Clinical, metabolic, and molecular genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in 30 dogs.

Genotype-phenotype correlations of humans and dogs with hereditary methemoglobinemia are not yet well characterized. We determined total hemoglobin and methemoglobin (MetHb) concentrations, cytochrome b5 reductase (CYB5R) enzyme activities, genotypes, and clinical signs in 30 dogs with persistent cyanosis without cardiopulmonary disease. Erythrocytic CYB5R enzyme activities were low in all dogs assayed. Owner-reported quality of life ranged from subclinical to occasional exertional syncope. Two previously reported and two novel CYB5R3 missense variants were identified among the methemoglobinemic cohort and were predicted to impair enzyme function. Two variants were recurrent: a homozygous Ile194Leu substitution was found in Pomeranians and other small dogs, and a homozygous Arg219Pro change occurred predominately in pit bull terriers. The other two variants were Thr202Ala and Gly76Ser substitutions in single dogs. Of the two common CYB5R3 genotypes, Arg219Pro was associated with a more severe metabolic phenotype. We conclude that CYB5R3 deficiency is the predominate cause of canine hereditary methemoglobinemia. Although this finding is unlikely to alter the clinical approach to hereditary methemoglobinemia in dogs, it demonstrates the possibility of how genotype-phenotype cohort analysis might facilitate precision medicine in the future in veterinary medicine.

Hair cortisol concentration in clinically healthy slaughter calves with and -without chronic bronchopneumonic -lesions.

INTRODUCTION: The hypothesis of this study was that healthy calves undergo less stress and thus have lower hair cortisol concentrations than calves with chronic bronchopneumonic lesions. Fifty healthy calves (group 1) and 50 calves with chronic bronchopneumonic lesions (group 2) were used immediately after slaughter, at which time hair samples and both adrenal glands were collected. The hair samples and the left adrenal gland were used for cortisol measurement and the right adrenal gland was used for histological and morphometrical examinations. The median hair cortisol concentrations of calves in groups 1 and 2 were 1.6 and 1.9 pg/mg hair, respectively, and did not differ significantly. The same was true for the mean cortisol concentration of the adrenal gland (1.1 and 1.4 µg/g tissue) and for the adrenal cortisol content (3.7 and 4.6 µg). The weights of the cortex (3.3, mean, and 3.5 g, median) and medulla (1.7 and 1.8 g, both median) did not differ significantly between the groups. This study did not detect differences in hair and adrenal cortisol concentrations between clinically healthy slaughter calves with and without chronic bronchopneumonic lesions. In further studies, calves with clinical signs should be taken into account.

INTRODUCTION: L'hypothèse de cette étude était que les veaux en bonne santé sont soumis à moins de stress et ont donc des concentrations de cortisol dans les poils plus faibles que les veaux présentant des lésions broncho-pneumoniques chroniques. Cinquante veaux sains (groupe 1) et 50 veaux présentant des lésions broncho-pneumoniques chroniques (groupe 2) ont été utilisés immédiatement après l'abattage, moment auquel des échantillons de poils et les deux glandes surrénales ont été prélevés. Les échantillons de poil et la glande surrénale gauche ont été utilisés pour la mesure du cortisol et la glande surrénale droite a été utilisée pour des examens histologiques et morphométriques. Les concentrations médianes de cortisol dans les poils des veaux des groupes 1 et 2 étaient respectivement de 1,6 et 1,9 pg/mg de poil et ne différaient pas significativement. Il en a été de même pour la concentration moyenne en cortisol de la glande surrénale (1,1 et 1,4 µg/g de tissu) et pour la teneur en cortisol surrénalien (3,7 et 4,6 µg). Les poids du cortex (3,3, moyenne et 3,5 g, médiane) et de la médulla (1,7 et 1,8 g, médiane) ne différaient pas significativement entre les groupes. Cette étude n'a pas mis en évidence de différences dans les concentrations de cortisol dans les poils et les surrénales entre les veaux abattus cliniquement en bonne santé avec ou sans lésions broncho-pneumoniques chroniques. Dans des études ultérieures, les veaux présentant des signes cliniques doivent être pris en compte.

Molecular analysis of intragenic recombination at the tryptophan synthetase locus in Neurospora crassa.

Fifteen different classically generated and mapped mutations at the tryptophan synthetase locus in Neurospora crassa have been characterized to the level of the primary sequence of the gene. This sequence analysis has demonstrated that intragenic recombination is accurate to order mutations within one open reading frame. While classic genetic analysis correctly ordered the mutations, the position of mutations characterized by gene sequence analysis was more accurate. A leaky mutation was found to have a wild-type primary sequence. The presence of unique polymorphisms in the primary sequence of the trp-3 gene from strain 861 confirms that it has a unique history relative to the other strains studied. Most strains that were previously shown to be immunologically nonreactive with antibody preparations raised against tryptophan synthetase protein were shown to have nonsense mutations. This work defines 14 alleles of the N. crassa trp-3 gene.

Fatigue and corrosion of a Pd-based bulk metallic glass in various environments.

Bulk metallic glasses (BMGs) possess attractive properties for biomedical applications, including high strength, hardness and corrosion resistance, and low elastic modulus. In this study, we conduct rotating beam fatigue tests on Pd43Ni10Cu27P20 bulk metallic glass in air and Eagle's medium (EM) and measure the corrosive resistance of the alloy by submersion in acidic and basic electrolytes. Fatigue results are compared to those of commonly used biometals in EM. Rotating beam fatigue tests conducted in air and in Eagle's medium show no deterioration in fatigue properties in this potentially corrosive environment out to 10(7) cycles. A specimen size effect is revealed when comparing fatigue results to those of a similar alloy of larger minimum dimensions. Corrosion tests show that the alloy is not affected by highly basic (NaOH) or saline (NaCl) solutions, nor in EM, and is affected by chlorinated acidic solutions (HCl) to a lesser extent than other commonly used biometals. Corrosion in HCl initiates with selective leaching of late transition metals, followed by dissolution of Pd.

Molecular analysis of mutants of the Neurospora adenylosuccinate synthetase locus.

The ad-8 gene of Neurospora crassa, in addition to being used for the study of purine biology, has been extensively studied as a model for gene structure, mutagenesis and intralocus recombination. Because of this there is an extensive collection of well-characterized N. crassa ad-8 mutants in the Fungal Genetics Stock Center collection. Among these are spontaneous mutants and mutants induced with X-ray, UV or chemical mutagens. The specific lesions in these mutants have been genetically mapped at high resolution. We have sequenced the ad-8 locus from 13 of these mutants and identified the molecular nature of the mutation in each strain. We compare the historical fine-structure map to the DNA and amino acid sequence of each allele. The placement of the individual lesions in the fine-structure map was more accurate at the 5' end of the gene and no mutants were identified in the 3' untranslated region of this gene. We additionally analysed ad-8(+) alleles in 18 N. crassa strains subjected to whole-genome sequence analysis and describe the variability among Neurospora strains and among fungi and other organisms.

The Fungal Genetics Stock Center: a repository for 50 years of fungal genetics research.

The Fungal Genetics Stock Center (FGSC) was established in 1960 to ensure that important strains used in early genetics research were available to subsequent generations of fungal geneticists. Originally, only mutant strains were held. At present, any organism that has had its genome sequenced is a genetic system and so the FGSC has added many new organisms. The FGSC is well integrated in its core community and, as research came to depend on cloned genes, vectors and gene libraries, the FGSC included these materials. When the community expanded to include plant and human pathogens, the FGSC adopted these systems as well. Wild isolates from around the world have also proven instrumental in answering important questions. The FGSC holds tremendous diversity of the Neurospora species, which form the core of the collection. The growth in the number of strains distributed illustrates the growth in research on fungi. Because of its position near the centre of the fungal genetics effort, the FGSC is also the first to see trends in research directions. One recent example is the 300% jump in requests for strains of Neurospora crassa carrying a mutation that makes them sensitive to high salt concentration. These strains were seldom requested over many years, but became among our most popular resources following the demonstration of their utility in studying fungicide resistance. This exemplifies why materials need to be preserved without regard to their immediate perceived value and reinforces the need for long-term support for preservation of a broad variety of genetic resources.

Lest we forget. A recap on Beijing's Platform J.

PIP: In March 1995, more than 200 women media professionals met in Toronto to devise recommended strategies which they hoped would be forwarded by the Fourth World Conference on Women (WCW) to strengthen women's status and role in relation to the mass media. The recommendations addressed obstacles to increased involvement of women in the media and denounced the trivial use of violent images of women. The WCW temporarily shelved some of the issues debated in Toronto and inserted the phrase "in accordance with freedom of expression" in several proposed recommendations. The WCW also called for voluntary codes of professional conduct rather than for regulation. The WCW did seek a greater role for women in the media and called upon the media to promote realistic, diverse, and nonstereotypical images of women. The reality is that the categories of news that gets covered often separate women from media headlines unless the women transgress norms or commit crimes. This could be countered if more women reach positions where they can make decisions about news content without simply mimicking masculine values. As a strategic tool, women can gain many advantages by organizing in networks and by staying aware of their potential to make an impact.^ieng