A mechanosensory complex that mediates the endothelial cell response to fluid shear stress

Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis, but the mechanisms of transduction are poorly understood. Previous work showed that the conversion of integrins to a high-affinity state mediates a subset of shear responses, including cell alignment and gene expression. Here we investigate the pathway upstream of integrin activation. PECAM-1 (which directly transmits mechanical force), vascular endothelial cell cadherin (which functions as an adaptor) and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) comprise a mechanosensory complex. Together, these receptors are sufficient to confer responsiveness to flow in heterologous cells. In support of the relevance of this pathway in vivo, PECAM-1-knockout mice do not activate NF-kappaB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.     

Short-term variations in the oxidizing power of the atmosphere

The hydroxyl radical is the predominant atmospheric oxidant, responsible for removing a wide range of trace gases, including greenhouse gases, from the atmosphere. Determination of trends and variability in hydroxyl radical concentrations is critical to understanding whether the 'cleansing' properties of the atmosphere are changing. The variability in hydroxyl radical concentrations on annual to monthly timescales, however, is difficult to quantify. Here we show records of carbon monoxide containing radiocarbon (14CO), which is oxidized by hydroxyl radicals, from clean-air sites at Baring Head, New Zealand, and Scott Base, Antarctica, spanning 13 years. Using a model study, we correct for known variations in production of 14CO (refs 6, 7), allowing us to exploit this species as a diagnostic for short term changes in hydroxyl radical concentrations. We find no significant long-term trend in hydroxyl radical concentrations but provide evidence for recurring short-term variations of around ten per cent persisting for a few months. We also find decreases in hydroxyl radical concentrations of up to 20 per cent, apparently triggered by the eruption of Mt Pinatubo in 1991 and by the occurrence of extensive fires in Indonesia in 1997.     

Determinants of woody cover in African savannas

Savannas are globally important ecosystems of great significance to human economies. In these biomes, which are characterized by the co-dominance of trees and grasses, woody cover is a chief determinant of ecosystem properties. The availability of resources (water, nutrients) and disturbance regimes (fire, herbivory) are thought to be important in regulating woody cover, but perceptions differ on which of these are the primary drivers of savanna structure. Here we show, using data from 854 sites across Africa, that maximum woody cover in savannas receiving a mean annual precipitation (MAP) of less than approximately 650 mm is constrained by, and increases linearly with, MAP. These arid and semi-arid savannas may be considered 'stable' systems in which water constrains woody cover and permits grasses to coexist, while fire, herbivory and soil properties interact to reduce woody cover below the MAP-controlled upper bound. Above a MAP of approximately 650 mm, savannas are 'unstable' systems in which MAP is sufficient for woody canopy closure, and disturbances (fire, herbivory) are required for the coexistence of trees and grass. These results provide insights into the nature of African savannas and suggest that future changes in precipitation may considerably affect their distribution and dynamics.     

Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.     

Magnesium sulphate salts and the history of water on Mars

Recent reports of approximately 30 wt% of sulphate within saline sediments on Mars--probably occurring in hydrated form--suggest a role for sulphates in accounting for equatorial H2O observed in a global survey by the Odyssey spacecraft. Among salt hydrates likely to be present, those of the MgSO4*nH2O series have many hydration states. Here we report the exposure of several of these phases to varied temperature, pressure and humidity to constrain their possible H2O contents under martian surface conditions. We found that crystalline structure and H2O content are dependent on temperature-pressure history, that an amorphous hydrated phase with slow dehydration kinetics forms at <1% relative humidity, and that equilibrium calculations may not reflect the true H2O-bearing potential of martian soils. Mg sulphate salts can retain sufficient H2O to explain a portion of the Odyssey observations. Because phases in the MgSO4*nH2O system are sensitive to temperature and humidity, they can reveal much about the history of water on Mars. However, their ease of transformation implies that salt hydrates collected on Mars will not be returned to Earth unmodified, and that accurate in situ analysis is imperative.     

The Collaborative Cross, a community resource for the genetic analysis of complex traits

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.