Sensing gravity with acid: Scientists discover role for protons in neurotransmission

While probing how organisms sense gravity and acceleration, scientists at the Marine Biological Laboratory (MBL) and the University of Utah uncovered evidence that acid (proton concentration) plays a key role in communication between neurons. The surprising discovery is reported this week in the Proceedings of the National Academy of Sciences.

The team, led by the late MBL senior scientist Stephen M. Highstein, discovered that sensory cells in the inner ear continuously transmit information on orientation of the head relative to gravity and low-frequency motion to the brain using protons as the key means of synaptic signal transmission. (The synapse is the structure that allows one neuron to communicate with another by passing a chemical or electrical signal between them.)

"This addresses how we sense gravity and other low-frequency inertial stimuli, like acceleration of an automobile or roll of an airplane," says co-author Richard Rabbitt, a professor at University of Utah and adjunct faculty member in the MBL's Program in Sensory Physiology and Behavior. "These are very long-lasting signals requiring a a synapse that does not fatigue or lose sensitivity over time. Use of protons to acidify the space between cells and transmit information from one cell to another could explain how the inner ear is able to sense tonic signals, such as gravity, in a robust and energy efficient way."

The team found that this novel mode of neurotransmission between the sensory cells (type 1 vestibular hair cells) and their target afferent neurons (calyx nerve terminals), which send signals to the brain, is continuous or nonquantal. This nonquantal transmission is unusual and, for low-frequency stimuli like gravity, is more energy efficient than traditional synapses in which chemical neurotransmitters are packaged in vesicles and released quantally.

The calyx nerve terminal has a ball-in-socket shape that envelopes the sensory hair cell and helps to capture protons exiting the cell. "The inner-ear vestibular system is the only place where this particular type of synapse is present," Rabbitt says. "But the fact that protons are playing a key role here suggests they are likely to act as important signaling molecules in other synapses as well."

Previously, Erik Jorgensen of University of Utah (who recently received a Lillie Research Innovation Award from the MBL and the University of Chicago) and colleagues discovered that protons act as signaling molecules between muscle cells in the worm C. elegans and play an important role in muscle contraction. The present paper is the first to demonstrate that protons also act directly as a nonquantal chemical neurotransmitter in concert with classical neurotransmission mechanisms. The discovery suggests that similar intercellular proton signaling mechanisms might be at play in the central nervous system.

Stephen Highstein, who died in January 2014, was associate director of the MBL's Program in Sensory Physiology and Behavior. Mary Anne Mann, a research associate in the program, also participated in this research, as did Gay Holstein of Mt. Sinai School of Medicine.

Story Source:

The above story is based on materials provided by Marine Biological Laboratory. The original article was written by Diana Kenney. Note: Materials may be edited for content and length.

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Scientists make advance in cancer research

Jan. 3, 2014 — A protein that has been at the center of cancer drug design for the last 20 years should not be given up on according to new research from the University of East Anglia (UEA).

The most advanced version of αvβ3-integrin antagonists failed clinical trials to treat aggressive forms of brain cancer.

But research published today in the American Heart Association's journal Circulation Research shows that targeting the protein in question could still be vital in stopping the growth of tumors. Not least because the drugs targeting it cause minimal side effects compared to other drugs -- which can cause bleeding in the gut and high blood pressure.

tumors must recruit their own blood supply to grow beyond a very small size. The research team studied the cells that line blood vessels (endothelial cells) in mice, and in particular the role of a widely expressed protein called beta3-integrin.

Dr Stephen Robinson, from UEA's school of Biological Sciences, said: "This protein has been the focus of drug design over the last two decades because its expression is vastly increased in endothelial cells during blood vessel recruitment.

"The most advanced of these drugs, however, has recently failed a phase III clinical trial to treat an aggressive form of brain cancer. In line with other clinical work, patients respond to treatment for a short while but then their cancers escape the treatment.

"This research helps to explain why these very promising drugs aren't meeting with the success that was anticipated and it suggests a way forward -- how to make them work better.

"We have shown how tumors continue to grow despite treatment which should block blood vessel recruitment. They modulate how they are recruiting their blood vessels by using a different pathway from the one that is being targeted. We have identified some molecular changes in endothelial cells that occur with long-term inhibition of beta3-integrin that might help the cells escape the beta3-integrin blockade.

"Our research also shows that timing is critical when targeting the protein beta3-integrin.

"Importantly, these findings have re-established the expression of beta3-integrin as a valid clinical target when treating cancer. Efforts must now be re-focused to either develop new drugs to target beta3-integrin, or figure out how to more effectively use the drugs that already exist."

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Scientists achieve most detailed picture ever of key part of hepatitis C virus

Nov. 28, 2013 — Scientists at The Scripps Research Institute (TSRI) have determined the most detailed picture yet of a crucial part of the hepatitis C virus, which the virus uses to infect liver cells. The new data reveal unexpected structural features of this protein and should greatly speed efforts to make an effective hepatitis C vaccine.

The findings, which appear in the November 29, 2013 issue of the journal Science, focus on a protein known as E2 envelope glycoprotein.

"We're excited by this development," said Ian A. Wilson, the Hansen Professor of Structural Biology at TSRI and a senior author of the new research with TSRI Assistant Professors Mansun Law and Andrew B. Ward. "It has been very hard to get a high resolution structure of E2 and it took years of painstaking work to finally accomplish that."

Any successful hepatitis C vaccine is likely to target the E2 protein. Scientists already have isolated rare antibodies from patients that can bind E2 in ways that neutralize a broad range of viral strains.

"It took our team six years to crack this very difficult scientific problem, but we didn't give up," said Law. "Now that we can visualize the structural details of these binding sites, we can design vaccine molecules that mimic them."

A Silent Killer

There has long been an urgent need for an effective vaccine against hepatitis C virus. Once confined to isolated geographical regions, the virus spread globally during the 20th century, chiefly via blood transfusions, unsterilized medical instruments and re-used hypodermic needles. Although hospitals have screened blood products for hepatitis C virus (HCV) since the early 1990s, as many as 200 million people currently are thought to harbor the virus. These include more than 3 million people in the United States, where the virus is responsible for more deaths each year than HIV.

HCV was able to spread so widely because it typically causes few or no symptoms when it infects someone. In many cases it establishes a long-term infection of the liver, damaging it slowly for decades -- until liver cirrhosis and/or cancer develop. "It's known as a 'silent killer'," said Law. Expensive and risky liver transplantation is often the only way to save a patient's life. Some antiviral drugs are useful in treating and even curing chronic HCV infection, but the more effective ones are extremely expensive -- and most HCV-positive people don't even know that they're infected and need treatment.

An HCV vaccine could put an end to the global pandemic by preventing new infections. "It could be given to people when they're young and healthy, and they'd never have to worry about developing HCV-related liver diseases," said Ward.

However, like HIV and some other viruses, HCV uses several effective countermeasures to evade the immune system. These include fast-mutating regions on the E2 protein, which ensure that antibodies to one HCV strain typically are ineffective against other strains. The E2 protein also coats itself with relatively antibody-proof sugar molecules.

To defeat these viral countermeasures, scientists have wanted to "see" the high-resolution atomic structure of HCV, particularly E2 and its CD81 receptor binding site, which does not vary much from strain to strain. In recent years, Law's laboratory and others have isolated antibodies that manage to grab hold of this relatively conserved region of E2, thereby blocking the infectivity of a large fraction of HCV strains. In principle, a vaccine that prompts the body to make similar antibodies would effectively and cheaply immunize people against most of their risk of HCV infection.

Unruly E2

But precisely mimicking these antibody-binding sites in a vaccine means first determining their high-resolution structures, which has been difficult even to attempt. "Usually if you try to express the E2 protein in cultured cells, you either can't express it in useful quantities or you can but it aggregates and becomes a big mess," said Leopold Kong, a research associate in the Wilson laboratory who was the study's lead author.

Over the past several years, Kong and his colleagues have run dozens of experiments to find the right way to modify E2 -- enough that the protein doesn't aggregate so readily and also so that the antibody-binding sites are maintained. This would enable the protein to be soluble and pure enough to grow crystals to determine its structure by the technique known as X-ray crystallography. "It was a Herculean effort," said Ward. "This is one of the most difficult and unstable viral envelope proteins around."

In the end, the team succeeded, using a slightly altered version of E2 -- the E2 core -- with some of its glycans (sugar molecules) and outer variable and stalk segments removed. The scientists were then able to obtain the high-resolution structure of the protein while it was bound to a known broadly neutralizing antibody developed at TSRI. The scientists then followed up by imaging a more complete version of E2 using electron microscopy to extend the structural model.

When finally revealed, E2's structure surprised the researchers. "It had been thought that HCV's E2 belongs to a family of viral fusion proteins called class 2 fusion proteins, which includes envelope proteins for West Nile and dengue viruses, for example," said Kong. "But we showed that E2 is structurally distinct and probably works differently than what had been widely assumed."

Based on the new structural data, Law and colleagues at TSRI are already designing and testing novel antibody-stimulating components of a future HCV vaccine. "Having the E2 structure has certainly helped us," said Law.

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Scientists find 'missing link' in important tumor suppression mechanism

Nov. 12, 2013 — RUNX3, a gene that is intensively studied for its function as a tumor suppressor, is likely to be a key and critical component of the body's first line of defense against lung cancer development, according to a recent study by scientists from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS), together with their collaborators from Chungbuk National University in Korea.

The team, led by Professor Yoshiaki Ito of CSI Singapore, showed that RUNX3 is a major component in a well-established tumor suppression mechanism involving p53, a tumor suppressor protein that regulates cell proliferation and prevent cancer. In addition, the research team also demonstrated that RUNX3 plays a pivotal role in preventing early tumor formation.

Although the current study focused on lung cancer, the results help to explain the development of other types of human cancers.

These novel findings were published in leading scientific journal Cancer Cell on 11 November 2013.

Implications on early cancer detection and prevention

Mutations of the p53 gene occur in 50 per cent of virtually all cancer types, indicating that p53 inactivation constitutes one of the main drivers of cancer development. p53 has since been shown to exert multiple effects -- be it enhancing DNA repair, arresting cell proliferation or promoting cell death -- to inhibit cancer growth.

"This study uncovered an important missing component of the tumor suppressor pathway that regulates p53 function. The identification of RUNX3 as the key component throws light on why RUNX3 gene inactivation, particularly via epigenetic mechanisms, is so prevalent in cancer," Prof Ito explained.

"From a clinical viewpoint, this finding has applications in early cancer detection and prevention. Cancer-specific epigenetic inactivation of RUNX3 is marked by DNA methylation, which can be readily screened for early detection or prognosis of a wide variety of cancer. It also suggests the exciting possibility that RUNX3 inactivation, if reversed by therapeutic means, may restrain cancer growth. It is therefore likely that many new approaches of cancer treatment or prevention will be generated," he added.

Role of RUNX3 in suppressing tumor formation

Lung cancer is the most frequently occurring cancer worldwide, and it is also the No. 1 killer cancer for both men and women in Asia-Pacific and Singapore. The prevalent type of lung cancer, called adenocarcinoma, is frequently observed to harbour genetic alterations in the oncogene K-Ras.

In normal cells, K-Ras is activated by a short-lived signal to promote cell growth and then rapidly deactivated. However, in lung cancer, a mutated version of K-Ras gene -- K-Ras^G12D -- is expressed. Instead of responding to the growth signal, the mutant K-Ras^G12D constantly stimulates cell growth, causing the uncontrolled and rapid growth of the cancer cells. Confronted with the activation of such oncogenes, normal cells would turn on tumor suppressor pathways to stop cell growth or kill abnormal cells.

Currently, the best studied tumor suppressor is p53, which is frequently inactivated in various human cancers. The activity of p53 is tightly regulated by a gene called MDM2 (which acts to limit the p53 growth-suppressive function) and its inhibitor p14^ARF. While scientists have found that p14^ARF inhibits MDM2 and thus promotes p53 activity, it is unclear how p14^ARF is induced.

To fill this gap in knowledge, the research team studied the molecular mechanism underlying K-Ras-induced lung adenocarcinoma. They found that p14^ARF is induced by the RUNX3 in collaboration with another protein called BRD2, in response to K-Ras^G12D. This suggests that RUNX3 is one of the major components of the well-established tumor suppressor pathway involving p53.

The discovery of the link between RUNX3 and BRD2 will also initiate new directions in studies on complex mechanisms that regulate gene expression, the impairment of which is often associated with cancer development.

RUNX3 as first line of defense against cancer formation

Another important breakthrough achieved by Prof Ito and the team was the discovery of different roles of RUNX3 and p53 in tumor suppression.

Since 2010, it has been known that while p53 can effectively destroy well-developed cancer cells, but it cannot respond to low levels of oncogenic stimuli and prevent the early stages of cancer development.

The research team showed that the sole inactivation of RUNX3 results in the rapid development of pre-cancerous adenoma (a benign tumor that may become malignant over time) in less than four months. On the other hand, inactivation of p53 alone has not been shown to induce adenoma. By showing that RUNX3 prevents adenoma formation, the team contributes to a better understanding of an important aspect of tumor suppression mechanism.

Commenting on the findings, Prof Ito said, "It is very likely that our body is protected by two lines of defense mechanisms against lung cancer development -- RUNX3 forms the first line which protects against adenoma formation while p53 forms the second line in protecting against adenocarcinoma formation. It will be important to examine whether other types of cancer also show two lines of defense mechanisms, since p53 is frequently inactivated in various cancer types."

The next step

p53 is often mutated and it is practically impossible to revert this mutation for the purpose of treatment. By contrast, RUNX3 is inactivated by DNA methylation (ie. epigenetic inactivation), a chemical event that silences the gene without altering its coding information.

"Clinical trials have shown that reactivation of epigenetically inactivated genes is feasible. Indeed, RUNX3 gene can be reactivated by chemicals in cancer cells in laboratory. Therefore, the team's immediate task is to find a way to effectively re-ignite RUNX3 gene activity. Since RUNX3 functions at early stages of cancer, reversal of RUNX3 inactivation could halt cancer development by timely prevention of permanent neoplastic changes," said Prof Ito.

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Scientists who share data publicly receive more citations

Oct. 1, 2013 — A new study finds that papers with data shared in public gene expression archives received increased numbers of citations for at least five years. The large size of the study allowed the researchers to exclude confounding factors that have plagued prior studies of the effect and to spot a trend of increasing dataset reuse over time. The findings will be important in persuading scientists that they can benefit directly from publicly sharing their data.

The study, which adds to growing evidence for an open data citation benefit across different scientific fields, is entitled "Data reuse and the open citation advantage." It was conducted by Dr. Heather Piwowar of Duke University and Dr. Todd Vision of the University of North Carolina at Chapel Hill, and published today in PeerJ, a peer reviewed open access journal in which all articles are freely available to everyone.

The study examined citations to over ten thousand articles that generated new gene expression data, a quarter of which had data publicly archived in the GEO and ArrayExpress repositories. Papers with publicly available data received about 9% more citations overall, with the difference increasing over time. The researchers concluded that much of this citation difference was due to actual data reuse.

"Professional advancement in science is still highly dependent on how well your paper gets cited, even in a field like genomics where the data underlying that paper may have far more scientific impact over the long term." said Dr. Vision, a biologist affiliated with the National Evolutionary Synthesis Center and the Dryad Digital Repository. "Until the happy day when hiring and promotion committees catch up with how to value data sharing for its own sake, it is comforting to know that scientists can still receive credit for data sharing in a currency that counts."

The researchers also mined the full text of articles for references to dataset identifiers in order to study trends in data reuse directly. They took the unusual step of discussing the obstacles they encountered in the paper. Dr. Piwowar, at the time of the study a postdoc with the DataONE project, said "We need more open and cohesive infrastructure to support collecting evidence about the process and products of science. This evidence is needed to inform important policy decisions. For example, data archiving requirements, infrastructure, and education should be informed by evidence about how data is and is not reused."

The mined references revealed that scientists generally stopped publishing papers using their own datasets within two years, while other scientists continued to reuse their data for at least six years. It also showed that data reuse is on the rise. "Not only were the number of reuse papers higher," says Dr. Piwowar, "but analyses from 2002 to 2004 were reusing only one or two datasets, while a quarter of the studies by 2010 were using three or more."

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Scientists urge Europe to shift focus to bowel cancer screening

By Kate Kelland

AMSTERDAM (Reuters) - European governments should divert funds to routine bowel cancer tests from less effective breast and prostate screening programs, scientists said on Saturday, presenting what they called "irrefutable" evidence that bowel screening saves lives.

Many governments devote significant funds to breast cancer screening, but studies in recent years have found that routine breast mammograms can also lead to so-called "over-diagnosis" when tests pick up tumors that would not have caused a problem.

And a new study presented at the European Cancer Conference (ECC) in Amsterdam at the weekend showed men experience more harm than good from routine prostate cancer screening tests.

In bowel cancer screening, however, the risk of over-diagnosis is very low, while gains in terms of reducing deaths are large - making routine testing cost-effective, Philippe Autier, a professor at France's International Prevention Research Institute (IPPR), told the conference.

"There is now an irrefutable case for devoting some of the resources from breast and prostate cancer screening to the early detection of colorectal (bowel) cancer," he said.

A large European study published last year found that breast screening programs over-diagnose about four cases for every 1,000 women aged between 50 and 69 who are screened.

The IPPR's research director Mathieu Boniol, who studied the impact of prostate screening, said his results showed routine use of prostate-specific antigen (PSA) tests creates more harm in terms of incontinence, impotence and other side-effects from prostate cancer treatments than benefit in terms of detecting life-threatening cancers.

"PSA testing should be reduced and more attention should be given to the harmful effects of screening," he told delegates.

Meanwhile, results of a study conducted by Autier using data from 11 European countries between 1989 and 2010 showed that the greater the proportions of men and women routinely screened for bowel cancer, the greater the reductions in death rates.

Colorectal cancer kills more than 600,000 people a year worldwide, according to the World Health Organization. In Europe some 400,000 people are diagnosed with the disease each year.

In Austria, for example, where 61 percent of those studied reported having had colorectal screening tests, deaths from this form of cancer dropped by 39 percent for men and 47 percent for women over the decade.

Meanwhile in Greece, where only 8 percent of males had had bowel cancer screening, death rates rose by 30 percent for men.

In the light of the results, Cornelis van de Velde, an oncologist at Leiden University Medical Centre in the Netherlands and president of the European Cancer Organisation, said it was "very disappointing" there are such wide differences in European governments' approaches to colorectal screening.

"People over 50 should be informed of the availability of the test, and pressure should be put on national health services to put more effort into organizing screening programs," he told the conference.

Screening for early signs of bowel cancer involves either a fecal occult blood test, which checks a sample of feces for hidden blood, or endoscopy, where a tiny camera is introduced into the large bowel to look for the polyps that can be a precursor of cancer.

In some European countries, such as France, Germany and Austria, many men and women over the age of 50 have regular colorectal screening examinations, while in others, such as The Netherlands and Britain, screening is much less common.

(Editing by David Evans)

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Europe should shift focus to bowel cancer screening to save lives: scientists

By Kate Kelland

AMSTERDAM (Reuters) - European governments should divert funds to routine bowel cancer tests from less effective breast and prostate screening programs, scientists said on Saturday, presenting what they called "irrefutable" evidence that bowel screening saves lives.

Many governments devote significant funds to breast cancer screening, but studies in recent years have found that routine breast mammograms can also lead to so-called "over-diagnosis" when tests pick up tumors that would not have caused a problem.

The risk of over-diagnosis in bowel cancer screening is very low, while gains in terms of reducing deaths are large - making routine testing cost-effective, Philippe Autier, a professor at France's International Prevention Research Institute, told the European Cancer Conference in Amsterdam.

"There is now an irrefutable case for devoting some of the resources from breast and prostate cancer screening to the early detection of colorectal (bowel) cancer," he said.

A large European study published last year found that breast screening programs over-diagnose about four cases for every 1,000 women aged between 50 and 69 who are screened.

Colorectal cancer kills more than 600,000 people a year worldwide, according to the World Health Organization. In Europe some 400,000 people are diagnosed with the disease each year.

Results of a study conducted by Autier using data from 11 European countries between 1989 and 2010 showed that the greater the proportions of men and women routinely screened for bowel cancer, the greater the reductions in death rates.

In Austria, for example, where 61 percent of those studied reported having had colorectal screening tests, deaths from this form of cancer dropped by 39 percent for men and 47 percent for women over the decade.

Meanwhile in Greece, where only 8 percent of males had had bowel cancer screening, death rates rose by 30 percent for men.

In the light of the results, Cornelis van de Velde, an oncologist at Leiden University Medical Centre in the Netherlands and president of the European Cancer Organisation, said it was "very disappointing" there are such wide differences in European governments' approaches to colorectal screening.

"People over 50 should be informed of the availability of the test, and pressure should be put on national health services to put more effort into organizing screening programs," he told the conference.

Screening for early signs of bowel cancer involves either a faecal occult blood test, which checks a sample of feces for hidden blood, or endoscopy, where a tiny camera is introduced into the large bowel to look for the polyps that can be a precursor of cancer.

In some European countries, such as France, Germany and Austria, many men and women over the age of 50 have regular colorectal screening examinations, while in others, such as The Netherlands and Britain, screening is much less common.

(Editing by Louise Ireland)

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Scientists find a Martian igneous rock that is surprisingly Earth-like

Sep. 27, 2013 — During the nearly 14 months that it has spent on the red planet, Curiosity, the Mars Science Laboratory (MSL) rover, has scooped soil, drilled rocks, and analyzed samples by exposing them to laser beams, X-rays, and alpha particles using the most sophisticated suite of scientific instruments ever deployed on another planet. One result of this effort was evidence reported last March that ancient Mars could have supported microbial life.

But Curiosity is far more than a one-trick rover, and in a paper published today in the journal Science, a team of MSL scientists reports its analysis of a surprisingly Earth-like martian rock that offers new insight into the history of Mars's interior and suggests parts of the red planet may be more like our own than we ever knew.

The paper -- whose lead author is Edward Stolper, Caltech's William E. Leonhard Professor of Geology, provost, and interim president -- is one of five appearing in the journal with results from the analysis of data and observations obtained during Curiosity's first 100 martian days (sols). The other papers include an evaluation of fine- and coarse-grained soil samples and detailed analyses of the composition and formation process of a windblown drift of sand and dust.

"The results presented go beyond the question of habitability," says John Grotzinger, MSL project scientist and Caltech's Fletcher Jones Professor of Geology. "Mars Science Laboratory also has a major mission objective to explore and characterize the geological environment at all scales and also the atmosphere. In doing this we learn about the fundamental physical and chemical properties that distinguish the terrestrial planets from each other and also what they share in common."

The paper by Stolper and his colleagues -- including Caltech senior research scientist Michael Baker and graduate student Megan Newcombe -- examines in detail a 50-centimeter-tall pyramid-shaped rock named "Jake_M" (after MSL surface operations systems chief engineer Jacob "Jake" Matijevic, who passed away two weeks after Curiosity's landing).

The rock was encountered by Curiosity a few weeks after it landed, during its slow drive across Gale Crater on the way toward the crater's central peak, Mount Sharp. Visual inspection of the dark gray rock suggested that it was probably a fine-grained basaltic igneous rock formed by the crystallization of magma near the planet's surface. The absence of obvious mineral grains on its essentially dust-free surface further suggested that it would have a relatively uniform (i.e., homogeneous) chemical composition.

For that reason, MSL's scientists decided it would be a good test case for comparing the results obtained by two of the rover's scientific instruments, the Alpha Particle X-ray Spectrometer (APXS) and ChemCam, both of which are used to measure the chemical compositions of rocks, sediments, and minerals.

The APXS analyses, however, produced some unanticipated results. Far from being similar in its chemical composition to the many martian igneous rocks analyzed by the Spirit and Opportunity rovers on the surface of Mars or to martian meteorites found on Earth, Jake_M is highly enriched in sodium and potassium, making it chemically alkaline.

Although Jake_M is very different from known martian rocks, Stolper and colleagues realized that it is very similar in its chemical composition to a relatively rare type of terrestrial igneous rock, known as a mugearite, which is typically found on ocean islands and in continental rift zones.

"We realized right away that although nothing like it had ever been found on Mars, Jake_M is similar in composition to terrestrial mugearites, which although uncommon are very well known to igneous petrologists who study volcanic rocks on Earth," Stolper says. "In fact, if this rock were found on Earth, we would be hard pressed, based on its elemental composition, to tell it was not an Earth rock." However, he notes, "such rocks are so uncommon on Earth that it would be highly unlikely that, if you landed a spacecraft on Earth in a random location, the first rock you encountered within a few hundred meters of your landing site would be an alkaline rock like Jake_M."

On both Earth and Mars, basaltic liquids form by partial melting of rocks deep inside the planet. By analogy with terrestrial mugearites, Jake_M probably evolved from such a partial melt that cooled as it ascended toward the surface from the martian interior; as it cooled, crystals formed, and the chemical composition of the remaining liquid changed (just as, in the making of rock candy, a sugar-water solution becomes less sweet as it cools and sugar crystallizes from it).

"The minerals that crystallize have different elemental compositions than the melt and are either more dense or less dense than the liquid and thus tend to physically separate, that is, to settle to the bottom of the magma chamber or float to the top, causing the chemical composition of the remaining liquid to change," Baker explains.

The MSL team then modeled the conditions required to produce a residual liquid similar in composition to Jake_M by crystallization of plausible partial melts. From those results, they inferred that the cooling and crystallization that eventually produced Jake_M probably occurred at pressures of several kilobars, the equivalent of the pressure at a depth of a few tens of kilometers beneath the martian surface. The modeling also suggested -- particularly by analogy with terrestrial mugearites -- that the martian magmas were relatively rich in dissolved water.

According to Stolper, Baker, and their colleagues, Jake_M probably originated via the melting of a relatively alkali- and water-rich martian mantle that was different from the sources of other known martian basalts. Because the primitive martian mantle is believed to have been as much as two times richer in sodium and potassium than Earth's mantle, the researchers say that, in hindsight, it might not be surprising if alkaline magmas, which are so uncommon on Earth, are more common on Mars.

Moreover, Stolper adds, "there are many hypotheses for origin of alkaline magmas on Earth that are similar to Jake_M. Perhaps the most plausible is that regions deep in the mantle become enriched in alkalis by a process known as metasomatism, in which the chemical compositions of rocks are altered by the flow of water- and carbon-dioxide-rich fluids. The existence of Jake_M may be evidence that such processes also occur in the interior of Mars."

Intriguingly, the potassium-rich nature of many of the sedimentary rocks that have been analyzed by the MSL mission may turn out to reflect the presence of such a region enriched in alkalis in the mantle underlying Gale Crater.

However, he says, "with only one rock having this odd chemical composition, we don't want to get carried away. Is it a one-off, or is it a representative of an important class of igneous rocks from the Gale Crater region? Determining the answer to this will be an important goal for the ongoing MSL mission."

"The paper by Stolper et al. shows that the internal composition of Mars is more similar to Earth than we had thought and illustrates how even a single rock can provide insight into the evolution of the planet as a whole," Grotzinger says.

The work in the paper, "The Petrochemistry of Jake_M: A Martian Mugearite," was supported by grants from the National Science Foundation, the National Aeronautics and Space Administration, the Canadian Space Agency, and the Centre National d'Etudes Spatiales.

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Adjust the cells of the USC scientists ID protein anticancer therapy, human trafficking and potential.

Molecular microbiologist South California University （ USC Norris Comprehensive Cancer Center home ） but could lead to treatment for cancer and other disease treatment within a cell complex control mechanisms have been found. Have significance over the years on basic understanding of cell biology, their findings appear in the journal nature cell biology.

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Scientists closer to universal flu vaccine after pandemic 'natural experiment'

Sep. 22, 2013 — Scientists have moved closer to developing a universal flu vaccine after using the 2009 pandemic as a natural experiment to study why some people seem to resist severe illness.

Researchers at Imperial College London asked volunteers to donate blood samples just as the swine flu pandemic was getting underway and report any symptoms they experienced over the next two flu seasons.

They found that those who avoided severe illness had more CD8 T cells, a type of virus-killing immune cell, in their blood at the start of the pandemic.

They believe a vaccine that stimulates the body to produce more of these cells could be effective at preventing flu viruses, including new strains that cross into humans from birds and pigs, from causing serious disease.

The findings are published in Nature Medicine.

Professor Ajit Lalvani from the National Heart and Lung Institute at Imperial College London, who led the study, said: "New strains of flu are continuously emerging, some of which are deadly, and so the Holy Grail is to create a universal vaccine that would be effective against all strains of flu."

Today's flu vaccines make the immune system produce antibodies that recognise structures on the surface of the virus to prevent infection with the most prevalent circulating strains. But they are usually one step behind as they have to be changed each year as new viruses with different surface structures evolve.

Previously, experimental models had suggested that T cells may protect against flu symptoms but until now this idea has not been tested in humans during a pandemic.

Professor Lalvani's team rapidly recruited 342 staff and students at Imperial to take part in their study in autumn 2009. The volunteers donated blood samples and were given nasal swabs. They were sent emails every three weeks asking them to fill in a survey about their health. If they experienced flu symptoms, they took a nasal swab and sent it back to the lab.

They found that those who fell more severely ill with flu had fewer CD8 T cells in their blood, and those who caught flu but had no symptoms or only mild symptoms had more of these cells.

Professor Lalvani said, "The immune system produces these CD8 T cells in response to usual seasonal flu. Unlike antibodies, they target the core of the virus, which doesn't change, even in new pandemic strains. The 2009 pandemic provided a unique natural experiment to test whether T cells could recognise, and protect us against, new strains that we haven't encountered before and to which we lack antibodies.

"Our findings suggest that by making the body produce more of this specific type of CD8 T cell, you can protect people against symptomatic illness. This provides the blueprint for developing a universal flu vaccine.

"We already know how to stimulate the immune system to make CD8 T cells by vaccination. Now that we know these T cells may protect, we can design a vaccine to prevent people getting symptoms and transmitting infection to others. This could curb seasonal flu annually and protect people against future pandemics."

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