A second generation human haplotype map of over 3.1 million SNPs

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.     

Genome-wide detection and characterization of positive selection in human populations

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.     

Iterative Reconstruction for Transmission Tomography on GPU Using Nvidia CUDA

The iterative reconstruction algorithms for X-ray CT image reconstruction suffer from their high computational cost.Recently Nvidia releases common unified device architecture(CUDA),allowing developers to access to the processing power of Nvidia graphical processing units(GPUs),in order to perform general purpose computations.The use of the GPU,as an alternative computation platform,allows decreasing processing times,for parallel algorithms.This paper aims to demonstrate the feasibility of such an implement...     

Burrowing mechanics: burrow extension by crack propagation

Until now, the analysis of burrowing mechanics has neglected the mechanical properties of impeding, muddy, cohesive sediments, which behave like elastic solids. Here we show that burrowers can progress through such sediments by using a mechanically efficient, previously unsuspected mechanism--crack propagation--in which an alternating 'anchor' system of burrowing serves as a wedge to extend the crack-shaped burrow. The force required to propagate cracks through sediment in this way is relatively small: we find that the force exerted by the annelid worm Nereis virens in making and moving into such a burrow amounts to less than one-tenth of the force it needs to use against rigid aquarium walls.     

BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain

Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability of neurons in the dorsal horn of the spinal cord. Spinal microglia stimulated by ATP contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury. Signalling between microglia and neurons is therefore an essential link in neuropathic pain transmission, but how this signalling occurs is unknown. Here we show that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (E(anion)) in spinal lamina I neurons. This shift inverts the polarity of currents activated by GABA (gamma-amino butyric acid), as has been shown to occur after peripheral nerve injury. Applying brain-derived neurotrophic factor (BDNF) mimics the alteration in E(anion). Blocking signalling between BDNF and the receptor TrkB reverses the allodynia and the E(anion) shift that follows both nerve injury and administration of ATP-stimulated microglia. ATP stimulation evokes the release of BDNF from microglia. Preventing BDNF release from microglia by pretreating them with interfering RNA directed against BDNF before ATP stimulation also inhibits the effects of these cells on the withdrawal threshold and E(anion). Our results show that ATP-stimulated microglia signal to lamina I neurons, causing a collapse of their transmembrane anion gradient, and that BDNF is a crucial signalling molecule between microglia and neurons. Blocking this microglia-neuron signalling pathway may represent a therapeutic strategy for treating neuropathic pain.     

Alcaloïde des Canneberges du Nouveau-Brunswick

Summary A new alkaloid C₂₀H₂₂O₂N₂ (cannagunine) obtained from canadian Vaccinium Oxycoccus is shown to have structure 1. The structure of this compound was supported by NMR-, SM-, IR- and UV-spectra.     

Method of Stabilizing the Surface Energy of Fabrics Coated with Silicone

Silicone coatings have been used in this study. The method adopted was the liquid drop analysis on the coated fabrics. The contact angle between a liquid drop and the fabric surface was measured with two liquids continuously and recorded by a computer. The surface energy was calculated by means of Owens method. Kinetic measurement was adopted. The contact angle of liquids on the fabric coated silicone decreased with time was found. A compound solution DX has been found, so that the contact angle of the liquids on the fabric washed with DX becomes constant, and the surface energy of the fabric can be reduced to below 15 mJ/m2.     

Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain

Modern pain-control theory predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes. However, the nature of the mechanisms that underlie such disinhibition has remained controversial. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.