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11.
Summary The effect of thyroid deficiency and treatment with tri-iodothyronine (T3) on oxygen consumption by neonatal (6-day-old and 15-day-old) rat brain was examined using glutamate, -hydroxybutyrate, succinate and ascorbate+TMPD as substrates. The respiration rates decreased significantly in 15-day-old hypothyroid pups. Treatment of normal and of hypothyroid pups with T3 resulted in a significant increase in the respiration rate at both ages. Respiration rates with glucose as the substrate were not affected under these conditions. 相似文献
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INTRODUCTIONIn non-wet strength paper, cellulose fibres are held together by hydrogen bonds. In the presence of water, these hydrogen bonds break and paper integrity is lost. Typically, paper treated with wet strength resin retains at least 15% of the paper’s dry strength after complete wetting with water. Paper without resin retains only 2-7% of its dry strength on wetting. The wet strength paper keeps its integrity because of its chemistry. This chemistry also defends it in the pulper… 相似文献
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Stuart PE Nair RP Ellinghaus E Ding J Tejasvi T Gudjonsson JE Li Y Weidinger S Eberlein B Gieger C Wichmann HE Kunz M Ike R Krueger GG Bowcock AM Mrowietz U Lim HW Voorhees JJ Abecasis GR Weichenthal M Franke A Rahman P Gladman DD Elder JT 《Nature genetics》2010,42(11):1000-1004
We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10?11), one at FBXL19 (rs10782001, combined P = 9 × 10?1?) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10??). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 4 × 10??; and rs12586317, combined P = 6 × 1??) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 2 × 10??; and rs12586317, combined P = 1 × 10??). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10??). 相似文献
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Whipple predicted the existence of micrometeorites, small interplanetary particles which enter the Earth's atmosphere without being melted by frictional heating. During the past 2 yr, large numbers of micrometre sized stratospheric particles have been collected which are believed to be extraterrestrial, because their elemental compositions closely match those of primitive meteorites. We report here the detection of large concentrations of 4He in some of the particles. This not only suggests an exposure to solar wind, but also indicates that these particles are true micrometeorites in the sense that they were not strongly heated by entry into the atmosphere. Strong heating would have caused much of the helium to escape. 相似文献
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Sun LD Cheng H Wang ZX Zhang AP Wang PG Xu JH Zhu QX Zhou HS Ellinghaus E Zhang FR Pu XM Yang XQ Zhang JZ Xu AE Wu RN Xu LM Peng L Helms CA Ren YQ Zhang C Zhang SM Nair RP Wang HY Lin GS Stuart PE Fan X Chen G Tejasvi T Li P Zhu J Li ZM Ge HM Weichenthal M Ye WZ Zhang C Shen SK Yang BQ Sun YY Li SS Lin Y Jiang JH Li CT Chen RX Cheng J Jiang X Zhang P Song WM Tang J Zhang HQ Sun L Cui J Zhang LJ Tang B Huang F Qin Q Pei XP Zhou AM Shao LM Liu JL Zhang FY Du WD Franke A Bowcock AM Elder JT Liu JJ 《Nature genetics》2010,42(11):1005-1009
We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10??) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10?21) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10?3 and P = 7.9 × 10?3, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10?3 and P = 1.5 × 10?3, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis. 相似文献
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Turner DJ Miretti M Rajan D Fiegler H Carter NP Blayney ML Beck S Hurles ME 《Nature genetics》2008,40(1):90-95
Meiotic recombination between highly similar duplicated sequences (nonallelic homologous recombination, NAHR) generates deletions, duplications, inversions and translocations, and it is responsible for genetic diseases known as 'genomic disorders', most of which are caused by altered copy number of dosage-sensitive genes. NAHR hot spots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at four NAHR hot spots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been underascertained clinically, most notably that resulting from the duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren syndrome. 相似文献
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The ion selectivity of pumps and channels is central to their ability to perform a multitude of functions. Here we investigate the mechanism of the extraordinary selectivity of the human voltage-gated proton channel, H(V)1 (also known as HVCN1). This selectivity is essential to its ability to regulate reactive oxygen species production by leukocytes, histamine secretion by basophils, sperm capacitation, and airway pH. The most selective ion channel known, H(V)1 shows no detectable permeability to other ions. Opposing classes of selectivity mechanisms postulate that (1) a titratable amino acid residue in the permeation pathway imparts proton selectivity, or (2) water molecules 'frozen' in a narrow pore conduct protons while excluding other ions. Here we identify aspartate 112 as a crucial component of the selectivity filter of H(V)1. When a neutral amino acid replaced Asp?112, the mutant channel lost proton specificity and became anion-selective or did not conduct. Only the glutamate mutant remained proton-specific. Mutation of the nearby Asp?185 did not impair proton selectivity, indicating that Asp?112 has a unique role. Although histidine shuttles protons in other proteins, when histidine or lysine replaced Asp?112, the mutant channel was still anion-permeable. Evidently, the proton specificity of H(V)1 requires an acidic group at the selectivity filter. 相似文献
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Stouffer AL Acharya R Salom D Levine AS Di Costanzo L Soto CS Tereshko V Nanda V Stayrook S DeGrado WF 《Nature》2008,451(7178):596-599
The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers. 相似文献
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The response of human pleura in organ culture to asbestos 总被引:5,自引:0,他引:5