Estimators of repeatability

Summary Analysis of variance and principal components methods have been suggested for estimating repeatability. In this study, six estimation procedures are compared: ANOVA, principal components based on the sample covariance matrix and also on the sample correlation matrix, a related multivariate method (structural analysis) based on the sample covariance matrix and also on the sample correlation matrix, and maximum likelihood estimation. A simulation study indicates that when the standard linear model assumptions are met, the estimators are quite similar except when the repeatability is small. Overall, maximum likelihood appears the preferred method. If the assumption of equal variance is relaxed, the methods based on the sample correlation matrix perform better although others are surprisingly robust. The structural analysis method (with sample correlation matrix) appears to be best.Paper number 776 from the Department of Meat and Animal Science, University of Wisconsin-Madison.     

Identification and structural characterization of Lyt-1 glycoproteins from tunicate hemocytes and mouse thymocytes.

1. A panel of monoclonal antibodies specific to murine Lyt-1 allotypic and framework determinants was used to investigate the possible occurrence of a Lyt-1 homolog in tunicate (protochoradte) hemocytes. 2. In immunoprecipitation experiments, antigenic activities were associated with a major 67 kDa component on tunicate hemocytes and C57Bl/6 mouse thymocytes. 3. Tunicate and mouse Lyt-1 molecules were compared, in terms of glycosylation, by their sensitivity to glycosidases and analyses on one- and two-dimensional gel electrophoresis. 4. Each of the two molecules appeared to bear two N-linked oligosaccharides, one high-mannose and one complex-type glycan. 5. Both molecules revealed charge microheterogeneity with differences in sialic acid content accounting for the charge difference between each other. 6. However, the difference in the glycans did not account for the microheterogeneity within each molecule, suggesting that other post-translational modifications might be responsible. 7. At the polypeptide level, comparisons of chymotryptic and endoproteinase-Arg-C peptide maps, as well as CNBr-cleavage products, suggested that tunicate and mouse Lyt-1 molecules are structurally similar and that each may contain at least one intra-chain disulfide bridge. 8. The significance of these findings is discussed in terms of the possible biological role of Lyt-1 glycoproteins at different levels of evolution.     

Biochemical interactions of carbamates and ecothiophate with the activated conformation of nicotinic acetylcholine receptor

Purified Torpedo nobiliana electric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)-stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3-H]-phencyclidine ([3-H]-PCP) binding to the channel sites, acting as a weak agonist. The activation of [3-H]-PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb-activated [3-H]-PCP binding with K_i values of 10, 20, and 1,600 μM, respectively. The inhibition was mixed competitivenoncompetitive in nature. The characteristic response of CRPVF to carb-stimulated [22-Na] influx was inhibited by the three carbamates, with IC-50 values of 6,50, and 1,000 μM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb-stimulated [22-Na] influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125-I]-α- bungarotoxin ([125-I]-α-BGT) with the following decreasing order of potency: Neo < Physo < Eco < Pyrido. Calcium has a direct modulatory role on the time-course inhibition of [125-I]-α-BGT binding by these drugs. While we observed a high potency of Neo and Physo in inhibiting [125-I]-α-BGT binding, it was undetectable for the carbamate insecticide 2-methyl-2-(methylthio)propionaldehyde-O-(methylcarbamoyl)oxime (aldicarb). These data suggest that the potent anticholinesterase carbamate agents interact differently with the AChR and its ionic channel. Their interactions with the nicotinic AChR channel system can be described as (a) weakly agonist, (b) directly acting on the open conformation of the channel, and (c) blocking the AChR-binding sites.     

Unusual clustering of diseases in a Canadian Old Colony (Chortitza) Mennonite kindred and community.

We investigated a large Old Colony (Chortitza) Mennonite kindred with branches across Canada. Six generations of the kindred were traced. There was intermarriage among numerous family members. Insulin-dependent diabetes mellitus (IDDM) was identified in 10 members; all 7 living patients were found to carry the immunogenetic marker HLA-DR4. Nine other close relatives had disorders of carbohydrate metabolism, including gestational diabetes mellitus and non-insulin-dependent diabetes mellitus progressing to insulin use. Ten other relatives had autoimmune diseases, including rheumatoid arthritis, hyperthyroidism, hypothyroidism and multiple sclerosis. Cases of Alport''s syndrome, congenital malformations, inborn errors of metabolism and unusual malignant diseases were also found in the kindred. In the small Alberta community in which the kindred was ascertained there were people of Old Colony Mennonite descent with genetic conditions such as Gilles de la Tourette''s syndrome and congenital malformations, including congenital heart disease. This kindred represents the largest reported familial aggregation of IDDM. This disease and other disorders of carbohydrate metabolism occur in the context of a strong familial predisposition to autoimmune disease. Study of this family may permit empiric testing of proposed models of inheritance of diseases of complex origin such as IDDM. We report this Old Colony (Chortitza) Mennonite community because it is one of the settlements populated by this religious and genetic isolate, which extends across Canada and Central and South America and affords opportunities for the study of both common and rare inherited diseases.     

Alteration in sialidase and other glycosidase activities in the kidney of spontaneously hypertensive rats: persistence after preventive treatment with hydralazine

Because kidney microangiopathy with capillary basement membrane thickening has been reported in spontaneous hypertension, we have studied the activities of three lysosomal glycosidases able to degrade the carbohydrate moieties of basement membrane constituents in the kidney cortex of 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). These activities were also determined in SHR and WKY treated from 6 to 12 weeks of age with hydralazine (mean dose, 18 mg/kg per day in drinking water). Sialidase specific activity on sialyl-alpha 2-3-[3H]lactitol was markedly decreased in the kidney of untreated SHR, 40% activity remaining relative to that found in untreated age-matched WKY (p less than 0.001). beta-Galactosidase specific activity on p-nitrophenyl-beta-D-galactoside was also decreased, 86% activity remaining relative to that found in untreated WKY (p less than 0.001). Glucosyl-galactosyl-hydroxylysyl glucohydrolase specific activity on glucosyl-galactosyl-hydroxylysine was equally diminished, 74% activity remaining relative to that found in untreated age-matched WKY (p less than 0.001). In contrast, the activities of two control glycosidases inactive on the carbohydrate moieties of basement membrane constituents, alpha-glucosidase assayed with p-nitrophenyl-alpha-D-glucoside as substrate and beta-glucosidase assayed with p-nitrophenyl-beta-D-glucoside as substrate, were significantly increased. All the alterations in enzyme activities observed in the kidney of SHR were also present in the long-term treated normotensive SHR. No effect of the hydralazine treatment on the three enzyme activities investigated could be demonstrated in the WKY. Thus the alterations observed in the kidneys of SHR appear to be independent of blood pressure level.     

Biology of Greenland cod,Gadus ogac,at Saqvaqjuac,northwest coast of Hudson Bay

Synopsis The distribution and relative abundance, life history parameters, food habits, and metabolic rate were determined forGadus ogac in Sagvagjuac Inlet, northwest coast of Hudson Bay (63° N). Fish were demersal, non-schooling, and distributed evenly down to 35 m depth. Growth was slow (maximum age 12 y) and mortality relatively low (0.5 y^–1).G. ogac first spawned at 2–3 y and spawned annually thereafter, in late March – early April. They tended to remain in the inlet and were not taken on the open coast. They are top carnivores, taking primarily capelin when available, benthic crustacea (crabs, amphipods) when not. The metabolic rate ofG. ogac is intermediate between the elevated rate of Arctic cod,Boreogadus saida, and eurythermal temperate species. Available data indicate they are not important in marine mammal and bird food webs. Their biology is contrasted with that of Arctic cod, which are short-lived, cryopelagic, feed on pelagic crustacea, and are an extremely important component of Arctic marine food webs.Direct reprint requests