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今天没有忘，作业来了~~
速度
[速度1] 333 words
The value of a good editor
A hitherto-unknown way to evolve
Jan 7th 2012 | from the print edition
IN 1958 Francis Crick, one of the co-discoverers of the double-helical structure of DNA, spelled out what came to be called the “central dogma” of molecular biology. In a nutshell, this says that DNA makes RNA, which makes proteins. In other words DNA—which carries an organism’s genetic code—“writes” that code into bits of RNA, a similar, but not identical molecule. These then act as messengers which tell a cell’s protein-making machinery what to make.
It is a pithy and memorable summary. Sadly, reality is not quite so clear-cut. In a paper in Science, Sandra Garrett and Joshua Rosenthal of the University of Puerto Rico illustrate how the instructions in the DNA are not always followed faithfully. The RNA message can be rewritten before it is read. And that provides an extra opportunity for evolution to occur.
Dr Rosenthal and Ms Garrett were studying octopuses, looking for differences between those that live in warm, tropical water and those that inhabit the poles. They concentrated on the make-up of the ion channels in the animals’ cell membranes. These channels are cylindrical assemblages of protein molecules which help to control such things as the electrical activity of nerve cells and the release of hormones. The two researchers suspected that the channels found in warm-water species would not work well in the freezing temperatures that their polar cousins endure.
That turned out to be correct. What was odd was that the genes for the proteins involved were almost identical in warm- and cold-water animals. This surprised Dr Rosenthal and Ms Garrett, who had expected that natural selection would have changed the DNA, and thus the composition of the resulting protein.
[速度 2] 377 words
Instead, differences in composition between warm-water and cold-water ion channels were the result of a phenomenon called RNA editing, in which special enzymes alter the structure of the RNA messenger, and thus of the final protein.
Though RNA editing has been observed before, in animals ranging from humans to nematode worms, this is the first time an edit has been tied to a clear evolutionary difference caused by a feature of the environment—in this case ambient temperature. Of course, it is not strictly a departure from Crick’s dogma. Enzymes, too, are proteins, and so are the transcription factors that regulate their production. Eventually, when the chain of causation is traced in full, the chances are that the underlying difference between polar and tropical octopuses will be in the DNA itself. RNA editing of this sort does, however, provide another way to drive evolution, and may help explain why animals (as opposed to, say, bacteria) are so complex.
Cancer research
Take five
An ambitious plan for curing cancer in a businesslike way is in the works
Dec 31st 2011 | NEW YORK | from the print edition
RON DEPINHO is a man on a mission. Oddly, though, he does not yet know exactly what that mission is. Dr DePinho is the new president of the MD Anderson Cancer Centre in Houston, Texas. (He took over in September, having previously headed the Belfer Institute, part of Harvard’s Dana-Farber Cancer Institute.) Mindful of his adopted city’s most famous scientific role, as home to Mission Control for the Apollo project, he says his own mission is akin to a moon shot. He aims to cure not one but five varieties of cancer. What he has not yet decided is: which five?
That it is possible to talk of curing even one sort of cancer is largely thanks to an outfit called the International Cancer Genome Consortium. Researchers belonging to this group, which involves 39 projects in four continents, are using high-throughput DNA-sequencing to examine 50 sorts of tumour. They are comparing the mutations in many examples of each type, to find which are common to a type (and thus, presumably, causative) and which are mere accidents. (The DNA-repair apparatus in malignant cells often goes wrong, so such accidents are common.)
[速度 3] 385 words
The consortium’s work is progressing fast, and preliminary results for many tumours are already in. But such knowledge is useless unless it can be translated into treatment. That is where Dr DePinho comes in—for his career has taken him into the boardroom as well as the clinic. He is a serial entrepreneur: he helped found Aveo Pharmaceuticals, which is developing a drug to block the growth of blood vessels in tumours, Metamark Genetics, which works on diagnosing cancers, and Karyopharm Therapeutics, which is trying to regulate the passage of molecules into and out of the cell nucleus, and thus control the nucleus’s activities. His aim in coming to MD Anderson, he says, is to “industrialise” other aspects of biological research in the way that genetics has been pushed forward by high-throughput sequencing.
That will cost billions of dollars. Fortunately, the state of Texas—no pushover when it comes to spending taxpayers’ cash—is creating a $3 billion cancer-research fund to help pay for it. Local philanthropists, including T. Boone Pickens and Ross Perot, are chipping in, too. Their model is the original Human Genome Project, during which the cost of sequencing a single genetic “letter” (a DNA base pair) fell from $10 in 1991 to ten cents in 2001—and is now 3,000 base pairs a cent. They hope their dollars will encourage people working with what are now, essentially, craft technologies to think about how they might industrialise them.
Several techniques look ripe for such industrialisation. Dr DePinho sets great store, for example, by the use of genetically modified mice (he calls them “little patients”) in which mutations found in human cancers can be replicated precisely, but one at a time, to discover the shape of each piece of the jigsaw. If this process can be scaled up it will, as he puts it, allow cancer’s genetic generals to be distinguished from the foot soldiers.
Another field that has great potential is imaging technology—in particular, a combination of positron-emission tomography (which uses radioactive sugar to measure how metabolically active tissue is) and computerised tomography (which uses X-rays to map the body’s internal anatomy). Together these can show whether a treatment is reducing a cancer’s energy consumption, and thus its metabolism. This gives a good indication of how well that treatment is working.
[速度4] 243 words
A family business
Dr DePinho himself will have more duties at MD Anderson than just dealing with the five chosen tumours. The donkey work of creating the Institute for Applied Cancer Science, as the new mission control is to be known, will be done by Lynda Chin. Dr Chin, too, worked at the Belfer Institute. She is part of the International Scientific Steering Committee of the cancer-genome project. And she is also Dr DePinho’s wife. Dr Chin will be assisted by some 55 other scientists from the Belfer, who are making the journey to Texas with her and her husband. That sort of team poaching is common in investment banking but rarer in academic research. Dr DePinho refers to it, jokingly, as metastasis, since a clone of his primary creation will be taking root elsewhere in the country.
As to which five cancers to attack, that decision will be made by the middle of 2012. A crucial consideration will be how likely it looks that research into the tumour in question could get rapidly to the “proof of concept” stage—the point at which it could be taken forward by a business that relied on commercial sources of capital, rather than on the sorts of grants that usually propel academic research. At that moment a new firm might be spun out of the institute, or a deal might be done with an established pharmaceutical firm, to try to get a new drug developed.
[速度 5] 296 words
In recent years many big drug companies have gutted their research departments. This is partly because those departments have failed to come up with new “blockbuster” drugs of the sort that created Big Pharma in the first place, and partly because the big firms’ bosses had hoped that smaller biotechnology companies, of the sort Dr DePinho has helped set up, would do the hard work of drug discovery instead, and then let themselves be bought by the big firms.
Unfortunately, it hasn’t quite worked out like that. The output of the biotech firms has been a trickle, rather than a torrent. They have been one of the worst-performing parts of the private-equity market since 2007, according to Dr DePinho. He hopes to change that—and in the matter of new anti-cancer drugs, the science is looking auspicious. For example, a drug called vemurafenib, which was approved for use in America in August 2011, gives months of extra life to people with metastasising melanoma, one of the deadliest cancers. Vemurafenib is so powerful that some people call it a “Lazarus” drug, after the chap Jesus is said to have raised from the dead.
Crucially for Dr DePinho’s project, the development of vemurafenib was stimulated by the identification of a mutated gene often present in melanomas. He and others like him hope that the cancer-genome consortium will throw up dozens of similar genes, and that they, too, will prove tractable targets for drug development.
Of course, if Dr DePinho had a penny for every time a “cure for cancer” headline proved premature, he wouldn’t need munificent donors. But if his bets on the science and on adopting business methods pay off, the drug industry and millions of patients will benefit. That would be one benign sort of metastasis.
越障
Evolution World Tour: The Cradle of Humankind, South Africa
The world's greatest source of hominid fossils is among dozens of caves just hours from Johannesburg
? By Erin Wayman
? Smithsonian magazine, January 2012, Subscribe
Three million years ago, an eagle soared above an enormous forest in South Africa and zeroed in on its target. Among a group of hominids searching for fruits, nuts and seeds, a 3-year-old child had strayed too far away from its mother. The eagle swooped down, grabbed the 25-pound toddler with its talons and flew off to its nest, perched above the opening to an underground cave. As the eagle dined on its meal, scraps fell into the cave below.
Similarly hair-raising tales—hominids being dragged into caves by leopards or accidentally falling into hidden holes—explain why South Africa’s limestone caves are the world’s greatest source of hominid fossils. About 900 have been recovered from more than a dozen sites scattered over 180 square miles of grassland within a few hours’ drive from Johannesburg. The area is known as the Cradle of Humankind. Scientists have identified at least four hominid species—in addition to our own, Homo sapiens—that lived in this region at various times over the past 3.5 million years.
“Fossils from South African caves have played a critically significant role in the development of our concepts of human evolution,” says C.K. “Bob” Brain, a curator emeritus at South Africa’s Transvaal Museum, who began studying the caves in the 1950s.
The first major discovery of a hominid from the Cradle came in 1924, when the anatomist Raymond Dart found an unusual, bumpy rock among rubble that had been sent to him from a quarry. After months of chipping away at it with one of his wife’s knitting needles, Dart liberated a skull and stared into the face of what appeared to be a young ape that looked surprisingly human. Now known as the Taung Child after the town where it was discovered, it was the first evidence of the species Australopithecus africanus. (More recently scientists have determined that two holes in the skull were made by an eagle’s talons.)
Prior to Dart’s discovery, scientists thought human ancestors emerged in Europe or Asia. The Taung and other fossils—more primitive than Eurasian hominids but still possessing human characteristics, such as the ability to walk upright—compelled early-hominid hunters to shift their search to Africa.
Hominids began to diverge from chimpanzees about seven million years ago. In the Cradle, the oldest-known species is Australopithecus africanus. The four-foot-tall hominid with long arms for tree climbing lived in the region 3.3 million to 2.1 million years ago, when the area was partly forested. As the climate became drier, the forests gave way to more open grasslands, and new hominids evolved. Paranthropus robustus— famous for its massive jaw and giant molars, which allowed the species to chew tough plants—inhabited the area 1.8 million to 1.2 million years ago. It lived alongside the taller, more modern-looking Homo erectus, which also came onto the scene about 1.8 million years ago before disappearing from Africa 500,000 years ago. Farther afield from the Cradle, spread out along South Africa’s southern coast, cave sites such as Blombos Cave, Pinnacle Point and the Klasies River Caves record key evidence of early complex behavior in our own species. Homo sapiens began using red pigments, making blades and eating seafood as early as 164,000 years ago.
Visitors to the Cradle of Humankind can take guided walking tours of Sterkfontein and see a replica of “Little Foot,” a specimen recovered in 1997 that is among the most complete Australopithecus skeletons ever found. The location of one of the Cradle’s most famous specimens—the roughly two-million-year-old Australopithecus africanus skull nicknamed Mrs. Ples (who scientists now think is actually Mr. Ples)—is another highlight of the tour. Those who want to see an active excavation site can arrange private tours of Swartkrans—a cave that is home to an abundance of stone and bone tools dating back almost two million years and some 270 burned bones estimated to be more than one million years old. These bones may be evidence of the earliest known controlled fires. “There’s a rich behavioral record at Swartkrans that we’re trying to plumb for as much information as we can,” says Travis Pickering, a paleoanthropologist at the University of Wisconsin-Madison and director of the Swartkrans Paleoanthropological Research Project.
One question Pickering is trying to answer is who made the tools and tended the fires. Both species that lived in the area at the time—Homo erectus and Paranthropus robustus—were probably capable of manufacturing tools, he says. “We’re trying to investigate and disentangle...what behaviors distinguish these two closely related species.”
One of the most exciting discoveries from the Cradle of Humankind came in 2010, when researchers led by Lee Berger, a paleoanthropologist at the University of the Witwatersrand, announced they had unearthed a new hominid species, Australopithecus sediba, in South Africa’s Malapa Cave. The hominid, nearly two million years old, shares enough crucial features with the genus Homo that its discoverers think it might be the long-sought direct ancestor of our genus, filling in a blank spot in the fossil record. If so, then the Cradle could be the site where hominids evolved beyond their more ape-like features and moved closer to being human.
http://www.smithsonianmag.com/travel/evotourism/Evotourism-World-Tour-The-Cradle-of-Humankind-South-Africa.html |
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发表于 2012-1-9 22:25:13
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