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81.
Zhang G Karns R Sun G Indugula SR Cheng H Havas-Augustin D Novokmet N Rudan D Durakovic Z Missoni S Chakraborty R Rudan P Deka R 《PloS one》2011,6(12):e29475
Background
Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia.Methodology/Principal Findings
In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20∼50 SNPs reported by the remaining individual GWA studies explained 3∼5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent.Conclusions/Significance
We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent. 相似文献82.
Chrisanthar R Knappskog S Løkkevik E Anker G Ostenstad B Lundgren S Risberg T Mjaaland I Skjønsberg G Aas T Schlichting E Fjösne HE Nysted A Lillehaug JR Lønning PE 《PloS one》2011,6(4):e19249
Background
TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP) T309G increases MDM2 activity and may reduce wild-type p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy.Experimental Design
Each patient was randomly assigned to treatment with epirubicin 90 mg/m2 (n = 109) or paclitaxel 200 mg/m2 (n = 114) every 3rd week as monotherapy for 4–6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy.Principal Findings
While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007) but also MDM2 309TG/GG genotype status (p = 0.012) were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039) but not among individuals with TP53 mutated tumors (p>0.5).Conclusion
TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy. 相似文献83.
84.
In the present work we report the variation in swimming speed ofVibrio cholerae with respect to the change in concentration of sodium ions in the medium. We have also studied the variation in swimming
speed with respect to temperature. We find that the swimming speed initially shows a linear increase with the increase of
the sodium ions in the medium and then plateaus. The range within which the swimming speed attains saturation is approximately
the same at different temperatures. 相似文献
85.
Aligned alpha helix peptide dipoles sum to a "macroscopic" dipole parallel to the helix axis that has been implicated in protein folding and function. However, in aqueous solution the dipole is counteracted by an electrostatic reaction field generated by the solvent, and the strength of the helix dipole may reduce drastically from its value in vacuum. Here, using atomic-detail helix models and Poisson-Boltzmann continuum electrostatics calculations, the net effective dipole moment, mu(eff), is calculated. Some initially surprising results are found. Whereas in vacuum mu(eff) increases with helix length, the opposite is found to be the case for transmembrane helices. In soluble proteins, mu(eff) is found to vary strongly with the orientation and position of the helix relative to the aqueous medium. A set of rules is established to estimate of the strength of mu(eff) from graphical inspection of protein structures. 相似文献
86.
Summary An efficient protocol for plant regeneration from stem segments of Murraya koenigii was developed by culturing on Murashige and Skoog (MS) medium supplemented with 2.5 mg l−1 benzyladenine (BA), 25 mgl−1 adenine sulfate, 0.25 mgl−1 indole-3-acetic acid (IAA), and 3% sucrose. The frequency of shoot bud regeneration was higher on similar medium in subsequent
subcultures. The regenerated shoots were rooted on half-strength basal MS medium supplemented with 0.25–0.5 mgl−1 IAA or 1-naphthaleneacetic acid (NAA) within 8–12 d of culture. The maximum percentage of rooting was obtained on MS medium
supplemented with IAA and NAA, each at 0.25 mgl−1. During acclimatization, 95% of rooted plantlets survived were grown normally under greenhouse conditions. 相似文献
87.
Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene 总被引:17,自引:0,他引:17
Zhang W Yang H Kong X Mohapatra S San Juan-Vergara H Hellermann G Behera S Singam R Lockey RF Mohapatra SS 《Nature medicine》2005,11(1):56-62
Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory tract infection for which no vaccine or antiviral treatment is available. The RSV NS1 protein seems to antagonize the host interferon (IFN) response; however, its mechanism is unknown. Here, we used a plasmid-borne small interfering RNA targeting the NS1 gene (siNS1) to examine the role of NS1 in modulating RSV infection. RSV replication was reduced in A549 cells, but not IFN-deficient Vero cells, transfected with siNS1. siNS1 induced upregulated expression of IFN-beta and IFN-inducible genes in A549 cells. siNS1-transfected human dendritic cells, upon RSV infection, produced elevated type-1 IFN and induced differentiation of naive CD4+ T cells to T helper type 1 (TH1) cells. Mice treated intranasally with siNS1 nanoparticles before or after infection with RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. Thus, siNS1 nanoparticles may provide an effective inhibition of RSV infection in humans. 相似文献
88.
Identified germplasm is an important component for efficient and effective management of plant genetic resources. Traditionally, cultivars or species identification has relied on morphological characters like growth habit or floral morphology like flower colour and other characteristics of the plant. Studies were undertaken for identification and analysis of genetic variation within 34 rose cultivars through random amplified polymorphic DNA (RAPD) markers. Analysis was made by using twenty five decamer primers. Out of twenty five, ten primers were selected and used for identification and analysis of genetic relationships among 34 rose cultivars. A total of 162 distinct DNA fragments ranging from 0.1 to 3.4 kb was amplified by using 10 selected random decamer primers. The genetic similarity was evaluated on the basis of presence or absence of bands. The cluster analysis indicated that the 34 rose cultivars form 9 clusters. The first cluster consists of eight hybrid cultivars, three clusters having five cultivars each, one cluster having four cultivars, two clusters having three cultivars each and two clusters having one cultivar each. The genetic distance was very close within the cultivars. Thus, these RAPD markers have the potential for identification of clusters and characterization of genetic variation within the cultivars. This is also helpful in rose breeding programs and provides a major input into conservation biology. 相似文献
89.
Protocorm like bodies (PLBs), callus and shoot buds developed in culture from in vitro raised foliar explants of Cleisostoma racimeferum. Among the different basal media, better result was obtained on MS medium containing sucrose (3%) and BA (2 microM) with approximately 80% frequency after 40 days of culture. Young leaves (15 week old) produced better PLBs. Whole leaf placed vertically upside-up orientation can regenerate PLBs and shoot buds (80%). PLBs and shoot buds formed on entire surface of the leaves. Cultures on BA and NAA (2 and 2 microM respectively in combination) stimulated callus mediated regeneration (68%). The rooted plantlets regenerated within 8-10 week from PLBs and shoot buds on MS medium containing IAA and kinetin (2 microM each in combination). BA containing medium triggered multiple shoot bud formation, while NAA alone or in combination with other growth regulators was inhibitory. Incorporation of activated charcoal (0.01%) in the medium stimulated formation of repetitive PLBs and multiple shoot buds. Rooted plants were ready for harvest after 20-22 week of initiation of culture. About 65% of the potted plants survived after 3 months in the poly house. 相似文献
90.
Swarup R Kramer EM Perry P Knox K Leyser HM Haseloff J Beemster GT Bhalerao R Bennett MJ 《Nature cell biology》2005,7(11):1057-1065
Re-orientation of Arabidopsis seedlings induces a rapid, asymmetric release of the growth regulator auxin from gravity-sensing columella cells at the root apex. The resulting lateral auxin gradient is hypothesized to drive differential cell expansion in elongation-zone tissues. We mapped those root tissues that function to transport or respond to auxin during a gravitropic response. Targeted expression of the auxin influx facilitator AUX1 demonstrated that root gravitropism requires auxin to be transported via the lateral root cap to all elongating epidermal cells. A three-dimensional model of the root elongation zone predicted that AUX1 causes the majority of auxin to accumulate in the epidermis. Selectively disrupting the auxin responsiveness of expanding epidermal cells by expressing a mutant form of the AUX/IAA17 protein, axr3-1, abolished root gravitropism. We conclude that gravitropic curvature in Arabidopsis roots is primarily driven by the differential expansion of epidermal cells in response to an influx-carrier-dependent auxin gradient. 相似文献