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101.
Verhoeven VJ Hysi PG Saw SM Vitart V Mirshahi A Guggenheim JA Cotch MF Yamashiro K Baird PN Mackey DA Wojciechowski R Ikram MK Hewitt AW Duggal P Janmahasatian S Khor CC Fan Q Zhou X Young TL Tai ES Goh LK Li YJ Aung T Vithana E Teo YY Tay W Sim X Rudan I Hayward C Wright AF Polasek O Campbell H Wilson JF Fleck BW Nakata I Yoshimura N Yamada R Matsuda F Ohno-Matsui K Nag A McMahon G Pourcain BS Lu Y Rahi JS Cumberland PM Bhattacharya S Simpson CL Atwood LD Li X Raffel LJ Murgia F Portas L 《Human genetics》2012,131(9):1467-1480
Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87?×?10(-12) for SNP rs634990 in Caucasians, and 9.65?×?10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20?×?10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95?% CI 1.64, 2.16, P?0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95?% CI 1.19, 1.49, P?0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81?×?10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide. 相似文献
102.
In northwestern Iberia, two largely allopatric Lacerta lepida mitochondrial lineages occur, L5 occurring to the south of Douro River and L3 to the north, with a zone of putative secondary contact in the region of the Douro River valley. Cytochrome b sequence chromatograms with polymorphisms at nucleotide sites diagnostic for the two lineages were detected in individuals in the region of the Douro River and further north within the range of L3. We show that these polymorphisms are caused by the presence of four different numts (I-IV) co-occurring with the L3 genome, together with low levels of heteroplasmy. Two of the numts (I and II) are similar to the mitochondrial genome of L5 but are quite divergent from the mitochondrial genome of L3 where they occur. We show that these numts are derived from the mitochondrial genome of L5 and were incorporated in L3 through hybridization at the time of secondary contact between the lineages. The additional incidence of these numts to the north of the putative contact zone is consistent with an earlier postglacial northward range expansion of L5, preceding that of L3. We show that genetic exchange between the lineages responsible for the origin of these numts in L3 after secondary contact occurred prior to, or coincident with, the northward expansion of L3. This study shows that, in the context of phylogeographic analysis, numts can provide evidence for past demographic events and can be useful tools for the reconstruction of complex evolutionary histories. 相似文献
103.
104.
David J. Leibly Trang Nhu Nguyen Louis T. Kao Stephen N. Hewitt Lynn K. Barrett Wesley C. Van Voorhis 《PloS one》2012,7(12)
Insoluble recombinant proteins are a major issue for both structural genomics and enzymology research. Greater than 30% of recombinant proteins expressed in Escherichia coli (E. coli) appear to be insoluble. The prevailing view is that insolubly expressed proteins cannot be easily solubilized, and are usually sequestered into inclusion bodies. However, we hypothesize that small molecules added during the cell lysis stage can yield soluble protein from insoluble protein previously screened without additives or ligands. We present a novel screening method that utilized 144 additive conditions to increase the solubility of recombinant proteins expressed in E. coli. These selected additives are natural ligands, detergents, salts, buffers, and chemicals that have been shown to increase the stability of proteins in vivo. We present the methods used for this additive solubility screen and detailed results for 41 potential drug target recombinant proteins from infectious organisms. Increased solubility was observed for 80% of the recombinant proteins during the primary and secondary screening of lysis with the additives; that is 33 of 41 target proteins had increased solubility compared with no additive controls. Eleven additives (trehalose, glycine betaine, mannitol, L-Arginine, potassium citrate, CuCl2, proline, xylitol, NDSB 201, CTAB and K2PO4) solubilized more than one of the 41 proteins; these additives can be easily screened to increase protein solubility. Large-scale purifications were attempted for 15 of the proteins using the additives identified and eight (40%) were prepared for crystallization trials during the first purification attempt. Thus, this protocol allowed us to recover about a third of seemingly insoluble proteins for crystallography and structure determination. If recombinant proteins are required in smaller quantities or less purity, the final success rate may be even higher. 相似文献
105.
Shao L Hewitt M Jerussi TP Wu F Malcolm S Grover P Fang K Koch P Senanayake C Bhongle N Ribe S Bakale R Currie M 《Bioorganic & medicinal chemistry letters》2008,18(5):1674-1680
Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. O-Alkyl, N-desmethyl, and non-phenol containing derivatives of tramadol were synthesized to probe their effect on metabolic stability and both in vitro and in vivo potency. 相似文献
106.
J Ellis V CummingsJ Hewitt S ThrushA Norkko 《Journal of experimental marine biology and ecology》2002,267(2):147-174
The horse mussel Atrina zelandica (Gray) is a large, suspension feeding pinnid bivalve, common in coastal and estuarine areas of northern New Zealand. As a suspension feeder, Atrina is likely to be influenced by suspended sediment loads. We conducted a laboratory experiment to determine the effect of short-term elevations in turbidity levels, such as those commonly recorded during storms, on the physiological condition and clearance rates of Atrina. We also conducted a field survey and a 3-month transplant experiment at multiple sites along a gradient of increasing suspended sediment load in a New Zealand estuary. Laboratory clearance rates of Atrina declined above a threshold suspended sediment concentration, and Atrina physiological condition at the end of this experiment was lower in high cf. low turbidity treatments. Decreases in Atrina condition were detected after exposure to elevated levels for only 3 days. The field survey and transplant experiment provided empirical evidence of a strong, negative effect of increasing suspended sediment flux on the physiological condition of Atrina. We suggest that relationships between the physiological condition of suspension feeders and sediment settling flux could provide a link between sediment inputs, which commonly occur as a result of catchment runoff during rainfall events, and the ecological health of estuarine and shallow coastal areas. Our study also demonstrated that Atrina have a natural distribution limit controlled by suspended sediment load. Thus, there is potential for larger-scale functional and structural effects on benthic communities in estuarine and coastal areas with high rates of sedimentation. 相似文献
107.
108.
An interchange which raises chiasma frequency 总被引:2,自引:0,他引:2
G M Hewitt 《Chromosoma》1967,21(1):285-295
109.
β-Glucosidase, β-galactosidase, and cellulase were present in the alimentary canal of Hodotermes mossambicus workers, larvae, and soldiers. Chitinase was absent. The pH and temperature optima, Michaelis constants, and energies of activation of β-glucosidase and β-galactosidase were determined. The enzymes showed different characteristics in all three castes. Enzyme content was found to differ from one developmental stage to the next. The termites lost their intestinal symbionts when ecdysing and re-inoculation took place after ecdysis. 相似文献
110.