized to phage DNA.

Karnaugh map analysis and synthesis of threshold functions

A unate function can easily be identified on a Karnaugh map from the well-known property that it cons ist s only ofess en ti al prime implicante which intersect at a common implicant. The additional property that the plot of a unate function F(x, ... XII) on a Karnaugh map should possess in order that F may also be Ivrealizable (n';:; 6) has been found. It has been sh own that the I- realizability of a unate function F corresponds to the ' compac tness' of the plot of F. No resort to tho inequalities is made, and no pre-processing such as positivizing and ordering of the given function is required.

The diet-related health of the Australian population and potential opportunities for the food retail sector

This report describes the diet-related health of the Australian population and identifies potential opportunities for the food retail sector.

Early post-operative mortality after major lower limb amputation: A systematic review of population and regional based studies

OBJECTIVE: Lower limb amputation is often associated with a high risk of early post-operative mortality. Mortality rates are also increasingly being put forward as a possible benchmark for surgical performance. The primary aim of this systematic review is to investigate early post-operative mortality following a major lower limb amputation in population/regional based studies, and reported factors that might influence these mortality outcomes. METHODS: Embase, PubMed, Cinahl and Psycinfo were searched for publications in any language on 30 day or in hospital mortality after major lower limb amputation in population/regional based studies. PRISMA guidelines were followed. A self developed checklist was used to assess quality and susceptibility to bias. Summary data were extracted for the percentage of the population who died; pooling of quantitative results was not possible because of methodological differences between studies. RESULTS: Of the 9,082 publications identified, results were included from 21. The percentage of the population undergoing amputation who died within 30 days ranged from 7% to 22%, the in hospital equivalent was 4-20%. Transfemoral amputation and older age were found to have a higher proportion of early post-operative mortality, compared with transtibial and younger age, respectively. Other patient factors or surgical treatment choices related to increased early post-operative mortality varied between studies. CONCLUSIONS: Early post-operative mortality rates vary from 4% to 22%. There are very limited data presented for patient related factors (age, comorbidities) that influence mortality. Even less is known about factors related to surgical treatment choices, being limited to amputation level. More information is needed to allow comparison across studies or for any benchmarking of acceptable mortality rates. Agreement is needed on key factors to be reported.