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.     

Life histories of stoneflies (Plecoptera) in the Rio Conejos of southern Colorado

Thirty-one stonefly species representing eight families were collected during the March 1987 to May 1990 study period. Genera represented by more than one species included Capnia, Utacapnia, Taenionema, Suwallia, Triznaka, Isogenoides, and Isoperla . Peak species richness was recorded on or near the summer solstice in 1988 and 1989. Climatic differences between years were reflected in nymphal development and emergence phenology of most species. New or important corroborative life history data are presented for 11 stonefly species of this assemblage. The hyporheic nymphal development of most cholroperlid species limited the number of early instars sampled and our capacity to interpret voltinism. Limited nymphal data suggested a univoltine-slow cycle for Plumiperla diversa (Frison). Adults of Suwallia pallidula (Banks) and S. wardi (Banks) were present for an extended summer period, but the bulk of their respective emergence times was temporally separated. Isogenoides zionensis Hanson, Pteronarcella badia (Hagen), and Pteronarcys californica Newport were all shown for the first time to have a 9-10 mo egg diapauses, and all three species have a semivoltine life cycle. Skwala Americana (Klápalek) and Isoperla fulva Claassen were further confirmed to have univoltine-slow cycles. Univoltine-fast and univoltine-slow life cycles are reported for the first time in I. phalerata and I. quinquepunctata , respectively. Regression analysis revealed that six of the eight abunduant species had extended emergence patterns (slopes of < 5%/d), while only two had synchronous patterns. Warmer spring and summer temperatures in 1989 increased the slopes for five of the eight species studied, but did not change their synchrony designation. Nine of 11 abundant species advanced their median emergence date in 1989 over 1988. This and the higher slope values are consistent with a hurried nymphal development and narrower emergence period due to the warmer thermal regime of 1989.     

Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status

Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.     

Combining multiple forecasts given multiple objectives

This paper is concerned with expanding the decision support capabilities of computerized forecasting systems. The expansion allows for the systematic combination of multiple forecasts and the explicit consideration of multiple objectives in the forecast selection process. The methodology used is multiple objective linear programming. Selecting an individual forecast based upon a single objective may not make the best use of available information for a variety of reasons. Combined forecasts may provide a better fit with respect to a single objective than any individual forecast. Even if an individual forecast does provide a good fit with respect to a single objective, a combined forecast may provide a better fit with respect to multiple objectives. An example is used to illustrate the expanded decision support system, its outputs and their properties.     

Animal behaviour: geomagnetic map used in sea-turtle navigation

Migratory animals capable of navigating to a specific destination, and of compensating for an artificial displacement into unfamiliar territory, are thought to have a compass for maintaining their direction of travel and a map sense that enables them to know their location relative to their destination. Compasses are based on environmental cues such as the stars, the Sun, skylight polarization and magnetism, but little is known about the sensory mechanism responsible for the map sense. Here we show that the green sea-turtle (Chelonia mydas) has a map that is at least partly based on geomagnetic cues.     

Inactivation of hCDC4 can cause chromosomal instability

Aneuploidy, an abnormal chromosome number, has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive. Here we report the identification of mutations in hCDC4 (also known as Fbw7 or Archipelago) in both human colorectal cancers and their precursor lesions. We show that genetic inactivation of hCDC4, by means of targeted disruption of the gene in karyotypically stable colorectal cancer cells, results in a striking phenotype associated with micronuclei and chromosomal instability. This phenotype can be traced to a defect in the execution of metaphase and subsequent transmission of chromosomes, and is dependent on cyclin E--a protein that is regulated by hCDC4 (refs 2-4). Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion.     

What was classical genetics?

I present an account of classical genetics to challenge theory-biased approaches in the philosophy of science. Philosophers typically assume that scientific knowledge is ultimately structured by explanatory reasoning and that research programs in well-established sciences are organized around efforts to fill out a central theory and extend its explanatory range. In the case of classical genetics, philosophers assume that the knowledge was structured by T. H. Morgan’s theory of transmission and that research throughout the later 1920s, 30s, and 40s was organized around efforts to further validate, develop, and extend this theory. I show that classical genetics was structured by an integration of explanatory reasoning (associated with the transmission theory) and investigative strategies (such as the ‘genetic approach’). The investigative strategies, which have been overlooked in historical and philosophical accounts, were as important as the so-called laws of Mendelian genetics. By the later 1920s, geneticists of the Morgan school were no longer organizing research around the goal of explaining inheritance patterns; rather, they were using genetics to investigate a range of biological phenomena that extended well beyond the explanatory domain of transmission theories. Theory-biased approaches in history and philosophy of science fail to reveal the overall structure of scientific knowledge and obscure the way it functions.     

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.