Polyadenylate-polyuridylate enhancement of 7,12-dimethylbenz-anthracene skin carcinogenesis.

Double-stranded polynucleotide polyadenylate-polyuridylate (Poly AU) enhanced skin tumor formation in Swiss mice by 75% when injected prior to a single application of 7,12-dimethylbenzanthracene (DMBA). When given after the carcinogen application Poly AU did not significantly enhance tumor formation.     

A non-spherical core in the explosion of supernova SN 2004dj

An important and perhaps critical clue to the mechanism driving the explosion of massive stars as supernovae is provided by the accumulating evidence for asymmetry in the explosion. Indirect evidence comes from high pulsar velocities, associations of supernovae with long-soft gamma-ray bursts, and asymmetries in late-time emission-line profiles. Spectropolarimetry provides a direct probe of young supernova geometry, with higher polarization generally indicating a greater departure from spherical symmetry. Large polarizations have been measured for 'stripped-envelope' (that is, type Ic; ref. 7) supernovae, which confirms their non-spherical morphology; but the explosions of massive stars with intact hydrogen envelopes (type II-P supernovae) have shown only weak polarizations at the early times observed. Here we report multi-epoch spectropolarimetry of a classic type II-P supernova that reveals the abrupt appearance of significant polarization when the inner core is first exposed in the thinning ejecta (approximately 90 days after explosion). We infer a departure from spherical symmetry of at least 30 per cent for the inner ejecta. Combined with earlier results, this suggests that a strongly non-spherical explosion may be a generic feature of core-collapse supernovae of all types, where the asphericity in type II-P supernovae is cloaked at early times by the massive, opaque, hydrogen envelope.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.     

Volatility forecasting with double Markov switching GARCH models

This paper investigates inference and volatility forecasting using a Markov switching heteroscedastic model with a fat‐tailed error distribution to analyze asymmetric effects on both the conditional mean and conditional volatility of financial time series. The motivation for extending the Markov switching GARCH model, previously developed to capture mean asymmetry, is that the switching variable, assumed to be a first‐order Markov process, is unobserved. The proposed model extends this work to incorporate Markov switching in the mean and variance simultaneously. Parameter estimation and inference are performed in a Bayesian framework via a Markov chain Monte Carlo scheme. We compare competing models using Bayesian forecasting in a comparative value‐at‐risk study. The proposed methods are illustrated using both simulations and eight international stock market return series. The results generally favor the proposed double Markov switching GARCH model with an exogenous variable. Copyright © 2008 John Wiley & Sons, Ltd.     

The preprotein translocase of the outer mitochondrial membrane: receptors and a general import pore

Cytosol-synthesized preproteins destined for the mitochondria are transported across the outer membrane by the translocase of the mitochondrial outer membrane (TOM complex). This dynamic transport machinery can be divided into receptors that recognize preprotein targeting signals and components of the general import pore complex that mediate preprotein transport across the outer membrane. This review focuses on recent studies dealing with the central questions regarding the pore-forming subunits, and architecture and gating of the translocation channel of the outer membrane.     

Ocean currents mediate evolution in island lizards

Islands are considered to be natural laboratories in which to examine evolution because of the implicit assumption that limited gene flow allows tests of evolutionary processes in isolated replicates. Here we show that this well-accepted idea requires re-examination. Island inundation during hurricanes can have devastating effects on lizard populations in the Bahamas. After severe storms, islands may be recolonized by over-water dispersal of lizards from neighbouring islands. High levels of gene flow may homogenize genes responsible for divergence, and are widely viewed as a constraining force on evolution. Ultimately, the magnitude of gene flow determines the extent to which populations diverge from one another, and whether or not they eventually form new species. We show that patterns of gene flow among island populations of Anolis lizards are best explained by prevailing ocean currents, and that over-water dispersal has evolutionary consequences. Across islands, divergence in fitness-related morphology decreases with increasing gene flow. Results suggest that over-water dispersal after hurricanes constrains adaptive diversification in Anolis lizards, and that it may have an important but previously undocumented role in this classical example of adaptive radiation.     

An immunohistochemical and ultrastructural comparison of the effects of 2-bromo-α-ergocryptine on intrasellar and transplanted rat pituitaries

Summary Following 2 weeks of administration of 2-bromo--ergocryptine, a marked decrease was observed in prolactin immunoreactivity of the grafted pituitaries, whereas no reduction was noted in the intrasellar pituitaries. No evidence of crinophagy was revealed by electron microscopy in prolactin cells of 2-bromo--ergocryptine-treated rats.Acknowledgments. This work was supported in part by the Medical Research Council of Canada (grant MA-6349). The excellent technical assistance of Mrs Cynthia Edwards and secretarial help of Mrs Wanda Wlodarski are gratefully acknowledged.     

Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease

Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.