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Reprogrammed cells generate blood vessels

Researchers findings could make crucial difference in treatment of cardiovascular disease
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The biological microprocessor, or how to build a computer with biological parts

Gerd Moe-Behrens

"Systemics, a revolutionary paradigm shift in scientific thinking, with applications in systems biology, and synthetic biology, have led to the idea of using silicon computers and their engineering principles as a blueprint for the engineering of a similar machine made from biological parts. Here we describe these building blocks and how they can be assembled to a general purpose computer system, a biological microprocessor.  Such a system consists of biological parts building an input / output device, an arithmetic logic unit, a control unit, memory, and wires (busses) to interconnect these components. A biocomputer can be used to monitor and control a biological system."

#biologicalcomputing   #cellularcomputing  
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Memory-Boosting Chemical is Identified in Mice

Memory improved in mice injected with a small, drug-like molecule discovered by UCSF San Francisco researchers studying how cells respond to biological stress.

The same biochemical pathway the molecule acts on might one day be targeted in humans to improve memory, according to the senior author of the study, Peter Walter, PhD, UCSF professor of biochemistry and biophysics and a Howard Hughes Investigator.

In one memory test included in the study, normal mice were able to relocate a submerged platform about three times faster after receiving injections of the potent chemical than mice that received sham injections.

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The results were published in eLife, an online scientific open-access journal.
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New research finds that astroctyes - the brain's support cells - can perform active trauma interventions for damaged neurons. It's so cool to see these "quiet cells" get the respect they deserve!

"After an injury, however, the subventricular niche pumps out more astrocytes. Significantly, the Duke team found they are different from astrocytes produced in most other regions of the brain. These cells make their way to the injured area to help make an organized scar, which stops the bleeding and allows tissue recovery. When the generation of these astrocytes in the subventricular niche was experimentally blocked after a brain injury, hemorrhaging occurred around the injured areas and the region did not heal."

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Original journal paper here:

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"If you ask a rat whether it knows how it came to acquire a certain coveted piece of chocolate, Indiana University neuroscientists conclude, the answer is a resounding, “Yes.” A study newly published in the journal Current Biology offers the first evidence of source memory in a nonhuman animal"

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SciTech #ScienceSunday Digest 7 - 17th Feb 2013
Sensory neuroprostheses, RoboRat tormentor, improved optogenetics, nanotube synapses, IBM's Watson, gene therapy for diabetes, etc.

1. Infrared Neuroprosthesis Enables Rats to Process Infrared Light with Tactile Neural Circuits.
Animals can learn to perceive otherwise invisible infrared light through a neuroprosthesis that couples the output of a head-mounted infrared sensor to their somatosensory cortex via intracortical microstimulation In this proof-of-concept rats were able to use this new information from the infrared sensor to help navigate environments, but were also able to maintain normal whisker sensation and utility despite the microstimulation from the infrared prosthesis being “plugged into” the same cortical circuits as the whiskers; the original tactile representation of these circuits was not displaced by this new type of visual information. The implication is that not only might sensory neuroprostheses provide the opportunity to restore normal sensory function, there is now evidence that such prostheses might expand the sensory perceptual capabilities of humans beyond normal forms and abilities. Who wouldn’t want to see in the infrared, ultraviolet, or sonar? Or hear sounds fainter than normally possible and smell scents better than a dog? Sign me up!

2. RoboRat Programmed to Torment Rats and Deliberately Induce Depression.
In order to develop better drugs to treat depression in humans, better animal models of depression are needed because current models are inadequate. So to develop a better model of depression in animals, researchers have created a robot, shaped like a large rat, that is programmed to “attack” rats by either (i) chasing, (ii) continuously attacking, or most deviously (iii) interactively attacking whenever the rat moves to a set distance Apparently the RoboRat was most successful when it constantly harassed young rats, and then intermittently harassed them again when they were older. There are of course lots of thoughts and issues that come to mind. On the one hand this seems rather sinister, but on the other this is arguably a more humane way of inducing depression than conventional means that include frequent electric shocks and “endurance” swimming / drowning risk. The goal of creating better animal models to develop better drugs has at its heart the best interests of human welfare in mind with the aim of improving the lives of millions of people suffering from depression. Hopefully they never make a RoboHuman to do a similar thing. 

3. Simpler & More Effective Optogenetics Device.
Researchers have developed a polymer implant that combines microfluidic channels to deliver genetic vectors to brain cells, a waveguide to deliver light into the brain, and electrodes to record the subsequent activity of the optogenetically-engineered neurons These devices have been christened “optrodes” and they solve the very tricky problem of accurately getting individual probes for genetic vector delivery, light delivery, and electrical sensing to precisely the same tiny targeted region of the brain. Further, the new polymer device is more flexible and biocompatible than the silicon tools used for optogenetics today and subsequent tests in rats showed that the implant could turn neurons on and off as expected. Current optogenetics experiments involve a small cable exiting from the animal’s skull, but this current team has plans to integrate a light source and electronics with the implant with the goal of making the device wireless and completely implanted. How long until we all have optrodes implanted into our brains? One or two decades? Three at most?

4. An Artificial Synapse Made of Carbon Nanotubes.
Researchers have developed a carbon nanotube synapse that demonstrates the basic dynamic logic, learning, and memory functions of a biological synapse This synaptic architecture displayed extremely low energy consumption, which could be significantly reduced by further scaling down the device, and these carbon nanotube synapses could be integrated in a large-scale circuit to emulate the massively parallel signal processing and learning functions of a biological neural network for speech recognition, pattern recognition, statistical inference, and other intelligent behaviors. I’m guessing they’re already aware of DARPA’s SyNAPSE program. Pre- and post-synaptic spikes demonstrated the plasticity of the artificial synapse, with the synaptic strength itself able to be continuously and reversibly modified to desired analog values. 

5. IBM’s Watson Demonstrates Value to Oncologists.
IBM unveiled the first commercially-focused application of the Watson-based cognitive computing system in the field of oncology This is the result of thousands of hours of “teaching and instruction” Watson received from clinicians and cancer experts, the acquisition of 600,000 pieces of medical evidence and two million pages from 42 medical journals and clinical trials in the field of oncology research. As an example use-case Watson can now sift through 1.5 million patient records (decades of cancer treatment history) and provide doctors evidence-based treatment options in seconds. One of the leaders of the initiative stated; “It can take years for the latest developments in oncology to reach all practice settings. The combination of transformational technologies found in Watson with our cancer analytics and decision-making process has the potential to revolutionize the accessibility of information for the treatment of cancer in communities across the country and around the world.” This Watson-based advisor is available through the cloud and is expected to be rolled out to 1,600 specialist providers this year. 

6. 3D Holographic Video Images of Living Cells.
Scientists have developed a device that can create 3D images of living cells and track their reaction to various stimuli without the use of contrast dyes or fluorophores The device combines holographic microscopy and computational image processing to observe living biological tissues at the nanoscale at sub-100nm resolutions and does not involve the use of substances that might alter or influence the behaviour of the cells. Using the technique the group was able to film the growth of a neuron and the birth of a synapse over the course of an hour and the image processing algorithms are sophisticated enough that the virtual cell can be sliced so that internal structures can be observed if desired. The group plans a spin-out company and has aspirations to develop the device to the point where such observations are possible in vivo without the need to remove tissue. 

7. Self-Assembling Complex 3-Dimensional Structures.
Chemists have developed self-assembling particles that fold from a flat pre-fabricated sheet into complex 3-dimensional structures The work is demonstrated as part of a full video-article that shows the two main areas of the work, (i) particles that fold up and seal their edges because of special glue-like material at the edges, and (ii) foldable structures that reconfigure in response to a stimulus. They use photolithography to etch structural designs and flexible hinges on to a 2-D surface that can then be manipulated to fold and seal or open and close. Applications for the structures range from drug delivery, sensing, remote micro-robotic surgery, and probably many other things that we can’t yet think of. The videos are well worth the watch if you get the chance. 

8. Gene Therapy Cures Type 1 Diabetes.
Dogs with type 1 diabetes have been successfully cured after a single session of gene therapy that introduced a glucose sensor into muscle cells The work was done some time ago however, and even after four years the dogs showed no recurrence of symptoms and the adeno viral vector was demonstrated as safe. The sensor comprises insulin and glucokinase genes that together are able to regulate glucose in the blood. This is also an example of advanced tissue engineering in which the essential function of an organ (in this case the pancreas) is restored despite not targeting or treating that specific organ at all - so this therapeutic approach to curing diabetes might also be applicable to other diseases of organs like the spleen for example. A wide range of other hormone therapies might be enabled with the system although we first need to see this used to cure diabetes in humans too. 

9. Advances in Understanding Superconductivity.
In what is regarded as a breakthrough for developing superconductivity applications, researchers have discovered a way to efficiently stabilize tiny magnetic vortices that interfere with superconductivity (a problem that has plagued scientists trying to engineer real-world applications for decades) The group was able to pin down superconductivity-destroying magnetic vortices by using 50nm diameter superconducting wires in which only a single row of vortices can form and discovered that increasing the magnetic field in this case restored the superconductivity instead of destroying it. While the work was only carried out with low-temperature superconductors the team believes that the principles will also translate to high-temperature materials. 

10. Spherical Nucleic Acids & DNAzymes.
Researchers have developed spherical nucleic acids that consist of densely packed, highly oriented nucleic acids arranged on the surface of a spherical nanoparticle These 15nm non-toxic structures have a range of interesting properties including (i) easily crossing the blood-brain barrier and the layers that make up skin, (ii) don't elicit an immune response and resist degradation in the body, (iii) the sequence or code of the coating DNA strands is able to target and regulate genes. In an earlier proof-of-concept with the material the group used commercial moisturizers to deliver the particles and regulated the genes involved in skin cancer; the drug, consisting of the spherical nucleic acids penetrated the skin's layers and selectively targeted the cancerous cells. In related news we also had DNAzymes (DNA molecules that can enzymatically split other DNA strands) coated onto gold nanoparticles and demonstrated in a successful infectious disease diagnostic application

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First Time: Chemical Reactions Imaged !

When Felix Fischer of the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) set out to develop nanostructures made of graphene using a new, controlled approach to chemical reactions, the first result was a surprise: spectacular images of individual carbon atoms and the bonds between them.

What the microscope showed the researchers, says Fischer, “was amazing.” The specific outcomes of the reaction were themselves unexpected, but the visual evidence was even more so. “Nobody has ever taken direct, single-bond-resolved images of individual molecules, right before and immediately after a complex organic reaction,” Fischer says.

The researchers report their results online in the May 30, 2013 edition of Science Express.

Graphene nanostructures can form the transistors, logic gates, and other elements of exquisitely tiny electronic devices, but to become practical they will have to be mass produced with atomic precision. Hit-or-miss, top-down techniques, such as exfoliating graphite or unzipping carbon nanotubes, can’t do the job.

Fischer and his colleagues set out to engineer graphene nanostructures from the bottom up, by converting linear chains of carbon atoms into extended hexagonal sheets (polyaromatic hydrocarbons), using a reaction originally discovered by UC Berkeley professor Robert Bergman. The first requirement was to perform the reactions under controlled conditions.

The single-atom tip of the noncontact atomic force microscope “feels” changes in the strength of electronic forces as it moves across the surface at a constant height. Resulting movements of the stylus are detected by a laser beam to compute images.
Fischer’s group collaborated with microscopy expert Crommie to devise the best possible view. The first attempt to track the reactions used a scanning tunneling microscope (STM), which senses electronic states when brought within a few billionths of a meter (nanometers) of the surface of the sample. But the image resolution of the tiny molecule and its products – each only about one nanometer across – wasn’t good enough to reliably identify the molecular structures.

The collaborators then turned to a technique called noncontact atomic force microscopy (nc-AFM), which probes the surface with a sharp tip. The tip is mechanically deflected by electronic forces very close to the sample, moving like a phonograph needle in a groove.

The single-atom moving finger of the nc-AFM could feel not only the individual atoms but the forces representing the bonds formed by the electrons shared between them. The resulting images bore a startling resemblance to diagrams from a textbook or on the blackboard, used to teach chemistry, except here no imagination is required.

The original reactant molecule, resting on a flat silver surface, is imaged both before and after the reaction, which occurs when the temperature exceeds 90 degrees Celsius. The two most common final products of the reaction are shown. The three-angstrom scale bars (an angstrom is a ten-billionth of a meter) indicate that both reactant and products are about a billionth of a meter across.

A chemical bond is not as simple a concept as it may appear, however. From the dozens of possibilities, the starting molecule’s reaction did not yield what had intuitively seemed to Fischer and his colleagues the most likely products. Instead, the reaction produced two different molecules. The flat silver surface had rendered the reaction visible but also shaped it in unexpected ways.

The nc-AFM microscopy provided striking visual confirmation of the mechanisms that underlie these synthetic organic chemical reactions, and the unexpected results reinforced the promise of this powerful new method for building advanced nanoscale electronic devices from the bottom up.

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Metabolic Molecule Drives Growth Of Aggressive Brain Cancer

A study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) has identified an abnormal metabolic pathway that drives cancer-cell growth in a particular glioblastoma subtype.

The finding might lead to new therapies for a subset of patients with glioblastoma, the most common and lethal form of brain cancer.

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The research is featured in Proceedings of the National Academy of Sciences.

The glioblastoma multiforme image is courtesy of Dr. Rodney D. McComb and credited to The Armed Forces Institute of Pathology.
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Anti-Cancer Drug Viewed as Possible Alzheimer’s Treatment Doesn’t Work in UF Study

An anti-cancer drug about to be tested in a clinical trial by a biomedical company in Ohio as a possible treatment for Alzheimer’s disease has failed to work with the same type of brain plaques that plague Alzheimer’s patients, according to results of a study by University of Florida researchers.

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The enyzmes and beta-amyloid image is credited to NIH/NIA.
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''Glioblastoma multiforme (GBM) are malignant brain tumors, classified by the World Health Organization (WHO), as grade IV tumors of neuroepithelial tissue and are the most common and deadly intracranial tumors, accounting for more than 70% of all brain tumors.  The current course of GBM treatment entails surgical resection followed by administration of radiation and chemotherapy.  However, despite this aggressive regimen and their devastating side effects on the patient, there are several obstacles that hinder their effectiveness; surgical resection of the primary tumor leads to injury to the surrounding normal tissue, while chemotherapy and radiotherapy cause toxicity to the healthy tissue in the brain. Furthermore, some anatomical feature unique to the central nervous system (CNS) such as the blood brain barrier (BBB) and the densely packed structure of brain’s parenchyma inhibits effective drug delivery throughout the brain"
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New research sheds light on the tiny war machines that bacteria wield in surprisingly precise and selective counterattacks against their bacterial foes.

#bacteria   #research  
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