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91.
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.  相似文献   
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Triglochin maritima L. (arrow grass), an herbaceous perennial in the family Juncaginacea, is widely distributed in inland and coastal salt marshes of North America. Triglochin maritima seeds from a population growing in a salt marsh at Faust, Utah, were germinated at 4 temperature regimes (12-h night/12-h day, 5-15° C, 10-20° C, and 15-25° C) and 5 salinities (0, 100, 200, 300, 400, and 500 mol m -3 NaCl) to determine optimal conditions for germination and level of salt tolerance. Ungerminated seeds were returned to distilled water after 20 d to determine whether seeds could recover from salinity treatments. Maximum germination occurred in distilled water, and increases in NaCl concentration progressively inhibited seed germination. No seeds germinated at concentrations higher than 400 mol m -3 NaCl. A temperature regime of low night (5° C) and high day (25° C) temperature yielded maximum germination; all other temperature regimes significantly inhibited seed germination relative to this optimum. Recovery of germination was highest at 5-25° C and lowest at 5-15° C. Recovery of seed germination when seeds were transferred to distilled water from salt solutions was highest at 5-25° C (72%) for seeds exposed to the 500 mol m -3 NaCl pretreatment and significantly reduced at other temperature regimes. The recovery germination response indicates a synergistic inhibitory interaction effect on germination when seeds were exposed to high salinities at suboptimal thermoperiods.  相似文献   
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Wang YC  Khan Z  Kaschube M  Wieschaus EF 《Nature》2012,484(7394):390-393
During tissue morphogenesis, simple epithelial sheets undergo folding to form complex structures. The prevailing model underlying epithelial folding involves cell shape changes driven by myosin-dependent apical constriction. Here we describe an alternative mechanism that requires differential positioning of adherens junctions controlled by modulation of epithelial apical-basal polarity. Using live embryo imaging, we show that before the initiation of dorsal transverse folds during Drosophila gastrulation, adherens junctions shift basally in the initiating cells, but maintain their original subapical positioning in the neighbouring cells. Junctional positioning in the dorsal epithelium depends on the polarity proteins Bazooka and Par-1. In particular, the basal shift that occurs in the initiating cells is associated with a progressive decrease in Par-1 levels. We show that uniform reduction of the activity of Bazooka or Par-1 results in uniform apical or lateral positioning of junctions and in each case dorsal fold initiation is abolished. In addition, an increase in the Bazooka/Par-1 ratio causes formation of ectopic dorsal folds. The basal shift of junctions not only alters the apical shape of the initiating cells, but also forces the lateral membrane of the adjacent cells to bend towards the initiating cells, thereby facilitating tissue deformation. Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding.  相似文献   
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JP Ebran  E Khan  T Nikšić  D Vretenar 《Nature》2012,487(7407):341-344
Nucleonic matter displays a quantum-liquid structure, but in some cases finite nuclei behave like molecules composed of clusters of protons and neutrons. Clustering is a recurrent feature in light nuclei, from beryllium to nickel. Cluster structures are typically observed as excited states close to the corresponding decay threshold; the origin of this phenomenon lies in the effective nuclear interaction, but the detailed mechanism of clustering in nuclei has not yet been fully understood. Here we use the theoretical framework of energy-density functionals, encompassing both cluster and quantum liquid-drop aspects of nuclei, to show that conditions for cluster formation can in part be traced back to the depth of the confining nuclear potential. For the illustrative example of neon-20, we show that the depth of the potential determines the energy spacings between single-nucleon orbitals in deformed nuclei, the localization of the corresponding wavefunctions and, therefore, the degree of nucleonic density clustering. Relativistic functionals, in particular, are characterized by deep single-nucleon potentials. When compared to non-relativistic functionals that yield similar ground-state properties (binding energy, deformation, radii), they predict the occurrence of much more pronounced cluster structures. More generally, clustering is considered as a transitional phenomenon between crystalline and quantum-liquid phases of fermionic systems.  相似文献   
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The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.  相似文献   
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