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Monday, December 13, 2010

Alzheimer's: 'Cleansing' Brain of Plaques


New molecular tools developed at the University of Michigan show promise for "cleansing" the brain of amyloid plaques, implicated in Alzheimer's disease.
Small Molecules for Metal-Amyloid Species in the Brain. 
(Credit: Mi Hee Lim and Joseph J. Braymer)

A hallmark of Alzheimer's disease -- a neurodegenerative disease with no cure -- is the aggregation of protein-like bits known as amyloid-beta peptides into clumps in the brain called plaques. These plaques and their intermediate messes can cause cell death, leading to the disease's devastating symptoms of memory loss and other mental difficulties.

The mechanisms responsible for the formation of these misfolded proteins and their associations with Alzheimer's disease are not entirely understood, but it's thought that copper and zinc ions are somehow involved.

The research, led by assistant professor Mi Hee Lim, was published online Dec. 3 in the Proceedings of the National Academy of Science.
 
In earlier work, Lim and her team developed dual-purpose molecular tools that both grab metal ions and interact with amyloid-beta. The researchers went on to show that in solutions with or without living cells, the molecules were able to regulate copper-induced amyloid-beta aggregation, not only disrupting the formation of clumps, but also breaking up clumps that already had formed.

Building upon that first generation of compounds, Lim and lab members Jung-Suk Choi and Joseph Braymer now report a second generation of compounds that are more stable in biological environments. The researchers tested one of those compounds, described in the PNAS paper, in homogenized brain tissue samples from Alzheimer's disease patients.

"We found that our compound is capable of disassembling the misfolded amyloid clumps to form smaller amyloid pieces, which might be 'cleansed' from the brain more easily, demonstrating a therapeutic application of our compound," said Lim, who has joint appointments in the Life Sciences Institute and the Department of Chemistry. In addition, preliminary tests show that the bi-functional small molecules have a strong potential to cross the blood-brain barrier, the barricade of cells that separates brain tissue from circulating blood, protecting the brain from harmful substances in the bloodstream.

"Crossing this barrier is essential for any treatment like this to be successful," Lim said.

Next steps include more intensive testing of the new compounds for diagnostic and therapeutic properties.

Lim and her team collaborated with Ayyalusamy Ramamoorthy, professor of chemistry and biophysics on this work, with funding from the U-M Horace H. Rackham School of Graduate Studies, the Alzheimer's Art Quilt Initiative, and the National Institutes of Health.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment.

Friday, December 10, 2010

Brains Wired So We Can Better Hear Ourselves


Like the mute button on the TV remote control, our brains filter out unwanted noise so we can focus on what we're listening to. But when it comes to following our own speech, a new brain study from the University of California, Berkeley, shows that instead of one homogenous mute button, we have a network of volume settings that can selectively silence and amplify the sounds we make and hear.
Activity in the auditory cortex when we speak and listen 
is amplified in some regions of the brain and muted in 
others. In this image, the black line represents muting 
activity when we speak. (Credit: Courtesy 
of Adeen Flinker)

Neuroscientists from UC Berkeley, UCSF and Johns Hopkins University tracked the electrical signals emitted from the brains of hospitalized epilepsy patients. They discovered that neurons in one part of the patients' hearing mechanism were dimmed when they talked, while neurons in other parts lit up.

Their findings, published Dec. 8, 2010 in the Journal of Neuroscience, offer new clues about how we hear ourselves above the noise of our surroundings and monitor what we say. Previous studies have shown a selective auditory system in monkeys that can amplify their self-produced mating, food and danger alert calls, but until this latest study, it was not clear how the human auditory system is wired.

"We used to think that the human auditory system is mostly suppressed during speech, but we found closely knit patches of cortex with very different sensitivities to our own speech that paint a more complicated picture," said Adeen Flinker, a doctoral student in neuroscience at UC Berkeley and lead author of the study.

"We found evidence of millions of neurons firing together every time you hear a sound right next to millions of neurons ignoring external sounds but firing together every time you speak," Flinker added. "Such a mosaic of responses could play an important role in how we are able to distinguish our own speech from that of others."

While the study doesn't specifically address why humans need to track their own speech so closely, Flinker theorizes that, among other things, tracking our own speech is important for language development, monitoring what we say and adjusting to various noise environments.

"Whether it's learning a new language or talking to friends in a noisy bar, we need to hear what we say and change our speech dynamically according to our needs and environment," Flinker said.

He noted that people with schizophrenia have trouble distinguishing their own internal voices from the voices of others, suggesting that they may lack this selective auditory mechanism. The findings may be helpful in better understanding some aspects of auditory hallucinations, he said.

Moreover, with the finding of sub-regions of brain cells each tasked with a different volume control job -- and located just a few millimeters apart -- the results pave the way for a more detailed mapping of the auditory cortex to guide brain surgery.

In addition to Flinker, the study's authors are Robert Knight, director of the Helen Wills Neuroscience Institute at UC Berkeley; neurosurgeons Edward Chang, Nicholas Barbaro and neurologist Heidi Kirsch of the University of California, San Francisco; and Nathan Crone, a neurologist at Johns Hopkins University in Maryland.

The auditory cortex is a region of the brain's temporal lobe that deals with sound. In hearing, the human ear converts vibrations into electrical signals that are sent to relay stations in the brain's auditory cortex where they are refined and processed. Language is mostly processed in the left hemisphere of the brain.

In the study, researchers examined the electrical activity in the healthy brain tissue of patients who were being treated for seizures. The patients had volunteered to help out in the experiment during lulls in their treatment, as electrodes had already been implanted over their auditory cortices to track the focal points of their seizures.

Researchers instructed the patients to perform such tasks as repeating words and vowels they heard, and recorded the activity. In comparing the activity of electrical signals discharged during speaking and hearing, they found that some regions of the auditory cortex showed less activity during speech, while others showed the same or higher levels.

"This shows that our brain has a complex sensitivity to our own speech that helps us distinguish between our vocalizations and those of others, and makes sure that what we say is actually what we meant to say," Flinker said.

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

No Wrong Side To This Bad


US researchers have created a smart hospital bed that is aware of its surrounding. The intelligent bed will make important decisions regarding the patients' healthcare which will involve both improving and saving precious lives.
A prototype of the smart bed that is being tested at the University of New Hampshire could revolutionise health care In the future


John LaCourse, professor at the University of New Hampshire, is currently negotiating with hospital bed manufacturers

to adopt his prograq~.med algorithm, which could become the basis for computerised hospital beds.

These smart hospital beds would communicate with and respond to medical devices that monitor a patient's condition.

"Perhaps a sleeping patient moves, causing a drop in blood pressure. The blood pressure monitor would communicate

this change to the bed and the bed, in turn, would move up or down until the patients' blood pressure is stabilised," he says.

IMPROVED POST-SURGERY CARE

Post-surgical needs may also be met with this bed. "Procedures such as retinal surgery require exact blood pressure levels," says LaCourse. "A smart hospital bed would adjust itself to maintain these levels for patients."

Even quality-of-life conditions such as bed sores could be addressed. "Instead of requiring hospital staff to move the patient, monitors could send signals to the bed to roll the patient to his left or right to avoid bed sores," says LaCourse.

"Microprocessors installed into the bed can also sense respiration patterns to determine when breathing has ceased, the bed moves in such a way that the breathing resumes," said Jonathan Waters, who is working on modifying the bed for sleep apnoea.

PLUG AND PLAY

The ultimate success of LaCourse's project rests with the plug-and-play component. Plug-and-play means that medical devices – everything from blood pressure monitors to breathing machines- "can talk to each other and share patient information which greatly reduces care errors," explains LaCourse.

To realise plug-and-play capability, however, LaCourse's technology must become the industry standard for hospital bed manufacturers. 1n this way, medical devices could seamlessly connect to and exchange patient data.

LaCourse is hopeful that, within two to three years, his technology may be accepted by most if not all hospital bed companies.

Monday, December 6, 2010

Dark Matter Could Transfer Energy in the Sun


Researchers from the Institute for Corpuscular Physics (IFIC) and other European groups have studied the effects of the presence of dark matter in the Sun. According to their calculations, low mass dark matter particles could be transferring energy from the core to the external parts of the Sun, which would affect the quantity of neutrinos that reach Earth.
Scientists believe that the majority of the dark matter 
particles gather together in the centre of the Sun, 
but in their elliptic orbits they also travel to the outer
part, interacting and exchanging with the solar atoms. 
In this way, the WIMPs transport the energy from the 
burning central core to the cooler peripheral
parts. (Credit: Hinode JAXA/NASA/PPARC)

"We assume that the dark matter particles interact weakly with the Sun's atoms, and what we have done is calculate at what level these interactions can occur, in order to better describe the structure and evolution of the Sun," Marco Taoso, researcher at the IFIC, a combined centre of the Spanish National Research Council and the University of Valencia, explains.

The astrophysical observations suggest that our galaxy is situated in a halo of dark matter particles. According to the models, some of these particles, the WIMPs (Weakly Interacting Massive Particles) interact weakly with other normal ones, such as atoms, and could be building up on the inside of stars. The study, recently published in the journal Physical Review D, carries out an in-depth study of the case of the Sun in particular.

"When the WIMPs pass through the Sun they can break up the atoms of our star and lose energy. This prevents them from escaping the gravitational force of the Sun which captures them, and they become trapped, orbiting inside it, with no way of escaping," the researcher points out.

The dark matter cools down the Sun's core

Scientists believe that the majority of the dark matter particles gather together in the centre of the Sun, but in their elliptic orbits they also travel to the outer part, interacting and exchanging with the solar atoms. In this way, the WIMPs transport the energy from the burning central core to the cooler peripheral parts.

"This effect produces a cooling down of the core, the region from where the neutrinos originate due to the nuclear reactions of the Sun," Taoso points out. "And this corresponds to a reduction in the flux of solar neutrinos, since these depend greatly on the temperature of the core."

The neutrinos that reach Earth can be measured by means of different techniques. These data can be used to detect the modifications of the solar temperature caused by the WIMPs. The transport of energy by these particles depends on the likelihood of them interacting with the atoms, and the "size" of these interactions is related to the reduction in the neutrino flux.

"As a result, current data about solar neutrinos can be used to put limits on the extent of the interactions between dark matter and atoms, and using numerical codes we have proved that certain values correspond to a reduction in the flux of solar neutrinos and clash with the measurements," the scientist reveals.

The team has applied their calculations to better understand the effects of low mass dark matter particles (between 4 and 10 gigaelectronvolts). At this level we find models that attempt to explain the results of experiments such as DAMA (beneath an Italian mountain) or CoGent (in a mine in the USA), which look for dark material using "scintillators" or WIMP detectors.

Debate about WIMP and solar composition

This year another study by scientists from Oxford University (United Kingdom) also appeared. It states that WIMPs not only reduce the fluxes of solar neutrinos, but also, furthermore, modify the structure of the Sun and can explain its composition.

"Our calculations, however, show that the modifications of the star's structure are too small to support this claim and that the WIMPs cannot explain the problem of the composition of the sun," Taoso concludes.

Saturday, December 4, 2010

The Future of Metabolic Engineering: Designer Molecules, Cells and Microorganisms


Will we one day design and create molecules, cells and microorganisms that produce specific chemical products from simple, readily-available, inexpensive starting materials? Will the synthetic organic chemistry now used to produce pharmaceutical drugs, plastics and a host of other products eventually be surpassed by metabolic engineering as the mainstay of our chemical industries? Yes, according to Jay Keasling, chemical engineer and one of the world's foremost practitioners of metabolic engineering.
Metabolic engineering - the practice of 
altering genes and metabolic pathways 
within a cell or microorganism -- could 
one day be used to mass-produce biofuels, 
pharmaceuticals and other chemical 
products from inexpensive and renewable 
starting materials. (Credit: Flavio Robles, 
Berkeley Lab Public Affairs)

In a paper published in the journal Science Keasling discusses the potential of metabolic engineering -- one of the principal techniques of modern biotechnology -- for the microbial production of many of the chemicals that are currently derived from non-renewable resources or limited natural resources. Examples include, among a great many other possibilities, the replacement of gasoline and other transportation fuels with clean, green and renewable biofuels.

"Continued development of the tools of metabolic engineering will be necessary to expand the range of products that can be produced using biological systems, Keasling says. "However, when more of these tools are available, metabolic engineering should be just as powerful as synthetic organic chemistry, and together the two disciplines can greatly expand the number of chemical products available from renewable resources."

Keasling is the chief executive officer for the Joint BioEnergy Institute, a U.S. Department of Energy (DOE) bioenergy research center. He also holds joint appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab), where he oversees that institute's biosciences research programs, and the University of California (UC), Berkeley, where he serves as director of the Synthetic Biology Engineering Research Center, and is the Hubbard Howe Jr. Distinguished Professor of Biochemical Engineering.

Metabolic engineering is the practice of altering genes and metabolic pathways within a cell or microorganism to increase its production of a specific substance. Keasling led one of the most successful efforts to date in the application of metabolic engineering, when he combined it with synthetic organic chemistry techniques to develop a microbial-based means of producing artemisinin, the most potent of all anti-malaria drugs. He and his research group at JBEI are now applying that same combination to the synthesis of liquid transportation fuels from lignocellulosic biomass. In all cases, the goal is to engineer microbes to perform as much of the chemistry required to produce a desired final product as possible.

"To date, microbial production of natural chemical products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered," Keasling says. "Production of non-natural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism, and by engineering enzymes to have new function."

These efforts have utilized well-known, industrial microorganisms, but future efforts, he says, may include designer molecules and cells that are tailor-made for the desired chemical and production process.

"In any future, metabolic engineering will soon rival and potentially eclipse synthetic organic chemistry," Keasling says.

Keasling cites the production of active pharmaceutical ingredients as one area where metabolic engineering enjoys a distinct advantage over synthetic organic chemistry. This includes three specific classes of chemicals -- alkaloids, which are primarily derived from plants; polyketides and non-ribosomal peptides, which are produced by various bacteria and fungi; and isoprenoids, which also are typically produced by microbes.

"Many of these natural products are too complex to be chemically synthesized and yet have a value that justifies the cost of developing a genetically engineered microorganism," Keasling says. "The cost of starting materials is generally a small fraction of the complete cost of these products, and relatively little starting material is necessary so availability is not an issue."

Keasling also says that metabolic engineering could provide a valuable alternative means of producing variations of terpenes, the hydrocarbon compounds common to the resins of conifers, in a form that could yield pharmaceuticals that are more effective for the treatment of human disease than the forms that nature has provided.

Perhaps the ripest targets of opportunity for future metabolic engineering efforts are petroleum-based bulk chemical products, including gasoline and other fuels, polymers and solvents. Because such products can be inexpensively catalyzed from petroleum, microbial production has until now been rare, but with fluctuating oil prices, dwindling resources and other considerations, the situation, Keasling says, has changed.

"It is now possible to consider production of these inexpensive bulk chemicals from low-cost starting materials, such as starch, sucrose, or cellulosic biomass with a microbial catalyst," he says. "The key to producing these bulk chemicals in metabolically-engineered cells will be our ability to make the exact molecule needed for existing products rather than something 'similar but green' that will require extensive product testing before it can be used."

In his Science paper, Keasling discusses the formidable roadblocks that stand in the way of a future in which microorganisms and molecules can be tailor-made through metabolic engineering, including the need for "debugging routines" that can find and fix errors in engineered cells. However, he is convinced these roadblocks can and will be overcome.

"One can even envision a day when cell manufacturing is done by different companies, each specializing in certain aspects of the synthesis, with one company constructing the chromosome, one company building the membrane and cell wall bag, and one company filling this bag with the basic molecules needed to boot up the cell."

The Joint BioEnergy Institute (JBEI) is one of three Bioenergy Research Centers funded by the U.S. Department of Energy to advance the development of the next generation of biofuels. It is a scientific partnership led by Berkeley Lab and including the Sandia National Laboratories, the University of California campuses of Berkeley and Davis, the Carnegie Institution for Science, and the Lawrence Livermore National Laboratory.

The Synthetic Biology Engineering Research Center (SynBERC) is a multi-institution partnership, funded by the National Science Foundation, that is aimed at "making biology easier to engineer." The SynBERC partnership is led by UC Berkeley and includes UC San Francisco, Harvard, MIT, Stanford, and Prairie View A&M University.

Wednesday, December 1, 2010

Antibacterial Soaps: Being Too Clean Can Make People Sick, Study Suggests


Young people who are overexposed to antibacterial soaps containing triclosan may suffer more allergies, and exposure to higher levels of Bisphenol A among adults may negatively influence the immune system, a new University of Michigan School of Public Health study suggests.
Young people who are overexposed to antibacterial 
soaps containing triclosan may suffer more allergies, and 
exposure to higher levels of Bisphenol A among adults 
may negatively influence the immune system, a new 
University of Michigan School of Public Health study 
suggests. (Credit: iStockphoto/Jorge Salcedo)

Triclosan is a chemical compound widely used in products such as antibacterial soaps, toothpaste, pens, diaper bags and medical devices. Bisphenol A (BPA) is found in many plastics and, for example, as a protective lining in food cans. Both of these chemicals are in a class of environmental toxicants called endocrine-disrupting compounds (EDCs), which are believed to negatively impact human health by mimicking or affecting hormones.

Using data from the 2003-2006 National Health and Nutrition Examination Survey, U-M researchers compared urinary BPA and triclosan with cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in a sample of U.S. adults and children over age 6. Allergy and hay fever diagnosis and CMV antibodies were used as two separate markers of immune alterations.

"We found that people over age 18 with higher levels of BPA exposure had higher CMV antibody levels, which suggests their cell-mediated immune system may not be functioning properly," said Erin Rees Clayton, research investigator at the U-M School of Public Health and first author on the paper.

Researchers also found that people age 18 and under with higher levels of triclosan were more likely to report diagnosis of allergies and hay fever.

There is growing concern among the scientific community and consumer groups that these EDCs are dangerous to humans at lower levels than previously thought.

"The triclosan findings in the younger age groups may support the 'hygiene hypothesis,' which maintains living in very clean and hygienic environments may impact our exposure to micro-organisms that are beneficial for development of the immune system," said Allison Aiello, associate professor at the U-M School of Public Health and principal investigator on the study.

As an antimicrobial agent found in many household products, triclosan may play a role in changing the micro-organisms to which we are exposed in such a way that our immune system development in childhood is affected.

"It is possible that a person can be too clean for their own good," said Aiello, who is also a visiting associate professor of epidemiology at Harvard.

Previous animal studies indicate that BPA and triclosan may affect the immune system, but this is the first known study to look at exposure to BPA and triclosan as it relates to human immune function, Aiello said.

One surprise finding is that with BPA exposure, age seems to matter, said Rees Clayton. In people 18 or older, higher amounts of BPA were associated with higher CMV levels, but in people younger than 18 the reverse was true.

"This suggests the timing of the exposure to BPA and perhaps the quantity and length of time we are exposed to BPA may be affecting the immune system response," Rees Clayton said.

This is just the first step, she said, but a very important one. Going forward, researchers would like to study the long-term effects of BPA and triclosan in people to see if they can establish a causal relationship.

One limitation of the study is that it measured disease and exposure simultaneously and thus shows only part of the picture, Aiello said.

"It is possible, for example, that individuals who have an allergy are more hygienic because of their condition, and that the relationship we observed is, therefore, not causal or is an example of reverse causation," Aiello said.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment.

Monday, November 29, 2010

Same Face May Look Male or Female, Depending on Where It Appears in a Person's Field of View


Neuroscientists at MIT and Harvard have made the surprising discovery that the brain sees some faces as male when they appear in one area of a person's field of view, but female when they appear in a different location.
Neuroscientists at MIT and Harvard have made the
surprising discovery  that the brain sees some faces
as male when they appear in one area of a  person's
field of view, but female when they appear
in a different  location.

The findings challenge a longstanding tenet of neuroscience -- that how the brain sees an object should not depend on where the object is located relative to the observer, says Arash Afraz, a postdoctoral associate at MIT's McGovern Institute for Brain Research and lead author of a new paper on the work.

"It's the kind of thing you would not predict -- that you would look at two identical faces and think they look different," says Afraz. He and two colleagues from Harvard, Patrick Cavanagh and Maryam Vaziri Pashkam, described their findings in the Nov. 24 online edition of the journal Current Biology.

In the real world, the brain's inconsistency in assigning gender to faces isn't noticeable, because there are so many other clues: hair and clothing, for example. But when people view computer-generated faces, stripped of all other gender-identifying features, a pattern of biases, based on location of the face, emerges.

The researchers showed subjects a random series of faces, ranging along a spectrum of very male to very female, and asked them to classify the faces by gender. For the more androgynous faces, subjects rated the same faces as male or female, depending on where they appeared.

Study participants were told to fix their gaze at the center of the screen, as faces were flashed elsewhere on the screen for 50 milliseconds each. Assuming that the subjects sat about 22 inches from the monitor, the faces appeared to be about three-quarters of an inch tall.

The patterns of male and female biases were different for different people. That is, some people judged androgynous faces as female every time they appeared in the upper right corner, while others judged faces in that same location as male. Subjects also showed biases when judging the age of faces, but the pattern for age bias was independent from the pattern for gender bias in each individual.

Sample size
 
Afraz believes this inconsistency in identifying genders is due to a sampling bias, which can also be seen in statistical tools such as polls. For example, if you surveyed 1,000 Bostonians, asking if they were Democrats or Republicans, you would probably get a fairly accurate representation of these percentages in the city as a whole, because the sample size is so large. However, if you took a much smaller sample, perhaps five people who live across the street from you, you might get 100 percent Democrats, or 100 percent Republicans. "You wouldn't have any consistency, because your sample is too small," says Afraz.

He believes the same thing happens in the brain. In the visual cortex, where images are processed, cells are grouped by which part of the visual scene they analyze. Within each of those groups, there is probably a relatively small number of neurons devoted to interpreting gender of faces. The smaller the image, the fewer cells are activated, so cells that respond to female faces may dominate. In a different part of the visual cortex, cells that respond to male faces may dominate.

"It's all a matter of undersampling," says Afraz.

Michael Tarr, codirector of the Center for the Neural Basis of Cognition at Carnegie Mellon University, says the findings add to the growing evidence that the brain is not always consistent in how it perceives objects under different circumstances. He adds that the study leaves unanswered the question of why each person develops different bias patterns. "Is it just noise within the system, or is some other kind of learning occurring that they haven't figured out yet?" asks Tarr, who was not involved in the research. "That's really the fascinating question."

Afraz and his colleagues looked for correlations between each subject's bias pattern and other traits such as gender, height and handedness, but found no connections.

He is now doing follow-up studies in the lab of James DiCarlo, associate professor of neuroscience at MIT, including an investigation of whether brain cells can be recalibrated to respond to faces differently.

Admin's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Saturday, November 27, 2010

Do Brain's 'Traffic Lights' Direct Our Actions?


In every waking minute, we have to make decisions -- sometimes within a split second. Neuroscientists at the Bernstein Center Freiburg have now discovered a possible explanation how the brain chooses between alternative options. The key lies in extremely fast changes in the communication between single nerve cells.
The timing of exciting (red curve) and inhibiting 
(blue curve) signals could be a way to control the 
"traffic flow" of activity in the brain. (Illustration: 
Bernstein Center Freiburg) (Credit: Illustration 
courtesy of Bernstein Center Freiburg)

The traffic light changes from green to orange -- should I push down the accelerator a little bit further or rather hit the brakes? Our daily lives present a long series of decisions we have to make, and sometimes we only have a split second at our disposal. Often the problem of decision-making entails the selection of one set of brain processes over multiple others seeking access to same resources. Several mechanisms have been suggested how the brain might solve this problem. However, up to now, it is a mystery what exactly happens when during a rapid choice between two options.

In the current issue of the Journal of Neuroscience, Jens Kremkow, Arvind Kumar, and Ad Aertsen from the Bernstein Center Freiburg propose a mechanism how the brain can choose between possible actions -- already at the level of single nerve cells.

As the structure and activity of the brain are just too complex to answer this question through a simple biological experiment, the scientists constructed a network of neurons in the computer. An important aspect of the model in this context is the property of nerve cells to influence the activity of other nerve cells, either in an excitatory or inhibitory manner. In the constructed network, two groups of neurons acted as the senders of two different signals. Further downstream in the network, another group of neurons, the "gate" neurons, were to control which of the signals would be transmitted onward.

As the cells within the network were connected both with exciting and inhibiting neurons, the signals reached the gate as excitatory and, after a short delay, inhibitory activity. In their simulations, the scientists found that the key for the gate neurons' "decision" in favour of one signal over the other was the time delay of the inhibitory signal relative to the excitatory signal. If the delay was set to be very small, the activity of the cells in the gate was quenched too quickly for the signal to be propagated.

Conversely, a larger delay caused the gate to open for the signal. Results from neurophysiological experiments have already shown that a change in delay properties is possible in real neurons. These findings therefore support the hypothesis of Kremkow and colleagues that such temporal gating can form the basis for selecting one of several alternative options in our brain.

Admin's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Friday, November 26, 2010

Stem Cells from Amniotic Fluid: Reprogrammed Amniotic Fluid Cells Can Generate All Types of Body Cells


Reprogrammed amniotic fluid cells can generate all types of body cells. High hopes rest on stem cells: one day, they may be used to treat many diseases. To date, embryos are the main source of these cells, but this raises ethical problems. Scientists at the Max Planck Institute for Molecular Genetics in Berlin have now managed to convert amniotic fluid cells into pluripotent stem cells. These amniotic fluid-derived iPS cells are hardly distinguishable from embryonic stem cells. However, they "remember" where they came from.
Top: Before their reprogramming into amniotic fluid iPS cells, 
human amniotic fluid cells are outwardly distinguishable from 
embryonic stem cells. Bottom left: Amniotic fluid iPS cells 
produce OCT4 (green), one of the most important marker 
proteins for embryonic stem cells. Bottom right: Starting from 
this embryonic stem cell phase, the amniotic fluid iPS cells can 
form hepatocyte-like cells and others. They produce the plasma
protein alpha-fetoprotein (red), which is abundant in fetal 
liver. (Credit: Max Planck Institute for Molecular Genetics)

The research appears in the online journal PLoS ONE, published by the Public Library of Science.

The special abilities of embryonic stem cells can today be used in multiple "grown-up" cells (e.g. skin and hair cells). This is done by reprogramming the cells and converting them to "induced pluripotent stem cells" (iPS cells). These then possess the typical properties of embryonic stem cells, meaning they can generate any of the cell types of the human body (pluripotency), and they can multiply endlessly.

Stem cells with memory
 
The scientists have shown that the amniotic fluid iPS cells can form different human cell types. They have also discovered that induced pluripotent stem cells can remember the original cell type from which they were generated. During cellular reprogramming, various genes that control the development of stem cells are apparently switched on or remain active. This confirms other current research results, which show that iPS cells derived from distinct tissues are prone to follow their pre-destined developmental path upon spontaneous differentiation. "We don't know just yet whether this donor-cell type memory will have an impact on possible medical treatment, or which type of somatic cell-derived iPS cell will be most suitable for treatment," cautions Katharina Wolfrum of the Max Planck Institute for Molecular Genetics.

Amniotic fluid cells have a number of advantages over other cell types. For one thing, amniotic fluid cells are routinely harvested in antenatal examinations to enable the early detection of disease. In most cases, more cells are obtained than are actually needed. In addition, the amniotic fluid mixture contains different types of cells from the unborn child, including stem-cell-like cells. As they are not very old, they have fewer environmentally-induced mutations, making them genetically more stable. "This may mean that it is possible to reprogram these amniotic fluid cells faster and more easily than other cell types, making amniotic fluid-derived iPS cells an interesting complement to embryonic stem cells," explains James Adjaye of the Max Planck Institute in Berlin.

Moreover, amniotic fluid cells could be extracted for cellular reprogramming before the birth of a child and be prepared for their intended use while the pregnancy is still ongoing. "This would make it possible to test which drugs work for a baby and whether they are tolerated, before that baby is born. Moreover, in the future, sick newborns can be treated with cells from their own body," says Adjaye.

Admin's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Thursday, November 25, 2010

Early Universe Was a Liquid, Nuclei Collisions at the Large Hadron Collider Show


In an experiment to collide lead nuclei together at CERN's Large Hadron Collider physicists from the ALICE detector team including researchers from the University of Birmingham have discovered that the very early Universe was not only very hot and dense but behaved like a hot liquid.
Another Real lead-lead collision in ALICE inner 
detector. (Credit: CERN)

By accelerating and smashing together lead nuclei at the highest possible energies, the ALICE experiment has generated incredibly hot and dense sub-atomic fireballs, recreating the conditions that existed in the first few microseconds after the Big Bang. Scientists claim that these mini big bangs create temperatures of over ten trillion degrees.

At these temperatures normal matter is expected to melt into an exotic, primordial 'soup' known as quark-gluon plasma. These first results from lead collisions have already ruled out a number of theoretical physics models, including ones predicting that the quark-gluon plasma created at these energies would behave like a gas.

Although previous research in the USA at lower energies, indicated that the hot fire balls produced in nuclei collisions behaved like a liquid, many expected the quark-gluon plasma to behave like a gas at these much higher energies.

Scientists from the University of Birmingham's School of Physics and Astronomy are playing a key role in this new phase of the LHC's programme which comes after seven months of successfully colliding protons at high energies. Dr David Evans, from the University of Birmingham's School of Physics and Astronomy, and UK lead investigator at ALICE experiment, said: "Although it is very early days we are already learning more about the early Universe."

He continues: "These first results would seem to suggest that the Universe would have behaved like a super-hot liquid immediately after the Big Bang."

The team has also discovered that more sub-atomic particles are produced in these head-on collisions than some theoretical models previously suggested. The fireballs resulting from the collision only lasts a short time, but when the 'soup' cools down, the researchers are able to see thousands of particles radiating out from the fireball. It is in this debris that they are able to draw conclusions about the soup's behaviour.

Two papers detailing this research have been submitted for publication and posted on: http://xxx.lanl.gov/abs/1011.3914| and http://xxx.lanl.gov/abs/1011.3916|.

This research is funded by the Science and Technology Facilities Council (STFC).