Molecular identification of a danger signal that alerts the immune system to dying cells

In infections, microbial components provide signals that alert the immune system to danger and promote the generation of immunity. In the absence of such signals, there is often no immune response or tolerance may develop. This has led to the concept that the immune system responds only to antigens perceived to be associated with a dangerous situation such as infection. Danger signals are thought to act by stimulating dendritic cells to mature so that they can present foreign antigens and stimulate T lymphocytes. Dying mammalian cells have also been found to release danger signals of unknown identity. Here we show that uric acid is a principal endogenous danger signal released from injured cells. Uric acid stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from CD8+ T cells. Eliminating uric acid in vivo inhibits the immune response to antigens associated with injured cells, but not to antigens presented by activated dendritic cells. Our findings provide a molecular link between cell injury and immunity and have important implications for vaccines, autoimmunity and inflammation.     

Notch1 functions as a tumor suppressor in mouse skin

Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin.     

Application of ICP-MS trace element analysis in study of ancient Chinese ceramics

Chemical analysis plays a significant role in the study of ancient ceramics[1,2]. Most ancient Chinese kilns used clays mined from the local areas and differences in the geochemistry and mineralogy of these raw materials may be expected. The chemical composition of ceramics may also be influenced by production techniques, such as processing by washing and mixing of different sorts of raw materials. These may also vary from kiln to kiln and even change over time. Thus the raw materials and pro…     

Female mating bias results in conflicting sex-specific offspring fitness

Indirect-benefit models of sexual selection assert that females gain heritable offspring advantages through a mating bias for males of superior genetic quality. This has generally been tested by associating a simple morphological quality indicator (for example, bird tail length) with offspring viability. However, selection acts simultaneously on many characters, limiting the ability to detect significant associations, especially if the simple indicator is weakly correlated to male fitness. Furthermore, recent conceptual developments suggest that the benefits gained from such mating biases may be sex-specific because of sexually antagonistic genes that differentially influence male and female reproductive ability. A more suitable test of the indirect-benefit model would examine associations between an aggregate quality indicator (such as male mating success) and gender-specific adult fitness components, under the expectation that these components may trade off. Here, we show that a father's mating success in the cricket, Allonemobius socius, is positively genetically correlated with his son's mating success but negatively with his daughter's reproductive success. This provides empirical evidence that a female mating bias can result in sexually antagonistic offspring fitness.     

Common variation at 10p12.31 near MLLT10 influences meningioma risk

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.     

Least Bell's Vireo breeding records in the Central Valley following decades of extirpation

The Least Bell’s Vireo ( Vireo bellii pusillus ) was listed as state endangered in 1980 and federally endangered in 1986 in response to a sharp population decline and range reduction. This vireo commonly bred in riparian forests throughout the Central Valley of California, but prior to 2005, no nesting pairs had been confirmed in the region in over 50 years. On 29 June 2005, a Least Bell’s Vireo nest was located in a 3-year-old riparian restoration site at the San Joaquin River National Wildlife Refuge in Stanislaus County, California. In 2006, a Least Bell’s Vireo pair returned to the refuge to successfully breed, followed by an unsuccessful attempt in 2007 by an unpaired female. These records are approximately 350 km from the nearest known breeding population and appear to be part of a growing number of sightings outside of the species’ current southern California breeding range. These nesting attempts lend credence to the idea that extirpated species can recolonize restored habitat by long-distance dispersal.