C. elegans ORFeome version 1.1: experimental verification of the genome annotation and resource for proteome-scale protein expression

To verify the genome annotation and to create a resource to functionally characterize the proteome, we attempted to Gateway-clone all predicted protein-encoding open reading frames (ORFs), or the 'ORFeome,' of Caenorhabditis elegans. We successfully cloned approximately 12,000 ORFs (ORFeome 1.1), of which roughly 4,000 correspond to genes that are untouched by any cDNA or expressed-sequence tag (EST). More than 50% of predicted genes needed corrections in their intron-exon structures. Notably, approximately 11,000 C. elegans proteins can now be expressed under many conditions and characterized using various high-throughput strategies, including large-scale interactome mapping. We suggest that similar ORFeome projects will be valuable for other organisms, including humans.     

Type II supernovae as a significant source of interstellar dust

Large amounts of dust (>10(8)M(o)) have recently been discovered in high-redshift quasars and galaxies corresponding to a time when the Universe was less than one-tenth of its present age. The stellar winds produced by stars in the late stages of their evolution (on the asymptotic giant branch of the Hertzsprung-Russell diagram) are thought to be the main source of dust in galaxies, but they cannot produce that dust on a short enough timescale (&<1 Gyr) to explain the results in the high-redshift galaxies. Supernova explosions of massive stars (type II) are also a potential source, with models predicting 0.2-4M(o) of dust. As massive stars evolve rapidly, on timescales of a few Myr, these supernovae could be responsible for the high-redshift dust. Observations of supernova remnants in the Milky Way, however, have hitherto revealed only 10(-7)-10(-3)M(o) each, which is insufficient to explain the high-redshift data. Here we report the detection of approximately 2-4M(o) of cold dust in the youngest known Galactic supernova remnant, Cassiopeia A. This observation implies that supernovae are at least as important as stellar winds in producing dust in our Galaxy and would have been the dominant source of dust at high redshifts.     

Defects in whirlin,a PDZ domain molecule involved in stereocilia elongation,cause deafness in the whirler mouse and families with DFNB31

The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia.     

From genomics to proteomics

Proteomics is the study of the function of all expressed proteins. Tremendous progress has been made in the past few years in generating large-scale data sets for protein-protein interactions, organelle composition, protein activity patterns and protein profiles in cancer patients. But further technological improvements, organization of international proteomics projects and open access to results are needed for proteomics to fulfil its potential.     

Genome-wide association study identifies multiple loci influencing human serum metabolite levels

Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10(-10)) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders.     

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.     

Insect communication: 'no entry' signal in ant foraging

Forager ants lay attractive trail pheromones to guide nestmates to food, but the effectiveness of foraging networks might be improved if pheromones could also be used to repel foragers from unrewarding routes. Here we present empirical evidence for such a negative trail pheromone, deployed by Pharaoh's ants (Monomorium pharaonis) as a 'no entry' signal to mark an unrewarding foraging path. This finding constitutes another example of the sophisticated control mechanisms used in self-organized ant colonies.     

Statistical analyses of freeway traffic flows

This paper concerns the exploration of statistical models for the analysis of observational freeway flow data, and the development of empirical models to capture and predict short‐term changes in traffic flow characteristics on sequences of links in a partially detectorized freeway network. A first set of analyses explores regression models for minute‐by‐minute traffic flows, taking into account time of day, day of the week, and recent upstream detector‐based flows. Day‐ and link‐specific random effects are used in a hierarchical statistical modelling framework. A second set of analyses captures day‐specific idiosyncrasies in traffic patterns by including parameters that may vary throughout the day. Model fit and short‐term predictions of flows are thus improved significantly. A third set of analyses includes recent downstream flows as additional predictors. These further improvements, though marginal in most cases, can be quite radically useful in cases of very marked breakdown of freeway flows on some links. These three modelling stages are described and developed in analyses of observational flow data from a set of links on Interstate Highway 5 (I‐5) near Seattle. Copyright © 2002 John Wiley & Sons, Ltd.     

Table of replaceable amino acids in proteins

Zusammenfassung Auf Grund vorausgegangener Experimente, besonders über degenerierte Triplettcodons, wird ein Verfahren entwickelt, aus dem sich die Austauschmöglichkeiten von Aminosäuren in Eiweißstoffe ergeben, dann nämlich, wenn im Codon nur je eine Base des Tripletts ersetzt wird.