Eating less keeps the brain young

Eating less keeps the brain young

  10:13:00 AM    Science Lover

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Overeating may cause brain aging while eating less turns on a molecule that helps the brain stay young.

A team of Italian researchers at the Catholic University of Sacred Heart in Rome have discovered that this molecule, called CREB1, is triggered by "caloric restriction" (low caloric diet) in the brain of mice. They found that CREB1 activates many genes linked to longevity and to the proper functioning of the brain.

This work was led by Giovambattista Pani, researcher at the Institute of General Pathology, Faculty of Medicine at the Catholic University of Sacred Heart in Rome, directed by Professor Achille Cittadini, in collaboration with Professor Claudio Grassi of the Institute of Human Physiology. The research appears this week in the Proceedings of the National Academy of Sciences (PNAS).

"Our hope is to find a way to activate CREB1, for example through new drugs, so to keep the brain young without the need of a strict diet," Dr Pani said.

Caloric restriction means the animals can only eat up to 70 percent of the food they consume normally, and is a known experimental way to extend life, as seen in many experimental models. Typically, caloric-restricted mice do not become obese and don't develop diabetes; moreover they show greater cognitive performance and memory, are less aggressive. Furthermore they do not develop, if not much later, Alzheimer's disease and with less severe symptoms than in overfed animals.

Many studies suggest that obesity is bad for our brain, slows it down, causes early brain aging, making it susceptible to diseases typical of older people as the Alzheimer's and Parkinson's. In contrast, caloric restriction keeps the brain young. Nevertheless, the precise molecular mechanism behind the positive effects of an hypocaloric diet on the brain remained unknown till now.

The Italian team discovered that CREB1 is the molecule activated by caloric restriction and that it mediates the beneficial effects of the diet on the brain by turning on another group of molecules linked to longevity, the "sirtuins". This finding is consistent with the fact that CREB1 is known to regulate important brain functions as memory, learning and anxiety control, and its activity is reduced or physiologically compromised by aging.

Moreover, Italian researchers have discovered that the action of CREB1 can be dramatically increased by simply reducing caloric intake, and have shown that CREB is absolutely essential to make caloric restriction work on the brain. In fact, if mice lack CREB1 the benefits of caloric restriction on the brain (improving memory, etc.) disappeear. So the animals without CREB1 show the same brain disabilities typical of overfed and/or old animals.

"Thus, our findings identify for the first time an important mediator of the effects of diet on the brain," Dr. Pani said. "This discovery has important implications to develop future therapies to keep our brain young and prevent brain degeneration and the aging process. In addition, our study shed light on the correlation among metabolic diseases as diabetes and obesity and the decline in cognitive activities."

Provided by Catholic University of Rome

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New genetic technique converts skin cells into brain cells

New genetic technique converts skin cells into brain cells

  12:34:00 AM    Science Lover

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A research breakthrough has proven that it is possible to reprogram mature cells from human skin directly into brain cells, without passing through the stem cell stage. The unexpectedly simple technique involves activating three genes in the skin cells; genes which are already known to be active in the formation of brain cells at the foetal stage.

converts skin cells into brain cells

The new technique avoids many of the ethical dilemmas that stem cell research has faced.

For the first time, a research group at Lund University in Sweden has succeeded in creating specific types of nerve cells from human skin. By reprogramming connective tissue cells, called fibroblasts, directly into nerve cells, a new field has been opened up with the potential to take research on cell transplants to the next level. The discovery represents a fundamental change in the view of the function and capacity of mature cells. By taking mature cells as their starting point instead of stem cells, the Lund researchers also avoid the ethical issues linked to research on embryonic stem cells.

Head of the research group Malin Parmar was surprised at how receptive the fibroblasts were to new instructions.

"We didn't really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions."

The study, which was published in the latest issue of the scientific journal PNAS, also shows that the skin cells can be directed to become certain types of nerve cells.

In experiments where a further two genes were activated, the researchers have been able to produce dopamine brain cells, the type of cell which dies in Parkinson's disease. The research findings are therefore an important step towards the goal of producing nerve cells for transplant which originate from the patients themselves. The cells could also be used as disease models in research on various neurodegenerative diseases.

Unlike older reprogramming methods, where skin cells are turned into pluripotent stem cells, known as IPS cells, direct reprogramming means that the skin cells do not pass through the stem cell stage when they are converted into nerve cells. Skipping the stem cell stage probably eliminates the risk of tumours forming when the cells are transplanted. Stem cell research has long been hampered by the propensity of certain stem cells to continue to divide and form tumours after being transplanted.

Before the direct conversion technique can be used in clinical practice, more research is needed on how the new nerve cells survive and function in the brain. The vision for the future is that doctors will be able to produce the brain cells that a patient needs from a simple skin or hair sample. In addition, it is presumed that specifically designed cells originating from the patient would be accepted better by the body's immune system than transplanted cells from donor tissue.

"This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson's disease", says Malin Parmar, who is now continuing the research to develop more types of brain cells using the new technique.

More information: 'Direct conversion of human fibroblasts to dopaminergic neurons', publ. PNAS 2011; 6 June 2011: http://www.pnas.or … 108.abstract

Provided by Lund University

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Parts of Brain Can Switch Functions: In People Born Blind, Brain Regions That Usually Process Vision Can Tackle Language

Parts of Brain Can Switch Functions: In People Born Blind, Brain Regions That Usually Process Vision Can Tackle Language

  9:52:00 AM    Science Lover

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When your brain encounters sensory stimuli, such as the scent of your morning coffee or the sound of a honking car, that input gets shuttled to the appropriate brain region for analysis. The coffee aroma goes to the olfactory cortex, while sounds are processed in the auditory cortex.

MRI scan of brain. (Credit: iStockphoto)

 

That division of labor suggests that the brain's structure follows a predetermined, genetic blueprint. However, evidence is mounting that brain regions can take over functions they were not genetically destined to perform. In a landmark 1996 study of people blinded early in life, neuroscientists showed that the visual cortex could participate in a nonvisual function -- reading Braille.

Now, a study from MIT neuroscientists shows that in individuals born blind, parts of the visual cortex are recruited for language processing. The finding suggests that the visual cortex can dramatically change its function -- from visual processing to language -- and it also appears to overturn the idea that language processing can only occur in highly specialized brain regions that are genetically programmed for language tasks.

"Your brain is not a prepackaged kind of thing. It doesn't develop along a fixed trajectory, rather, it's a self-building toolkit. The building process is profoundly influenced by the experiences you have during your development," says Marina Bedny, an MIT postdoctoral associate in the Department of Brain and Cognitive Sciences and lead author of the study, which appears in the Proceedings of the National Academy of Sciences the week of Feb. 28.

Flexible connections

For more than a century, neuroscientists have known that two specialized brain regions -- called Broca's area and Wernicke's area -- are necessary to produce and understand language, respectively. Those areas are thought to have intrinsic properties, such as specific internal arrangement of cells and connectivity with other brain regions, which make them uniquely suited to process language.

Other functions -- including vision and hearing -- also have distinct processing centers in the sensory cortices. However, there appears to be some flexibility in assigning brain functions. Previous studies in animals (in the laboratory of Mriganka Sur, MIT professor of brain and cognitive sciences) have shown that sensory brain regions can process information from a different sense if input is rewired to them surgically early in life. For example, connecting the eyes to the auditory cortex can provoke that brain region to process images instead of sounds.

Until now, no such evidence existed for flexibility in language processing. Previous studies of congenitally blind people had shown some activity in the left visual cortex of blind subjects during some verbal tasks, such as reading Braille, but no one had shown that this might indicate full-fledged language processing.

Bedny and her colleagues, including senior author Rebecca Saxe, assistant professor of brain and cognitive sciences, and Alvaro Pascual-Leone, professor of neurology at Harvard Medical School, set out to investigate whether visual brain regions in blind people might be involved in more complex language tasks, such as processing sentence structure and analyzing word meanings.

To do that, the researchers scanned blind subjects (using functional magnetic resonance imaging) as they performed a sentence comprehension task. The researchers hypothesized that if the visual cortex was involved in language processing, those brain areas should show the same sensitivity to linguistic information as classic language areas such as Broca's and Wernicke's areas.

They found that was indeed the case -- visual brain regions were sensitive to sentence structure and word meanings in the same way as classic language regions, Bedny says. "The idea that these brain regions could go from vision to language is just crazy," she says. "It suggests that the intrinsic function of a brain area is constrained only loosely, and that experience can have really a big impact on the function of a piece of brain tissue."

Bedny notes that the research does not refute the idea that the human brain needs Broca's and Wernicke's areas for language. "We haven't shown that every possible part of language can be supported by this part of the brain [the visual cortex]. It just suggests that a part of the brain can participate in language processing without having evolved to do so," she says.

Redistribution

One unanswered question is why the visual cortex would be recruited for language processing, when the language processing areas of blind people already function normally. According to Bedny, it may be the result of a natural redistribution of tasks during brain development.

"As these brain functions are getting parceled out, the visual cortex isn't getting its typical function, which is to do vision. And so it enters this competitive game of who's going to do what. The whole developmental dynamic has changed," she says.

This study, combined with other studies of blind people, suggest that different parts of the visual cortex get divvied up for different functions during development, Bedny says. A subset of (left-brain) visual areas appears to be involved in language, including the left primary visual cortex.

It's possible that this redistribution gives blind people an advantage in language processing. The researchers are planning follow-up work in which they will study whether blind people perform better than sighted people in complex language tasks such as parsing complicated sentences or performing language tests while being distracted.

The researchers are also working to pinpoint more precisely the visual cortex's role in language processing, and they are studying blind children to figure out when during development the visual cortex starts processing language.
 

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Artificial Cells Behave Like Biological Cells

Artificial Cells Behave Like Biological Cells

  7:42:00 PM    Science Lover

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Inspired by the social interactions of ants and slime molds, University of Pittsburgh engineers have designed artificial cells capable of self-organizing into independent groups that can communicate and cooperate.

The above image shows the cells in “snake” formation 
as competing signaling capsules (shown in red) pull 
respective lines of target cells in opposite 
directions. (Credit: University of Pittsburgh)

Recently reported in the Proceedings of the National Academy of Sciences (PNAS), the research is a significant step toward producing synthetic cells that behave like natural organisms and could perform important, microscale functions in fields ranging from the chemical industry to medicine.

The team presents in the PNAS paper computational models that provide a blueprint for developing artificial cells -- or microcapsules -- that can communicate, move independently, and transport "cargo" such as chemicals needed for reactions. Most importantly, the "biologically inspired" devices function entirely through simple physical and chemical processes, behaving like complex natural organisms but without the complicated internal biochemistry, said corresponding author Anna Balazs, Distinguished Professor of Chemical Engineering in Pitt's Swanson School of Engineering.

The Pitt group's microcapsules interact by secreting nanoparticles in a way similar to that used by biological cells signal to communicate and assemble into groups. And with a nod to ants, the cells leave chemical trails as they travel, prompting fellow microcapsules to follow. Balazs worked with lead author German Kolmakov and Victor Yashin, both postdoctoral researchers in Pitt's Department of Chemical and Petroleum Engineering, who produced the cell models; and with Pitt professor of electrical and computer engineering Steven Levitan, who devised the ant-like trailing ability.

The researchers write that communication hinges on the interaction between microcapsules exchanging two different types of nanoparticles. The "signaling" cell secretes nanoparticles known as agonists that prompt the second "target" microcapsule to emit nanoparticles known as antagonists.

In one video of the interaction, as the signaling cell emits the agonist nanoparticles, the target cell responds with antagonists that stop the first cell from secreting. Once the signaling cell goes dormant, the target cell likewise stops releasing antagonists -- which makes the signaling cell start up again. The microcapsules get locked into a cycle that equates to an intercellular conversation, a dialogue humans could control by adjusting the capsules' permeability and the quantity of nanoparticles they contain.

Locomotion results as the released nanoparticles alter the surface underneath the microcapsules. The cell's polymer-based walls begin to push on the fluid surrounding the capsule and the fluid pushes back even harder, moving the capsule. At the same time, the nanoparticles from the signaling cell pull it toward the target cells. Groups of capsules begin to form as the signaling cell rolls along, picking up target cells. In practical use, Balazs said, the signaling cell could transport target cells loaded with cargo; the team's next step is to control the order in which target cells are collected and dropped off.

The researchers adjusted the particle output of the signaling cell to create various cell formations. One video clip shows the trailing "ants," wherein the particle secretions of one microcapsule group are delayed until another group passes by and activates it. The newly awakened cluster then follows the chemical residue left behind by the lead group.

A second film depicts a "dragon" formation comprising two cooperating signaling cells (shown as red) leading a large group of targets. Similar to these are "snakes" made up of competing signaling capsules pulling respective lines of target cells.

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Nanoelectronic Transistor Combined With Biological Machine Could Lead To Better Electronics

Nanoelectronic Transistor Combined With Biological Machine Could Lead To Better Electronics

  9:44:00 PM    Science Lover

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If artificial devices could be combined with biological machines, laptops and other electronic devices could get a boost in operating efficiency.

An artist's representation of a nanobioelectronic device incorporating alamethycin biological pore. In the core of the device is a silicon nanowire (grey), covered with a lipid bilayer (blue). The bilayer incorporates bundles of alamethicin molecules (purple) that form pore channels in the membrane. Transport of protons though these pore channels changes the current through the nanowire. (Credit: Image by Scott Dougherty, LLNL)

Lawrence Livermore National Laboratory researchers have devised a versatile hybrid platform that uses lipid-coated nanowires to build prototype bionanoelectronic devices.

Mingling biological components in electronic circuits could enhance biosensing and diagnostic tools, advance neural prosthetics such as cochlear implants, and could even increase the efficiency of future computers.

While modern communication devices rely on electric fields and currents to carry the flow of information, biological systems are much more complex. They use an arsenal of membrane receptors, channels and pumps to control signal transduction that is unmatched by even the most powerful computers. For example, conversion of sound waves into nerve impulses is a very complicated process, yet the human ear has no trouble performing it.

“Electronic circuits that use these complex biological components could become much more efficient,” said Aleksandr Noy, the LLNL lead scientist on the project.

While earlier research has attempted to integrate biological systems with microelectronics, none have gotten to the point of seamless material-level incorporation.

“But with the creation of even smaller nanomaterials that are comparable to the size of biological molecules, we can integrate the systems at an even more localized level,” Noy said.

To create the bionanoelectronic platform the LLNL team turned to lipid membranes, which are ubiquitous in biological cells. These membranes form a stable, self-healing,and virtually impenetrable barrier to ions and small molecules.

“That's not to mention that these lipid membranes also can house an unlimited number of protein machines that perform a large number of critical recognition, transport and signal transduction functions in the cell,” said Nipun Misra, a UC Berkeley graduate student and a co-author on the paper.

Julio Martinez, a UC Davis graduate student and another co-author added: “Besides some preliminary work, using lipid membranes in nanoelectronic devices remains virtually untapped.”

The researchers incorporated lipid bilayer membranes into silicon nanowire transistors by covering the nanowire with a continuous lipid bilayer shell that forms a barrier between the nanowire surface and solution species.

“This 'shielded wire' configuration allows us to use membrane pores as the only pathway for the ions to reach the nanowire,” Noy said. “This is how we can use the nanowire device to monitor specific transport and also to control the membrane protein.”

The team showed that by changing the gate voltage of the device, they can open and close the membrane pore electronically.

The research appears Aug. 10 in the online version of the Proceedings of the National Academy of Sciences.

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