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Genetic background influences loss of heterozygosity patterns in radiation-induced mouse thymic lymphoma. 遗传背景影响辐射诱导的小鼠胸腺淋巴瘤杂合性模式的丧失。
Pub Date : 2015-01-01
Michael Hang, Yurong Huang, Antoine M Snijders, Jian-Hua Mao

Previous studies have revealed that p53 heterozygous (p53+/-) mice are extremely susceptible to radiation-induced tumorigenesis. To investigate whether genetic background influences radiation induced tumor susceptibility, we crossed p53+/- 129/Sv mice with genetically diverse strains to generate p53+/- F1 hybrids. The results showed that genetic background had a profound impact on tumor latency after exposure to gamma radiation, while the tumor spectrum did not change. We further characterized the thymic lymphomas that arose in the p53+/- mice by genome-wide loss of heterozygosity (LOH) analyses and found that genetic background strongly influenced the frequency of LOH and the loss of which parental allele on different chromosomes. Further research is needed to identify which genetic variations control the LOH patterns in radiation-induced thymic lymphomas and to evaluate its relevance to human cancers.

先前的研究表明,p53杂合(p53+/-)小鼠对辐射诱导的肿瘤发生极为敏感。为了研究遗传背景是否影响辐射诱导的肿瘤易感性,我们将p53+/- 129/Sv小鼠与遗传多样性的菌株杂交,产生p53+/- F1杂种。结果表明,遗传背景对γ辐射照射后的肿瘤潜伏期有深远影响,而肿瘤谱没有改变。我们通过全基因组杂合性缺失(LOH)分析进一步描述了p53+/-小鼠中出现的胸腺淋巴瘤,发现遗传背景强烈影响LOH的频率和不同染色体上亲本等位基因的缺失。需要进一步的研究来确定哪些遗传变异控制辐射诱导的胸腺淋巴瘤的LOH模式,并评估其与人类癌症的相关性。
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引用次数: 0
Increasing Influenza Vaccination Rates in a Busy Urban Clinic. 在繁忙的城市诊所提高流感疫苗接种率。
Pub Date : 2015-01-01
Rebecca C Pierson, Anita M Malone, David M Haas

Influenza infection is the cause of thousands of hospitalizations and deaths each year; infection during pregnancy results in increased morbidity and mortality. Underserved women are particularly susceptible to not receiving recommended vaccinations. This project explored the effect of a simple paper based prompt on the influenza vaccination rate in a resident continuity clinic for the underserved. Using this reminder to providers to discuss the influenza vaccination with their patients, we were able to increase vaccination rates in our clinic from 2.2% to 14.2%. This implementation of a simple, low cost, low tech prompt to providers increased the rate of influenza vaccination in our clinic and we present this approach as an easy to implement method of improving vaccination rates. We also suggest this method as an alternative to an alert in the electronic medical record in situations where the electronic medical record may not be accessed during every patient encounter.

流感感染每年导致数千人住院和死亡;孕期感染会增加发病率和死亡率。医疗服务不足的妇女尤其容易得不到推荐的疫苗接种。本项目探讨了在为未得到充分服务的居民提供的连续性诊所中,基于纸张的简单提示对流感疫苗接种率的影响。通过提醒医疗服务提供者与患者讨论流感疫苗接种问题,我们将诊所的疫苗接种率从 2.2% 提高到了 14.2%。这种向医疗服务提供者提供简单、低成本、低技术含量提示的方法提高了我们诊所的流感疫苗接种率,我们将这种方法作为一种易于实施的提高疫苗接种率的方法加以介绍。我们还建议,在每次接诊病人时都无法访问电子病历的情况下,可以用这种方法替代电子病历中的提示。
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引用次数: 0
Learning and memory during aggression in Drosophila: handling affects aggression and the formation of a "loser" effect. 果蝇攻击过程中的学习和记忆:处理影响攻击和“失败者”效应的形成。
Pub Date : 2015-01-01
Severine Trannoy, Edward A Kravitz

Aggressive behavior in Drosophila melanogaster serves to acquire or defense vital resources such as food, territory or access to mates. Flies learn from previous fighting experience and modify and adapt their behavior to new situations, suggesting that learning and memory play a major role in agonistic encounters. Prior fighting experience influences the outcome of later contests: losing a fight increases the probability of losing second contests, revealing the formation of a "loser" effect. In a recent publication, we developed a new behavioral arena that eliminates handling of flies prior to, during and after fights to study the learning and memory associated with aggression. We compared two handling procedures commonly used in laboratories to study aggression with the new chambers and demonstrated that handling negatively influences aggression and prevents "loser" effect formation. In addition, we observed new aspects of behavior such as the formation of robust winner effects.

黑腹果蝇的攻击行为是为了获取或保护重要资源,如食物、领土或获得配偶的机会。苍蝇从以前的战斗经验中学习,并根据新的情况修改和调整自己的行为,这表明学习和记忆在对抗中起着重要作用。先前的战斗经验会影响后来的比赛结果:输掉一场比赛会增加输掉第二次比赛的可能性,揭示了“失败者”效应的形成。在最近发表的一篇文章中,我们开发了一个新的行为领域,消除了在战斗之前,期间和之后处理苍蝇的方法,以研究与攻击相关的学习和记忆。我们比较了实验室中常用的两种处理方法,用新的实验室研究了攻击行为,并证明了处理对攻击行为有负面影响,并防止了“失败者”效应的形成。此外,我们还观察到行为的新方面,如形成稳健的赢家效应。
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引用次数: 0
LIF is a new p53 negative regulator. LIF是一种新的p53负调控因子。
Pub Date : 2015-01-01
Juan Liu, Haiyang Yu, Wenwei Hu

Leukemia inhibitory factor (LIF), a cytokine that belongs to the interleukin-6 family, regulates multiple important biological functions. Recently, we found that LIF is an important negative regulator of p53 in human colorectal cancer cells. LIF negatively regulates p53 protein levels and functions by activation of the Stat3 signaling pathway, which in turn induces the expression of ID1, the helix-loop-helix (HLH) protein inhibitor of differentiation and DNA binding. ID1 increases MDM2 expression at both mRNA and protein levels to accelerate p53 protein degradation. Overexpression of LIF increases chemoresistance of cultured colorectal cancer cells and colorectal xenograft tumors in a largely p53-dependent manner. Furthermore, LIF is overexpressed in a large percentage of human colorectal cancer specimens and LIF overexpression is associated with a poor prognosis in colorectal cancer patients. Our study revealed a new role of LIF in tumorigenesis through regulation of the p53 signaling pathway.

白血病抑制因子(Leukemia inhibitory factor, LIF)是一种属于白细胞介素-6家族的细胞因子,调节多种重要的生物学功能。最近,我们发现在人类结直肠癌细胞中,LIF是p53的重要负调控因子。LIF通过激活Stat3信号通路负向调节p53蛋白水平和功能,进而诱导分化和DNA结合的螺旋-环-螺旋(HLH)蛋白抑制剂ID1的表达。ID1在mRNA和蛋白水平上增加MDM2的表达,加速p53蛋白降解。LIF的过表达在很大程度上以p53依赖的方式增加了培养的结直肠癌细胞和结直肠癌异种移植肿瘤的化疗耐药。此外,在很大比例的人类结直肠癌标本中,LIF过表达,并且LIF过表达与结直肠癌患者预后不良有关。我们的研究揭示了LIF通过调控p53信号通路在肿瘤发生中的新作用。
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引用次数: 0
The temporal specific role of WNT/β-catenin signaling during myogenesis. WNT/β-连环蛋白信号在肌发生过程中的时间特异性作用。
Pub Date : 2015-01-01
Akiko Suzuki, Anne Scruggs, Junichi Iwata

Disruption of WNT/β-catenin signaling causes muscle developmental defects. However, it has been unclear how WNT/β-catenin signaling regulates each step of myogenesis. The in vitro culture of primary myoblasts and C2C12 cells (a myoblast cell line) has the ability to differentiate into myofibers in culture with differentiation inducers. These in vitro systems are useful to investigate each step of muscle development, ranging from cell proliferation to homeostasis, under the control of experimental conditions. Our recent study shows that WNT/β-catenin signaling can regulate myogenesis in a temporal specific manner by controlling the gene expression of cyclin A2 (Ccna2) and cell division cycle 25C (Cdc25c) during myoblast proliferation and fermitin family homolog 2 (Fermt2) during myoblast fusion and differentiation, respectively. In the well-differentiated myofibers, WNT/β-catenin signaling plays a role in the maintenance of their structure through a cadherin/β-catenin/actin complex formation, which is important for connecting a myofiber's cytoskeleton to the surrounding extracellular matrix. Thus, our recent study coupled with previous findings indicates that WNT/β-catenin signaling regulates myogenesis in a variety of ways, and any failure of these steps of myogenesis causes muscle developmental defects.

WNT/β-连环蛋白信号的破坏导致肌肉发育缺陷。然而,目前尚不清楚WNT/β-catenin信号如何调节肌生成的每一步。原代成肌细胞和C2C12细胞(一种成肌细胞系)的体外培养在分化诱导剂的培养下具有向肌纤维分化的能力。这些体外系统有助于在实验条件的控制下研究肌肉发育的每一步,从细胞增殖到体内平衡。我们最近的研究表明,WNT/β-catenin信号可以通过控制成肌细胞增殖过程中细胞周期蛋白A2 (Ccna2)和细胞分裂周期25C (Cdc25c)的基因表达以及成肌细胞融合和分化过程中fermittin家族同源物2 (Fermt2)的基因表达,以时间特异性的方式调节肌发生。在分化良好的肌纤维中,WNT/β-catenin信号通过钙粘蛋白/β-catenin/肌动蛋白复合物的形成在维持肌纤维结构中发挥作用,这对于将肌纤维的细胞骨架与周围的细胞外基质连接非常重要。因此,我们最近的研究结合先前的发现表明,WNT/β-catenin信号以多种方式调节肌肉发生,任何这些肌肉发生步骤的失败都会导致肌肉发育缺陷。
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引用次数: 0
Advances in Theory of Solid-State Nuclear Magnetic Resonance. 固态核磁共振理论研究进展》。
Pub Date : 2015-01-01
Eugene S Mananga, Jalil Moghaddasi, Ajaz Sana, Andrew Akinmoladun, Mostafa Sadoqi

Recent advances in theory of solid state nuclear magnetic resonance (NMR) such as Floquet-Magnus expansion and Fer expansion, address alternative methods for solving a time-dependent linear differential equation which is a central problem in quantum physics in general and solid-state NMR in particular. The power and the salient features of these theoretical approaches that are helpful to describe the time evolution of the spin system at all times are presented. This review article presents a broad view of manipulations of spin systems in solid-state NMR, based on milestones theories including the average Hamiltonian theory and the Floquet theory, and the approaches currently developing such as the Floquet-Magnus expansion and the Fer expansion. All these approaches provide procedures to control and describe the spin dynamics in solid-state NMR. Applications of these theoretical methods to stroboscopic and synchronized manipulations, non-synchronized experiments, multiple incommensurated frequencies, magic-angle spinning samples, are illustrated. We also reviewed the propagators of these theories and discussed their convergences. Note that the FME is an extension of the popular Magnus Expansion and Average Hamiltonian Theory. It aims is to bridge the AHT to the Floquet Theorem but in a more concise and efficient formalism. Calculations can then be performed in a finite-dimensional Hilbert space instead of an infinite dimensional space within the so-called Floquet theory. We expected that the FME will provide means for more accurate and efficient spin dynamics simulation and for devising new RF pulse sequence.

固态核磁共振(NMR)理论的最新进展,如 Floquet-Magnus 扩展和 Fer 扩展,解决了解决与时间相关的线性微分方程的替代方法,这是量子物理学,特别是固态 NMR 的核心问题。文章介绍了这些理论方法的威力和突出特点,它们有助于描述自旋系统在任何时候的时间演化。这篇综述文章基于包括平均哈密顿理论和 Floquet 理论在内的里程碑式理论,以及目前正在发展的 Floquet-Magnus 扩展和 Fer 扩展等方法,对固态 NMR 中的自旋系统操作进行了广泛的介绍。所有这些方法都提供了控制和描述固态 NMR 自旋动力学的程序。我们说明了这些理论方法在频闪和同步操作、非同步实验、多不相容频率、魔角旋转样品中的应用。我们还回顾了这些理论的传播者,并讨论了它们的趋同性。请注意,FME 是流行的马格努斯展开理论和平均哈密顿理论的延伸。它的目的是以一种更简洁、更高效的形式连接平均哈密顿理论和弗洛克定理。这样,计算就可以在有限维的希尔伯特空间中进行,而不是在所谓的 Floquet 理论的无限维空间中进行。我们预计,FME 将为更精确、更高效的自旋动力学模拟和设计新的射频脉冲序列提供手段。
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引用次数: 0
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