#Planarian Regeneration Model Discovered by Artificial intelligence An artificial intelligence system has for the first time reverse-engineered the regeneration mechanism of planariahe small worms
whose extraordinary power to regrow body parts has made them a research model in human regenerative medicine. The discovery by Tufts University biologists presents the first model of regeneration discovered by a nonhuman intelligence and the first comprehensive model of planarian regeneration,
which had eluded human scientists for over 100 years. The work, published in the June 4, 2015, issue of PLOS Computational biology, demonstrates how obot sciencecan help human scientists in the future.
In order to bioengineer complex organs scientists need to understand the mechanisms by which those shapes are produced normally by the living organism.
However, a significant knowledge gap persists between molecular genetic components identified as being necessary to produce a particular organism shape
and understanding how and why that particular complex shape is generated in the correct size, shape and orientation, said the paper senior author, Michael Levin, Ph d,
. Vannevar bush professor of biology and director of the Tufts Center for Regenerative and Developmental biology. ost regenerative models today derived from genetic experiments are arrow diagrams,
showing which gene regulates which other gene. That fine but it doesn tell you what the ultimate shape will be.
in order to know what triggers could be applied to such a system to cause regeneration of particular components,
However, no such tools yet exist for mining the fast-growing mountain of published experimental data in regeneration
and developmental biology, said the paper first author, Daniel Lobo, Ph d, . postdoctoral fellow in the Levin lab. To address this challenge,
Lobo and Levin developed an algorithm that would use evolutionary computation to produce regulatory networks able to volveto accurately predict the results of published laboratory experiments that the researchers entered into a database. ur goal was to identify a regulatory network that could be executed in every cell
so that the head-tail patterning outcomes of simulated experiments would match the published data, Lobo said.
Tufts biologists devloped an algorithm that used evolutionary computation to produce regulatory networks able to volveto accurately predict the results of published research on planarian regeneration.
The algorithm compared the resulting shape from the simulation with real published data in the database.
gradually the new networks could explain more experiments in the database comprising most of the known planarian experimental literature regarding head vs. tail regeneration.
First Regenerative Model Discovered by Artificial intelligence The researchers ultimately applied the algorithm to a combined experimental dataset of 16 key planarian regeneration experiments to determine
After 42 hours, the algorithm returned the discovered regulatory network, which correctly predicted all 16 experiments in the dataset.
and is the first regenerative model discovered by artificial intelligence, said Levin. Lobo and Levin are trained both in computer science
and bring an unusual perspective to the field of developmental biology. Levin majored in computer science and biology at Tufts before earning his Ph d. in genetics.
Lobo earned a Ph d. in the field before joining the Levin lab. The paper represents a successful application of the growing field of obot sciencewhich Levin says can help human researchers by doing much more than crunch enormous datasets quickly. hile
the artificial intelligence in this project did have to do a whole lot of computations, the outcome is a theory of
what the worm is doing, and coming up with theories of what going on in nature is pretty much the most creative, intuitive aspect of the scientist job,
Levin said. ne of the most remarkable aspects of the project was that the model it found was not a hopelessly-tangled network that no human could actually understand,
All this suggests to me that artificial intelligence can help with every aspect of science, not only data mining but also inference of meaning of the data. n
#Injectable Device Delivers a Nano-View of the Brain Promise against disease in electronic scaffolds.
It a notion that might have come from the pages of a science-fiction novel an electronic device that can be injected directly into the brain,
or other body parts, and treat everything from neurodegenerative disorders to paralysis. Sounds unlikely, until you visit Charles Lieber lab. Led by Lieber, the Mark Hyman Jr.
Professor of Chemistry, an international team of researchers has developed a method of fabricating nanoscale electronic scaffolds that can be injected via syringe.
The scaffolds can then be connected to devices and used to monitor neural activity, stimulate tissues, or even promote regeneration of neurons.
The research is described in a June 8 paper in Nature Nanotechnology. Contributors to the work include Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter
Kruskal, Chong Xie, Zhigang Suo, and Ying Fang. do feel that this has the potential to be said revolutionary,
Lieber. his opens up a completely new frontier where we can explore the interface between electronic structures and biology.
but no one has addressed this issue the electronics/cellular interface at the level at which biology works.
like a polymer, and could literally be sucked into a glass needle or pipette. From there, we simply asked,
ould it be possible to deliver the mesh electronics by syringe needle injection??Though not the first attempt at implanting electronics into the brain deep brain stimulation has been used to treat a variety of disorders for decades the nanofabricated scaffolds operate on a completely different scale. xisting techniques are crude relative to the way the brain is wired,
Lieber said. hether it a silicon probe or flexible polymers they cause inflammation in the tissue that requires periodically changing the position or the stimulation. ut with our injectable electronics, it as if it not there at all.
They are one million times more flexible than any state-of-the-art flexible electronics and have subcellular feature sizes.
Theye what I call euro-philicthey actually like to interact with neurons. The process for fabricating the scaffolds is similar to that used to etch microchips,
and begins with a dissolvable layer deposited on a substrate. To create the scaffold, researchers lay out a mesh of nanowires sandwiched in layers of organic polymer.
The first layer is dissolved then, leaving the flexible mesh, which can be drawn into a needle
and administered like any other injection. The input-output of the mesh can then be connected to standard measurement electronics
so that the integrated devices can be addressed and used to stimulate or record neural activity. hese type of things have never been done before, from both a fundamental neuroscience and medical perspective,
Lieber said. t really exciting there are a lot of potential applications. Going forward, researchers hope to better understand how the body reacts to the injectable electronics over longer periods.
Harvard Office of Technology Development has filed for a provisional patent on the technology and is actively seeking commercialization opportunities. he idea of being able to precisely position
and record from very specific areas, or even from specific neurons over an extended period of time this could,
I think, make a huge impact on neuroscience, Lieber said
#Immune system Linked to Motor neuron Death in ALS A previously unknown link between the immune system and the death of motor neurons in Amyotrophic lateral sclerosis (ALS),
also known as Lou Gehrig disease, has been discovered by scientists at the CHUM Research Centre and the University of Montreal.
The finding paves the way to a whole new approach for finding a drug that can cure
or at least slow the progression of such neurodegenerative diseases as ALS, Alzheimer, Parkinson and Huntington diseases.
and trigger the disease, said Alex Parker, CRCHUM researcher and associate professor in the Department of Neuroscience at the University of Montreal.
Amyotrophic lateral sclerosis is a neuromuscular disease that attacks neurons and the spinal cord. Those affected gradually become paralyzed and typically die less than five years after the onset of symptoms.
If a mutation occurs in one of them the person develops the disease. Scientists introduced a mutated human gene (TDP-43 or FUS) into C. elegans,
a nematode worm widely used for genetic experiments. The worms became paralyzed within about 10 days.
The challenge was to find a way of saving them from certain death. e had the idea of modifying another gene tir-1 known for its role in the immune system,
lead investigator and doctoral student under the supervision of Alex Parker. Results were remarkable. orms with an immune deficit resulting from the tir-1 gene mutation were in better health
and suffered far less paralysis, she added. This study highlights a never previously suspected mechanism:
even if the C. elegans worm has a very rudimentary immune system, that system triggers a misguided attack against the worm own neurons. he worm thinks it has a viral or bacterial infection and launches an immune response.
But the reaction is toxic and destroys the animal motor neurons, Alex Parker explained. Is the same scenario at work with people?
Most likely. The human equivalent of the tir-1 gene SARM1 has proved crucial to the nervous system integrity.
This makes the TIR-1 protein (or SARM1 in humans) an excellent therapeutic target for development of a medication.
because we caused the disease. This allows us to administer treatment very early in the worm life.
But ALS is a disease of aging, which usually appears in humans around the age of 55.
But we have demonstrated clearly that blocking this key protein curbs the disease progress in this worm
All authors are affiliated with the CHUM Research Centre and the University of Montreal: Julie Veriepe, Lucresse Fossouo and J. Alex Parker.
University of Montrealimage Credit: The image is credited to the NIHORIGINAL Research: Abstract for eurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neuronsby Julie Vérièpe, Lucresse Fossouo and J Alex Parker
10.1038/ncomms8319abstractneurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neuronsamyotrophic lateral sclerosis (ALS) is a neurodegenerative disease thought to employ cell nonautonomous
mechanisms where neuronal injury engages immune responses to influence disease progression. Here we show that the expression of mutant proteins causative for ALS in Caenorhabditis elegans motor neurons induces an innate immune response via TIR-1/Sarm1.
Loss of function mutations in tir-1, associated downstream kinases, and the transcription factor atf-7 all suppress motor neuron degeneration.
recruiting a pathogen resistance response that is ultimately harmful and drives progressive neurodegeneration. eurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neuronsby Julie Vérièpe, Lucresse Fossouo and J Alex
Parker in Nature Communications. Published online June 10 2015 doi: 10.1038/ncomms831 o
#Imaging Technique Provides Color Coded Map Showing Cancerous Brain areas New imaging technique could make brain tumor removal safer and more effective,
study suggests. Brain surgery is famously difficult for good reason: When removing a tumor, for example, neurosurgeons walk a tightrope as they try to take out as much of the cancer as possible
while keeping crucial brain tissue intact and visually distinguishing the two is often impossible. Now Johns Hopkins researchers report they have developed an imaging technology that could provide surgeons with a color-coded map of a patient brain showing
which areas are and are not cancer. A summary of the research appears June 17 in Science Translational Medicine. s a neurosurgeon,
I in agony when I taking out a tumor. If I take out too little the cancer could come back;
too much, and the patient can be disabled permanently, says Alfredo Quinones-Hinojosa, M d.,a professor of neurosurgery,
neuroscience and oncology at the Johns hopkins university School of medicine and the clinical leader of the research team. e think optical coherence tomography has strong potential for helping surgeons know exactly where to cut.
First developed in the early 1990s for imaging the retina, optical coherence tomography (OCT) operates on the same echolocation principle used by bats and ultrasound scanners,
but it uses light rather than sound waves, yielding a higher-resolution image than does ultrasound.
One unique feature of OCT is that unlike X-ray, CT SCANS or PET scans, it delivers no ionizing radiation to patients.
For the past decade, research groups around the globe, including a group at Johns Hopkins led by Xingde Li, Ph d,
. a professor of biomedical engineering, has been working to further develop and apply the technology to other organs beyond the relatively transparent eye.
Carmen Kut, an M d./Ph d. student working in Li lab, thought OCT might provide a solution to the problem of separating brain cancers from other tissue during surgery.
Working with Li, Quinones-Hinojosa and other collaborators Kut first built on the idea that cancers tend to be relatively dense,
which affects how they scatter and reflect lightwaves. The team tried for three years to build their technique on this principle.
Eventually, the researchers figured out that a second special property of brain cancer cells that they lack the so-called myelin sheaths that coat healthy brain cells had a greater effect on the OCT readings than did density.
Once they had found the characteristic OCT ignatureof brain cancer, the team devised a computer algorithm to process OCT data and,
nearly instantaneously, generate a color-coded map with cancer in red and healthy tissue in green. e envision that the OCT would be aimed at the area being operated on,
and the surgeon could look at a screen to get a continuously updated picture of where the cancer is
and isn, Li says. So far, says Kut, the team has tested the system on fresh human brain tissue removed during surgeries
and in surgeries to remove brain tumors from mice. The researchers hope to begin clinical trials in patients this summer.
If those trials are successful and the system goes to market, it will be a big step up from imaging technologies now available during surgeries,
says Quinones-Hinojosa. ltrasound has a much lower resolution than OCT, and MRI SCANNERS designed to be wheeled over a patient on the operating table cost several millions of dollars each
and require an extra hour of operating room time to obtain a single image, he says.
By comparison, the team anticipates that the cost of an OCT-based system would run in the hundreds of thousands of dollars.
The system can potentially be adapted to detect cancers in other parts of the body, Kut says.
She is working on combining OCT with a different imaging technique that would detect blood vessels to help surgeons avoid cutting them s
#Long term Musical Memory Spared in Alzheimer Patients Max Planck researchers discover the anatomic reasons for the persistence of musical memory in Alzheimer patients.
In comparison to other memory functions, long-term musical memory in Alzheimer patients often remains intact and functional for a surprisingly long time.
In a recent study, scientists from the Max Planck Institute for Human Cognitive and Brain sciences in Leipzig, the University of Amsterdam and INSERM Caen have pinpointed the location of musical memory for the first time
In practice, carers and therapists take advantage of this phenomenon to stimulate their patients with music. It is often possible for music to reactivate memories, emotions and impressions.
says Jörn-Henrik Jacobsen, scientist at the Max Planck Institute in Leipzig and the University of Amsterdam.
the researchers first located the seat of long-term musical memory in the brain with the help of functional ultra-high-field magnetic resonance imaging.
The data were analyzed then with the help of statistical pattern-recognition methods. The scientists were able to conclude from the various active brain areas which of the three categories (long-known, recently heard,
In the process, they considered three important features of the disease: loss of neurons, reduced metabolism and deposition of amyloid protein in the affected brain areas.
They found that the brain area that had been identified as the seat of long-term musical memory does in fact lose fewer neurons than the rest of the brain.
but does not lead to the deficits otherwise associated with advanced stages of the disease.
It can therefore remain largely intact even in advanced stages of the disease. ur findings also lend support to a theory previously proposed in connection with other studies that found stronger network connections between the anterior gyrus cinguli and other nodes
This suggests that this area of the brain also provides specific compensatory functions as the disease progresses,
a sound understanding of the complex relationships could lead to a real therapeutic benefit of music in patient care,
This technology has shown that it works well and is easy to use. For someone suffering from paralysis or limited mobility, visiting with other people is extremely difficult.
A team of researchers at the Defitech Foundation Chair in Brain-Machine Interface (CNBI), headed by José del R. Millán,
For several weeks, each of the subjects put on an electrode-studded hat capable of analysing their brain signals.
transmitting their instructions in real time via internet from their home country. By virtue of its video camera
screen and wheels, the robot, located in a laboratory of Ecole polytechnique fédérale de Lausanne (EPFL, Switzerland), was able to film as it moved
while displaying the face of the remote pilot via Skype. The person at the controls,
as if moving in place of the robot, was able to interact with whoever the robot crossed paths with. ach of the 9 subjects with disabilities managed to remotely control the robot with ease after less than 10 days of training,
said Professor Millán. Shared control between human and machine The brain-machine interface developed by the researchers goes even further.
The robot is able to avoid obstacles by itself even when it is told not to.
and the computer, allowing the pilot to rest while navigating. No difference between healthy and disabled subjects In the end, the tests revealed no difference in piloting ability between healthy and disabled subjects.
The TOBI project, funded by the European commission, aims at developing brain-machine interfaces for people with disabilities to control telepresence robots or a wheelchair using only mental commands.
project called TOBI (Tools for Brain-Computer Interaction which began in 2008. Will robots soon become a fact of daily life for people suffering from a disability?
Too soon to say, according to Professor Millán . or this to happen, insurance companies will have to help finance these technologies. e
#Artificial Neurons Can Communicate in the Same Way as Human Neurons Scientists at Karolinska Institutet have managed to build a fully functional neuron by using organic bioelectronics.
This artificial neuron contain no ivingparts, but is capable of mimicking the function of a human nerve cell
However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet Department of Neuroscience in collaboration with colleagues at Linköping University, have created now an organic bioelectronic device that is capable of receiving chemical signals,
which it can then relay to human cells. ur artificial neuron is made of conductive polymers
professor of cellular microbiology. he sensing component of the artificial neuron senses a change in chemical signals in one dish,
by adding the concept of wireless communication, the biosensor could be placed in one part of the body,
or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged. unding This study was made possible by funding from Carl Bennet AB,
KI Press Office Karolinska Instituteimage Credit: Image is adapted from the Karolinska Institute video and is credited to the researchersvideo Source:
The video is available at the karolinskainstitutet Youtube pageoriginal Research: Abstract for n organic electronic biomimetic neuron enables auto-regulated neuromodulationby Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, Dagmar
Galter, Magnus Berggren, and Agneta Richter-Dahlfors in Biosensors & Bioelectronics. Published online April 22 2015 doi:
10.1016/j. bios. 2015.04. 058abstractan organic electronic biomimetic neuron enables auto-regulated neuromodulationcurrent therapies for neurological disorders are based on traditional medication and electric stimulation.
Here, we present an organic electronic biomimetic neuron, with the capacity to precisely intervene with the underlying malfunctioning signalling pathway using endogenous substances.
Selective biosensors transduce chemical signals into an electric current, which regulates electrophoretic delivery of chemical substances without necessitating liquid flow.
When exceeding defined threshold concentrations, biosensor output signals, connected via custom hardware/software, activated local or distant neurotransmitter delivery from the organic electronic ion pump.
The results demonstrate the potential of the organic electronic biomimetic neuron in therapies involving long-range neuronal signalling by mimicking the function of projection neurons.
applicable for bridging injured sites and active prosthetics. se of Brain MRI Atlases to Determine Boundaries Of age-Related Pathology:
The Importance of Statistical Methodby David Alexander Dickie, Dominic E. Job, David Rodriguez Gonzalez, Susan D. Shenkin,
how we develop the next generation of medications for chronic painhich is by far the most prevalent human health conditionnd the way we execute basic biomedical research using mice. esearch has demonstrated that men
. E. P. Taylor Professor of Pain Studies at Mcgill University and Director of the Alan Edwards Centre for Research on Pain. he realization that the biological basis for pain between men and women
The research was conducted by teams from Mcgill University, The Hospital for Sick Children (Sickkids), and Duke university,
and looked at the longstanding theory that pain is transmitted from the site of injury or inflammation through the nervous system using an immune system cell called microglia.
said Michael Salter, M d.,Ph d.,Head and Senior Scientist, Neuroscience & Mental health at Sickkids and Professor at The University of Toronto,
The discovery comes as there is increased attention to the inclusion of female animals and cells in preclinical research.
and cell lines in preclinical research . or the past 15 years scientists have thought that microglia controlled the volume knob on pain,
#Researchers Discover New Epigenetic Mecahnism in Brain cells For decades, researchers in the genetics field have theorized that the protein spools around
which DNA is wound, histones, remain constant in the brain, never changing after development in the womb.
Now, researchers from the Icahn School of medicine at Mount sinai have discovered that histones are replaced steadily in brain cells throughout life a process
This histone replacement, known as turnover, enables our genetic machinery to adapt to our environment by prompting gene expression,
described in a study led by researchers in the Department of Pharmacology and Systems Therapeutics at the Icahn School of medicine at Mount sinai,
and at the Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, was published today in the journal Neuron.
and protect genetic material in chromosomes, are highly stable proteins in non-dividing cells like nerve cells.
The newfound mechanism is epigenetic meaning it fine-tunes gene expression without changing the DNA code we inherit from our parents.
The study results revolve around the fact that, although some cell types, such as skin cells, constantly self-destruct and are replaced in an ongoing turnover that keeps tissues viable, others,
such as nerve and heart cells, are programmed to perform specific functions with complex genetic memory involved,
The research team found that histone turnover regulates how genes in the brain are turned on and off in response to various stimuli,
creating a new front in the field of chromatin biology, said Ian Maze, Phd, Assistant professor of Pharmacology and Systems Therapeutics at the Icahn School of medicine at Mount sinai. y identifying this new mechanism of epigenetic regulation,
or changes to gene expression caused by external and environmental factors, this work provides a novel conceptual framework for further studies aimed at identifying the molecular underpinnings of neurodevelopmental disease and psychiatric illness. pecifically,
the study examined a specific type of histone called H3. 3 in human and rodent brains.
H3. 3 is a version of the histone H3 with a small random genetic change in its code
To study histone composition in mouse nerve cells and related turnover, researchers fed young, post-weaning rodents a special diet containing heavy labeled lysines,
The prevalence of the labeled H3. 3 demonstrated the fact that the older histones had been replaced with newer ones, indicating histone turnover.
In humans, researchers used a technique called 14c/12c bomb pulse dating to measure turnover.
when open-air nuclear bomb testing occurred following the Second world war. Researchers can take samples from cells in this case
As with the rodent observations, the researchers found that H3. 3 turnover occurs in the human brain throughout life.
confirming the role of histone turnover in neuronal plasticity. The findings thus establish histone turnover as a critical,
and new, regulator of cell-type specific transcription in the brain. istone turnover, shown through our work with H3. 3,
is essential for the behavior of brain cells, said Dr. Maze. urthering our understanding of how the brain works,
learns, forms new memories and reacts to changes in the environment can help us to find new ways to treat neurodegenerative diseases and mental illness. ource:
David Slotnick Icahn School of medicine at Mount Sinaiimage Credit: Image is credited to Zephyris and is licensed CC BY-SA 3. 0original Research:
Abstract for ritical Role of Histone Turnover in Neuronal Transcription and Plasticityby Ian Maze, Wendy Wenderski, Kyung-Min Noh, Rosemary C. Bagot, Nikos Tzavaras
, Immanuel Purushothaman, Simon J. Elsässer, Yin Guo, Carolina Ionete, Yasmin L. Hurd, Carol A. Tamminga, Tobias Halene, Lorna Farrelly, Alexey A. Soshnev
, Duancheng Wen, Shahin Rafii, Marc R. Birtwistle, Schahram Akbarian, Bruce A. Buchholz, Robert D. Blitzer, Eric J. Nestler, Zuo-Fei Yuan
10.1016/j. neuron. 2015.06.014 Abstractcritical Role of Histone Turnover in Neuronal Transcription and Plasticityhighlights 3. 3 displays a unique saturating profile of nucleosome occupancy in postnatal brain
and behavioral plasticity istone turnover is critical for cell type-specific gene expressionsummary Turnover and exchange of nucleosomal histones and their variants,
with the histone variant H3. 3 accumulating to near-saturating levels throughout the neuronal genome by mid-adolescence.
Despite such accumulation, H3. 3-containing nucleosomes remain highly dynamicn a modification-independent mannero control neuronal-and glial-specific gene expression patterns throughout life.
Our findings establish histone turnover as a critical and previously undocumented regulator of cell type-specific transcription and plasticity in mammalian brain. ritical Role of Histone Turnover in Neuronal Transcription and Plasticityby
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