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Is this why naked mole rats don’t get cancer?

Thu, 02/05/2015 - 07:42

A newly found protein may be the naked mole rat’s secret weapon in warding off cancer.

The hairless, subterranean rodents don’t appear to get cancer despite having a 30-year lifespan.

(Credit: Brandon Vick/University of Rochester)

The new protein is associated with a cluster of genes, called a locus, that is also found in humans and mice. It’s the job of that locus to encode—or carry the genetic instructions for synthesizing —several cancer-fighting proteins. The locus found in naked mole rats encodes a total of four cancer-fighting proteins. The human and mouse version encodes only three.

The findings are published in the Proceedings of the National Academy of Sciences.

Stop the cancer

Researchers know that the genes in question—referred to as INK4 gene locus—synthesize the same three cancer-suppressing proteins in both species: p15INK4b, p16INK4a, and ARF, all of which stop cells from dividing when the cells are stressed or mutated.

Researchers wanted to clone the p16 protein of the naked mole rat for a separate experiment and noticed something unexpected: The presence of a fourth protein, which was the result of p15INK4b and p16INK4a being fused together.

This fourth protein was as good or even better than p15INK4b and p16INK4a at stopping cells from dividing, says Vera Gorbunova, professor of biology at University of Rochester.

“We named this novel product pALTINK4a/b and we believe it may contribute to the longevity of the naked mole rat, including its ability to prevent tumors from developing.”

Aging-related diseases

Previous research by Gorbunova and colleague Andrei Seluanov identified HMW-HA as the chemical that activates the anti-cancer response of the INK4 locus.

“INK4 is the most commonly mutated gene locus in the human cancer,” Seluanov says. “When that gene is deleted or silenced, it often results in the formation of tumors.” There is also growing evidence to support the protein’s role in atherosclerosis and other aging-related diseases.

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“Considering how mutations in the INK4 gene are linked to human cancers,” Gorbunova says, “the better we understand that gene and control its mutations, the better our chances of controlling some cancers.”

In order to determine the significance of pALTINK4a/b, researchers examined the expression of the proteins under different cell growth conditions and found the presence of the hybrid protein does increase when cells become crowded, as long as HMW-HA is present.

On the other hand, when HMW-HA was removed, pALTINK4a/b was not expressed, but it was also induced by a variety of stresses such as oncogenes, which have the potential to cause cancer. The researchers conclude that the protein does respond to high-cell density and to HMW-HA, which initiates the anti-cancer response of the INK4 gene.

The presence of the fourth protein makes naked mole rats more likely to stop growth when there is a risk of malignancy, compared to other mammals that have only three proteins, the researchers say.

To see whether the extra protein is also found in mice and humans, researchers tried to screen mouse and human cells and tissues for the protein hybrid, but were unsuccessful.

“While our work doesn’t eliminate the possibility that the protein exists under some conditions in mice and humans, the results suggest that it’s highly unlikely,” Gorbunova says.

Other researchers from University of Rochester and from Harvard University and Albert Einstein College of Medicine are coauthors of the study.

Source: University of Rochester

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Baby horses raise new questions about autism

Thu, 02/05/2015 - 07:26

Newborn horses with a troubling disorder display some of the same symptoms as children with autism, including detachment, a failure to recognize their mothers, and a lack of interest in nursing.

Abnormal levels of naturally occurring neurosteroids may be the connection, researchers say.

“The behavioral abnormalities in these foals seem to resemble some of the symptoms in children with autism,” says John Madigan, a veterinary professor at the University of California, Davis.

(Credit: Kate/Flickr)

Detachment in kids and foals

Neonatal maladjustment syndrome in foals also caught the attention of Isaac Pessah, professor of molecular biosciences at the UC Davis School of Veterinary Medicine and a faculty member of the UC Davis MIND Institute, who investigates environmental factors that may play a role in the development of autism in children.

“There are thousands of potential causes for autism, but the one thing that all autistic children have in common is that they are detached,” Pessah says.

In newborn foals, neonatal maladjustment syndrome, or dummy foal syndrome, occurs in 3 to 5 percent of live births. With around-the-clock bottle or tube feeding plus intensive care in a veterinary clinic for up to a week or 10 days, 80 percent of the foals recover.

For years, the syndrome has been attributed to hypoxia—insufficient oxygen during the birthing process. Madigan and veterinary neurologist Monica Aleman began sleuthing around for other potential causes, noting that hypoxia usually causes serious, permanent damage and most foals with the maladjustment syndrome survive with no lingering health problems.

Biochemical ‘on switch’

One of their prime suspects was a group of naturally occurring neurosteroids, which are key to sustaining pregnancies in horses, especially in keeping the foal “quiet” before birth.

“Foals don’t gallop in utero,” Madigan says, pointing out the dangers to the mare if a four-legged, hoofed fetus were to suddenly become active in the womb. The prenatal calm is made possible by neurosteroids that act as sedatives for the unborn foal.

However, immediately after birth, the infant horse must make an equally important transition to consciousness. In nature, a baby horse would be easy prey for many natural enemies, so the foal must be ready to run just a few hours after it is born.

In short, somewhere between the time a foal enters the birth canal and the moment it emerges from the womb, a biochemical “on switch” must be flicked that enables the foal to recognize the mare, nurse, and become mobile. Madigan and Aleman suspect that the physical pressure of the birthing process may be that important signal.

Blood-brain barrier

“We believe that the pressure of the birth canal during the second stage of labor, which is supposed to last 20 to 40 minutes, is an important signal that tells the foal to quit producing the sedative neurosteroids and ‘wake up,'” Madigan says.

The theory is supported by the fact that the maladjusted foal syndrome appears more frequently in horses that were delivered via cesarean section or experienced unusually rapid births, Madigan says. Perhaps those foals don’t experience significant physical pressure to trigger the change in neurosteroids.

Furthermore, researchers have found for the first time that sedative neurosteroids persist, and their levels often rise, in the bloodstream of foals born with symptoms of the maladjustment syndrome. These neurosteroids are known to be able to cross the blood-brain barrier and impact the central nervous system, acting on the same receptor as do sedatives and anesthetics.

They also have demonstrated that maladjustment symptoms can be brought on temporarily in normal, healthy foals by administering short infusions of a neurosteroid called allopregnanolone. When the neurosteroid levels drop, the foals return to their normal state.

Gentle ‘hug’ wakes foals up

Amazingly, the veterinary researchers have found that they can reduce maladjustment symptoms in foals by using several loops of a soft rope to gently squeeze the foal’s upper torso and mimic the pressure normally experienced in the birth canal. When pressure is applied with the rope, the foal lies down and appears to be asleep.

John Madigan squeezes a maladjusted foal. The squeezing simulates the foal’s trip through the birth canal. (Credit: UC Davis)

After 20 minutes—about the same time a foal would spend in the birth canal—the rope is loosened and the squeeze pressure released. In initial cases, the foals have responded well to the procedure and recovered, some rising to their feet within minutes and then bounding over to join the mare and nurse.

The researchers suspect that the pressure triggers biochemical changes in the central nervous system that are critical for transitioning the foal from a sleeplike state in the womb to wakefulness at birth.

In spite of the strong observational effects, a larger, controlled clinical trial of national and international scope is now needed to reproduce those observed results and provide a better understanding of the mechanisms at work in the foals.

Links to autism?

The early findings have compelling implications for the health of newborn foals, and have caused the researchers to also explore possible links to autism, which includes a group of complex brain-development disorders. While the symptoms vary, these disorders are generally marked by difficulties with social interactions, verbal and nonverbal communication, and repetitive behaviors.

“The concept that a disruption in the transition of fetal consciousness may be related to children with autism is intriguing,” said Pessah, noting that the behaviors seen in the maladjusted foal syndrome truly are reminiscent of those in some autistic children.

Some children with autism do outgrow autistic behaviors by the time they reach their teen years, Pessah says. Could this be a parallel to the recovery of the foals with the maladjustment syndrome?

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A new group called the Comparative Neurology Research Group, consisting of veterinarians, physicians, epidemiologists, and basic-science researchers, has formed to pursue further studies in this area. Madigan is working with researchers at the Stanford University School of Medicine, exploring the mechanisms of post-birth transitions of consciousness related to neonatal care of infants.

Using data from the foal research, Pessah and Madigan are also working with environmental epidemiologist Irva Hertz-Picciotto at the MIND Institute to investigate neurosteroids in children with varying degrees of autism, ranging from some developmental delay to full-spectrum autism.

The researchers are exploring whether abnormal regulation of neurosteroids during the time around childbirth could be one of many factors that might contribute to autism and related neurodevelopmental disorders. A recent study has reported elevated levels of neurosteroids in children with autism spectrum disorder.

Researchers will next look to see whether there are alterations in blood levels of certain neurosteroids that may serve as a marker for the disorder. They caution, however, that the relationship right now is just a theory that remains to be validated or disproven.

Source: UC Davis

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Did stinky conditions create tons of gold?

Thu, 02/05/2015 - 06:51

The Witwatersrand Basin in South Africa holds the world’s largest gold deposits. But how did it get there?

Some 40 percent of the precious metal that has been found so far comes from this area, and hundreds of tons of gold deposits still lie beneath the earth. Across the 124 mile-long (200 km) swath, individual ore deposits occur in thin layers over areas up to 6 by 6 miles.

Geologists debate how these giant deposits formed. Christoph Heinrich, professor of mineral resources at ETH Zurich and the University of Zurich, recently published a new explanation in Nature Geoscience, in which he tries to reconcile the contradictions of two previously published theories.

Gold ore from the Witwatersrand region. (Credit: James St. John/Flickr)

Competing theories

The prevailing “placer gold” theory states that the gold at Witwatersrand was transported and concentrated through mechanical means as metallic particles in river sediment. Such a process has led to the gold-rich river gravels that gave rise to the Californian gold rush.

Here, nuggets of placer gold have accumulated locally in river gravels in the foothills of the Sierra Nevada, where primary gold-quartz veins provide a nearby source of the nuggets.

But no sufficiently large source exists in the immediate sub-surface of the Witwatersrand Basin. This is one of the main arguments of proponents of the “hydrothermal hypothesis,” according to which gold, chemically dissolved in hot fluid, passed into the sediment layers half a billion years after their deposition.

For this theory to work, a 6-mile-thick (10 km) blanket of later sediments would be required in order to create the required pressure and temperature. However, the hydrothermal theory is contradicted by geological evidence that the gold concentration must have taken place during the formation of host sediments on the Earth’s surface.

Hydrogen sulfide in the atmosphere

Heinrich believes the concentration of gold took place at the Earth’s surface, by flowing river water, but in chemically dissolved form. With such a process, the gold could be easily “collected” from a much larger catchment area of weathered, slightly gold-bearing rocks.

He examined the possibility of this middle way by calculating the chemical solubility of the precious metal in surface water under the prevailing atmospheric and climatic conditions.

Experimental data show that the chemical transport of gold was indeed possible in the early stages of Earth evolution. The prerequisite was that the rainwater had to be at least occasionally very rich in hydrogen sulfide. Hydrogen sulfide binds itself in the weathered soil with widely distributed traces of gold to form aqueous gold sulfide complexes, which significantly increases the solubility of the gold.

However, hydrogen sulfide in the atmosphere and sulfurous gold complexes in river water are stable only in the absence of free oxygen.

“Quite inhospitable environmental conditions must have dominated, which was possible only three billion years ago during the Archean eon,” says Heinrich. “It required an oxygen-free atmosphere that was temporarily very rich in hydrogen sulfide—the smell of rotten eggs.”

In today’s atmosphere, oxygen oxidizes all hydrogen sulfide, thus destroying gold’s sulfur complex in a short time, which is why gold is practically insoluble in today’s river water.

Volcanoes and bacteria

In order to increase the sulfur concentration of rainwater sufficiently in the Archean eon, basaltic volcanism of gigantic proportions was required at the same time. Indeed, in other regions of South Africa there is evidence of giant basaltic eruptions overlapping with the period of the gold concentration.

A third factor required for the formation of gold deposits at Witwatersrand is a suitable location for concentrated precipitation of the gold. The richest deposits of gold ore in the basin are found in carbon-rich layers, often just millimeters to centimeters thick, but which stretch for many kilometers.

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These thin layers contain such high gold concentrations that mining tunnels scarcely a meter high, some three kilometers below the Earth’s surface, are still worthwhile.

The carbon probably stems from the growth of bacteria on the bottom of shallow lakes and it’s here that the dissolved gold precipitated chemically, according to Heinrich’s interpretation.

The nature of these life forms is not well known. “It’s possible that these primitive organisms actively adsorbed the gold,” Heinrich speculates. “But a simple chemical reduction of sulfur-complexed gold in water to elementary metal on an organic material is sufficient for a chemical ‘gilding’ of the bottom of the shallow lakes.”

The gold deposits in the Witwatersrand, which are unique worldwide, could have thus been formed only during a certain period of the Earth’s history: after the development of the first continental life forms in shallow lakes at least 3 billion years ago, but before the first emergence of free oxygen in the Earth’s atmosphere approximately 2.5 billion years ago.

Source: ETH Zurich

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Could optical fibers treat jet lag?

Thu, 02/05/2015 - 05:48

A new way to reset the brain’s biological clock could potentially treat the negative effects of night shift work and seasonal affective disorder—and even jet lag.

“We found we can change an animal’s sleep/wake rhythms by artificially stimulating the neurons in the master biological clock, which is located in an area of the brain called the suprachiasmatic nucleus (SCN), with a laser and an optical fiber,” says Douglas McMahon, a biology professor at Vanderbilt University who directed the study.

Optical fiber used to reset the circadian clock in mice. (Credit: Steve Green/Vanderbilt)

Until now, neuroscientists had thought that the firing rate of SCN neurons was strictly an output of the biological clock’s activity. They did not think altering the level of neuronal activity could affect how the clock operates.

But McMahon and colleagues showed that stimulating and suppressing the SCN’s neurons in a fashion that emulates their day and night activity levels can force the clock to reset.

The study was done using mice. Neuroscientists have found that mice possess a biological clock nearly identical to that of humans with the exception that it is tuned for a nocturnal lifestyle.

Exposed to light

The researchers used a new technique called optogenetics to manipulate the firing rate of the SCN neurons. The technique inserts genes that express optically sensitive proteins into target cells in order to make the cells respond to light.

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“This puts clock neurons under our control for the first time,” says doctoral student Jeff Jones, who conducted the study with fellow doctoral student Michael Tackenberg.

The project involved genetically engineering two strains of mice. The neurons in the brain of one strain contained an optically sensitive protein that triggers neuronal activity when exposed to light.

The neurons in the brain of the other had a similar protein that suppressed neuronal activity when exposed to light.

“Of course, this exact approach isn’t ready for human use yet,” says Tackenberg. “But others are making progress toward eventually using optogenetics as therapy.”

Implanted LED

This would involve an experimental technique that uses viruses to insert new genes into cells, which is considered a promising potential treatment for a number of diseases. This could be used to implant optically sensitive proteins in SCN neurons that could be activated by an implanted LED.

Tackenberg is currently testing whether strains of mice that suffer from seasonal affective disorder respond to this new approach.

“The fact that the SCN firing rate is a key component of circadian rhythmicity, rather than solely an output as we had thought, shows that we still have a lot to learn about how our biological clocks work,” McMahon says.

Grants from the National Institutes of Health and National Science Foundation supported the study, which was published in the journal Nature Neuroscience.

Source: Vanderbilt University

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Transistors made of the world’s thinnest silicon

Wed, 02/04/2015 - 13:23

Silicene is made of a one-atom-thick layer of silicon, and now scientists have used it to create transistors.

The material has outstanding electrical properties but has—until now—proved difficult to produce and work with.

Buckled honeycomb lattice structure of silicene. (Credit: UT Austin)

Deji Akinwande, an assistant professor in the University of Texas at Austin’s Cockrell School of Engineering, and his team solved one of the major challenges surrounding silicene by demonstrating that it can be made into transistors—semiconductor devices used to amplify and switch electronic signals and electrical power.

The first-of-their-kind devices could pave the way for future generations of faster, energy-efficient computer chips. The work was published in the journal Nature Nanotechnology.

Structured like graphene

Until a few years ago, human-made silicene was a purely theoretical material. Looking at carbon-based graphene, another atom-thick material with promise for chip development, researchers speculated that silicon atoms could be structured in a broadly similar way.

Akinwande, who also works on graphene transistors, sees value in silicene’s relationship to silicon, which chipmakers already know how to work with.

“Apart from introducing a new player in the playground of 2-D materials, silicene, with its close chemical affinity to silicon, suggests an opportunity in the road map of the semiconductor industry,” Akinwande says. “The major breakthrough here is the efficient low-temperature manufacturing and fabrication of silicene devices for the first time.”

Vacuum chamber

Despite its promise for commercial adaptation, silicene has proved extremely difficult to create and work with because of its complexity and instability when exposed to air.

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To work around these issues, Akinwande teamed with Alessandro Molle at the Institute for Microelectronics and Microsystems in Agrate Brianza, Italy, to develop a new method for fabricating the silicene that reduces its exposure to air.

To start, the researchers let a hot vapor of silicon atoms condense onto a crystalline block of silver in a vacuum chamber.

They then formed a silicene sheet on a thin layer of silver and added a nanometer-thick layer of alumina on top. Because of these protective layers, the team could safely peel it of its base and transfer it silver-side-up to an oxidized-silicon substrate.

They were then able to gently scrape some of the silver to leave behind two islands of metal as electrodes, with a strip of silicene between them.

The US Army Research Laboratory’s Army Research Office, the Cockrell School’s Southwest Academy of Nanoelectronics, and the European Commission’s Future and Emerging Technologies Programme funded Akinwande’s research.

Source: UT Austin

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Drinking red wine may help you remember

Wed, 02/04/2015 - 13:14

A compound found in foods like red grapes, peanuts, and some berries may help ward off age-related memory decline, new research suggests.

Resveratrol has been widely touted for its potential to prevent heart disease, but researchers say it also has positive effects on the hippocampus, an area of the brain crucial to functions such as memory, learning, and mood.

(Credit: Christian Schnettelker/Flickr)

Mood and memory

Because both humans and animals show a decline in cognitive capacity after middle age, the findings may have implications for treating memory loss in the elderly. Researchers say resveratrol may even be able to help people afflicted with severe neurodegenerative conditions such as Alzheimer’s disease.

Published in Scientific Reports, the study reports that resveratrol offers apparent benefits in terms of learning, memory, and mood function in aged rats.

“The results of the study were striking,” says Ashok K. Shetty, professor of molecular and cellular medicine at Texas A&M University.

“They indicated that for the control rats who did not receive resveratrol, spatial learning ability was largely maintained but ability to make new spatial memories significantly declined between 22 and 25 months. By contrast, both spatial learning and memory improved in the resveratrol-treated rats.”

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Neurogenesis—the growth and development of neurons—approximately doubled in rats that were given resveratrol compared to the control rats. The treated rats also had significantly improved microvasculature, indicating improved blood flow, and had a lower level of chronic inflammation in the hippocampus.

“The study provides novel evidence that resveratrol treatment in late middle age can help improve memory and mood function in old age,” Shetty says.

Shetty and colleagues are now examining the molecular mechanisms that underlie the improved cognitive function following resveratrol treatment and plan to conduct studies to see whether lower doses of resveratrol in the diet for prolonged periods would offer similar benefits to the aged brain.

The National Institutes of Health provided funding for the study.

Source: Texas A&M University

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Why third parties jump in on civil wars

Wed, 02/04/2015 - 12:01

Conspiracy theorists have long thought that oil is a motivation for interfering in another country’s war. New research may back them up.

Throughout recent history, countries that need oil have found reasons to interfere in countries with a good supply of it and, the researchers argue, this could help explain the US interest in ISIS in northern Iraq.

Researchers modeled the decision-making process of third-party countries in interfering in civil wars and examined their economic motives.

They found that the decision to interfere was dominated by the interveners’ need for oil over and above historical, geographical, or ethnic ties.

“The ‘thirst for oil’ is often put forward as a near self-evident explanation behind the intervention in Libya and the absence of intervention in Syria,” says Vincenzo Bove. “Many claims are often simplistic but, after a rigorous and systematic analysis, we found that the role of economic incentives emerges as a key factor in intervention.” (Credit: Niecieden/Flickr)

When civil wars ‘erupt’

Civil wars have made up more than 90 percent of all armed conflicts since World War II and the research builds on a near-exhaustive sample of 69 countries which had a civil war between 1945 and 1999. About two thirds of civil wars during the period saw third party intervention either by another country or outside organization.

The team wanted to find out which factors made it more likely that a third party state would militarily intervene in an ongoing intrastate war.

“We found clear evidence that countries with potential for oil production are more likely to be targeted by foreign intervention if civil wars erupt,” says study coauthor Petros Sekeris of the University of Portsmouth.

“Military intervention is expensive and risky. No country joins another country’s civil war without balancing the cost against their own strategic interests and what possible benefits there are.

“We wanted to go beyond conspiracy theories and conduct a careful, nuanced analysis to see whether oil acts as an economic incentive in the decision on whether to intervene in an internal war in another country.

“The results show that outsiders are much more motivated to join a fight if they have a vested financial interest.”

‘Thirst for oil’

Among the findings, published in the Journal of Conflict Resolution, are:

  • The more oil a country has, the more likely a third party will intervene in their civil war;
  • The more oil a country imports, the greater the likelihood it will intervene in an oil-producing country’s civil war;

“Before the ISIS forces approached the oil-rich Kurdish north of Iraq, ISIS was barely mentioned in the news,” says coauthor Vincenzo Bove of the University of Warwick. “But once ISIS got near oil fields, the siege of Kobani in Syria became a headline and the US sent drones to strike ISIS targets.

“We don’t claim that our findings can be applied to every decision made on whether to intervene in another country’s war, but the results clearly demonstrate supply of and demand for oil motivates a significant number of decisions taken to intervene in civil wars in the post-World War II period,” says Bove.

“The ‘thirst for oil’ is often put forward as a near self-evident explanation behind the intervention in Libya and the absence of intervention in Syria. Many claims are often simplistic but, after a rigorous and systematic analysis, we found that the role of economic incentives emerges as a key factor in intervention.”

Oil-rich and oil-free

The research found that a third party country was more likely to intervene if:

  • They were a major power;
  • The rebels were strong and well-armed;
  • There were close ethnic ties between the two countries; and/or
  • The civil war took place during the Cold War, a period of global competition between superpowers.
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Among the examples highlighted by the researchers are the US’s involvement in Angola’s civil war from 1975 to the end of the Cold War and in Guatemala, Indonesia, and the Philippines, and the US’s support of conservative autocratic states in oil-rich areas.

The study also cites the UK’s involvement in Nigeria’s 1967-70 civil war, in contrast to the non-intervention in civil wars in other former colonies that had no oil reserves (Sierra Leone and Rhodesia, later Zimbabwe); and the former Soviet Union’s involvement in Indonesia (1958), Nigeria (1967-68), and Iraq (1973).

The researchers say that at the other end of the spectrum, oil-rich states including the Gulf States, Mexico, and Indonesia have no history of military intervention in other countries’ civil wars, even if they have advanced and well equipped military forces.

With the West becoming less energy-dependent and China becoming more energy-dependent, the incentives for third party countries to intervene in other countries’ wars was likely to change in the future, they say.

Kristian Skrede Gleditsch of the University of Essex is a coauthor of the study.

Source: University of Warwick

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To watch mice make memories, tickle their whiskers

Wed, 02/04/2015 - 11:19

Researchers tickled mice whiskers and peered into their brains so precisely they were able to see how proteins clustered on nerve cells as memories formed.

The technique could be broadly useful for future studies not only on memory and learning but also on what goes wrong in disorders like autism, Alzheimer’s disease, and schizophrenia.

Pictured above is a single nerve cell in the cortex of a live mouse. Individual branches are pseudo-colored to differentiate them. The bumps on the branches are where synapses form. (Credit: Yong Zhang)

“As far as we know, no one has ever been able to look at receptor proteins in live animals before,” says Richard Huganir, director of neuroscience at Johns Hopkins University School of Medicine.

“This allows us to get a more accurate picture of what’s really happening as the brain processes experiences into memories.”

Glowing receptors

At the heart of the story are AMPA receptors, proteins that live on the outside of nerve cells. They receive signals in the form of AMPA molecules and play an important role in strengthening and weakening synapses, the connections between nerve cells that form memories.

Until now, scientists were limited to studying AMPA receptors in nerve cells grown in the laboratory or in tissue samples; neither of those fully reflects the complex circuitry, hormones, and neurochemicals of a living brain.

For the new study, published in Nature Neuroscience, researchers created mice with AMPA receptors that glow under light from a special microscope. The microscope can focus at a depth of 0.5 millimeters, seeing into the outer layer of the brain, called the cortex.

There, thousands of nerve cells carry information from every part of the body; each mouse whisker has a group of dedicated nerve cells there called barrel fields.

Deeper into the brain

The team imaged each mouse immediately before and after tickling a single whisker for an hour. What they saw surprised them: tickling alone was sufficient to increase the number of AMPA receptors in and strengthen the synapses of the barrel fields for the tickled whiskers.

Checking back over the next few days, the researchers found that the AMPA receptor levels remained high, suggesting that the whisker-tickling experience had a long-term effect on the mice’s memories.

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“The mysteries are the purpose that is served by strengthening these synapses, and whether more AMPA receptors are being made or if they are moving in from somewhere else,” says postdoctoral fellow Yong Zhang. “Future studies will address those questions.”

“This technique opens up many more possibilities, like visualizing learning at the molecular level as it is happening in the intact brain in healthy mice and in mouse models of brain disorders.”

The group first plans to apply the new technique to see what happens as mice learn a complex motor task. With better optics, they also hope to one day be able to go deeper into the brain to areas like the hippocampus, which has a crucial role in memory formation and has been implicated in neurological disorders like autism, Alzheimer’s disease, and schizophrenia.

The National Institute of Mental Health and the Howard Hughes Medical Institute funded the study.

Source: Johns Hopkins University

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A lesson in birth control from your dermatologist

Wed, 02/04/2015 - 10:39

Unintended pregnancies and serious birth defects might be prevented if women who take a powerful acne drug receive contraception literature while at the dermatologist.

Isotretinoin, formerly marketed as Accutane, is an effective drug for the treatment of acne, but is considered a teratogen—a drug that can cause birth defects.

(Credit: Morgan/Flickr)

Because of this, the Food and Drug Administration (FDA) strictly regulates the distribution of the drug to women of childbearing age.

Through the FDA’s iPLEDGE program, woman who are prescribed the drug must pledge to use two forms of contraception, in addition to taking regular pregnancy tests while on the drug and online tests to make sure they understand the dangers of getting pregnant while taking the drug.

How handouts help

Despite the regulations, 122 pregnancies affected by isotretinoin were reported in the United States during the first year of the iPLEDGE program. Gaps in patients’ knowledge about the most effective forms of contraception may be a reason.

“While contraceptive counseling isn’t something a dermatologist has to do on a daily basis—like an obstetrician or gynecologist would—it does matter for young women using these drugs,” says lead author Carly A. Werner, a resident in the obstetrics, gynecology and seproductive sciences department at University of Pittsburgh Medical Center.

“Our goal was to show that a simple intervention like our handout could be added to dermatology office visits to enhance contraceptive counseling and decrease the number of exposed fetuses through more effective means of contraception.”

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For the study, published in the journal JAMA Dermatology,  researchers surveyed 100 women from a single dermatology clinic between April and May 2014. Prior to viewing the contraceptive fact sheet, 75 percent overestimated the effectiveness of condoms, while 51 percent did the same for oral contraceptives.

Thirty-four percent of women said they had never heard of contraceptive implants, and 16 percent had never heard of IUDs, or intrauterine contraceptive devices, despite their effectiveness being much higher than that of condoms and oral options.

Researchers surveyed those women again after they had reviewed the fact sheet and found significant improvement in knowing about contraceptives.

“This shows us that dermatologists can make a difference by providing women who take this drug more education regarding effective forms of contraception,” says Laura Ferris, director of clinical trials for the dermatology department, who was a coauthor of the study.

Future study is needed to determine how much the information provided on the fact sheet was retained and if it does reduce the risk of medication-induced birth defects.

The study was funded in part by a grant from the FDA.

Source: University of Pittsburgh

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Can drinking green tea make supplements safer?

Wed, 02/04/2015 - 10:01

Dozens of people have ended up with liver toxicity from taking high doses of green tea supplements for weight loss. New research suggests that drinking the tea for weeks beforehand could reduce this risk.

Researchers gave mice high doses of the green tea polyphenol epigallocatechin-3-gallate (EGCG). The dosage was equivalent to the amount of the polyphenol found in some dietary supplements taken by humans.

One group of mice was pretreated with a diet containing a low level of ECGC for two weeks prior to receiving high doses of the polyphenol. Another group was fed a diet that did not include EGCG prior to receiving the high, supplement-like doses.

After three days of high doses, the scientists tested the blood of the mice to determine how their livers handled the EGCG. Pretreated mice had a 75 percent reduction in liver toxicity compared to untreated mice.

The research data show that dietary pretreatment with the green tea polyphenol protects mice from liver toxicity caused by subsequent high oral doses of the same compound, explains Josh Lambert, associate professor of food science at Penn State’s College of Agricultural Sciences.

(Credit: Adam Clarke/Flickr)

Weeks or months of tea

Lambert suggests that the research has relevance to people who are taking or are considering taking supplements containing green tea extract.

“We believe this study indicates that those who are chronic green tea consumers would be less sensitive to potential liver toxicity from green-tea-based dietary supplements,” he says. “If you are going to take green tea supplements, drinking green tea for several weeks or months ahead of time may reduce your potential side effects.”

Lambert has another suggestion for people considering green tea supplements—drink green tea instead.

“Drinking green tea rather than taking supplements will allow you to realize the benefits and avoid the risk of liver toxicity,” he says.

“The beneficial effects that people have reported as being associated with green tea are the result of dietary consumption rather than the use of supplements. The relative risk of using supplements remains unclear.”

Tea—Camellia sinensis—is rich in catechins, polyphenols that are natural antioxidants. A number of animal studies have shown the preventive effects of green tea polyphenols against obesity. And Lambert points out that a recent analysis of 11 human trials with green tea preparations reported a nearly three-pound average body weight loss in intervention groups compared to control groups.

Green tea plus exercise

Green tea’s effect on weight loss may be more noticeable if a person exercises. In research published last year, Lambert showed that mice on a high-fat diet that consumed decaffeinated green tea extract and exercised regularly experienced sharp reductions in final body weight and significant improvements in health.

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Approximately 34 percent of adults in the United States are classified as obese, Lambert notes, leading to a strong interest in the potential benefits of including green tea and green tea supplements in weight-loss efforts. The liver toxicity research, recently published online in Food and Chemical Toxicology, reveals a unique property of the green tea polyphenol EGCG.

“It appears that EGCG can modulate its own bioavailability and that dietary treatment may reduce the toxic potential of acute high oral doses of EGCG,” says lead researcher Sarah Forester, assistant professor of chemistry at California State University, Bakersfield, and a former Penn State postdoctoral fellow.

“These data may partly explain the observed variation in liver toxicity response to dietary supplements containing green tea.”

Some people drink surprisingly large volumes of green tea, according to Lambert, as much as 10-20 cups a day, but liver toxicity has never been reported in that context.

“No person can sit down and drink 16 cups of green tea all at once,” he says. “However if you take a supplement you can get that type of green tea extract dose, so there is some indication that the dosage form has an influence on the potential to cause liver toxicity.”

Source: Penn State

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Brains of ‘SuperAgers’ look 50 not 80

Wed, 02/04/2015 - 08:30

Researchers are trying to figure out why the brains of some older adults look 30 years younger than their peers.

While these so-called cognitively elite “SuperAgers” may be 80 or more years old, they have memories as sharp as those decades younger. SuperAgers were first identified in 2007 by scientists at Northwestern University’s Cognitive Neurology and Alzheimer’s Disease Center.

(Credit: Andreas Lindmark/Flickr)

3 big differences

A new study published in the Journal of Neuroscience is the first to quantify brain differences of SuperAgers compared to normal older people.

Their unusual brain signature has three common components when compared with normal persons of similar ages:

  • thicker region of the cortex
  • significantly fewer tangles (a primary marker of Alzheimer’s disease)
  • whopping supply of a specific neuron—von Economo—linked to higher social intelligence

“The brains of the SuperAgers are either wired differently or have structural differences when compared to normal individuals of the same age,” says Changiz Geula, the study’s senior author and a research professor at the Cognitive Neurology and Alzheimer’s Disease Center. “It may be one factor, such as expression of a specific gene, or a combination of factors that offers protection.”

“Identifying the factors that contribute to the SuperAgers’ unusual memory capacity may allow us to offer strategies to help the growing population of ‘normal’ elderly maintain their cognitive function and guide future therapies to treat certain dementias,” says Tamar Gefen, the first study author and a clinical neuropsychology doctoral candidate.

What brain scans show

MRI imaging and an analysis of the SuperAger brains after death showed that the anterior cingulate cortex of SuperAgers (31 subjects) was not only significantly thicker than the same area in aged individuals with normal cognitive performance (21 subjects), but also larger than the same area in a group of much younger, middle-aged individuals (ages 50 to 60, 18 subjects).

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This region is indirectly related to memory through its influence on related functions such as cognitive control, executive function, conflict resolution, motivation, and perseverance.

Analysis of the brains of five SuperAgers showed the anterior cingulate cortex had approximately 87 percent less tangles than age-matched controls and 92 percent less tangles than individuals with mild cognitive impairment. The neurofibrillary brain tangles, twisted fibers consisting of the protein tau, strangle and eventually kill neurons.

The number of von Economo neurons was approximately three to five times higher in the anterior cingulate of SuperAgers compared with age-matched controls and individuals with mild cognitive impairment.

“It’s thought that these von Economo neurons play a critical role in the rapid transmission of behaviorally relevant information related to social interactions,” Geula says, “which is how they may relate to better memory capacity.”

These cells are present in such species as whales, elephants, dolphins, and higher apes.

Grants from the National Institute on Aging and the Davee Foundation supported the work.

Source: Northwestern University

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How computers know one monkey from another

Wed, 02/04/2015 - 08:20

Computers can learn to recognize a monkey’s face much the same way other monkeys do—by overall facial pattern, eyebrow patches, and nose spots—not by sex or age.

The findings, based on a study with guenon monkeys, suggest sex and age may not have been important in the evolution of appearance.

The results also suggest machine learning can be an effective way to not only correctly identify species, but also distinguish individuals within those species.

(Credit: Tim Sackton/Flickr)

Photos of monkey faces

“Studying the cues that species use to discriminate each other often poses a challenge to scientists,” says James Higham, assistant professor of anthropology at New York University. “Many species are now rare and, in the case of these particular monkeys, they live high in the rainforest canopy, so are very difficult to reach.”

“Driving our study was the premise that if a characteristic such as individual identity can be classified reliably from physical appearance, or what we call ‘visual signals,’ then these signals may have evolved in part for the purpose of communicating this characteristic,” says study author William Allen, who undertook the work while at NYU and is now a postdoctoral researcher at University of Hull in the UK.

“We sought to test a computer’s ability to do something close to what a guenon viewing other guenons’ faces would do,” he says. “We did so by taking measurements of visual attributes from photographs of guenon faces and asking a computer to try and separate different groups as accurately as possible on the basis of these measurements.”

The study, reported in the journal Proceedings of the Royal Society B, relied on more than 500 photographs of 12 species of guenons collected in various settings: in zoos in the United States and the United Kingdom and in a wildlife sanctuary in Nigeria. Guenons are a particularly interesting and visually striking group, with many closely related species that exhibit a remarkable diversity of colorful patterned faces.

Eyebrows and noses

The analysis focused on specific guenon visual signals—facial patterns generally as described using the “eigenface” technique, a method used in computer vision for human facial recognition, as well as eyebrow patches and nose spots segmented from images.

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From here, the researchers tested whether or not an algorithm could accurately accomplish the following: identify individual guenons, classify them by species from among the 12 in the sample, and determine the age and sex of each individual.

The results show that the computer could employ both overall facial pattern and eyebrow patches and nose spots to correctly categorize species and identify individuals, but not their age or sex.

“The reason that machine learning cannot classify age and sex is because facial patterns do not seem to be different between males and females and do not seem to change as individuals age,” observes Higham. “This suggests that conveying these characteristics to others has not been an important factor in the evolution of guenon appearance.”

“In contrast, the fact that species and individual identity can both be reliably classified suggests that the ability to indicate these things to others has been a strong factor in the evolution of guenon faces,” he adds.

“More broadly, these results demonstrate that faces are highly reliable for classification by species and that visual cues have played an important role in the radiation of this group into so many different species.”

Source: NYU

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Why climate debates get people so angry

Wed, 02/04/2015 - 07:14

Improving the public’s understanding of science isn’t enough to build support for policies that would fight climate change, say researchers.

A new study, published in Nature Climate Change, finds that when it comes to human-induced climate change, the actions and beliefs of both skeptics and believers could be understood as integrated expressions of self, underpinning specific social identities.

Using an online survey of climate change skeptics and believers living in the US, researchers measured differences between the two groups: their environmental behaviors, emotional responses, national and global identification, and a number of other variables.

Social scientist Ana-Maria Bliuc from the Monash University School of Social Sciences says that although there was a growing belief among the general public that climate change was real, there was also a sharp division in beliefs about its causes, with many people skeptical of human-induced change.

“We found the contrasting opinions of believers and skeptics about the causes of climate change provided the basis of social identities that define who they are, what they stand for, and who they stand with (and against),” says Bliuc.

“In making up an aspect of self, these beliefs and emotional reactions can predict support for actions that advance the positions of each group.”

‘Angry opposition’

The researchers also find that part of both sides’ group consciousness was anger at the opposing side.

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“This finding suggests that antagonizing skeptics and increasing their anger towards their opponents is likely to polarize them further, making them more committed to act in support of their cause,” says Bliuc.

The researchers suggest that communication and education strategies alone are unlikely to overcome the divisions between the two groups.

“Interventions that increase angry opposition to action on climate change are especially problematic,” says Bliuc.

“Strategies for building support for mitigation policies should go beyond attempts to improve the public’s understanding of science, to include approaches that will change the relationship between the two groups.”

Researchers from the University of Western Sydney, Murdoch University, and Flinders University also contributed to the work.

Source: Monash University

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In the Senate, it’s better to keep ‘em separated

Wed, 02/04/2015 - 07:11

Close contact with adversaries can occasionally help people find common ground—unless they’re US senators, new research suggests.

When researchers studied interactions among senators from the 1970s to the 2000s a pattern emerged. Senators either moved closer together or further apart in their voting behavior as a function of their political identities and how much contact they had with each other.

This pattern was especially pronounced when contact occurred in Senate committees that were more divided.

The findings by Christopher C. Liu, assistant professor of strategy at the University of Toronto’s Rotman School of Management, and Sameer B. Srivastava, an assistant professor at University of California, Berkeley’s Haas School of Business, appear in the February issue of the American Sociological Review.

“Conventional wisdom says interpersonal contact between people will foster collaboration and consensus,” according to the researchers. “We found that increasing physical contact between people who have opposing and public political identities can instead promote divergence of attitudes or behavior.

“This tendency is further amplified in environments involving high conflict, which makes political identities more salient.”

Seating arrangements

Liu and Srivastava used two measures of political identity: senators’ party affiliation and the religious climate in the senators’ home states. They also measured senators’ interactions in two ways: seating arrangements in the Senate chamber and committee assignments.

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Senators from the same party who had more contact—as indicated by the proximity of their seats on the Senate chamber floor and by co-memberships on Senate committees—subsequently moved closer together in their voting behavior, while senators from different parties who had more contact in later sessions of Congress moved further apart in their voting behavior.

“Co-location can induce both positive and negative outcomes. Sometimes keeping some distance is the better option,” says Liu.

The authors say the Senate is an “apt setting for the study of interaction, identity, and influence” because senators have highly visible political identities and are continually seeking to influence each other through interaction.

Srivastava and Liu contend that their findings also have implications in corporate organizations with oppositional political identities that are seeking to bridge differences between polarized groups.

“Post-merger integration, particularly following a contested takeover, can produce oppositional identities in a very public setting. In such cases, it may help to move interactions into more private settings and find common ground on less divisive issues before tackling the more controversial ones.”

Source: University of Toronto

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This toothy ‘guinea pig’ weighed 2,200 pounds

Wed, 02/04/2015 - 07:06

Scientists think that the biggest rodent ever may have used its front teeth the way an elephant uses its tusks.

Josephoartigasia monesi, a rodent closely related to guinea pigs, lived in South America approximately 3 million years ago. It is the largest fossil rodent ever found, with an estimated body mass of over 2,200 pounds (1,000 kg). That’s roughly the size of a buffalo.

The full artist’s impression of Josephoartigasia monesi. (Credit: James Gurney)

Philip Cox of the Centre for Anatomical and Human Sciences at the University of York used computer modeling to estimate the power of Josephoartigasia‘s bite.

He found that, although the bite forces were very large—around 1400 N, similar to that of a tiger—the incisors would have been able to withstand almost three times that force, based on earlier estimates by coauthors who first described the fossil in 2008.

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“We concluded that Josephoartigasia must have used its incisors for activities other than biting, such as digging in the ground for food, or defending itself from predators,” says Cox. “This is very similar to how a modern day elephant uses its tusks.”

The research involved CT scanning the Josephoartigasia monesi specimen and making a virtual reconstruction of its skull. The researchers then used finite element analysis, an engineering technique that predicts stress and strain in a complex geometric object, on the reconstruction.

Andres Rinderknecht of the Museo Nacional de Historia Natural and Ernesto Blanco of Facultad de Ciencias, Instituto de Física, both in Montevideo, are coauthors of the study in press at the Journal of Anatomy.

Source: University of York

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Tiny worms test nanoparticles for safety

Tue, 02/03/2015 - 12:57

Scientists tested 20 types of nanoparticles on roundworms and found that 5, including carbon-60 molecules called “buckyballs,” showed little to no toxicity.

Others were moderately or highly toxic to Caenorhabditis elegans, which the researchers observed over several generations to see the particles’ health effects.

“Nanoparticles are basically new materials, and we don’t know much about what they will do to human health and the health of the ecosystem,” says Qilin Li, an associate professor of civil and environmental engineering and of materials science and nanoengineering at Rice University.

“There have been a lot of publications showing certain nanomaterials are more toxic than others. So before we make more products that incorporate these nanomaterials, it’s important that we understand we’re not putting anything toxic into the environment or into consumer products.

“The question is, ‘How much cost can we bear?'” she says. “It’s a long and expensive process to do a thorough toxicological study of any chemical, not just nanomaterials.”

She says that due to the large variety of nanomaterials being produced at high speed and at such a large scale, there is “an urgent need for high-throughput screening techniques to prioritize which to study more extensively.”

The new pilot study proves it’s possible to gather a lot of toxicity data at low cost, says coauthor Weiwei Zhong, an assistant professor of biosciences, who has performed extensive studies on C. elegans, particularly on their gene networks.

Materials alone for each assay, including the worms and the bacteria they consumed and the culture media, cost about 50 cents, she says.

4 ways to test a nematode

The researchers used four assays to see how worms react to nanoparticles: fitness, movement, growth, and lifespan. The most sensitive assay of toxicity was fitness. In this test, the researchers mixed the nanoparticles in solutions with the bacteria that worms consume. Measuring how much bacteria they ate over time served as a measure of the worms’ “fitness.”

“If the worms’ health is affected by the nanoparticles, they reproduce less and eat less,” Zhong says. “In the fitness assay, we monitor the worms for a week. That is long enough for us to monitor toxicity effects accumulated through three generations of worms.”

C. elegans has a life cycle of about three days, and since each can produce many offspring, a population that started at 50 would number more than 10,000 after a week. Such a large number of tested animals also enabled the fitness assay to be highly sensitive.

The researchers’ “QuantWorm” system allowed fast monitoring of worm fitness, movement, growth, and lifespan.

3 types of nanoparticles

The researchers studied a representative sampling of three classes of nanoparticles: metal, metal oxides and carbon-based. “We did not do polymeric nanoparticles because the type of polymers you can possibly have is endless,” Li explains.

They examined the toxicity of each nanoparticle at four concentrations. Their results showed C-60 fullerenes, fullerol (a fullerene derivative), titanium dioxide, titanium dioxide-decorated nanotubes, and cerium dioxide were the least damaging to worm populations.

Their “fitness” assay confirmed dose-dependent toxicity for carbon black, single- and multiwalled carbon nanotubes, graphene, graphene oxide, gold nanoparticles, and fumed silicon dioxide.

They also determined the degree to which surface chemistry affected the toxicity of some particles. While amine-functionalized multiwalled nanotubes proved highly toxic, hydroxylated nanotubes had the least toxicity, with significant differences in fitness, body length and lifespan.

Adding variables

Zhong says the method could prove its worth as a rapid way for drug or other companies to narrow the range of nanoparticles they wish to put through more expensive, dedicated toxicology testing.

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“Next, we hope to add environmental variables to the assays, for example, to mimic ultraviolet exposure or river water conditions in the solution to see how they affect toxicity,” she says. “We also want to study the biological mechanism by which some particles are toxic to worms.”

Rice postdoctoral researcher Sang-Kyu Jung and alumna Xiaolei Qu, now an associate professor at Nanjing University, are lead authors of the paper. Coauthors are Rice research scientist Boanerges Aleman-Meza, graduate students Tianxiao Wang and Zheng Liu and alumna Celeste Riepe, now a graduate student at the University of California, Berkeley.

The National Institutes of Health and a Searle Scholar grant funded the research, which appears in the journal Environmental Sciences and Technology. The findings are also available on the researchers’ open-source website.

Source: Rice University

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This ancient star has five Earth-size planets

Tue, 02/03/2015 - 12:56

Astronomers have discovered a star that’s 11.2 billion years old and has at least five Earth-size planets.

They found it while poring over four years of data from NASA’s Kepler spacecraft.

They say the discovery shows that planets the size of Earth have formed throughout the universe’s history, which means there’s a chance very ancient life exists in the galaxy.

The research published in the Astrophysical Journal describes Kepler-444, a star that’s 25 percent smaller than our sun and is 117 light years from Earth. The star’s five known planets have sizes that fall between Mercury and Venus.

Those planets are so close to their star that they complete their orbits in fewer than 10 days. At that distance, they’re all much hotter than Mercury and aren’t habitable.

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Steve Kawaler, an Iowa State University professor of physics and astronomy and a coauthor of the study, says Kepler-444 is very bright and can be easily seen with binoculars.

Kawaler’s role within the research team was to help with the stellar seismology work that determined the size of Kepler-444. To do that, Kawaler and the rest of the team studied sound waves within the star. Those sound waves affect the star’s temperature, creating pulsating changes in brightness that offer clues to the star’s diameter, mass and age.

Kepler takes high-precision measurements of those changes in brightness. That’s how Kepler does its primary job: finding distant planets by measuring tiny changes in brightness as they pass in front of their stars.

“This is one of the oldest systems in the galaxy,” Kawaler says of the Kepler discovery, noting that our sun is 4.5 billion years old. “Kepler-444 came from the first generation of stars. This system tells us that planets were forming around stars nearly 7 billion years before our own solar system.

“Planetary systems around stars have been a common feature of our galaxy for a long, long time.”

Tiago Campante, a research fellow at the University of Birmingham, is leader of the research project and first author of the paper.

Source: Iowa State University

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Engineered antibodies grab on to HIV ‘spikes’

Tue, 02/03/2015 - 11:47

Genetically engineered antibodies are more than 100 times better than our body’s own defenses at binding to HIV, new tests show.

Researchers capitalized on new insight into HIV’s strategy for evading antibodies—proteins produced by the immune system to identify and wipe out invading objects such as viruses—to develop the new molecules.

“Based on the work that we have done, we now think we know how to make a really potent therapeutic that would not only work at relatively low concentrations but would also force the virus to mutate along pathways that would make it less fit and therefore more susceptible to elimination,” says Pamela Bjorkman, a biology professor at the California Institute of Technology (Caltech).

“If you were able to give this to someone who already had HIV, you might even be able to clear the infection.”

Researchers hypothesized that one of the reasons the immune system is less effective against HIV than other viruses is because of the small number and low density of spikes on HIV’s surface.

Fewer spikes

These spikes, each one a cluster of three protein subunits, stick up from the surface of the virus and are the targets of antibodies that neutralize HIV. While most viruses are covered with hundreds of these spikes, HIV has only 10 to 20, making the average distance between the spikes quite long.

That distance is important with respect to the mechanism that naturally occurring antibodies use to capture their viral targets, researchers say.

Antibodies are Y-shaped proteins that evolved to grab onto their targets with both “arms.” However, if the spikes are few and far between—as is the case with HIV—it is likely that an antibody will bind with only one arm, making its connection to the virus weaker (and easier for a mutation of the spike to render the antibody ineffective).

To test their hypothesis, researchers genetically engineered antibody-based molecules that can bind with both arms to a single spike.

They started with the virus-binding parts, or Fabs, of broadly neutralizing antibodies—proteins produced naturally by a small percentage of HIV-positive individuals that are able to fight multiple strains of HIV until the virus mutates.

When given in combination, these antibodies are quite effective. Rather than making Y-shaped antibodies, researchers simply connected two Fabs—often from different antibodies, to mimic combination therapies—with different lengths of spacers composed of DNA.

Why DNA?

In order to engineer antibodies that could latch onto a spike twice, they needed to know which Fabs to use and how long to make the connection between them so that both could readily bind to a single spike.

Previously, researchers had tried to make educated guesses based on what is known of the viral spike structure, but the large number of possible variations in terms of which Fabs to use and how far apart they should be, made the problem intractable.

In the new work, published in the journal Cell, researchers struck upon the idea of using DNA as a “molecular ruler.” It is well known that each base pair in double-stranded DNA is separated by 3.4 angstroms. Therefore, by incorporating varying lengths of DNA between two Fabs, they could systematically test for the best neutralizer and then derive the distance between the Fabs from the length of the DNA.

They also tested different combinations of Fabs from various antibodies—sometimes incorporating two different Fabs, sometimes using two of the same.

“Most of these didn’t work at all,” says Bjorkman, which was reassuring because it suggested that any improvements the researchers saw were not just created by an artifact, such as the addition of DNA.

But some of the fabricated molecules worked very well. The researchers found that the molecules that combined Fabs from two different antibodies performed the best, showing an improvement of 10 to 1,000 times in their ability to neutralize HIV, as compared to naturally occurring antibodies.

Depending on the Fabs used, the optimal length for the DNA linker was between 40 and 62 base pairs (corresponding to 13 and 21 nanometers, respectively).

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Taking this finding to the next level in the most successful of these new molecules, the researchers replaced the piece of DNA with a protein linker of roughly the same length composed of 12 copies of a protein called tetratricopeptide repeat. The end product was an all-protein antibody-based reagent designed to bind with both Fabs to a single HIV spike.

“That one also worked, showing more than 30-fold average increased potency compared with the parental antibodies,” Bjorkman says. “That is proof of principle that this can be done using protein-based reagents.”

The greater potency suggests that a reagent made of these antibody-based molecules could work at lower concentrations, making a potential therapeutic less expensive and decreasing the risk of adverse reactions in patients.

“I think that our work sheds light on the potential therapeutic strategies that biotech companies should be using—and that we will be using—in order to make a better antibody reagent to combat HIV,” says Rachel Galimidi, a graduate student in Bjorkman’s lab who is lead author of the paper.

“A lot of companies discount antibody reagents because of the virus’s ability to evade antibody pressure, focusing instead on small molecules as drug therapies. Our new reagents illustrate a way to get around that.”

The researchers are currently working to produce larger quantities of the new reagents so that they can test them in humanized mice—specialized mice carrying human immune cells that, unlike most mice, are sensitive to HIV.

Other coauthors of the paper are from Case Western Reserve University School of Medicine and Rockefeller University. The National Institutes of Health, the HIV Vaccine Research and Design Program, the Collaboration for AIDS Vaccine Discovery, and the Bill and Melinda Gates Foundation supported the research.

Source: Caltech

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Should biobank consent be more specific?

Tue, 02/03/2015 - 08:46

Most people are willing to donate a bodily sample—like blood, plasma, and tissue—for research, according to a new study. But when they hear more about specific scenarios, that willingness changes.

“We really wanted to document the concerns people have that may affect their desire to donate,” says Tom Tomlinson, director of Michigan State University’s Center for Ethics and Humanities in the Life Sciences.

“Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.”

Stem cells: yes, Abortion: no

Tomlinson, who led the study with coauthor Raymond De Vries, a bioethics professor at the University of Michigan, surveyed nearly 1,600 people within the United States and found 68 percent were willing to donate using a blanket consent method. This approach gives a biobank one-time permission to use a donation for whatever research they deem acceptable.

Yet, that percentage drops when specific projects are mentioned dealing with abortion, vaccines, embryonic stem cells, and studies used for commercial profit.

More than half of the participants refused to give blanket consent if their sample might be used in research involving abortion, while 45 percent would not give this type of permission if it might be used for commercial purposes.

The only project that saw an increase in donor willingness involved the creation of stem cells to grow tissues or organs for use in research. Seventy percent indicated they would give blanket consent knowing the biobank might sponsor this type of study.

Biobank consent

“These scenarios present people with a moral question where they have to balance their competing goals,” Tomlinson says. “They want to contribute to medical progress, but on the other hand, there are certain things they don’t want to be involved in.”

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Tomlinson says these results give biobanks reason to rethink the way they get consent and how transparent they need to be about the research they support, without making the process more difficult on the donor and more costly on the facility.

“In the end, the recruitment of donors is essential to the success of biobanks,” Tomlinson says. “As research efforts continue to grow, getting more people to donate becomes even more important. These concerns have to be addressed in order to control possible effects on donation rates in the future.”

The National Institutes of Health funded the three-year project. The findings appear in the Journal of the American Medical Association.

Source: Michigan State University

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Breast cancer: How to predict risk for African Americans

Tue, 02/03/2015 - 08:39

A new way to predict breast cancer risk may lead to more African-American women taking part in breast cancer prevention trials.

Researchers use models to predict risk to determine eligibility for recruitment into prevention trials.

The Gail Model, which accurately predicts breast cancer risk in white women, is known to underestimate African-American women’s risk.

For a new study, published in the Journal of Clinical Oncology, researchers used prospective data from 55,000 African-American women between the ages of 30 and 69 to develop a breast cancer risk prediction model specifically for African-American women.

The model included family history of breast cancer, history of benign breast disease, age at menarche, age at first birth, bilateral oophorectomy, oral contraceptive use, hormone use, body mass index at age 18, and adult height.

“The model was well calibrated in that it predicted 486 cases in comparison to an observed 506 cases during the additional five years of follow-up,” says Julie Palmer, senior epidemiologist at Boston University’s Slone Epidemiology Center and professor of epidemiology at Boston University School of Public Health.

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“Based on the Black Women’s Health Study model, 14.6 percent of women age 30-69 were predicted to have a five-year risk of at least 1.66 percent. This is considerably higher than the proportion predicted by previous models to be above that end point.”

Previous breast cancer risk prediction models for African-American women have used information on only a few factors and may have underestimated risk, Palmer says.

“The new model appears to improve prediction and, if used for determining eligibility for entry into prevention trials, would likely result in a greater number of African-American women invited to enroll in the trials.”

The Susan G. Komen for the Cure Foundation and the National Cancer Institute funded the research.

Source: Boston University

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