Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).     

Evolution of genes and genomes on the Drosophila phylogeny

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.     

Total synthesis of marine natural products without using protecting groups

The field of organic synthesis has made phenomenal advances in the past fifty years, yet chemists still struggle to design synthetic routes that will enable them to obtain sufficient quantities of complex molecules for biological and medical studies. Total synthesis is therefore increasingly focused on preparing natural products in the most efficient manner possible. Here we describe the preparative-scale, enantioselective, total syntheses of members of the hapalindole, fischerindole, welwitindolinone and ambiguine families, each constructed without the need for protecting groups--the use of such groups adds considerably to the cost and complexity of syntheses. As a consequence, molecules that have previously required twenty or more steps to synthesize racemically in milligram amounts can now be obtained as single enantiomers in significant quantities in ten steps or less. Through the extension of the general principles demonstrated here, it should be possible to access other complex molecular architectures without using protecting groups.     

Introducing the area classification of output areas

This article provides a brief introduction to the Area Classification of Output Areas. The classification uses data from the 2001 Census to group the 223,060 output areas into groups of similarity based on their census attributes. The classification is freely available as a 'National Statistic' via the National Statistics website.     

Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress.     

The potential for giant tsunamigenic earthquakes in the northern Bay of Bengal

The great Sumatra-Andaman earthquake and Indian Ocean tsunami of 2004 came as a surprise to most of the earth science community. Although it is now widely recognized that the risk of another giant earthquake is high off central Sumatra, just east of the 2004 earthquake, there seems to be relatively little concern about the subduction zone to the north, in the northern Bay of Bengal along the coast of Myanmar. Here I show that similar indicators suggest a high potential for giant earthquakes along the coast of Myanmar. These indicators include the tectonic environment, which is similar to other subduction zones that experience giant megathrust earthquakes, stress and crustal strain observations, which indicate that the seismogenic zone is locked, and historical earthquake activity, which indicates that giant tsunamigenic earthquakes have occurred there in the past. These are all consistent with active subduction in the Myanmar subduction zone and I suggest that the seismogenic zone extends beneath the Bengal Fan. I conclude therefore that giant earthquakes probably occur off the coast of Myanmar, and that a large and vulnerable population is thereby exposed to a significant earthquake and tsunami hazard.     

Parasitic plants indirectly regulate below-ground properties in grassland ecosystems

Parasitic plants are one of the most ubiquitous groups of generalist parasites in both natural and managed ecosystems, with over 3,000 known species worldwide. Although much is known about how parasitic plants influence host performance, their role as drivers of community- and ecosystem-level properties remains largely unexplored. Parasitic plants have the potential to influence directly the productivity and structure of plant communities because they cause harm to particular host plants, indirectly increasing the competitive status of non-host species. Such parasite-driven above-ground effects might also have important indirect consequences through altering the quantity and quality of resources that enter soil, thereby affecting the activity of decomposer organisms. Here we show in model grassland communities that the parasitic plant Rhinanthus minor, which occurs widely throughout Europe and North America, has strong direct effects on above-ground community properties, increasing plant diversity and reducing productivity. We also show that these direct effects of R. minor on the plant community have marked indirect effects on below-ground properties, ultimately increasing rates of nitrogen cycling. Our study provides evidence that parasitic plants act as a major driver of both above-ground and below-ground properties of grassland ecosystems.