Chinese Academy of Sciences

Researchers use cryo-electron microscopy to learn how DNA wraps tightly around nucleosomes.

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A team of researchers working at the Chinese Academy of Sciences, in Beijing, has used cryo-electron microscopy to reveal how it is that DNA wraps so tightly around nuclesomes. In their paper published in the journal Science, the team describes how they managed to identify the path of linker DNA. Andrew Travers offers a Perspective piece in the same issue explaining the team’s findings and what it might mean for DNA research in the future.

Researchers use cryo-electron microscopy to learn how DNA wraps tightly around nucleosomes
DNA in eukaryote cells (those with a nucleus surrounded by a membrane) comes packaged inside of what are known as nucleosomes, which are materials made up primarily of histone proteins—together they form chromatin. Prior research has shown that nucleosomes exist (due to folding) as coiled structured helix shapes, approximately 30nm in diameter. Inside each helix is a “linker” histone—a fiber that runs the length of the helix. Up until now, the molecular makeup of the linker has been a bit of a mystery, with competing researchers suggesting different ideas. In this new effort, the researchers in China appear to have settled the debate using cryo-electron microscopy, a form of transition electron microscopy where the material being studied is kept at cryogenic temperatures. Examination by the team revealed the linker histone fiber to be constructed from arrays of 12 nucleosomes.
The arrayed nucleosomes constitute the longest segment of chromatin observed to date, and help explain how it is that genomes can be packaged, yet remain easily accessible. The researchers found that the linker histone (type H1) binds nucleosomes together into structures known as tetranucleosomal units—they in turn form double-helical structures similar to the DNA that they serve to package. The team notes that the binding that occurs results in stacking, which is how the double-helix is able to form.
This video demonstrates how nucleosomes compact into higher-order chromatin fibers and how the hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Credit: Institute of Biophysics, Chinese Academy of Sciences.
The findings by the research team point out the important role H1 linker histones play in stacking nucleosomes, which, they note, serves to make chromatin compact. They also note that nucleosomes can fold into other helical structures under different circumstances, which opens the door to other research efforts in the future. Also as Travers points out, their results lead to other questions, such as whether the structures they’ve uncovered correspond to the fiber in its natural state or if there are others. There’s also the question of what happens when the helix is unwound, does it cause changes to internucleosomal interactions? Finding answers to such questions will likely be the focus of the research team in China as well as others working in the field for many years to come.
Explore further: A specific ratio of DNA packaging proteins ensures normal gene expression during early embryonic development

ABSTRACT
The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom–resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.

Nobel winner declares boycott of top science journals.

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  • Randy Schekman
Randy Schekman, centre, at a Nobel prize ceremony in Stockholm. Photograph: Rob Schoenbaum/Zuma Press/Corbis

Leading academic journals are distorting the scientific process and represent a “tyranny” that must be broken, according to a Nobel prize winner who has declared a boycott on the publications.

Randy Schekman, a US biologist who won the Nobel prize in physiology or medicine this year and receives his prize in Stockholm on Tuesday, said his lab would no longer send research papers to the top-tier journals, Nature, Cell and Science.

Schekman said pressure to publish in “luxury” journals encouraged researchers to cut corners and pursue trendy fields of science instead of doing more important work. The problem was exacerbated, he said, by editors who were not active scientists but professionals who favoured studies that were likely to make a splash.

The prestige of appearing in the major journals has led the Chinese Academy of Sciences to pay successful authors the equivalent of $30,000 (£18,000). Some researchers made half of their income through such “bribes”, Schekman said in an interview.

Writing in the Guardian, Schekman raises serious concerns over the journals’ practices and calls on others in the scientific community to take action.

“I have published in the big brands, including papers that won me a Nobel prize. But no longer,” he writes. “Just as Wall Street needs to break the hold of bonus culture, so science must break the tyranny of the luxury journals.”

Schekman is the editor of eLife, an online journal set up by the Wellcome Trust. Articles submitted to the journal – a competitor to Nature, Cell and Science – are discussed by reviewers who are working scientists and accepted if all agree. The papers are free for anyone to read.

Schekman criticises Nature, Cell and Science for artificially restricting the number of papers they accept, a policy he says stokes demand “like fashion designers who create limited-edition handbags.” He also attacks a widespread metric called an “impact factor”, used by many top-tier journals in their marketing.

A journal’s impact factor is a measure of how often its papers are cited, and is used as a proxy for quality. But Schekman said it was “toxic influence” on science that “introduced a distortion”. He writes: “A paper can become highly cited because it is good science – or because it is eye-catching, provocative, or wrong.”

Daniel Sirkis, a postdoc in Schekman’s lab, said many scientists wasted a lot of time trying to get their work into Cell, Science and Nature. “It’s true I could have a harder time getting my foot in the door of certain elite institutions without papers in these journals during my postdoc, but I don’t think I’d want to do science at a place that had this as one of their most important criteria for hiring anyway,” he told the Guardian.

Sebastian Springer, a biochemist at Jacobs University in Bremen, who worked with Schekman at the University of California, Berkeley, said he agreed there were major problems in scientific publishing, but no better model yet existed. “The system is not meritocratic. You don’t necessarily see the best papers published in those journals. The editors are not professional scientists, they are journalists which isn’t necessarily the greatest problem, but they emphasise novelty over solid work,” he said.

Springer said it was not enough for individual scientists to take a stand. Scientists are hired and awarded grants and fellowships on the basis of which journals they publish in. “The hiring committees all around the world need to acknowledge this issue,” he said.

Philip Campbell, editor-in-chief at Nature, said the journal had worked with the scientific community for more than 140 years and the support it had from authors and reviewers was validation that it served their needs.

“We select research for publication in Nature on the basis of scientific significance. That in turn may lead to citation impact and media coverage, but Nature editors aren’t driven by those considerations, and couldn’t predict them even if they wished to do so,” he said.

“The research community tends towards an over-reliance in assessing research by the journal in which it appears, or the impact factor of that journal. In a survey Nature Publishing Group conducted this year of over 20,000 scientists, the three most important factors in choosing a journal to submit to were: the reputation of the journal; the relevance of the journal content to their discipline; and the journal’s impact factor. My colleagues and I have expressed concerns about over-reliance on impact factors many times over the years, both in the pages of Nature and elsewhere.”

Monica Bradford, executive editor at Science, said: “We have a large circulation and printing additional papers has a real economic cost … Our editorial staff is dedicated to ensuring a thorough and professional peer review upon which they determine which papers to select for inclusion in our journal. There is nothing artificial about the acceptance rate. It reflects the scope and mission of our journal.”

Emilie Marcus, editor of Cell, said: “Since its launch nearly 40 years ago, Cell has focused on providing strong editorial vision, best-in-class author service with informed and responsive professional editors, rapid and rigorous peer-review from leading academic researchers, and sophisticated production quality. Cell’s raison d’etre is to serve science and scientists and if we fail to offer value for both our authors and readers, the journal will not flourish; for us doing so is a founding principle, not a luxury.”

• This article was amended on 10 December 2013 to include a response from Cell editor Emilie Marcus, which arrived after the initial publication deadline.

Scientists unveil energy-generating window.

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Scientists in China said Thursday they had designed a “smart” window that can both save and generate energy, and may ultimately reduce heating and cooling costs for buildings.

Scientists unveil energy-generating window

While allowing us to feel close to the outside world, windows cause heat to escape from buildings in winter and let the Sun‘s unwanted rays enter in summer.

This has sparked a quest for “smart” windows that can adapt to weather conditions outside.

Today’s  are limited to regulating light and heat from the sun, allowing a lot of potential  to escape, study co-author Yanfeng Gao of the Chinese Academy of Sciences told AFP.

“The main innovation of this work is that it developed a concept smart window device for simultaneous generation and saving of energy.”

Engineers have long battled to incorporate energy-generating solar cells into window panes without affecting their transparency.

Gao’s team discovered that a material called  (VO2) can be used as a transparent coating to regulate infrared radiation from the Sun.

VO2 changes its properties based on temperature. Below a certain level it is insulating and lets through infrared light, while at another temperature it becomes reflective.

A window in which VO2 was used could regulate the amount of Sun energy entering a building, but also scatter light to  the team had placed around their glass panels, where it was used to generate energy with which to light a lamp, for example.

“This smart window combines energy-saving and generation in one device, and offers potential to intelligently regulate and utilise solar radiation in an efficient manner,” the study authors wrote in the journal Nature Scientific Reports.



Li-Fi to replace Wi-Fi in China?

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Chinese scientists have successfully developed a new cheaper way of getting connected to internet by using signals sent through light bulbs instead of radio frequencies as in Wi-Fi, a move expected to radically change process of online connectivity.

Four computers can be connected to internet through one- watt LED bulb using light as a carrier instead of traditional radio frequencies, as in Wi-Fi, said Chi Nan, an information technology professor with Shanghai‘s Fudan University.

Under the new discovery dubbed as ‘Li-Fi‘, a light bulb with embedded microchips can produce data rates as fast as 150 megabits per second, which is speedier than the average broadband connection in China, said Chi, who leads a Li-Fi research team including scientists from the Shanghai Institute of Technical Physics of the Chinese Academy of Sciences.

The term Li-Fi was coined by Harald Haas from the University of Edinburgh in the UK and refers to a type of visible light communication technology that delivers a networked, mobile, high-speed communication solution in a similar manner as Wi-Fi.

With Li-Fi cost-effective as well as efficient, netizens should be excited to view 10 sample Li-Fi kits that will be on display at the China International Industry Fair that will kick off on November 5 in Shanghai.

The current wireless signal transmission equipment is expensive and low in efficiency, Chi said.

“As for cell phones, millions of base stations have been established around the world to strengthen the signal but most of the energy is consumed on their cooling systems,” she said.

“The energy utilisation rate is only 5 per cent,” state-run Xinhua news agency quoted her as saying.

Li-Fi was touted as a boon to China netizen community, the highest in the world with about 600 million connections.

Compared with base stations, the number of light bulbs that can be used is practically limitless.

Meanwhile, Chinese people are replacing the old-fashioned incandescent bulbs with LED light bulbs at a fast pace.

“Wherever there is an LED light bulb, there is an internet signal. Turn off the light and there is no signal,” Chi said.

However, there is still a long way to go to make Li-Fi a commercial success.

“If the light is blocked, then the signal will be cut off,” Chi said.

More importantly, according to the scientist, the development of a series of key related pieces of technology, including light communication controls as well as microchip design and manufacturing, is still in an experimental period.

Scientists create hybrid flu that can go airborne.

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H5N1 virus with genes from H1N1 can spread through the air between mammals.

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.

“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.

Source: Nature