Estimular o cérebro com eletricidade acelera aprendizado

Choque de aprendizado

Aplicar uma pequena corrente elétrica em partes específicas do cérebro parece aumentar sua atividade.

Segundo a Dra. Heidi Johansen-Berg, da Universidade de Oxford, no Reino Unido, essa estimulação elétrica pode otimizar o processo de aprendizado.

Os cientistas estudaram o cérebro de pacientes que sofreram derrame e que estavam reaprendendo a executar movimentos com os braços e as pernas.

As imagens de ressonância magnética foram então comparadas com imagens do cérebro de pessoas saudáveis.

Áreas do cérebro

A principal conclusão do estudo confirma a elevada plasticidade do cérebro, que se reestrutura, criando novas conexões e transferindo funções das partes danificadas para partes saudáveis.

Esta é mais uma pesquisa que questiona o paradigma atualmente aceito de que o cérebro é dividido em zonas funcionais. Em vez disso, o cérebro parece atribuir as tarefas conforme a necessidade e as contingências.

• Descobertas revolucionam conhecimento do cérebro

A seguir, eles queriam saber se é possível estimular eletricamente o cérebro das pessoas que sofreram derrame - de forma não invasiva - para que ele reaprenda as aptidões motoras mais rapidamente.

Deu certo.

Velocidade de aprendizado

Mas o melhor estava por vir.

Os cientistas perceberam que a velocidade de aprendizado dos adultos saudáveis que serviam como parâmetro para a pesquisa também aumentou quando eles receberam a estimulação elétrica.

No experimento, os voluntários tinham que memorizar uma sequência de botões.

A seguir, o experimento foi repetido colocando nos voluntários um aparelho de estimulação transcraniana, que possui dois eletrodos para aplicar uma corrente de 1 miliampere em uma posição específica da cabeça.

Os resultados mostraram que a atividade dessa parte do cérebro aumenta ou diminui dependendo da direção da corrente elétrica - a direção é alterado invertendo-se os pólos negativo e positivo entre os dois eletrodos.

O efeito foi obtido após 10 minutos de aplicação da corrente.

Agora os cientistas querem avaliar se o mecanismo também funciona para "aprendizados educacionais".

First Fluorescence-Guided Ovarian Cancer Surgery

ScienceDaily (Sep. 19, 2011) — The first fluorescence-guided surgery on an ovarian cancer patient was performed using a cancer cell "homing device" and imaging agent created by a Purdue University researcher.

The surgery was one of 10 performed as part of the first phase of a clinical trial to evaluate a new technology to aid surgeons in the removal of malignant tissue from ovarian cancer patients. The method illuminates cancer cells to help surgeons identify and remove smaller tumors that could otherwise be missed.

Philip Low, the Ralph C. Corely Distinguished Professor of Chemistry who invented the technology, said surgeons were able to see clusters of cancer cells as small as one-tenth of a millimeter, as opposed to the earlier average minimal cluster size of 3 millimeters in diameter based on current methods of visual and tactile detection.

"Ovarian cancer is notoriously difficult to see, and this technique allowed surgeons to spot a tumor 30 times smaller than the smallest they could detect using standard techniques," Low said. "By dramatically improving the detection of the cancer -- by literally lighting it up -- cancer removal is dramatically improved."

The technique attaches a fluorescent imaging agent to a modified form of the vitamin folic acid, which acts as a "homing device" to seek out and attach to ovarian cancer cells. Patients are injected with the combination two hours prior to surgery and a special camera system, called a multispectral fluorescence camera, then illuminates the cancer cells and displays their location on a flat-screen monitor next to the patient during surgery.

The surgeons involved in this study reported finding an average of 34 tumor deposits using this technique, compared with an average of seven tumor deposits using visual and tactile observations alone. A paper detailing the study was published online in Nature Medicine.

Gooitzen van Dam, a professor and surgeon at the University of Groningen in The Netherlands where the surgeries took place, said the imaging system fits in well with current surgical practice.

"This system is very easy to use and fits seamlessly in the way surgeons do open and laparoscopic surgery, which is the direction most surgeries are headed in the future," said van Dam, who is a surgeon in the division of surgical oncology and Bio-Optical Imaging Center at the University of Groningen. "I think this technology will revolutionize surgical vision. I foresee it becoming a new standard in cancer surgery in a very short time."

Research has shown that the less cancerous tissue that remains, the easier it is for chemotherapy or immunotherapy to work, Low said.

"With ovarian cancer it is clear that the more cancer you can remove, the better the prognosis for the patient," he said. "This is why we chose to begin with ovarian cancer. It seemed like the best place to start to make a difference in people's lives."

By focusing on removal of malignant tissue as opposed to evaluating patient outcome, Low dramatically reduced the amount of time the clinical trial would take to complete.

"What we are really after is a better outcome for patients, but if we had instead designed the clinical trial to evaluate the impact of fluorescence-guided surgery on life expectancy, we would have had to follow patients for years and years," he said. "By instead evaluating if we can identify and remove more malignant tissue with the aid of fluorescence imaging, we are able to quantify the impact of this novel approach within two hours after surgery. We hope this will allow the technology to be approved for general use in a much shorter time."

Low and his team are now making arrangements to work with the Mayo Clinic for the next phase of clinical trials.

The technology is based on Low's discovery that folic acid, or folate, can be used like a Trojan horse to sneak an imaging agent or drug into a cancer cell. Most ovarian cancer cells require large amounts of the vitamin to grow and divide, and special receptors on the cell's surface grab the vitamin -- and whatever is linked to it -- and pull it inside. Not all cancer cells express the folate receptor, and a simple test is necessary to determine if a specific patient's cancer expresses the receptor in large enough quantities for the technique to work, he said.

Ovarian cancer has one of the highest rates of folate receptor expression at about 85 percent. Approximately 80 percent of endometrial, lung and kidney cancers, and 50 percent of breast and colon cancers also express the receptor, he said.

Low also is investigating targeting molecules that could be used to carry attached imaging agents or drugs to forms of cancer that do not have folate receptors.

He next plans to develop a red fluorescent imaging agent that can be seen through the skin and deep into the body. The current agent uses a green dye that had already been through the approval process to be used in patients, but cannot easily be seen when present deep in tissue. Green light uses a relatively short wavelength that limits its ability to pass through the body, whereas the longer wavelengths of a red fluorescent dye can easily be seen through tissue.

"We want to be able to see deeper into the tissue, beyond the surface," Low said. "Different cancers have tumors with different characteristics, and some branch and wind their way deeper into tissue. We will continue to evolve this technology and make improvements that help cancer patients."

In addition to Low and van Dam, the paper's authors include George Themelis, Athanasios Sarantopoulos and Vasilis Ntziachristos of the Institute for Biological and Medical Imaging at the Technical University of Munich in Germany; Lucia Crane, Niels Harlaar, Rick Pleijhuis, Wendy Kelder and Johannes de Jong of the division of surgical oncology of the BioOptical Imaging Center at the University of Groningen; Henriette Arts and Ate van der Zee of the division of gynaecological oncology at the University of Groningen; and Joost Bart of the Department of Pathology and Molecular Biology of the University Medical Center of Groningen.

Low is the chief science officer for Endocyte Inc., a Purdue Research Park-based company that develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte holds the license to the folate receptor-targeting technology and is spinning this technology off into a new company called OnTarget.

Ntziachristos led the team at the Technical University of Munich that developed the camera system. A startup company named SurgOptix BV is working to commercialize the camera system.

The clinical trial was funded by Endocyte Inc. and the University Medical Center of Groningen.

Gamers Succeed Where Scientists Fail: Molecular Structure of Retrovirus Enzyme Solved, Doors Open to New AIDS Drug Design

ScienceDaily (Sep. 19, 2011) — Gamers have solved the structure of a retrovirus enzyme whose configuration had stumped scientists for more than a decade. The gamers achieved their discovery by playing Foldit, an online game that allows players to collaborate and compete in predicting the structure of protein molecules.

The "unsolved monkey virus protein" Foldit puzzle, highlighting the tool used by online gamers. 

After scientists repeatedly failed to piece together the structure of a protein-cutting enzyme from an AIDS-like virus, they called in the Foldit players. The scientists challenged the gamers to produce an accurate model of the enzyme. They did it in only three weeks.

This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates. Intensive research is under way to try to find anti-AIDS drugs that can block these enzymes, but efforts were hampered by not knowing exactly what the retroviral protease molecule looks like.

"We wanted to see if human intuition could succeed where automated methods had failed," said Dr. Firas Khatib of the University of Washington Department of Biochemistry. Khatib is a researcher in the protein structure lab of Dr. David Baker, professor of biochemistry.

Remarkably, the gamers generated models good enough for the researchers to refine and, within a few days, determine the enzyme's structure. Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme.

"These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs," wrote the authors of a paper appearing Sept. 18 in Nature Structural & Molecular Biology. The scientists and gamers are listed as co-authors.

This is the first instance that the researchers are aware of in which gamers solved a longstanding scientific problem.

Fold-it was created by computer scientists at the University of Washington Center for Game Science in collaboration with the Baker lab.

"The focus of the UW Center for Game Sciences," said director Dr. Zoran Popovic, associate professor of computer science and engineering, "is to solve hard problems in science and education that currently cannot be solved by either people or computers alone."

The solution of the virus enzyme structure, the researchers said, "indicates the power of online computer games to channel human intuition and three-dimensional pattern matching skills to solve challenging scientific problems."

With names like Foldit Contenders Group and Foldit Void Crushers Group, the gamer teams were fired up for the task of real-world molecule modeling problems. The online protein folding game captivates thousands of avid players worldwide and engages the general public in scientific discovery.

Players come from all walks of life. The game taps into their 3-D spatial abilities to rotate chains of amino acids in cyberspace. New players start at the basic level, "One Small Clash," proceed to "Swing it Around" and step ahead until reaching "Rubber Band Reversal."

Direct manipulation tools, as well as assistance from a computer program called Rosetta, encourage participants to configure graphics into a workable protein model. Teams send in their answers, and UW researchers constantly improve the design of the game and its puzzles by analyzing the players' problem-solving strategies.

Figuring out the shape and misshape of proteins contributes to research on causes of and cures for cancer, Alzheimer's, immune deficiencies and a host of other disorders, as well as to environmental work on biofuels.

Referring to this week's report of the online gamers' molecule solution opening new avenues for anti-viral drug research, Carter Kimsey, program director, National Science Foundation Division of Biological Infrastructure, observed, "After this discovery, young people might not mind doing their science homework. This is an innovative approach to getting humans and computer models to 'learn from each other' in real-time."

The researchers noted that much attention has been given to the possibilities of crowd-sourcing and game playing in scientific discovery. Their results indicate the potential for integrating online video games into real-world science.

Dr. Seth Cooper, of the UW Department of Computing Science and Engineering, is a co-creator of Foldit and its lead designer and developer. He studies human-computer exploration methods and the co-evolution of games and players.

"People have spatial reasoning skills, something computers are not yet good at," Cooper said. "Games provide a framework for bringing together the strengths of computers and humans. The results in this week's paper show that gaming, science and computation can be combined to make advances that were not possible before."

Games like Foldit are evolving. To piece together the retrovirus enzyme structure, Cooper said, gamers used a new Alignment Tool for the first time to copy parts of know molecules and test their fit in an incomplete model.

"The ingenuity of game players," Khatib said, "is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems.

According to Popovic, "Foldit shows that a game can turn novices into domain experts capable of producing first-class scientific discoveries. We are currently applying the same approach to change the way math and science are taught in school."

The other scientists involved in this project were Frank DiMaio and James Thompson, both of the UW Department of Biochemistry, and Maciej Kazmierczyk, Miroslaw Gilski, Szymon Krzywda, Helena Zabranska, and Mariusz Jaskolski, all of the Faculty of Chemistry of A. Mickiewicz University in Poznan, Poland, and Iva Pichova of the Academy of Sciences of the Czech Republic, Prague.

The project was supported by the UW Center for Game Science, the U.S. Defense Advanced Research Projects Agency (DARPA), the U.S. National Science Foundation, the Howard Hughes Medical Institute, and Microsoft Corp.

Early Detection Is Key in the Fight Against Ovarian Cancer

ScienceDaily (Sep. 19, 2011) — Ovarian cancer is a rare but often deadly disease that can strike at any time in a woman's life. It affects one in 70 women and in the past was referred to as a silent killer, but researchers have found there are symptoms associated with ovarian cancer that can assist in early detection. Experts at Northwestern Memorial say the best defense is to make use of preventive methods, understand the risks and recognize potential warning signs of ovarian cancer.

"Currently, there is no reliable screening test to identify early ovarian cancer. Women need to focus on good health habits, listen to their bodies and tell their doctor if a change occurs," said Diljeet Singh, MD, gynecological oncologist and co-director of the Ovarian Cancer Early Detection and Prevention Program at Northwestern Memorial Hospital.

Catching ovarian cancer early increases five-year survival odds from 30 percent to more than 90 percent. But the symptoms of ovarian cancer often mimic other less dangerous conditions making it difficult to recognize. Singh says women should be aware of possible early warning signs which include:

Bloating

Pelvic or abdominal pain

Difficulty eating or feeling full quickly

Urinary symptoms (urgency or frequency)

Increased abdominal size (pants getting tighter around waist)

Singh comments that the frequency and number of symptoms is important and women who experience a combination of these symptoms almost daily for two to three weeks should see their doctor.

Doctors say it is not clear what causes ovarian cancer but there are factors that increase the odds of developing the disease including carrying a mutation of the BRCA gene, having a personal history of breast cancer or a family history of ovarian cancer, being over the age of 45 or if a woman is obese. If a woman is high-risk, doctors recommend screening begin at age 20 to 25, or five to 10 years earlier than the youngest age of diagnosis in the family. In addition, there are genetic tests available that can identify women who are at a substantially increased risk.

While ovarian cancer is difficult to detect, specialized centers such as the Northwestern Ovarian Cancer Early Detection and Prevention Program, a collaborative effort between the hospital and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, have strategies for monitoring women at risk. Patients are monitored with physical examinations, ultrasound and blood tests every six months. "The goals of the program are to help women understand their personal risks and what they can do to decrease their risk, to help develop methods of early detection and prevention and to identify women who would benefit from preventive surgery," said Singh, also an associate professor at the department of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and member of the Lurie Cancer Center.

Studies have shown there are ways to reduce the risk of developing the disease. Women who use birth control pills for at least five years are three-times less likely to develop ovarian cancer. In addition, permanent forms of birth control such as tubal ligation have been found to reduce the risk of ovarian cancer by 50 percent. In cases where women have an extensive family history of breast or ovarian cancer, or who carry altered versions of the BRCA genes, may receive a recommendation to remove the ovaries and fallopian tubes which lowers the risk of ovarian cancer by more than 95 percent.

"Eating a diet rich in fruits and vegetables, getting regular exercise, maintaining a normal body weight and managing stresses are all ways women can help decrease their risk of ovarian cancer," added Singh.

Treatment for ovarian cancer usually begins with surgery to determine if the cancer has spread. Doctors at Northwestern Memorial also use a form of chemotherapy called intraperitoneal chemotherapy, which is injected directly into the abdominal cavity and has been linked to a 15-month improvement in survival.

"The best scenario would be to prevent this cancer entirely but until that day comes women need to focus on good health behaviors, listen to their bodies and know their family history" stated Singh.

Learning How Gut Bacteria Influence Health: Scientists Crack Sparse Genome of Microbe Linked to Autoimmunity

ScienceDaily (Sep. 19, 2011) — Scientists have deciphered the genome of a bacterium implicated as a key player in regulating the immune system of mice. The genomic analysis provides the first glimpse of its unusually sparse genetic blueprint and offers hints about how it may activate a powerful immune response that protects mice from infection but also spurs harmful inflammation.

A little-known bacterial species called segmented filamentous bacterium, or SFB, can activate the production of specialized immune cells in mice. This scanning electron microscope image of an SFB colony shows a mass of long hair-like filaments created when the bacteria stay attached to each other after they divide.

The researchers, led by Dan Littman, the Helen L. and Martin S. Kimmel Professor of Molecular Immunology at NYU School of Medicine and a Howard Hughes Medical Institute Investigator, and Ivaylo Ivanov, PhD, of Columbia University Medical Center, published their findings in the September 15, 2011, issue of Cell Host and Microbe. The study suggests that the gut-dwelling microorganism, named segmented filamentous bacteria (SFB), is genetically distinct from all 1,200 bacterial genomes studied so far, reflecting its relatively unique role in the gut.

Although SFB was first identified more than 40 years ago, it wasn't until 2009 that Dr. Littman and an international team of collaborators discovered that it can recruit specialized T cells, called Th17 cells, in the small intestine of mice. These potent immune cells, they subsequently found, protected the mice from disease-causing Citrobacter rodentium bacteria, but also made them more susceptible to inflammation and autoimmune arthritis. Those initial results suggested other intestinal bacteria might also regulate immune function.

"What has become clear in the last couple of years is that individual bacteria can specifically influence particular branches of the immune system," says Dr. Littman. In the new study, his team deciphered SFB's 1.57 million letters of DNA, almost 2,000 times smaller than our own genome and about one-third the size of its closest relative.

The microbe's sparse genome lacks many genes needed for its own survival, such as ones for making amino acids and other essential nutrients. As a result, it is dependent on other gut-dwelling bacteria or its host for food, according to the study. The examination of its 1,500 genes, however, suggests it is well adapted to the small intestine, where it clings to the thin lining and may help prevent other microbes from breaching the barrier.

Although the study didn't uncover any definitive signs of the SFB living within us, Dr. Littman suspects the resourceful bacteria have adapted to certain human populations. Even if it isn't found in our intestinal tract, scientists could apply what they have learned to obtain insights into the function of similarly acting microorganisms within us.

"Maybe in humans, there is another bacterium that is different from SFB but behaves functionally in the same way," says Dr. Ivanov, who conducted the latest analysis as a postdoctoral researcher in Dr. Littman's lab.

Recently, Japanese researchers found intestinal bacteria in humans that can boost development of regulatory immune cells in mice, thereby keeping the inflammatory activity of Th17 cells in check. Dr. Littman and his NYU collaborators may have also uncovered a microbe in the intestinal tract of rheumatoid arthritis patients that alters immune function. These emerging results underscore the need to understand how the microbes living in our bodies may impact our health.

"This research brings us the potential genetic mechanisms that trigger differentiation of Th17 cells which we have long believed to have a strong role in the development of autoimmune diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and Crohn's disease," said Steven Abramson, MD, professor, Departments of Medicine and Pathology and director of the Rheumatology Division at NYU Langone Medical Center. "With more than 50 million Americans suffering from at least one autoimmune disease, this research gives scientists and clinicians a greater ability to apply knowledge gained in the laboratory to actual clinical cases, moving it from 'bench-to-beside' to give patients a tremendous advantage and physicians the ability to fine-tune medications and protocols based on patient response."