ScienceDaily (May 26, 2012) For 5,000 years, the Chinese have used a system of medicine based on the flow and balance of positive and negative energies in the body. In this system, the appearance of the tongue is one of the measures used to classify the overall physical status of the body, or zheng. Now, University of Missouri researchers have developed computer software that combines the ancient practices and modern medicine by providing an automated system for analyzing images of the tongue.

“Knowing your zheng classification can serve as a pre-screening tool and help with preventive medicine,” said Dong Xu, chair of MU’s computer science department in the College of Engineering and study co-author. “Our software helps bridge Eastern and Western medicine, since an imbalance in zheng could serve as a warning to go see a doctor. Within a year, our ultimate goal is to create an application for smartphones that will allow anyone to take a photo of their tongue and learn the status of their zheng.”

The software analyzes images based on the tongue’s color and coating to distinguish between tongues showing signs of “hot” or “cold” zheng. Shades of red and yellow are associated with hot zheng, whereas a white coating on the tongue is a sign of cold zheng.

“Hot and cold zheng doesn’t refer directly to body temperature,” said Xu, who is also on the faculty of the Bond Life Sciences Center. “Rather, it refers to a suite of symptoms associated with the state of the body as a whole.”

For example, a person with cold zheng may feel chills and coolness in the limbs and show a pale flushing of face. Their voice may have a high pitch. Other symptoms of cold sheng are clear urine and loose stool. They also may prefer hot foods and drinks and desire warm environments.

In Chinese traditional medicine both hot and cold zheng can be symptoms of gastritis, an inflammation of the stomach lining frequently caused by bacterial infection.

For the study, 263 gastritis patients and 48 healthy volunteers had their tongues analyzed. The gastritis patients were classified by whether they showed infection by a certain bacteria, known as Helicobacter pylori, as well as the intensity of their gastritis symptoms. In addition, most of the gastritis patients had been previously classified with either hot or cold zheng. This allowed the researchers to verify the accuracy of the software’s analysis.

“Our software was able to classify people based on their zheng status,” said study co-author Ye Duan, associate professor of computer science at MU.

“As we continue to work on the software we hope to improve its ability,” Duan said. “Eventually everyone will be able to use this tool at home using webcams or smartphone applications. That will allow them to monitor their zheng and get an early warning about possible ailments.”

The study “Automated Tongue Feature Extraction for ZHENG Classification in Traditional Chinese Medicine” was accepted for publication in the journal Evidence Based Complementary and Alternative Medicine. The study’s first author was doctoral student Ratchadaporn Kanawong and the second author was post-doctoral researcher Tayo Obafemi-Ajayi.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by University of Missouri-Columbia.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 26, 2012) Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter serious pushback from primary care physicians, according to results of a survey by Johns Hopkins investigators.

In a survey of 125 primary care doctors, the researchers found that while doctors agreed with older recommendations to curtail routine screening in men over age 75 and among those not expected to live 10 or more years, a large number said they faced significant barriers to stopping PSA testing in men who had been receiving it regularly. The most frequently cited reason by 74.4 percent of physicians was, “My patients expect me to continue getting yearly PSA tests,” followed by 66 percent of them who said, “It takes more time to explain why I’m not screening than to just continue screening.” More than half of those surveyed in the new study believed that, “By not ordering a PSA, it puts me at risk for malpractice.”

The survey was conducted in November 2011, right after draft recommendations were made to end routine screening of all men, but before last week, when the draft recommendations were officially approved.

“It can be very difficult for doctors to break down the belief that all cancer screening tests are invariably good for all people all the time,” says Craig E. Pollack, M.D., M.H.S., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine, and leader of the study published online in the journal Cancer. “Everyone agrees that PSA screening isn’t as good as we want it to be. If we had a test that was a slam dunk, it would be different. But now we know that for many men, the benefits may be small and the harms significant.”

Each year, more than 33,000 American men die of prostate cancer, and 20 million get the PSA test to detect the disease early.

According to the USPSTF, evidence suggests the potential harms caused by PSA screening of healthy men as a means of identifying prostate cancer outweigh its potential to save lives and that routine annual screening should be eliminated in the healthy. Elevated PSA readings are not necessarily evidence of prostate cancer, and can lead to unnecessary prostate biopsy. In addition, even when biopsies reveal signs of prostate cancer cells, evidence shows that a large proportion will never cause harm, even if left untreated. The disease in older men often progresses slowly so that those who have it frequently die of other causes.

Treatments for prostate cancer can include the removal of the prostate, radiation or other therapies, each of which has the potential to cause serious problems like erectile dysfunction, complete impotence, urinary incontinence or bowel damage. And men who choose to “watch and wait” after elevated PSA readings must live with the anxiety of knowing they have an untreated cancer that could start to progress.

In the new study, Pollack and his colleagues found that while most physicians said they took age and life expectancy into account when deciding to order PSA screening, many also said they had a hard time estimating life expectancy in their patients and could use a better tool. H. Ballentine Carter, M.D., a professor of urology at Johns Hopkins and the senior investigator on the study, is planning to investigate the potential of individualized prostate cancer screening recommendations. Specifically, he and colleagues plan to create a decision-making tool that incorporates age, life expectancy, family history and prior PSA results in order to help doctors and their patients make better choices for prostate cancer screening.

In another report derived from results of Pollack’s and Carter’s survey, published in April in the Archives of Internal Medicine, the researchers say nearly half of the providers agreed with the new USPSTF recommendations to eliminate routine screening for healthy men. Still, less than two percent said they would no longer order routine PSA screening in response to the draft recommendations; 21.9 percent said they would be much less likely to do so; 38.6 percent said they would be somewhat less likely to do so; and 37.7 percent said they would not change their screening practices.

“Men often expect PSA screening to be part of their annual physical,” Pollack says. “To change their minds, we need to address their perceptions about screening, allow time for screening discussions and reduce concerns regarding malpractice litigation.”

The studies were supported in part by a Maryland Cigarette Restitution Fund Research Grant to Johns Hopkins.

Other Johns Hopkins researchers involved with the studies included Elizabeth A. Platz, Sc.D., M.P.H.; Nrupen A. Bhavsar, Ph.D., M.P.H.; Gary Noronha, M.D.; Gene E. Green, M.D.; and Sean Chen, B.A.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Johns Hopkins Medical Institutions.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

26 May 2012
Last updated at 11:56 ET

A Cornish MP says an inspection into the county’s out-of-hours medical service is a result of mounting pressure from patients and MPs.

Andrew George, Liberal Democrat MP for St Ives, said he had heard allegations of response times being amended and doctor numbers being stretched.

The Care Quality Commission (CQC) said an inspection took place in April.

The company behind the service, Serco, said it was performing well and the allegations about it were false.

Mr George said he had also heard claims Serco was using non-clinical staff to answer calls.

He added: “I have heard cases involving young infants and very old patients…

“Many of the relatives have come to me with concerns about the service.”

The company provides an out-of-hour GPs service for people living in Cornwall and has a team of more than 180 doctors, 50 other clinicians and about 140 support staff.

The Guardian newspaper has reported that the unannounced inspection was in response to whistleblowers who claimed Serco allowed queues of up to 90 patients at a time ¹ to build up at its telephone helpline and adjusted figures to blame delays on patients in order to meet targets.

Whistleblowers also reportedly claimed the service repeatedly took visiting doctors off duties to operate clinics and hotlines because there were too few staff on duty.

‘False allegations’

The CQC said the inspection was in response to information brought to its attention.

It said it would not disclose details until the report had been published in the next few weeks.

The Cornwall and Isles of Scilly Primary Care Trust said it had not been informed of any concerns which would have had a serious or urgent impact on patients’ safety.

Bridget Sampson, director of the trust, said: “We are confident the service is adequately resourced and meeting the required national quality standards.

“The contract provides a value-for-money, high quality service for patients, with equitable access to GP appointments out-of-hours.”

A Serco spokesman said the service had previously been found to be one of the best performing in the UK by The Primary Care Foundation.

It added it was fully committed to provide the best possible care for patients.

The spokesman added: “Since the out-of-hours service started, Serco has not scored less than 95% in the monthly patient satisfaction survey and over 86% of patients rate the service either excellent or good.

“A substantial number of the allegations considered have been raised before, fully investigated by a number of independent bodies and found to be false and without foundation.”

References

1. ^{^} Serco allowed queues of up to 90 patients at a time (www.guardian.co.uk)
2. ^{^} (www.bbc.co.uk)

26 May 2012
Last updated at 11:56 ET

A Cornish MP says an inspection into the county’s out-of-hours medical service is a result of mounting pressure from patients and MPs.

Andrew George, Liberal Democrat MP for St Ives, said he had heard allegations of response times being amended and doctor numbers being stretched.

The Care Quality Commission (CQC) said an inspection took place in April.

The company behind the service, Serco, said it was performing well and the allegations about it were false.

Mr George said he had also heard claims Serco was using non-clinical staff to answer calls.

He added: “I have heard cases involving young infants and very old patients…

“Many of the relatives have come to me with concerns about the service.”

The company provides an out-of-hour GPs service for people living in Cornwall and has a team of more than 180 doctors, 50 other clinicians and about 140 support staff.

The Guardian newspaper has reported that the unannounced inspection was in response to whistleblowers who claimed Serco allowed queues of up to 90 patients at a time ¹ to build up at its telephone helpline and adjusted figures to blame delays on patients in order to meet targets.

Whistleblowers also reportedly claimed the service repeatedly took visiting doctors off duties to operate clinics and hotlines because there were too few staff on duty.

‘False allegations’

The CQC said the inspection was in response to information brought to its attention.

It said it would not disclose details until the report had been published in the next few weeks.

The Cornwall and Isles of Scilly Primary Care Trust said it had not been informed of any concerns which would have had a serious or urgent impact on patients’ safety.

Bridget Sampson, director of the trust, said: “We are confident the service is adequately resourced and meeting the required national quality standards.

“The contract provides a value-for-money, high quality service for patients, with equitable access to GP appointments out-of-hours.”

A Serco spokesman said the service had previously been found to be one of the best performing in the UK by The Primary Care Foundation.

It added it was fully committed to provide the best possible care for patients.

The spokesman added: “Since the out-of-hours service started, Serco has not scored less than 95% in the monthly patient satisfaction survey and over 86% of patients rate the service either excellent or good.

“A substantial number of the allegations considered have been raised before, fully investigated by a number of independent bodies and found to be false and without foundation.”

References

1. ^{^} Serco allowed queues of up to 90 patients at a time (www.guardian.co.uk)
2. ^{^} (www.bbc.co.uk)

ScienceDaily (May 24, 2012) A new type of male contraceptive could be created thanks to the discovery of a key gene essential for sperm development.

The finding could lead to alternatives to the conventional male contraceptives that rely on disrupting the production of hormones, such as testosterone. These treatments can cause side-effects such as irritability, mood swings and acne.

Research, led by the University of Edinburgh, has shown how a gene — Katnal1 — is critical to enable sperm to mature in the testes.

If scientists can regulate the Katnal1 gene in the testes, they could prevent sperm from maturing completely, making them ineffective without changing hormone levels.

The research, which is published in the journal PLoS Genetics, could also help in finding treatments for cases of male infertility when malfunction of the Katnal1 gene hampers sperm development.

Dr Lee Smith, Reader in Genetic Endocrinology at the University of Edinburgh’s Centre for Reproductive Health, said: “If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive.

“The important thing is that the effects of such a drug would be reversible because Katnal1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm.

“Although other research is being carried out into non-hormonal male contraceptives, identification of a gene that controls sperm production in the way Katnal1 does is a unique and significant step forward in our understanding of testis biology.”

Scientists found that male mice that were modified so they did not have the Katnal1 gene were infertile.

Further investigation showed that this was because the gene was needed to allow the sperm to develop and mature.

The researchers showed that Katnal1 was needed to regulate the scaffolding structures known as microtubules, which form part of the cells that support and provide nutrients to developing sperm.

Breaking down and rebuilding these microtubules enables the sperm cells to move within the testes as they mature. Katnal1 acts as the essential controller of this process.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Lee B. Smith, Laura Milne, Nancy Nelson, Sharon Eddie, Pamela Brown, Nina Atanassova, Moira K. O’Bryan, Liza O’Donnell, Danielle Rhodes, Sara Wells, Diane Napper, Patrick Nolan, Zuzanna Lalanne, Michael Cheeseman, Josephine Peters. KATNAL1 Regulation of Sertoli Cell Microtubule Dynamics Is Essential for Spermiogenesis and Male Fertility. PLoS Genetics, 2012; 8 (5): e1002697 DOI: 10.1371/journal.pgen.1002697

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 25, 2012) An overgrowth of bacteria in the gut has been definitively linked to Irritable Bowel Syndrome in the results of a new Cedars-Sinai study which used cultures from the small intestine. This is the first study to use this “gold standard” method of connecting bacteria to the cause of the disease that affects an estimated 30 million people in the United States.

Previous studies have indicated that bacteria play a role in the disease, including breath tests detecting methane — a byproduct of bacterial fermentation in the gut. This study was the first to make the link using bacterial cultures.

The study, in the current issue of Digestive Diseases and Sciences, examined samples of patients’ small bowel cultures to confirm the presence of small intestinal bacterial overgrowth — or SIBO — in more than 320 subjects. In patients with IBS, more than a third also were diagnosed with small intestine bacterial overgrowth, compared to fewer than 10 percent of those without the disorder. Of those with diarrhea-predominant IBS, 60 percent also had bacterial overgrowth.

“While we found compelling evidence in the past that bacterial overgrowth is a contributing cause of IBS, making this link through bacterial cultures is the gold standard of diagnosis,” said Mark Pimentel, MD, director of the Cedars-Sinai GI Motility Program and an author of the study. “This clear evidence of the role bacteria play in the disease underscores our clinical trial findings, which show that antibiotics are a successful treatment for IBS.”

IBS is the most common gastrointestinal disorder in the U.S., affecting an estimated 30 million people. Patients with this condition suffer symptoms that can include painful bloating, constipation, diarrhea or an alternating pattern of both. Many patients try to avoid social interactions because they are embarrassed by their symptoms. Pimentel has led clinical trials that have shown rifaximin, a targeted antibiotic absorbed only in the gut, is an effective treatment for patients with IBS.

“In the past, treatments for IBS have always focused on trying to alleviate the symptoms,” said Pimentel, who first bucked standard medical thought more than a decade ago when he suggested bacteria played a significant role in the disease. “Patients who take rifaximin experience relief of their symptoms even after they stop taking the medication. This new study confirms what our findings with the antibiotic and our previous studies always led us to believe: Bacteria are key contributors to the cause of IBS.”

The study is a collaboration with researchers at Sismanogleion General Hospital in Athens, Greece, and at the University of Athens.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Cedars-Sinai Medical Center, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Gene Kim, Fnu Deepinder, Walter Morales, Laura Hwang, Stacy Weitsman, Christopher Chang, Robert Gunsalus, Mark Pimentel. Methanobrevibacter smithii Is the Predominant Methanogen in Patients with Constipation-Predominant IBS and Methane on Breath. Digestive Diseases and Sciences, 2012; DOI: 10.1007/s10620-012-2197-1

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 25, 2012) Millions of Europeans undergo abdominal surgery each year to treat a range of different disorders, from cancer and heart disease to obesity. EU-funded researchers are developing innovative micro-robotics and micro-system technologies to make such surgeries less complicated, invasive and costly.

Surgical procedures have improved rapidly in recent years aided by technology that is gradually making the surgeon’s scalpel a thing of the past — increasingly replaced by robotics, miniature devices and innovative procedures that have fewer health risks, speed patient recovery and leave less scarring. But there is always room for further improvement.

‘There are issues with abdominal surgery at present, both with the technology and the procedure,’ says Professor Arianna Menciassi of the BioRobotics Institute at Scuola Superiore Sant’Anna in Italy.

At present, abdominal surgery is either performed by a surgeon manually, using a key-hole technique also known as laparoscopy, or with the aid of a teleoperated robotic device. The most widely used surgical robot for the procedure is highly precise — more so than manual surgery — but it is also bulky, expensive and still requires several incisions to be made in the abdomen.

This current system makes the surgery easier for the surgeon, ‘but it is just as invasive as the traditional laparoscopic procedure for the patient, requiring a minimum of four incisions in the abdomen: two for the robotic tools, one for further manoeuvres and one for a camera,’ Prof Menciassi explains. ‘We set out to develop an alternative system using state-of-the-art micro-robotics and micro-system technologies that would be less expensive and less invasive.’

Working in the ‘Array of robots augmenting the kinematics of endoluminal surgery’ (Araknes) project, Prof Menciassi and a team of researchers from across Europe focused on an approach to abdominal surgery that integrates the advantages of traditional open surgery, ‘Minimally invasive surgery’ (MIS) — also known as laparoscopic or key-hole surgery — and robotic surgery. Supported by EUR 8.1 million in funding from the European Commission, the Araknes team developed highly innovative devices and technologies that greatly reduce the invasiveness of surgical procedures, minimise scarring, decrease the risk of infection and speed patient recovery time at potentially much lower cost than existing commercial systems.

One of the results of Araknes is a teleoperated robotic system called the ‘Single-port laparoscopy bimanual robot’ (Sprint) that, like the DaVinci system, replicates with high precision the hand movements of a surgeon sitting at a console interface. However, the system is specifically designed for ‘Single-port laparoscopy’ (SPL) — a relatively new type of key-hole surgery in which the surgeon operates through a single incision, usually in the patient’s navel.

‘Instead of four incisions, this technique uses only one incision — the access port — of around three centimetres in diameter. And because the incision is made through the navel — a natural scar — there is no visible scarring,’ Prof Menciassi, the Araknes scientific manager, explains.

Sprint is composed of two arms with six degrees of freedom of movement with rotating grippers at the end, providing a very high degree of dexterity for performing a wide variety of surgical tasks inside the patient’s body.

‘The arms function much like our own and, through the teleoperated interface, replicate precisely the movements of the surgeon who views the procedure via a 3D high-definition camera,’ Prof Menciassi says.

Crucially, thanks to state-of-the-art micro-robotics technology, the motors that control the grippers and the ‘elbows’ of each arm are located on the device, while the motors for the ‘shoulders’ are external.

‘This is a key difference with existing commercial systems, as it means the entire system is much less bulky. It fits much more easily into the operating room and allows better access to the patient,’ the project manager explains.

The reduced size of the system was one of several highly regarded features by surgeons who conducted in-vivo tests on a pig at a lab run by project partner Novineon in Germany in January.

‘Surgeons accustomed to using DaVinci welcomed the small size and increased visibility of the patient as well as the reduced invasiveness, while surgeons who normally perform the single-port procedure manually saw an immediate advantage in terms of precision,’ Prof Menciassi says.

Another device developed by the Araknes team is designed to eliminate the need for incisions entirely. Developed for ‘Natural orifice translumenal endoscopic surgery’ (Notes), the device consists of a magnetic platform coupled with miniature robotic arms that can be inserted into the patient through a natural orifice such as the mouth or anus with no other incision necessary.

Notes itself is still considered an experimental surgical technique, but one that potentially has many advantages for the patient over invasive methods.

‘The Notes platform is experimental, and unlikely to be used in surgery for some time for both technical and clinical reasons. Nonetheless, it consists of many innovative enabling technologies that could find more immediate applications,’ the project manager says.

On the other hand, the Sprint robotic system is much closer to market in light of the success of the in-vivo trials carried out by the project partners. The Sprint technology is currently being patented and the partners are looking to use it as the basis for a commercial system.

‘We are currently seeking funding from both public and private sources for further development,’ Prof. Menciassi explains. ‘It’s still a prototype, but we are confident that if produced commercially it would be less expensive than existing systems. Plus the faster recovery time using the SPL technique should reduce hospitalisation time for the patient, lowering healthcare costs.’

The Araknes team initially focused their work on developing systems for weight-loss surgery, a procedure to reduce the size of the stomach, or bypass it entirely, that is undergone by tens of thousands of Europeans each year. However, Prof Menciassi emphasizes that the devices could be used for any type of abdominal surgery, for example, to remove cancerous tumours or treat problems with the heart, liver or kidneys.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by CORDIS Features, formerly ICT Results, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 25, 2012) Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven’t known how a deletion in one gene from one parent, called a “hemizygous” deletion, can contribute to cancer.

A research team led by Stephen Elledge, a professor in the Department of Genetics at Harvard Medical School, and his post-doctoral fellow Nicole Solimini, has now provided an answer. The most common hemizygous deletions in cancer, their research shows, involve a variety of tumor suppressing genes called STOP genes (suppressors of tumorigenesis and proliferation) that scatter randomly throughout the genome, but that sometimes cluster in the same place on a chromosome. And these clusters, said Elledge, who is also a professor of medicine at Brigham and Women’s Hospital, tend to be deleted as a group. “Eliminating the cluster gives a bigger bang for the deletion buck,” he said.

This finding is especially interesting in light of the two-hit model of cancer formation, which holds that both copies of a recessive gene need to be inactivated to trigger a biological effect. Thus the loss of a single tumor suppressor copy should have little or no influence on tumor cell proliferation because the remaining copy located on the other chromosome is there to pick up the slack.

Elledge’s research points to a different hypothesis, namely that STOP genes in a hemizygous deletion aren’t recessive but are instead haploinsufficient, meaning that they depend on two copies to function normally. “If a tumor suppressor is haploinsufficient, then a single gene copy lacks the potency needed to fully restrain tumorigenesis,” Elledge explained, who is also a Howard Hughes Medical Institute Investigator. “So by removing clusters of haploinsufficient genes all at once, the cancer cell immediately propels its growth forward without having to wait for the other copies to also be lost.”

Angelika Amon, a professor of biology at the Massachusetts of Technology, said she’s surprised by the findings. “We’ve known from a lot of human syndromes that haploinsufficiency is widespread in the development of complex multicellular organisms,” she said. “But these data show it’s also critical for individual cells and cell proliferation.”

The results also offer a different take on the two-hit model in carcinogenesis, Amon said. Being remarkably unstable, cancer cells can delete gene copies at every turn of the corner. If the loss of a single tumor suppressor copy provides no survival advantage for the tumor, then the tumor has no incentive to retain the cell with that deletion. But if the loss of that copy boosts proliferation, then the probability of a second hit later is greatly increased. “So haploinsufficiency is a way for the cancer cell to dramatically accelerate the acquisition of growth beneficial mutations,” Amon said.

In other words, all it takes is a 50 percent reduction in gene activity for a cancer cell to grow. “That tells us it’s a lot easier to get cancer than we might have hoped,” Amon said.

According to Elledge, the number of hemizygotic deletions averages roughly six per tumor, with some tumors — breast and pancreatic, for instance — averaging up to ten. Each deletion involves 25 to 40 genes, many of them STOP genes, but also a few GO genes (growth enhancers and oncogenes) that enhance proliferation. That the STOP genes substantially outnumber their GO counterparts is important, Elledge explained, because it means cancer cells can tilt scales toward proliferation without also compromising it at the same time.

“The data reveal a lot of haploinsufficient players that have small effects individually, but large effects in combination,” Elledge said. “Unfortunately, it’s not easy to see how to take advantage of that chemotherapeutically.”

What’s important about the results, he emphasized, is that they open up new views on how tumors evolve. Moreso, they underscore the importance of proliferation as a fundamental feature of tumor growth, he added.

The challenge now, Elledge said, will be to find out which of the genes in a recurring deletion are haploinsufficient. “At the moment, we estimate roughly 25 percent,” he said. “So these findings could also have important ramifications for other human diseases in addition to cancer.”

This work was supported by grants from the NCI/NHGRI funded Cancer Genome Atlas (TCGA) project, from the NIH (U54CA143798) to R.B. and by grants from the NIH, SU2C, and DOD.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Harvard Medical School.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. N. L. Solimini, Q. Xu, C. H. Mermel, A. C. Liang, M. R. Schlabach, J. Luo, A. E. Burrows, A. N. Anselmo, A. L. Bredemeyer, M. Z. Li, R. Beroukhim, M. Meyerson, S. J. Elledge. Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential. Science, 2012; DOI: 10.1126/science.1219580

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 25, 2012) UC Davis mathematicians have helped biologists figure out why platelets, the cells that form blood clots, are the size and shape that they are. Because platelets are important both for healing wounds and in strokes and other conditions, a better understanding of how they form and behave could have wide implications.

“Platelet size has to be very specific for blood clotting,” said Alex Mogilner, professor of mathematics, and neurobiology, physiology and behavior at UC Davis and a co-author of the paper, published this week in the journal Nature Communications. “It’s a longstanding puzzle in platelet formation, and this is the first quantitative solution.”

Mogilner and UC Davis postdoctoral scholars Jie Zhu and Kun-Chun Lee developed a mathematical model of the forces inside the cells that turn into platelets, accurately predicting their final size and shape.

They were collaborating with a team led by Joseph Italiano and Jonathon Thon at Harvard Medical School and Brigham and Women’s Hospital, Boston.

Platelets are made by bone marrow cells called megakaryocytes. They bud off first as large, circular pre-platelets, form into a dumbbell-shaped pro-platelet, then finally divide into a standard-sized, disc-shaped platelet. A typical person has about a trillion platelets in circulation at a time, and makes about 100 billion new platelets a day, each living for 8 to 10 days.

Inside the pre- and pro-platelets is a ring of protein microtubules, which exerts pressure to straighten and broaden the nascent cells. But overlying the ring is a rigid cortex of proteins that prevents the platelets from expanding.

By tweaking the number of microtubules in the bundles, Mogilner, Zhu and Lee found that they could correctly predict how pro-platelets would flip into a dumbbell shape, as well as the size and shape of mature platelets.

The work grew out of a long-standing collaboration between Mogilner and the Harvard team — the kind of cross-disciplinary research that makes UC Davis a center for innovation. It was supported by the National Institutes of Health and the National Science Foundation.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by University of California – Davis.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Jonathan N Thon, Hannah Macleod, Antonija Jurak Begonja, Jie Zhu, Kun-Chun Lee, Alex Mogilner, John H. Hartwig, Joseph E. Italiano. Microtubule and cortical forces determine platelet size during vascular platelet production. Nature Communications, 2012; 3: 852 DOI: 10.1038/ncomms1838

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

ScienceDaily (May 25, 2012) In a study published in the journal Cell on May 24, Cold Spring Harbor Laboratory (CSHL) scientists describe the three-dimensional atomic structure of a human protein bound to a piece of RNA that “guides” the protein’s ability to silence genes. The protein, Argonaute-2, is a key player in RNA interference (RNAi), a powerful cellular phenomenon that has important roles in diverse biological processes, including an organism’s development.

“Detailed knowledge of the structure of human Argonaute-2 and the way it interacts with its RNA guides will greatly improve our understanding of its biological mechanism of action,” says CSHL Professor and HHMI Investigator Leemor Joshua-Tor, Ph.D., the study’s leader. “Such precise structural information of the human Argonaute bound to an important RNA guide could potentially aid both basic research to understand the function of genes and also advance the development of RNAi as a therapeutic strategy in clinical settings.”

Upon the activation of a gene within a cell, the gene’s DNA is copied into a messenger RNA (mRNA) “transcript.” The instructions encoded within this transcript are then used as a blueprint by the cell’s protein synthesis machinery to generate a working protein. The gene is “silenced” or prevented from giving rise to the protein, however, when an Argonaute-2 protein that is bound to a small piece of “guide” RNA — either a short-interfering RNA or a microRNA — intercepts the mRNA molecule. The guide RNA, whose nucleotide sequence matches that of the target mRNA, acts as a homing device that helps the Argonaute-2 protein zero in on the mRNA target.

A few years ago, Joshua-Tor collaborated with CSHL Professor and HHMI Investigator Gregory Hannon, Ph.D., who is also a co-author in this study, to show that Argonaute proteins, which are made up of different domains or parts, act like a pair of molecular scissors that slice up target mRNAs, thus preventing proteins from being made and enforcing the silencing of their genes. The discovery of the Argonautes’ “slicer” activity stemmed in part from solving the crystal structure of an Argonaute protein from Pyrococcus furiosus, an archebacterium that thrives in extremely high temperatures.

“But we still know nothing about the biological functions or mechanisms of action of archebacterial Argonautes,” says Joshua-Tor. “We therefore next focused on solving the structures of Argonautes from higher organisms such as mammals, in which Argonaute functions and target recognition are well documented.”

Joshua-Tor’s team and other research groups subsequently determined the atomic structures of individual parts of Argonaute proteins from higher organisms. While these studies revealed several important details — for example, the interaction between two parts of the Argonaute protein, called the PAZ and Mid domains, with the two ends of guide RNAs — Joshua-Tor’s goal was to solve the structure of the entire human Argonaute protein in complex with a single human guide RNA.

Overcoming a complicated series of technical challenges, her team has achieved this goal by analyzing the structure of a full-length human Argonaute-2 protein bound to a small RNA called miR-20a, which is known to play a role in cancer development. Although Argonautes from higher organisms diverged from their archebacterial cousins more than three billion years ago, the team’s analysis shows remarkable similarity between the two structures, especially in the regions that are important for target recognition and slicing activity.

“Our structure shows that the guide RNA, which is anchored at both ends by the PAZ and Mid domains, kinks and twists its way through the structure of the entire protein, making several points of contact within each domain and with the linker loops that join them,” explains Joshua-Tor. “The guide RNA thus acts like a backbone that rigidly locks together the otherwise flexible Argonaute protein and gives it stability.”

The researchers speculate that the path threaded through the Argonaute by the guide RNAs could have evolved to maximize mutual stability, in turn making the protein-RNA complexes long-lived. This long life is critical for many biological processes that are mediated by Argonautes. “This is also the kind of information that might help us to design better synthetic guide RNAs for therapeutic use,” explains Joshua-Tor. “It will also be useful to researchers who are trying to find more precise ways of blocking Argonaute activity.”

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Cold Spring Harbor Laboratory.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Elad Elkayam, Claus-D. Kuhn, Ante Tocilj, Astrid D. Haase, Emily M. Greene, Gregory J. Hannon, and Leemor Joshua-Tor. The structure of human Argonaute-2 in complex with miR-20a. Cell, May 24, 2012 DOI: 10.1016/j.cell.2012.05.017

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.