Evaluating potential for whole-genome studies in Kosrae, an isolated population in Micronesia

Whole-genome association studies are predicted to be especially powerful in isolated populations owing to increased linkage disequilibrium (LD) and decreased allelic diversity, but this possibility has not been empirically tested. We compared genome-wide data on 113,240 SNPs typed on 30 trios from the Pacific island of Kosrae to the same markers typed in the 270 samples from the International HapMap Project. The extent of LD is longer and haplotype diversity is lower in Kosrae than in the HapMap populations. More than 98% of Kosraen haplotypes are present in HapMap populations, indicating that HapMap will be useful for genetic studies on Kosrae. The long-range LD around common alleles and limited diversity result in improved efficiency in genetic studies in this population and augments the power to detect association of 'hidden SNPs'.     

A functional RNAi screen for regulators of receptor tyrosine kinase and ERK signalling

Receptor tyrosine kinase (RTK) signalling through extracellular-signal-regulated kinases (ERKs) has pivotal roles during metazoan development, underlying processes as diverse as fate determination, differentiation, proliferation, survival, migration and growth. Abnormal RTK/ERK signalling has been extensively documented to contribute to developmental disorders and disease, most notably in oncogenic transformation by mutant RTKs or downstream pathway components such as Ras and Raf. Although the core RTK/ERK signalling cassette has been characterized by decades of research using mammalian cell culture and forward genetic screens in model organisms, signal propagation through this pathway is probably regulated by a larger network of moderate, context-specific proteins. The genes encoding these proteins may not have been discovered through traditional screens owing, in particular, to the requirement for visible phenotypes. To obtain a global view of RTK/ERK signalling, we performed an unbiased, RNA interference (RNAi), genome-wide, high-throughput screen in Drosophila cells using a novel, quantitative, cellular assay monitoring ERK activation. Here we show that ERK pathway output integrates a wide array of conserved cellular processes. Further analysis of selected components-in multiple cell types with different RTK ligands and oncogenic stimuli-validates and classifies 331 pathway regulators. The relevance of these genes is highlighted by our isolation of a Ste20-like kinase and a PPM-family phosphatase that seem to regulate RTK/ERK signalling in vivo and in mammalian cells. Novel regulators that modulate specific pathway outputs may be selective targets for drug discovery.     

Embryological evidence for developmental lability during early angiosperm evolution

Recent advances in angiosperm phylogeny reconstruction, palaeobotany and comparative organismic biology have provided the impetus for a major re-evaluation of the earliest phases of the diversification of flowering plants. We now know that within the first fifteen million years of angiosperm history, three major lineages of flowering plants-monocotyledons, eumagnoliids and eudicotyledons-were established, and that within this window of time, tremendous variation in vegetative and floral characteristics evolved. Here I report on a novel type of embryo sac (angiosperm female gametophyte or haploid egg-producing structure) in Amborella trichopoda, the sole member of the most ancient extant angiosperm lineage. This is the first new pattern of embryo sac structure to be discovered among angiosperms in well over half a century. This discovery also supports the emerging view that the earliest phases of angiosperm evolution were characterized by an extensive degree of developmental experimentation and structural lability, and may provide evidence of a critical link to the gymnospermous ancestors of flowering plants.     

Scanning electron microscopy of antibody-dependent cell-mediated cytotoxicity of Friend leukemia virus-infected spleen cells.

Friend leukemia virus (FLV) infected splenocytes treated with rabbit anti-FLV serum and subsequently incubated with splenic lymphocytes from non-immune Balb/c mice were examined by scanning electron microscopy. Villous-covered lymphocytes adherred to the tumor cells and induced surface blebs, numerous membrane pores and eventual tumor cell lysis.     

Increased erythrocyte permeability to Li and Na in the spontaneously hypertensive rat.

Red blood cells incubated in a physiological medium in which Li replaces Na (LiPSS) gain Li in exchange for Na and K. The rate of Li uptake is modestly but significantly increased in the spontaneously hypertensive rat (SHR) at 37 degrees C and at 22 degrees C. The slow rate of Na gain and K loss during cooling at 2 degrees C was about doubled in unmodified whole blood samples from the SHR.     

Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase.

The LD50 of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in the acute toxicity of DMN.