China Science & Technology Forum

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Analysis of largest set of genomes from pregnant women reveals genetic links to disease, birth outcomes
October 4, 2018, University of California - Berkeley

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Credit: CC0 Public Domain

Analysis of the world's largest set of genome data from pregnant women, totaling 141,431 expectant mothers from across China, has uncovered unsuspected associations between genes and birth outcomes, including the birth of twins and a woman's age at first pregnancy.

The analysis also allowed researchers to reconstruct the recent movement and intermarriage of different ethnic groups in China, and promises to help identify genes that make people susceptible to infectious diseases.

"It's amazing that this is even possible—that you can take these massive samples and do association mapping to see what the genetic variants are that explain human traits," said co-author Rasmus Nielsen, a professor of integrative biology at the University of California, Berkeley, who oversaw the computational analysis performed by researchers at BGI in Shenzhen, China.

It's even more amazing because the researchers sequenced, on average, only 10 percent of each mother's genome, relying on large numbers of poor-quality genomes so as to leverage cheaper tests to discover new genetic links.

The mothers-to-be had provided blood samples to be tested for fetal chromosomal abnormalities, primarily Down syndrome. This technique, called cell-free fetal DNA testing, a form of non-invasive prenatal testing, is possible because mothers have DNA from their unborn child floating in their bloodstream. With rapid shotgun sequencing, labs can break up all the free-floating DNA in the blood and sequence just enough of the bits to diagnose Down syndrome.

Though not yet widespread in the United States, non-invasive prenatal testing is common in China: 70 percent of such tests worldwide have been performed in China. Sampling the mother's blood can be done early and risk-free, whereas standard prenatal testing in the U.S. involves amniocentesis or chorionic villus sampling, both of which require obtaining fetal cells from inside the uterus and risk harming the unborn child.

BGI was paid by maternity hospitals to conduct these tests, but obtained informed consent from each mother to also analyze the partially sequenced genomes for research purposes, maintaining anonymity. All the analyses were performed in China and the data is hosted in the China National GeneBank.

The data analysis revealed, for example, that variation in a gene called NRG1 is linked to a greater or lesser incidence of twins. One variant of the gene is more common in mothers with twins and is associated with hyperthyroidism, tightening a link between thyroid function and twinning that had previously been seen in mice.

A variant of another gene, EMB, was associated with older first-time mothers.

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BGI-Shenzhen researchers Siyang Liu, Xun Xu, and Xin Jin (left to right). Credit: BGI-Shenzhen

The analysis also pulled out several genes that had not previously been associated with height and body mass index.

Perhaps most interesting, Nielsen said, is what sequencing of all the DNA in maternal blood tells us about viruses circulating through the body, and thus the link between viruses and genes that determine susceptibility to disease.

A variation in one gene, for example, was associated with a higher concentration of herpesvirus 6 in a mother's blood. Herpesvirus 6 is the most common cause of the relatively benign baby rash called roseola, but a high "viral load" correlates with more severe symptoms. People with Alzheimer's disease also have higher levels of herpesvirus 6 in their brains.

"Most people are infected by herpesvirus 6 at some point in their life, but some people seem to be less affected than others. We have now found a human genetic variant that helps control the severity of the infection," Nielsen said. "This is quite interesting because we don't know much about the genetic variants that control why some people seem more susceptible to viral infection and not others."

More correlations remain to be discovered. The BGI team to date has sequenced genomes from more than 3 million pregnant women, much of it accompanied by information on the mothers' and babies' health that can be used to find genetic associations.

"If you have these genotypes and compare them to phenotypes, that is, something you can measure, you can find genetic variants that explain human traits," said Xun Xu, a leader of the BGI team and the study's lead author.

Nielsen, Xu, Siyang Liu and other BGI colleagues will report initial findings from the analysis on Oct. 4 in the journal Cell.

Sequencing by imputation

To find genes associated with human traits—height and weight, for instance—researchers typically sequence thoroughly a small number of genomes—hundreds to thousands—and scan the genomes for variations in the sequence that are more common in people with the trait. The gold standard now is to sequence each genome 60 times to insure accuracy given inherent errors in the sequencing process. Even if each genome is sequenced a mere 20 times, which is good but not great, it still gets expensive.

The new study relies on only partial genomes—which are cheaper to get—but massive numbers of them. On average, about one-tenth of each mothers' genome was sequenced, because that is all that is necessary for a doctor to diagnose a chromosomal anomaly in the fetus. For example, Down syndrome, or trisomy 21, is caused by three rather than two copies of chromosome 21. A single cycle of sequencing is enough to determine whether some genes are 50 percent more common than normal, indicative of one extra chromosome.

But partial genomes can tell researchers a lot too, Nielsen said.

Think of reconstructing a lost book from thousands of error-prone copies, complicated by the fact that you have only about 10 percent of each copy. By looking for overlaps and inferring words from context—called imputation—you could reconstruct a lost manuscript.

In reconstructing partial genomes, scientists have another important data set: all the complete human genomes sequenced to date, with all their individual variations.

Proof that imputation using more than 141,000 partial genomes works is that the reconstructed geographical distribution in China of minority groups and the dominant Han Chinese reflect known population movements in the country over the last 100 years.

"Because the sample size is so large, we can get at recent population movements, including relocations as a consequence of China's governmental policies," Nielsen said. Many populations of Han Chinese in western China are more closely related to the populations of large cities on the East Coast, for example, reflecting relocation of large numbers of people into the sparsely populated countryside.

The researchers also found that many Chinese had genetic variants common among Indians, Southeast Asians and, along the route of the old Silk Road, Europeans.

Nielsen is currently working with his BGI colleagues to analyze the genomes of 1 million Chinese women who underwent non-invasive prenatal testing.



Analysis of largest set of genomes from pregnant women reveals genetic links to disease, birth outcomes | MedicalXpress.com

Siyang Liu, Shujia Huang, Fang Chen, Lijian Zhao, Yuying Yuan, Stephen Starko Francis, Lin Fang, Zilong Li, Long Lin, Rong Liu, Yong Zhang, Huixin Xu, Shengkang Li, Yuwen Zhou, Robert W. Davies, Qiang Liu, Robin G. Walters, Kuang Lin, Jia Ju, Thorfinn Korneliussen, Melinda A. Yang, Qiaomei Fu, Jun Wang, Lijun Zhou, Anders Krogh, Hongyun Zhang, Wei Wang, Zhengming Chen, Zhiming Cai, Ye Yin, Huanming Yang, Mao Mao, Jay Shendure, Jian Wang, Anders Albrechtsen, Xin Jin, Rasmus Nielsen & Xun X. Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History. Cell (2018). DOI: 10.1016/j.cell.2018.08.016.​

 

[JSCh]

Graphene moves from hype to reality
By ANGUS McNEICE | China Daily | Updated: 2018-10-05 08:15

A lightbulb with a filament made using graphene. [Photo by ANGUS McNEICE/China Daily]

It's been 14 years since the discovery of graphene, and the world is still waiting for the "wonder material" to provide the groundbreaking innovations the initial headlines promised.

We were told our cars, computers and smartphones would be enhanced by graphene, and that the ultra-versatile form of carbon would usher in an era of wearable electronics and prevent droughts by enabling the filtering of salt from seawater.

One entrepreneur promised unlimited energy from below the Earth's surface via a graphene cable, and another suggested a graphene space elevator tethered at the equator.

In a world currently void of futuristic graphene-based gadgets, many are now questioning whether the material will live up to the hype. According to James Baker, chief executive of Graphene@Manchester, it will, and that moment may be just around the corner, he said.

"We are approaching a tipping point," said Baker. "In 12 to 18 months, you will start to see graphene products hit the marketplace at an ever-increasing pace."

Baker leads business-related development of graphene at the University of Manchester, where the National Graphene Institute is known as the heart of global graphene research.

"Having all of these capabilities in one building is what attracts people from everywhere," said Xiao Ping, a professor of materials science at the University of Manchester. "They come here and say this is the place for fundamental research. We can't compete with you, so we will collaborate with you."

Both Chinese telecommunications giant Huawei and the Aero Engine Corporation of China are conducting research at the NGI, a facility President Xi Jinping toured during his state visit to the United Kingdom in 2015.

The Chinese and British governments have since formed joint graphene working groups that make it possible for researchers to work together to create a future built on graphene.

Through these efforts, Baker said graphene and many of its associated products are close to overcoming two major obstacles faced by all emergent technologies. First, the "valley of death", in which a lack of funding kills off prototypes on their journey from lab to factory. And, second, the "trough of disillusionment", which lies between the initial hype around an innovation and its eventual real-world applications.

Looking beyond the hype

Grab a pencil and some sticky tape, and you're holding the lab equipment necessary to win a Nobel Prize.

In 2004, Konstantin Novoselov and Andre Geim, two physicists at the University of Manchester, discovered graphene by peeling apart layers of graphite using adhesive strips.

At just the width of an atom across, graphene is the thinnest material known to humans, and also the strongest.

In graphene, carbon atoms are arranged in a hexagonal lattice formation, similar to the pattern of chicken wire.

Strong covalent bonds between the atoms give graphene a tensile strength 325 times greater than steel, while maintaining flexibility and elasticity. Graphene is also an efficient conductor of heat and electricity, and is ultra-lightweight.

The discovery instigated a whirlwind of speculation into how the new material could change the world.

"But graphene is just a teenager," said Baker. "Right now, we are in the 'trough of disillusionment', and we are starting to climb out of it."

Part of the journey through a hype cycle requires an adjustment of expectations, said Khasha Ghaffarzadeh, a director at Cambridge consultancy IDTechEx who has been conducting market research into graphene since 2006.

"There is a difference between ideal graphene, the wonder material, and commercial graphene, which is more down-to-earth," said Ghaffarzadeh.

He explains that there are numerous varieties of graphene－sheets, flakes, and powders made of multi-layered or few-layered graphene to name but a few－and most are currently used as an additive to improve the performance of other materials.

There is even debate over whether certain additives can be classed as graphene. Last year, China and the UK formed a graphene standardization working group aimed at ensuring quality control in the market.

On the nano level, single-layer graphene has fantastic properties. On a larger scale, some forms of graphene act like graphite, while others behave like an oxide.

This makes it challenging to convince industry to turn to graphene, where the material would compete with other additives that are cheaper and only marginally poorer performers.

Graphene nerve sensors control the movement of a robotic hand. [Photo provided to China Daily]

But several products enhanced by graphene are already on the market in China. Beijing Carbon Century Technology produces an energy-saving graphene modifier for engine oil. Wuxi-based GMCC Electronic Technology makes a graphene-enhanced supercapacitor that is an alternative to electrochemical batteries and has a shorter charge time. Beijing-based Xiaomi and Guangzhou-based FiiO have incorporated graphene into headphone drivers. And other Chinese companies sell optical displays, LED light bulbs, and tires that are all enhanced with graphene.

Huawei has been tipped to release a smartphone with graphene-assisted batteries in the near future. The batteries are said to be able to charge fully in a matter of minutes and have an increased capacity.

Huawei has been one of the fastest adopters of graphene in its industry. The company's founder, Ren Zhengfei, is optimistic about the material's ability to dramatically change the electronics technology.

In 2016, Huawei developed a graphene-enhanced lithiumion battery for mobile network-base stations that remains functional at extreme temperatures.

Huawei is currently three years into a joint research program at the NGI that is exploring how graphene could be used in next-generation communications technologies.

"The University of Manchester has enormous expertise and the best facilities for working with the material," said Chen Lifang, a corporate senior vice-president at Huawei.

Elsewhere within the NGI's labyrinth of laboratories, Xiao Ping is leading a project for the Beijing Institute of Aeronautical Materials, or BIAM, which is a subsidiary of the Aero Engine Corporation of China.

The project he is working on is looking to accelerate the use of graphene in the aviation industry.

"Right now, we are focused on fundamental research," said Xiao. "And we have found that graphene can be used as an additive to increase the performance of several other materials."

Xiao's research has shown that graphene can prevent the growth of cracks in ceramics, which are used in internal combustion engines.

Xiao Ping, a professor of materials science at the NGI, shows a graphene composite. [Photo by ANGUS McNEICE/China Daily]

Bridging the valley

Baker said that for graphene based products to move from concept to commercialization, they must overcome the "valley of death" problem.

Governments and universities will back initial research, and the private sector will invest in a product that can be replicated at scale. But there is a gap between those two development phases in which innovation is starved of funding.

To bridge this gap, the University of Manchester and the UK government have invested 60 million pounds ($78 million) into the Graphene Engineering and Innovation Center, otherwise known as GEIC (pronounced "geek"). The cavernous facility will switch on its machines later this year. It will allow companies to use the equipment to replicate prototypes by the dozen, proving to investors that inventions are scalable.

"Companies from China and elsewhere can come here with an idea for a product and develop it," said Baker. "It's a make-or-break space for some of the ideas we've come up with around graphene. If we do that successfully, we will increase the pace of graphene products into the commercial sphere."

And those Chinese companies have the support of a government that has doubled down on advanced materials.

Scientists conduct research at the National Graphene Institute in Manchester, United Kingdom. [Photo by ANGUS McNEICE/China Daily]

China leads the way

China has emerged as a key territory for graphene production. In China's 13th Five-Year Plan (2016-2020) that started in 2016, new materials development is listed among the leading sectors of the national economy.

Around 3,000 Chinese companies are exploring uses for graphene, according to government statistics, while half of the world's graphene-related patents have been filed in China.

China now has close to 75 percent of the nominal global production capacity for graphene, according to IDTechEx, and the price of graphene has fallen from several thousand dollars a gram to around $75 a kilogram during the last decade. Production capacity is expanding, as foreign companies follow demand and establish operations in China.

UK-based advanced materials engineering company Versarien is currently building a graphene factory in Jinan, Shandong province.

"It's a brand-new science, and China is trying to take the lead, and is willing to invest heavily to create that lead," said Neill Ricketts, chief executive at Versarien.

Ghaffarzadeh predicts that, during the next five to 10 years, graphene will mostly be restricted to the additive market.

"But that is not to say that there won't eventually be those truly groundbreaking results down the line," he said. "Graphene really does have fantastic properties and its potential is huge."

 

[JSCh]

CRISPR Can Make Old Tomatoes, New Tomatoes | Discover magazine
By Anna Groves | October 4, 2018 4:15 pm

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Ground tomatoes, still in their papery husks. (Credit: F_studio/Shutterstock)

It’s a big week for CRISPR! Despite being a world apart, two separate research groups had the same idea: to see if CRISPR gene editing can really mimic conventional plant breeding.

One group re-domesticated a wild tomato plant; the other used a similar approach to domesticate an entirely new crop: the ground cherry, a tomato relative.

Together, the new work demonstrates how dramatically gene editing technology could speed up crop improvement efforts worldwide.

How to Make a Crop Worth Growing
In the past few decades, conventional breeding of the tomato plant has dramatically increased its yield, fruit size, and shelf life.

To get a plant from its wild form to something growable as a large-scale food crop is not an easy feat. Conventional breeding requires decades of work from breeders who select the best plants, cross them, and select the best plants again from their offspring.

But this kind of plant breeding leaves quite a bit of room for Mother Nature to get in the way. A good trait and a bad trait might be coded by two genes that are just too close to each other in the DNA to ever hope to keep one while ditching the other.

And breeding for certain traits can let other traits fall through the cracks. Years of focus on breeding red, intact, storable tomatoes can result in red, intact, storable tomatoes that no longer taste like anything.

On top of all that, conventional breeders have to constantly fight to keep a certain level of genetic variation in their plants. If all the genes in their population end up the same, all the plant traits end up the same, and there are no longer any “best plants” to choose from.

To combat this, breeders traditionally have to cross-breed crop plants with wild relatives. This comes with its own challenges, including a risk of losing important crop genes in the process.

But advances in gene editing technology might make those worries disappear.

Researchers have learned a lot about which genes in the modern tomato are responsible for which traits. They can point to specific places in the DNA and say, changes here and here are what made the fruits bigger. This allows them to pinpoint, for example, which genes changed a sprawling vine into a compact plant with fruits that ripen all at the same time.

With CRISPR, changes to genes could be made in a single generation, and with a gene-level precision that doesn’t cause unintended effects.

Tom-ay-to, Tom-ah-to
But this idea hadn’t been thoroughly tested. In Nature Biotechnology, researchers from the State Key Laboratory of Plant Cell and Chromosome Engineering in Beijing attempted to ditch some of the genetic baggage in the conventionally bred tomato and instead “re-domesticate” it from its wild ancestor using CRISPR.

They grew wild tomatoes and engineered the DNA to alter a few key traits. They wanted compact (rather than sprawling) plants, synchronous fruit ripening, larger fruits, and higher vitamin C production, among other things.

The wild plants they used had a few bonus features, either being resistant to bacterial spot disease, tolerant of salt, or both. So when they flipped a few key switches from “wild” to “domesticated,” the resulting plants had a combination of traits that conventional breeding would have taken years to get just right.

The success of this process could have implications for all sorts of crops, dramatically speeding up the continuing quest for improved tolerance to drought, resistance to diseases, and other traits that will be critical for crops to survive future climate.

A Brand New Tomato
Meanwhile researchers from the Howard Hughes Medical Institute in Maryland domesticated, for the first time, a tomato relative — the ground cherry. Their work is published in Nature Plants.

The team wanted to see if they could use what we know about tomato genetics to achieve a similar result in a related species with untapped crop potential.

The ground cherry, a species of Physalis, is a weedy plant native to the Americas. Sometimes called a “strawberry tomato,” the sweet-and-sour fruit is already available commercially. But it’s relatively rare: you might come across it in a U.S. farmers market, but it hasn’t achieved the breeding attention or commodification that other crops have. Plants like this are called “orphan crops” — quinoa is probably the most well-known right now.

After quite a bit of genetic and genomic legwork, the team engineered the DNA to alter a few key traits, using tomatoes as a guide. Some of the traits will sound familiar: they wanted compact (rather than sprawling) plants and larger fruits. They also fixed a few other wild tomato problems, like stems that drop their fruits too easily.

So, should we watch for new-and-improved ground cherries in stores?

Not quite yet.

“We are not at the end yet,” says Zak Lemmon, lead author on the study. “What we were able to do is rapidly show some very rapid improvements in key traits that will be needed for a larger scale adoption into the mainstream agriculture market.”

“(Physalis) was a lot of fun to work on. I think it’s a really interesting specialty crop that has a lot of promise and potential for some bigger impact,” says Lemmon.

 

[JSCh]

Chinese Materials Firm Starts Up Graphene Plant in Heilongjiang
TANG SHIHUA
DATE: TUE, 10/09/2018 - 17:03 / SOURCE:YICAI

Chinese Materials Firm Starts Up Graphene Plant in Heilongjiang​

(Yicai Global) Oct. 9 -- Chinese coke company Baotailong New Materials has completed construction of a CNY66.2 million (USD9.6 million) graphene production project in the north of the country and has launched trial-stage operations.

Baotailong completed all work on the facility located in its hometown of Qitaihe in northern Heilongjiang province at the end of last month, the firm said in a statement. The plant boasts an annual graphene output of 50 tons.

The company will apply to the relevant departments for production licenses after it has completed half a year of trial production. Baotailong completed construction and equipment installation at the end of July and began commissioning and product process adjustments in August.

The company will expand capacity to yearly output will to 150 tons once the project enters full-scale production, which is in addition to the 100 tons per year made through chemical techniques.

Compared with the physical technique, the chemical technique, mainly used in the civilian field, is quite complicated and produces graphene of a lower quality, despite higher output. Physical production results in a lower yield and high energy consumption but higher product quality. It is used for military and other high-end fields.

 

[JSCh]

R&D spending reaches new levels in China
By Ouyang Shijia | chinadaily.com.cn | Updated: 2018-10-09 20:05

A research staff member tests new vaccine (S-IPV) against poliomyelitis at the Institute of Medical Biology of the Chinese Academy of Medical Sciences, located in Kunming, capital of Southwest China's Yunnan province, Jan 22, 2015. [Photo/Xinhua]

China's spending on research and development accounted for 2.13 percent of the nation's gross domestic product in 2017, reaching the level of moderately developed countries, the National Bureau of Statistics said on Tuesday.

R&D spending hit 1.76 trillion yuan ($254 billion) with a whopping 12.3 percent growth year-on-year by 2017. And the country saw its annual per capita spending on R&D reach 436,000 yuan in 2017, an increase of 32,000 yuan over previous years.

The structure of R&D spending improved as more money was invested to boost fundamental research, said Zhang Peng, a senior statistician from the NBS.

The spending on fundamental research rose 18.5 percent year-on-year to 97.55 billion yuan last year, 3.6 percent points higher than the rate in 2016. Specifically, the growth rate is at its highest level in the last five years.

Eastern China continues to be the leader domestically, contributing 61.9 percent to the growth of the nation's R&D inputs. The Central China, Western China and Northeastern China regions lag behind, reporting 22.9 percent, 13.1 percent and 2.1 percent, respectively.

 

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PUBLIC RELEASE: 8-OCT-2018
Success is sweet: Researchers unlock the mysteries of the sugarcane genome
Third-generation sequencing technologies and analytical methods have enabled the once-impossible effort to assemble complete, detailed sequence for sugarcane's complex genome

CARL R. WOESE INSTITUTE FOR GENOMIC BIOLOGY, UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

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Harvesting sugarcane or Sugarcane field: Modern sugarcane cultivars are polyploid interspecific hybrids, combining high sugar content from S. officinarum with hardiness, disease resistance and ratooning of S. spontaneum. The sequenced genome is a haploid accession AP85-441 generated by anther culture from octoploid S. spontaneum SES208.
CREDIT: Ray Ming

For centuries, sugarcane has supplied human societies with alcohol, biofuel, building and weaving materials, and the world's most relied-upon source of sugar. Now, researchers have extracted a sweet scientific prize from sugarcane: its massive and complex genome sequence, which may lead to the development of hardier and more productive cultivars.

Producing the comprehensive sequence required a concerted effort by over 100 scientists from 16 institutions; the work took five years and culminated in a publication in Nature Genetics. But the motivation to tackle the project arose long before.

"Personally, I waited for 20 years to get this genome sequenced," said Ray Ming, a University of Illinois plant biology professor who instigated and led the sequencing effort. "I dreamed about having a reference genome for sugarcane when I worked on sugarcane genome mapping in the late 1990s." Ming is a member of the Carl R. Woese Institute for Genomic Biology, one of a group of researchers interested in developing sugarcane and related crops to boost food and biofuel production.

The complete genome sequence was well worth the wait and the effort because of its potential to aid the effort to improve sugarcane. The sugarcane grown by most farmers is a hybrid of two species: Saccharum officinarum, which grows large plants with high sugar content, and Saccharum spontaneum, whose lesser size and sweetness is offset by increased disease resistance and tolerance of environmental stress. Lacking a complete genome sequence, plant breeders have made high-yielding, robust strains through generations of crossing and selection, but this is an arduous process relying on time and luck.

"Sugarcane is the fifth most valuable crop, and the lack of a reference genome hindered genomic research and molecular breeding for sugarcane improvement," Ming said. ". . . Sequencing technology was not ready to handle large autopolyploid genomes until 2015 when the throughput, read length, and cost of third generation sequencing technology [e.g. that developed by biotechnology company Pacific Biosciences] became competitive enough."

Why was sequencing the sugarcane genome so difficult? A naturally occurring phenomenon common in plants created a significant technical barrier. Sometime during the evolutionary history of sugarcane, its genome had been duplicated twice, resulting in four slightly different versions of each pair of chromosomes all crammed into the same nucleus together.

These events not only quadrupled the size of the genome (and therefore the sheer volume of DNA sequence), they also made highly similar sequences from the genome wide duplication much more difficult to assemble into distinct chromosomes. Genomic DNA is typically sequenced, or read, in small, overlapping fragments, and the sequence data from those fragments become overlapping pieces of an enormous linear puzzle. As the sugarcane genome size doubled, then doubled again, this puzzle didn't just get larger; it took on repeated but not-quite-identical elements into which those many tiny pieces were difficult to correctly fit.

To conquer this challenge, the sequencing team used a technique called high-throughput chromatin conformation capture or Hi-C. This method allows researchers to discover what parts of the long, tangled strands of chromosomal DNA lie in contact with one another inside the cell. When analyzed using a customized algorithm called ALLHIC developed by the team, the resulting data served the purpose of the picture on the lid of a jigsaw puzzle box, providing a rough map of which sections of sequence most likely belonged to which chromosome.

"The biggest surprise was that by combining long sequence reads and the Hi-C physical map, we assembled an autotetraploid [quadrupled] genome into 32 chromosomes and realized our goal of allele-specific annotation among homologous chromosomes," Ming said. In other words, the researchers now knew which gene sequences belonged to each of the four variations on the original, pre-duplications genome--a much higher level of detail than they expected to attain.

With this information, the researchers could form better hypotheses about the mysteries of the sugarcane genome's evolutionary history.

Through comparison with the genomes of related species, researchers knew that at some point the number of unique chromosomes had dropped from 10 to eight. To the team's surprise, the new sequence data revealed that two different chromosomes had split apart, and all four halves had then fused to different existing chromosomes, a more complex set of events than the one they hypothesized.

How does understanding these physical changes help? Along with these large physical rearrangements within the genome come changes to the genes in the affected regions. For example, Ming and his colleagues found that the large chunks of chromosome that had been moved to new locations contained many more genes that help plants resist disease than were found in other locations.

"It resolved a mystery why S. spontaneum is such a superior source of disease resistance and stress tolerance genes," Ming said. "The chromosomal rearrangements are likely the cause, not the consequence of this enrichment, although the underlining mechanism of this enrichment remains to be investigated. This discovery will accelerate mining effective alleles of disease resistance genes that have incorporated into elite modern sugarcane hybrid cultivars, and subsequently the implement of molecular breeding [of sugarcane]."

The high quality of the genome sequence also allowed researchers to identify possible origins of modern sugarcane's incredible sweetness: even in the less sweet S. spontaneum, mutations that produced multiple copies of genes for sugar-transporting proteins have accumulated. They were also able to observe that in the hybridization between S. officinarum and S. spontaneum, the S. spontaneum-derived DNA sequence is scattered randomly throughout the hybrid genome.

"The ALLHIC method has already proven to be effective for the construction of the autopolyploid sugarcane genome," Ming said. He anticipates that the techniques used successfully for the sugarcane genome will also assist researchers in sequencing other complex genomes.



Success is sweet: Researchers unlock the mysteries of the sugarcane genome | EurekAlert! Science News

Jisen Zhang, Xingtan Zhang, Haibao Tang, Qing Zhang, Xiuting Hua, Xiaokai Ma, Fan Zhu, Tyler Jones, Xinguang Zhu, John Bowers, Ching Man Wai, Chunfang Zheng, Yan Shi, Shuai Chen, Xiuming Xu, Jingjing Yue, David R. Nelson, Lixian Huang, Zhen Li, Huimin Xu, Dong Zhou, Yongjun Wang, Weichang Hu, Jishan Lin, Youjin Deng, Neha Pandey, Melina Mancini, Dessireé Zerpa, Julie K. Nguyen, Liming Wang, Liang Yu, Yinghui Xin, Liangfa Ge, Jie Arro, Jennifer O. Han, Setu Chakrabarty, Marija Pushko, Wenping Zhang, Yanhong Ma, Panpan Ma, Mingju Lv, Faming Chen, Guangyong Zheng, Jingsheng Xu, Zhenhui Yang, Fang Deng, Xuequn Chen, Zhenyang Liao, Xunxiao Zhang, Zhicong Lin, Hai Lin, Hansong Yan, Zheng Kuang, Weimin Zhong, Pingping Liang, Guofeng Wang, Yuan Yuan, Jiaxian Shi, Jinxiang Hou, Jingxian Lin, Jingjing Jin, Peijian Cao, Qiaochu Shen, Qing Jiang, Ping Zhou, Yaying Ma, Xiaodan Zhang, Rongrong Xu, Juan Liu, Yongmei Zhou, Haifeng Jia, Qing Ma, Rui Qi, Zhiliang Zhang, Jingping Fang, Hongkun Fang, Jinjin Song, Mengjuan Wang, Guangrui Dong, Gang Wang, Zheng Chen, Teng Ma, Hong Liu, Singha R. Dhungana, Sarah E. Huss, Xiping Yang, Anupma Sharma, Jhon H. Trujillo, Maria C. Martinez, Matthew Hudson, John J. Riascos, Mary Schuler, Li-Qing Chen, David M. Braun, Lei Li, Qingyi Yu, Jianping Wang, Kai Wang, Michael C. Schatz, David Heckerman, Marie-Anne Van Sluys, Glaucia Mendes Souza, Paul H. Moore, David Sankoff, Robert VanBuren, Andrew H. Paterson, Chifumi Nagai & Ray Ming. Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L. Nature Genetics (2018). DOI: 10.1038/s41588-018-0237-2​

 

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CEPC Study Group Completes Accelerator Conceptual Design Report---Chinese Academy of Sciences
Sep 10, 2018

The Conceptual Design Report (CDR), Volume I – Accelerator for the Circular Electron Positron Collider (CEPC) was published on September 2, 2018. The CEPC Accelerator CDR has reached its goal in multiple energy ranges, including the Higgs, W and Z poles.

The CEPC Study Group has been working on the conceptual design of the CEPC since the publication of the Preliminary Conceptual Design Report (Pre-CDR) in March 2015. The Fully Partial Double-Ring with Crab-Waist Collision scheme is the baseline accelerator design used in the CDR. A number of accelerator designs, including Single-Ring Pretzel, Partial Double-Ring, Advanced Partial Double-Ring and Fully Partial Double-Ring, were considered and optimized by the CEPC Study Group. The detailed comparison of various design options and the final choice of the baseline was documented in CEPC-SppC Progress Report – Accelerator, published in April 2017.

The CEPC accelerator team completed the first draft of the current CDR in November 2017. The team soon conducted a preliminary review and revised it. A committee of international experts then reviewed the CDR from June 28-30 at Institute of High Energy Physics (IHEP) of Chinese Academy of Sciences.

In its subsequent report, the committee said it “unanimously congratulates the CEPC team on the completion of the CDR, with remarkable successes in various aspects of the design.” The review committee also said it believes “the CDR has already reached a sufficient level of maturity to allow approval to proceed to a Technical Design Report.” The CEPC Study Group incorporated the comments from the reviewers into the CDR and released the document on September 2, 2018.

The CEPC Accelerator CDR comprises 505 pages, 12 chapters and eight appendices. It covers machine layout, design of the collider, the booster, linac accelerator, the injector, design of the superconducting radio frequency (RF), RF power source, magnets, power supply, vacuum, and monitoring, control and mechanical systems. It also covers the cryogenic system, common facilities, civil engineering, radiation protection, and the option of upgrading to a Super proton-proton Collider (SppC). Alternative options for CEPC accelerator and opportunities for polarization at Z-pole are discussed in the appendices.

The CEPC Accelerator CDR can be found at https://arXiv.org (document 1809.00285) or at the official CEPC website: http://cepc.ihep.ac.cn/CDR_v6_201808s.pdf.

IHEP Develops First CMOS Pixel Sensor Prototype for Circular Electron Positron Collider---Chinese Academy of Sciences
Oct 09, 2018

Scientists from the Institute of High Energy Physics (IHEP) have developed the first pixel sensor prototype based on the 180 nm Complementary Metal–Oxide–Semiconductor (CMOS) imaging sensor process recently. This represents significant progress in the key technology of the micro-vertex detector, the core component for the detector at the Circular Electron Positron Collider (CEPC).

CMOS pixel sensors allow integration of the sensing element and its readout electronics on the same silicon substrate, which make them attractive for charged particle tracking. The CEPC micro-vertex detector, located closest to the e+e- interaction point, will use state-of-the-art pixel technologies that provide high spatial resolution, are capable of high readout speed and adequate radiation hardness, and feature low power consumption.

The first prototype sensors, named JadePix 1, have been characterized with radioactive resources, and recently by the electron test beam at DESY in Hamburg, Germany. Preliminary results show that spatial resolutions better than 5 μm and 3.5 μm can be achieved for pixel sizes of 33×33 μm2 and 16×16 μm2, respectively. More importantly, there is no significant resolution degradation after exposure to neutron irradiation up to 1013 1 MeV neq/cm2.

The proposed Circular Electron Positron Collider (CEPC) aims at measuring Higgs properties with high precision and probing new physics beyond the Standard Model of particle physics. The CEPC Study Group has completed the conceptual design report (CDR) for the e+e- collider, and is completing the CDR for the detector. The group is pursuing an R&D program involving technologies critical for realizing the CEPC.

IHEP's Experimental Physics Division (EPD) initiated the R&D project to develop the novel CMOS pixel sensors. The advanced silicon tracking detectors and associated electronics have been the focal research direction at EPD. The division has been actively participating in several international projects, including the ATLAS Inner Tracker Upgrade, to gain design and construction experience for silicon detectors.

In addition, the division has developed pixel detectors for X-ray imaging. These detectors will soon be deployed at various stations of the High Energy Photon Source (HEPS), which will be constructed near Beijing. Meanwhile, EPD is pushing forward pixel detector R&D for the CEPC using both CMOS and SOI technologies. The goal is to design a fully functional pixel sensor and construct a larger scale prototype detector in near future.

JadePix 1 prototype sensor (Image by IHEP)

position resolutions obtained with electron test (Image by IHEP)​

 

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R&D spending reaches new levels in China
By Ouyang Shijia | chinadaily.com.cn | Updated: 2018-10-09 20:05

A research staff member tests new vaccine (S-IPV) against poliomyelitis at the Institute of Medical Biology of the Chinese Academy of Medical Sciences, located in Kunming, capital of Southwest China's Yunnan province, Jan 22, 2015. [Photo/Xinhua]

China's spending on research and development accounted for 2.13 percent of the nation's gross domestic product in 2017, reaching the level of moderately developed countries, the National Bureau of Statistics said on Tuesday.

R&D spending hit 1.76 trillion yuan ($254 billion) with a whopping 12.3 percent growth year-on-year by 2017. And the country saw its annual per capita spending on R&D reach 436,000 yuan in 2017, an increase of 32,000 yuan over previous years.

The structure of R&D spending improved as more money was invested to boost fundamental research, said Zhang Peng, a senior statistician from the NBS.

The spending on fundamental research rose 18.5 percent year-on-year to 97.55 billion yuan last year, 3.6 percent points higher than the rate in 2016. Specifically, the growth rate is at its highest level in the last five years.

Eastern China continues to be the leader domestically, contributing 61.9 percent to the growth of the nation's R&D inputs. The Central China, Western China and Northeastern China regions lag behind, reporting 22.9 percent, 13.1 percent and 2.1 percent, respectively.

The world’s largest radio telescope, the Five-hundred-meter Aperture Spherical radio Telescope is one product of China’s growing spending on research.
STR/AFP/GETTY IMAGES
Surging R&D spending in China narrows gap with United States | Science | AAAS
By Dennis Normile
Oct. 10, 2018 , 12:45 PM

China’s total spending on R&D rose a robust 12.3% last year to a record 1.76 trillion yuan ($254 billion), according to a government report released yesterday. Already second in the world in R&D spending behind the United States, China has narrowed the gap.

Figures from the Organisation for Economic Co-operation and Development (OECD) show that in 2012, China spent about 34% as much as the United States, a figure that rose to 44% in 2016, the most recent year for which data are available. In terms of purchasing power parity, however, China’s 2016 spending was equivalent to 88% of U.S. spending.

"The year-to-year growth in R&D spending indicates firm governmental and social support for making China a scientific power," says Xie Xuemei, a specialist in innovation economics at Shanghai University in China. "However, there is still a long way to go" to match the research capabilities of developed countries, she adds.

The report from the ministries of science and finance and the National Bureau of Statistics highlights other notable trends in 2017, including a 12.5% increase in spending by businesses—including foreign-owned corporations—to 1.36 trillion yuan ($196.4 billion). "More and more enterprises realize that to improve their competitive advantage, they must rely on their independent innovation capabilities, [which] rely on greater spending on R&D," Xie says. Basic research expenditures were also up, hitting 97.55 billion yuan ($14.1 billion), an increase of 18.5%. For comparison, the United States spent $86.32 billion on basic research in 2016, according to OECD. A national innovation strategy that strives to harness R&D to economic growth has been driving the increase in both government and industrial R&D spending in recent years, Xie says.

Accounting differences between China and other countries make international comparisons tricky, says Cao Cong, a science policy specialist at the University of Nottingham Ningbo in China. China’s statistics lump R&D funding with a range of other science and technology expenditures, such as support for science communications, administration, and scientific exchanges and cooperation. On the other hand, when figuring spending on basic research, China often excludes capital investment in facilities and university faculty salaries, costs typically included in the basic category by other countries. But even if basic spending is undercounted, it is probably a smaller share of overall research spending than in the United States and other advanced countries, Cao says. And that level "is not enough for China to become a scientific power."

A government mid- to long-term science and technology plan sets a spending target for R&D of 2.5% of gross domestic product (GDP) by 2020, up from 2.13% in 2017. By comparison, the United States spent 2.7% of GDP in 2016, according to OECD. "The question is whether the increased amount of money spent on R&D is effective and efficient," Cao says. This spring the National People's Congress decided to merge the National Natural Science Foundation, which supported a large share of the country’s basic research efforts through reviewed grants, into the Ministry of Science and Technology, which has managed nationally important big science projects. The move has raised concerns that support for basic research by small groups might suffer. The future impact on science funding and management "is something worth paying attention to," Cao says.

 

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Analysis of largest set of genomes from pregnant women reveals genetic links to disease, birth outcomes
October 4, 2018, University of California - Berkeley

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Credit: CC0 Public Domain

Analysis of the world's largest set of genome data from pregnant women, totaling 141,431 expectant mothers from across China, has uncovered unsuspected associations between genes and birth outcomes, including the birth of twins and a woman's age at first pregnancy.

The analysis also allowed researchers to reconstruct the recent movement and intermarriage of different ethnic groups in China, and promises to help identify genes that make people susceptible to infectious diseases.

"It's amazing that this is even possible—that you can take these massive samples and do association mapping to see what the genetic variants are that explain human traits," said co-author Rasmus Nielsen, a professor of integrative biology at the University of California, Berkeley, who oversaw the computational analysis performed by researchers at BGI in Shenzhen, China.

It's even more amazing because the researchers sequenced, on average, only 10 percent of each mother's genome, relying on large numbers of poor-quality genomes so as to leverage cheaper tests to discover new genetic links.

The mothers-to-be had provided blood samples to be tested for fetal chromosomal abnormalities, primarily Down syndrome. This technique, called cell-free fetal DNA testing, a form of non-invasive prenatal testing, is possible because mothers have DNA from their unborn child floating in their bloodstream. With rapid shotgun sequencing, labs can break up all the free-floating DNA in the blood and sequence just enough of the bits to diagnose Down syndrome.

Though not yet widespread in the United States, non-invasive prenatal testing is common in China: 70 percent of such tests worldwide have been performed in China. Sampling the mother's blood can be done early and risk-free, whereas standard prenatal testing in the U.S. involves amniocentesis or chorionic villus sampling, both of which require obtaining fetal cells from inside the uterus and risk harming the unborn child.

BGI was paid by maternity hospitals to conduct these tests, but obtained informed consent from each mother to also analyze the partially sequenced genomes for research purposes, maintaining anonymity. All the analyses were performed in China and the data is hosted in the China National GeneBank.

The data analysis revealed, for example, that variation in a gene called NRG1 is linked to a greater or lesser incidence of twins. One variant of the gene is more common in mothers with twins and is associated with hyperthyroidism, tightening a link between thyroid function and twinning that had previously been seen in mice.

A variant of another gene, EMB, was associated with older first-time mothers.

​

BGI-Shenzhen researchers Siyang Liu, Xun Xu, and Xin Jin (left to right). Credit: BGI-Shenzhen

The analysis also pulled out several genes that had not previously been associated with height and body mass index.

Perhaps most interesting, Nielsen said, is what sequencing of all the DNA in maternal blood tells us about viruses circulating through the body, and thus the link between viruses and genes that determine susceptibility to disease.

A variation in one gene, for example, was associated with a higher concentration of herpesvirus 6 in a mother's blood. Herpesvirus 6 is the most common cause of the relatively benign baby rash called roseola, but a high "viral load" correlates with more severe symptoms. People with Alzheimer's disease also have higher levels of herpesvirus 6 in their brains.

"Most people are infected by herpesvirus 6 at some point in their life, but some people seem to be less affected than others. We have now found a human genetic variant that helps control the severity of the infection," Nielsen said. "This is quite interesting because we don't know much about the genetic variants that control why some people seem more susceptible to viral infection and not others."

More correlations remain to be discovered. The BGI team to date has sequenced genomes from more than 3 million pregnant women, much of it accompanied by information on the mothers' and babies' health that can be used to find genetic associations.

"If you have these genotypes and compare them to phenotypes, that is, something you can measure, you can find genetic variants that explain human traits," said Xun Xu, a leader of the BGI team and the study's lead author.

Nielsen, Xu, Siyang Liu and other BGI colleagues will report initial findings from the analysis on Oct. 4 in the journal Cell.

Sequencing by imputation

To find genes associated with human traits—height and weight, for instance—researchers typically sequence thoroughly a small number of genomes—hundreds to thousands—and scan the genomes for variations in the sequence that are more common in people with the trait. The gold standard now is to sequence each genome 60 times to insure accuracy given inherent errors in the sequencing process. Even if each genome is sequenced a mere 20 times, which is good but not great, it still gets expensive.

The new study relies on only partial genomes—which are cheaper to get—but massive numbers of them. On average, about one-tenth of each mothers' genome was sequenced, because that is all that is necessary for a doctor to diagnose a chromosomal anomaly in the fetus. For example, Down syndrome, or trisomy 21, is caused by three rather than two copies of chromosome 21. A single cycle of sequencing is enough to determine whether some genes are 50 percent more common than normal, indicative of one extra chromosome.

But partial genomes can tell researchers a lot too, Nielsen said.

Think of reconstructing a lost book from thousands of error-prone copies, complicated by the fact that you have only about 10 percent of each copy. By looking for overlaps and inferring words from context—called imputation—you could reconstruct a lost manuscript.

In reconstructing partial genomes, scientists have another important data set: all the complete human genomes sequenced to date, with all their individual variations.

Proof that imputation using more than 141,000 partial genomes works is that the reconstructed geographical distribution in China of minority groups and the dominant Han Chinese reflect known population movements in the country over the last 100 years.

"Because the sample size is so large, we can get at recent population movements, including relocations as a consequence of China's governmental policies," Nielsen said. Many populations of Han Chinese in western China are more closely related to the populations of large cities on the East Coast, for example, reflecting relocation of large numbers of people into the sparsely populated countryside.

The researchers also found that many Chinese had genetic variants common among Indians, Southeast Asians and, along the route of the old Silk Road, Europeans.

Nielsen is currently working with his BGI colleagues to analyze the genomes of 1 million Chinese women who underwent non-invasive prenatal testing.



Analysis of largest set of genomes from pregnant women reveals genetic links to disease, birth outcomes | MedicalXpress.com

Siyang Liu, Shujia Huang, Fang Chen, Lijian Zhao, Yuying Yuan, Stephen Starko Francis, Lin Fang, Zilong Li, Long Lin, Rong Liu, Yong Zhang, Huixin Xu, Shengkang Li, Yuwen Zhou, Robert W. Davies, Qiang Liu, Robin G. Walters, Kuang Lin, Jia Ju, Thorfinn Korneliussen, Melinda A. Yang, Qiaomei Fu, Jun Wang, Lijun Zhou, Anders Krogh, Hongyun Zhang, Wei Wang, Zhengming Chen, Zhiming Cai, Ye Yin, Huanming Yang, Mao Mao, Jay Shendure, Jian Wang, Anders Albrechtsen, Xin Jin, Rasmus Nielsen & Xun X. Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History. Cell (2018). DOI: 10.1016/j.cell.2018.08.016.​

Country's largest genome project proves its value
By CHAI HUA | China Daily | Updated: 2018-10-11 07:30

Researchers at BGI work in the lab in Shenzhen, Guangdong province. [File photo/VCG]

Study will improve development of medicines and health management

A genome study of more than 140,000 people has greatly expanded China's knowledge of its vast population and ethnic groups.

Previous Chinese population studies had only involved thousands of people, mainly Han Chinese from the eastern coast.

The largest of its kind for the Chinese population to date, the study was conducted by Shenzhen-based Beijing Genomics Institute and published in the international academic journal Cell on Oct 4.

"The study is significant to the development of China's medicine and health management industry, which has relied on foreign technology and studies for a long time because we didn't have enough genome data from the Chinese population to work on," said Xu Xun, president of BGI Research and the study's lead author.

It discovered the genetic structure of the various ethnic groups, found six genes that display significant differences of people across latitudes, and identified the gene flow patterns between Europeans, South Asians, East Asians and Chinese.

For instance, people from the southern part of China have developed stronger immunity against malaria than those in the north, but a gene related to fatty acid metabolism has a much higher frequency in most of the northern provinces.

In addition, people in Gansu and Qinghai provinces, a key area of the Silk Road, share more similar genes with Europeans.

It also discovered new associations among Chinese between genes and conditions such as birth defects, infectious diseases and cancers.

About 78 percent of studies in the world about the relationship of gene and diseases are based on European individuals, Xu added.

The latest data cover all 31 provincial-level administrative units in the Chinese mainland and represent Han Chinese and 36 ethnic minorities.

"In the next three years, BGI plans to further expand the database to 1 million," Xu said. BGI started its Million Chinese Genome Project in 2016 and Xu's study represents its first phase.

Genomic study on a national level has been widely regarded as a significant factor for a nation's core competence in the biomedical field.

In the United Kingdom, the leader in the field, one study of 500,000 samples has finished and another project based on a population of five million was announced earlier this month.

BGI researchers admitted there is still a gap between China's genetic research and that in Europe and the United States, but they said it is narrowing.

 

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PUBLIC RELEASE: 10-OCT-2018
Blue roses could be coming soon to a garden near you
AMERICAN CHEMICAL SOCIETY

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By expressing bacterial genes, white rose petals can take on a blue hue. CREDIT: American Chemical Society

For centuries, gardeners have attempted to breed blue roses with no success. But now, thanks to modern biotechnology, the elusive blue rose may finally be attainable. Researchers have found a way to express pigment-producing enzymes from bacteria in the petals of a white rose, tinting the flowers blue. They report their results in ACS Synthetic Biology.

Although blue roses do not exist in nature, florists can produce blue-hued flowers by placing cut roses in dye. Also, in a painstaking 20-year effort, biotechnologists made a "blue rose" through a combination of genetic engineering and selective breeding. However, the rose is more mauve-colored than blue. Yihua Chen, Yan Zhang and colleagues wanted to develop a simple process that could produce a true-blue rose.

For this purpose, the researchers chose two bacterial enzymes that together can convert L-glutamine, a common constituent of rose petals, into the blue pigment indigoidine. The team engineered a strain of Agrobacterium tumefaciens that contains the two pigment-producing genes, which originate from a different species of bacteria. A. tumefaciens is often used in plant biotechnology because the bacteria readily inserts foreign DNA into plant genomes. When the researchers injected the engineered bacteria into a white rose petal, the bacteria transferred the pigment-producing genes to the rose genome, and a blue color spread from the injection site. Although the color is short-lived and spotty, the team states that the rose produced in this study is the world's first engineered blue rose. They say that the next step is to engineer roses that produce the two enzymes themselves, without the need for injections.


Blue roses could be coming soon to a garden near you | EurekAlert! Science News

 

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China develops high-power laser film for aeronautics
By Yin Han Source:Global Times Published: 2018/10/11 22:58:45

China's scientists achieved a milestone in laser fusion, long blocked by Western countries, which could be used to increase the efficiency of detectors in aeronautics and astronautics.

This high-power laser film, developed by a laboratory supported by the Chinese Academy of Sciences' Shanghai Institute of Optics and Fine Mechanics, won first prize at an international competition because of its high damage threshold, Science and Technology Daily reported on Thursday.

The film's damage threshold of the China-developed film was 20 percent higher than the second placer, the report said.

The high-power laser film is an indispensable component of a laser fusion device or other intense laser systems, and would be used for research in laser inertial confinement fusion and in aeronautics and astronautics, the report said.

The film can re-direct the high-power laser without weakening its power, and the damage threshold measures the film's ability to guide the laser to its target.

The film can better focus the laser in one direction without losing much power, which could "enable detectors, communication devices, and other laser-based devices to use lower energy for a better effect," Wang Yanan, deputy editor of Aerospace Knowledge magazine, told the Global Times on Thursday.

The report also noted that preparing the high-power laser film is complex and interdisciplinary.

However, it was blocked by Western countries, with related products prevented from being sent to China.

 

[JSCh]

First Mouse Embryos Made from Two Fathers
The bipaternal pups died soon after birth, but mice with two mothers grew into fertile adults.

Oct 11, 2018, ABBY OLENA

ABOVE: A healthy adult bimaternal mouse with offspring of her own
LEYUN WANG

Over the last decade or so, researchers have generated mouse pups with genetic contributions from two female parents by manipulating imprinted genomic regions, where epigenetic modifications of the DNA restrict the expression of certain genes to one parent’s copy. In a study published today (October 11) in Cell Stem Cell, a team from the Chinese Academy of Sciences has improved on prior work by producing mice with two mothers that appear to grow normally—unlike the mice produced in previous efforts—and live to have pups of their own. They used a similar strategy to make embryos with two fathers, but the progeny did not survive long after birth.

“This is basically the first study that shows that you can generate a mouse from two fathers. It is impressive,” says Hendrik Marks, a biologist at Radboud University in the Netherlands who was not involved in the work. It was known that imprinting was important because of previous difficulty producing bimaternal and bipaternal embryos, he adds, “but now that [the authors] actually are able to generate these mice, this is a starting point. You can start looking at each imprinted gene and ask how it contributes.”

The most important part of this paper is that they managed to generate bipaternal embryos and let them develop to term.

—Yi Zhang, Boston Children's Hospital and Harvard Medical School​

In 2012, a team made up of many of the same researchers at the Chinese Academy of Sciences made mouse embryonic stem cells with half the normal number of chromosomes by injecting a single sperm into an egg without a nucleus. They followed up in 2013 by creating haploid embryonic stem cells from unfertilized eggs. Then, in 2015, the scientists injected the maternal haploid cells into oocytes to generate mice with genetic contributions from two mothers. Although the pups grew to be able to reproduce, they were overall smaller than wildtype animals.

In the current study, the authors wanted to both improve upon bimaternal mice and use their haploid stem cells to create the first mice with two fathers.

“The biggest challenge is that we didn’t know whether bipaternal reproduction” would be possible in mice, writes coauthor Baoyang Hu in an email to The Scientist. “Bimaternal reproduction, or parthenogenesis, is quite common among vertebrates in the nature, such as amphibians, reptiles, and fish. However, successful reproduction from two males is very rare,” and has only been shown in lab experiments in zebrafish, he adds.

Hu and colleagues found that bimaternal mice made with haploid stem cells bearing genetic deletions in two imprinted regions performed abnormally in behavioral tests and had a smaller body stature. To nudge them closer to typical mice, the team then deleted a third, 12.1-kilobase imprinted region upstream of Rasgrf1. They chose this gene because it is expressed differently in the brains of wildtype and bimaternal adults. They apparently chose right. The resulting offspring grew normally and showed no differences from controls in behavioral tests.

To tackle the problem of bipaternal embryos, the researchers harkened back to their 2012 work, in which they generated haploid stem cells by injecting a sperm into an enucleated egg. When the researchers inserted one of these haploid stem cells and another sperm into a fresh enucleated egg, development started to happen but the embryos stopped growing around day 8, and the placenta ceased growth shortly thereafter.

So they turned to a technique called tetraploid complementation that facilitates placenta development in embryos derived from embryonic stem cells. The authors derived diploid embryonic stem cells from a bipaternal embryo and after letting those cells grow into a blastocyst, they injected another haploid stem cell into the blastocyst.

Even with the extra steps, the research team had to delete seven imprinted regions, which had been shown previously to affect embryonic development, in order to successfully end up with bipaternal pups. Just one fewer deletion resulted in embryos that died quickly after birth from breathing problems and were double the weight of wildtype pups, with swelling throughout their bodies. The pups with seven deleted regions were still slightly larger than wildtype offspring, and died soon after being born, but two of the pups lived more than 48 hours.

“To derive an alive bipaternal mouse, we need to introduce no less than six deletions, which implied that compared to the bimaternal reproduction, more obstacles needed to be crossed,” Hu tells The Scientist.

Constructing embryos from same-sex parents using any of these strategies is inefficient. Only about 14 percent of attempts led to bimaternal embryos, while just 2.5 percent of tetraploid complementation attempts worked for bipaternal embryos with seven genes deleted.

“The most important part of this paper is that they managed to generate bipaternal embryos and let them develop to term,” says Yi Zhang, a biologist at Boston Children’s Hospital and Harvard Medical School who did not participate in the work. Yet, based on the efficiency issues, the short lifespan of the bipaternal pups, and the unknowns about the health of the mice with two moms, he cautions that the authors’ strategies are “still far away from real application” in people.

Z. Li et al., “Generation of uniparental mice from hypomethylated haploid ESCs with imprinting region deletions,” Cell Stem Cell, doi:10.1016/j.stem.2018.09.004, 2018.


First Mouse Embryos Made from Two Fathers | The Scientist Magazine®

 

[JSCh]

Oscillations provide insights into the brain's navigation system
Date: October 12, 2018
Source: Ruhr-University Bochum

The brain creates a map of our environment, which enables reliable spatial navigation. The Nobel Prize was awarded in 2014 for research into how this navigation system works at the cellular level. Researchers at the Medical Center -- University of Freiburg, Ruhr-Universität Bochum, and the Chinese Academy of Sciences in Beijing have now shown that the characteristics of this navigation system are also present in brain oscillations that can be measured using depth electrodes in the human brain. The possibility of testing the neuronal navigation system in this way may open up new approaches for the early diagnosis of Alzheimer's disease. A worsening sense of orientation is one of the first signs of the disease. The researchers published the results in the journal Current Biology on 11 October 2018.

Insights into neural activity

Alzheimer's disease leads to the symptom of spatial disorientation at an early stage in the course of the disease. "The loss of spatial orientation is a major limitation in everyday life for people suffering from Alzheimer's disease," says shared first-author Dr. Lukas Kunz, a scientist at the Epilepsy Centre in the Department of Neurosurgery at the Medical Center -- University of Freiburg. The disorientation may be caused by impairment of the entorhinal cortex. This brain structure is one of the first to be affected by Alzheimer's disease -- and this is where so-called grid cells are located. Together with place cells, these cells form fundamental components of the brain's navigation system.

The scientists from Freiburg, Bochum, and Beijing have now been able to show that brain oscillations can be used to draw conclusions about the activity of grid cells. They recorded brain activity in epilepsy patients using depth electrodes from the entorhinal cortex while the participants were moving in a virtual environment. This was possible because the electrodes had to be placed in the brain anyway in preparation for epilepsy surgery.

Long-term goal: earlier Alzheimer's diagnosis

In the brain activity, they found clear indications that important characteristics of grid cells can also be measured at the network level. "We have found a way to measure the activity of grid cells indirectly using oscillations. Over the long term, this may lead to specific tests of impaired functionality of the neuronal navigation system, such as in the context of the onset of Alzheimer's disease," says Kunz. A very early diagnosis of Alzheimer's might then enable timely therapy with drugs that would otherwise be ineffective.

Story Source:

Materials provided by Ruhr-University Bochum. Note: Content may be edited for style and length.

Journal Reference:

1. Dong Chen, Lukas Kunz, Wenjing Wang, Hui Zhang, Wen-Xu Wang, Andreas Schulze-Bonhage, Peter C. Reinacher, Wenjing Zhou, Shuli Liang, Nikolai Axmacher, Liang Wang. Hexadirectional Modulation of Theta Power in Human Entorhinal Cortex during Spatial Navigation. Current Biology, 2018; DOI: 10.1016/j.cub.2018.08.029

Oscillations provide insights into the brain's navigation system -- ScienceDaily

 

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Quake warning system to be in place by 2023
By Hou Liqiang | China Daily | Updated: 2018-10-13 07:43

Primary school students crouch under desks during an earthquake drill on Friday in Handan, Hebei province. [Photo by Hao Qunying/For China Daily]

China will build a nationwide earthquake early warning system by 2023, said a senior emergency management official.

It has already finished testing an earthquake alert system for high-speed trains, and the system is expected to be extended to the country's entire high-speed rail network, said Zheng Guoguang, vice-minister of emergency management. He made the remarks ahead of the International Day for Disaster Reduction, which falls on Saturday this year.

The early warning system, known as the National Seismic Intensity Rapid Reporting and Early Warning project, was approved by central authorities early last year. It will include more than 15,000 observation stations across the country, at a cost of almost 1.9 billion yuan ($274 million), and 3,360 service terminals in national and provincial government bodies that are related to earthquake relief, as well as in public institutions and vital infrastructure and utilities, such as nuclear power plants.

Observation stations will be set in different areas according to earthquake frequency and the potential risk of and effects from disasters. The North-South Seismic Belt, which encircles most of Sichuan, Gansu and Yunnan provinces, will be one of the key areas for such stations, said Zheng, who also is head of the China Earthquake Administration.

Seismic sensors could detect the first energy that emerges from a quake before the jolt begins. This makes it possible to warn those in affected areas before they feel the impact. The farther people are from the epicenter, the longer they would have to respond in the event of a quake.

Even before the system won approval, the administration teamed up in 2012 with the Ministry of Railways, which has since been reshuffled into China Railway Corp, to establish a team to research an earthquake alert system for high-speed railway.

The system developed by the team has been tested on several railway lines in Fujian and Shanxi provinces and works very well, Zheng said, adding that his administration will continue to cooperate with China Railway to extend the system to all high-speed trains in the country.

The completion of the field test of the alert system on the Datong-Xi'an high-speed railway in August marks the quake alert system's shift from the research and development stage to actual use, the administration said.

Zheng said the system will probably be put into operation first in Southwest China, considering the high frequency of earthquakes there. For example, the Sichuan-Tibet railway, which is under construction, crosses four earthquake faults where 14 earthquakes above magnitude 7.0 have occurred.

Although China's quake alert system for high-speed trains uses advanced technology, the nationwide early warning system is needed for it to work best, Zheng said. Therefore, the country should accelerate construction of the National Seismic Intensity Rapid Reporting and Early Warning project, he said.

Zheng said one challenge that China faces in earthquake alerts is the particular nature of earthquakes in the country. Most earthquake epicenters around the world occur along tectonic plate boundaries, many of which are located in the ocean. In China, however, most tremor epicenters occur within the plate on which the country sits, he said. Such countries as Japan and Mexico usually have more time to alert people to a quake, since it takes time for a quake originating in the ocean to affect land, Zheng added.

In addition to earthquake early warning, China also has been trying to forecast quakes, which is much more difficult, Zheng said.

"The Chinese government is the only one in the world that considers earthquake forecast research as its duty," he said.

China is among the countries that suffer the most from earthquakes. From 1900 to 2017, China was hit by an annual average of 18 earthquakes above magnitude 5.0. So far this year, the number stands at 10.

 

[JSCh]

Sober moment: climate change predicted to push up beer prices
Source: Xinhua| 2018-10-15 23:11:04|Editor: Mu Xuequan


by Xinhua Writer Yao Yuan

BEIJING, Oct. 15 (Xinhua) -- A mug of ice-cold beer might be the best cure for a hot summer's day, but as Earth turns hotter and drier, a sharp reduction in barley output may push up the cost of this inexpensive beverage beyond what many can afford.

Beer is the most popular alcoholic drink in the world by volume consumed, but a new article published in scientific journal Nature Plants says that as climate change impinges on barley farming, beer may see a bitter price hike.

According to the study, the world may see beer prices double on average this century in the highest temperature increase scenario, and even in lowest increase scenarios, beer lovers will still have to dig deeper to cope with a 15-percent price rise.

Scientists from China, Britain, the United States and Mexico worked on the study, which analyzed over 300 extreme weather events predicted before 2099 under different climate change scenarios and their impact on barley and beer production.

Xie Wei, lead author of the article and researcher at China's Peking University, said concurrent drought and heat waves, which will become more frequent and severe in the backdrop of global warming, are estimated to reduce global barley output by between 3 and 17 percent this century.

"This will lead to even larger decreases in supplies to brewing industries as barley used in food production (as animal fodder) will be prioritized," he said.

As beer supplies shrink, wealthy, traditionally beer-loving countries are likely to see the most drastic price hikes. Ireland, for instance, is expected to see an average price hike of 193 percent in the worse case scenario.

Though not falling into that category, China, the largest beer-consuming country, may also witness an 83-percent rise in price, according to the study.

Co-author Nathan Mueller, assistant professor of Earth system science with the University of California, Irvine, said that if current levels of fossil fuel consumption and carbon dioxide emission remained "business as usual," the world's beer market would face the worse-case scenario.

"Our study showed that even modest warming will lead to increases in drought and heat extremes in barley-growing areas," he said.

Xie told Xinhua that the research tried to fill in the blank of climate change studies on "high value-added agricultural products," as previous research mostly focused on the impact on food crops.

He also said the world needs to be more sober about climate change by realizing that it, apart from causing extreme weather events, could also affect consumer good prices, public well-being and employment.

"The public may care more about the changing climate after realizing how it will affect their weekend parties, socialization and even their watching of the World Cup," the researcher said.