ΔF508 frequency and associated haplotypes near the cystic fibrosis locus in the Yugoslav population

Summary Chromosomes from 19 unrelated Southern Yugoslav families in which cystic fibrosis (CF) occurs were analysed for the presence of the ΔF508 mutation, using polymerase chain reaction amplification followed by dot blot and polyacrylamide gel analysis. Of the 38 CF chromosomes, 15 (39.5%) carry the ΔF508 deletion. Restriction fragment length polymorphism haplotypes for KM19/PstI, XV2c/TaqI and J3.11/PstI marker loci were determined and are compared for a total of 34 N and 37 CF chromosomes.     

The levels of ζ, γ, and δ chains in patients with Hb H disease

Summary Details are given of a study of blood samples from 24 patients with Hb H disease from different Mediterranean countries and from the Far East. Four different types of -thal-1 (--) were observed, namely-() ( 20.5-kb deletion);--MED-I ( 17.5-kb deletion);--MED-II (>26.5-kb deletion); and--SEA ( 18-kb deletion, in Orientals only). The -thal-2 was mainly of the deletion type (16 with the 3.7-kb deletion; 1 with the 4.2-kb deletion), while 4 of the 7 patients with a nondeletional type had the five-nucleotide deletion at the donor splice site of the first intron of the 2 gene. All patients had a mild-to-moderate hemolytic anemia; no significant differences in hematology were observed between the groups. Hb A₂ was decreased to about one-third of the normal level. The Hb H formation varied considerably and its quantitation was not always satisfactory. Patients with Hb H disease due to any -thal-1 combined with a nondeletional -thal-2 had the highest Hb H levels and a more marked anemia. The chain production was small and absent in patients with the MED-II type of -thal-1 because this deletion included the and genes. The highest chain levels were present in the four patients with the SEA type of -thal-1. The chain production was increased, particularly in patients with a mutation of C T at position-158 to the ^G globin gene. This chain was primarily present as Hb Bart's (or ₄) and only about 15% was recovered as Hb F or ₂₂. The evaluation of the rate of chains produced in these patients was greatly facilitated by data from one patient who had Hb H disease and a heterozygosity for the ^A-⁺. The low levels of Hb A₂ and of Hb F (relative to Hb Bart's) can be explained by a decreased affinity of chains for and chains as compared with chains in conditions of severe chain deficiency.     

Natural Occurrence of Entomogenous Nematodes in Tennessee Nursery Soils

To isolate potential insect biocontrol agents, entomogenous nematodes were surveyed in Tennessee plant nurseries in 1991. Soil samples from 113 nursery sites were baited with greater wax moth (Galleria mellonella) larvae, house cricket (Acheta domesticus) adults, lesser mealworm (Alphitobius diaperings) adults, and house fly (Musca domestica) larvae. Heterorhabditis bacteriophora and Steinernema carpocapsae were each recovered from 17 soil samples. Heterorhabditis bacteriophora was more common in habitats with crape myrtle (Lagerstroemia indica) and Chinese juniper (Juniperus chinensis) than other nursery plants, and S. carpocapsae was more frequently recovered from habitats with juniper and Southern magnolia (Magnolia grandiflora). Bulk density, electrical conductivity, organic matter, pH, temperature, and moisture content of the entomogenous-nematode positive soil samples were compared. Other nematode genera recovered with insect baits included Rhabditis sp., Pelodera sp., Cryptaphelenchoides sp., and Mesodiplogaster sp., which was recovered from a greater percentage of soil samples than the other five genera.     

Intra- and Interpopulation Genome Variation In Meloidogyne arenaria

The genetic heterogeneity of two M. arenaria race 2 populations (designated Pelion and Govan) was examined using RFLP analysis of 12 clonal lines established from single egg masses (six distinct clonal lines from each population). These populations are essentially identical by traditional biochemical and race identification schemes; however, the Govan population is more aggressive than the Pelion population, producing larger galls and exhibiting greater reproductive capabilities on many soybean cultivars and experimental accessions. Variation at the genomic DNA level was examined using probes representative of expressed DNA sequences present in the eukaryotic genome. Ribosomal DNA, interspersed repeated sequences, and cDNA probes were tested for detection of polymorphism within and between single egg mass lines of each population. Cloned cDNAs and ribosomal intergenic spacer sequences detect polymorphism both within and between populations, demonstrating the usefulness of these sequence classes for molecular genetic analysis of population structure and genome evolution.     

Dynamics of viscoelastic spherical membranes—the balloon model of the alveolus

Double-valued pressure-volume relationships in dynamic conditions for spherical membranes, modelling the lung alveoli, were obtained at small deformations. This hysteretic behavior was considered to be produced by at least three independent mechanisms: (1) the lung parenchyma exhibits viscoelastic properties; (2) the lung surface film, independent of the tissue, exhibits viscoelastic properties and (3) the pressure acting on the inner membrane surface depends on the rate of the alveolus volume change, due to the air viscous resistance in the bronchial tree. In each case, the maximum volume change, the hysteresis loop area, the tilt angle of the hysteresis loop and the relaxation time of the system were calculated. The results show pronounced hysteresis at normal breathing due to the air viscous resistance and smaller one due to the tissue and surface viscoelastic properties. In quasistatic conditions the values of the surface viscoelasticity and the tissue viscoelasticity effects are comparable or different, depending on the concrete external conditions. Comparison with the available experimental data is discussed in detail.     

Mechanical Signaling on the Single Protein Level Studied Using Steered Molecular Dynamics

Efficient communication between the cell and its external environment is of the utmost importance to the function of multicellular organisms. While signaling events can be generally characterized as information exchange by means of controlled energy conversion, research efforts have hitherto mainly been concerned with mechanisms involving chemical and electrical energy transfer. Here, we review recent computational efforts addressing the function of mechanical force in signal transduction. Specifically, we focus on the role of steered molecular dynamics (SMD) simulations in providing details at the atomic level on a group of protein domains, which play a fundamental role in signal exchange by responding properly to mechanical strain. We start by giving a brief introduction to the SMD technique and general properties of mechanically stable protein folds, followed by specific examples illustrating three general regimes of signal transfer utilizing mechanical energy: purely mechanical, mechanical to chemical, and chemical to mechanical. Whenever possible the physiological importance of the example at hand is stressed to highlight the diversity of the processes in which mechanical signaling plays a key role. We also provide an overview of future challenges and perspectives for this rapidly developing field.     

The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent

Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.