The ring of life provides evidence for a genome fusion origin of eukaryotes

Genomes hold within them the record of the evolution of life on Earth. But genome fusions and horizontal gene transfer seem to have obscured sufficiently the gene sequence record such that it is difficult to reconstruct the phylogenetic tree of life. Here we determine the general outline of the tree using complete genome data from representative prokaryotes and eukaryotes and a new genome analysis method that makes it possible to reconstruct ancient genome fusions and phylogenetic trees. Our analyses indicate that the eukaryotic genome resulted from a fusion of two diverse prokaryotic genomes, and therefore at the deepest levels linking prokaryotes and eukaryotes, the tree of life is actually a ring of life. One fusion partner branches from deep within an ancient photosynthetic clade, and the other is related to the archaeal prokaryotes. The eubacterial organism is either a proteobacterium, or a member of a larger photosynthetic clade that includes the Cyanobacteria and the Proteobacteria.     

The mechanical and biochemical effects of pentoxifylline on the perfused rat heart

Summary Perfusion of the isolated rat heart at constant heart rate and coronary flow with the inhibitor of cyclic nucleotide phosphodiesterase, pentoxifylline (10^–4 moles/l), produced no significant effect on the maximum rate and the peak of contraction, but increased the maximum rate of relaxation. cAMP level and cAMP-dependent protein kinase activity were increased in the absence of changes in cGMP. The results were identical in hearts of reserpinized rats.This work was supported by grants from the Consejo Nacional de Investigaciones Cientificas y Técnicas and the Comisión de Investigaciones Científicas. Buenos Aires, Argentina.We thank Hoechst Laboratories for the partial support and Mrs Alicia R. Ramirez and María Prinzo for the excellent technical assistance.     

Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus

Animals and higher plants express endogenous peptide antibiotics called defensins. These small cysteine-rich peptides are active against bacteria, fungi and viruses. Here we describe plectasin-the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella. Plectasin has primary, secondary and tertiary structures that closely resemble those of defensins found in spiders, scorpions, dragonflies and mussels. Recombinant plectasin was produced at a very high, and commercially viable, yield and purity. In vitro, the recombinant peptide was especially active against Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin showed extremely low toxicity in mice, and cured them of experimental peritonitis and pneumonia caused by S. pneumoniae as efficaciously as vancomycin and penicillin. These findings identify fungi as a novel source of antimicrobial defensins, and show the therapeutic potential of plectasin. They also suggest that the defensins of insects, molluscs and fungi arose from a common ancestral gene.     

MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction

Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a -168A --> G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-gamma. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components.     

Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer

CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.     

Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

We have previously reported a large Danish pedigree with autosomal dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD3). Here we identify a mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of this family. We also describe an additional missense mutation in an unrelated individual with FTD. Aberration in the endosomal ESCRTIII complex may result in FTD and neurodegenerative disease.     

Wave acceleration of electrons in the Van Allen radiation belts

The Van Allen radiation belts are two regions encircling the Earth in which energetic charged particles are trapped inside the Earth's magnetic field. Their properties vary according to solar activity and they represent a hazard to satellites and humans in space. An important challenge has been to explain how the charged particles within these belts are accelerated to very high energies of several million electron volts. Here we show, on the basis of the analysis of a rare event where the outer radiation belt was depleted and then re-formed closer to the Earth, that the long established theory of acceleration by radial diffusion is inadequate; the electrons are accelerated more effectively by electromagnetic waves at frequencies of a few kilohertz. Wave acceleration can increase the electron flux by more than three orders of magnitude over the observed timescale of one to two days, more than sufficient to explain the new radiation belt. Wave acceleration could also be important for Jupiter, Saturn and other astrophysical objects with magnetic fields.     

Malaria risk: estimation of the malaria burden

Accurate estimates of the global burden of malaria are important for planning, monitoring and advocacy. Snow et al. attempt to address the shortcomings of previous estimates of the incidence of malaria caused by Plasmodium falciparum by combining current and historical data. However, we believe that the design of their model and its inputs have led to a significant overestimate of the malaria burden outside Africa--as in the example of the World Health Organization (WHO) western Pacific region (WPR), for which their model predicts 60 times the 2002 incidence reported by national malaria-control programmes.     

Stereospecific reduction of geraniol to (R)-(+)-citronellol bySaccharomyces cerevisiae

Summary (R)-(+)-citronellol, a useful C₁₀ chiral synthon for natural terpenoid products, can be obtained in enantiomerically pure form and satisfactory yield by yeast reduction of geraniol.