Structural studies on transfer RNA: preliminary crystallographic analysis

Single-crystal diffraction patterns from Escherichia coli leucine tRNA and yeast formylmethionine tRNA show a tetragonal lattice for the former, with a = 46 angstroms and c = 137 angstroms, and a hexagonal lattice for the latter, with a = 115 angstroms and c = 137 angstroms. Initial analysis suggests a molecule with a long, double helix parallel to the c-axis for both crystals.     

Fluorine Is a Major Constituent of the Marine Sponge Halichondria moorei

Fluorine constitutes about 10 percent of the dry weight of the marine sponge Halichondria moorei. The fluorine occurs as potassium fluorosilicate, which is a potent anti-inflammatory agent. A closely related sponge living in the same habitat does not contain any fluorine. The habitat was found to be free of fluorine except for the small amount naturally present in seawater.     

A single IGF1 allele is a major determinant of small size in dogs

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.     

A new strategy for the synthesis of glycoproteins

Posttranslational modifications of proteins regulate many biological processes, including metabolism, signal transduction, and gene expression. The synthetic challenges associated with generating homogeneous populations of selectively modified proteins, however, have hindered detailed studies of the effects of these modifications on protein structure and function. Here, we report an approach to the cotranslational synthesis of selectively glycosylated proteins in which the modified amino acid is genetically encoded. We show that myoglobin containing beta-N-acetylglucosamine (GlcNAc)-serine at a defined position can be expressed in Escherichia coli in good yield and with high fidelity. The beta-GlcNAc moiety can be recognized by a saccharide-binding protein, or subsequently modified with a galactosyltransferase to build more complex carbohydrates. This approach should be generally applicable to other posttranslational modifications such as protein phosphorylation, acetylation, and methylation.     

A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death

We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity. The compound binds to X chromosome- encoded IAP (XIAP), cellular IAP 1 (cIAP-1), and cellular IAP 2 (cIAP-2) and synergizes with both tumor necrosis factor alpha (TNFalpha) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells. The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors. The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases.     

Detection of hydrothermal precursors to large northern california earthquakes

During the period 1973 to 1991 the interval between eruptions from a periodic geyser in Northern California exhibited precursory variations 1 to 3 days before the three largest earthquakes within a 250-kilometer radius of the geyser. These include the magnitude 7.1 Loma Prieta earthquake of 18 October 1989 for which a similar preseismic signal was recorded by a strainmeter located halfway between the geyser and the earthquake. These data show that at least some earthquakes possess observable precursors, one of the prerequisites for successful earthquake prediction. All three earthquakes were further than 130 kilometers from the geyser, suggesting that precursors might be more easily found around rather than within the ultimate rupture zone of large California earthquakes.