Evolution of bacterial pathogenesis

The evolution of bacteria is associated with continuous generation of novel genetic variants. The major driving forces in this process are point mutations, genetic rearrangements, and horizontal gene transfer. A large number of human and animal bacterial pathogens have evolved the capacity to produce virulence factors that are directly involved in infection and disease. Additionally, many bacteria express resistance traits against antibiotics. Both virulence factors and resistance determinants are subject to intrastrain genetic and phenotypic variation. They are often encoded on unstable DNA regions. Thus, they can be readily transferred to bacteria of the same species or even to non-related prokaryotes. This review article focuses on the main mechanisms of bacterial microevolution responsible for the rapid emergence of variants with novel virulence and resistance properties. In addition, processes of macroevolution are described with special emphasis on gene transfer and fixation of adaptive mutations in the genome of pathogens.     

Normal faulting in central Tibet since at least 13.5 Myr ago

Tectonic models for the evolution of the Tibetan plateau interpret observed east-west thinning of the upper crust to be the result of either increased potential energy of elevated crust or geodynamic processes that may be unrelated to plateau formation. A key piece of information needed to evaluate these models is the timing of deformation within the plateau. The onset of normal faulting has been estimated to have commenced in southern Tibet between about 14 Myr ago and about 8 Myr ago and, in central Tibet, about 4 Myr ago. Here, however, we report a minimum age of approximately 13.5 Myr for the onset of graben formation in central Tibet, based on mineralization ages determined with Rb-Sr and 40Ar-39Ar data that post-date a major graben-bounding normal fault. These data, along with evidence for prolonged activity of normal faulting in this and other Tibetan grabens, support models that relate normal faulting to processes occurring beneath the plateau. Thinning of the upper crust is most plausibly the result of potential-energy increases resulting from spatially and temporally heterogeneous changes in thermal structure and density distribution within the crust and upper mantle beneath Tibet. This is supported by recent geophysical and geological data, which indicate that spatial heterogeneity exists in both the Tibetan crust and lithospheric mantle.     

Cardiac angiogenic imbalance leads to peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.