Induction of tumors in mice by genomic hypomethylation

Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.     

Self-incompatibility: a self-recognition system in plants

Self-incompatibility (SI), a genetically controlled mechanism to prevent inbreeding in plants, offers a relatively simple model system for studying the interactions between plant cells or between a plant cell and the secreted product or products of another cell. Examples of two major types of SI, gametophytic and sporophytic, have been studied by cloning cDNAs corresponding to glycoproteins of the female tissues that segregate with particular variants encoded by the putative S locus. These secreted glycoproteins are envisaged to interact with the currently undescribed pollen component to cause arrest of pollen tube growth.     

Requirement for activin A and transforming growth factor--beta 1 pro-regions in homodimer assembly

Many proteins are initially synthesized as part of a large precursor. The role of the pro-region in the biosynthesis of transforming growth factor--beta 1 (TGF-beta 1) and activin A, two structurally related disulfide-linked homodimers synthesized as large precursors, was studied. Vectors that expressed either the pro-region or the mature regions of these molecules were used in complementation experiments, only when the pro-region was coexpressed with the mature region did intracellular dimerization and secretion of biologically active homodimers occur. The pro-regions of activin A and TGF-beta 1, therefore, aid the folding, disulfide bond formation, and export of their respective homodimers.     

Heme-heme orientation and electron transfer kinetic behavior of multisite oxidation-reduction enzymes

Analysis of the polarized single-crystal absorption spectra of cytochrome cd1 of Pseudomonas aeruginosa shows that the heme c and heme d1 groups in each subunit are oriented perpendicularly to each other in both oxidized and reduced forms of the enzyme. These results, together with those of previous kinetic studies, indicate that a perpendicular heme-heme orientation may be an important factor in specifying kinetically slow steps in a sequential series of electron transfer reactions.     

Quantitative analysis of culture using millions of digitized books

We constructed a corpus of digitized texts containing about 4% of all books ever printed. Analysis of this corpus enables us to investigate cultural trends quantitatively. We survey the vast terrain of 'culturomics,' focusing on linguistic and cultural phenomena that were reflected in the English language between 1800 and 2000. We show how this approach can provide insights about fields as diverse as lexicography, the evolution of grammar, collective memory, the adoption of technology, the pursuit of fame, censorship, and historical epidemiology. Culturomics extends the boundaries of rigorous quantitative inquiry to a wide array of new phenomena spanning the social sciences and the humanities.     

Polypeptide composition of fraction 1 protein from parasexual hybrid plants in the genus Nicotiana

Analysis of the subunit polypeptide composition of Fraction 1 proteins gives information on the expression of both nuclear and chloroplast genomes; the large subunits of the protein are coded by chloroplast DNA, whereas the small subunits are coded by nuclear DNA. Fraction 1 protein isolated from the leaves of parasexual hybrid plants derived from the fusion of protoplasts of Nicotiana glauca and N. langsdorffii contains the small subunit polypeptides of both parent species and the large subunit polypeptides of only N. glauca. Fraction 1 protein isolated from the leaves of a hybrid plant obtained after the uptake of chloroplasts of N. suaveolens by protoplasts of white tissue of a variegating mutant of N. tabacum contains the large subunit polypeptides of both N. suaveolens and N. tabacum, as well as the small subunit polypeptides of both these species.     

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.