Neuroscience

Articles and news from the latest research reports.

Posts tagged science

231 notes

Are Babies Born Good?
Arber Tasimi is a 23-year-old researcher at Yale University’s Infant Cognition Center, where he studies the moral inclinations of babies—how the littlest children understand right and wrong, before language and culture exert their deep influence.“What are we at our core, before anything, before everything?” he asks. His experiments draw on the work of Jean Piaget, Noam Chomsky, his own undergraduate thesis at the University of Pennsylvania and what happened to him in New Haven, Connecticut, one Friday night last February.
It was about 9:45 p.m., and Tasimi and a friend were strolling home from dinner at Buffalo Wild Wings. Just a few hundred feet from his apartment building, he passed a group of young men in jeans and hoodies. Tasimi barely noticed them, until one landed a punch to the back of his head.
There was no time to run. The teenagers, ignoring his friend, wordlessly surrounded Tasimi, who had crumpled to the brick sidewalk. “It was seven guys versus one aspiring PhD,” he remembers. “I started counting punches, one, two, three, four, five, six, seven. Somewhere along the way, a knife came out.” The blade slashed through his winter coat, just missing his skin.
At last the attackers ran, leaving Tasimi prone and weeping on the sidewalk, his left arm broken. Police later said he was likely the random victim of a gang initiation.
After surgeons inserted a metal rod in his arm, Tasimi moved back home with his parents in Waterbury, Conn­­ecticut, about 35 minutes from New Haven, and became a creature much like the babies whose social lives he studies. He couldn’t shower on his own. His mom washed him and tied his shoes. His sister cut his meat.
Spring came. One beautiful afternoon, the temperature soared into the 70s and Tasimi, whose purple and yellow bruises were still healing, worked up the courage to stroll outside by himself for the first time. He went for a walk on a nearby jogging trail. He tried not to notice the two teenagers who seemed to be following him. “Stop ca­tastrophizing,” he told himself again and again, up until the moment the boys demanded his headphones.
The mugging wasn’t violent but it broke his spirit. Now the whole world seemed menacing. When he at last resumed his morality studies at the Infant Cognition Center, he parked his car on the street, feeding the meter every few hours rather than risking a shadowy parking garage.
“I’ve never been this low in life,” he told me when we first met at the baby lab a few weeks after the second crime. “You can’t help wonder: Are we a failed species?”
At times, he said, “only my research gives me hope.”
Continue reading

Are Babies Born Good?

Arber Tasimi is a 23-year-old researcher at Yale University’s Infant Cognition Center, where he studies the moral inclinations of babies—how the littlest children understand right and wrong, before language and culture exert their deep influence.“What are we at our core, before anything, before everything?” he asks. His experiments draw on the work of Jean Piaget, Noam Chomsky, his own undergraduate thesis at the University of Pennsylvania and what happened to him in New Haven, Connecticut, one Friday night last February.

It was about 9:45 p.m., and Tasimi and a friend were strolling home from dinner at Buffalo Wild Wings. Just a few hundred feet from his apartment building, he passed a group of young men in jeans and hoodies. Tasimi barely noticed them, until one landed a punch to the back of his head.

There was no time to run. The teenagers, ignoring his friend, wordlessly surrounded Tasimi, who had crumpled to the brick sidewalk. “It was seven guys versus one aspiring PhD,” he remembers. “I started counting punches, one, two, three, four, five, six, seven. Somewhere along the way, a knife came out.” The blade slashed through his winter coat, just missing his skin.

At last the attackers ran, leaving Tasimi prone and weeping on the sidewalk, his left arm broken. Police later said he was likely the random victim of a gang initiation.

After surgeons inserted a metal rod in his arm, Tasimi moved back home with his parents in Waterbury, Conn­­ecticut, about 35 minutes from New Haven, and became a creature much like the babies whose social lives he studies. He couldn’t shower on his own. His mom washed him and tied his shoes. His sister cut his meat.

Spring came. One beautiful afternoon, the temperature soared into the 70s and Tasimi, whose purple and yellow bruises were still healing, worked up the courage to stroll outside by himself for the first time. He went for a walk on a nearby jogging trail. He tried not to notice the two teenagers who seemed to be following him. “Stop ca­tastrophizing,” he told himself again and again, up until the moment the boys demanded his headphones.

The mugging wasn’t violent but it broke his spirit. Now the whole world seemed menacing. When he at last resumed his morality studies at the Infant Cognition Center, he parked his car on the street, feeding the meter every few hours rather than risking a shadowy parking garage.

“I’ve never been this low in life,” he told me when we first met at the baby lab a few weeks after the second crime. “You can’t help wonder: Are we a failed species?”

At times, he said, “only my research gives me hope.”

Continue reading

Filed under evolution infant morality cognition morality psychology neuroscience science

123 notes

How Neuroscientists Observe Brains Watching Movies

Unless you have been deaf and blind to the world over the past decade, you know that functional magnetic resonance brain imaging (fMRI) can look inside the skull of volunteers lying still inside the claustrophobic, coffinlike confines of a loud, banging magnetic scanner. The technique relies on a fortuitous property of the blood supply to reveal regional activity. Active synapses and neurons consume power and therefore need more oxygen, which is delivered by the hemoglobin molecules inside the circulating red blood cells. When these molecules give off their oxygen to the surrounding tissue, they not only change color—from arterial red to venous blue—but also turn slightly magnetic.

image

(Image: Todd Davidson/Stock Illustration Source)

Activity in neural tissue causes an increase in the volume and flow of fresh blood. This change in the blood supply, called the hemodynamic signal, is tracked by sending radio waves into the skull and carefully listening to their return echoes. FMRI does not directly measure synaptic and neuronal activity, which occurs over the course of milliseconds; instead it uses a relatively sluggish proxy—changes in the blood supply—that rises and falls in seconds. The spatial resolution of fMRI is currently limited to a volume element (voxel) the size of a pea, encompassing about one million nerve cells.

Neuroscientists routinely exploit fMRI to infer what volunteers are seeing, imagining or intending to do. It is really a primitive form of mind reading. Now a team has taken that reading to a new, startling level.

A number of groups have deduced the identity of pictures viewed by volunteers while lying in the magnet scanner from the slew of map­like representations found in primary, secondary and higher-order visual cortical regions underneath the bump on the back of the head.

Jack L. Gallant of the University of California, Berkeley, is the acknowledged master of these techniques, which proceed in two stages. First, a volunteer looks at a couple of thousand images while lying in a magnet. The response of a few hundred voxels in the visual cortex to each image is carefully registered. These data are then used to train an algorithm to predict the magnitude of the fMRI response for each voxel. Second, this procedure is inverted. That is, for a given magnitude of hemodynamic response, a probabilistic technique called Bayesian decoding infers the most likely image that gave rise to the observed response in that particular volunteer (human brains differ substantially, so it is difficult to use one brain to predict the responses of another).

The best of these techniques exploit preexisting, or prior, knowledge about pictures that could have been seen before. The number of mathematically possible images is vast, but the types of actual scenes that are encountered in a world populated by people, animals, trees, buildings and other objects encompass a tiny fraction of all possible images. Appropriately enough, the images that we usually encounter are called natural images. Using a database of six million natural images, Gallant’s group showed in 2009 how brain responses of volunteers to photographs they had not previously encountered could be reconstructed.

(Source: scientificamerican.com)

Read more …

Filed under fMRI neuronal activity nerve cells brain Bayesian decoding neuroscience science

82 notes

The Role of Medial Prefrontal Cortex in Memory and Decision Making
Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.

The Role of Medial Prefrontal Cortex in Memory and Decision Making

Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.

Filed under mPFC prefrontal cortex decision making memory memory consolidation learning neuroscience science

100 notes

Alzheimer’s Muddles Memory of How Things Work
Which is bigger, a key or an ant? That question might be easy for you to answer quickly, but it could be a little more confusing for a person with Alzheimer’s.
The most obvious trait of the mind-ruining disease is memory loss, with patients forgetting once-familiar people, places and experiences. New research shows how this mental deterioration extends to semantic memory, which has more to do with remembering facts and concepts and underlies a basic understanding of how things works.
For their study, researchers recruited 70 cognitively healthy people, 27 patients with Alzheimer’s 25 patients with mild cognitive impairment (MCI), often considered a precursor to dementia. All were tested on their ability to make size judgments about two pictures shown to them — the premise being that the bigger the difference in size between two objects, the faster a person would be able to answer the question.
"If you ask someone what is bigger, a key or an ant, they would be slower in their response than if you asked them what is bigger, a key or a house," researcher Terry Goldberg, of the Hofstra North Shore-LIJ School of Medicine, said in a statement.
This held true in the experiments, but the MCI and Alzheimer’s patients had much more trouble when asked to respond to a task with small size differences.
The experiment was then tweaked so that the participants were shown pictures of a small ant and a big house or a big ant and a small house. The MCI and Alzheimer’s patients did not have a problem making judgments about the small ant and big house, but had trouble with the more incongruent set. They were confused about which object was actually larger when shown a big ant and a small house, and were more likely to answer incorrectly or take longer to arrive at a response, the researchers said.
Goldberg said the findings indicate “that something is slowing down the patient and it is not episodic memory but semantic memory.”
The team will continue to study these patients over time to see if these semantic problems get worse as the disease advances.

Alzheimer’s Muddles Memory of How Things Work

Which is bigger, a key or an ant? That question might be easy for you to answer quickly, but it could be a little more confusing for a person with Alzheimer’s.

The most obvious trait of the mind-ruining disease is memory loss, with patients forgetting once-familiar people, places and experiences. New research shows how this mental deterioration extends to semantic memory, which has more to do with remembering facts and concepts and underlies a basic understanding of how things works.

For their study, researchers recruited 70 cognitively healthy people, 27 patients with Alzheimer’s 25 patients with mild cognitive impairment (MCI), often considered a precursor to dementia. All were tested on their ability to make size judgments about two pictures shown to them — the premise being that the bigger the difference in size between two objects, the faster a person would be able to answer the question.

"If you ask someone what is bigger, a key or an ant, they would be slower in their response than if you asked them what is bigger, a key or a house," researcher Terry Goldberg, of the Hofstra North Shore-LIJ School of Medicine, said in a statement.

This held true in the experiments, but the MCI and Alzheimer’s patients had much more trouble when asked to respond to a task with small size differences.

The experiment was then tweaked so that the participants were shown pictures of a small ant and a big house or a big ant and a small house. The MCI and Alzheimer’s patients did not have a problem making judgments about the small ant and big house, but had trouble with the more incongruent set. They were confused about which object was actually larger when shown a big ant and a small house, and were more likely to answer incorrectly or take longer to arrive at a response, the researchers said.

Goldberg said the findings indicate “that something is slowing down the patient and it is not episodic memory but semantic memory.”

The team will continue to study these patients over time to see if these semantic problems get worse as the disease advances.

Filed under alzheimer's disease cognitive impairment memory semantic memory neuroscience science

313 notes

Neural Pointillism: Lighting Up the Brain in Psychedelic Relief

During the last decade, researchers have labored intensively to find new methods to photograph the complex networks of nerve cells that make up the brain and spinal cord, an attempt to overcome the severe limitations of earlier imaging technologies. The emerging science of connectomics, intended to map such connections, will be made possible by deploying these techniques.

In 2007, Jeff Lichtman, Joshua Sanes and colleagues at Harvard University came up with one of the most notable examples of the new brain-cell imaging methods. Brainbow lights up neurons in about 100 different hues, enabling a precise tracking of neural circuitry and synapses, the gaps between brain cells.

Scientists engineer a mouse or another model animal with a gene that randomly causes each neuron to express differing amounts of a red, green or blue fluorescent protein, producing a palette of varying pastel-like colors. Slices of tissue are photographed and recombined to produce detailed imagery of the brain’s structural topography. (The original discovery of what is called green fluorescent protein by Martin Chalfie, Osamu Shinomura and Roger Y. Tsien, from which these new multi-colored fluorescent proteins are derived, was awarded the 2008 Nobel Prize in Chemistry.)

Filed under brain nerve cells neuroimaging brainbow connectomics neuroscience science

53 notes

Virtual Reality and Robotics in Neurosurgery—Promise and Challenges
Robotic technologies have the potential to help neurosurgeons perform precise, technically demanding operations, together with virtual reality environments to help them navigate through the brain, according to a special supplement to Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
"Virtual Reality (VR) and robotics are two rapidly expanding fields with growing application within neurosurgery," according to an introductory article by Garnette Sutherland, MD. The 22 reviews, commentaries, and original studies in the special supplement provide an up-to-the-minute overview of "the benefits and ongoing challenges related to the latest incarnations of these technologies."
Robotics and VR in Neurosurgery—What’s Here and What’s NextVirtual reality and robotic technologies present exciting opportunities for training, planning, and actual performance of neurosurgical procedures. Robotic tools under development or already in use can provide mechanical assistance, such as steadying the surgeon’s hand or “scaling” hand movements. “Current robots work in tandem with human operators to combine the advantages of human thinking with the capabilities of robots to provide data, to optimize localization on a moving subject, to operate in difficult positions, or to perform without muscle fatigue,” writes Dr. Sutherland.
Virtual reality technologies play an important role, providing “spatial orientation” between robotic instruments and the surgeon. Virtual reality environments “recreate the surgical space” in which the surgeon works, providing 3-D visual images as well as haptic (sense of touch) feedback. The ability to plan, rehearse, and “play back” operations in the brain could be particularly valuable for training neurosurgery residents—especially since recent work hour changes have limited opportunities for operating room experience.
The special supplement to Neurosurgery presents authoritative updates by experts working in the field of surgical robotics and VR technology, drawn from a wide range of disciplines. Topics include robotic technologies already in use, such as the “neuroArm” image-guided neurosurgical robot; reviews of progress in areas such as 3-D neurosurgical planning and virtual endoscopy; and new thinking on the best approaches to development, evaluation, and clinical uses of VR and robotic technologies.
But numerous and daunting technical challenges remain to be met before robotic and VR technologies become widely used in clinical neurosurgery. For example, VR environments require extremely fast processing times to provide the surgeon with continuously updated sensory information—equal to or faster than the brain’s ability to perceive it.
Economic challenges include the high costs of developing and implementing VR and robotic technologies, especially in terms of showing that the costs are justified by benefits to the patient. Continued progress in miniaturization will play an important role both in overcoming the technical challenges and in making the technology cost-effective.
The editors of Neurosurgery hope their supplement will stimulate interest and further progress in the development and practical implementation of VR and robotic technologies for neurosurgery. Dr. Sutherland adds, “Collaboration between the fields of medicine, engineering, science, and technology will allow innovations in these fields to converge in new products that will benefit patients with neurosurgical disease.”
(Image courtesy: Imperial College London)

Virtual Reality and Robotics in Neurosurgery—Promise and Challenges

Robotic technologies have the potential to help neurosurgeons perform precise, technically demanding operations, together with virtual reality environments to help them navigate through the brain, according to a special supplement to Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

"Virtual Reality (VR) and robotics are two rapidly expanding fields with growing application within neurosurgery," according to an introductory article by Garnette Sutherland, MD. The 22 reviews, commentaries, and original studies in the special supplement provide an up-to-the-minute overview of "the benefits and ongoing challenges related to the latest incarnations of these technologies."

Robotics and VR in Neurosurgery—What’s Here and What’s Next
Virtual reality and robotic technologies present exciting opportunities for training, planning, and actual performance of neurosurgical procedures. Robotic tools under development or already in use can provide mechanical assistance, such as steadying the surgeon’s hand or “scaling” hand movements. “Current robots work in tandem with human operators to combine the advantages of human thinking with the capabilities of robots to provide data, to optimize localization on a moving subject, to operate in difficult positions, or to perform without muscle fatigue,” writes Dr. Sutherland.

Virtual reality technologies play an important role, providing “spatial orientation” between robotic instruments and the surgeon. Virtual reality environments “recreate the surgical space” in which the surgeon works, providing 3-D visual images as well as haptic (sense of touch) feedback. The ability to plan, rehearse, and “play back” operations in the brain could be particularly valuable for training neurosurgery residents—especially since recent work hour changes have limited opportunities for operating room experience.

The special supplement to Neurosurgery presents authoritative updates by experts working in the field of surgical robotics and VR technology, drawn from a wide range of disciplines. Topics include robotic technologies already in use, such as the “neuroArm” image-guided neurosurgical robot; reviews of progress in areas such as 3-D neurosurgical planning and virtual endoscopy; and new thinking on the best approaches to development, evaluation, and clinical uses of VR and robotic technologies.

But numerous and daunting technical challenges remain to be met before robotic and VR technologies become widely used in clinical neurosurgery. For example, VR environments require extremely fast processing times to provide the surgeon with continuously updated sensory information—equal to or faster than the brain’s ability to perceive it.

Economic challenges include the high costs of developing and implementing VR and robotic technologies, especially in terms of showing that the costs are justified by benefits to the patient. Continued progress in miniaturization will play an important role both in overcoming the technical challenges and in making the technology cost-effective.

The editors of Neurosurgery hope their supplement will stimulate interest and further progress in the development and practical implementation of VR and robotic technologies for neurosurgery. Dr. Sutherland adds, “Collaboration between the fields of medicine, engineering, science, and technology will allow innovations in these fields to converge in new products that will benefit patients with neurosurgical disease.”

(Image courtesy: Imperial College London)

Filed under neuroscience neurosurgery robotics robots virtual reality neuroArm science

160 notes

NCKU unveils i-Transport for the disabled

A new generation of intelligent robot with functions of mobility, lifting, and standing for the disabled called “i-Transport,” which can be adjusted to the user’s height and position while taking stuff or talking to others, has been developed by a National Cheng Kung University (NCKU) research team.

The team was led by Fong-Chin Su and Tain-Song Chen, professors from the NCKU Department of BioMedical Engineering (BME).

This novel smart light-weight robot has aroused great attention and been regarded as a great impact on the biomedical innovation when it was displayed at the recent forum hosted by the Ministry of Education (MOE), Taiwan.

“The invention is definitely a boon for the physically challenged people,” said a student who tried out the equipment Dec. 19 at BME, adding that the weight of the device has become much lighter with greater mobility to help with the daily life of the disabled.

Su pointed out that i-Transport was designed with an embedded health monitoring system for tracking blood pressure and breathing conditions, providing the disabled with the basic pride of standing and moving.

I-Transport is a multi-functional carrier which can help adjust the action of lifting, shifting, standing, moving while also serving as a physiological monitor, thus assisting the disabled to move and stand in order to undertake daily chores, as well as fulfill their desire to move around and meet their demand for independence, added Su.

Chen explained that i-Transport uses Altera FPGA, a newly developed intelligent control chip which has the Nios II embedded multi-core processor for developing software and hardware design of the cart’s control systems.

Filed under robots robotics AI i-Transport disability health monitoring system science

59 notes

Strange behavior: new study exposes living cells to synthetic protein
One approach to understanding components in living organisms is to attempt to create them artificially, using principles of chemistry, engineering and genetics. A suite of powerful techniques—collectively referred to as synthetic biology—have been used to produce self-replicating molecules, artificial pathways in living systems and organisms bearing synthetic genomes. 
In a new twist, John Chaput, a researcher at Arizona State University’s Biodesign Institute and colleagues at the Department of Pharmacology, Midwestern University, Glendale, AZ have fabricated an artificial protein in the laboratory and examined the surprising ways living cells respond to it. 
“If you take a protein that was created in a test tube and put it inside a cell, does it still function,” Chaput asks. “Does the cell recognize it? Does the cell just chew it up and spit it out?” This unexplored area represents a new domain for synthetic biology and may ultimately lead to the development of novel therapeutic agents. 
The research results, reported in the advanced online edition of the journal ACS Chemical Biology, describe a peculiar set of adaptations exhibited by Escherichia coli bacterial cells exposed to a synthetic protein, dubbed DX. Inside the cell, DX proteins bind with molecules of ATP, the energy source required by all biological entities.

Strange behavior: new study exposes living cells to synthetic protein

One approach to understanding components in living organisms is to attempt to create them artificially, using principles of chemistry, engineering and genetics. A suite of powerful techniques—collectively referred to as synthetic biology—have been used to produce self-replicating molecules, artificial pathways in living systems and organisms bearing synthetic genomes. 

In a new twist, John Chaput, a researcher at Arizona State University’s Biodesign Institute and colleagues at the Department of Pharmacology, Midwestern University, Glendale, AZ have fabricated an artificial protein in the laboratory and examined the surprising ways living cells respond to it. 

“If you take a protein that was created in a test tube and put it inside a cell, does it still function,” Chaput asks. “Does the cell recognize it? Does the cell just chew it up and spit it out?” This unexplored area represents a new domain for synthetic biology and may ultimately lead to the development of novel therapeutic agents. 

The research results, reported in the advanced online edition of the journal ACS Chemical Biology, describe a peculiar set of adaptations exhibited by Escherichia coli bacterial cells exposed to a synthetic protein, dubbed DX. Inside the cell, DX proteins bind with molecules of ATP, the energy source required by all biological entities.

Filed under cells living cells artificial protein E. coli cellular systems biology science

51 notes

A model-free way to characterize polymodal ion channel gating
Two studies in The Journal of General Physiology (JGP) help pave the way for a “shortcut” model-free approach to studying activation of “polymodal” ion channels—channels that open in response to multiple stimuli. Transmembrane ion channels respond to various physiological stimuli to regulate numerous cellular functions. Different classes of channels respond to different types of stimuli; some channels, for instance, respond to changes in membrane potential whereas others are activated by ligand binding. Polymodal channels integrate different cellular signals, enabling them to mediate a more precise and flexible physiological response. Understanding the mechanisms involved in polymodal channel activation has been a challenge, however, in part because of the complexity of the models required.
Now, two studies in the January issue of JGP use straightforward thermodynamically rigorous analysis to parse the free energy of polymodal voltage- and ligand-dependent ion channels.
In one study, University of Wisconsin–Madison researchers Sandipan Chowdhury and Baron Chanda examine the BK channel—a channel activated by both changes in membrane potential and calcium binding to an intracellular domain. In the second study, Daniel Sigg (dPET Professional Services) explores gating of polymodal ion channels in general. Specifically, the authors show how to use G-V (conductance-voltage), Q-V (charge-voltage) and conductance vs. ligand concentration measurements to extract the free energies of interaction of the modules of a polymodal channel that respond to these distinct modalities.
This new approach opens the door for a model-independent way to studying ion channel gating, which could be useful both for constraining future atomic-scale models of channel gating, and in understanding the disruptions that result from disease causing genetic mutations.
Chowdhury, S., and B. Chanda. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210860Sigg, D., et al. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210859Yifrach, O. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210929

A model-free way to characterize polymodal ion channel gating

Two studies in The Journal of General Physiology (JGP) help pave the way for a “shortcut” model-free approach to studying activation of “polymodal” ion channels—channels that open in response to multiple stimuli. Transmembrane ion channels respond to various physiological stimuli to regulate numerous cellular functions. Different classes of channels respond to different types of stimuli; some channels, for instance, respond to changes in membrane potential whereas others are activated by ligand binding. Polymodal channels integrate different cellular signals, enabling them to mediate a more precise and flexible physiological response. Understanding the mechanisms involved in polymodal channel activation has been a challenge, however, in part because of the complexity of the models required.

Now, two studies in the January issue of JGP use straightforward thermodynamically rigorous analysis to parse the free energy of polymodal voltage- and ligand-dependent ion channels.

In one study, University of Wisconsin–Madison researchers Sandipan Chowdhury and Baron Chanda examine the BK channel—a channel activated by both changes in membrane potential and calcium binding to an intracellular domain. In the second study, Daniel Sigg (dPET Professional Services) explores gating of polymodal ion channels in general. Specifically, the authors show how to use G-V (conductance-voltage), Q-V (charge-voltage) and conductance vs. ligand concentration measurements to extract the free energies of interaction of the modules of a polymodal channel that respond to these distinct modalities.

This new approach opens the door for a model-independent way to studying ion channel gating, which could be useful both for constraining future atomic-scale models of channel gating, and in understanding the disruptions that result from disease causing genetic mutations.

Chowdhury, S., and B. Chanda. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210860
Sigg, D., et al. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210859
Yifrach, O. 2013. J. Gen. Physiol. doi:10.1085/jgp.201210929

Filed under ion channels polymodal channels channel activation genetic mutations neuroscience science

138 notes

Investigators’ Study Hints That Stem Cells Prepare for Maturity Much Earlier Than Anticipated
Unlike less versatile muscle or nerve cells, embryonic stem cells are by definition equipped to assume any cellular role. Scientists call this flexibility “pluripotency,” meaning that as an organism develops, stem cells must be ready at a moment’s notice to activate highly diverse gene expression programs used to turn them into blood, brain, or kidney cells.
Scientists from the lab of Stowers Investigator Ali Shilatifard, Ph.D., report in the December 27, 2012 online issue of Cell that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA known as “enhancers” required to activate a neighboring gene. Their findings suggest that Ell3 parked at the enhancer of a developmentally regulated gene, even one that is silent, primes it for future expression. This finding is significant as many of these same genes are abnormally switched on in cancer.
“We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances,” says Shilatifard. “But a problem in the field has been how to identify inactive or poised enhancer elements. Our discovery that Ell3 interacts with enhancers in ES cells gives us a hand-hold to identify and to study them.”

Investigators’ Study Hints That Stem Cells Prepare for Maturity Much Earlier Than Anticipated

Unlike less versatile muscle or nerve cells, embryonic stem cells are by definition equipped to assume any cellular role. Scientists call this flexibility “pluripotency,” meaning that as an organism develops, stem cells must be ready at a moment’s notice to activate highly diverse gene expression programs used to turn them into blood, brain, or kidney cells.

Scientists from the lab of Stowers Investigator Ali Shilatifard, Ph.D., report in the December 27, 2012 online issue of Cell that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA known as “enhancers” required to activate a neighboring gene. Their findings suggest that Ell3 parked at the enhancer of a developmentally regulated gene, even one that is silent, primes it for future expression. This finding is significant as many of these same genes are abnormally switched on in cancer.

“We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances,” says Shilatifard. “But a problem in the field has been how to identify inactive or poised enhancer elements. Our discovery that Ell3 interacts with enhancers in ES cells gives us a hand-hold to identify and to study them.”

Filed under stem cells embryonic stem cells pluripotency proteins gene expression science

free counters