Rodent of the Week: Reversing age-related memory loss

In a truly exciting area of neuroscience, researchers reported this week that they were able to identify specific changes in the brain that impair age-related memory and learning in elderly mice. These are the kind of gradual memory glitches that humans begin to experience in their late 40s and continue during the aging process. It appears that epigenetic changes -- changes in the way genes function but that do not involve changes in DNA -- cause this type of memory decline. But reversing these changes may yield treatments for cognitive loss.

Researchers in Germany determined that memory decline became impaired in aging mice around 16 months of age. Examining the mice, they found changes in the proteins that control gene expression in their brains. One particular change was found in enzymes called histone acetyltransferases. When the researchers treated the mice with a drug that reinstated the change in the enzymes and in the gene expression, they saw improved memory function in the mice. The study was published Thursday in the journal Science.
"This study presents a major advance in thinking about the role of histone modifications in synaptic plasticity and memory formation," J. David Sweatt, chairman of the University of Alabama at Birmingham department of neurobiology, said in a commentary accompanying the study. Sweatt, in a paper published recently, showed that drugs that affect histone acetyltransferases also benefit mice with Alzheimer's disease.
"These studies will hopefully lead to more effective prevention strategies to improve quality of life in the aged, as well as contribute to a better understanding of memory," Sweatt said in a news release.

BP carries out 'BOP brain surgery'

BP is carrying out surgery on the “brain” of the subsea blowout preventer (BOP) it recovered yesterday, with plans to reinstall it in the hopes it will provide accurate readings of the pressures inside the Macondo oil well blowout in the deep-water Gulf of Mexico.

A better handle on the well pressures may help BP refine its options for bringing the well under control sooner rather than later.

“We retrieved what is called the yellow pod, this is the sort of brain on the blowout preventer, and brought it to the surface,” chief operating officer Doug Suttles said yesterday afternoon at a press conference in Houma, Louisiana.

“We are currently working to re-wire that brain. We’re going to redeploy back on the blowout preventer and we hope that will allow us to read pressures inside of it.”

Depending on the information derived from the yellow pod, including the internal pressure in the BOP, BP may be able to try one of two options to bring the well under control.

BOP II

First, BP could try to shear the lower marine riser package and install a second BOP on top of the first, which appears to be too damaged to close the well.

It is understood that the BOP on board the Discoverer Enterprise, which is on location, will be used.

According to Transocean's fleet inventory, the BOP is a Hydril 18¾ inch 15,000 psi, six-ram system with a Cameron 15,000 psi wellhead connector.

Depending on the pressures, BP also may be able to tap into the existing BOP and circulate heavy fluids to kill the well.

Suttles said BP has already manufactured the equipment it would need to inject the fluid and it is being shipped to the location.

Either course of action could likely be done faster than the 90 days Suttles estimated it would take for the relief well to intercept the Macondo bore but neither has been done before at this depth.

“We don’t take any action which could make the spill worse,” Suttles cautioned. “Gathering pressure data from inside the blowout preventer is part of that.”

A video outlining about BP's efforts to halt the Macondo flow is available here.

Macondome

BP has started lowering a containment dome to the seabed. The dome - the first of three - is designed to cover the largest leak at the end of the marine riser.

The "Macondome" traveled to Mississippi Canyon Block 252 on the Edison Chouest Offshore's M/V Joe Griffin on Wednesday.

BP will now bring in Transocean’s drillship Discoverer Enterprise and connect the 70-tonne structure, which measures 14 feet by 24 feet by 40 feet, to the ship via a rigid 2" steel riser with a 6 5/8" drill string.

That operation will take about two days and BP hopes to have the system working by early next week.

BP spokesman Robert Wine said: "The plan is to pump sea water down the annulus to help lift the oil - oil is lighter than sea water - and to keep it fairly warm.

"It's a fairly gassy oil - it has a gas-to-oil ratio of about 3000 - so a major challenge for at least the first 2000 feet is hydrate management. It's at those first couple of thousand feet where the risk of gas hydrate formation is the highest."

Wine added that methanol will be injected at the top of the riser to help reduce the risk of hydrate formation.

Remotely-operated vehicles (ROVs) will assist with the operation. Wine did not know whether ROVs currently working on attempting to activate the Deepwater Horison's crippled BOP would be called to the site to assist.

Gas will be separated out, while oil - the Discoverer Enterprise has a storage capacity of 128,000 barrels - will be shuttled to shore and be stored at one of BP's Gulf coast refineries.

Suttles warned of potential “start-up trouble” since a similar operation has never been done at this water depth.

“We’ll have to learn how to make it operate,” he said.

Work continues on two more domes, one of which is set to go over a smaller leak at the juncture of the riser and the other on the lower marine riser package.

Valve

Earlier this week, BP capped one of the three leaks identified in the Macondo infrastructure, installing a valve over the end of the broken drill pipe that sticks out beyond the end of the riser.

Suttles said the capping operation involved crews first cutting the jagged end of the drill pipe, which extended beyond the end of the broken riser.

They then fabricated and installed the valve.

But Suttles has said capping the drill pipe has not reduced the volume of oil into the Gulf of Mexico from the blownout well.

Landfall

Rear Admiral Mary Landry confirmed that oil had hit the beach at Chandeleur Island.

The Coast Guard has refused to release information on the size of the slick, with Landry repeatedly saying such a figure would be misleading because the slick changes size and shape.

It is believed that at least two offshore gas processing platforms, which move about 6.2 million cubic feet per day, have been shut in due to the spill.

Suttles said “good weather” has aided efforts to place 42,000 feet of booms yesterday to contain the spread and light fires to burn off more of the oil on the water’s surface.

Suttles said over 700,000 feet of total boom is now deployed.

The Coast Guard has begun controlled burns on the spill again and Suttles estimated that “several thousand barrels” of oil have been consumed over the last couple days.

Dispersant

Though planes are still dropping dispersant on the surface slick, officials are analysing the effectiveness of the subsea dispersants applied at the source of the leaks and no decision has been made whether to proceed with untested method.

People living near the spill zone are becoming increasingly concerned about the possible effects of the dispersants in the water.

Crews are using the same two dispersants, Corexit 9500 and Corexit EC9527A above and below the water, Suttles said.

Corexit 9500 can cause skin and respiratory tract irritation, according to material safety data sheets provided by the Coast Guard.

Its overall human hazard potential is “moderate,” the sheets state, while the potential environmental hazard is listed as “low”.

Corexit EC9527A can also irritate the skin and respiratory tract, but it also can damage the liver and central nervous system.

Its human hazard potential is “high” and potential environmental hazard is “moderate”, according to the material safety data sheet.

Industry change

BP executive vice president for the Americas and Asia Robert Dudley said yesterday that the leak would change the global offshore industry "forever".

"Once the clean up is done, the investigation is complete and the lessons learned and spread around the globe from this activity occurring (at) the frontiers of human effort, we will consider the trade-offs of exploring for new sources of domestic energy in the frontiers of deep water," Dudley told business leaders in Boston.

A BP spokesman later told Reuters that Dudley’s comments referred to society’s commitment to oil exploration and not to BP’s own exploration and development work.

Spud

The Transocean semi-submersible rig Development Driller III spudded the first of two planned relief wells shortly after 3pm local time on Sunday.

The well will take between two to three months drill to about 18,000 feet and then intercept the blown-out well.

BP said that the well reached 6805 feet below sea level on Wednesday, or about 1800 feet below the seabed. A 28-inch cashing string has been set and cemented and the well is drilling ahead.

The UK supermajor has decided to bring in a third rig, the Transocean semi-submersible rig Development Driller II, to spud a second relief well.

The rig will arrive on location in about 10 days and will "race" to spud a second relief bore.

Fury

This week US Senate Democratic Leader Harry Reid voiced support for calls to raise the liability cap on companies responsible for oil spills from $75 million to $10 billion.

Calls to increase the spill penalty also drew support from the White House, with Obama press secretary Robert Gibbs saying the president would be open to the proposal.

Democratic Senator Bill Nelson proposed lifting the liability cap.

Disaster

The Macondo well - a discovery well which was to be temporarily abandoned ahead of later completion as a subsea producer - blew out on 20 April.

The well had been drilled to 18,000 feet by the rig Deepwater Horizon. An explosion rocked the semisub before the rig was engulfed in flames.

The semisub sank on 22 April, extinguishing the blaze.

The initial cause of the accident is still unknown, although a senior Transocean executive, Adrian Rose, earlier indicated it seems likely the well blew out.

“We don’t know what caused the accident,” he said. When asked if the incident involved a blowout, he replied: "Basically, yes."

Eleven of the 126 crew on board the Deepwater Horizon at the time of the explosion are missing, presumed dead.

Drilling giant Transocean has confirmed nine of its employees are among the missing. Two worked for services outfit Smith International and Schlumberger's M-I Swaco joint venture.

In gambling, brain explains attraction of near-misses

You pull the lever on the slot machine and get two strawberries and an apple. Or you throw down dice and get a six, then an eight, when you were aiming for a seven. So close! Play again!
We get a rush from playing games that we feel like we've almost won, but have lost by a small margin. For people who gamble, the allure of the "near miss" can keep the dice rolling, the slots turning, and the money slipping away.
A new study in the Journal of Neuroscience looks deeper into the mind of the gambler. Psychology researchers Henry Chase and Luke Clark looked at 20 regular gamblers. Participants varied from recreational gamblers to "pathological gamblers," meaning their habits may interfere with everyday life.
Researchers scanned the brains of these gamblers while they performed a simplified slot machine task. Although the sample size is small, studies that make use of functional magnetic resonance imaging (fMRI) tend to have fewer participants than survey-based experiments, and can still have important implications.
The study found that near-miss outcomes during gambling involve the brain's reward system; in particular, areas called the ventral striatum and the anterior insula.
A previous study on healthy volunteers also found that near misses are linked with heightened activity in these same brain regions associated with monetary wins.
Scientists have long known that a small cluster of brain cells that release a chemical called dopamine have been associated with addiction, but there has never been a clear explanation for it.
"This study provides an important advance in our understanding of how the brain's reward circuits underlie one form of addictive behavior, pathological gambling," said Steven Quartz, director of the California Institute of Technology’s Brain, Mind, and Society Ph.D. program, who was not involved in the study. "Many modern games of chance, especially slot machines, compel some people to play repeatedly even when they are not winning," he said in an e-mail.
Chase and Clark also showed that the more severe a person's gambling is, the more these near misses trigger the reward circuit. But the brain region in question is also involved in learning. That means the gambler's brain may be "tricked" into thinking that it is learning new information about the environment through near misses, Quartz said.
"Ultimately, a better understanding of the rewarding effects of near misses may have implications for both treating problem gambling and for regulatory practices of the gambling industry," he said.
The authors noted that they did not take into account such conditions as nicotine dependence and personality disorders, which may have impacted the brains and behaviors of participants. Also,the group of regular gamblers in this study was almost all male.
Further research is necessary to determine more conclusively how the minds of gamblers work.

Discoveries: 'The Secret Life of the Grown-Up Brain'

The Secret Life of the Grown-Up Brain
The Surprising Talents of the Middle-aged Mind

Barbara Strauch
Viking: 218 pp., $26.95

Good news! Our middle-aged brains are surprisingly competent and surprisingly talented. We're smarter, calmer, happier and, as one scientist (herself in middle age) puts it: "We just know stuff." We may forget names, or even what we had for breakfast, but Barbara Strauch amasses study after study that shows the human brain is "at its peak in those years and stays there longer than any of us dared to hope." We start, on the whole, to get happier "in part because we start to use our brains differently. There may be evolutionary reasons for this as well. A happier, calmer middle-aged human is better able to help the younger humans in his care."

There is a decline in some chemicals like dopamine and, as some scientists have discovered, a "default mode" we enter—a "daydreaming state of quiet" but also "continuous inner chatter." In middle age we use "two sides of the brain instead of one"; if we strengthen the brain's frontal cortex (through exercise, brain training and good eating) we create a "cognitive reserve that is a buffer against aging, helps us get to the gist of things faster and act judiciously rather than rashly."

In the book's last part, Strauch recommends steps we can take to help our brains meet their full potential in middle age and onward. Exercise is key: Studies show it strengthens the dentate gyrus (a section of the hippocampus), helps increase new neuron production, strengthens and builds myelin (the fatty coating around neurons) and even increases brain volume. (Stress, of course, retards neuron production.) Strauch also suggests foods to eat that are rich in antioxidants and limit inflammation; and then there's also brain training. There are a lot of brain books out there now, and this is one of the best.

Take Good Care of the Garden and Dogs
Family, Friendships, and Faith in Small-Town Alaska

Heather Lende
Algonquin Books of Chapel Hill: 287 pp., $22.95

Heather Lende is one of those increasingly rare species: a small-town newspaper reporter. She has lived for 25 years in Haines, Alaska, where she writes obituaries for the Chilkat Valley News and a regular column on daily life in a small town for the Anchorage Daily News. In April 2005 she was riding her bike when she fell and was run over by Kevin, the local grocery store manager, in his truck. This is the story of her recovery, with the help of friends, family and all kinds of people in her community, but it is also the story of how she found true grace and gratitude. A year after the bike accident, Lende's mother, one of those equally rare utterly stable role models, died of leukemia. "Take good care of the garden and dogs," she said before she died. Writing a small town's obituaries gave Lende a good platform from which to carry out her mother's advice. The book is full of vivid characters (a librarian who collects overdue books in person) and strange, sad deaths. Lende is not one for looking back. She has a simple, chatty style most readers will find oddly comforting. Life does, in fact, go on.

Cold Earth
A Novel

Sarah Moss
Counterpoint: 278 pp., $14.95

I'm not one for thrillers (they scare me and make me feel stupid, which can lead to behavior that resembles that of a large, cornered animal), but "Cold Earth" had too many good ingredients to pass up: six archeologists working in Greenland; a plague that destroys the world they left behind; and hauntings by the ancient people whose bones they are digging up. Caught between a dead past and a terrifying future, the six interact in increasingly complicated ways. What? You've seen this plot before? Who cares! Moss draws six unforgettable individuals, through their interactions with fellow archeologists and through letters home to their loved ones. Bugs in amber, carbon in ice—a reader watches their existence constrict to survival: "Like Shackleton, it's better to stay put and wait for the cavalry."

Wait
Poems

C.K. Williams
Farrar, Straus & Giroux: 124 pp., $25

There's a whole lifetime in this collection, from beauty and simplicity all the way to shame. The voice of conscience and regret: "There was nothing I could have done—-/a flurry of blackbirds burst/from the weeds at the edge of a field/and one veered out into my wheel/and went under. I had a moment/to hope he'd emerge as sometimes/they will…." The people he could have helped, the children he heard crying, the girl on the train tracks, the cows about to be eaten, the wasps. There is the failure of flesh and the failure of poetry: "Better stay here, with eyes of glass,/like people in advertisements,/and without bodies or blood,/like people in poems."

"All the beautiful poems/about plum trees in flower" he writes, "and not one of them mentions/that the damned things/if you don't pay attention/will pull themselves apart." Then there are poems to the "slayer and the slain," to war, to junk, lucre and decay: "teetering stacks of dung:/poetry, love, poetry, slime." Before you know it, the book is over: "I was a panther: I swaggered,/my shoulders rolled: coarse I was, cruel."

Did you take it in, you wonder, or move on too quickly? Did you get every last drop of wisdom from it?

DNA study promises brain cancer insights: genetic markers

ADVANCES in DNA technology are giving cancer experts their best hope in a generation of improving treatments for brain cancer which, although rare, remains one of the least understood and most deadly of all malignancies. A five-year study of Australian brain cancer patients is gathering steam. It aims to detect genetic markers linked to better prognoses, and environmental factors that may worsen outcomes.
The work involves taking blood samples from patients who have had brain cancer, also known as glioma, finding out if any family members have suffered from the disease, and tracing the patients' treatment and response to it.
Once it's clear which patients are faring well and which are doing less well, their DNA profiles will be compared against a genomic database in Western Australia.
Experts are excited about the research, the Australian Genomics and Clinical Outcomes of High-Grade Glioma study, as it relies on DNA analysis techniques that until recently would have been unsustainable in terms of time and money.

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This brightness on the horizon hasn't come before time.
Five-year survival for those diagnosed with brain cancer is one of the lowest in Australia at just 19 per cent, beaten only by lung cancer (12 per cent), pancreatic cancer (4.6 per cent) and cancers that have already spread through the body leaving doctors in the dark about the original source (9.1 per cent).
Yet treatments for glioma have barely improved in 30 years, partly as few patients survive long enough to provide insights into causes and therapies. Also, in contrast to other cancers such as breast cancer, few glioma patients remain well enough to advocate for more research funds.
That's starting to change with the launch by federal Health Minister Nicola Roxon this week of Australia's first Brain Cancer Action Week, an initiative of Cancer Council NSW.
Four widows of prominent Australians claimed by high-grade glioma lent their support to the launch, including Sue Dale, whose husband Matt Price died in November 2007.
Price, who had endeared himself to readers and even the subjects of his acerbic yet warmly witty columns as The Australian's parliamentary sketch writer, survived for just seven weeks after he was diagnosed with HGG.
Another of the four widows, Gail O'Brien, whose cancer surgeon husband Chris O'Brien died in June last year, said Australia was "still too dependent on the US" for work on HGG, as demonstrated when samples of her husband's tumour had to be sent to California for advanced testing.
"It got caught up with patent issues in California and it wasn't tested," she said. "Would Chris still be alive today if it had been? I don't know."
Medical oncologist Helen Wheeler, who treated O'Brien during his illness and is involved with AGOG, said preliminary results from Europe and the US suggested a cluster of genes acting together might increase the risk of brain cancer.
But the interplay was complex and it's unlikely that glioma could be inherited, unlike breast cancer where an estimated 10 per cent of cases are linked to a single gene.
"By unravelling this, we will be able to look at what this complex of genes does, and the environmental factors that exacerbate the risk, and treatments that could be developed," Wheeler said.
"We are hoping this project will roll out eventually throughout Australia. It's incredibly important we have local data that can contribute to all these international studies that are going on."

Danger Room What’s Next in National Security Pentagon Turns to Brain Implants to Repair Damaged Minds

An estimated 10 to 20 percent of troops coming home from Iraq and Afghanistan are suffering from traumatic brain injuries, or TBIs, which afflict 1.7 million Americans each year. Now the Pentagon’s rolling out a revolutionary initiative to treat the condition: brain implants that one researcher likens to “replacement parts” for damaged gray matter.
“When something happens to the brain right now, there’s so little that the medical community can do,” Krishna Shenoy, associate professor of electrical engineering and bioengineering at Stanford University, told Danger Room. “Our goal is to understand — and then be able to change — how a brain responds to trauma.”
No surprise that military extreme science agency Darpa is behind the project, which is called REPAIR, or Reorganization and Plasticity to Accelerate Injury Recovery. Yesterday, they announced an initial two-year round of $14.9 million in funding for four institutions, led by Stanford and Brown universities, that will collaborate on the brain-chip project. All in, it’ll involve 10 professors and their research teams, working in neuroscience, psychiatry, brain modeling and even semiconductors.

Significant progress has already been made in understanding brain injury. Scientists can create conceptual, mathematical models of brain activity, and are also able to record the electrical pulses emitted by individual neurons in the brain, which offers insight into how those neurons communicate. That knowledge has spurred rapid progress in neural-assisted prosthetic devices, a program that Shenoy collaborated on with Geoffrey Ling, the same Darpa program manager behind REPAIR.
But what experts can’t yet do, Shenoy said, is alter those electrical pulses to turn brain circuits on or off. His team will use optogenetics, an emerging technique that involves emitting light pulses to precisely trigger neural activity, to develop an implanted TBI treatment device.
“Before this, emitting light into the brain would be like hitting it with a hammer,” Shenoy said. “What we’re doing now is pin-pointing a single neuron, and that neuron will naturally change its activity depending on the cue.”
The implants developed by the project will likely be composed of electrodes or optical fibers, and will sit on the surface of the brain. They’ll read electrical signals from neurons, and deliver appropriate light pulses to stimulate other brain regions in response. The implants would allow the brain to operate normally, by acting as substitutes for areas that were damaged or “unavailable.”
First up for Shenoy and company are optogenetic tests on mice, rats and eventually monkeys, to better understand how different regions of the brain interact. For example, how one area of the brain knows which signals to send to other parts. Once they’ve got that down, the researchers hope to develop chips that essentially mimic those interactions, so that an implant can “read a signal from region A, bypass damaged area B, and get that signal to C,” Shenoy said.
And while Darpa’s interested in ailing vets, the implants could have broad civilian application, including help for those who’ve suffered a stroke or undergone surgery to remove a brain tumor. If all goes according to plan, Shenoy expects implants for lab animals within four years.