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标题: 中国农科院新成果 [打印本页]

作者: 镇州大萝卜 时间: 2013-5-5 10:07
标题: 中国农科院新成果

来自中国农业科学院的科学家们通过将来自H5N1病毒的基因，与2009年禽流感大流行H1N1病毒株的基因相融合，构建出了可通过空气在豚鼠之间传播的杂合流感病毒（hybrid flu viruse），相关研究结果发表在5月2日的《科学》（Science）杂志上。

　　Nature和Science网站都对这一研究成果表示高度关注，分别以“Scientists create hybrid flu that can go airborne”和“Single Gene Swap Helps Bird Flu Virus Switch Hosts”为题，第一时间对该研究进行了新闻报道。

　　新型H7N9禽流感病毒正在整个中国传播的事实让世界都为之震惊，中国农业科学院的这项新研究则提醒我们，另一种不同的禽流感病毒H5N1仍然可能造成大流行的威胁

　　当两种病毒株感染同一细胞，并进行基因交换之时，可能会自然发生流感病毒杂合。通过这一重组（reassortment）过程生成的病毒株，导致了过去至少三次流感大流行，其中包括2009年的那次禽流感大流行。

　　尽管没有证据表明H5N1和H1N1发生了自然重组，但它们有大量的机会这样做。这两种病毒的地理分布和感染的物种存在相互重叠，尽管H5N1大都倾向于在自身谱系内交换基因，但流行性H1N1病毒株却似乎特别容易发生重组。

　　该研究的领导者、中国农学院哈尔滨兽医研究所病毒学家陈化兰（Hualan Chen）说：“如果这些能在哺乳动物之间传播的H5N1病毒可自然生成，就极有可能发生大流行。”

　　“这是一项了不起的研究工作，清楚地表明了H5N1病毒株在亚洲和埃及持续的传播，将继续对人类和动物健康造成非常现实的威胁，”越南胡志明市牛津大学临床研究中心主任eremy Farrar,说。

　　对流感的恐惧

　　陈化兰的研究结果，有可能重新激起去年流感研究群体之间的争论。当时，有两个研究小组发现，如果H5N1病毒的血凝素（HA）编码基因发生某些突变，它就可以在空气中传播。这项研究工作引起了对于生物安全问题的激烈辩论，之后流感团体提出暂停一年的研究，防止生成更具传播力的病毒株。陈化兰的实验在暂停令生效之前就已全部完成，现在既然禁令已经解除，有望针对这一特性开展更多的研究工作。

　　Farrar说：“我相信，这样的研究是我们了解流感的关键。但这样的工作，在世界上的任何地方，都需要受到严格的监管，在已注册并通过国际通用标准认证的、最安全的设施中进行。”

此前病毒学家曾经构建出H5N1重组。一项研究发现，H5N1与一种H3N24流感病毒株重组时，不能生成可传染的杂合病毒。然而在2011年，St. Jude儿童研究医院的病毒学家Stacey Schultz-Cherry证实，如果流行性H1N1携带来自H5N1的HA基因会变得更具毒力。　　陈化兰研究小组将来自H5N1和H1N1的7个基因片段在每种可能的组合中进行了融合和匹配，生成了127种重组病毒，所有病毒都携带H5N1的HA基因。其中一些杂合病毒可以通过空气在笼子相邻的豚鼠之间传播，它们携带着来自H1N1的PA (polymerase acidic，酸性聚合酶蛋白)和/或NS（non-structural protein，非结构蛋白）基因。另外两个来自H1N1的基因， NA（神经氨酸酶）和M（基质蛋白）在较小的程度上促进了空气传播，而NP（核蛋白）基因联合PA也促进了空气传播。　　Schultz-Cherry说：“这是一篇具有广泛意义的论文。它确实地表明了，不仅HA，其他的蛋白也非常重要，能够推动病毒传播。”陈化兰认为，卫生组织应该监控野生病毒，看看是否存在她们在最新研究中鉴别的基因组合。“如果发现这些类型的重组，我们需要予以高度重视。　　认识缺口　　目前还不清楚这些结果是否适用于人类。豚鼠的上呼吸道除了具有哺乳动物受体蛋白，还具有鸟样的受体蛋白，因此相比在人体中，重组病毒有可能更容易于豚鼠体内结合。　　科学家们也不知道杂合病毒是否和亲代H5N1一样致命。这些杂合病毒并没有杀死它们传播的任何一只豚鼠，但陈化兰认为，这些啮齿动物并不是好的人类致病性模型。　　还有一种可能就是，流行性H1N1病毒株发生全球性传播，实际上可能让人们产生了一些免疫对抗其与H5N1重组，从而降低了未来大流行的风险。在早些时候的一项研究中，陈化兰和同事们证实，由流行性H1N1制成的一种疫苗可为小鼠提供保护，对抗H5N1感染。　　Schultz-Cherry 说：“如果你从已接种疫苗或自然感染的人群处获取到抗体，那它们是否能与这些病毒产生交叉反应？这是一项需要去完成的重要研究。”　　不过，陈化兰研究组现在正忙于应对新出现的H7N9禽流感病毒威胁。关于H5N1的研究还需等待。

作者: 镇州大萝卜 时间: 2013-5-5 10:13
本帖最后由镇州大萝卜于 2013-5-5 10:18 编辑

Scientists create hybrid flu that can go airborne
H5N1 virus with genes from H1N1 can spread through the air between mammals.

Ed Yong
02 May 2013

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Researchers have crossed two strains of avian flu virus to create one that can be transmitted through the air — and possibly settle on the cilia of lung cells as in this conceptual image.

As the world is transfixed by a new H7N9 bird flu virus spreading through China, a study reminds us that a different avian influenza — H5N1 — still poses a pandemic threat.

A team of scientists in China has created hybrid viruses by mixing genes from H5N1 and the H1N1 strain behind the 2009 swine flu pandemic, and showed that some of the hybrids can spread through the air between guinea pigs. The results are published in Science1.

Flu hybrids can arise naturally when two viral strains infect the same cell and exchange genes. This process, known as reassortment, produced the strains responsible for at least three past flu pandemics, including the one in 2009.

There is no evidence that H5N1 and H1N1 have reassorted naturally yet, but they have many opportunities to do so. The viruses overlap both in their geographical range and in the species they infect, and although H5N1 tends mostly to swap genes in its own lineage, the pandemic H1N1 strain seems to be particularly prone to reassortment.

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“If these mammalian-transmissible H5N1 viruses are generated in nature, a pandemic will be highly likely,” says Hualan Chen, a virologist at the Harbin Veterinary Research Institute of the Chinese Academy of Sciences, who led the study.

“It's remarkable work and clearly shows how the continued circulation of H5N1 strains in Asia and Egypt continues to pose a very real threat for human and animal health,” says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

Flu fears
Chen's results are likely to reignite the controversy that plagued the flu community last year, when two groups found that H5N1 could go airborne if it carried certain mutations in a gene that produced a protein called haemagglutinin (HA)2, 3. Following heated debate over biosecurity issues raised by the work, the flu community instigated a voluntary year-long moratorium on research that would produce further transmissible strains. Chen’s experiments were all finished before the hiatus came into effect, but more work of this nature can be expected now that the moratorium has been lifted.

“I do believe such research is critical to our understanding of influenza,” says Farrar. “But such work, anywhere in the world, needs to be tightly regulated and conducted in the most secure facilities, which are registered and certified to a common international standard.”

Virologists have created H5N1 reassortants before. One study found that H5N1 did not produce transmissible hybrids when it reassorts with a flu strain called H3N24. But in 2011, Stacey Schultz-Cherry, a virologist at St. Jude Children's Research Hospital in Memphis, Tennessee, showed that pandemic H1N1 becomes more virulent if it carries the HA gene from H5N15.

Chen’s team mixed and matched seven gene segments from H5N1 and H1N1 in every possible combination, to create 127 reassortant viruses, all with H5N1’s HA gene. Some of these hybrids could spread through the air between guinea pigs in adjacent cages, as long as they carried either or both of two genes from H1N1 called PA and NS. Two further genes from H1N1, NA and M, promoted airborne transmission to a lesser extent, and another, the NP gene, did so in combination with PA.

“It’s a very extensive paper,” says Schultz-Cherry. “It really shows that it’s more than just the HA. The other proteins are just as important and can drive transmission.” Chen says that health organisations should monitor wild viruses for the gene combinations that her team identified in the latest study. “If those kinds of reassortants are found, we’d need to pay high attention.”

Knowledge gap
It is unclear how the results apply to humans. Guinea pigs have bird-like receptor proteins in their upper airways in addition to mammalian ones, so reassortant viruses might bind in them more easily than they would in humans.

And scientists do not know whether the hybrid viruses are as deadly as the parent H5N1. The hybrids did not kill any of the guinea pigs they spread to, but Chen says that these rodents are not good models for pathogenicity in humans.

There is also a chance that worldwide exposure that already occurred to the pandemic H1N1 strain might actually mitigate the risk of a future pandemic by providing people with some immunity against reassortants with H5N1. In an earlier study, Chen and her colleagues showed that a vaccine made from pandemic H1N1 provided some protection against H5N1 infections in mice6.

“If you take [antibodies] from people who have been vaccinated or naturally infected, will they cross-react with these viruses?” asks Schultz-Cherry. “That’s an important study that would need to be done.”

Ironically, Chen’s team is now too busy reacting to the emerging threat of a different bird flu — H7N9. Research on H5N1 will have to wait.

Nature doi:10.1038/nature.2013.12925

作者: 镇州大萝卜 时间: 2013-5-5 10:15
Borrowing a single gene from a human influenza strain can make a dangerous strain of bird flu easily transmissible between guinea pigs, researchers report in a paper published online today in Science. The scientists conclude that there is a substantial risk that the strain, H5N1, which so far has not infected many people, could touch off a pandemic.

The paper is another example of so-called gain-of-function studies, a controversial field in which researchers deliberately manipulate viruses in ways that can make them more dangerous. Flu scientists argue that such studies are needed to better gauge pandemic risks—in this case, from H5N1, which has caused massive outbreaks in poultry and wild birds in Asia, Africa, and Europe since 2003. More than 600 people have also become infected—and more than half of them have died. But in almost all cases, their infection was due to contact with sick birds. H5N1 does not transmit efficiently from person to person. If it develops a way to do so, scientists say that a pandemic would be virtually inevitable.

Last year, controversial papers published by influenza scientists Yoshihiro Kawaoka of the University of Wisconsin, Madison, in Nature, and Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, in Science suggested that a few mutations in H5N1 sufficed to make the virus transmissible through coughing and sneezing between ferrets, the most widely used animal model for flu. The researchers interpreted the results as a sign that the same mutations might cause the strain to go pandemic. Most of the changes were in hemagglutinin, a protein on the viral surface, and they made the protein a better fit for human receptors, their entry point into cells. Publication of both papers was delayed because a U.S. biosecurity panel recommended against publishing them in full; it later reversed its opinion.

Chen Hualan of China's Harbin Veterinary Research Institute took a different approach. Instead of focusing on mutations in the hemagglutinin gene, she wondered whether H5N1 might become pandemic by picking up entire genes from H1N1, the human influenza strain that first swept the globe in 2009. The flu genome consists of eight gene segments that strains can readily swap; this exchange can happen, for instance, when a person or an animal is infected with both strains.

For the study, Chen's team created 127 hybrids, or reassortants, in which H5N1 had anywhere between one and seven gene segments from H1N1. They then took the most pathogenic hybrids—based on tests in mice—and gauged whether these composite viruses would transmit between guinea pigs that didn't have direct contact but were housed in adjoining cages, a common setup to test whether a virus can be spread by respiratory droplets through the air. To their surprise, introducing either the H1N1 gene for the polymerase enzyme or the gene for the so-called nonstructural protein was sufficient to cause airborne transmission. Several other H1N1 genes didn't do the trick by themselves but added to the effect if they came along.

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作者: 镇州大萝卜 时间: 2013-5-5 10:21
看到这个词：crossed——h1n1和h5n1跨界，好象比艺术家们跨界让人恐慌多了……

作者: 镇州大萝卜 时间: 2013-5-20 09:46
据《自然》杂志网站报道，来自美国新罕布什尔大学的华人数学家张益唐日前证明，存在无穷多个之差小于7000万的素数对，从而在解决孪生素数猜想这一终极数论问题的道路上前进了一大步。

素数是指只可被1和其本身整除的数字。一般来说，两个相邻素数之间的间隔，会随着数字大小的增加而变得越来越大。但是，孪生素数，也就是之差仅为2的相邻素数，例如，3和5、17和19以及2003663613×2195000-1和2003663613×2195000+1却是例外。

关于孪生素数，数学界存在一个推测：存在无穷多对孪生素数。这被认为是最古老的开放性数学问题之一，由希腊数学家欧几里得提出。目前，多种试图证明该猜想的方法都不甚奏效。其中，一个重要里程碑是美国圣何塞州立大学数论教授Dan Goldston及两位同事提出，存在无穷多个之差小于16的素数对。但是，该推论尚不知如何证明。

在最新研究中，张益唐在不依赖未经证明推论的前提下，发现存在无穷多个之差小于7000万的素数对。

虽然7000万貌似一个非常大的数字，但不管数字多大，有限范围的存在意味着，相连素数之差并不是一直增长的。而且，从2到7000万的跨越，与7000万到无穷大的跨越不可同日而语。对此，Dan Goldston评论说：“每缩小一段范围，都是在获得终极答案的道路上踏上一个脚印。”

据悉，张益唐于5月13日在哈佛大学展示了最新研究。

作者: 镇州大萝卜 时间: 2013-5-20 09:47
本帖最后由镇州大萝卜于 2013-5-20 09:48 编辑

First proof that infinitely many prime numbers come in pairs
Mathematician claims breakthrough towards solving centuries-old problem.

Mathematician Yitang Zhang has outlined a proof of a 'weak' version of the twin prime conjecture.

It’s a result only a mathematician could love. Researchers hoping to get ‘2’ as the answer for a long-sought proof involving pairs of prime numbers are celebrating the fact that a mathematician has wrestled the value down from infinity to 70 million.

“That’s only [a factor of] 35 million away” from the target, quips Dan Goldston, an analytic number theorist at San Jose State University in California who was not involved in the work. “Every step down is a step towards the ultimate answer.”

That goal is the proof to a conjecture concerning prime numbers. Those are the whole numbers that are divisible only by one and themselves. Primes abound among smaller numbers, but they become less and less frequent as one goes towards larger numbers. In fact, the gap between each prime and the next becomes larger and larger — on average. But exceptions exist: the ‘twin primes’, which are pairs of prime numbers that differ in value by 2. Examples of known twin primes are 3 and 5, or 17 and 19, or 2,003,663,613 × 2195,000 − 1 and 2,003,663,613 × 2195,000 + 1.

The twin prime conjecture says that there is an infinite number of such twin pairs. Some attribute the conjecture to the Greek mathematician Euclid of Alexandria, which would make it one of the oldest open problems in mathematics.

The problem has eluded all attempts to find a solution so far. A major milestone was reached in 2005 when Goldston and two colleagues showed that there is an infinite number of prime pairs that differ by no more than 16 (ref. 1). But there was a catch. “They were assuming a conjecture that no one knows how to prove,” says Dorian Goldfeld, a number theorist at Columbia University in New York.

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The new result, from Yitang Zhang of the University of New Hampshire in Durham, finds that there are infinitely many pairs of primes that are less than 70 million units apart without relying on unproven conjectures. Although 70 million seems like a very large number, the existence of any finite bound, no matter how large, means that that the gaps between consecutive numbers don’t keep growing forever. The jump from 2 to 70 million is nothing compared with the jump from 70 million to infinity. “If this is right, I’m absolutely astounded,” says Goldfeld.

Zhang presented his research on 13 May to an audience of a few dozen at Harvard University in Cambridge, Massachusetts, and the fact that the work seems to use standard mathematical techniques led some to question whether Zhang could really have succeeded where others failed.

But a referee report from the Annals of Mathematics, to which Zhang submitted his paper, suggests he has. “The main results are of the first rank,” states the report, a copy of which Zhang provided to Nature. “The author has succeeded to prove a landmark theorem in the distribution of prime numbers. … We are very happy to strongly recommend acceptance of the paper for publication in the Annals.”

Goldston, who was sent a copy of the paper, says that he and the other researchers who have seen it “are feeling pretty good” about it. “Nothing is obviously wrong,” he says.

For his part, Zhang, who has been working on the paper since a key insight came to him during a visit to a friend’s house last July, says he expects that the paper’s mathematical machinery will allow for the value of 70 million to be pushed downwards. “We may reduce it,” he says.

Goldston does not think the value can be reduced all the way to 2 to prove the twin prime conjecture. But he says the very fact that there is a number at all is a huge breakthrough. “I was doubtful I would ever live to see this result,” he says.

Zhang will resubmit the paper, with a few minor tweaks, this week.

Nature doi:10.1038/nature.2013.12989

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