大家好,胖胖翔来也!这次的科技文数量不多,速度部分与基因有关,越障部分则是天上飞的~
Part I:Speed
【Time 1】
Article 1 Stem cells reprogrammed using chemicals alone Patient-specific cells could be made without genetic manipulation.
Scientists have demonstrated a new way to reprogram adult tissue to become cells as versatile as embryonic stem cells — without the addition of extra genes that could increase the risk of dangerous mutations or cancer.
Researchers have been striving to achieve this since 2006, when the creation of so-called induced pluripotent (iPS) cells was first reported. Previously, they had managed to reduce the number of genes needed using small-molecule chemical compounds, but those attempts always required at least one gene, Oct4.
Now, writing in Science, researchers report success in creating iPS cells using chemical compounds only — what they call CiPS cells.
Hongkui Deng, a stem-cell biologist at Peking University in Beijing, and his team screened 10,000 small molecules to find chemical substitutes for the gene. Whereas other groups looked for compounds that would directly stand in for Oct4, Deng's team took an indirect approach: searching for small-molecule compounds that could reprogram the cells in the presence of all the usual genes except Oct4.
Then came the most difficult part. When the group teamed the Oct4 replacements with replacements for the other three genes, the adult cells did not become pluripotent, or able to turn into any cell type, says Deng.
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【Time 2】
Fine-tuning
The researchers tinkered with the combinations of chemicals for more than a year, until they finally found one that produced some cells that were in an early stage of reprogramming. But the cells still lacked the hallmark genes indicating pluripotency. By adding DZNep, a compound known to catalyse late reprogramming stages, they finally got fully reprogrammed cells, but in only very small numbers. One further chemical increased efficiency by 40 times. Finally, using a cocktail of seven compounds, the group was able to get 0.2% of cells to convert — results comparable to those from standard iPS production techniques.
The team proved that the cells were pluripotent by introducing them into developing mouse embryos. In the resulting animals, the CiPS cells had contributed to all major cell types, including liver, heart, brain, skin and muscle.
“People have always wondered whether all factors can be replaced by small molecules. The paper shows they can,” says Rudolf Jaenisch, a cell biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, who was among the first researchers to produce iPS cells. Studies of CiPS cells could give insight into the mechanisms of reprogramming, says Jaenisch.
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【Time 3】
The frog's secret
The achievement could even help regenerative biologists to work out how amphibians grow new limbs. Deng’s group found that one gene indicative of pluripotency, Sall4, was expressed much earlier in the CiPS-cell reprogramming process than in iPS-cell reprogramming. The same Sall4 involvement is seen in frogs that regenerate a lost a limb4: before the regeneration, cells in the limb de-differentiate, a process akin to reprogramming, and Sall4 is active early in that process.
The discovery “provides an important framework to decipher the signalling pathways leading to Sall4 expression” in regulating limb regeneration, says Anton Neff, who studies organ regeneration at Indiana University in Bloomington.
Sheng Ding, a reprogramming researcher at the Gladstone Institutes in San Francisco, California, says that the study marks “significant progress” in the field, but notes that chemical reprogramming is unlikely to be used widely until the team can show that it can work for human cells, not just mouse ones. Other strategies, including one that uses RNA, can complete reprogramming with less risk of disturbing the genes than the original iPS-generation method, and are already in use in humans. Indeed, clinical trials with iPS cells derived through such means are already being planned.
Deng has made some progress towards using his method in human cells, but it will require tweaks. ”Maybe some additional small molecules are needed,” he says.
If it the technique is found to be safe and effective in humans, it could be useful for the clinic. It does not risk causing mutations, and the compounds themselves seem to be safe — four of them are in fact already in clinical use. The small molecules can easily pass through cell membranes, so they can be washed away after they have initiated the reprogramming.
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Resource: http://www.nature.com/news/stem-cells-reprogrammed-using-chemicals-alone-1.13416
【Time 4】
Article 2
'Female' Chromosome May Leave a Mark on Male Fertility
Behind every great man, the saying goes, there's a great woman. And behind every sperm, there may be an X chromosome gene. In humans, the Y chromosome makes men, men, or so researchers have thought: It contains genes that are responsible for sex determination, male development, and male fertility. But now a team has discovered that X—"the female chromosome"—could also play a significant role in maleness. It contains scores of genes that are active only in tissue destined to become sperm. The finding shakes up our ideas about how sex chromosomes influence gender and also suggests that at least some parts of the X chromosome are playing an unexpectedly dynamic role in evolution.
Each mammal has a pair of sex chromosomes. Females have two copies of the X chromosome, and males have one, along with a Y chromosome. The body needs only one active copy of the X chromosome, so in females, the second copy is disabled. Almost 50 years ago, a geneticist named Susumu Ohno proposed that this shutdown slowed the evolution of the X chromosome, and he predicted that its genes would be very similar across most mammals. David Page, a geneticist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, wanted to check if that was true between mice and humans, which are separated by 80 million years of evolution.
Although the genomes of both species had already been decoded, there were gaps and mistakes in the DNA sequence of the human X chromosome that first needed to be filled in or fixed. Using a special sequencing technique that it developed, Page's research team determined the order of the DNA bases in those gaps—many contained multiple duplicated regions of DNA that were impossible to decipher with the technology available when the X chromosome was first sequenced. Then the researchers compared the genes in the mouse and human versions of the chromosome.
The two share a majority of their 800 or so genes, Page and his colleagues report online today in Nature Genetics. Those shared, relatively stable genes are active in both males and females and exist as single copies on the chromosomes. Mutations in these previously described genes are responsible for the so-called X-linked recessive diseases such as hemophilia and Duchenne muscular dystrophy. "These are the genes of the X chromosome of textbooks," Page says.
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【Time 5】
But his team's search uncovered a different, wilder side to this chromosome as well. There are 144 human X chromosome genes with no counterparts in mice, and 197 such mice genes are unique. Of the 144 human ones, 107 exist in multiple copies in the newly sequenced duplicated regions of the X and seem to be changing rapidly. Based on such evidence, Page concludes that these genes have appeared since the ancestors of mice and humans split off from each other.
"I am surprised by the large number of unshared genes between the human X and mouse X," says Jianzhi Zhang, an evolutionary geneticist at the University of Michigan, Ann Arbor, who was not involved with the work. "The finding suggests that X chromosome gene content is probably changing all the time."
When genes change, they have the opportunity to influence evolution, and Page thinks that the new X chromosome genes may be particularly potent. Some previously identified X chromosome genes, for example, seem to have played a role in mouse speciation. He and his colleagues surveyed eight human male and female tissues to begin to see what the genes do. Unlike the textbook X genes, "in many cases these [unshared] genes are not even expressed in females," Page says. Instead, they are active in the testis, primarily in tissue destined to become sperm, Page's team reports. "We think the X chromosome is leading a double life," he says, with one part being stable and behaving as the textbooks say, and another part changing and influencing male traits.
Elsewhere in the genome, duplicated regions "are already known to be of immense biomedical significance" in cancer and other diseases, Page says. He is hoping that other researchers will start looking more closely at whether genes in the duplicated regions of the X chromosome are likewise important, particularly with respect to male fertility and testis cancer.
Zhang is cautious. "We must first know the function of these genes," he says, to understand their impact on health and on speciation. One thing is for certain, however: "People will start paying attention to the recent evolution of the X chromosome."
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Resource: http://news.sciencemag.org/sciencenow/2013/07/female-chromosome-may-leave-a-ma.html
Part II: Obstacle
【Time 6】
Article 3
Minions on the Ground May Be Leaders in the Sky
When a flock of birds changes direction on a dime, it's easy to imagine that the group is controlled by a single, collective mind. But in reality, the individual matters. That's the message of new research on group navigation in homing pigeons. The study used computer tracking to reveal a complex hierarchy, where even birds with a low social rank on the ground may be trusted leaders in the air.
In research on animal social dynamics, large mammals such as wolves and gorillas have received a lot of attention, because their groups' smaller numbers make them easier to study, says Andrew King, a behavioral ecologist at Swansea University in the United Kingdom who was not involved in the study. But when hundreds or thousands of creatures synchronize their movements, the decision-making process is harder to sort out. King says that these big groups have traditionally been viewed as hoards of anonymous agents in a democracy. "Five or so years ago, papers were saying that you should be finding consensus decisions where everybody has an equal say."
And yet elaborate synchronized movements arise from individuals with various abilities and social roles. Zoologist Dora Biro of the University of Oxford in the United Kingdom wanted to investigate how a flock of pigeons manages to stay organized as it navigates the skies. "Different individuals within these flocks might have different ideas about where they want to go," she says "but at the same time, they want to maintain a kind of cohesive flock, because there's safety in numbers." Computerized tracking methods make this type of research possible. Remote visual sensors and GPS units on the birds can keep tabs on every bird at every moment, and complex data analysis can tease out meaningful social patterns.
Biro teamed up with a group of statistical physicists at Eötvös Loránd University and the Hungarian Academy of Sciences in Budapest to search for a leadership structure in flight and to find how it relates to the overall social structure of the flock. The team followed a single flock of pigeons in two different situations: competitive feeding on the ground and navigating in the air. This cross-context approach is "a really important contribution to the field," says behavioral ecologist Darren Croft of the University of Exeter in the United Kingdom who was not involved in the work. "We knew about dominance and we knew about flight, but no one has put those two things together."
The team first identified the birds more likely to win out in confrontations and gain access to food. In the lab, each bird wore a unique three-colored barcode on its back, and a camera attached to the ceiling tracked the animals as they clambered around a cup of grain. A program evaluated birds in pairs and picked the dominant one based on how quickly he or she approached or avoided the other birds and who ended up reaching the snack. Dominant birds tended to be both larger and more aggressive.
When the same birds took to the air in a flock of 30, each wore a tiny GPS unit on its back, which took 10 position readings every second. Every time the flock made a decision—to shift directions, for example—the researchers compared the movement of each bird to the others to find who shifted first, and by how much time. "You can draw an arrow between Bird A and Bird B to show which one tends to lead the other," Biro says, "and you can draw up, basically, a network of these interactions to cover the entire flock."
The network that emerged was far from a perfect democracy. The birds formed a stable hierarchy, where certain individuals made decisions and others waited for cues. A leading bird might swerve first, prompting a neighbor to adopt the same direction. (Some in-between birds were both trusted leaders and devoted followers.) What's more, the leaders in flight weren't the dominant birds on the ground, meaning that the pigeons ignore their land-based social structure while in the air, the team reports online today in the Proceedings of the National Academy of Sciences.
An individual's leadership role in the air remained constant, regardless of the composition of its flock, suggesting that certain qualities inspire the trust and obedience of others. But exactly what makes a natural leader isn't yet clear. Biro thinks there are likely multiple factors at play, from better navigational skills and more decisive movements to motivational factors, such as eagerness to get back to a nest. Croft points out that the physical demands of flight make it more difficult to display aggression and that when birds collectively decide how to move on the ground, they might stick to their dominance structure.
The same approach could be used to find out how other species, from insects to primates, choose leaders to form stable and successful groups, Biro says. "We know that who you're going to elect as your next president or your prime minister is going to make a huge difference for how happy people will be in the country." The team now hopes to sort out which traits are most valuable for leadership in the animal world。
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Resource: http://news.sciencemag.org/sciencenow/2013/07/minions-on-the-ground-may-be-lea.html |