Neuroscience

Articles and news from the latest research reports.

100 notes

Suspicions confirmed: Common cause for brain tumors in children An overactive signaling pathway is a common cause in cases of pilocytic astrocytoma, the most frequent type of brain cancer in children. This was discovered by a network of scientists coordinated by the German Cancer Research Center (as part of the International Cancer Genome Consortium, ICGC). In all 96 cases studied, the researchers found defects in genes involved in a particular pathway. Hence, drugs can be used to help affected children by blocking components of the signaling cascade. The project is funded by the German Cancer Aid (Deutsche Krebshilfe) and the Federal Ministry of Education and Research (BMBF). The findings are published in the latest issue of the journal “Nature Genetics”. Brain cancer is the primary cause of cancer mortality in children. Even in cases when the cancer is cured, young patients suffer from the stress of a treatment that can be harmful to the developing brain. In a search for new target structures that would create more gentle treatments, cancer researchers are systematically analyzing all alterations in the genetic material of these tumors. This is the mission of the PedBrain consortium, which was launched in 2010. Led by Professor Stefan Pfister from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), the PedBrain researchers have now published the results of the first 96 genome analyses of pilocytic astrocytomas. Pilocytic astrocytomas are the most common childhood brain tumors. These tumors usually grow very slowly. However, they are often difficult to access by surgery and cannot be completely removed, which means that they can recur. The disease may thus become chronic and have debilitating effects for affected children. In previous work, teams of researchers led by Professor Dr. Stefan Pfister and Dr. David Jones had already discovered characteristic mutations in a major proportion of pilocytic astrocytomas. All of the changes involved a key cellular signaling pathway known as the MAPK signaling cascade. MAPK is an abbreviation for “mitogen-activated protein kinase.” This signaling pathway comprises a cascade of phosphate group additions (phosphorylation) from one protein to the next – a universal method used by cells to transfer messages to the nucleus. MAPK signaling regulates numerous basic biological processes such as embryonic development and differentiation and the growth and death of cells. “A couple of years ago, we had already hypothesized that pilocytic astrocytomas generally arise from a defective activation of MAPK signaling,” says David Jones, first author of the publication. “However, in about one fifth of the cases we had not initially discovered these mutations. In a whole-genome analysis of 96 tumors we have now discovered activating defects in three other genes involved in the MAPK signaling pathway that have not previously been described in astrocytoma.” “Aside from MAPK mutations, we do not find any other frequent mutations that could promote cancer growth in the tumors. This is a very clear indication that overactive MAPK signals are necessary for a pilocytic astrocytoma to develop,” says study director Stefan Pfister. The disease thus is a prototype for rare cancers that are based on defects in a single biological signaling process. In total, the genomes of pilocytic astrocytomas contain far fewer mutations than are found, for example, in medulloblastomas, a much more malignant pediatric brain tumor. This finding is in accordance with the more benign growth behavior of astrocytomas. The number of mutations increases with the age of the affected individuals. About one half of pilocytic astrocytomas develop in the cerebellum, the other 50 percent in various other brain regions. Cerebellar astrocytomas are genetically even more homogenous than other cases of the disease: In 48 out of 49 cases that were studied, the researchers found fusions between the BRAF gene, a central component of the MAPK signaling pathway, and various other fusion partners. “The most important conclusion from our results,” says study director Stefan Pfister, “is that targeted agents for all pilocytic astrocytomas are potentially available to block an overactive MAPK signaling cascade at various points. We might thus in the future be able to also help children whose tumors are difficult to access by surgery.”

Suspicions confirmed: Common cause for brain tumors in children

An overactive signaling pathway is a common cause in cases of pilocytic astrocytoma, the most frequent type of brain cancer in children. This was discovered by a network of scientists coordinated by the German Cancer Research Center (as part of the International Cancer Genome Consortium, ICGC). In all 96 cases studied, the researchers found defects in genes involved in a particular pathway. Hence, drugs can be used to help affected children by blocking components of the signaling cascade. The project is funded by the German Cancer Aid (Deutsche Krebshilfe) and the Federal Ministry of Education and Research (BMBF). The findings are published in the latest issue of the journal “Nature Genetics”.

Brain cancer is the primary cause of cancer mortality in children. Even in cases when the cancer is cured, young patients suffer from the stress of a treatment that can be harmful to the developing brain. In a search for new target structures that would create more gentle treatments, cancer researchers are systematically analyzing all alterations in the genetic material of these tumors. This is the mission of the PedBrain consortium, which was launched in 2010. Led by Professor Stefan Pfister from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), the PedBrain researchers have now published the results of the first 96 genome analyses of pilocytic astrocytomas.

Pilocytic astrocytomas are the most common childhood brain tumors. These tumors usually grow very slowly. However, they are often difficult to access by surgery and cannot be completely removed, which means that they can recur. The disease may thus become chronic and have debilitating effects for affected children.

In previous work, teams of researchers led by Professor Dr. Stefan Pfister and Dr. David Jones had already discovered characteristic mutations in a major proportion of pilocytic astrocytomas. All of the changes involved a key cellular signaling pathway known as the MAPK signaling cascade. MAPK is an abbreviation for “mitogen-activated protein kinase.” This signaling pathway comprises a cascade of phosphate group additions (phosphorylation) from one protein to the next – a universal method used by cells to transfer messages to the nucleus. MAPK signaling regulates numerous basic biological processes such as embryonic development and differentiation and the growth and death of cells.

“A couple of years ago, we had already hypothesized that pilocytic astrocytomas generally arise from a defective activation of MAPK signaling,” says David Jones, first author of the publication. “However, in about one fifth of the cases we had not initially discovered these mutations. In a whole-genome analysis of 96 tumors we have now discovered activating defects in three other genes involved in the MAPK signaling pathway that have not previously been described in astrocytoma.”

“Aside from MAPK mutations, we do not find any other frequent mutations that could promote cancer growth in the tumors. This is a very clear indication that overactive MAPK signals are necessary for a pilocytic astrocytoma to develop,” says study director Stefan Pfister. The disease thus is a prototype for rare cancers that are based on defects in a single biological signaling process.

In total, the genomes of pilocytic astrocytomas contain far fewer mutations than are found, for example, in medulloblastomas, a much more malignant pediatric brain tumor. This finding is in accordance with the more benign growth behavior of astrocytomas. The number of mutations increases with the age of the affected individuals.

About one half of pilocytic astrocytomas develop in the cerebellum, the other 50 percent in various other brain regions. Cerebellar astrocytomas are genetically even more homogenous than other cases of the disease: In 48 out of 49 cases that were studied, the researchers found fusions between the BRAF gene, a central component of the MAPK signaling pathway, and various other fusion partners.

“The most important conclusion from our results,” says study director Stefan Pfister, “is that targeted agents for all pilocytic astrocytomas are potentially available to block an overactive MAPK signaling cascade at various points. We might thus in the future be able to also help children whose tumors are difficult to access by surgery.”

Filed under brain cancer pilocytic astrocytoma brain tumor genes mutations genetics neuroscience science

134 notes

Breakthrough Study Reveals Biological Basis for Sensory Processing Disorders in Kids Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet it receives far less attention partly because it’s never been recognized as a distinct disease. In a groundbreaking new study from UC San Francisco, researchers have found that children affected with SPD have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopmental disorders. One of the reasons SPD has been overlooked until now is that it often occurs in children who also have ADHD or autism, and the disorders have not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists. “Until now, SPD hasn’t had a known biological underpinning,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. “Our findings point the way to establishing a biological basis for the disease that can be easily measured and used as a diagnostic tool,” Mukherjee said. The work is published in the open access online journal NeuroImage:Clinical. ‘Out of Sync’ Kids Sensory processing disorders affect 5 to 16 percent of school-aged children. Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with social interaction. Furthermore, a sound that one day is an irritant can the next day be sought out.  The disease can be baffling for parents and has been a source of much controversy for clinicians, according to the researchers. “Most people don’t know how to support these kids because they don’t fall into a traditional clinical group,” said Elysa Marco, MD, who led the study along with postdoctoral fellow Julia Owen, PhD. Marco is a cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital, ranked among the nation’s best and one of California’s top-ranked centers for neurology and other specialties, according to the 2013-2014 U.S. News & World Report Best Children’s Hospitals survey. “Sometimes they are called the ‘out of sync’ kids. Their language is good, but they seem to have trouble with just about everything else, especially emotional regulation and distraction. In the real world, they’re just less able to process information efficiently, and they get left out and bullied,” said Marco, who treats affected children in her cognitive and behavioral neurology clinic. “If we can better understand these kids who are falling through the cracks, we will not only help a whole lot of families, but we will better understand sensory processing in general. This work is laying the foundation for expanding our research and clinical evaluation of children with a wide range of neurodevelopmental challenges – stretching beyond autism and ADHD,” she said. Imaging the Brain’s White Matter In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. DTI shows the direction of the white matter fibers and the integrity of the white matter. The brain’s white matter is essential for perceiving, thinking and learning. The study examined 16 boys, between the ages of eight and 11, with SPD but without a diagnosis of autism or prematurity, and compared the results with 24 typically developing boys who were matched for age, gender, right- or left-handedness and IQ. The patients’ and control subjects’ behaviors were first characterized using a parent report measure of sensory behavior called the Sensory Profile.  The imaging detected abnormal white matter tracts in the SPD subjects, primarily involving areas in the back of the brain, that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing, including their connections between the left and right halves of the brain.  “These are tracts that are emblematic of someone with problems with sensory processing,” said Mukherjee. “More frontal anterior white matter tracts are typically involved in children with only ADHD or autistic spectrum disorders. The abnormalities we found are focused in a different region of the brain, indicating SPD may be neuroanatomically distinct.”  The researchers found a strong correlation between the micro-structural abnormalities in the white matter of the posterior cerebral tracts focused on sensory processing and the auditory, multisensory and inattention scores reported by parents in the Sensory Profile. The strongest correlation was for auditory processing, with other correlations observed for multi-sensory integration, vision, tactile and inattention. The abnormal microstructure of sensory white matter tracts shown by DTI in kids with SPD likely alters the timing of sensory transmission so that processing of sensory stimuli and integrating information across multiple senses becomes difficult or impossible. “We are just at the beginning, because people didn’t believe this existed,” said Marco. “This is absolutely the first structural imaging comparison of kids with research diagnosed sensory processing disorder and typically developing kids. It shows it is a brain-based disorder and gives us a way to evaluate them in clinic.” Future studies need to be done, she said, to research the many children affected by sensory processing differences who have a known genetic disorder or brain injury related to prematurity.

Breakthrough Study Reveals Biological Basis for Sensory Processing Disorders in Kids

Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet it receives far less attention partly because it’s never been recognized as a distinct disease.

In a groundbreaking new study from UC San Francisco, researchers have found that children affected with SPD have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopmental disorders.

One of the reasons SPD has been overlooked until now is that it often occurs in children who also have ADHD or autism, and the disorders have not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.

“Until now, SPD hasn’t had a known biological underpinning,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. “Our findings point the way to establishing a biological basis for the disease that can be easily measured and used as a diagnostic tool,” Mukherjee said.

The work is published in the open access online journal NeuroImage:Clinical.

‘Out of Sync’ Kids

Sensory processing disorders affect 5 to 16 percent of school-aged children.

Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with social interaction. Furthermore, a sound that one day is an irritant can the next day be sought out.  The disease can be baffling for parents and has been a source of much controversy for clinicians, according to the researchers.

“Most people don’t know how to support these kids because they don’t fall into a traditional clinical group,” said Elysa Marco, MD, who led the study along with postdoctoral fellow Julia Owen, PhD. Marco is a cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital, ranked among the nation’s best and one of California’s top-ranked centers for neurology and other specialties, according to the 2013-2014 U.S. News & World Report Best Children’s Hospitals survey.

“Sometimes they are called the ‘out of sync’ kids. Their language is good, but they seem to have trouble with just about everything else, especially emotional regulation and distraction. In the real world, they’re just less able to process information efficiently, and they get left out and bullied,” said Marco, who treats affected children in her cognitive and behavioral neurology clinic.

“If we can better understand these kids who are falling through the cracks, we will not only help a whole lot of families, but we will better understand sensory processing in general. This work is laying the foundation for expanding our research and clinical evaluation of children with a wide range of neurodevelopmental challenges – stretching beyond autism and ADHD,” she said.

Imaging the Brain’s White Matter

In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. DTI shows the direction of the white matter fibers and the integrity of the white matter. The brain’s white matter is essential for perceiving, thinking and learning.

The study examined 16 boys, between the ages of eight and 11, with SPD but without a diagnosis of autism or prematurity, and compared the results with 24 typically developing boys who were matched for age, gender, right- or left-handedness and IQ. The patients’ and control subjects’ behaviors were first characterized using a parent report measure of sensory behavior called the Sensory Profile. 

The imaging detected abnormal white matter tracts in the SPD subjects, primarily involving areas in the back of the brain, that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing, including their connections between the left and right halves of the brain. 

“These are tracts that are emblematic of someone with problems with sensory processing,” said Mukherjee. “More frontal anterior white matter tracts are typically involved in children with only ADHD or autistic spectrum disorders. The abnormalities we found are focused in a different region of the brain, indicating SPD may be neuroanatomically distinct.” 

The researchers found a strong correlation between the micro-structural abnormalities in the white matter of the posterior cerebral tracts focused on sensory processing and the auditory, multisensory and inattention scores reported by parents in the Sensory Profile. The strongest correlation was for auditory processing, with other correlations observed for multi-sensory integration, vision, tactile and inattention.

The abnormal microstructure of sensory white matter tracts shown by DTI in kids with SPD likely alters the timing of sensory transmission so that processing of sensory stimuli and integrating information across multiple senses becomes difficult or impossible.

“We are just at the beginning, because people didn’t believe this existed,” said Marco. “This is absolutely the first structural imaging comparison of kids with research diagnosed sensory processing disorder and typically developing kids. It shows it is a brain-based disorder and gives us a way to evaluate them in clinic.”

Future studies need to be done, she said, to research the many children affected by sensory processing differences who have a known genetic disorder or brain injury related to prematurity.

Filed under autism ADHD neurodevelopmental disorders white matter neuroimaging neuroscience science

70 notes

New Research Points to Biomarker that Could Track Huntington’s Disease Progression

A hallmark of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s is that by the time symptoms appear, significant brain damage has already occurred—and currently there are no treatments that can reverse it. A team of SRI International researchers has demonstrated that measurements of electrical activity in the brains of mouse models of Huntington’s disease could indicate the presence of disease before the onset of major symptoms. The findings, “Longitudinal Analysis of the Electroencephalogram and Sleep Phenotype in the R6/2 Mouse Model of Huntington’s Disease,” are published in the July 2013 issue of the neurology journal Brain, published by Oxford University Press.

image

SRI researchers led by Stephen Morairty, Ph.D., a director in the Center for Neuroscience in SRI Biosciences, and Simon Fisher, Ph.D., a postdoctoral fellow at SRI, used electroencephalography (EEG), a noninvasive method commonly used in humans, to measure changes in neuronal electrical activity in a mouse model of Huntington’s disease. Identification of significant changes in the EEG prior to the onset of symptoms would add to evidence that the EEG can be used to identify biomarkers to screen for the presence of a neurodegenerative disease. Further research on such potential biomarkers might one day enable the tracking of disease progression in clinical trials and could facilitate drug development.

“EEG signals are composed of different frequency bands such as delta, theta and gamma, much as light is composed of different frequencies that result in the colors we call red, green and blue,” explained Thomas Kilduff, Ph.D., senior director, Center for Neuroscience, SRI Biosciences. “Our research identified abnormalities in all three of these bands in Huntington’s disease mice. Importantly, the activity in the theta and gamma bands slowed as the disease progressed, indicating that we may be tracking the underlying disease process.”

EEG has shown promise as an indicator of underlying brain dysfunction in neurodegenerative diseases, which otherwise occurs surreptitiously until symptoms appear. Until now, most investigations of EEG in patients with neurodegenerative diseases and in animal models of neurodegenerative diseases have shown significant changes in EEG patterns only after disease symptoms occurred.

“Our breakthrough is that we have found an EEG signature that appears to be a biomarker for the presence of disease in this mouse model of Huntington’s disease that can identify early changes in the brain prior to the onset of behavioral symptoms,” said Morairty, the paper’s senior author. “While the current study focused on Huntington’s disease, many neurodegenerative diseases produce changes in the EEG that are associated with the degenerative process. This is the first step in being able to use the EEG to predict both the presence and progression of neurodegenerative diseases.”

Although previous studies have shown there are distinct and extensive changes in EEG patterns in Alzheimer’s and Huntington’s disease patients, researchers are looking for changes that may occur decades before disease onset.

Huntington’s disease is an inherited disorder that causes certain nerve cells in the brain to die, resulting in motor dysfunction, cognitive decline and psychiatric symptoms. It is the only major neurodegenerative disease where the cause is known with certainty: a genetic mutation that produces a change in a protein that is toxic to neurons.

(Source: sri.com)

Filed under neurodegenerative diseases huntington's disease neuronal activity biomarkers animal model neuroscience science

44 notes

Brain and eye combined monitoring breakthrough could lead to fewer road accidents

Latest advances in capturing data on brain activity and eye movement are being combined to open up a host of ‘mindreading’ possibilities for the future. These include the potential development of a system that can detect when drivers are in danger of falling asleep at the wheel.

image

The research has been undertaken at the University of Leicester with funding from the Engineering and Physical Sciences Research Council (EPSRC), and in collaboration with the University of Buenos Aires in Argentina.

The breakthrough involves bringing two recent developments in the world of technology together: high-speed eye tracking that records eye movements in unprecedented detail using cutting-edge infra-red cameras*; and high-density electroencephalograph** (EEG) technology that measures electrical brain activity with millisecond precision through electrodes placed on the scalp.

The research has overcome previous technological challenges which made it difficult to monitor eye movement and brain activity simultaneously. The team has done this by developing novel signal processing techniques.

This could be the first step towards a system that combines brain and eye monitoring to automatically alert drivers who are showing signs of drowsiness. The system would be built into the vehicle and connected unobtrusively to the driver, with the EEG looking out for brain signals that only occur in the early stages of sleepiness. The eye tracker would reinforce this by looking for erratic gaze patterns symptomatic of someone starting to feel drowsy and different from those characteristic of someone driving who is constantly looking out for hazards. Fatigue has been estimated to account for around 20 per cent of traffic accidents on the UK’s motorways.***

The breakthrough achieved by the University of Leicester could also ultimately be built on to deliver many other everyday applications in the years ahead. For example:

  • Computer games of the future could dispense with the need for the player to physically interact with any type of console, mouse or other hand-operated system. Instead, eye movement and brain activity data would be collected and processed to indicate what action the player wants to take. By distinguishing the tiny differences in various types of brain activity, the EEG would identify the precise action the player desires (e.g. run, jump or throw), while the eye movement data would show exactly where on the screen the player was looking when they had this thought. This information could be combined to enable the correct action to occur. An unobtrusive headset would be all that would be required to capture the necessary data.
  • People who have no arm functionality could move their wheelchairs simply through their eye movements. These movements could be tracked and the corresponding brain activity analysed to identify when these indicate a desire to move in a certain direction. This would then automatically activate a steering and propulsion mechanism that would drive the wheelchair to that place.
  • The breakthrough could also provide the basis for improved tests to diagnose dyslexia and other reading disorders. Current tests revolve around a rapid succession of single words flashed onto a computer screen, with the resulting brain activity monitored by EEG. The new technique could enable the person being tested to move their eyes and read longer passages of text in a natural way, making the tests much more realistic and revealing.
  • With the basic concept now demonstrated successfully, the team aim to continue their work and eventually develop software that, in real time, automatically monitors both eye movement and brain activity.
  • Dr Matias Ison, who has led the research, says: “Historically, eye-tracking and EEG have evolved as independent fields. We have managed to overcome the challenges that were standing in the way of integrating these technologies. This is already leading to a much better understanding of how the brain responds when the eyes are moving. Monitoring the alertness of drivers is just one of many potential applications for this work. Building on the foundation provided by our EPSRC-funded project, we hope to see the first of these starting to become feasible within the next three to five years.”

(Source: epsrc.ac.uk)

Filed under brain activity eye movement eye tracking EEG neuroscience science

107 notes

How well can you see with your ears? Device offers new alternative to blind people A device that trains the brain to turn sounds into images could be used as an alternative to invasive treatment for blind and partially-sighted people, researchers at the University of Bath have found. The vOICe sensory substitution device is a revolutionary tool that helps blind people to use sounds to build an image in their minds of the things around them. A research team, led by Dr Michael Proulx, from the University’s Department of Psychology, looked at how blindfolded sighted participants responded to an eye test using the device. They were asked to perform a standard eye chart test called the Snellen Tumbling E test, which asked participants to view the letter E turned in four different directions and in various sizes. Normal, best-corrected visual acuity is considered 20/20, calculated in terms of the distance (in feet) and the size of the E on the eye chart. The participants, even without any training in the use of the device, were able to perform the best performance possible, nearly 20/400. This limit appears to be the highest resolution currently possible with the ever-improving technology. Dr Michael Proulx said: “This level of visual performance exceeds that of the current invasive techniques for vision restoration, such as stem cell implants and retinal prostheses after extensive training. "A recent study found successful vision at a level of 20/800 after the use of stem cells. Although this might improve with time and provide the literal sensation of sight, the affordable and non-invasive nature of The vOICe provides another option. "Sensory substitution devices are not only an alternative, but might also be best employed in combination with such invasive techniques to train the brain to see again or for the first time."

How well can you see with your ears? Device offers new alternative to blind people

A device that trains the brain to turn sounds into images could be used as an alternative to invasive treatment for blind and partially-sighted people, researchers at the University of Bath have found.

The vOICe sensory substitution device is a revolutionary tool that helps blind people to use sounds to build an image in their minds of the things around them.

A research team, led by Dr Michael Proulx, from the University’s Department of Psychology, looked at how blindfolded sighted participants responded to an eye test using the device.

They were asked to perform a standard eye chart test called the Snellen Tumbling E test, which asked participants to view the letter E turned in four different directions and in various sizes. Normal, best-corrected visual acuity is considered 20/20, calculated in terms of the distance (in feet) and the size of the E on the eye chart.

The participants, even without any training in the use of the device, were able to perform the best performance possible, nearly 20/400. This limit appears to be the highest resolution currently possible with the ever-improving technology.

Dr Michael Proulx said: “This level of visual performance exceeds that of the current invasive techniques for vision restoration, such as stem cell implants and retinal prostheses after extensive training.

"A recent study found successful vision at a level of 20/800 after the use of stem cells. Although this might improve with time and provide the literal sensation of sight, the affordable and non-invasive nature of The vOICe provides another option.

"Sensory substitution devices are not only an alternative, but might also be best employed in combination with such invasive techniques to train the brain to see again or for the first time."

Filed under vOICe sensory substitution blindness sensory substitution device acuity neuroscience science

90 notes

New tissue engineering breakthrough encourages nerve repair

A new combination of tissue engineering techniques could reduce the need for nerve grafts, according to new research by The Open University. Regeneration of nerves is challenging when the damaged area is extensive, and surgeons currently have to take a nerve graft from elsewhere in the body, leaving a second site of damage. Nerve grafts contain aligned tissue structures and Schwann cells that support and guide neuron growth through the damaged area, encouraging function to be restored. The research, published in Biomaterials, reported a way to manufacture artificial nerve tissue with the potential to be used as an alternative to nerve grafts.

Pieces of Engineered Neural Tissue (EngNT) are formed by controlling natural Schwann cell behaviour in a three-dimensional collagen gel so that the cells elongate and align, then a stabilisation process removes excess fluid to leave robust artificial tissues. These living biomaterials contain aligned Schwann cells in an aligned collagen environment, recreating key features of normal nerve tissue.

Incorrect orientation of regenerating nerve cells can lead to delays in repair, scarring and poor restoration of nerve function. Much research has taken place into how support cells (Schwann cells) can be combined with materials to guide nerve regeneration. The new technology from The Open University avoids the use of synthetic materials by building neural tissue from collagen, a protein that is abundant in normal nerve tissue. Building the artificial tissue from natural proteins and directing the cellular alignment using normal cell-material interactions means the EngNT can integrate effectively at the repair site.

Dr James Phillips, Lecturer in Health Sciences at The Open University, said: “We previously reported how self-alignment of Schwann cells could be achieved by using a tethered collagen hydrogel, which exploited cells’ natural ability to orientate in the appropriate direction by using their internal contraction forces. Our current research shows that cell-alignment in the hydrogel can be stabilised using plastic compression. The compression removes fluid from the gels, leaving a strong and stable aligned structure that has many features in common with nerve tissue.”

The team incorporated Schwann cells within the aligned material to form artificial neural tissue that could potentially be used in peripheral nerve repair. The technique could be applied to other regenerative medicine scenarios, where a stable artificial tissue containing aligned cellular architecture would be of benefit.

(Source: www3.open.ac.uk)

Filed under tissue engineering artificial nerve tissue schwann cells nerve cells neuroscience science

88 notes

Researchers Investigate Mechanism of Alzheimer’s Therapy Researchers at the University of Kentucky Sanders-Brown Center on Aging, led by faculty member Donna Wilcock, have recently published a new paper in the Journal of Neuroscience detailing an advance in treatment of Alzheimer’s disease. Gammagard™ IVIg is a therapy that has been investigated for treatment of Alzheimer’s. Despite small clinical studies that have reported efficacy of the approach, the mechanism of action is poorly understood. The UK researchers set out to investigate the mechanism by which the treatment may act in the brain to lower amyloid deposition (amyloid deposits being a key pathology in Alzheimer’s). To conduct their investigation, researchers introduced IVIg directly into the brains of mice which carry a human gene causing them to develop amyloid plaques. They found that IVIg lowers amyloid deposits in the brains of the mice over the course of seven days. Their data suggest that the modulation of inflammation in the brain by IVIg is a key event that leads to the reduction in amyloid deposition. The scientists hypothesize that the IVIg acts as an immune modulator, and this immune modulation is responsible for the reductions in amyloid pathology. The data suggests that modulating the immune response in the brain may help ameliorate the Alzheimer’s pathology. Researchers are currently investigating other ways to produce the same modulation of the immune response because the access of IVIg to the brain when administered peripherally is very limited.

Researchers Investigate Mechanism of Alzheimer’s Therapy

Researchers at the University of Kentucky Sanders-Brown Center on Aging, led by faculty member Donna Wilcock, have recently published a new paper in the Journal of Neuroscience detailing an advance in treatment of Alzheimer’s disease.

Gammagard™ IVIg is a therapy that has been investigated for treatment of Alzheimer’s. Despite small clinical studies that have reported efficacy of the approach, the mechanism of action is poorly understood.

The UK researchers set out to investigate the mechanism by which the treatment may act in the brain to lower amyloid deposition (amyloid deposits being a key pathology in Alzheimer’s).

To conduct their investigation, researchers introduced IVIg directly into the brains of mice which carry a human gene causing them to develop amyloid plaques. They found that IVIg lowers amyloid deposits in the brains of the mice over the course of seven days. Their data suggest that the modulation of inflammation in the brain by IVIg is a key event that leads to the reduction in amyloid deposition.

The scientists hypothesize that the IVIg acts as an immune modulator, and this immune modulation is responsible for the reductions in amyloid pathology.

The data suggests that modulating the immune response in the brain may help ameliorate the Alzheimer’s pathology. Researchers are currently investigating other ways to produce the same modulation of the immune response because the access of IVIg to the brain when administered peripherally is very limited.

Filed under alzheimer's disease brain inflammation dementia amyloid deposition neuroscience science

102 notes

University experts spot early signs of Alzheimer’s Early signs of Alzheimer’s disease can be detected years before diagnosis, according to researchers at Birmingham City University. The study found that sufferers of a specific type of cognitive impairment have an increased loss of cells in certain parts of the brain, which can be vital in detecting which patients will progress to a diagnosis of Alzheimer’s. A team of researchers from Birmingham City University (UK), in association with colleagues from Lanzhou University (China) and the Alzheimer’s Disease Neuroimaging Initiative, conducted a brain scan analysis over two years, of patients suffering from amnestic mild cognitive impairment (aMCI) – a condition involving the diminishing of cognitive abilities, from which 80% of patients progress to a diagnosis of Alzheimer’s. Scans showed that the loss of grey matter in the left hemisphere of the brain was particularly widespread and degenerative for those patients at high risk of developing Alzheimer’s, compared with those with no active neurological disorders. This region of the brain has been associated with language, decision making, expressing personality, executing movement, planning complex cognitive behaviour and moderating social behaviour.  One of the researchers involved in the study, Professor Mike Jackson, from Birmingham City University, said: “Continuous loss of cells within the regions of the brain highlighted in this study should act as alarm bells for doctors, as they may indicate that the patient is on course to developing Alzheimer’s.” The brains parahippocampal gyrus, a region which is known to be related to memory encoding and retrieval, was highlighted as an area that should be looked at carefully when examining brain scans to detect early signs of the disease. Treating Alzheimer’s early is thought to be vital to prevent damage to memory and thinking. Although treatments are available to temporarily ease symptoms, there has been little in the way of success in slowing down the cognitive decline in patients with mild to moderate Alzheimer’s, which has been partly put down to the late timing of the diagnosis. Experts at Birmingham City University hope that this study will aid other researchers to find an effective clinical treatment to delay the conversion to Alzheimer’s.

University experts spot early signs of Alzheimer’s

Early signs of Alzheimer’s disease can be detected years before diagnosis, according to researchers at Birmingham City University.

The study found that sufferers of a specific type of cognitive impairment have an increased loss of cells in certain parts of the brain, which can be vital in detecting which patients will progress to a diagnosis of Alzheimer’s.

A team of researchers from Birmingham City University (UK), in association with colleagues from Lanzhou University (China) and the Alzheimer’s Disease Neuroimaging Initiative, conducted a brain scan analysis over two years, of patients suffering from amnestic mild cognitive impairment (aMCI) – a condition involving the diminishing of cognitive abilities, from which 80% of patients progress to a diagnosis of Alzheimer’s.

Scans showed that the loss of grey matter in the left hemisphere of the brain was particularly widespread and degenerative for those patients at high risk of developing Alzheimer’s, compared with those with no active neurological disorders.

This region of the brain has been associated with language, decision making, expressing personality, executing movement, planning complex cognitive behaviour and moderating social behaviour. 

One of the researchers involved in the study, Professor Mike Jackson, from Birmingham City University, said: “Continuous loss of cells within the regions of the brain highlighted in this study should act as alarm bells for doctors, as they may indicate that the patient is on course to developing Alzheimer’s.”

The brains parahippocampal gyrus, a region which is known to be related to memory encoding and retrieval, was highlighted as an area that should be looked at carefully when examining brain scans to detect early signs of the disease.

Treating Alzheimer’s early is thought to be vital to prevent damage to memory and thinking. Although treatments are available to temporarily ease symptoms, there has been little in the way of success in slowing down the cognitive decline in patients with mild to moderate Alzheimer’s, which has been partly put down to the late timing of the diagnosis.

Experts at Birmingham City University hope that this study will aid other researchers to find an effective clinical treatment to delay the conversion to Alzheimer’s.

Filed under alzheimer's disease cognitive impairment grey matter memory parahippocampal gyrus neuroscience science

50 notes

Robot mom would beat robot butler in popularity contest If you tickle a robot, it may not laugh, but you may still consider it humanlike — depending on its role in your life, reports an international group of researchers. Designers and engineers assign robots specific roles, such as servant, caregiver, assistant or playmate. Researchers found that people expressed more positive feelings toward a robot that would take care of them than toward a robot that needed care. "For robot designers, this means greater emphasis on role assignments to robots,” said S. Shyam Sundar, Distinguished Professor of Communications at Penn State and co-director of University’s Media Effects Research Laboratory. “How the robot is presented to users can send important signals to users about its helpfulness and intelligence, which can have consequences for how it is received by end users.” To determine how human perception of a robot changed based on its role, researchers observed 60 interactions between college students and Nao, a social robot developed by Aldebaran Robotics, a French company specializing in humanoid robots. Each interaction could go one of two ways. The human could help Nao calibrate its eyes, or Nao could examine the human’s eyes like a concerned eye doctor and make suggestions to improve vision. Participants then filled out a questionnaire about their feelings toward Nao. Researchers used these answers to calculate the robot’s perceived benefit and social presence in both scenarios. They published their results in the current issue of Computers in Human Behavior. "When (humans) perceive greater benefit from the robot, they are more satisfied in their relationship with it, and even trust it more," Sundar said. "In addition, we found that when the robot cares for you, it seems to have greater social presence." A robot with a strong social presence behaves and interacts like an authentic human, according to Ki Joon Kim, doctoral candidate in the department of interaction science, Sungkyunkwan University, Korea, and lead author of the journal article. The research team found that when participants perceived a strong social presence, they considered the caregiving robot smarter than the robot in the alternate scenario. Participants were also more likely to attribute human qualities to the caregiving robot. "Social presence is particularly important in human-robot interactions and areas of artificial intelligence because the ultimate goal of designing and interacting with social robots is to provide users with strong feelings of socialness,” said Kim. The next immediate goal is to confirm these experimental findings in real-life situations where caretaker robots are already working. Examining how other robot roles influence human perception toward them is also important. "We have just finished collecting data at a local retirement village in State College with the Homemate robot which we brought in from Korea,” said Sundar. “In that study, we are examining differences in user reactions to a robot that is an assistant versus one that is framed as a companion.”

Robot mom would beat robot butler in popularity contest

If you tickle a robot, it may not laugh, but you may still consider it humanlike — depending on its role in your life, reports an international group of researchers.

Designers and engineers assign robots specific roles, such as servant, caregiver, assistant or playmate. Researchers found that people expressed more positive feelings toward a robot that would take care of them than toward a robot that needed care.

"For robot designers, this means greater emphasis on role assignments to robots,” said S. Shyam Sundar, Distinguished Professor of Communications at Penn State and co-director of University’s Media Effects Research Laboratory. “How the robot is presented to users can send important signals to users about its helpfulness and intelligence, which can have consequences for how it is received by end users.”

To determine how human perception of a robot changed based on its role, researchers observed 60 interactions between college students and Nao, a social robot developed by Aldebaran Robotics, a French company specializing in humanoid robots.

Each interaction could go one of two ways. The human could help Nao calibrate its eyes, or Nao could examine the human’s eyes like a concerned eye doctor and make suggestions to improve vision.

Participants then filled out a questionnaire about their feelings toward Nao. Researchers used these answers to calculate the robot’s perceived benefit and social presence in both scenarios. They published their results in the current issue of Computers in Human Behavior.

"When (humans) perceive greater benefit from the robot, they are more satisfied in their relationship with it, and even trust it more," Sundar said. "In addition, we found that when the robot cares for you, it seems to have greater social presence."

A robot with a strong social presence behaves and interacts like an authentic human, according to Ki Joon Kim, doctoral candidate in the department of interaction science, Sungkyunkwan University, Korea, and lead author of the journal article.

The research team found that when participants perceived a strong social presence, they considered the caregiving robot smarter than the robot in the alternate scenario. Participants were also more likely to attribute human qualities to the caregiving robot.

"Social presence is particularly important in human-robot interactions and areas of artificial intelligence because the ultimate goal of designing and interacting with social robots is to provide users with strong feelings of socialness,” said Kim.

The next immediate goal is to confirm these experimental findings in real-life situations where caretaker robots are already working. Examining how other robot roles influence human perception toward them is also important.

"We have just finished collecting data at a local retirement village in State College with the Homemate robot which we brought in from Korea,” said Sundar. “In that study, we are examining differences in user reactions to a robot that is an assistant versus one that is framed as a companion.”

Filed under human-robot interaction AI robotics robots psychology neuroscience science

91 notes

Peering into the Protein Pathways of a Cell As a cell’s central power plant, the mitochondrion is a busy place. Specially-coded proteins from the nucleus are constantly being ferried across the mitochondrion’s inner membrane, where they help the mighty organelle do its work – producing the cell’s high-energy molecules, carrying out signaling duties, and controlling cell growth. Scientists have long known that the central channel through which most of these proteins must pass – a critical gatekeeper known as the translocase of the inner mitochondrial membrane 23 or TIM23 for short – requires an electrical field for its gating capabilities to function. But they weren’t quite sure how the whole process worked. Until now. Using highly sensitive fluorescent probes, a team of scientists based at UConn has managed to peer deep into the inner workings of a cell, capturing the never-before-seen structural dynamics of the TIM23 channel complex while it functioned in its natural environment. In doing so, the team, led by Nathan N. Alder, an assistant professor in the Department of Molecular and Cell Biology in the College of Liberal Arts and Sciences, discovered that the TIM23 complex not only opens and closes in response to fluctuations in the energized state of the mitochondrion’s inner membrane, as the scientific community suspected, it also changes its very structure – altering the helical shape of protein segments that line the channel – as the electrical field across the membrane drops. The research, which appears this week in the peer-reviewed journal Nature Structural & Molecular Biology, explains how the energized state of the membrane drives the structural dynamics of membrane proteins and sheds new light on how cellular transport systems harness energy to perform their work inside the cell. It also shows how fluorescent mapping at the subcellular level may reveal new insights into the underlying causes of neurodegenerative and metabolic disorders associated with mitochondrial function. In an overview of the research accompanying the paper’s publication, Nikolaus Pfanner of the University of Freiburg, Germany, an international leader in the field of cellular protein trafficking, and several members of his research group, called the study “a major step towards a molecular understanding of a voltage-gated protein translocase.” “The molecular nature of voltage sensors in membrane proteins is a central question in biochemical research,” Pfanner and his colleagues said. “The study … is not only of fundamental importance for our understanding of mitochondrial biogenesis, but also opens up new perspectives in the search for voltage-responsive elements in membrane proteins.” Applying a new technique The fluorescent mapping technique used in the research was a key to the project’s success. Alder says he first realized the application’s potential when he successfully mapped channel proteins in a functioning mitochondrion in 2008. In the current study, he advanced the process further, using probes to capture the behavior of a particular segment of the TIM23 channel complex as it was impacted by voltage changes in the membrane’s electrical field. “Fluorescent mapping made this possible,” says Alder, who, as a post-doctoral student, worked with protein fluorescent labeling pioneer Arthur E. Johnson of Texas A&M’s Health Science Center. “It allowed us to peer into the functioning dynamics of a protein import channel complex that is responsible for building up the power plant of the cell … What we found was that these protein-trafficking complexes are certainly not static. This is a very, very dynamic channel.” To monitor the fluorescence probes inside the mitochondria, the research team used advanced spectrofluorimeters equipped with xenon lamps and laser diodes to measure steady-state and time-resolved fluorescence, respectively. To conduct the study, Alder incorporated cysteine residues modified with a fluorescent probe at specific positions along a transmembrane segment of a TIM23 complex derived from a common species of yeast, Saccharomyces cerevisiae. The team then monitored the probes in real time to observe how the channel’s voltage-gating and structure responded to induced changes in the inner membrane’s electrical field. “It’s an indirect way of looking at the structure of something, but because we are able to look into an actually functioning mitochondrion, it’s given us a whole world of new information,” says Alder. “That the magnitude of the voltage gradient across the membrane could play a significant role in defining the structure of these proteins is probably one of the most significant elements of this research,” he adds. A defining moment Watching the process was, for Alder, a defining moment in his professional career. “When I first saw a certain kind of structure that told me I was in the middle of a channel, that was one of the most exciting times in my professional life,” he says. “I knew I was getting insight into a fundamental natural phenomenon, something no one has ever seen before.” When Alder saw the protein-conducting channel bending and collapsing in response to changes in the membrane’s voltage levels, he was equally thrilled. “That was one of those rare technical moments in my professional life that showed we were really getting insight into a fundamental process going on inside a cell,” he says. “It’s always been known that you need an energized membrane to make these channels work, but no one had a clue why.” Joining Alder on the project were UConn graduate students Ketan Malhotra and Murugappan Sathappa and research associate Judith S. Landin. Johnson, Alder’s former mentor at Texas A&M, is also listed as a co-author. The work in the Alder Lab was funded by the National Science Foundation; work done in the Johnson Lab was additionally sponsored by the National Institutes of Health and the Robert A. Welch Foundation. Alder says the next phase of the research will look toward isolating the TIM23 protein channel complex in an artificial system to see if it continues to respond to voltage fluctuations outside of its natural habitat. The research team is also hoping to identify the particular parts of the protein complex that are acting as voltage sensors. “Once we start to identify exactly what is the voltage sensor, we will have a better understanding of the translocase process, and ultimately we can apply this knowledge to other kinds of protein transporters whose dysfunction has been implicated in the etiology of diseases such as cardiovascular disease and cancer,” Alder says. “If their function is tied to the energized state of the membrane, we’ll be able to see whether defects in that ability to couple to the membrane might be associated with the pathogenesis of these diseases.”

Peering into the Protein Pathways of a Cell

As a cell’s central power plant, the mitochondrion is a busy place.

Specially-coded proteins from the nucleus are constantly being ferried across the mitochondrion’s inner membrane, where they help the mighty organelle do its work – producing the cell’s high-energy molecules, carrying out signaling duties, and controlling cell growth.

Scientists have long known that the central channel through which most of these proteins must pass – a critical gatekeeper known as the translocase of the inner mitochondrial membrane 23 or TIM23 for short – requires an electrical field for its gating capabilities to function. But they weren’t quite sure how the whole process worked.

Until now.

Using highly sensitive fluorescent probes, a team of scientists based at UConn has managed to peer deep into the inner workings of a cell, capturing the never-before-seen structural dynamics of the TIM23 channel complex while it functioned in its natural environment.

In doing so, the team, led by Nathan N. Alder, an assistant professor in the Department of Molecular and Cell Biology in the College of Liberal Arts and Sciences, discovered that the TIM23 complex not only opens and closes in response to fluctuations in the energized state of the mitochondrion’s inner membrane, as the scientific community suspected, it also changes its very structure – altering the helical shape of protein segments that line the channel – as the electrical field across the membrane drops.

The research, which appears this week in the peer-reviewed journal Nature Structural & Molecular Biology, explains how the energized state of the membrane drives the structural dynamics of membrane proteins and sheds new light on how cellular transport systems harness energy to perform their work inside the cell. It also shows how fluorescent mapping at the subcellular level may reveal new insights into the underlying causes of neurodegenerative and metabolic disorders associated with mitochondrial function.

In an overview of the research accompanying the paper’s publication, Nikolaus Pfanner of the University of Freiburg, Germany, an international leader in the field of cellular protein trafficking, and several members of his research group, called the study “a major step towards a molecular understanding of a voltage-gated protein translocase.”

“The molecular nature of voltage sensors in membrane proteins is a central question in biochemical research,” Pfanner and his colleagues said. “The study … is not only of fundamental importance for our understanding of mitochondrial biogenesis, but also opens up new perspectives in the search for voltage-responsive elements in membrane proteins.”

Applying a new technique

The fluorescent mapping technique used in the research was a key to the project’s success. Alder says he first realized the application’s potential when he successfully mapped channel proteins in a functioning mitochondrion in 2008. In the current study, he advanced the process further, using probes to capture the behavior of a particular segment of the TIM23 channel complex as it was impacted by voltage changes in the membrane’s electrical field.

“Fluorescent mapping made this possible,” says Alder, who, as a post-doctoral student, worked with protein fluorescent labeling pioneer Arthur E. Johnson of Texas A&M’s Health Science Center. “It allowed us to peer into the functioning dynamics of a protein import channel complex that is responsible for building up the power plant of the cell … What we found was that these protein-trafficking complexes are certainly not static. This is a very, very dynamic channel.”

To monitor the fluorescence probes inside the mitochondria, the research team used advanced spectrofluorimeters equipped with xenon lamps and laser diodes to measure steady-state and time-resolved fluorescence, respectively.

To conduct the study, Alder incorporated cysteine residues modified with a fluorescent probe at specific positions along a transmembrane segment of a TIM23 complex derived from a common species of yeast, Saccharomyces cerevisiae. The team then monitored the probes in real time to observe how the channel’s voltage-gating and structure responded to induced changes in the inner membrane’s electrical field.

“It’s an indirect way of looking at the structure of something, but because we are able to look into an actually functioning mitochondrion, it’s given us a whole world of new information,” says Alder.

“That the magnitude of the voltage gradient across the membrane could play a significant role in defining the structure of these proteins is probably one of the most significant elements of this research,” he adds.

A defining moment

Watching the process was, for Alder, a defining moment in his professional career.

“When I first saw a certain kind of structure that told me I was in the middle of a channel, that was one of the most exciting times in my professional life,” he says. “I knew I was getting insight into a fundamental natural phenomenon, something no one has ever seen before.”

When Alder saw the protein-conducting channel bending and collapsing in response to changes in the membrane’s voltage levels, he was equally thrilled.

“That was one of those rare technical moments in my professional life that showed we were really getting insight into a fundamental process going on inside a cell,” he says. “It’s always been known that you need an energized membrane to make these channels work, but no one had a clue why.”

Joining Alder on the project were UConn graduate students Ketan Malhotra and Murugappan Sathappa and research associate Judith S. Landin. Johnson, Alder’s former mentor at Texas A&M, is also listed as a co-author. The work in the Alder Lab was funded by the National Science Foundation; work done in the Johnson Lab was additionally sponsored by the National Institutes of Health and the Robert A. Welch Foundation.

Alder says the next phase of the research will look toward isolating the TIM23 protein channel complex in an artificial system to see if it continues to respond to voltage fluctuations outside of its natural habitat. The research team is also hoping to identify the particular parts of the protein complex that are acting as voltage sensors.

“Once we start to identify exactly what is the voltage sensor, we will have a better understanding of the translocase process, and ultimately we can apply this knowledge to other kinds of protein transporters whose dysfunction has been implicated in the etiology of diseases such as cardiovascular disease and cancer,” Alder says. “If their function is tied to the energized state of the membrane, we’ll be able to see whether defects in that ability to couple to the membrane might be associated with the pathogenesis of these diseases.”

Filed under mitochondria membrane potential neurodegenerative diseases synaptic plasticity neuroscience science

free counters