A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.     

Further details concerning the Darwin–Wallace presentation to the Linnean Society in 1858, including its submission on 1 July,not 30 June

Evidence from the Linnean Society’s ledger of papers received in 1858 points to 1 July as the date of submission of the Darwin–Wallace papers for the famous meeting of the same evening. It has been widely assumed, and repeatedly stated, that the submission was on 30 June. but this article shows that this seems to be a wrong assumption. Acceptance of this later submission date also provides an explanation of the ‘oddities’ in the letter of transmittal. In turn, this reading implies further details about the separate roles of Hooker and Lyell in the crucial 13 days before the meeting.     

CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR

Centromere-binding protein B (CENP-B) is a widely conserved DNA binding factor associated with heterochromatin and centromeric satellite repeats. In fission yeast, CENP-B homologues have been shown to silence long terminal repeat (LTR) retrotransposons by recruiting histone deacetylases. However, CENP-B factors also have unexplained roles in DNA replication. Here we show that a molecular function of CENP-B is to promote replication-fork progression through the LTR. Mutants have increased genomic instability caused by replication-fork blockage that depends on the DNA binding factor switch-activating protein 1 (Sap1), which is directly recruited by the LTR. The loss of Sap1-dependent barrier activity allows the unhindered progression of the replication fork, but results in rearrangements deleterious to the retrotransposon. We conclude that retrotransposons influence replication polarity through recruitment of Sap1 and transposition near replication-fork blocks, whereas CENP-B counteracts this activity and promotes fork stability. Our results may account for the role of LTR in fragile sites, and for the association of CENP-B with pericentromeric heterochromatin and tandem satellite repeats.     

Gravity modes as a way to distinguish between hydrogen- and helium-burning red giant stars

Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ～ 50 seconds) and those that are also burning helium (period spacing ～ 100 to 300 seconds).     

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan

Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.     

Geobacter metallireducens accesses insoluble Fe(III) oxide by chemotaxis

Microorganisms that use insoluble Fe(III) oxide as an electron acceptor can have an important function in the carbon and nutrient cycles of aquatic sediments and in the bioremediation of organic and metal contaminants in groundwater. Although Fe(III) oxides are often abundant, Fe(III)-reducing microbes are faced with the problem of how to access effectively an electron acceptor that can not diffuse to the cell. Fe(III)-reducing microorganisms in the genus Shewanella have resolved this problem by releasing soluble quinones that can carry electrons from the cell surface to Fe(III) oxide that is at a distance from the cell. Here we report that another Fe(III)-reducer, Geobacter metallireducens, has an alternative strategy for accessing Fe(III) oxides. Geobacter metallireducens specifically expresses flagella and pili only when grown on insoluble Fe(III) or Mn(IV) oxide, and is chemotactic towards Fe(II) and Mn(II) under these conditions. These results suggest that G. metallireducens senses when soluble electron acceptors are depleted and then synthesizes the appropriate appendages to permit it to search for, and establish contact with, insoluble Fe(III) or Mn(IV) oxide. This approach to the use of an insoluble electron acceptor may explain why Geobacter species predominate over other Fe(III) oxide-reducing microorganisms in a wide variety of sedimentary environments.     

Disruption of fragmented parent bodies as the origin of asteroid families

Asteroid families are groups of small bodies that share certain orbit and spectral properties. More than 20 families have now been identified, each believed to have resulted from the collisional break-up of a large parent body in a regime where gravity controls the outcome of the collision more than the material strength of the rock. The size and velocity distributions of the family members provide important constraints for testing our understanding of the break-up process, but erosion and dynamical diffusion of the orbits over time can erase the original signature of the collision. The recently identified young Karin family provides a unique opportunity to study a collisional outcome almost unaffected by orbit evolution. Here we report numerical simulations modelling classes of collisions that reproduce the main characteristics of the Karin family. The sensitivity of the outcome of the collision to the internal structure of the parent body allows us to show that the family must have originated from the break-up of a pre-fragmented parent body, and that all large family members formed by the gravitational reaccumulation of smaller bodies. We argue that most of the identified asteroid families are likely to have had a similar history.     

Motion-induced spatial conflict

Borders defined by small changes in brightness (luminance contrast) or by differences in colour (chromatic contrast) appear to move more slowly than those defined by strong luminance contrast. As spatial coding is influenced by motion, if placed in close proximity, the different types of moving border might appear to drift apart. Using this configuration, we show here that observers instead report a clear illusory spatial jitter of the low-luminance-contrast boundary. This visible interaction between motion and spatial-position coding occurred at a characteristic rate (approximately 22.3 Hz), although the stimulus motion was continuous and invariant. The jitter rate did not vary with the speed of movement. The jitter was not due to small involuntary movements of the eyes, because it only occurred at a specific point within the stimulus, the low-luminance-contrast boundary. These findings show that the human visual system contains a neural mechanism that periodically resolves the spatial conflict created by adjacent moving borders that have the same physical but different perceptual speeds.