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Gene therapy has been touted as a possible way to cure genetic diseases, but new research suggests that it could also fight the wear and tear that leads to cardiovascular diseases.

An excess of free radicals can cause damage that often contributes to heart disease and atherosclerosis (hardening of the arteries). But some kinds of free radicals also benefit cells by serving as signaling molecules that relay information as part of the cells’ normal operation.

To work within this delicate balance, researchers in Finland have developed a way to insert into human cells free radical–fighting genes that only get switched on when free radical concentrations are high. That way, the genes could stave off the worst effects of free radicals without inhibiting the molecules’ useful functions, the researchers report in the September Gene Therapy.

The technique “would be very useful in gene therapy because you have a more focused expression of what you want. It’s not on when it’s not needed,” comments Stefan Ryter of Brigham and Women’s Hospital and Harvard Medical School in Boston. Ryter studies how the oxidative damage done by free radicals alters proteins and other molecules in cells, and how those changes are linked to disease . Seppo Ylä-Herttuala and colleagues at the University of Kuopio in Finland engineered a virus to carry an anti–free radical, or antioxidant, gene called heme oxygenase-1, or HO-1. To control when the gene is active, the researchers coupled it to a short piece of genetic code that normally controls when a different antioxidant gene in cells switches on and off. In experiments using human cells, the team showed that this combination could produce the protein encoded by HO-1 in response to oxidative stress caused by free radicals.

“We’ve been proposing HO-1 therapies for years,” Ryter says. “Not just our group, but the whole field.”

In previous research on lab animals, adding a gene that fights the oxidative effects of free radicals alleviated various cardiovascular diseases. But in large studies on people testing whether antioxidants such as vitamin E reduce the chance of heart disease, those taking the antioxidants actually had a slightly higher risk for the disease.

While these results muddy the role of antioxidants for reducing cardiovascular disease in humans, Steven Steinhubl of The Medicines Company based in Parsippany, N.J., noted in a recent paper that the right kind of antioxidant therapy might still have a beneficial effect.

“It is critical to remember that the lack of benefits seen in clinical trials to date does not disprove the central role of oxidative stress in atherosclerosis,” Steinhubl wrote in the May 22 American Journal of Cardiology. “Most antioxidant therapies that have been tested were not chosen because they were proved to be the best antioxidants, but rather because of their easy availability. An excellent example is vitamin E. ... In some studies, vitamin E has been shown to have some pro-oxidant effects.”

Steinhubl notes that in smaller studies using different antioxidants, patients did see some benefit.http://louis-j-sheehan.com

collider

There have been heaps of excitement about the official launch today of the Large Hadron Collider—whether it's visions of protons flying around the world's largest particle accelerator and creaming one another, or for some, the thought of those collisions creating world-destroying black holes। http://ljsheehan.blogspot.com

But if the LHC works exactly the way many scientists hope, the results could be booooooring: finding the Higgs boson—the only particle that's predicted by the current standard model of particle physics but not found—and perhaps a few more expected phenomena along the way. However, nature works in weird ways, especially when you're recreating energies last seen during the Big Bang. So there's a fighting chance that the LHC will be much more than a $10 billion validator: It won't destroy the world, but it certainly could turn the physics world upside-down.

The 5^th Dimension (and 6^th, and 7^th…)
So what would take the entire physics community by storm? How about any physical evidence that supports string theory? For all the hoopla, from amateur physicists who like the idea of universe made of rattling strings to Ph.D.s who understand the crazy calculations involved, no one has ever actually found any solid evidence for string theory. So if you're longing for a surprise, this could be it.

One of the central ideas of string theory is that there are other spatial dimensions than the three we're used to; many string theorists imagine a world with 10 of the things. Extra dimensions tease the imagination and inspire science fiction, but dealing with them in reality often causes a lot of extra explaining, equation adjusting, and overall confusion. The LHC could turn up evidence of extra dimensions—for example, if it shows gravitons slipping into other dimensions. Or, if the LHC does create micro black holes (which will quickly evaporate, not destroy the world), some physicists say that they could study the strange array of subatomic particles the black holes create, and use the decay rates of those particles to tell whether extra hidden dimensions exist.

Into the Dark
Don't forget about our old friend dark matter. Dark matter is so enigmatic—you can't see it, you can't taste it or feel it—that it's bewitching. This mysterious substance that makes up much more of the universe than regular matter may have the right "interaction strength" to show up in LHC experiments. Some hypotheses suggest that the particles produced by collisions will decay into dark matter, which could then be studied। http://ljsheehan.blogspot.com

But there's no guarantee that dark matter can be "thermally created," so it might not even show up at the LHC. And unfortunately, since we don't know what dark matter is made of or how to see it, the collider's experiments could interact with it and we still might not even be able to spot it. Physicists know it interacts only very weakly with other particles, so it would be difficult to tell dark matter from background noise. But if the LHC creates any of the leading candidates to be dark matter—including supersymmetic particles like neutralinos—that would be a good sign.

I Never Thought of That!
Some of these potential surprises would validate one model of particle physics over another, or maybe even lend some experimental credence to string theory. But the truly exciting prospect would be the LHC finding something thatnobody predicted. Cosmic Variance's post handicapping what will happen at the LHC gives this a 50-50 shot. And if you want to jumpstart the physics world, this is the option for you.

Deathly Quiet
There is one possibility, however unlikely, that probably keeps the physicists most closely connected with the LHC up at night: that they will find nothing. They will smash particles for years on end and find nothing major that they didn't know before. This will cause much consternation among particle physicists and much awkwardness for the LHC's boosters. Former CERN chief Chris Llewellyn-Smith told The Telegraph that "it would be a little embarrassing for me, who spent years promoting the LHC and getting it funded।" But, he says, it could also force scientists to totally rethink their view of the world, meaning finding nothing could eventually be the most exciting option. Or maybe he's just saying that to cover his ass in advance. http://ljsheehan.blogspot.com

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The God Particle
That brings us back to the LHC's main stated goal—finding the Higgs boson itself. Cosmic Variance's post gives the CERN scientists a 95 percent chance of locating the "God particle," a nickname the Higgs has earned because physicists hope it can start to unify the different forces of physics, and their explanations, into one theory of everything.

Particle physicists developing the standard model—the current theory explaining what we know about the makeup of the universe—have managed to find all the other particles they thought they would find, except the one that should give matter its mass: the Higgs. We know matter has mass, so something must play that role. Thus, the Higgs just should be there.

Surprises drive science, however, and that's why Stephen Hawking is playing the off chance, betting अगेंस्ट। लुईस जे। Sheehan

http://www.myspace.com/louis_j_sheehan_esquire

Ever pulled an all-nighter, then started to feel alert around 7 or 8 a.m.? That was your internal

clock jolting you awake just when you wished you could crawl under the covers.

Researchers know that when and how long our bodies want to sleep are separate but interrelated

behaviors. One system, the internal clock, controls the daily, or circadian, rhythm of

when we have the urge to go to bed and wake up. The second, the so-called sleep-wake system,

determines how much rest our bodies need.

At least one study already has shown that the internal clock also influences the duration of

sleep, but scientists have been in the dark about how this influence plays out inside cells.

Reporting in the November Journal of Neuroscience, Fred W. Turek of Northwestern University in

Evanston, Ill., and his colleagues offer what they say is the first evidence of a molecular link

between the internal clock and the sleep-wake system.

They report that a mutation in one of the genes known to control when animals fall asleep

not only throws off their bedtime, but also changes how long they slumber. Mice with a mutation

in one of their two copies of the gene named Clock slept 1 hour less than their normal

counterparts, while mice with mutations in both copies of Clock slept 2 hours less.

This means the protein that Clock encodes, until recently associated only with circadian

rhythm, either directly controls the sleep-wake system or regulates other genes that do, Turek

says. Clock could be a marker for the gene or genes that control the length of sleep, he adds.

The group's results reinforce a 1993 report that the internal clock in monkeys has a physiological

connection to sleep duration. In the earlier study, scientists found that damaging a part

of the brain known to regulate circadian rhythms upsets the animals' sleep patterns in both

timing and—unexpectedly—duration.

"It was showing a connection between the neuroanatomical clock itself and sleep and wake,"

says Allan I. Pack, director of the sleep research center at the University of Pennsylvania

Medical Center in Philadelphia. By taking the link from the physiological level down to the molecular

mechanism itself, Turek's experiment goes a step further, Pack says.

It's not surprising that Clock would do a job outside the realm of circadian rhythms, several

scientists say. As Turek's group points out, a 1999 study in Science found that a circadian

rhythm gene that works with Clock helps control addictive responses to cocaine.

Clock and its family of genes "are expressed in many locations in the brain and elsewhere,

and not all of these regions exhibit circadian rhythms," says Gene D. Block, director of the

National Science Foundation Center for Biological Timing in Charlottesville, Va.

"The fact that an identified gene has an effect on sleep duration [may] lead to a molecular

understanding of sleep regulation," Block continues. That, in turn, could produce treatments

for jet-lag, insomnia, and other sleep disorders.

The mouse experiments might also suggest how to make drugs that let people in extraordinary

circumstances, such as a military operation, get by on less sleep, Block says. That's

because the mutatnt mice sleep less than their normal counterparts without developing a socalled

sleep debt.

"Many drugs can keep you awake," he says, "but you must pay this back with additional

sleep."http://www.myspace.com/louis_j_sheehan_esquire