A consensus amino-acid sequence repeat in Torpedo and mammalian Ca2+-dependent membrane-binding proteins

A group of calcium-binding proteins which bind to biomembranes has recently been identified in widely different cells and tissues (refs 1-7, reviewed in ref. 8). Three of these proteins (p70, p36 and p32.5) cross-react with antiserum to calelectrin, a Ca2+-binding protein (relative molecular mass 34,000 (34K] from the ray Torpedo marmorata, giving rise to their designation as calelectrin-related proteins. We now report that calelectrin, p36 and p32.5 contain a 17-amino-acid consensus sequence which is conserved and present in multiple copies. We suggest that this sequence may be common to other members of this new group of Ca2+-binding proteins and may underlie their unusual mode of combination with biomembranes.     

Egalitarian motives in humans

Participants in laboratory games are often willing to alter others' incomes at a cost to themselves, and this behaviour has the effect of promoting cooperation. What motivates this action is unclear: punishment and reward aimed at promoting cooperation cannot be distinguished from attempts to produce equality. To understand costly taking and costly giving, we create an experimental game that isolates egalitarian motives. The results show that subjects reduce and augment others' incomes, at a personal cost, even when there is no cooperative behaviour to be reinforced. Furthermore, the size and frequency of income alterations are strongly influenced by inequality. Emotions towards top earners become increasingly negative as inequality increases, and those who express these emotions spend more to reduce above-average earners' incomes and to increase below-average earners' incomes. The results suggest that egalitarian motives affect income-altering behaviours, and may therefore be an important factor underlying the evolution of strong reciprocity and, hence, cooperation in humans.     

Hyperion's sponge-like appearance

Hyperion is Saturn's largest known irregularly shaped satellite and the only moon observed to undergo chaotic rotation. Previous work has identified Hyperion's surface as distinct from other small icy objects but left the causes unsettled. Here we report high-resolution images that reveal a unique sponge-like appearance at scales of a few kilometres. Mapping shows a high surface density of relatively well-preserved craters two to ten kilometres across. We have also determined Hyperion's size and mass, and calculated the mean density as 544 +/- 50 kg m(-3), which indicates a porosity of >40 per cent. The high porosity may enhance preservation of craters by minimizing the amount of ejecta produced or retained, and accordingly may be the crucial factor in crafting this unusual surface.     

Genome-wide association study identifies novel breast cancer susceptibility loci

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.     

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.     

IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy

Jeune asphyxiating thoracic dystrophy, an autosomal recessive chondrodysplasia, often leads to death in infancy because of a severely constricted thoracic cage and respiratory insufficiency; retinal degeneration, cystic renal disease and polydactyly may be complicating features. We show that IFT80 mutations underlie a subset of Jeune asphyxiating thoracic dystrophy cases, establishing the first association of a defective intraflagellar transport (IFT) protein with human disease. Knockdown of ift80 in zebrafish resulted in cystic kidneys, and knockdown in Tetrahymena thermophila produced shortened or absent cilia.     

A common coding variant in CASP8 is associated with breast cancer risk

The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.     

Seed bank dynamics and habitat indicators of Arctomecon californica, a rare plant in a fragmented desert environment

Protection of endangered desert plant species is frequently complicated by a lack of information about seeds, the most stress-resistant and populous life stage. We studied the relative locations of seeds and plants of a rare endangered herbaceous perennial, the Las Vegas bearpoppy ( Arctomecon californica ) in seven 1-ha sites randomly located within a 100-ha study area that was slated for development in Las Vegas, Nevada. We also measured the physical and biological attributes of the environment supporting the seeds and plants, including soil hardness, rock cover, cryptogamic crust cover, and associated vegetation. Arctomecon californica seed density was 0.651 seeds &middot; m &ndash;2 , and seeds were found throughout the top 4 cm of soil. Seed viability among sites ranged from 26% to 79%; however, no significant changes between depths were detected. The spatial distribution of the seed bank coincided with the current A. californica adult distribution only in sites with both a high plant density and high numbers of seeds. Arctomecon californica adults occupied open areas within the gypsum environment that supported significantly less vegetative cover than the surrounding area. We observed a positive association between A. californica adults and shadscale ( Atriplex confertifolia ) and a negative association with 7 other plant species among sites. Sites with an indurated abiotic crust hosted higher numbers of A. californica adults than sites with softer soils. However, rock cover, cryptogamic crust cover, and soil hardness were poor explanatory factors for characterizing A. californica presence. We suggest that land managers should incorporate seed bank census into monitoring programs due to the extreme year-to-year fluctuations in A. californica plant population densities. A menudo la protecci&oacute;n de especies de plantas des&eacute;rticas en peligro de extinci&oacute;n se ve complicada por la falta de informaci&oacute;n sobre las semillas, la etapa de vida m&aacute;s abundante y resistente al estr&eacute;s. Estudiamos la ubicaci&oacute;n relativa de semillas y plantas de &ldquo;Las Vegas bearpoppy&rdquo; ( Arctomecon californica ), una planta perenne en peligro de extinci&oacute;n, en 7 sitios de 1 ha. localizados al azar dentro de un &aacute;rea de estudio de 100 ha que estaba destinada a la urbanizaci&oacute;n en Las Vegas, Nevada (E.U.A.). Tambi&eacute;n medimos los atributos f&iacute;sicos y biol&oacute;gicos del ambiente que sostiene las semillas y plantas, tales como dureza del suelo, rocosidad, cobertura de costra crypt&oacute;gama y vegetaci&oacute;n asociada. La densidad de semillas de A. californica fue 0.651 semillas &middot; m &ndash;2 y se observ&oacute; en los 4 cm superiores del suelo. La viabilidad de las semillas vari&oacute; del 26% al 79% entre los sitios; sin embargo, no detectamos cambios significativos entre profundidades. La distribuci&oacute;n espacial del banco de semillas coincidi&oacute; con la distribuci&oacute;n actual de adultos de A. californica, s&oacute;lo en sitios que tuvieron una alta densidad de plantas y altos n&uacute;meros de semillas. Los adultos de A. californica ocuparon &aacute;reas abiertas dentro del ambiente de yeso que sosten&iacute;a significativamente menos cobertura vegetal que las &aacute;reas circunvecinas. Observamos una asociaci&oacute;n positiva entre los adultos de A. californica y el chamizo ( Atriplex confertifolia ) y una asociaci&oacute;n negativa con siete otras especies de plantas entre sitios. Los sitios con una costra abi&oacute;tica endurecida albergaron m&aacute;s adultos de A. californica que los sitios con suelos m&aacute;s blandos. No obstante, la cubierta rocosa, la costra crypt&oacute;gama y la dureza del suelo fueron inadecuadas como factores para caracterizar la presencia de A. californica. Sugerimos que los manejadores de tierras deben incorporar censos de bancos de semillas en los programas de monitoreo, debido a las fluctuaciones extremas de un a&ntilde;o a otro en la densidad poblacional de A. californica. Normal 0 MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman";}