Protecting the brain when energy runs low

 by Biomechanism 

Researchers from the Universities of Leeds, Edinburgh and Dundee have shed new light on the way that the brain protects itself from harm when ‘running on empty.’

The findings could lead to new treatments for patients who are at risk of stroke because their energy supply from blood vessels feeding the brain has become compromised.

Many regions of the brain constantly consume as much energy as leg muscles during marathon running. Even when we are sleeping, the brain needs regular fuel.

Much of this energy is needed to fire up ‘action potentials’, tiny electrical impulses that travel along nerve cells in the brain. These electrical impulses trigger the release of chemical messages at nerve endings, allowing the brain to process information and control bodily functions.

Normally, the bloodstream supplies enough glucose and oxygen to the brain to generate the large amount of energy required for these action potentials to be fired up. But things can go wrong if the blood vessels feeding the brain become narrowed or blocked, restricting the supply of vital nutrients.

A team led jointly by Professors Chris Peers (Leeds), Mark Evans (Edinburgh) and Grahame Hardie (Dundee) has now identified a way for the brain to protect itself when its energy supply is running low. This protective strategy, which is triggered by a protein known as AMPK, reduces the firing frequency of electrical impulses, conserving energy.

The energy-sensing protein AMPK was first discovered by Professor Graham Hardie of the University of Dundee. He said: “When we first defined the AMPK system by studying fat metabolism in the liver back in the 1980s, we had no idea that it might regulate completely different functions in other organs, like nervous conduction in the brain.”

“There are drugs currently on the market that stimulate AMPK, which are used to treat other conditions. In future these and other drugs could be given to at-risk patients to give them a better chance of surviving a stroke.”

Professor Chris Peers, of the University of Leeds’ School of Medicine, said: “Our new findings suggest that if brain cells run short of energy, they start to work more slowly. However, it is better to work slowly than not at all. It is possible that this discovery could, in the long term, lead to new treatments for patients who have problems with circulation to the brain, placing them at higher risk of conditions such as stroke.”

“This research is a good example of what can happen if you pool the expertise of research groups who work in different areas.”

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Full details of the work are published in the Proceedings of the National Academy of Sciences.

For more information:

1. The paper, Ikematsu et al, Phosphorylation of the voltage-gated potassium channel Kv2 :1 by AMP-activated protein kinase, is published in the Proceedings of the National Academy of Sciences[doi/10.1073/pnas.1106201108].

NJIT researcher testing micro-electronic stimulators for spinal cord injuries

 by Biomechanism 

A new wireless device to help victims of spinal cord injury is receiving attention in the research community. Mesut Sahin, PhD, associate professor, in the department of biomedical engineering at NJIT, recently has published and presented news of his findings to develop micro-electrical stimulators for individuals with spinal cord injuries.

Caption: Mesut Sahin, a bioengineer at NJIT, works on developing and testing an embedded micro-electrical stimulator for people with spinal cord injuries. Credit: NJIT

The work, now in its third year of support from a four-year, $1.4 million National Institutes of Health (NIH) grant, has resulted in the development and testing of a technology known by its acronym, FLAMES (floating light activated micro-electrical stimulators). The technology, really a tiny semiconductor device, will eventually enable people with spinal cord injuries to restore some of the motor functions that are lost due to injury. Energized by an infrared light beam through an optical fiber located just outside the spinal cord these micro-stimulators will activate the nerves in the spinal cord below the point of injury and thus allow the use of the muscles that were once paralyzed.

“Our in vivo tests suggest that the FLAMES can be used for intraspinal micro-stimulation even for the deepest implant locations in the rat spinal cord,” said Sahin.

“The power required to generate a threshold arm movement was investigated as the laser source was moved away from the micro-stimulator. The results indicate that the photon density does not decrease substantially for horizontal displacements of the source that are in the same order as the beam radius. This gives confidence that the stimulation threshold may not be very sensitive to small displacement of the spinal cord relative to the spine-mounted optical power source.” Sahin spoke about this work at the IEEE Engineering in Medicine and Biology Conference in Boston, also in September of 2011.

FLAMES is a semiconductor device that is remotely controlled by an optical fiber attached to a low power near-infrared laser. The device is implanted into the spinal cord, and is then allowed to float in the tissue. There are no attached wires. A patient pushes a button on the external unit to activate the laser, the laser then activates the FLAMES device.

“The unique aspect of the project is that the implanted stimulators are very small, in the sub-millimeter range,” Sahin said. “A key benefit is that since our device is wireless, the connections can’t deteriorate over time plus, the implant causes minimal reaction in the tissue which is a common problem with similar wired devices.”

The electrical activation of the central and peripheral nervous system has been investigated for treatment of neural disorders for many decades and a number of devices have already successfully moved into the clinical phase, such as cochlear implants and pain management via spinal cord stimulation. Others are on the way, such as micro stimulation of the spinal cord to restore locomotion, micro stimulation of the cochlear nucleus, midbrain, or auditory cortex to better restore hearing and stimulation of the visual cortex in the blind subject. All of them, however, are wired, unlike FLAMES, which is not.

Selim Unlu, professor of electrical and computer engineering at Boston University, is working with Sahin. “We hope that once FLAMES advances to the clinical stage, patients paralyzed by spinal injury will be able to regain vital functions,” Sahin said.

___________________

NJIT, New Jersey’s science and technology university is internationally recognized for being at the edge in knowledge in architecture, applied mathematics, wireless communications and networking, solar physics, advanced engineered particulate materials, nanotechnology, neural engineering and e-learning. Many courses and certificate programs, as well as graduate degrees, are available online through the Office of Continuing Professional Education.

YOU CAN'T BELIEVE THIS

Facts and Figures on Rural Women

POVERTY

• Countries with the highest levels of hunger also have very high levels of gender inequality (2009 Global Hunger Index. The Challenge of Hunger: Focus on Financial Crisis and Gender Inequality. IFPRI Issue Brief 62.)
• Gender inequality is a major cause and effect of hunger and poverty: it is estimated that 60 percent of chronically hungry people are women and girls (WFP Gender Policy and Strategy).
• In the context of Latin America 110 women aged 20 to 59 are living in poor rural households for every 100 men in Colombia and 114 women for every 100 men in Chile. In sub-Saharan Africa (Cameroon, Malawi, Namibia, Rwanda and Zimbabwe) there are more than 120 women aged 20 to 59 living in poor households for every 100 men (UN Women Progress report 2011).

AGRICULTURE

• Estimates suggest that if women had the same access to productive resources as men, they could increase yields on their farms by 20–30 percent, lifting 100-150 million out of hunger (FAO (2011). The State of Food and Agriculture: Women in Agriculture, Closing the Gender Gap for Development, Rome).
• Equal access to resources will raise total agricultural output in developing countries by 2.5–4 percent, thereby contributing to both food security and economic growth (FAO (2011). The State of Food and Agriculture: Women in Agriculture, Closing the Gender Gap for Development’, Rome)
• The OECD estimates from recent years show that only 5 percent of aid directed to the agricultural sector specifically focused on gender equality. (OECD, The Development Co-operation Report 2011)
• Women constitute half of the agricultural labour force in least developed countries (FAO, The Role of Women in Agriculture).

LAND RIGHTS

• For those developing countries for which data are available, only between 10 and 20 percent of all land holders are women FAO (2011). The State of Food and Agriculture: Women in Agriculture, Closing the Gender Gap for Development’, Rome).

LABOUR FORCE

• In most countries women in rural areas who work for wages are more likely than men to hold seasonal, part-time and low-wage jobs and women receive lower wages for the same work (FAO (2011). The State of Food and Agriculture: Women in Agriculture, Closing the Gender Gap for Development’, Rome).

ACCESS TO CREDIT

• The share of female smallholder farmers who can access credit is 5-10 percentage points lower than for male smallholders.  (FAO (2011). The State of Food and Agriculture: Women in Agriculture, Closing the Gender Gap for Development’, Rome)
• In rural sub-Saharan Africa, women in smallholder agriculture access less than 10 percent of available credit (UN (2011). Report of the Secretary-General on Ten-year appraisal and review of the implementation of the Brussels Programme of Action for the Least Developed Countries for the Decade 2001-2010, A/66/66.)

HEALTH

• Only one third of rural women receive prenatal care compared to 50 per cent in developing regions as a whole. (United Nations, The Millennium Development Goals Report 2010 and 2011 (New York, 2010 and 2011), available from www.un.org/millenniumgoals/reports.shtml .)

INFRASTRUCTURE AND ICTS

• In LDCs, the electrification rate ranges from below 10 to 40 per cent and the percentage of population with improved access to drinking water in rural areas ranges from 9 to 97 per cent with significant disparities between urban and rural areas. People in LDCs rely on open fires and traditional cooking stoves (e.g. wood, crop waste and charcoal) to earn a living and feed their families. Women walk long distances every day to collect fuels (and water) (UNIDO (2011). Contribution to the LDC IV Conference on Energy Access).
• Access to new technology is crucial in maintaining and improving agricultural productivity. Gender gaps exist for a wide range of agricultural technologies, including machines and tools, improved plant varieties and animal breeds, fertilizers, pest control measures and management techniques. Labour saving and productivity enhancing technologies can also help reduce women’s time poverty.

RELATED LINKS

• Women and Hunger: 10 Facts 

New research links common RNA modification to obesity

 by Biomechanism 

An international research team has discovered that a pervasive human RNA modification provides the physiological underpinning of the genetic regulatory process that contributes to obesity and type II diabetes.

European researchers showed in 2007 that the FTO gene was the major gene associated with obesity and type 2 diabetes, but the details of its physiological and cellular functioning remained unknown.

Now, a team led by University of Chicago chemistry professor Chuan He has demonstrated experimentally the importance of a reversible RNA modification process mediated by the FTO protein upon biological regulation. He and 10 co-authors from Chicago, China and England published the details of their finding in the Oct. 16 advance online edition of Nature Chemical Biology.

Caption: Chuan He, professor in chemistry at the University of Chicago, works in his laboratory in the Gordon Center for Integrative Science. He led an international research team that has experimentally demonstrated that RNA modification wields greater genetic influence than previously suspected. Credit: Lloyd DeGrane

He and his colleagues have shown, for the first time, the existence of the reversible RNA modification process — called methylation — and that it potentially impacts protein expression and function through its action on a common RNA base: adenosine. The process is reversible because it can involve the addition or removal of a methyl group from adenosine. The team found that the FTO protein mediates cellular removal of the methyl group.

“An improved understanding of the normal functions of FTO, as exemplified by this work, could aid the development of novel anti-obesity therapies,” said Stephen O’Rahilly, professor of clinical biochemistry and director of the Metabolic Research Laboratories at the University of Cambridge. O’Rahilly, a leading researcher in obesity and metabolic disease who also has studied FTO, was not directly involved in He’s project.

“Variants around the FTO gene have consistently been associated with human obesity and artificial manipulation of the fto gene in mice clearly demonstrates that FTO plays a crucial role in the regulation of body weight,” O’Rahilly explained. “However, the development of a deeper understanding of the normal biological role of FTO has been challenging.”

Scientists already had demonstrated that FTO removes methyl groups from nucleic acids, but only on one rare type of DNA or RNA methylation. The new research from He and his colleagues shows that FTO also acts on the common messenger RNA modification called N6-methyladenosine, O’Rahilly said.

The paper arose from He’s investigations of the AlkB family of proteins that act on nucleic acids. Based on this work, He and his collaborators proved that human cells exhibit reversible methylation of RNA bases, which significantly impact critical life processes.

Important but mysterious

Every human messenger RNA carries on average three to six methylations on adenosine. Scientists knew these methylations were extremely important but their function remained a mystery, He said. “For the first time, we show that these methylations are reversible and play a key role in human energy homeostasis,” the process by which the body maintains a complex biochemical dynamic equilibrium.

The modification of N6-methyladenosine in messenger RNA is pervasive throughout the mammal kingdom and many other organisms. Despite its abundance, this modification’s exact functional role remains unknown, He said. But his team’s discovery strongly indicates that the modification has major roles in messenger RNA metabolism.

The finding may open a new research field — RNA epigenetics — for delving into the realm of biological regulatory processes, He said. The epigenetics of DNA and histones (proteins that package DNA in human cells) have become well-explored topics on the frontiers of biological research over the last 10 to 20 years. “It is safe to say 50 percent of biologists work on subjects related to epigenetics one way or another,” He said.

DNA (deoxyribonucleic acid) for decades has reigned as king over biological research on epigenetics of nucleic acids, as He noted in the December 2010 issue of Nature Chemical Biology. RNA (ribonucleic acid) modification was regarded more as a vassal that merely fine-tunes gene expression and regulation, until this recent discovery, which confirms the speculation by He and others that RNA modification has secretly wielded a far greater genetic influence than anyone had previously suspected. That’s why, as He wrote last year, “reversible RNA modification might represent another realm for biological regulation in the form of ‘RNA epigenetics.’”

____________

Citations: “N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO,” by Guifang Jia, Ye Fu, Xu Zhao, Qing Dai, Guanqun Zheng, Ying Yang, Chengqi Yi, Tomas Lindahl, Tao Pan, Yun-Gui Yang and Chuan He, Nature Chemical Biology, advance online publication Oct. 16, 2011.

Faulty molecular switch can cause infertility or miscarriage

by Biomechanism 

Scientists have discovered an enzyme that acts as a ‘fertility switch’, in a study published in Nature Medicine today. High levels of the protein are associated with infertility, while low levels make a woman more likely to have a miscarriage, the research has shown.

The findings have implications for the treatment of infertility and recurrent miscarriage and could also lead to new contraceptives. Around one in six women have difficulty getting pregnant and one in 100 women trying to conceive have recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

Researchers from Imperial College London looked at tissue samples from the womb lining, donated by 106 women who were being treated at Imperial College Healthcare NHS Trust either for unexplained infertility or for recurrent pregnancy loss.

The women with unexplained infertility had been trying to get pregnant for two years or more and the most common reasons for infertility had been ruled out. The researchers discovered that the womb lining in these women had high levels of the enzyme SGK1. Conversely, the women suffering from recurrent pregnancy loss had low levels of SGK1.

The team found further evidence of SGK1′s importance in experiments using mouse models. Levels of SGK1 in the womb lining decline during the fertile window in mice. When the researchers implanted extra copies of the SGK1 gene into the womb lining, the mice were unable to get pregnant, suggesting that a fall in SGK1 levels is essential for making the uterus receptive to embryos.

The research at the Institute of Reproductive and Developmental Biology (IRDB) at Imperial College London was led by Professor Jan Brosens, who is now based at the University of Warwick. “Our experiments on mice suggest that a temporary loss of SGK1 during the fertile window is essential for pregnancy, but human tissue samples show that they remain high in some women who have trouble getting pregnant,” he said. “I can envisage that in the future, we might treat the womb lining by flushing it with drugs that block SGK1 before women undergo IVF. Another potential application is that increasing SGK1 levels might be used as a new method of contraception.”

Any infertility treatment that blocks SGK1 would have to have a short-lived effect, as low levels of the protein after conception seem to be linked to miscarriage. When the researchers blocked the gene that codes for SGK1 in mice, the mice had no problem getting pregnant. However, they had smaller litters and showed signs of bleeding in the uterus, suggesting that lack of SGK1 made miscarriage more likely.

After an embryo is implanted, the lining of the uterus develops into a specialised structure called the decidua, and this process can be made to occur when cells from the uterus are cultured in the lab. Cultured cells from women who had had three or more consecutive miscarriages had significantly lower levels of SGK1 compared to cells from controls.

Blocking the SGK1 gene, both in pregnant mice and in human cell cultures, impaired the cells’ ability to protect themselves against oxidative stress, a condition in which there is an excess of reactive chemicals inside cells.

“We found that low levels of SGK1 make the womb lining vulnerable to cellular stress, which might explain why low SGK1 was more common in women who have had recurrent miscarriage,” said Madhuri Salker, the study’s first author, Institute of Reproductive and Developmental Biology (IRDB) at Imperial College London. “In the future, we might take biopsies of the womb lining to identify abnormalities that might give them a higher risk of pregnancy complications, so that we can start treating them before they get pregnant.”

Immersive Flight Simulation Dome Offers Seamless, Super-Real 360-Degree Views

Video: Immersive Flight Simulation Dome Offers Seamless, Super-Real 360-Degree Views

By Clay Dillow

Barco's R-360 Flight Simulation Dome Barco

Barco, a maker of large-format projector technologies, has just unveiled what it is calling abreakthrough in flight simulator technology, and for all the hardware involved we’re inclined to agree that his must be something big. The new flight simulator dome--it’s really more like a sphere--offers state of the art high-res visuals and full 360-degree views, allowing fighter pilot trainees to spot other aircraft from 12 miles away.

That’s something of a step up from that flight simulator you used to play on your mom’s PC. The dome is bathed in light from 13 or 14 10-megapixel projectors, which are calibrated by laser to ensure complete crispness in picture. The projectors can also display imagery in infrared so pilots can train for night flights--wearing night vision, pilots actually see the blooming and halo effects caused by night vision technology.

That kind of realism is critical to ensuring pilots are prepared for real-world scenarios, the company says, and should help launch a new generation of similar simulators designed around a completely immersive experience in which several pilots can actually work together to carry out a mission rather than just run through a set of programmed scenarios.

The setups are configurable and customizable so you’ll have to call up Barco if you want a price quote. The video below is mostly an extended commercial for the product, but it does provide some nice views from inside the cockpit.

[PhysOrg]

Electronic Circuits Rewire Themselves on Demand, Depending On What They're Needed For

By Clay Dillow

Static Circuitry Northwestern researchers are developing circuit technology that can rewire itself on demand. johnmuk via Flickr

Northwestern University researchers--the same ones that brought us self-erasing documents a couple of years ago--are envisioning a day when computers and other gadgets can rewire themselves automatically to better suit the user’s needs at a given moment. As a step in that direction, they have today published a paper in Nature Nanotechnology describing tiny circuits they’ve created from nano-scale materials that can be resistors, diodes, transistors, or other components depending on what the computer needs them to be at a given time.

Basically, they’ve created circuitry that can rewire itself in the lab. Harnessed for consumer electronics, this technology could enable a new breed of computers that are always optimized for the task at hand.

The nanoparticle-based electronics work by basically creating new and fluid ways of steering the flow of electrons through a material. Rather than being static, the particles in the material can be rearranged to create varying degrees of resistance, conductivity, or whatever the system needs at a given time, even creating multiple streams of electrons flowing in different directions at the same time through the same material.

This is all made possible by a few tiny, five-nanometer-wide electrically conductive particles coated in a positively charged chemical all immersed in a pool of negatively charged atoms. Signals from a computer can then move the negatively charged atoms around, creating regions of high or low conductivity that dictate where and how electrons will naturally find a path through the material. Once an electron path is no longer needed, it can scrubbed from the system by simply reconfiguring the negatively charged atoms in a different way. In doing this, the computer can basically conjure different electrical components--diodes or resistors or switches or what have you--on demand.

The result of all that could be computers that can quickly adapt to whatever task they are performing at that particular moment, making high-powered computing--or even the common tasks performed by a smartphone-far more efficient.

[The Register]

Virgin Galactic Announces Completion of Spaceport America, the World's First Commercial Spaceport

By Dan Nosowitz

Virgin Galactic Spaceport Virgin Galactic

Virgin Galactic and its thoroughly British CEO, Richard Branson, announced another milestone on their way to opening the world's first commercial spaceport: Construction is finished, and the terminal and hangar have been dedicated.

Virgin seems to be updating us fairly frequently, with equally frequent dedication ceremonies, on the progress of the spaceport. Just one year ago, they toasted the completed runway. But now, construction on Spaceport America, located a remote section of desert in New Mexico's Sierra County, seems to be finished. The hangar and terminal will be home to the new shuttle, mission control, and a waiting area for soon-to-be astronauts.

The company expects to begin test flights next year.

[Virgin