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队友们，周二的作业来了，大家排队练阅读哦。我把文章标题设置了回复可见。呵呵~
加油！
Cancer’s epicenter
New understanding of how cancers work is yielding new treatments
【Time1】
THE biggest conceptual breakthrough in the war on cancer was the realisation by the 1980s that it is always a genetic disease. Sometimes the genetic flaw is inherited. Sometimes it is the result of exposure to an outside agent such as tobacco smoke or radioactivity. Sometimes it is plain bad luck; a miscopying of a piece of DNA during the normal process of cell division.
Turning that breakthrough into medicine, though, is hard. No one has worked out how to repair DNA directly. It is, rather, a question of discovering the biochemical consequences of the genetic damage and trying to deal with those instead. But recently, another pattern has emerged. It is too early to call it a breakthrough as significant as the cancer-is-caused-by-broken-genes finding, but it might be.
The pattern in question is that many of the genes whose breakage leads to cancer are themselves involved in a specific sort of genetic regulation, known as epigenetics. This switches genes on and off by plastering either their DNA or the proteins which support that DNA in chromosomes with clusters of atoms called methyl and acetyl groups. The nature of these reactions means epigenetic processes are susceptible to chemical intervention in a way that genetic mutations are not. They are, in other words, open to drug treatment. And that is why epigenetics was the subject of a particularly interesting session, held on April 1st, at a meeting of the American Association for Cancer Research in Chicago.
【245】
【Time2】
A problem of overregulation
Dash Dhanak, who leads the epigenetics research group at GlaxoSmithKline, one of the world’s biggest drug companies, described to the meeting his efforts to develop a substance that will inhibit the activity of an enzyme called EZH2. This enzyme attaches methyl groups to histone proteins, which are part of the chromosomal packaging. A lot of lymphomas—cancers of the immune system—are caused by mutations that make EZH2 overactive. Such overactivity methylates histones more than they should be and thus silences the genes they surround, including so-called tumour-suppressor genes whose job is to stop the uncontrolled cell growth that causes cancer.
When Dr Dhanak and his colleagues treated lymphoma cells with a newly developed inhibitor, currently referred to by the unmemorable name GSK2816126, they found that the amount of histone overmethylation declined dramatically. And when they treated both cell cultures and laboratory animals with GSK2816126, they found it also reduces the proliferation of tumour cells while, crucially, having no apparent effect on nearby normal cells.
James Bradner of the Dana-Farber Cancer Institute, in Boston, described a second epigenetic approach to treating cancer. His group have shown that a substance known as JQ1, which inhibits an epigenetic regulator called BRD4, blocks the activity of a gene by the name of Myc. Myc encodes a protein called a transcription factor that is another part of the DNA-regulation system. This particular transcription factor is involved in the expression of about 15% of human genes. Not surprisingly, then, when it goes wrong it is one of the most common causes of cancer.
【262】
【Time3】
Despite numerous attempts, researchers have been unable to find a way to block the activity of Myc directly. Dr Bradner, however, reasoned that blocking BRD4, which is one of Myc’s collaborators, might do the job indirectly. To test this thought he and his colleagues treated mice suffering from Myc-driven myeloma with JQ1. And it worked. JQ1, they found, shut down Myc-activated genes and slowed the proliferation of myeloma cells.
Although neither GSK2816126 nor JQ1 is ready for human trials, two other sorts of epigenetic drugs are already on the market. DNA- demethylating agents, in the form of azacitidine, sold as Vidaza by Celgene, of Summit, New Jersey, and decitabine, sold as Dacogen by Eisai, a Japanese company, are used to treat myelodysplastic syndromes, the precursors of acute myelogenous leukaemia. And histone-deacetylase inhibitors, made by Celgene and by Merck, another New Jersey-based firm, are being used to treat a rare illness called cutaneous T-cell lymphoma.
More recently, researchers led by Stephen Baylin at Johns Hopkins School of Medicine, in Baltimore, have shown that a combination of a histone-deacetylase inhibitor and azacitidine slowed tumour growth in some people with advanced lung cancer. This result was notable for two reasons. It was the first time epigenetic drugs had been deployed successfully against a solid tumour, rather than a leukaemia or a lymphoma (solid tumours are harder to treat, because the drug has to penetrate them). And, second, some of the participants in Dr Baylin’s study who did not show much response to the trial itself then went on to show an unexpectedly good reaction to the routine chemotherapeutic drugs which were employed on them next. Although it is too early to say for sure, Dr Baylin speculates that his epigenetic drugs altered the tumour cells in some lasting way that made them more susceptible to standard chemotherapy.
【304】
【Rest】
That is quite possible. Unlike other forms of gene regulation (those involving transcription factors, for example), epigenetic changes are passed on during cell division to daughter and granddaughter cells until they are actively erased. Once erased, though, they do not return. It might therefore be that epigenetic therapies can effect changes which stop a cancer growing without having to kill all its cells.
That, indeed, appears to be what is happening in the case of GSK2816126. If it is, it would truly be a conceptual breakthrough, and epigenetics might justly take its place alongside genetics in the analysis and treatment of cancer.
【102】
How dung beetles navigate
【Time4】
THE number of animals that navigate by the stars is small. Only some birds, a few seals and, of course, humans have the ability. It had been assumed that other creatures that might do this would need reasonably well-developed brains. That notion has now been proved wrong as the celestial-navigation club welcomes its latest member: the humble dung beetle.
Life in the world of dung beetles is fiercely competitive. After rolling up a ball of highly nutritious dung, the beetle must race off with it or risk having the ball stolen by other beetles. Strength is important, but so too is the route taken. The ideal tactic on the open plains where many dung beetles live is to move in a straight line. This is easy enough during the day, but at night—when the beetles are most active—it is more challenging. Previous work has shown that dung beetles can make use of the moon to help them navigate, yet some still set a straight course on moonless nights.
To find out how, a team working in South Africa led by Eric Warrant and Marie Dacke, of Lund University in Sweden, designed an intriguing experiment. They made caps for 19 dung beetles. Ten wore caps made of cardboard to prevent them seeing the sky and, as a control, nine wore caps made of transparent plastic. The beetles and their dung balls were then released in the centre of a circular arena made of flattened sand and enclosed by a featureless circular wall. As the beetles rolled away under a moonless night sky they were filmed by infra-red cameras.
【269】
【Time5】
The team found that the beetles prevented from seeing the sky by their caps had path lengths that averaged 476.7cm, much longer than the average of 143.4cm travelled by the beetles wearing clear hats.
As the beetles might have used other overhead landmarks, like trees, a second arena was built with a high black wall and a small, dry moat around it. This time the beetles—minus their hats—were timed to see how long it took them to roll their balls from the centre to the point where they could be heard falling into the moat.
Under a full moon the beetles took an average of 21.4 seconds to reach the moat. On a moonless, starry night, their speed was somewhat reduced, but not significantly so. However, under overcast conditions, when neither moonlight nor the stars were visible, the beetles took an average of 117.4 seconds.
Curious as to what it was in the sky that the beetles were using to navigate, the team moved their arena inside the Johannesburg planetarium and reran their experiments. As they report in Current Biology, the beetles presented with a full starlit sky, including the Milky Way or just the Milky Way, took statistically the same amount of time to exit the arena (43.3 seconds and 53.3 seconds). Under a sky full of dim stars they were only a little slower (65.2 seconds). This, speculates Dr Warrant, is because they were still able to spot the cluster that forms the Milky Way.
When allowed to see only the 18 brightest stars or immersed in total darkness, the beetles took more than twice as long to exit the arena. The team now wonders how many other animals might be able to use the glowing strip of light created by the Milky Way to guide them.
【301】
Obstacle
Cities Affect Temperatures for Thousands of Miles
Even if you live more than 1,000 miles from the nearest large city, it could be affecting your weather.
In a new study that shows the extent to which human activities are influencing the atmosphere, scientists have concluded that the heat generated by everyday activities in metropolitan areas alters the character of the jet stream and other major atmospheric systems. This affects temperatures across thousands of miles, significantly warming some areas and cooling others, according to the study this week in Nature Climate Change.
The extra "waste heat" generated from buildings, cars, and other sources in major Northern Hemisphere urban areas causes winter warming across large areas of northern North America and northern Asia. Temperatures in some remote areas increase by as much as 1 degree Celsius (1.8 degrees Fahrenheit), according to the research by scientists at the Scripps Institution of Oceanography; University of California, San Diego; Florida State University; and the National Center for Atmospheric Research.
At the same time, the changes to atmospheric circulation caused by the waste heat cool areas of Europe by as much as 1 degree C (1.8 degrees F), with much of the temperature decrease occurring in the fall.
The net effect on global mean temperatures is nearly negligible -- an average increase worldwide of just 0.01 degrees C (about 0.02 degrees F). This is because the total human-produced waste heat is only about 0.3 percent of the heat transported across higher latitudes by atmospheric and oceanic circulations.
However, the noticeable impact on regional temperatures may explain why some regions are experiencing more winter warming than projected by climate computer models, the researchers conclude. They suggest that models be adjusted to take the influence of waste heat into account.
"The burning of fossil fuel not only emits greenhouse gases but also directly affects temperatures because of heat that escapes from sources like buildings and cars," says NCAR scientist Aixue Hu, a co-author of the study. "Although much of this waste heat is concentrated in large cities, it can change atmospheric patterns in a way that raises or lowers temperatures across considerable distances."
Distinct from urban heat island effect
The researchers stressed that the effect of waste heat is distinct from the so-called urban heat island effect. Such islands are mainly a function of the heat collected and re-radiated by pavement, buildings, and other urban features, whereas the new study examines the heat produced directly through transportation, heating and cooling units, and other activities.
The study, "Energy consumption and the unexplained winter warming over northern Asia and North America," appeared online January 27. It was funded by the National Science Foundation, NCAR's sponsor, as well as the Department of Energy and the National Oceanic and Atmospheric Administration.
Hu, along with lead author Guang Zhang of Scripps and Ming Cai of Florida State University, analyzed the energy consumption -- from heating buildings to powering vehicles -- that generates waste heat release. The world's total energy consumption in 2006 was equivalent to a constant-use rate of 16 terawatts (1 terawatt, or TW, equals 1 trillion watts). Of that, an average rate of 6.7 TW was consumed in 86 metropolitan areas in the Northern Hemisphere.
Using a computer model of the atmosphere, the authors found that the influence of this waste heat can widen the jet stream.
"What we found is that energy use from multiple urban areas collectively can warm the atmosphere remotely, thousands of miles away from the energy consumption regions," Zhang says. "This is accomplished through atmospheric circulation change."
The release of waste heat is different from energy that is naturally distributed in the atmosphere, the researchers noted. The largest source of heat, solar energy, warms Earth's surface and atmospheric circulations redistribute that energy from one region to another. Human energy consumption distributes energy that had lain dormant and sequestered for millions of years, mostly in the form of oil or coal.
Though the amount of human-generated energy is a small portion of that transported by nature, it is highly concentrated in urban areas. In the Northern Hemisphere, many of those urban areas lie directly under major atmospheric troughs and jet streams.
"The world's most populated and energy-intensive metropolitan areas are along the east and west coasts of the North American and Eurasian continents, underneath the most prominent atmospheric circulation troughs and ridges," Cai says. "The release of this concentrated waste energy causes the noticeable interruption to the normal atmospheric circulation systems above, leading to remote surface temperature changes far away from the regions where waste heat is generated."
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发表于 2013-1-28 23:04:10
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