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sity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. M1T1 GAS readily switch to a covRS mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate covRS mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent covRS mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections. Key Words Animal models ؒ Bacteriology ؒ Immunity ؒ Innate ؒ Neutrophils ؒ Streptococcus ؒ Virulence factors ؒ Invasive infection Abstract Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propen

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Plant communities and climate change in southeastern Australia during the early Paleogene

In this study, data from fossil macrofloras and microfloras in southeastern Australia are used to reconstruct vegetation and climates for the early Paleogene. Our data show that for much of the late Paleocene to middle Eocene, complex, species-rich forests were predominant in southeastern Australia, under mesothermal humid climates (mean annual temperature 16-22 °C, coldest quarter mean temperature >10 °C, mean annual precipitation >150 cm/yr). A minor cooling episode may have occurred in the mid-early Eocene. Megathermal climates may have been present in lowlands in the latest early Eocene, during the Cenozoic Global Climatic Optimum. These forests were dominated by taxa characteristic of present-day mesothermal-megathermal high-rainfall multistratal forests; e.g., Cunoniaceae, Elaeocarpaceae, Gymnostoma (Casuarinaceae), Lauraceae (e.g., Beilschmiedia, Cryptocarya and Endiandra), and Proteaceae. A prominent treefern element (Cyathea and Dicksonia types) was present in the early Eocene. A number of megathermal taxa, including Cupanieae (Sapindaceae) and Ilex (Aquifoliaceae), were present through the early and middle Eocene. Taxa characteristic of modern-day microthermal to mesothermal forests were also present, e.g., Nothofagus (Nothofagaceae), Eucryphia (Eucryphiaceae), Libocedrus (Cupressaceae) and Podocarpaceae (Acmopyle and Dacrycarpus). The relictual araucarian conifer, Wollemia, and other Araucariaceae were present through the late Paleocene to early Eocene. There is limited physiognomic evidence to suggest the late Paleocene to early Eocene forests contained some deciduous canopy trees

Parameters Governing Invasive Disease Propensity of Non-M1 Serotype Group A Streptococci

Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propensity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. M1T1 GAS readily switch to a covRS mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate covRS mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent covRS mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections