Multidomain Assembler (MDA) Generates Models of Large Multidomain Proteins

Homology modeling predicts protein structures using known structures of related proteins as templates. We developed MULTIDOMAIN ASSEMBLER (MDA) to address the special problems that arise when modeling proteins with large numbers of domains, such as fibronectin with 30 domains, as well as cases with hundreds of templates. These problems include how to spatially arrange nonoverlapping template structures, and how to get the best template coverage when some sequence regions have hundreds of available structures while other regions have a few distant homologs. MDA automates the tasks of template searching, visualization, and selection followed by multidomain model generation, and is part of the widely used molecular graphics package UCSF CHIMERA (University of California, San Francisco). We demonstrate applications and discuss MDA’s benefits and limitations.     

Epithelial IgG and its relationship to the loss of F508 in the common mutant form of the cystic fibrosis transmembrane conductance regulator

The most debilitating feature of cystic fibrosis (CF) disease is uncontrolled inflammation of respiratory epithelium. The relationship between the commonest mutated form of CFTR (F508del or ΔF508) and inflammation has not yet been elucidated. Here, we present a new paradigm suggesting that CFTR can interact with intra-epithelial IgG, establishing a direct link between normal CFTR and the immune system. Further, our data show that the amino-acid sequence local to F508 can bind IgG with high affinity, dependent on F508, such that loss of F508 abolishes this link both in vitro and in the intact cell.     

FOOD PREFERENCES OF TWO BLACK RHINOCEROS POPULATIONS

Food preferences of two discrete black rhinoceros (Diceros bicornis L.) populations were studied in northern Tanzania from 1964–1966 Feeding rhinoceros were watched for a period of one hour, and the plants which they selected and rejected were identified, either as they were feeding or when they had moved on. A technique was used which provided an indication of the relative importance of certain plants in the diet. Observations were made in six different habitat types used by the rhinoceros during the wet and dry seasons. A total of 307 hours was spent actually watching feeding rhinoceros. During this period they were observed eating 191 plant species from 49 botanical families. In all habitat types rhinoceros consume a wide variety of the spectrum of plants available, but are highly selective for herbs and shrubs. At certain periods of the year stenophagous characteristics are apparent, and the species shows a marked preference for legumes. Grasses make up a small proportion of the diet.     

Pharmacologic Disposition of a Phosphorothioate Oligodeoxynucleotide in Mice

Abstract

G3139, an 18mer phosphorothioate (S-labeled), was administered to mice by single i.v. bolus or continuous S.C. infusion. The latter schedule resulted in reduced liver metabolism and urinary excretion together with greater tissue accumulation, in particular to the liver, kidney and bone marrow, probably reflecting the dose received.     

Evidence for pleiotropism and recent selection in the PLAG1 region in Australian Beef cattle

A putative functional mutation (rs109231213) near PLAG1 (BTA14) associated with stature was studied in beef cattle. Data from 8199 Bos taurus, Bos indicus and Tropical Composite cattle were used to test the associations between rs109231213 and various phenotypes. Further, 23 496 SNPs located on BTA14 were tested for association with these phenotypes, both independently and fitted together with rs109231213. The C allele of rs109231213 significantly increased hip height, weight, net food intake, age at puberty in males and females and decreased IGF‐I concentration in blood and fat depth. When rs109231213 was fitted as a fixed effect in the model, there was an overall reduction in associations between other SNPs and these traits but some SNPs remained associated (P < 10^?4). Frequency of the mutant C allele of rs109231213 differed among B. indicus (0.52), B. taurus (0.96) and Tropical Composite (0.68). Most chromosomes carrying the C allele had the same surrounding 10 SNP haplotype, probably because the C allele was introgressed into Brahman from B. taurus cattle. A region of reduced heterozygosity surrounds the C allele; this is small in B. taurus but 20 Mb long in Brahmans, indicating recent and strong selection for the mutant allele. Thus, the C allele appears to mark a mutation that has been selected almost to fixation in the B. taurus breeds studied here and introduced into Brahman cattle during grading up and selected to a frequency of 0.52 despite its negative effects on fertility.