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Inherited neurodegenerative conditions such as Huntington's disease have proximal causes (a defective gene) and downstream causes (pathological events caused by that gene). Albert R. La Spada examines efforts to target bad genes with gene knockdown approaches on the eve of a clinical trial designed to silence the causative gene in familial amyotrophic lateral sclerosis. Masahisa Katsuno, Hiroaki Adachi and Gen Sobue examine the possibility of targeting a potentially damaging downstream event in Huntington's disease—dysregulated cholesterol metabolism in the brain.
With the global outsourcing of domestic drug manufacturing, the need to ensure the quality and safety of medical products has never been greater. But recent events show that the US Food and Drug Administration (FDA) is not up to the task.
A remote, downstream event in the pathology of muscular dystrophy may have a key role in the disease (pages 325–330). It seems that induction of nitric oxide synthase causes calcium to leak inside the cell through ryanodine receptors. The findings provide new options for therapeutic interventions.
Findings in knockout mice indicate that hypoxia-sensitive pathways modulate the glucose-sensing machinery of pancreatic beta cells. Conditions that mimic hypoxia severely impair glucose-stimulated insulin release.
Three studies implicate Kindlin-3, a molecule that mediates signaling through integrins, in a rare disorder characterized by spontaneous bleeding and susceptibility to infection (pages 300–305, 306–312 and 313–318).
Biological innovation typically takes place within the walls of academia and industry. But a new grassroots movement to organize hobby scientists is afoot. Mac Cowell and Jason Bobe, co-founders of the organization DIYBio, spoke with Prashant Nair about their plans for amateur biology.
An experimental simian immunodeficiency virus vaccine boosts production of memory T cells at the site where the virus first contacts the body—in the mucosa (pages 293–299). The approach has the potential to result in more effective HIV vaccines than those currently under development.
Activation of hypoxia-inducible factor, a molecule central to oxygen sensing, can promote the survival and growth of tumor cells. New experiments dissect a pathway behind this effect—upregulation of the epidermal growth factor receptor (pages 319–324).