The vascular endothelium is remarkably versatile in its ability to respond to both soluble chemical stimuli and mechanical stimuli. In the April 10 Proceedings of the National Academy of Sciences, Garcia-Cardena et al. report the results of a high-throughput genome-wide analysis of gene modulation by biomechanical activation (Proc Natl Acad Sci USA 2001, 98:4478-4485). They used cDNA arrays to examine the effects of biomechnical forces on gene expression in cultured monolayers of human umbilical

Most studies of parasite virulence have focused on identifying genes whose loss causes decreased virulence or infectivity. In the April 13 Science, Cunningham et al. report the characterization of two genes in the protozoan parasite Leishmania, mutation of which causes hypervirulence (Science 2001, 292:285-287). Stephen Beverley and colleagues at Washington University demonstrate that Leishmania mutants lacking the genes for pteridine reductase 1 (PTR1) or biopterin transporter BT1 exhibit incre

Current microarray analysis uses 'chips' containing either 25-residue oligonucleotides synthesized by photolithography or cDNAs placed by robotic spotting. In the April Nature Biotechnology, Hughes et al. describe a microarray technique that exploits an ink-jet printing method and standard phosphoramidite chemistry (Nature Biotechnology 2001, 19:342-347). The ink-jet synthesizer can deliver 25,000 phosphoramidite-containing microdroplets to a 25 x 75 mm glass slide. Hughes et al. examined a larg

Mutations that increase the life span of Caenorhabditis elegans encode components of the insulin/IGF signalling pathway. In the April 6 Science, two papers describe mutations that link insulin signaling with longevity in Drosophila melanogaster. Clancy et al. report that homozygous null mutations in chico, encoding an insulin receptor substrate protein, increased the female fly life span by up to 48% (Science 2001, 292:104-106). They were able to demonstrate that the effects of chico on longevit

Interactions of cells with the extracellular matrix (ECM), via the integrin receptors, modulate cell proliferation, survival and differentiation. In the April 10 Proceedings of the National Academy of Sciences, Yarwood and Woodgett describe how the make up of the ECM can affect the cellular response to growth-factor stimulation (Proc Natl Acad Sci USA 2001, 98:4472-4477). They used cDNA microarrays to analyse over 1,718 human genes and measure changes in gene expression when cells were plated on

There appears to be a genetic contribution to the susceptibility to leprosy, and high concordance rates have been observed amongst monozygotic Indian twins. In the April Nature Genetics, Siddiqui et al. report the identification of a major susceptibility locus for leprosy (Nature Genetics 2001, 27:439-441). They performed a genome-wide scan of 245 independent affected sibpairs from Southern India, using 396 highly polymorphic microsatellite markers. Only one region showed a MLS (maximum lod scor

In the April Nature Genetics, Marth et al. ask the question how useful are the single-nucleotide polymorphisms (SNPs) available in the public-access databases (Nature Genetics 2001, 27:371-372). The public database dbSNP currently holds over 2.8 million SNPs, but as few as 15% have been proven to be genuinely polymorphic. Marth et al. performed two pilot studies to test the genetic utility of candidate SNPs. They analysed over 1200 candidate SNPs and tested their frequency in three ethnic groups

Bloom syndrome is a disease characterized by increased tumorigenesis, immunodeficiency and partial sterility. It is caused by mutations in the BLM gene, which encodes a helicase. In the March 30th Science, Kusano et al. describe characterization of the Drosophila Dmblm homolog of BLM (Science 2001, 291:2600-2602). They show that Dmblm corresponds to mus309, which was originally identified in a mutagen-sensitivity screen. Disrupting the Dmblm gene causes mutagen sensitivity and female sterility,

Natural pathogenic bacteria populations can harbour mutator alleles (with high mutation rates) that may offer a selection advantage. In the March 30 Science, Giraud et al. describe a model to investigate the role of mutator alleles in influencing adaptation to complex environments in vivo (Science 2001, 291:2606-2608). They examined the colonization of the mouse gut by Escherichia coli strains with a high mutation rate due to a defective MutS protein. By examining bacteria in fecal samples they

Dysfunction of the mitochondrial respiratory chain is involved in diabetes, heart failure, neurodegeneration and aging. In the March 27 Proceedings of the National Academy of Sciences USA, Wang et al. described experiments to determine the effect of loss of the mitochondrial transcription factor A (Tfam) gene on cell death (Proc Natl Acad Sci USA 2001, 98:4038-4043). Tissue-specific knockout of the murine Tfam gene, which regulates transcription of mitochondrial DNA, caused mitoc

Caulobacter crescentus is a Gram-negative bacterium that exhibits cell differentiation, asymmetric division and cordinated cell-cycle progression. In the March 27 Proceedings of the National Academy of Sciences USA, Nierman et al. report the complete genome sequence of C. crescentus (Proc Natl Acad Sci USA 2001, 98:4136-4141). The sequence was assembled by whole-genome random sequencing. The single C. crescentus chromosome contains about 4 megabases of DNA and encodes 3,767 genes. Cell-cycle pro

Classic screens for genes that regulate the cell division cycle (CDC genes) in yeast have searched for temperature-sensitive mutants with a loss-of-function phenotype. In the March 27 Proceedings of the National Academy of Sciences, Stevenson et al describe an alternative approach to identifying novel CDC genes (Proc Natl Acad Sci USA 2001, 98:3946-3951). They screened for genes whose overexpression affects cell-cycle progression. They used a Saccharomyces cerevisiae expression library under the