BRIC science profiles ‘more like the G7’.


The pattern of science publishing in the emerging economies of Brazil, Russia, India and China (the ‘BRICs’) is becoming increasingly similar to that in developed G7 countries, the Chinese Academy of Sciences has reported.

Researchers sampled articles published across a wide range of disciplines in 1991, 2000 and 2009, and found that the output from the BRICs shifted steadily to more closely resemble that of the G7, according to the study in Scientometrics (14 March).

They found that the G7 continue to have a more balanced portfolio of disciplines than the BRICs. Of the four BRIC countries, they noted that China in particular had moved steadily towards a more even balance of output across the disciplines — partly through policy, and partly as a result of rapid economic growth, said lead researcher, Liying Yang.

Despite the shift, differences between BRIC and developed country outputs persist, the authors noted, pointing out that mathematics, physics, chemistry and engineering consistently accounted for the majority of Chinese and Russian publications from 1991 to 2009.

“After the Second World War, China, Russia and Eastern European countries paid sustained attention to basic research, including nuclear science, that is closely related to these disciplines,” Yang told SciDev.Net.

An exception to this trend is Brazil. While the United States and Britain continue to dominate the life sciences, Brazil has increased its published papers in this area from 50 to 70 per cent of national output.

“Brazil has been traditionally strong in biotech and the government emphasises its development,” Yang said. “Moreover, Brazil is more open about cooperating with the West and learning from its experiences, which is different from China’s emphasis on ‘self-dependent innovation’.”

But overall, the BRICs continue to lag behind developed nations in global life-sciences output, a trend Yang suggested could be problematic in the long term.

“There should be much stronger investment in this area,” she said, adding that unexpected challenges such as the SARS outbreak in 2002 suggested the need for greater balance in China’s research and development priorities.

Ronald Rousseau, a scientometrics researcher at the Catholic University College of Bruges-Ostend, Belgium, said the paper has a limitation as it is based only on national publication outputs rather than an assessment of the quality or efficacy of the research and its societal impact.

“China is number two in the world based on yearly number of publications, but it is certainly not number two in citations per publication,” he told SciDev.Net.

Source: SciVX

 

South Africa and Australasia may have to ‘share’ SKA.


Speculation is growing that South Africa and Australia may be asked to join forces in building and operating the Square Kilometre Array – the world’s most powerful radio telescope – following a decision last week to delay an announcement on where it will ultimately be based.

Scientists hope the telescope will help answer fundamental questions about the universe, including its origin and evolution, and whether it contains life beyond our planet.

Both countries had previously been asked to submit separate bids for the telescope, which is likely to cost at least $US2 billion, and whose 3,000 receptors have been designed to make the telescope 50 times more sensitive to radio waves than any existing facility.

The SKA Organisation – the international consortium responsible for the project – had been due to announce which bid had been successful last week, but at the end of a two-day meeting in the Netherlands, it issued a statement on 4 April saying that its members had recognised that it was “desirable to maintain an inclusive approach”.

The statement added that the members considered it to be “important to maximise the value from the investments made by both candidate host regions”. As a result, a small scientific working group has been set up “to explore possible implementation options that would achieve this”.

Officials from the organisation have declined to elaborate further or to provide any further details on what these options might be, citing the need to keep the negotiations confidential.

One possibility that has been raised is that receptors built in South Africa, Australia and New Zealand – which is a partner to the Australian bid – might be programmed to operate jointly.

However other commentators question whether the two sets of receptors can look at the same part of the sky simultaneously, given that Australia and South Africa are on opposite sides of the Southern hemisphere.

Unconfirmed reports in the Australian media have suggested that a panel of scientific experts had given their preference to the South Africa bid, which would involve building receiving stations in at least eight other African nations.

South Africa’s Science Ministry has strongly rejected suggestions that this option represented a “sympathy decision”. Officials insist the country has the capacity to host the facility, and supporters of the South African bid have also emphasised the potential role of the SKA project to boost the image of science and technology in Africa.

In an interview with SciDev.Net last year, the director of the South African bid, Bernie Fanaroff, described the importance of the SKA project for its potential to create “a significant legacy of skills and be a continuing attraction for young people in Africa to enter careers in science and technology”.

However the South African Ministry of Science and Technology has been quoted as describing accusations that such arguments had been used to sway the site adjudication process as “a not very subtle attempt to undermine [its] scientific and technical rigour”.

Source: SciVX

Indigenous Brazilian group certified to trade carbon credits.


RIO DE JANEIRO] Brazil’s Paiter Suruí community has become the first indigenous group in the country to receive international certification to sell carbon credits in return for protecting and restoring forests in their Amazonian territory.

The Suruí community, which numbers around 1300 people, was first contacted by outsiders in 1968. Over the past decade, with assistance from environmental advocates, they have conducted a sophisticated campaign to prove to the world that they are helping to preserve their 248,000 hectare forest territory.

Four years ago, they established the Suruí Forest Carbon Project, with a view to selling carbon credits under the so-called REDD+ (Reducing Emissions from Deforestation and Forest Degradation) mechanism.

In late 2008, their right to trade carbon credits on the global market was legally recognised — and this week (9 April) the project was formally certified under the Verified Carbon Standard (VCS) and the Climate, Community and Biodiversity Standard (CCB).

“The VCS guarantees that the indigenous group follows a strict methodology for evaluating emission reductions,” Mariano Cenamo, deputy executive secretary of the Institute for Conservation and Sustainable Development of Amazonas (IDESAM) — the non-governmental organisation (NGO) that helped the Suruí design the project — told SciDev.Net.

He added that the CCB certification will ensure that the project is carried out in a way that minimises climate change, supports sustainable development and conserves biodiversity.

According to Cenamo, the project could generate up to US$61 million for the community over the next 25 years.

“We are already negotiating with some investors,” he says, adding that the funds raised could be used to boost sustainable economic activities such as tourism.

Forest Trends, an environmental NGO that introduced the Suruí to the concept of carbon credits, said this week that documents from the Carbon Project validated by VCS had revealed that the Suruí’s actions have already prevented the emission of more than 200,000 tonnes of carbon dioxide from the Amazon.

Observers say the project’s success is being keenly watched by other indigenous communities in Brazil.

“All the documents of the process are available for anyone interested in the issue and can help other indigenous groups to explore similar strategies,” Cenamo told SciDev.Net.

“Lessons can [also] be learned from this project by the Brazilian government when designing policies for the [forest] sector.”

Marcos Amend, executive director of Brazil’s Conservation Strategy Fund, one of the project’s partners, said: “This is a very interesting project since it is headed by indigenous people and is part of a 50-year well-organised and structured plan for managing the indigenous territory.”

Source: SciVX

 

 

 

South Africa and Australasia may have to ‘share’ SKA.


Speculation is growing that South Africa and Australia may be asked to join forces in building and operating the  – the world’s most powerful radio telescope – following a decision last week to delay an announcement on where it will ultimately be based.

Scientists hope the telescope will help answer fundamental questions about the universe, including its origin and evolution, and whether it contains life beyond our planet.

Both countries had previously been asked to submit separate bids for the telescope, which is likely to cost at least $US2 billion, and whose 3,000 receptors have been designed to make the telescope 50 times more sensitive to radio waves than any existing facility.

The SKA Organisation – the international consortium responsible for the project – had been due to announce which bid had been successful last week, but at the end of a two-day meeting in the Netherlands, it issued a statement on 4 April saying that its members had recognised that it was “desirable to maintain an inclusive approach”.

The statement added that the members considered it to be “important to maximise the value from the investments made by both candidate host regions”. As a result, a small scientific working group has been set up “to explore possible implementation options that would achieve this”.

Officials from the organisation have declined to elaborate further or to provide any further details on what these options might be, citing the need to keep the negotiations confidential.

One possibility that has been raised is that receptors built in South Africa, Australia and New Zealand – which is a partner to the Australian bid – might be programmed to operate jointly.

However other commentators question whether the two sets of receptors can look at the same part of the sky simultaneously, given that Australia and South Africa are on opposite sides of the Southern hemisphere.

Unconfirmed reports in the Australian media have suggested that a panel of scientific experts had given their preference to the South Africa bid, which would involve building receiving stations in at least eight other African nations.

South Africa’s Science Ministry has strongly rejected suggestions that this option represented a “sympathy decision”. Officials insist the country has the capacity to host the facility, and supporters of the South African bid have also emphasised the potential role of the SKA project to boost the image of science and technology in Africa.

In an interview with SciDev.Net last year, the director of the South African bid, Bernie Fanaroff, described the importance of the SKA project for its potential to create “a significant legacy of skills and be a continuing attraction for young people in Africa to enter careers in science and technology”.

However the South African Ministry of Science and Technology has been quoted as describing accusations that such arguments had been used to sway the site adjudication process as “a not very subtle attempt to undermine [its] scientific and technical rigour”.

Source: SciVX

Brazil tests GM mosquitoes to fight dengue.


Scientists in Brazil say an experiment to reduce populations of the dengue-carrying Aedes aegypti mosquito, by releasing millions of genetically modified (GM) insects into the wild, is working.

More than ten million modified male mosquitoes were released in the city of Juazeiro, a city of 288,000 people, over a period of time starting a year ago.

The results were released at a workshop in Rio last week (28–29 March), where the project’s co-ordinator, Aldo Malavasi, said they were “very positive”.

“From samples collected in the field, 85 per cent of the eggs were transgenic, which means that the males released are overriding the wild population. This [should result] in the decrease of Aedes mosquitoes, and in the decrease of dengue transmission,” he told SciDev.Net.

Malavasi is also the president of Moscamed — the Brazilian firm that produced the mosquitoes. The mosquitoes, which carry a gene which causes their offspring to die before reaching adulthood, were originally developed by the British firm Oxitec.

They have already been tested in Malaysia and the Cayman Islands, but this is believed to be the largest experiment in the wild to date.

“We developed technology to efficiently create the transgenic insects here [in Brazil], so we won’t need to buy them from England in the future, reducing costs,” Malavasi said.

The method has been approved by the Brazilian National Biosafety Technical Committee, and will be used in other Brazilian cities. Ultimately, it is hoped the GM mosquitoes will lead to the eradication of dengue in areas where insect translocation is low, and substantially reduced elsewhere.

Before releasing the mosquitoes, Malavasi said his team visited homes, schools and churches in Juazeiro to seek the permission of residents, and said nearly 90 per cent were in favour.

Margareth Capurro, a biologist from the University of São Paulo, confirmed residents support of the experiment.

“They were worried when they saw so many mosquitoes [being released], but we worked closely with them to explain the experiment,” she told SciDev.Net.

Mark Benedict, from the University of Perugia, Italy, said the results were promising. “The data indicates that the system is working as expected. We’ve seen no major issues with the way they are doing things, so I think it’s very promising,” he told SciDev.Net.

Environmental advocates, including GeneWatch UK, have expressed concern over the potential of GM mosquitoes to survive and breed in the wild with unpredictable results.

Malavasi said he was confident the modified mosquitoes would be unable to produce viable offspring.

“But that doesn’t mean that we are not careful. We are always running control tests,” he said.

Malavasi said it would take time for lower Aedes populations to be reflected in lower dengue transmission rates, and said the researchers have yet to survey local communities to assess dengue incidence.

Source: SciVX

Depression in Teens Could Be Diagnosed with Blood Test.


A blood test based on 11 genetic markers could make early-onset diagnosis easier and possibly relieve the stigma of depression

Can a psychiatric disorder be diagnosed with a blood test? That may be the future if two recent studies pan out. Researchers are figuring out how to differentiate the blood of a depressed person from that of someone without depression.

In the latest study, published today (April 17) in the journal Translational Psychiatry, researchers identified 11 new markers, or chemicals in the blood, for early-onset depression. These markers were found in different levels in teens with depression compared with their levels in teens who didn’t have the condition.

Currently, depression is diagnosed by a subjective test, dependent upon a person’s own explanation of their symptoms, and a psychiatrist’s interpretation of them. These blood tests aren’t meant to replace a psychiatrist, but could make the diagnosis process easier.

If a worried parent could have a family physician run a blood test, it might ease the diagnosis process during the already tough time of adolescence, said Eva Redei, a professor at Northwestern University in Evanston, Ill., who was involved in the study of the teen-depression blood test.

If they hold up to further testing, blood tests could help young adults, who often go untreated because they aren’t aware of their disease, get treated. The biological basis of a blood test could also help to reduce that stigma, researchers suggest.

Depressing diagnosis
In the new study, Redei and her colleagues focused on early-onset depression, which occurs in teens and young adults before age 25. About 15 percent of young women and 7 percent of young men between ages 13 and 18 are estimated to have the disease.

This disease is a distinct condition, different from adult-onset depression, she said. In teens, “it has a somewhat greater genetic contribution, and also it has usually a harder course,” Redei told LiveScience.

The researchers first looked at the genes of rats that had been bred to be either more or less depressed, considered the “genetic model.” Next, they looked at four different strains of rats placed under chronic stress, an environmental factor that causes depression. They compared the gene-expression changes, which can occur as a result of stress, between the chronically stressed rats and individuals without extra stress.

The researchers then took 26 gene-expression changes they’d identified in theanimals to see if they held up in depressed humans; they tested 14 depressed and 14 non-depressed teens. Eleven of the genetic markers faithfully distinguished between teens with and without depression.

Building to a blood test
In an earlier study, published in the Feb. 28 issue of the journal Molecular Psychiatry, researchers focused on a blood test for adult-onset depression. The researchers used nine markers, consisting of proteins and other body chemicals that had previously been identified as related to depression and brain functioning.

With these markers, they came up with a formula to give each patient’s blood test a score, which indicated the likelihood of  having depression.

The researchers analyzed the blood of 70 depressed adults and 43 non-depressed controls. The average score of the depressed patients was 85, and the score of the non-depressed patients was 33. The researchers said the test could detect depression in 90 percent of people who actually have the condition.

“We expect that the biological basis of this test may provide patients with insight into their depression as a treatable disease rather than a source of self-doubt and stigma,” John Bilello, chief scientific officer of Ridge Diagnostics, which makes the blood test and sponsored the study, said in a statement.

Brain and the blood
Redei also said that a blood test could also help remove some of the stigma attached to depression.

“Only about 25 percent of depressed teens are being treated,” she said. “It has to do with the fact that they have to go through this process to be diagnosed, and then there is a stigma attached to it.”

Because a blood test provides physical evidence of a disease, it could help counter misconceptions about depression, such as that it is all in a person’s head, or is a sign of some personal weakness, the reasoning goes.

“It will help remove that stigma, if we have something you can attach a number to,” Redei said.”Eventually the whole society will accept that this disease, depression, isn’t something you can just get over by pulling yourself up.”

Source: Scientific American.

Where do the highest-energy cosmic rays come from? Not from gamma-ray bursts, says IceCube study.


The IceCube neutrino telescope encompasses a cubic kilometer of clear Antarctic ice under the South Pole, a volume seeded with an array of 5,160 sensitive digital optical modules (DOMs) that precisely track the direction and energy of speeding muons, massive cousins of the electron, which are created when neutrinos collide with atoms in the ice. The IceCube Collaboration recently announced the results of an exhaustive search for high-energy neutrinos that would likely be produced if the violent extragalactic explosions known as gamma-ray bursts (GRBs) are the source of ultra-high-energy cosmic rays.

“According to a leading model, we would have expected to see 8.4 events corresponding to GRB production of neutrinos in the IceCube data used for this search,” says Spencer Klein of the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), who is a long-time member of the IceCube Collaboration. “We didn’t see any, which indicates that GRBs are not the source of ultra-high-energy cosmic rays.”

“This result represents a coming-of-age of neutrino astronomy,” says Nathan Whitehorn from the University of Wisconsin-Madison, who led the recent GRB research with Peter Redl of the University of Maryland. “IceCube, while still under construction, was able to rule out 15 years of predictions and has begun to challenge one of only two major possibilities for the origin of the highest-energy cosmic rays, namely gamma-ray bursts and active galactic nuclei.”

Redl says, “While not finding a neutrino signal originating from GRBs was disappointing, this is the first neutrino astronomy result that is able to strongly constrain extra-galactic astrophysics models, and therefore marks the beginning of an exciting new era of neutrino astronomy.”

The IceCube Collaboration’s report on the search appears in the April 19, 2012, issue of the journal Nature.

Blazing fireballs and nature’s accelerators

Cosmic rays are energetic particles from deep in outer space – predominately protons, the bare nuclei of hydrogen atoms, plus some heavier atomic nuclei. Most probably acquire their energy when naturally accelerated by exploding stars. A few rare cosmic rays pack an astonishing wallop, however, with energies prodigiously greater than the highest ever attained by human-made accelerators like CERN’s Large Hadron Collider. Their sources are a mystery.

“Nature is capable of accelerating elementary particles to macroscopic energies,” says Francis Halzen, IceCube’s principal investigator and a professor of physics at the University of Wisconsin-Madison. “There are basically only two ideas on how she does this: in gravitationally driven particle flows near the supermassive black holes at the centers of active galaxies, and in the collapse of stars to a black hole, seen by astronomers as gamma ray bursts.”

 

Klein, the deputy director of Berkeley Lab’s Nuclear Science Division (NSD, explains that in active galactic nuclei (AGNs) “the black holes suck in matter and eject enormous particle jets, perpendicular to the galactic disk, which could act as strong linear accelerators.” Of gamma-ray bursts he says, “Some GRBs are thought to be collapses of supermassive stars – hypernova – while others are thought to be collisions of black holes with other black holes or neutron stars. Both types produce brief but intense blasts of radiation.”

The massive fireballs move away from the explosion at nearly the speed of light, releasing most of their energy as gamma rays. The fireballs that give rise to this radiation might also accelerate particles to very high energies through a jet mechanism similar to that in AGNs, although compressed into a much smaller volume.

Accelerated protons in a GRB’s jets should interact with the intense gamma-ray background and strong magnetic fields to produce neutrinos with energies about five percent of the proton energy, together with much higher-energy neutrinos near the end of the acceleration process.

 

Neutrinos come in three different types that change and mix as they travel to Earth; the total flux can be estimated from the muon neutrinos that IceCube concentrates on. The muons these neutrinos create can travel up to 10 kilometers through the Antarctic ice. Thus many neutrino interactions occur outside the actual dimensions of the IceCube array but are nevertheless visible to IceCube’s detectors, effectively enlarging the telescope’s aperture.

“The way we search for GRB neutrinos is that we build a huge detector and then we just watch and wait,” says Klein. “When it comes to detecting neutrinos, size really does matter.”

IceCube watches with its over 5,000 DOMs, digital optical modules conceived, designed, and proven by Berkeley Lab physicists and engineers, which detect the faint light from each passing muon. Scientists can rely on their remarkable dependability to wait as long as necessary. Almost no failures occurred after the DOMs were installed; 98 percent are working perfectly and another one percent are usable. Now frozen in the ice, they will never be seen again.

IceCube records a million times more muon tracks moving downward through the ice than upward, mainly debris from direct cosmic-ray hits on the surface or secondary products of cosmic-ray collisions with Earth’s atmosphere. Muons moving upward, however, signal neutrinos that have passed all the way through Earth. When the telescope is searching for bright neutrino sources in the northern sky, the planet makes a marvelous filter.

Zeroing in on gamma-ray bursts

A network of satellites circles the globe and reports almost 700 GRBs each year, which readily stand out from the cosmic background. They’re timed, their positions are triangulated, and the data are distributed by an international group of researchers. Some blaze for less than two seconds and others for a few minutes. Neutrinos they produce should arrive at IceCube during the burst or close to it.

“IceCube’s precision timing and charge resolution, plus its large size, allow it to precisely determine where a neutrino comes from – often to within one degree,” says Lisa Gerhardt of Berkeley Lab, whose research has focused on detecting ultra-high-energy neutrino interactions. Indeed, a GRB neutrino should send a muon track through the ice with an angular resolution of about one degree with respect to the GRB’s position in the sky.

IceCube researchers sifted through data on 307 GRBs from two periods in 2008 and 2009 when IceCube was still under construction, looking for records of muon trails coincident in time and space with GRBs. (Forty strings, with 60 DOMs each, had been installed by 2008, and 59 strings by 2009. The finished IceCube has 86 strings.) The fireball model predicted that when the expected flux from all the samples had been summed, at least 8.4 related muon events would be found within 10 degrees of a GRB during the seconds or minutes when it was blazing brightly.

“Different calculations of the neutrino flux from GRBs are based on slightly different assumptions about how the neutrinos are produced and on uncertainties such as how fast the fireball is moving toward us,” says Klein. “Among the published predictions, the lowest estimate of neutrino production is about a quarter of what the fireball model predicts. That’s barely consistent with our zero observations.”

Says Halzen, “After observing gamma-ray bursts for two years, we have not detected the telltale neutrinos for cosmic ray acceleration.”

If it’s likely that GRBs aren’t up to the task of accelerating cosmic rays to ultra-high-energies, what are the options? Klein points to a salient fact about natural accelerators: a small, rapidly spinning object must accelerate particles very rapidly; this requires an extremely energy-dense environment, and there are many ways the particles could lose energy during the acceleration process.

“But remember the other popular model of ultra-high-energy cosmic rays, active galactic nuclei,” says Klein. “GRBs are small, but AGNs are big – great big accelerators that may be able to accelerate particles to very high energies without significant loss.”

Are AGNs the real source of the highest-energy cosmic rays? IceCube has looked for neutrinos from active galactic nuclei, but as yet the data sets are not sensitive enough to set significant limits. For now, IceCube has nothing to say on the subject – beyond the fact that the fireball model of GRBs can’t meet the specs.

Source:  Lawrence Berkeley National

Exposure to Alcohol Use by Parents and in Movies Correlates with Onset of Adolescent Drinking.


But only exposure in movies predicts transition to binge drinking.

Understanding what influences adolescents to start drinking and transition to binge drinking is critical to reduce alcohol-related harms. Investigators examined the influence of peer and family factors as well as media alcohol exposure on onset of drinking and transition to binge drinking using longitudinal data from a representative sample of 6522 U.S. adolescents (age range at baseline, 10–14 years). Respondents were surveyed about onset of alcohol use every 8 months for 2 years. Risk factors included adolescent-reported peer alcohol use, frequency of parental alcohol use, availability of alcohol at home, perceived authoritative parenting, receptivity to alco hol marketing (owning alcohol-branded merchandise), and movie alcohol exposure.

Movie alcohol exposure was determined by calculating the number of seconds of on-screen alcohol use in movies that adolescents reported to have seen from a random sample of the top 100 U.S. box office hits. After controlling for demographic variables, high peer alcohol use was the most powerful predictor of drinking onset (adjusted hazard ratio, 2.9), followed by high movie alcohol exposure (2.1), less-authoritative parenting (1.8), alcohol availability at home (1.5), receptivity to alcohol marketing (1.4), and parent alcohol use (1.4). Predictors of the transition from drinking onset to binge drinking were high peer alcohol use (2.8), high movie alcohol exposure (1.6), and receptivity to alcohol marketing (1.2); unskilled (nonauthoritative) parenting and parental alcohol use did not predict transition to binge drinking.

Comment: It’s worth reminding parents that an authoritative parenting style (including restricting alcohol availability at home) can decrease the likelihood that teenagers will start to drink. This includes encouraging parents to be firm, regardless of any pushback that they might get from their children (e.g., “Isn’t it safer for me and my friends to drink at home?”). But authoritative parenting addresses only one dimension of the underage drinking problem. According to this study, movie alcohol exposure plays a greater role in both drinking onset and transition to binge drinking. The authors estimate that movie alcohol exposure accounts for 28% of transitions to drinking and 20% of transitions to binge drinking. A recent study of more than 16,000 students in six European countries also demonstrated that exposure to alcohol use in movies was linked to binge drinking in five of the countries (Pediatrics 2012; 129:1). Taken together, these studies argue for st ricter controls on alcohol product placement in movies and a ban (including a parent-enforced ban) on providing alcohol-branded merchandise to adolescents.

Source: Journal Watch Pediatrics and Adolescent Medicine.

 

Using Imaging to Pinpoint Genetic Mutations in Brain Tumors.


Recent studies suggest that a noninvasive imaging technique can identify the presence of certain genetic mutations in gliomas, the most common type of brain tumor, by detecting a substance produced as a consequence of those mutations. If further studies validate the finding, oncologists may be able to use this approach to diagnose tumors carrying the mutations, distinguish different glioma subtypes,monitor tumor progression, and detect recurrences—all without repeated surgeries or biopsies.

The technique uses magnetic resonance spectroscopy (MRS) to detect 2-hydroxyglutarate (2-HG), a chemical that is scarce in normal tissues but accumulates in gliomas that harbor mutations in two related genes, IDH1 and IDH2. Until now, the only way to detect IDH mutations or 2-HG in a tumor was a biopsy and analysis of tissue samples. Taken together, the new work provides evidence that 2-HG could serve as a noninvasive biomarker of tumors with IDH mutations.

More than 70 percent of adults with invasive, lower-grade (grade II or III) gliomas carry IDH mutations. IDH mutations are uncommon in primary forms of glioblastoma, but they are found in many secondary glioblastomas, which arise from lower-grade gliomas. Glioblastoma is the most aggressive type of glioma.

Tumors with IDH mutations make an aberrant form of the enzyme isocitrate dehydrogenase (IDH), which plays an essential part in a metabolic pathway that cells use to generate energy. The mutations not only impair the enzyme’s normal function but also give it the ability to make 2-HG.

MRS can be done at the same time and with the same magnetic resonance imaging (MRI) equipment medical centers use for diagnostic imaging. While MRI scans provide anatomical and structural information, MRS provides information on cellular activity by detecting metabolites in tissue, explained Dr. Ovidiu Andronesi, an instructor in radiology at Harvard Medical School and lead author of one of the recent studies.

Informative Mutations

Currently, a definitive diagnosis of glioma requires a biopsy and examination by a pathologist, who assigns a grade of I to IV to the tumor, with grade IV (glioblastoma) being the most aggressive. However, “two grade II tumors may look the same under the microscope, but one may be very slow-growing and another may kill the patient within 2 years,” noted Dr. Howard Fine, chief of NIH’s Neuro-Oncology Branch, who was not involved in the MRS studies. “We need to get to the point where we’re [classifying tumors] on the basis of the genetics and the molecular biology,” he said.

Thus, researchers were interested to find that patients with glioblastoma who have IDH mutations generally live longer than patients who lack the mutations. Several studies have also found that IDH mutations are associated with better outcomes in lower-grade gliomas, although this link is not as firmly established.

“Across [glioma] patients within the same tumor grade, there is a prognostic advantage to having an IDH mutation,” said Dr. Susan Chang, director of Neuro-Oncology at the University of California, San Francisco (UCSF), who collaborated on a study led by UCSF radiology and biomedical imaging professor Dr. Sarah Nelson. If further studies confirm this advantage, assessing a tumor’s 2-HG status with MRS could be used to divide patients into groups with similar prognoses for clinical trials of new therapies, Dr. Chang said.

MRS could also be used to diagnose IDH-mutated gliomas before surgery and to distinguish them from nonmalignant brain lesions, such as those due to multiple sclerosis, said Dr. Elizabeth Maher, a neuro-oncologist who led a study at the University of Texas Southwestern Medical Center with physicist Dr. Changho Choi. Although the approach is still experimental, Dr. Maher said she has already used it to diagnose a low-grade glioma in the brain stem of a 20-year-old patient, helping the patient avoid a risky biopsy procedure.

Study Results

Researchers have used several MRS techniques to detect 2-HG, which can be difficult to distinguish from some common brain metabolites with established clinical MRS methods. Dr. Nelson and colleagues noninvasively detected and measured 2-HG in small tissue samples taken from recurrent gliomas in 52 patients originally diagnosed with grade II glioma. They found a strong correlation between the presence of 2-HG in tissue samples and the presence of IDH1 mutations in tumor tissue. (IDH1 mutations are much more common than IDH2 mutations.) They also correlated varying levels of 2-HG in IDH-mutated tumors of different grades with several histopathology parameters, including the density of tumor cells in a sample.

While the UCSF researchers used MRS to detect 2-HG ex vivo (outside the body), Dr. Andronesi’s team showed that noninvasive MRS could also detect 2-HG unambiguously in vivo (in the body) in two glioma patients with IDH-mutated tumors. They did not detect 2-HG in four healthy volunteers or in four primary glioblastoma patients who lacked IDH mutations.

In a perspective article accompanying the two studies, Drs. Philippe Metellus and Dominique Figarella-Branger of the Hôpital de la Timone in Marseille, France, detailed the potential clinical applications of “these major findings.” However, they wrote, “the MRS methodology used in these studies is not available in all clinical radiology settings. Also, in vivo proof-of-principle data will need to be reproduced in a larger cohort.”

Physicians hope to use magnetic resonance spectroscopy to noninvasively detect tumor recurrence after surgery.

Those concerns were addressed at least in part by the UT Southwestern study and by a study led by Dr. Linda Liau, professor and vice chair in the Department of Neurosurgery at the University of California, Los Angeles. Both used in vivo MRS methods that could be done routinely in most hospitals and medical centers with relatively minor modifications of standard MRS techniques.

Dr. Liau’s team showed that, in 24 of 27 patients with gliomas of various grades, in vivo MRS could detect the higher 2-HG levels found in tumors with IDH1 mutations. They also showed that 2-HG levels measured noninvasively by MRS in patients prior to surgery correlated with 2-HG levels measured in corresponding tumor samples with a laboratory technique known as liquid chromatography-mass spectroscopy (LC-MS).

And, in their study of 30 patients with grade II, III, or IV gliomas, Dr. Maher and colleagues showed that in vivo MRS detection of 2-HG correlated with mutations in IDH1 or IDH2 and with increased 2-HG levels measured in tumor samples by LC-MS. The team also estimated the concentrations of 2-HG in patient’s tumors.

Taking It to the Next Level

The MRS methods used by each group have advantages and disadvantages, and most teams are still refining and optimizing their approaches. “The jury is still out on which is the best approach,” Dr. Nelson said. “One would have to do a head-to-head comparison under similar circumstances in order to establish [which is best].”

As Dr. Andronesi noted, researchers now need to “establish the sensitivity and specificity of these methods—so-called validation…using genomics as the gold standard” for detecting IDH mutations. “It’s important that validation is done not only in one center and by one group, but that other people can replicate [the findings],” he said.

In anticipation of testing possible clinical applications, researchers are working to show that in vivo MRS can be used not only to detect 2-HG but also to accurately measure the concentration of 2-HG in a tumor. “Showing [that] something is there is one thing,” Dr. Nelson noted. “Being able to measure it to a plus or minus 10 percent accuracy, which you need to do in order to look at subtle changes, is something else.”

If 2-HG levels are shown to reflect changes in tumor growth or progression, physicians could use MRS measurement of 2-HG levels to monitor responses to therapy, or to detect early signs of tumor progression in patients with IDH-mutated gliomas. “Eventually, about 80 percent of low-grade tumors will transform into the highest-grade tumors, and we have no way of picking that up [on an MRI] before there’s an outgrowth of a big tumor,” Dr. Maher said.

Similarly, physicians hope to use MRS to noninvasively detect tumor recurrence after surgery. Doing so is “one of the biggest challenges that face oncologists today,” Dr. Nelson noted, because changes on a standard MRI that suggest a recurrence may also be due to effects of treatment.

“In the broader scheme of things, it may be that 2-HG is not the only important metabolite,” Dr. Liau said. Her group as well as Dr. Maher’s and Dr. Nelson’s are using in vivo MRS to study changes in a range of metabolites in gliomas. Such information could be used to establish “molecular fingerprints” of tumor grade and disease progression and to understand more about the basic biology of why gliomas form and develop.

Source:NCI

Nature’s billion-year-old battery key to storing energy.


New research at Concordia University is bringing us one step closer to clean energy. It is possible to extend the length of time a battery-like enzyme can store energy from seconds to hours, a study published in the Journal of The American Chemical Society shows.

Concordia Associate Professor László Kálmán — along with his colleagues in the Department of Physics, graduate students Sasmit Deshmukh and Kai Tang — has been working with an enzyme found in bacteria that is crucial for capturing solar energy. Light induces a charge separation in the enzyme, causing one end to become negatively charged and the other positively charged, much like in a battery.

 

In nature, the energy created is used immediately, but Kálmán says that to store that electrical potential, he and his colleagues had to find a way to keep the enzyme in a charge-separated state for a longer period of time.

“We had to create a situation where the charges don’t want to or are not allowed to go back, and that’s what we did in this study,” says Kálmán.

 

Kálmán and his colleagues showed that by adding different molecules, they were able to alter the shape of the enzyme and, thus, extend the lifespan of its electrical potential.

In its natural configuration, the enzyme is perfectly embedded in the cell’s outer layer, known as the lipid membrane. The enzyme’s structure allows it to quickly recombine the charges and recover from a charge-separated state.

However, when different lipid molecules make up the membrane, as in Kálmán’s experiments, there is a mismatch between the shape of the membrane and the enzyme embedded within it. Both the enzyme and the membrane end up changing their shapes to find a good fit. The changes make it more difficult for the enzyme to recombine the charges, thereby allowing the electrical potential to last much longer.

 

“What we’re doing is similar to placing a racecar in on snow-covered streets,” says Kálmán. The surrounding conditions prevent the racecar from performing as it would on a racetrack, just like the different lipids prevent the enzyme from recombining the charges as efficiently as it does under normal circumstances.

Photosynthesis, which has existed for billions of years, is one of the earliest energy-converting systems. “All of our food, our energy sources (gasoline, coal) — everything is a product of some ancient photosynthetic activity,” says Kálmán.

But he adds that the main reason researchers are turning to these ancient natural systems is because they are carbon neutral and use resources that are in abundance: sun, carbon dioxide and water. Researchers are using nature’s battery to inspire more sustainable, man-made energy converting systems.

For a peek into the future of these technologies, Kálmán points to medical applications and biocompatible batteries. Imagine batteries made of enzymes and other biological molecules. These could be used to, for example, monitor a patient from the inside post-surgery. Unlike traditional batteries that contain toxic metals, biocompatible batteries could be left inside the body without causing harm.

We’re far from that right now but these devices are currently being explored and developed,” says Kálmán. “We have to take things step by step but, hopefully, we’ll get there one day in the not-too-distant future.”

Source:  Concordia University.