The pogo transposable element family of Drosophila melanogaster.

Summary A 190 by insertion is associated with the white-eosin mutation in Drosophila melanogaster. This insertion is a member of a family of transposable elements, pogo elements, which is of the same class as the P and hobo elements of D. melanogaster. Strains typically have many copies of a 190 by element, 10–15 elements 1.1–1.5 kb in size and several copies of a 2.1 kb element. The smaller elements all appear to be derived from the largest by single internal deletions so that all elements share terminal sequences. They either always insert at the dinucleotide TA and have perfect 21 bp terminal inverse repeats, or have 22 by inverse repeats and produce no duplication upon insertion. Analysis by DNA blotting of their distribution and occupancy of insertion sites in different strains suggests that they may be less mobile than P or hobo. The DNA sequence of the largest element has two long open reading frames on one strand which are joined by splicing as indicated by cDNA analysis. RNAs of this strand are made, whose sizes are similar to the major size classes of elements. A protein predicted by the DNA sequence has significant homology with a human centrosomal-associated protein, CENP-B. Homologous sequences were not detected in other Drosophila species, suggesting that this transposable element family may be restricted to D. melanogaster.     

Primary sequence heterogeneity and tissue expression of glutathione S-transferases of Fasciola hepatica.

Glutathione S-transferases (GSTs) from Fasciola hepatica have been purified by glutathione affinity chromatography. Two closely migrating species of Mr 26,000 and 26,500 were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and several species resolved by two-dimensional gel analysis, indicating substantial heterogeneity among the GSTs. N-terminal amino acid sequencing revealed one core sequence containing three polymorphisms, whereas the sequence of GST peptides implied a minimum of three different GSTs. The amino acid sequence data assigned the F. hepatica GSTs to the mu class of GSTs with high similarities to these proteins in other helminths and mammals. The native GSTs of F. hepatica appeared to behave as dimers as determined by molecular sieving chromatography. The observation that the GSTs of F. hepatica are heterogeneous in sequence and behave as dimers in the native state suggest that these isoenzymes may exhibit considerable functional heterogeneity which may be of importance to the parasite. Immunocytochemical studies suggest that the main source of GST in F. hepatica are the parenchymal cells and peripheral tissues of the parasite. Some extracellular GST is associated with the lamellae of the intestinal epithelium. The identification of an intestinal GST is unique among trematodes studied to date.     

The magnitude and origin of European-American admixture in the Gila River Indian Community of Arizona: a union of genetics and demography.

Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes at eight loci was used to estimate the proportion of European-American admixture, m(a), for the entire sample and within six categories of Caucasian admixture calculated from demographic data, md. The genetic analysis gave an estimate of total European-American admixture in the community of 0.054 (95% confidence interval [CI] .044-.063), while an estimate from demographic records was similar, .059. Regression of m(a) on md yielded a fitted line m(a) = .922md, r = .959 (P = .0001). When total European-American admixture is partitioned between the contributing populations, Mexican-Americans have provided .671, European-Americans .305, and African-Americans .023. These results are discussed within the context of the ethnic composition of the Gila River Indian Community, the assumptions underlying the methods, and the potential that demographic data have for enriching genetic measurements of human admixture. It is concluded that, despite the severe assumptions of the mathematical methods, accurate, reliable estimates of genetic admixture are possible from allele and haplotype frequencies, even when there is little demographic information for the population.     

Inference Based on Ranks with Tied Failure Time or Grouped Survival Data

Scores for the analysis of distinct failure time data using ranks are modified to deal with tied failure times or grouped data. Approximate techniques for inference for regression parameters are considered for ‘proportional odds’ and ‘proportional hazards’ survival data involving tied failures or grouped data. An illustration is given involving a two sample problem.     

Transient impaired glucose tolerance in Pima Indians: is it important?

As part of a continuing epidemiological study of non-insulin dependent diabetes among Pima Indians 154 subjects who had had a transient impairment of glucose tolerance were followed up for 1.2-16.9 (median 5.8) years after their glucose tolerance had returned to normal. Of these, 49 subsequently developed diabetes; 26 subsequently developed impaired glucose tolerance; and 79 had normal glucose tolerance at the last examination. The cumulative incidence of diabetes was 16% and 48% at five and 10 years of follow up respectively, compared with 3% and 8% for a control group of 1245 members of the same population. After adjustment for age, sex, body mass index, and plasma glucose concentration two hours after glucose loading the incidence of diabetes among the subjects who had had transient impaired glucose tolerance was 3.0 times that among the controls (95% confidence interval 2.1 to 4.3). Proportional hazards function analysis indicated that obesity was the most important predictor of subsequent development of diabetes. The results suggest that transient impairment of glucose tolerance indicates, at least in some subjects, a predisposition to diabetes and should not be considered clinically unimportant.     

Determination of the transition-state entropy for aggregation suggests how the growth of sickle cell hemoglobin polymers can be slowed

Sickle cell anemia is associated with the mutant hemoglobin HbS, which forms polymers in red blood cells of patients. The growth rate of the polymers is several micrometers per second, ensuring that a polymer fiber reaches the walls of an erythrocyte (which has a 7-μm diameter) within a few seconds after its nucleation. To understand the factors that determine this unusually fast rate, we analyze data on the growth rate of the polymer fibers. We show that the fiber growth follows a first-order Kramers-type kinetics model. The entropy of the transition state for incorporation into a fiber is 95 J mol^− 1 K^− 1, very close to the known entropy of polymerization. This agrees with a recent theoretical estimate for the hydrophobic interaction and suggests that the gain of entropy in the transition state is due to the release of the last layer of water molecules structured around contact sites on the surface of the HbS molecules. As a result of this entropy gain, the free-energy barrier for incorporation of HbS molecules into a fiber is negligible and fiber growth is unprecedentedly fast. This finding suggests that fiber growth can be slowed by components of the red cell cytosol, native or intentionally introduced, which restructure the hydration layer around the HbS molecules and thus lower the transition state entropy for incorporation of an incoming molecule into the growing fiber.