The quantification of Simpson's paradox and other contributions to contingency table theory.

The analysis of contingency tables is a powerful statistical tool used in experiments with categorical variables. This study improves parts of the theory underlying the use of contingency tables. Specifically, the linkage disequilibrium parameter as a measure of two-way interactions applied to three-way tables makes it possible to quantify Simpson's paradox by a simple formula.

Estimation of Recombination Rate and Maternal Linkage Disequilibrium in Half-Sibs.

A livestock population can be characterized by different population genetic parameters, such as linkage disequilibrium and recombination rate between pairs of genetic markers. The population structure, which may be caused by family stratification, has an influence on the estimates of these parameters. An expectation maximization algorithm has been proposed for estimating these parameters in half-sibs without phasing the progeny.

Covariance Between Genotypic Effects and its Use for Genomic Inference in Half-Sib Families.

In livestock, current statistical approaches utilize extensive molecular data, e.g., single nucleotide polymorphisms (SNPs), to improve the genetic evaluation of individuals.

A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability.

Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP).

Mendelian sampling covariability of marker effects and genetic values.

Background: Measures of the expected genetic variability among full-sibs are of practical relevance, such as in the context of mating decisions. An important application field in animal and plant breeding is the selection and allocation of mates when large or small amounts of genetic variability among offspring are desired, depending on user-specific goals. Estimates of the Mendelian sampling variance can be obtained by simulating gametes from parents with known diplotypes.

Fatty acid synthesis and pyruvate metabolism pathways remain active in dihydroartemisinin-induced dormant ring stages of Plasmodium falciparum.

Artemisinin (ART)-based combination therapy (ACT) is used as the first-line treatment of uncomplicated falciparum malaria worldwide. However, despite high potency and rapid action, there is a high rate of recrudescence associated with ART monotherapy or ACT long before the recent emergence of ART resistance. ART-induced ring-stage dormancy and recovery have been implicated as possible causes of recrudescence; however, little is known about the characteristics of dormant parasites, including whether dormant parasites are metabolically active.

Calculation of identity-by-descent probabilities of short chromosome segments.

For some purposes, identity-by-descent (IBD) probabilities for entire chromosome segments are required. Making use of pedigree information, length of the segment and the assumption of no crossing-over, a generalization of a previously published graph theory oriented algorithm accounting for nonzero IBD of common ancestors is given, which can be viewed as method of path coefficients for entire chromosome segments. Furthermore, rules for setting up a gametic version of a segmental IBD matrix are presented.

Optimum multistage genomic selection in dairy cattle.

The availability of different single nucleotide polymorphism (SNP) chips and the development of imputation algorithms allow for multistage dairy cattle breeding schemes applying various genomic selection strategies. These SNP genotypes yield genomically estimated breeding values (GEBV) with different accuracies at different costs. Thus, the optimum allocation of investments to different selection paths and strategies to maximize the genetic gain per year (ΔG(a)) and its sensitivity to changes in cost and accuracies of GEBV is of great interest.

Phenotypic changes in artemisinin-resistant Plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition.

The appearance of Plasmodium falciparum parasites with decreased in vivo sensitivity but no measurable in vitro resistance to artemisinin has raised the urgent need to characterize the artemisinin resistance phenotype. Changes in the temporary growth arrest (dormancy) profile of parasites may be one aspect of this phenotype. In this study, we investigated the link between dormancy and resistance, using artelinic acid (AL)-resistant parasites.

Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure.

Background: Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance.

Methods: In this study, an existing P.

Analysis of birth weight variability in pigs with respect to liveborn and total born offspring.

Reduction in the variability of piglet birth weight within litter and increased piglet survival are key objective in schemes aiming to improve sow prolificacy. In previous studies, variation in birth weight was described by the sample standard deviation of birth weights within one litter, and the genetic impact has been proved. In this study, we additionally considered the sex effect on piglet's birth weight and on its variability.

Statistical tools to detect genetic variation for a sex dimorphism in piglet birth weight.

Sex differences in birth weight contribute to within-litter variability, which itself is connected to piglet survival. Therefore, we studied whether the sex difference in piglet birth weight is a genetically variable sex dimorphism. For that purpose a linear mixed model including sex-specific additive genetic effects was set up.

Artemisinin‐induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure.

Background: Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon.

Methods: Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine.

Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa.

Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D (1H, 13C and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length.

Differences in muscle and fat accretion in Japanese Black and European cattle.

The development of different muscles and adipose tissues during growth was investigated in commercial Japanese Black (JB) cattle and compared with breeds of the largest variation to be found in Europe. Animals, reared under typical conditions for Japanese and European beef production systems, gained similar body weights but different carcass composition at 24months of age. The carcass of JB contained more adipose tissue and the least proportion of muscle.

Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte.

Comparison of statistical models to analyse the genetic effect on within-litter variance in pigs.

Genetics affects not only the weight of piglets at birth but also the variability of birth weight within litter. Previous studies on this topic assigned the sample standard deviation of piglet birth weights within litter as an observation to the sow. However, the contribution of the difference in mean birth weight per sex on the within-litter variance has been neglected so far.

Identification of phosphinate dipeptide analog inhibitors directed against the Plasmodium falciparum M17 leucine aminopeptidase as lead antimalarial compounds.

Previous studies have pinpointed the M17 leucyl aminopeptidase of Plasmodium falciparum (PfLAP) as a target for the development of new antimalarials. This metallo-exopeptidase functions in the terminal stages of hemoglobin digestion and is inhibited by bestatin, a natural analog of Phe-Leu. By screening novel phosphinate dipeptide analogues for inhibitory activity against recombinant PfLAP, we have discovered two compounds, 4 (hPheP[CH2]Phe) and 5 (hPheP[CH2]Tyr), with inhibitory constants better than bestatin.

The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum.

A member of the M18 family of aspartyl aminopeptidases is expressed by all intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum (PfM18AAP), with highest expression levels in rings. Functionally active recombinant enzyme, rPfM18AAP, and native enzyme in cytosolic extracts of malaria parasites are 560-kDa octomers that exhibit optimal activity at neutral pH and require the presence of metal ions to maintain enzymatic activity and stability. Like the human aspartyl aminopeptidase, the exopeptidase activity of PfM18AAP is exclusive to N-terminal acidic amino acids, glutamate and aspartate, making this enzyme of particular interest and suggesting that it may function alongside the malaria cytosolic neutral aminopeptidases in the release of amino acids from host hemoglobin-derived peptides.

Genetic improvement of traits affected by interactions among individuals: Sib selection schemes.

Livestock populations are usually kept in groups. As a consequence, social interactions among individuals affect productivity, health, and welfare. Current selection methods (individual selection), however, ignore those interactions and yield suboptimal or in some cases even negative responses.

Haplotype probabilities for multiple-strain recombinant inbred lines.

Recombinant inbred lines (RIL) derived from multiple inbred strains can serve as a powerful resource for the genetic dissection of complex traits. The use of such multiple-strain RIL requires a detailed knowledge of the haplotype structure in such lines. Broman (2005) derived the two- and three-point haplotype probabilities for 2(n)-way RIL; the former required hefty computation to infer the symbolic results, and the latter were strictly numerical.

Chaetopyranin, a benzaldehyde derivative, and other related metabolites from Chaetomium globosum, an endophytic fungus derived from the marine red alga Polysiphonia urceolata.

Cultivation of the endophytic fungus Chaetomium globosum, which was isolated from the inner tissue of the marine red alga Polysiphonia urceolata, resulted in the isolation of chaetopyranin (1), a new benzaldehyde secondary metabolite. Ten known compounds were also isolated, including two benzaldehyde congeners, 2-(2',3-epoxy-1',3'-heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl)benzaldehyde (2) and isotetrahydroauroglaucin (3), two anthraquinone derivatives, erythroglaucin (4) and parietin (5), five asperentin derivatives including asperentin (6, also known as cladosporin), 5'-hydroxy-asperentin-8-methylether (7), asperentin-8-methyl ether (8), 4'-hydroxyasperentin (9), and 5'-hydroxyasperentin (10), and the prenylated diketopiperazine congener neoechinulin A (11). The structures of these compounds were determined on the basis of their spectroscopic data analysis (1H, 13C, 1H-1H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution mass experiments).

Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase. A protease involved in amino acid regulation with potential for antimalarial drug development.

Amino acids generated from the catabolism of hemoglobin by intra-erythrocytic malaria parasites are not only essential for protein synthesis but also function in maintaining an osmotically stable environment, and creating a gradient by which amino acids that are rare or not present in hemoglobin are drawn into the parasite from host serum. We have proposed that a Plasmodium falciparum M17 leucyl aminopeptidase (PfLAP) generates and regulates the internal pool of free amino acids and therefore represents a target for novel antimalarial drugs. This enzyme has been expressed in insect cells as a functional 320-kDa homo-hexamer that is optimally active at neutral or alkaline pH, is dependent on metal ions for activity, and exhibits a substrate preference for N-terminally exposed hydrophobic amino acids, particularly leucine.

Growth- and breed-related changes of muscle bundle structure in cattle.

The objective of this study was to investigate the changes in muscle fiber bundles of cattle of different breeds during growth. Different numbers of muscle fibers are surrounded by connective tissue to form bundles macroscopically visible as meat fibers or meat grain, a common meat quality trait. To determine the influence of breed and age on morphological characteristics of muscle fiber bundles, 4 cattle breeds with different growth impetus and muscularity were reared and slaughtered under experimental conditions.

Growth- and breed-related changes of marbling characteristics in cattle.

The objective of this study was to investigate the growth- and breed-related changes of marbling characteristics in cattle. Four cattle breeds with different growth impetus and muscularity were reared and slaughtered under experimental conditions. German Angus, as a typical beef cattle; Galloway, as a smaller, environmentally resistant beef cattle; Holstein-Friesian, as a dairy-type cattle; and double-muscled Belgian Blue, as an extreme type for muscle growth, were used.