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101.
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《Vaccine》2020,38(14):2943-2948
Despite a critical need for a respiratory syncytial virus (RSV) vaccine and decades of development efforts, a vaccine to protect infants, elderly, and other at-risk populations from RSV infection remains elusive. We have previously generated a new, live-attenuated vaccine candidate against RSV using rational, computer-aided gene design and chemical synthesis through a process termed viral gene “deoptimization.” In this study, we assessed the attenuation, immunogenicity, and efficacy of this synthetic, live-attenuated RSV vaccine candidate, RSV-MinL4.0, in African Green Monkeys. RSV-MinL4.0 was produced under good-manufacturing-practice (GMP) in Vero cells. Vaccination with RSV-MinL4.0 resulted in minimal virus shedding after vaccination, generation of robust humoral and cellular immune responses (despite the presence of baseline RSV neutralizing antibodies in one animal) that were comparable to a wildtype infection, and protection from virus shedding post-challenge with wildtype RSV. These findings demonstrate the promise of RSV-MinL4.0 as a live-attenuated vaccine which will undergo clinical trials to test its ability to safely and effectively protect pediatric and elderly populations from infection with RSV. 相似文献
103.
甘露糖结合凝集素基因54号密码子多态性与川崎病易感性的研究 总被引:14,自引:0,他引:14
目的 探讨甘露糖结合凝集素 (MBL)基因第 5 4号密码子多态性与中国汉族儿童川崎病的易感性和临床表型的关系。方法 应用聚合酶链反应 限制性内切酶片段长度多态性分析 ,对16 0例中国汉族健康儿童及 95例川崎病患儿的MBL基因多态性进行检测。结果 ( 1)中国汉族健康儿童MBL基因多态性分布与文献报道的香港华人及高加索人种接近 ,无统计学差异。( 2 )川崎病患儿GAC等位基因频率高于健康对照组 ( 0 2 5 8vs 0 138,P <0 0 1) ,而GGC等位基因频率低于健康对照组 ( 0 74 2vs 0 86 2 ,P <0 0 1)。GAC型等位基因与中国汉族儿童川崎病密切相关 [OR =2 18,95 %CI(OR值的 95 %置信区间 )为 1 38~ 3 4 4 ,P <0 0 5 ]。 ( 3)在川崎病患儿中 ,GAC型等位基因携带者其病史有前驱感染史者多于GGC纯合子 (P <0 0 1)。结论 川崎病发病受遗传背景的影响 ,与MBL第 5 4号密码子基因多态性密切相关 相似文献
104.
目的:研究长链非编码RNA HOTAIRM1(lncRNA HOTAIRM1)与微小RNA-129-5p(miR-129-5p)的靶向关系及其对胶质瘤细胞增殖、迁移、侵袭的影响。 方法:荧光定量PCR(qPCR)检测HOTAIRM1和miR-129-5p在人正常脑组织和胶质瘤组织中的表达。建立抑制HOTAIRM1表达细胞株,研究其对U251细胞增殖、凋亡、迁移及侵袭的影响。MTT法检测细胞增殖;流式细胞仪检测细胞凋亡;Transwell小室法检测细胞迁移和侵袭;蛋白质印迹法(Western blot)检测细胞周期蛋白D1(Cyclin D1)、p21、B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)、上皮钙黏素(E-cadherin)、基质金属蛋白酶-2(MMP-2)水平。生物学信息预测和双荧光素酶报告基因法分析HOTAIRM1和miR-129-5p之间的靶向关系。共转染si-HOTAIRM1和anti-miR-129-5p,观察抑制miR-129-5p表达对抑制HOTAIRM1表达诱导的U251细胞增殖、凋亡、迁移及侵袭的影响。 结果:HOTAIRM1在胶质瘤组织中的表达明显上调(P<0.05),miR-129-5p表达下调(P<0.05)。抑制HOTAIRM1表达显著降低U251细胞24 h、48 h、72 h的细胞活性、迁移细胞数、侵袭细胞数及Cyclin D1、Bcl-2、MMP-2蛋白表达量(P<0.05),明显增加U251细胞凋亡率和p21、Bax、E-cadherin蛋白表达量(P<0.05)。miR-129-5p是HOTAIRM1的靶基因。上调或下调HOTAIRM1表达明显调控miR-129-5p表达(P<0.05)。抑制miR-129-5p表达逆转了抑制HOTAIRM1表达对U251细胞24 h、48 h、72 h的细胞活性、迁移细胞数、侵袭细胞数及Cyclin D1、MMP-2、Bcl-2蛋白表达的抑制作用,并逆转了抑制HOTAIRM1表达对U251细胞p21、E-cadherin、Bax蛋白表达和细胞凋亡率的促进作用。 结论:lncRNA HOTAIRM1通过靶向miR-129-5p影响胶质瘤细胞增殖、凋亡、迁移和侵袭。 相似文献
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107.
Peter J. Niedbalski Alexander S. Cochran Teckla G. Akinyi Robert P. Thomen Elizabeth M. Fugate Diana M. Lindquist Ronald G. Pratt Zackary I. Cleveland 《NMR in biomedicine》2020,33(7)
Fast apparent transverse relaxation (short T2*) is a common obstacle when attempting to perform quantitative 1H MRI of the lungs. While T2* times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous 129Xe), T2* can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T2* of HP 129Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi‐echo radial flyback imaging sequence and use it to measure HP 129Xe T2* at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T1 relaxation outside the animal by using multiple gradient‐refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the 129Xe T2* in vivo for 10 healthy C57Bl/6 J mice and found T2* ~ 5 ms in the lung airspaces. Interestingly, T2* was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O2 content of the inhaled gas mixture. These results are discussed in the context of T2* relaxation within porous media. 相似文献
108.
Elizabeth L. Adams Michele E. Marini Krista S. Leonard Danielle Symons Downs Ian M. Paul Jennifer L. Kraschnewski Kristen H. Kjerulff Jennifer S. Savage 《Women's health issues》2019,29(2):194-200
Introduction
Factors that occur between consecutive pregnancies may influence repeated excessive gestational weight gain (GWG) and infants born large-for-gestational age (LGA). We examined interpregnancy interval, weight retention, and GWG in women's first pregnancy as predictors of excessive GWG and LGA in women's second pregnancy.Methods
We used data from women's first two live births during the First Baby Study, a 3-year prospective observational cohort of first-time mothers (N = 549). GWG was calculated as weight at delivery minus prepregnancy weight for first and second pregnancies and categorized using the Institute of Medicine guidelines. Weight retention at 6 and 12 months and interpregnancy interval (time from first live birth to conception of second infant) were quantified. Infants were considered LGA if birthweight was in the 90th percentile or greater for gestational age.Results
Many women (51.7%) exceeded GWG recommendations in both pregnancies. Women who exceeded guidelines in their first pregnancy had a 5.08 greater odds (p < .01) for exceeding guidelines in their second pregnancy, compared with women who did not exceed guidelines in their first pregnancy. Interpregnancy interval and weight retention had no association with exceeding guidelines in women's second pregnancy. Exceeding guidelines in women's first pregnancy resulted in a 4.48 greater odds (p < .01) of first-born infants being LGA, and exceeding guidelines in women's second pregnancy resulted in a 1.82 greater odds of second-born infants being large-for-gestational age (p = .02), compared with women who met guidelines in their first or second pregnancy, respectively.Conclusions
Exceeding GWG guidelines in women's first pregnancy predicted exceeding guidelines in their second pregnancy, independent of interpregnancy interval and weight retention. 相似文献109.
110.
Kai Ruppert Jaime F Mata Hsuan-Tsung J Wang William A Tobias Gordon D Cates James R Brookeman Klaus D Hagspiel John P Mugler 《Magnetic resonance in medicine》2007,57(6):1099-1109
Xenon polarization Transfer Contrast (XTC) MRI pulse sequences permit the gas exchange of hyperpolarized xenon-129 in the lung to be measured quantitatively. However, the pulse sequence parameter values employed in previously published work were determined empirically without considering the now-known gas exchange rates and the underlying lung physiology. By using a theoretical model for the consumption of magnetization during data acquisition, the noise intensity in the computed gas-phase depolarization maps was minimized as a function of the gas-phase depolarization rate. With such optimization the theoretical model predicted an up to threefold improvement in precision. Experiments in rabbits demonstrated that for typical imaging parameter values the optimized XTC pulse sequence yielded a median noise intensity of only about 3% in the depolarization maps. Consequently, the reliable detection of variations in the average alveolar wall thickness of as little as 300 nm can be expected. This improvement in the precision of the XTC MRI technique should lead to a substantial increase in its sensitivity for detecting pathological changes in lung function. 相似文献