2.杰出研究成果展示
研究成果一：害怕和如何抗拒害怕
Researchers find underlying neurological mechanism for mediating fear response
A toddler may reach for a honeybee buzzing around a bright flower—but a child that has previously been stung by a bee may shrink from the insect. Humans, like all mammals, have dedicated circuits in their brains for expressing learned fearful behavior and for suppressing such fear.When something poses a threat or is painful, nerve cells in the brain’s basolateral amygdala (BLA) store that memory. Later, in similar circumstances, they can trigger fear-based behavior. If later experience repeatedly proves similar situations are not dangerous after all, then the original fear memory will typically be suppressed over time in a process called extinction learning.However, people suffering from post-traumatic stress disorder (PTSD) or other anxiety disorders may experience disabling recurrences of fear. By uncovering the precise mechanisms underlying fear memories and their suppression, researchers hope to find more effective treatments for such conditions.Now Leon Reijmers, an assistant professor of neuroscience, and his colleagues at Tufts School of Medicine and the Sackler School of Graduate Biomedical Sciences, have published findings in the journal Nature Neuroscience demonstrating that a particular type of BLA nerve cell, the PV interneuron, plays a key role in suppressing the neurons that store fear memories after fear extinction learning has occurred.The researchers were able to home in on the PV interneurons’ role by treating genetically modified mice, which had undergone fear extinction learning, with a chemogenetic agent that turned off these interneurons. Without functioning PV interneurons, the mice displayed fear behavior that had previously been extinguished.That finding confirmed a hypothesis proposed in Reijmers’ earlier work, but the researchers also made another, unexpected discovery: PV interneurons regulate an ongoing tug of war between a neural circuit that expresses fear memories and a competing circuit that extinguishes fear memories.When we recorded electrical activity in the BLA of our test mice, we saw brainwaves—or oscillations—at two different frequencies, each with a different relationship to fear expression. Oscillations around 4 Hz correlated with more fear behavior while oscillations around 8 Hz correlated with less fear, said Reijmers. Silencing the PV interneurons after fear extinction learning increased the activation of the fear-associated 3-6 Hz oscillation as well as increasing activation of the fear neurons. Our findings suggest that oscillatory activity could be a useful target for therapies to address disorders such as PTSD.First author on the paper is Patrick Davis, a fifth year student in the combined M.D./Ph.D. degree program offered by the Sackler School in conjunction with the School of Medicine, through a Medical Scientist Training Program grant from the National Institutes of Health. Other authors are Yosif Zaki, a Northeastern University undergraduate who was an intern in Reijmers’ lab, and Jamie Maguire, an assistant professor of neuroscience.We need a far better understanding of the basic mechanisms at work in the brain before we can start to apply them to treat disease, said Davis. While this type of work is many years away from being clinically beneficial, I firmly believe that collectively the neuroscience community can help patients who suffer from anxiety disorders.
一个蹒跚学步的孩子可能会在一朵明亮的花朵周围嗡嗡嗡嗡嗡嗡嗡呜呜呜呜呜呜呜呜呜呜呜呜呜呜呜呜呜呜，人类像所有的哺乳动物一样，在大脑中拥有专门的电路来表达学习的恐惧行为并抑制这种恐惧。当某些事物构成威胁或痛苦时，大脑的基底外侧杏仁核(BLA)中的神经细胞将存储该记忆。后来，在类似的情况下，他们可以触发恐惧行为。如果后来的经验反复证明，类似的情况毕竟不是危险的，那么在被称为灭绝学习的过程中，原来的恐惧记忆通常会随着时间的推移而被抑制。然而，患有创伤后应激障碍(PTSD)或其他焦虑症的人可能会遇到无法重复的恐惧。研究人员通过揭示恐惧记忆及其镇压的准确机制，希望找到更有效的治疗方法。现在，神经科学助理教授Leon Reijmers及其同事在塔夫茨医学院和萨克勒研究生生物医学科学院的研究人员发表了自然神经科学杂志的研究结果，证明了一种特殊类型的BLA神经细胞PV中枢神经元在恐惧灭绝学习发生后，抑制存储恐惧记忆的神经元的关键作用。研究人员通过用灭绝这些中间神经元的化学遗传剂处理经过恐怖灭绝学习的转基因小鼠，从而掌握了PV中间神经元的作用。没有功能的PV中间神经元，老鼠显示出以前已经熄灭的恐惧行为。这一发现证实了Reijmers 早期工作中提出的假设，但是研究人员还提出了另外一个意想不到的发现：PV中间神经元调节了表达恐惧记忆的神经回路与扑灭恐惧记忆的竞争电路之间持续的拔河。当我们在我们的测试小鼠的BLA中记录电活动时，我们看到脑电波或振荡 - 在两个不同的频率，每个与恐惧表达有不同的关系。约4 Hz的振荡与更多的恐惧行为相关，而8 Hz左右的振荡与较少的恐惧相关，Reijmers说。在恐惧灭绝学习后沉默PV中间神经元增加了与恐惧相关的3-6 Hz振荡的激活以及恐惧神经元的激活。我们的研究结果表明，振荡活动可能是治疗诸如PTSD等疾病的治疗的有用靶位。本文的第一作者是帕特里克·戴维斯(Patrick Davis)，MD / Ph.D组合是第五年学生。萨克勒学院与医学院合作，通过美国国立卫生研究院的医学科学家培训计划资助。其他作者是东芝大学本科生Yosif Zaki，他是Reijmers实验室的实习生，还有Jamie Maguire，神经科学助理教授。戴维斯说：我们需要更好地了解大脑工作中的基本机制，然后才能开始应用它们来治疗疾病。虽然这种类型的工作距离临床有益许多年，但我坚信，神经科学界可以共同帮助患有焦虑症的患者。
研究成果二：为了你的视力如何健康饮食
Age-related macular degeneration (AMD)—the leading cause of vision loss after age 50—can leave a person feeling powerless. Over months or years, AMD patients slowly lose their sight, moving ever closer to blindness. In most cases, there’s no cure, but a team at Tufts has found signs that arresting the disease may not require creating new drugs, but simply tweaking patients’ diets.Sheldon Rowan, a scientist in the Laboratory for Nutrition and Vision Research at the Human Nutrition Research Center on Aging at Tufts, said there are plenty of indications that the types of carbohydrates we eat play a role in the development of AMD. People who eat lots of simple carbohydrates, like those in white bread and sweetened beverages, are more likely to get the disease.This could be because simple carbs break down rapidly during digestion, creating a spike in blood sugar that can lead to widespread inflammation, a condition linked to AMD. Complex carbohydrates found in whole grains, however, break down more slowly, resulting in lower blood glucose. If that blood glucose stays low over a long period of time, Rowan said, it can lower incidence of AMD.To understand why, Rowan tested the two diets on laboratory mice. Over the course of a year, he fed one group of mice high-glycemic foods—ones with lots of simple starches. A second group got a low-glycemic diet, rich in complex carbs, but otherwise identical in calories and nutrients. In a third group, Rowan switched the mice’s diet from high- to low-glycemic foods halfway through the study.Sure enough, mice with the low-glycemic diet did not develop AMD, while mice fed the high-glycemic diet almost all came down with the disease, a result in keeping with previous research. In the mice that switched diets, though, Rowan saw something completely unexpected. Not only did they avoid AMD, but the existing damage to their retinas was reversed.No one had ever seen that before, Rowan said of the findings, which were reported in Proceedings of the National Academy of Sciences. The most common form of AMD doesn’t really have a treatment right now—but this suggests that just changing to a healthier eating pattern could have a huge impact.Exploring the reason behind the change, Rowan tested blood and urine samples from each group of mice. He found that those with high-glycemic diets also had high levels of molecules called advanced glycation end products (AGEs) in their bodies.AGEs are toxic end products of sugars, Rowan said. They can damage the proteins and lipids that a cell needs to function. In the retina, these damaged proteins slowly accumulate in a sort of cellular garbage pile, forming yellow deposits called drusen that destroy retinal cells.Rowan also identified certain chemicals, including serotonin, in the mice’s blood and urine that acted as markers for AMD. Because these chemicals have been linked to bacteria in the gut, Rowan wondered how microbes might be involved in AMD development. He reasoned that because simple carbohydrates are easy to digest, they are fully metabolized before entering the intestines and effectively starve microbes living deeper in the digestive tract. This could discourage the growth of protective bacteria, while allowing species that create inflammation and other stresses to thrive. After testing the levels of various bacteria living in each mouse’s gut, Rowan found some early evidence that may confirm this idea.There could be ‘good’ bacteria in the gut that are neuro-protective, and there could also be ‘bad’ bacteria, that are pro-inflammatory, he said. From this study, we can’t parse out good versus bad, but it does show us that molecules associated with gut bacteria are playing a role in AMD.Identifying those molecules could one day lead to new drug treatments. But until then, AMD patients may be able to improve their vision just by switching up their diet. This gives us a tremendous opportunity, said Tufts biochemist Allen Taylor, director of the Laboratory for Nutrition and Vision Research. In humans, this is the equivalent of switching out four or five slices of white bread each day for whole grains. It’s a minor alteration that will pay great benefits.Rowan added that the epidemiology is clear about these healthy-eating and dietary patterns protecting against AMD, he said. As a side effect, it’s also going to improve your cardiovascular health, diminish risk for diabetes and maybe even help you lose weight. There’s really no downside.
年龄相关性黄斑变性(AMD)——关于50岁以后视力丧失的主要原因让人感到无力。在过去的几个月或几年里，AMD的病人逐渐失去视力，越来越接近失明。在大多数情况下，没有治愈的方法，但是塔夫茨的一个研究小组发现，阻止这种疾病可能不需要制造新药，只是简单地调整病人的饮食。Sheldon Rowan是位于塔夫茨的人类营养研究中心的营养和视觉研究实验室的科学家，他说，有很多迹象表明，我们吃的碳水化合物在发展中扮演了一个角色。吃大量简单碳水化合物的人，如白面包和加糖饮料的人，更容易患这种疾病。这可能是因为简单的碳水化合物在消化过程中迅速分解，导致血糖升高，从而导致广泛的炎症，这是与AMD有关的一种疾病。然而，在全谷物中发现的复合碳水化合物分解得更慢，导致血糖降低。Rowan说，如果血糖在很长一段时间内保持在低水平，它可以降低AMD的发病率。为了理解为什么，Rowan在实验室老鼠身上测试了这两种饮食。在一年的时间里，他给了一组老鼠喂食高血糖指数食物，其中有许多简单的淀粉类食物。另一组人吃的是低糖饮食，富含复合碳水化合物，但在卡路里和营养方面却完全相同。在第三组中，Rowan在研究中把老鼠的饮食从高糖食物转变为低糖食物。果不其然，低糖饮食的老鼠并没有发展出AMD，而吃高糖食物的老鼠几乎都患上了这种疾病，这与之前的研究结果一致。然而，在那些改变饮食的老鼠中，Rowan看到了一些完全意想不到的事情。他们不仅避免了AMD，而且对他们的视网膜的损害也被逆转了。以前没有人见过这样的情况，Rowan说，这是在美国国家科学院院刊上发表的。最常见的AMD形式目前还没有真正的治疗，但这表明，只要改变健康饮食模式，就能产生巨大的影响。探索这一变化背后的原因，Rowan测试了每一组老鼠的血液和尿液样本。他发现，那些高血糖饮食的人体内也有高水平的分子，称为高级糖终产物(年龄)。Rowan说:年龄是糖的有毒成品。它们会破坏细胞需要功能的蛋白质和脂质。在视网膜中，这些受损的蛋白质慢慢积聚在一种细胞的垃圾堆里，形成一种叫做drusen的黄色沉积物，破坏视网膜细胞。Rowan还发现了一些化学物质，包括血清素，在老鼠的血液和尿液中，作为AMD的标记。由于这些化学物质与肠道内的细菌有关，Rowan想知道微生物可能如何参与到AMD的发展中。他解释说，因为简单的碳水化合物易于消化，它们在进入肠道之前就已经完全代谢了，并且有效地饿死了那些生活在消化道深处的微生物。这可能会阻碍保护细菌的生长，同时也会让那些产生炎症和其他压力的物种得以繁衍。在测试了每个老鼠肠道中各种细菌的水平后，Rowan发现了一些早期的证据，这可能证实了这一观点。他说:肠道内可能有一种具有神经保护功能的好细菌，也可能有坏细菌，它们是促炎症的。从这项研究中，我们无法分析出好与坏的关系，但它确实告诉我们，与肠道细菌有关的分子在AMD中起着重要作用。有朝一日，识别这些分子可能会导致新的药物治疗。但在此之前，AMD的病人可能通过改变他们的饮食来改善他们的视力。这给了我们一个巨大的机会，塔夫茨生物化学家艾伦泰勒说，他是营养和视觉研究实验室的主任。在人类中，这相当于每天换四到五片白面包吃全谷物。这是一个微小的改变，将会带来巨大的利益。Rowan还说，流行病学清楚地表明，这些健康饮食和饮食模式对AMD的保护是很明显的。作为副作用，它还能改善你的心血管健康，降低患糖尿病的风险，甚至还能帮助你减肥。没有缺点。
研究成果三：测量药物如何相互作用的新方法
Cancer, HIV and tuberculosis are among the many serious diseases that are frequently treated with combinations of three or more drugs, over months or even years. Developing the most effective therapies for such diseases requires understanding how combining drugs affects their efficacy.If drugs reinforce one another, that synergy may be enough to lower the doses required, potentially relieving side effects, reducing treatment time, and improving patient quality of life. But if drugs work against each other, efficacy will be reduced.Now researchers at Tufts, along with colleagues at Harvard University and Turkey’s Sabanci University, have developed a new method to measure how drugs act in combination. The new methodology is more efficient and less expensive than traditional testing, and provides a framework for systematic testing of any dose-dependent therapeutic agent.Identifying synergies early in the pre-clinical drug development process can help us prioritize drug combinations for further development, said Bree Aldridge, assistant professor of molecular biology and microbiology at Tufts School of Medicine and adjunct assistant professor of biomedical engineering. But studying such drug interactions is challenging because of the sheer number of combinations and the current method of measurement.Such testing has traditionally been done on pairs of drugs through a checkerboard methodology using an iPhone-sized plate containing a grid of tiny wells, typically 96 or 384 wells. A bacterium—or other target organism—is placed into each well along with a carefully calibrated dose of the two drugs in varying strengths. Bacterial growth in each well is measured to determine its response to the drugs.The complexity and cost of testing increase exponentially with the number of drugs being examined. To determine synergy of five drugs would require measuring 100,000 cell response combinations on 1,000 plates. As a result, combinations of more than two drugs—called high-order combinations—rarely undergo such testing.The new method, though, doesn’t require an exhaustive analysis of all cell behaviors in all possible dose combinations. Instead, in order to predict which high-order combinations are most likely to be synergistic, it targets only the most information-rich drug-dose combinations.In experiments using Mycobacterium tuberculosis, the bacterium that causes tuberculosis, Aldridge and her collaborators found that measuring only certain wells in the grid mirrored the results obtained by testing all the wells.Aldridge uses the analogy of assessing metropolitan rush hour traffic. Instead of monitoring traffic in every neighborhood and on every road, if you look at traffic at multiple key points—such as the Mass Turnpike and the airport tunnels in Boston—you’ll be able to get a pretty good picture of whether commuting will be a breeze or a nightmare.The new proof-of-concept study, recently reported in the journal Science Advances, analyzed pairwise and combination interactions among nine drugs now used against M. tuberculosis. Aldridge, whose work merges molecular and mathematical approaches to the study of mycobacteria, hopes to test additional drugs in future studies of the method, which is dubbed DiaMOND (diagonal measurement of n-way drug interactions).The paper’s first and co-corresponding author along with Aldridge is Murat Cokol, former visiting scientist in the Aldridge laboratory and the Laboratory of Systems Pharmacology (LSP) based at the Harvard University School of Medicine, where Aldridge is also an investigator. Other authors are Nurdan Kuru, of Sabanci University in Turkey; Ece Bicak, who formerly worked with Cokol at LSP; and Jonah Larkins-Ford, a Ph.D. student in molecular biology and microbiology at the Sackler School of Graduate Biomedical Sciences at Tufts.Aldridge stresses that drug synergy should be only one consideration in developing effective patient therapies. Synergies observed in the lab are not always associated with optimum clinical treatments, she said.For example, it may make sense to include less synergistic combinations in a regimen in order to help combat drug resistance. But, she added, DiaMOND can play an important role by enabling us to do a much better job of identifying potentially valuable synergies among candidate drugs in the pipeline.Kim Thurler is former executive director of the Office of Public Relations at Tufts University.
如果药物彼此强化，那么协同作用可能足以降低所需剂量，可能减轻副作用，减少治疗时间，提高患者生活质量。但如果药物相互作用，效果会降低。现在，塔夫茨大学的研究人员以及哈佛大学和土耳其萨班奇大学的同事已经开发出一种新的方法来衡量药物的联合作用。新方法比传统测试更有效率和更便宜，并为任何剂量依赖性治疗剂的系统测试提供了框架。塔夫茨医学院分子生物学和微生物学助理教授，生物医学工程兼职助理教授Bree Aldridge说：鉴于临床前药物开发过程早期的协同作用可以帮助我们优先考虑药物组合进一步发展。但是研究这种药物相互作用是有挑战性的，因为组合的数量和当前的测量方法。这种测试传统上是通过棋盘方法使用含有一个小孔的通常为96或384孔的iPhone尺寸的板进行的。将细菌或其他目标生物体与仔细校准的剂量的两种不同强度的药物一起放入每个孔中。测量每个孔中的细菌生长以确定其对药物的反应。测试的复杂性和成本随着被检查药物的数量呈指数增长。为了确定五种药物的协同作用，需要测量1000个板上的100,000个细胞反应组合。结果，两种以上药物(称为高级组合)的组合很少经历这种测试。然而，新方法不需要对所有可能的剂量组合中的所有细胞行为进行详尽的分析。相反，为了预测哪些高阶组合最有可能是协同增效的，它只针对最多信息丰富的药物 - 剂量组合。在使用结核分枝杆菌的实验中，导致结核病的细菌，阿尔德里奇和她的合作者发现，仅测量电网中的某些井反映了通过测试所有井获得的结果。阿尔德里奇使用评估大都市高峰时段交通的类比。而不是监测每个社区和每条路上的交通流量，如果您在多个关键点(如大众收费公路和波士顿的机场隧道)查看交通流量，您将可以获得一个很好的图像，说明是否上下班是微风或噩梦。新的证据的概念研究，最近在杂志上报道的科学进展，分析了中现在用而9种药物两两组合和相互作用的结核分枝杆菌。阿尔德里奇的工作将分子和数学方法融合到分枝杆菌研究中，希望在将来研究的方法中测试其他药物，该方法被称为DiaMOND(n-way药物相互作用的对角线测量)。该文件与Aldridge的第一个和共同作者是Murat Cokol，Aldridge实验室的前访问科学家和位于哈佛大学医学院的系统药理学实验室，Aldridge也是研究者。其他作者是土耳其萨班奇大学的Nurdan Kuru; Ece Bicak，曾在Cokol在LSP工作; 和Jonah Larkins-Ford博士 塔克夫斯萨克勒生物医学研究生学院的分子生物学和微生物学学士学位。阿尔德里奇强调，药物协同作用应该是开发有效的患者治疗方法中唯一的考虑因素。实验室观察到的协同效应并不总是与最佳的临床治疗相关联，她说。例如，在方案中包括较少的协同组合可能是有意义的，以帮助抵抗耐药性。但是，她补充说：DiaMOND可以发挥重要作用，使我们能够更好地识别候选药物之间潜在的有价值的协同效应。金瑟勒是塔夫茨大学公共关系办公室的前执行主任。
四、校园环境(源自网络，非本网站翻译)
塔夫茨大学目前有四个校区，其中三个校区位于大波士顿地区，另有一个在美国南部。其主校区坐落于波士顿外的梅德福(Medford)与萨莫埃尔(Somerville)交界处，距离波士顿市中心仅8英里(约12公里)。主校区始建于1852年，其中包含了文理学院，工程学院，弗莱彻法律与外交学院。在主校区中，红砖绿树，相映成辉，曾被评为全美国最美丽的校园之一。牙医学院，医学院，弗里德曼营养科学与政策学院坐落于波士顿市中心的中国城(China Town)，一边与众多中国美食仅仅一步之遥，一边紧邻塔夫茨医学中心。所有在塔夫茨医学院拥有全职教职的老师，同时也承担医学院临床工作。在波士顿的西面的Grafton镇上有卡明斯兽医学院。最后在法国的Falloires，有一座被称为塔夫茨欧洲中心的卫星校区。该校园建于11世纪，于1958年由Donald MacJannet和他的妻子Charlotte购买，并于1978年捐赠给塔夫茨大学。塔夫茨是有小常春藤之称的大学之一，并被《新闻周刊》命名为25个新常春藤之一。 2010年8月，美丽的校园景色Unigo命名其为生机勃勃的十个新常春藤中的一个。在《普林斯顿评论》2010-2011年的最佳363高校中，塔夫茨在最快乐的学生的大学中排名#14，其海外留学项目在美国排名#3。根据2010年10月由高等教育纪事(The Chronicle of Higher Education)的排名，塔夫茨在富布赖特学者(Fulbright scholars)数量上全美排名第12(与哈佛大学和约翰霍普金斯大学并列)。塔夫茨大学的校友作为财富100强的CEO数量也名列全美第二(与宾夕法尼亚大学和达特茅斯学院并列)。由于其作为一个持续增长的学术机构，塔夫茨大学在近十年热门学校(hottest school of the decade)的评比中名列第五。
五、杰出校友(源自网络)
塔夫茨大学的校友在美国政府，媒体和商业届有显着位置：eBay创始人彼埃尔·奥米迪亚(Pierre Omidyar)，希腊前总理科斯塔斯·卡拉曼利斯(Kostas Karamanlis)，新墨西哥州州长比尔·理查森(Bill Richardson)，美国参议员斯科特·布朗(Scott Brown)，记者和电视名人梅勒迪斯·维埃拉(Meredith Vieira)，和纽约时报发行人小阿瑟·奥克斯·苏兹贝格(Arthur Ochs Sulzberger, Jr.)均毕业于塔夫茨大学。塔夫茨大学虽然没有商学院，却有三位校友担任财富50强公司的CEO：摩根大通首席执行官杰米·戴蒙(Jamie Dimon)，辉瑞制药首席执行官杰夫·金德勒(Jeff Kindler)，和杜邦公司的首席执行官艾伦库尔曼(Ellen J. Kullman)。
塔夫茨著名学者包括哲学家丹尼尔·丹尼特(Daniel Dennett)，美国朝鲜政策特别代表斯蒂芬·博斯沃思，前美国心理协会的主席罗伯特·斯腾伯格(Robert Sternberg)，普利策奖获奖者历史学家马丁·舍温(Martin J. Sherwin)，和诺贝尔物理学奖获得者阿伦·科马克(Allan M. Cormack)(1924年-1998年)。日本著名作家村上春树也曾在九十年代在塔夫茨大学任客座讲师。
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