科普知识学英语研究人员发现导致心力衰竭的关键因素

1、.Some 5.8 million Americans suffer from heart failure, a currently incurable disease. But scientists at Temple University School of Medicine's TUSM Center for Translational Medicine have discovered a key biochemical step underlying the condition that could aid the development of new drugs to tre

2、at and possibly prevent it. "Drugs we currently use for heart failure are not very effective," explained lead investigator Walter J. Koch, PhD, Professor and Chairman of the Department of Pharmacology at TUSM, and Director of the Center for Translational Medicine at TUSM. But, he added, &q

3、uot;The more we learn about the disease mechanism, the more drug targets we'll find." That is what Koch and colleagues at Thomas Jefferson University and the University of California, Davis, achieved in their latest study, which appears in the March 5 issue of the online journal PLOS O

4、NE. The report is the first to show that an enzyme called GRK5 G-protein coupled receptor kinase 5 can gain access to a heart cell's nucleus - its command center, where control of its genes is maintained - by way of a transport mechanism involving calcium and a protein known as calmodulin钙调

5、蛋白. Once calcium and calmodulin deliver GRK5 to the nucleus, the enzyme usurps夺取 control over specific genes, ultimately causing hypertrophy, in which heart cells grow larger in size. Hypertrophy is a biological hallmark of heart failure. GRK5 had previously been identified as a key p

6、layer in maladaptive cardiac hypertrophy, which is the end stage of heart failure, when the heart muscle becomes enlarged and unable to pump enough blood to keep vital organs functioning. While GRK5's ability to get inside the nucleus was known, Koch and colleagues worked to fill in the missing

7、links in its transport mechanism. Those links, they hope, will not only allow them to better understand GRK5's role in causing heart cells to increase in size but also find ways to block that process to more effectively treat heart failure. The GRK5 enzyme is a unique member of the GRK fami

8、ly, owing to its presence in the nucleus. Its journey begins at the cell membrane, where signals received by a molecule at the cell surface known as a Gq-coupled receptor prompt "escorts" - one of which is calmodulin, as the researchers discovered - to attach to GRK5 and guide it to the nu

9、cleus. The team found that GRK5's transport requires calmodulin after examining different places on the enzyme where various escort molecules attach. They then introduced mutations that altered the attachment sites. Only when calmodulin-binding residues剩余物 on GRK5 were mutated was

10、 the enzyme prevented from reaching the nucleus. Those mutations led to dramatic decreases in nuclear GRK5 levels and corresponding declines in the activity of genes known to drive cardiac hypertrophy. Calmodulin's ability to bind to GRK5 is in turn dependent on calcium. The same results were ob

11、tained both in vitro, using human heart muscle cells cultivated under laboratory conditions, and in vivo, in mice. The team's research also marks a breakthrough in scientists' understanding of the role of neurohormones in hypertrophy. Released by specialized neurons into the bloodstream

12、, neurohormones have long been cited as a cause of heart cell enlargement. "One of the novel findings to fall out of this paper is that not all hypertrophic signals from neurohormones are the same," Koch explained. "That's something to keep in mind as we move forward."&#

13、160;The next step, according to Koch, is to test the ability of different agents to keep GRK5 out of the nucleus. "We are now discussing a trial on inhibition of another cardiac GRK, GRK2," he said. He cautioned, however, that trials in patients with GRK5 inhibition are years away. First,

14、agents capable of blocking GRK5 transport must be identified and tested in animals. The work is an important advance for Temple's Center for Translational Medicine. GRK5 enters the pipeline of novel drug targets under investigation by the Center's scientists and clinicians, who share th

15、e common goal of coordinating clinical practice and basic research to speed the delivery of new therapies to patients. "It's another entry into larger, pre-clinical animal studies," Koch said. "Something new to start down the path of translational medicine."约达580万美国人患有心脏

16、衰竭，目前无法治愈的疾病。但在坦普尔大学医学院的TUSM转化医学中心的科学家们发现了一个关键的根本条件，可以帮助开发新的药物来治疗，并可能防止它的生化步骤。“我们目前使用的心脏衰竭的药物都不是很有效的，解释说：首席研究员沃尔特·科赫博士，药理学教研室教授兼TUSM，在TUSM转化医学研究中心主任。但是，他补充说，“我们更理解疾病的机制，我们会发现更多的药物靶标。 这是什么Koch和他的同事们在托马斯·杰斐逊大学和加州大学戴维斯分校，实现了在其最新的研究中，出如今3月5日出版的在线期刊PLoS ONE。该报告是说明一种酶叫做GRK5G-蛋白偶联受体激酶5可以访问到心

17、脏细胞的细胞核-指挥中心，保持其基因控制-方式传输机制涉及钙离子和钙调蛋白的蛋白质被称为钙调蛋白。一旦钙和钙调蛋白提供GRK5到细胞核，酶篡夺夺取控制特定基因，最终导致肥大，心脏细胞生长在规模较大。肥大是心脏衰竭的生物标志。 GRK5此前被确定为一个关键球员在适应不良的心肌肥厚，这是终末期心脏衰竭，心脏肌肉变得扩大，不能泵出足够的血液，以保持重要器官运作时。虽然GRK5的才能得到细胞核内是众所周知的，科赫和他的同事们的工作，以填补其传输机制的缺失环节。他们希望，这些链接，不仅可以让他们更好地理解GRK5的作用导致心脏细胞的大小增加，但也想方设法阻止这个过程中，更有效地治疗心脏衰竭。&

18、#160;GRK5的酶GRK家族成员是一个独特的，由于它的存在，在细胞核中。开场的行程中，其中接收的信号Gq蛋白偶联型受体作为提示“护送在细胞外表分子在细胞膜 - 其中之一是钙调蛋白，作为研究人员发现 - 附加到单次给予，并引导它到细胞核。这个工作可让学生分组负责搜集整理,登在小黑板上,每周一换。要求学生抽空抄录并且阅读成诵。其目的在于扩大学生的知识面,引导学生关注社会,热爱生活,所以内容要尽量广泛一些,可以分为人生、价值、理想、学习、成长、责任、友谊、爱心、探究、环保等多方面。如此下去,除假期外,一年便可以积累40多那么材料。假如学生的脑海里有了众多的鲜活生动的材料,写起文章来还用乱翻参考书

19、吗? 该研究小组发现，钙调素研究不同的地方后，对酶的各种护送分子附着，GRK5的交通需要。然后，他们介绍了突变，改变了附着点。只有当上GRK5的钙调蛋白结合的残基剩余物突变是酶无法到达细胞核。这些突变导致大幅度降低核GRK5的程度和相应的驱动心肌肥厚的基因的活性下降。钙调蛋白的结合才能GRK5是反过来又依赖于钙。得到同样的结果，无论是在体外，在实验室条件下培养人的心脏肌肉细胞，在体内，在小鼠。 该小组的研究也标志着科学家理解神经激素的作用，肥大的打破。由专门的神经元释放进入血液，神经激素早就被引用作为心脏细胞肿大的原因。 “掉出本文的新发现之一是，并非所有的肥厚性

20、神经激素的信号是一样的，科赫解释。“这件事情要记住，作为我们前进。 观察内容的选择，我本着先静后动，由近及远的原那么，有目的、有方案的先安排与幼儿生活接近的，能理解的观察内容。随机观察也是不可少的，是相当有趣的，如蜻蜓、蚯蚓、毛毛虫等，孩子一边观察，一边提问，兴趣很浓。我提供的观察对象，注意形象逼真，色彩鲜明，大小适中，引导幼儿多角度多层面地进展观察，保证每个幼儿看得到，看得清。看得清才能说得正确。在观察过程中指导。我注意帮助幼儿学习正确的观察方法，即按顺序观察和抓住事物的不同特征重点观察，观察与说话相结合，在观察中积累词汇，理解词汇，如一次我抓住时机，引导幼儿观察雷雨，雷雨前天空急

21、剧变化，乌云密布，我问幼儿乌云是什么样子的，有的孩子说：乌云像大海的波浪。有的孩子说“乌云跑得飞快。我加以肯定说“这是乌云滚滚。当幼儿看到闪电时，我告诉他“这叫电光闪闪。接着幼儿听到雷声惊叫起来，我抓住时机说：“这就是雷声隆隆。一会儿下起了大雨，我问：“雨下得怎样?幼儿说大极了，我就舀一盆水往下一倒，作比较观察，让幼儿掌握“倾盆大雨这个词。雨后，我又带幼儿观察晴朗的天空，朗读自编的一首儿歌：“蓝天高，白云飘，鸟儿飞，树儿摇，太阳公公咪咪笑。这样抓住特征见景生情，幼儿不仅印象深化，对雷雨前后气象变化的词语学得快，记得牢，而且会应用。我还在观察的根底上，引导幼儿联想，让他们与以往学的词语、生活经历联络起来，在开展想象力中开展语言。如啄木鸟的嘴是长长的，尖尖的，硬硬的，像医生用的手术刀样，给大树开刀治病。通过联想，幼儿可以生动形象地描绘观察对象。下一步，根据科克，以测试不