High-resolution genetic mapping using the Mouse Diversity outbred population

The JAX Diversity Outbred population is a new mouse resource derived from partially inbred Collaborative Cross strains and maintained by randomized outcrossing. As such, it segregates the same allelic variants as the Collaborative Cross but embeds these in a distinct population architecture in which each animal has a high degree of heterozygosity and carries a unique combination of alleles. Phenotypic diversity is striking and often divergent from phenotypes seen in the founder strains of the Collaborative Cross. Allele frequencies and recombination density in early generations of Diversity Outbred mice are consistent with expectations based on simulations of the mating design. We describe analytical methods for genetic mapping using this resource and demonstrate the power and high mapping resolution achieved with this population by mapping a serum cholesterol trait to a 2-Mb region on chromosome 3 containing only 11 genes. Analysis of the estimated allele effects in conjunction with complete genome sequence data of the founder strains reduced the pool of candidate polymorphisms to seven SNPs, five of which are located in an intergenic region upstream of the Foxo1 gene.     

Pathogen specific carbohydrate antigen microarrays: a chip for detection of Salmonella O-antigen specific antibodies

A Salmonella O-antigen microarray was developed by covalent coupling of oligosaccharide antigens specific for serogroups Salmonella enterica sv. Paratyphi (group A), Typhimurium (group B) and Enteritidis (group D). Antibodies were correctly detected in sera from patients with culture verified salmonellosis. High serogroup-specificity was seen with the disaccharide antigens. With the larger antigens, containing the backbone sequence Manα1–2Rhaα1–2Gal (MRG), common backbone-specific antibodies (O-antigen 12) were also detected. This is “proof of principle” that pathogen-specific carbohydrate antigen microarrays constitute a novel technology for rapid and specific serological diagnosis in either individual patients or larger sero-epidemiological and vaccine studies.     

Mycobacterial glycoconjugates as vaccine candidates against tuberculosis

There is an urgent need for an efficient vaccine against tuberculosis. Here, we explore the potential role of carbohydrate antigens as part of a new tuberculosis vaccine. Emphasis is placed on carbohydrate-protein conjugate vaccines, using the arabinomannan portion of lipoarabinomannan, a major structural surface component of Mycobacterium tuberculosis covalently conjugated to (mycobacterial) protein antigens. Such conjugate vaccines show good protective efficacy in mice and guinea pigs in terms of prolonged survival and reduced pathology. Special attention is paid to the immunology underlying their protective capacity. Conjugate vaccines induce both cellular and humoral responses and, although antibody responses have been thought to be the main protective component, cellular responses - possibly through the CD1 pathway - are also likely to be involved.     

Spectrum of heart diseases in a new cardiac service in Nigeria: An echocardiographic study of 1441 subjects in Abeokuta

Background

The recent determination of the complete nucleotide sequence of several Mycobacterium tuberculosis (MTB) genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C), along with the genomes of laboratory strains (H37Rv and H37Ra), provides new insights on the mechanisms of adaptation of this bacterium to the human host.

Findings

The genetic variation found in six M. tuberculosis strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software islandsanalyser, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms.

Conclusion

The comparison of multiple genomes demonstrates that the M. tuberculosis genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium.     

Kinetic analysis of ethanol production by an acetate-resistant strain of recombinant Zymomonas mobilis

Zymomonas mobilis ZM4/Ac^R (pZB5), a mutant recombinant strain with increased acetate resistance, has been isolated following electroporation of Z. mobilis ZM4/Ac^R. This mutant strain showed enhanced kinetic characteristics in the presence of 12 g sodium acetate l^–1 at pH 5 in batch culture on 40 g glucose, 40 g xylose l^–1 medium when compared to ZM4 (pZB5). In continuous culture, there was evidence of increased maintenance energy requirements/uncoupling of metabolism for ZM4/Ac^R (pZB5) in the presence of sodium acetate; a result confirmed by analysis of the effect of acetate on other strains of Z. mobilis. Nomenclature m Cell maintenance energy coefficient (g g^–1 h^–1)Maximum overall specific growth rate (1 h^–1)Maximum specific ethanol production rate (g g^–1 h^–1)Maximum specific total sugar utilization rate (g g^–1 h^–1)Biomass yield per mole of ATP (g mole^–1 Ethanol yield on total sugars (g g^–1)Biomass yield on total sugars (g g^–1)True biomass yield on total sugars (g g^–1)     

Refining Hypertension Surveillance to Account for Potentially Misclassified Cases

Administrative health data have been used in hypertension surveillance using the 1H2P method: the International Classification of Disease (ICD) hypertension diagnosis codes were recorded in at least 1 hospitalization or 2 physician claims within 2 year-period. Accumulation of false positive cases over time using the 1H2P method could result in the overestimation of hypertension prevalence. In this study, we developed and validated a new reclassification method to define hypertension cases using regularized logistic regression with the age, sex, hypertension and comorbidities in physician claims, and diagnosis of hypertension in hospital discharge data as independent variables. A Bayesian method was then used to adjust the prevalence estimated from the reclassification method. We evaluated the hypertension prevalence in data from Alberta, Canada using the currently accepted 1H2P method and these newly developed methods. The reclassification method with Bayesian adjustment produced similar prevalence estimates as the 1H2P method. This supports the continued use of the 1H2P method as a simple and practical way to conduct hypertension surveillance using administrative health data.     

The sequence of cDNA encoding lipoprotein lipase. A member of a lipase gene family

cDNA clones corresponding to the entire coding region of mature lipoprotein lipase were identified by antibody screening of a mouse macrophage library and sequenced. The predicted amino acid sequence indicates that the mature protein contains 447 amino acids with a molecular weight of 50,314. Comparison of the nucleotide and amino acid sequence with those of rat hepatic lipase and porcine pancreatic lipase reveals extensive homology among the enzymes, indicating that they are members of a gene family of lipases. Most striking is a conservation of five disulfide bridges in all three enzymes, strongly suggesting that the enzymes have similar overall folding patterns. Lipoprotein lipase is also shown to be extraordinarily conserved among mouse, human, and bovine species. The mRNA for lipoprotein lipase is abundant in heart and adipose tissue but is also present in a wide variety of other tissues. There are two major species of mRNA in mouse and human tissues examined, 3.6 and 3.4 kilobases (kb) in size. Rat tissues, on the other hand, contain only the 3.6-kb species while bovine tissues contain an additional 1.7-kb species.     

Structural studies of the Escherichia coli O-antigen 6

The structure of the Escherichia coli O-antigen 6 has been investigated using n.m.r. spectroscopy, methylation analysis, and various specific degradations. It is concluded that the O-antigen is composed of pentasaccharide repeating-units having the following structure. (Formula: see text)     

A new genus and species (Cornucollis gen. n. masoalensis sp. n.) of praying mantis from northern Madagascar (Mantodea,Iridopterygidae, Tropidomantinae)

An examination of Malagasy specimens accessed within the Muséum national d’Histoire naturelle, Paris, France, produced a praying mantis (Insecta: Mantodea) of an undescribed genus and species. An investigation of the internal and external morphology, in addition to its collection locality, revealed that this specimen belongs to the Iridopterygidae subfamily Tropidomantinae. Furthermore, the specimen’s unique combination of characters justified the creation of a new genus. Geographic distributional records and external morphological character evidence are presented for Cornucollis gen. n. masoalensis sp. n. We provide a dichotomous key of the Tropidomantinae and Nilomantinae genera distributed within Madagascar. High-resolution images, illustrations of morphological characters, natural history information, and measurement data are presented.