Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods-recursive partitioning and regression-to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; P(combined) = 2.01 x 10(-19) and 2.35 x 10(-13), respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes.     

Occultation of X-rays from Scorpius X-1 by small trans-neptunian objects

Since the discovery of the trans-neptunian objects (TNOs) in 1992, nearly one thousand new members have been added to our Solar System, several of which are as big as--or even larger than--Pluto. The properties of the population of TNOs, such as the size distribution and the total number, are valuable information for understanding the formation of the Solar System, but direct observation is only possible for larger objects with diameters above several tens of kilometres. Smaller objects, which are expected to be more abundant, might be found when they occult background stars, but hitherto there have been no definite detections. Here we report the discovery of such occultation events at millisecond timescales in the X-ray light curve of Scorpius X-1. The estimated sizes of these occulting TNOs are < or =100 m. Their abundance is in line with an extrapolation of the distribution of sizes of larger TNOs.     

Nest-site characteristics of Burrowing Owls ( Athene cunicularia ) in the Snake River Birds of Prey National Conservation Area, Idaho, and application to artificial burrow installation

Burrowing Owl ( Athene cunicularia ) populations are declining in many portions of their range, and research and management efforts into stemming declines are underway. One tool with promise is the artificial burrow, which can supplement nesting opportunities and play a role in research, mitigation, translocation, and reintroduction studies. However, few studies directly assess important burrow and surrounding topographic features upon which owls choose sites and then construct and install artificial burrows accordingly. In this study we (1) measure physical, vegetative, and topographic characteristics of Burrowing Owl nest sites in the Snake River Birds of Prey National Conservation Area (SRBPNCA); (2) compare used and unused burrows to determine features important in nest-site selection; and (3) use this information to help guide current and future construction and placement of artificial burrows in the SRBPNCA. Owls nested in abandoned American badger ( Taxidea taxus ) burrows in areas with more than one burrow, close to roads and irrigated agricultural fields, and characterized by sparse and low vegetation dominated by nonnative plant species. Only one feature studied, tunnel entrance angle, corresponded with choice by owls; odds of burrow use decreased 17% with each 1° increase in slope of the tunnel entrance. Owls nesting near irrigated agricultural fields also had higher productivity. We discuss applications of our results to construction and placement of artificial burrows in the SRBPNCA and similar shrub-steppe environs in western North America.     

Conformational entropy in molecular recognition by proteins

Molecular recognition by proteins is fundamental to almost every biological process, particularly the protein associations underlying cellular signal transduction. Understanding the basis for protein-protein interactions requires the full characterization of the thermodynamics of their association. Historically it has been virtually impossible to experimentally estimate changes in protein conformational entropy, a potentially important component of the free energy of protein association. However, nuclear magnetic resonance spectroscopy has emerged as a powerful tool for characterizing the dynamics of proteins. Here we employ changes in conformational dynamics as a proxy for corresponding changes in conformational entropy. We find that the change in internal dynamics of the protein calmodulin varies significantly on binding a variety of target domains. Surprisingly, the apparent change in the corresponding conformational entropy is linearly related to the change in the overall binding entropy. This indicates that changes in protein conformational entropy can contribute significantly to the free energy of protein-ligand association.     

Linear processing of spatial cues in primary auditory cortex.

To determine the direction of a sound source in space, animals must process a variety of auditory spatial cues, including interaural level and time differences, as well as changes in the sound spectrum caused by the direction-dependent filtering of sound by the outer ear. Behavioural deficits observed when primary auditory cortex (A1) is damaged have led to the widespread view that A1 may have an essential role in this complex computational task. Here we show, however, that the spatial selectivity exhibited by the large majority of A1 neurons is well predicted by a simple linear model, which assumes that neurons additively integrate sound levels in each frequency band and ear. The success of this linear model is surprising, given that computing sound source direction is a necessarily nonlinear operation. However, because linear operations preserve information, our results are consistent with the hypothesis that A1 may also form a gateway to higher, more specialized cortical areas.