Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori.

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipα) and hitherto unknown functional genes.

The local configuration of a science and innovation policy : a city into the nanoworld

Local trajectories and arrangements play a significant role because the development of a research field, such as nanoscience and nanotechnology, requires substantial investments in human and instrumental resources. But why are there often concentrated in a limited number of places? What dynamics lead to such concentration? The hypothesis is that there is an assemblage of heterogeneous resources through the action of local actors. The chapter will explore, from an Actor Network Theory (ANT) perspective, how the local emergence of research dynamics from: the revival of local traditions, the local and national action of institutional entrepreneurs, controversial dynamics, and researchers' arrangements to involve other actors. It will examine how they connect up with each other and mutually commit themselves to the development of new technologies. It will focus on the role of narratives in this assembling: how were the local narratives of the past mobilized and to what effect.

Targeting iron-mediated retinal degeneration by local delivery of transferrin.

Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress.