Malignant catarrhal fever in free-ranging cervids associated with OvHV-2 and CpHV-2 DNA

Pathologic lesions were summarized in 18 free-ranging cervids (15 moose [Alces alces], two roe deer [Capreolus capreolus], and one red deer [Cervus elaphus]) diagnosed with malignant catarrhal fever (MCF) after examination at the National Veterinary Institute, Oslo 1982-2005. Eye lesions (conjunctivitis, corneal opacity, fibrin clots in the anterior eye chamber) were the most frequent gross finding. Erosive-ulcerative mucosal lesions in the nose and mouth were also commonly found. Histopathology revealed a nonpurulent vasculitis and perivasculitis in the central nervous system (CNS) typical of MCF in 16 of the cases. The diagnosis in the remaining two animals was based upon histologic eye lesions consistent with MCF (CNS not available for examination). Polymerase chain reaction was run on samples from 15 individuals for evidence of MCF-virus DNA, and ovine herpesvirus-2 (OvHV-2) DNA was detected in five moose, one roe deer, and one red deer, and caprine herpesvirus-2 (CpHV-2) DNA was detected in two moose and one roe deer. Sera from 1,000 free-ranging cervids were tested for specific antibodies to MCF-associated viruses (MCFV) by competitive inhibition enzyme-linked immunosorbent assay. The seroprevalences were: red deer 5%, reindeer (Rangifer tarandus) 4%, roe deer 2%, and moose 0.4% (n = 250 for all four species). The results indicate that sheep and goat MCFV may cause serious disease in wild moose, roe deer, and red deer. The seropositive cervids most likely represent individuals infected with either OvHV-2 or CpHV-2, but may also reflect infections with other related MCFV.     

Identification, typing, and insecticidal activity of Xenorhabdus isolates from entomopathogenic nematodes in United Kingdom soil and characterization of the xpt toxin loci

Xenorhabdus strains from entomopathogenic nematodes isolated from United Kingdom soils by using the insect bait entrapment method were characterized by partial sequencing of the 16S rRNA gene, four housekeeping genes (asd, ompR, recA, and serC) and the flagellin gene (fliC). Most strains (191/197) were found to have genes with greatest similarity to those of Xenorhabdus bovienii, and the remaining six strains had genes most similar to those of Xenorhabdus nematophila. Generally, 16S rRNA sequences and the sequence types based on housekeeping genes were in agreement, with a few notable exceptions. Statistical analysis implied that recombination had occurred at the serC locus and that moderate amounts of interallele recombination had also taken place. Surprisingly, the fliC locus contained a highly variable central region, even though insects lack an adaptive immune response, which is thought to drive flagellar variation in pathogens of higher organisms. All the X. nematophila strains exhibited a consistent pattern of insecticidal activity, and all contained the insecticidal toxin genes xptA1A2B1C1, which were present on a pathogenicity island (PAI). The PAIs were similar among the X. nematophila strains, except for partial deletions of a peptide synthetase gene and the presence of insertion sequences. Comparison of the PAI locus with that of X. bovienii suggested that the PAI integrated into the genome first and then acquired the xpt genes. The independent mobility of xpt genes was further supported by the presence of xpt genes in X. bovienii strain I73 on a type 2 transposon structure and by the variable patterns of insecticidal activity in X. bovienii isolates, even among closely related strains.     

A branched beta-D-(1-->3,1-->6)-glucan from the marine diatom Chaetoceros debilis (Bacillariophyceae) characterized by NMR

The chrysolaminaran from the marine diatom Chaetoceros debilis was isolated and characterized by NMR spectroscopy. Cells were harvested in the stationary phase of growth after the medium had been depleted of nitrate when the chrysolaminaran content was expected to be at its highest. The chrysolaminaran was isolated with an yield of 17.5 mg/L, which corresponds to 15.8 pg/cell. 1H NMR indicated that the structure was similar to that of a beta-(1-->3) main chain with beta-(1-->6)-linked side chains. The degree of polymerization was found to be 30, corresponding to a molecular weight of approximately 4900. Thirty-three percent of the residues were found to be beta-(1-->6)-linked branches. The characteristics of the beta-(1-->6) branching were examined by NOESY NMR, which suggested pustulan-like branches, being beta-(1-->6) linked chains connected to the main chain with few branch points. Confirmation of the 1H NMR data was done by 13C-DEPT, TOCSY, COSY and HMQC NMR spectroscopy. The assignment of the resonances of the main beta-(1-->3) and beta-(1-->6) chains is presented. The structure proposed from our analyses is compared against other chrysolaminaran structures.     

Relative index of inequality: definition, estimation, and inference

The relative index of inequality (RII) is a commonly used measure of the extent to which the occurrence of an outcome such as chronic illness or early death varies with socioeconomic status or some other background variable. The standard RII estimator applies only to linear variation in incidence rates. In this paper a general definition of the RII is introduced, alternative approaches to point estimation are considered, and a parametric bootstrap method is suggested for the construction of approximate confidence intervals. Estimation based on cubic splines fitted by maximum penalized likelihood is developed in some detail, and the proposed approach handles naturally the commonly needed adjustment for a 'standardizing' covariate such as age. Death rates in a large longitudinal study in England and Wales from 1996-2000 are analyzed in order to illustrate the various methods. A small simulation study explores the relative merits of different estimators. The approach based on cubic splines is found to reduce bias substantially, at the expense of some increase in variance, when variation in incidence rates is nonlinear.     

State-dependent incubation behaviour in the high arctic barnacle geese

Energetic trade-offs between time spent on incubation and times spent on foraging for nesting birds give individuals in good body condition the possibility to incubate more continuously. In the present paper, the incubation behaviour of female barnacle geese Branta leucopsis was quantified in a colony in Svalbard. Females were weighted in early incubation and feeding recess lengths and frequencies were recorded. The feeding behaviour during the course of incubation was significantly correlated to by body mass, and heavy females had both fewer and shorter feeding recesses than lighter females. Moreover, there was an increase in the number of feeding recesses and the total feeding time as the incubation period progressed. Neither clutch size nor egg laying date had an effect on incubation behaviour. However, clutch size was positively related to female body mass suggesting that high-quality females produce large clutches but also allocate more body reserves to incubation. Females left the nest to feed at all times of the day, but more frequently during day time. This was not related to their body mass. Females presumably leave their nest at the time of day when the costs to reheat eggs are at a minimum. The diurnal rhythm may also be adjusted to the activity by egg predators. Overall the results support the state-dependent hypothesis for incubation behaviour, suggesting that body condition at the start of incubation is an important factor for incubation behaviour in barnacle geese.     

Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines

The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (β-adrenoceptor activation), as well as intravenous boluses of norepinephrine (α-adrenoceptor activation). Further, the effects of β-blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r = 0.72; P < 0.001), as well as between pulse pressure and intramural shear strain (r = 0.48; P < 0.001). Following administration of norepinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during β-blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69-122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to α-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine.     

Undersulfation of heparan sulfate restricts differentiation potential of mouse embryonic stem cells

Heparan sulfate proteoglycans, present on cell surfaces and in the extracellular matrix, interact with growth factors and morphogens to influence growth and differentiation of cells. The sulfation pattern of the heparan sulfate chains formed during biosynthesis in the Golgi compartment will determine the interaction potential of the proteoglycan. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes have a key role during biosynthesis, greatly influencing total sulfation of the heparan sulfate chains. The differentiation potential of mouse embryonic stem cells lacking both NDST1 and NDST2 was studied using in vitro differentiation protocols, expression of differentiation markers, and assessment of the ability of the cells to respond to growth factors. The results show that NDST1 and NDST2 are dispensable for mesodermal differentiation into osteoblasts but necessary for induction of adipocytes and neural cells. Gene expression analysis suggested a differentiation block at the primitive ectoderm stage. Also, GATA4, a primitive endoderm marker, was expressed by these cells. The addition of FGF4 or FGF2 together with heparin rescued the differentiation potential to neural progenitors and further to mature neurons and glia. Our results suggest that the embryonic stem cells lacking both NDST1 and NDST2, expressing a very low sulfated heparan sulfate, can take the initial step toward differentiation into all three germ layers. Except for their potential for mesodermal differentiation into osteoblasts, the cells are then arrested in a primitive ectoderm and/or endoderm stage.     

Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity

Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity.