'Bionic' Nerve To Bring Damaged Limbs And Organs Back To Life

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http://www.sciencedaily.com/releases/2007/10/071017094047.htm

Science Daily — University of Manchester researchers have transformed fat tissue stem cells into nerve cells - and now plan to develop an artificial nerve that will bring damaged limbs and organs back to life.

In a study published in October's Experimental Neurology, Dr Paul Kingham and his team at the UK Centre for Tissue Regeneration (UKCTR) isolated the stem cells from the fat tissue of adult animals and differentiated them into nerve cells to be used for repair and regeneration of injured nerves. They are now about to start a trial extracting stem cells from fat tissue of volunteer adult patients, in order to compare in the laboratory human and animal stem cells.
Following that, they will develop an artificial nerve constructed from a biodegradable polymer to transplant the differentiated stem cells. The biomaterial will be rolled up into a tube-like structure and inserted between the two ends of the cut nerve so that the regrowing nerve fibre can go through it from one end to the other.
This 'bionic' nerve could also be used in people who have suffered trauma injuries to their limbs or organs, cancer patients whose tumour surgery has affected a nearby nerve trunk and people who have had organ transplants.
With a clinical trial on the biomaterial about to be completed, the researchers hope the treatment could be ready for use in four or five years.
Dr Kingham said: "The differentiated stem cells have great potential for future clinical use, initially for treatment of patients with traumatic injuries of nerves in the arms and legs.
"This work will also help to develop a similar surgical approach for organ transplant, to give full functional recuperation to the transplanted tissue.
"Furthermore, the technique of artificial nerve grafting could also be applicable when tumour mass has involved a nearby nerve trunk, which consequently has to be excised together with the tumour, such as the removal of a prostate tumour where damage to the nerve leads to male impotence."
Director of the UKCTR, Professor Giorgio Terenghi said: "This new research is a very exciting development with many future clinical applications that will improve the lives of many different types of patients and therefore many, many people.
"The frequency of nerve injury is one in every 1,000 of the population - or 50,000 cases in the UK - every year.
"The current repair method - a patient donating their own nerve graft to span the gap at the injury site - is far from optimal because of the poor functional outcome, the extra damage and the possibility of forming scars and tumours at the donor site. Tissue engineering using a combination of biomaterials and cell-based therapies, while at an early stage, promises a great improvement on that. Artificial nerve guides provide mechanical support, protect the re-growing nerve and contain growth factor and molecules favourable to regeneration. The patient will not be able to tell that they had ever 'lost' their limb and will be able carry on exactly as they did before."
He added: "The facilities available at the UKCTR have been developed jointly by the University of Manchester and the North West Development Agency, with exactly this aim - to provide the transition from experimental research to new clinical treatment."
Note: This story has been adapted from material provided by University of Manchester.

Fausto Intilla

www.oloscience.com

DNA Sequencing Becomes Much Quicker

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http://www.sciencedaily.com/releases/2007/10/071015093528.htm

Science Daily — A new technique that combines gene chip technology with the latest generation of gene sequencing machines to allow fast and accurate sequencing of selected parts of the genome has been developed by researchers from the Human Genome Sequencing Center at Baylor College of Medicine in Houston and NimbleGen Systems, Inc., a Wisconsin-based company recently purchased by Roche Applied Science.
"This new technology will replace polymerase chain reaction (PCR) for many purposes," said Dr. Richard Gibbs, director of the HGSC and senior author of the report. "If the aim is to sequence a whole genome for everybody, this is a huge step in that direction."
The report, which appears in Nature Methods, describes the use of microarrays to enrich or increase the volume of specific genomic sequences. High throughput DNA sequencing machines made by 454 Life Sciences then determine the exact genetic code of the material.
For example, if scientists were looking for a mutation in a particular cancer-causing gene (such as BRCA1 that is associated with breast and ovarian cancer), they could make a microarray that is complementary to the part of the genome in which one is interested. This takes advantage of the fact that the adenine (A) bases always attach to the thymine (T) and the cytosine (C) always attaches to the guanine (G) in reactions.
"You take the DNA and you hybridize it (allow the DNA to stick to its complement) on the chip," said Dr. George Weinstock, co-director of the HGSC. "Then you wash away everything that doesn't stick. This can enrich the portion of the genome to be studied by factors of three hundred or more."
The new process is simpler, more accurate and efficient than the multiplex PCR that was previously used to sequence portions of the genome. In one experiment, more than 6,400 exons (the part of the genetic code that carries the instructions for making proteins), were analyzed. Using the old technology this would have taken at least six months.
"We hope to be able to use this to sequence all the exons in the genome," Gibbs said.
Resequencing of genes or other genomic regions of interest is a key step in detecting mutations associated with various complex human diseases, such as cancer, asthma and heart disease. The predominant method for selection of specific genomic regions for resequencing has primarily relied on PCR (polymerase chain reaction) to enrich for specific DNA fragments.
However, PCR is limited in the length of sequence it can amplify, is difficult to scale or multiplex for the enrichment of thousands of fragments, and has limited performance in the repetitive regions typical of complex genomes, such as human. The sequence capture microarray technology bridges the gap between next-generation DNA sequencing technology and current sample preparation methods by providing an adaptable, massively parallel method for selective enrichment of genomic regions of interest. Roche NimbleGen's sequence capture technology enables high-performance targeting of thousands of specific genes or loci using a single microarray hybridization-based enrichment process.
The Nature Methods paper published by Baylor demonstrates that the sequence capture process is simpler, more accurate, more efficient and more cost-effective than the multiplex PCR that was previously used to prepare genomic samples for sequencing. In one experiment, more than 6,700 exons (the part of the genetic code that together form genes), were enriched and analyzed, as well as contiguous genomic regions of up to 5 million bases.
The study, entitled "Direct Selection of Human Genomic Loci by Microarray Hybridization," appears online (14 October 2007 ahead of print) in the journal Nature Methods.
The authors are Albert TJ, Molla MN, Muzny DM, Nazareth L, Wheeler D, Song X, Richmond TA, Middle CM, Rodesch MJ, Packard CJ, Weinstock GM, and Gibbs RA. (DOI:10.1038/NMETH1111)
Others who took part in this study include David Wheeler, Donna Muzny and Xingzhi Song of BCM and Thomas J. Albert, Michael N. Molla, Lynne Nazareth, Todd. A. Richmond, Chris M. Middle, Matthew J. Rodesch and Charles J. Packard of NimbleGen.
Funding for this work came from the U.S. National Human Genome Research Institute and the National Cancer Institute.
Note: This story has been adapted from material provided by Baylor College Of Medicine.

Fausto Intilla
www.oloscience.com

Neural Activity Connected To Blood Flow In New Brain Stimulation Technique

Source:

http://www.sciencedaily.com/releases/2007/10/071009080049.htm

Science Daily — euroscientists at the University of California, Berkeley, have for the first time measured the electrical activity of nerve cells and correlated it to changes in blood flow in response to transcranial magnetic stimulation (TMS), a noninvasive method to stimulate neurons in the brain.

Their findings, reported in the Sept. 28 issue of the journal Science, could substantially improve the effectiveness of brain stimulation as a therapeutic and research tool.
With technological advances over the past decade, TMS has emerged as a promising new tool in neuroscience to treat various clinical disorders, including depression, and to help researchers better understand how the brain functions and is organized.
TMS works by generating magnetic pulses via a wire coil placed on top of the scalp. The pulses pass harmlessly through the skull and induce short, weak electrical currents that alter neural activity. Yet the relative scarcity of data describing the basic effects of TMS, and the uncertainty in how the method achieves its effects, prompted the researchers to conduct their own study.
"There are potentially limitless applications in both the treatment of clinical disorders as well as in fundamental research in neuroscience," said Elena Allen, a graduate student at UC Berkeley's Helen Wills Neuroscience Institute (HWNI) and co-lead author of the study. "For example, TMS could be used to help determine what parts of the brain are used in object recognition or speech comprehension. However, to develop effective applications of TMS, it is first necessary to determine basic information about how the technique works."
Other techniques for studying neural activity in humans, such as functional magnetic resonance imaging (fMRI) or electroencephalogram (EEG), only measure ongoing activity. TMS, on the other hand, offers the opportunity to non-invasively and reversibly manipulate neural activity in a specific brain area.
In a set of experiments, the researchers used TMS to generate weak, electrical currents in the brain with quick 2- to 4-second bursts of magnetic pulses to the visual cortex of cats. Direct measurements of the electrical discharge of nerve cells in the region in response to the pulses revealed that TMS predictably caused an initial flurry of neural activity, significantly increasing cell firing rates. This increased activity lasted 30 to 60 seconds, followed by a relatively lengthy 5 to 10 minutes of decreased activity.
What the researchers were able to determine for the first time was that the neural response to TMS correlated directly to changes in blood flow to the region. Using oxygen sensors and optical imaging, the researchers found that an initial increase in blood flow was followed by a longer period of decreased activity after the magnetic pulses were applied.
"This long-lasting suppression of activity was surprising," said Brian Pasley, a graduate student at HWNI and co-lead author of the study. "We're still trying to understand the physiological mechanisms underlying this effect, but it has implications for how TMS could be used in clinical applications."
The critical confirmation of the connection between blood flow and neural activity means that researchers can use TMS to alter neural activity, and then use fMRI, which tracks blood flow changes, to assess how the nerve cells respond over time.
"One of the most exciting applications of TMS is the ability to non-invasively modify neural activity in specific ways," said Pasley. "The brain is malleable, so brain stimulation may be used to alter and promote specific functions, like learning and memory, or suppress abnormal activity that underlies neurological disorders. If we can figure out the right ways to stimulate the brain, TMS will likely be useful in attempts to improve neural function."
The researchers noted that one of the difficulties in using TMS for specific applications is the fact that its effects vary in different brain regions and individuals.
"Using TMS is inherently challenging because its neural effects can be so variable," said Ralph Freeman, UC Berkeley professor of vision science and optometry and principal investigator of the study. "Fortunately, we can determine empirically what the end result is by making measurements with fMRI. This should be valuable to clinicians who must evaluate the effectiveness of a stimulation treatment. In turn, fMRI may serve as a guide to determine adjustments in treatment parameters."
The study was also co-authored by Thang Duong, a UC Berkeley graduate student in vision science. The National Eye Institute of the National Institutes of Health and the National Science Foundation helped support this research.
Note: This story has been adapted from material provided by University of california - Berkeley.

Fausto Intilla

www.oloscience.com

System To Build Transplant Tissue Created

Source:

http://www.sciencedaily.com/releases/2007/10/071008161609.htm

Science Daily — One day soon, laboratories may grow synthetically engineered tissues such as muscle or cartilage needed for transplants. In a major step forward, Cornell engineers describe in the journal Nature Materials a microvascular system they have developed that can nourish growing tissues.

The researchers have engineered tiny channels within a water-based gel that mimic a vascular system at the cellular scale and can supply oxygen, essential nutrients and growth factors to feed individual cells. The so-called gel scaffold can hold tens of millions of living cells per milliliter in a 3-D arrangement, such as in the shape of a knee meniscus, to create a template for tissue to form.
In theory, the system could accommodate many kinds of tissue.
"A significant impediment to building engineered tissues is that you can't feed the core," said Abraham Stroock, Cornell assistant professor of chemical and biomolecular engineering and one of the paper's senior authors. "Simply embedding this mimic of a microvascular system allows you to maintain the core of the tissue during culture." Gel scaffolds, he said, "are the culture flasks of the future."
The embedded microchannels allow fluid with oxygen, sugar and proteins to travel through the system. The researchers can control the distributions of these solutes over both time and space within the developing tissue, allowing the fine-tuning of the biochemical environment of the cells while the tissue develops. For example, the tissue may need to develop into bone on one side and cartilage on the other. Now the researchers can supply the right nutrients and proteins to certain parts of the growing tissue to ensure an intended outcome.
The research provides solutions to the physical engineering aspects of growing tissues synthetically. Still, many biological challenges remain, such as finding a source of cells that can be harvested from a patient and grown without changing the cell's characteristics. Co-author Lawrence Bonassar, a Cornell associate professor of biomedical engineering who was instrumental in developing the gel for tissue growth and in determining the proper biological requirements for cell growth, is also among those trying to direct stem cells to produce desired tissue types. Currently, stem cell-derived cartilage has been made but is not functional.
As new tools develop, researchers hope to use these engineered tissues in non-clinical applications, such as replacements for animals in the testing of pharmaceuticals and chemicals. The technology, researchers believe, also offers the hope of growing implants from the patient's own cells to replace damaged or diseased tissue.
The research was funded by the Office of Naval Research, Cornell's Nanobiotechnology Center, Beckman Foundation, the Center for Life Science Enterprise at Cornell and the Cornell Center for Materials Research.
Note: This story has been adapted from material provided by Cornell University.

Fausto Intilla

www.oloscience.com

How Do Cells Sense And Respond To Messages? Major Signal Transduction Discovery Made

Source:

http://www.sciencedaily.com/releases/2007/10/071004121038.htm

Science Daily — The chemical process known as acetylation plays a central role in cytokine receptor signal transduction – a fundamental biochemical cascade inside cells that controls the activity of antiviral and tumor-suppressing genes.
A team of cell biologists led by Eugene Chin, M.D., a research professor at The Warren Alpert Medical School of Brown University and a staff researcher at Rhode Island Hospital, reports its findings in the journal Cell. Their results are surprising.
Scientists have long known that phosphorylation, an amino acid modifying process in proteins, is critical for switching receptors on and off on the surface of cells. Chin and his team studied how type 1 interferon binds to a receptor complex, known as the IFN-α receptor, on the cell surface to trigger an immune response. Chin and his team found that acetylation, another chemical process that modifies amino acids, plays a central role in activating interferon receptors.
Interferons play a crucial role in the body’s defense against infection and uncontrolled cell growth. Type 1 interferon is widely used to treat hepatitis B and C and cancers such as melanoma and leukemia.
“This is a major discovery in the field of signal transduction,” Chin said. “Tyrosine phosphorylation has so far been considered the major player in signal transduction. But what we discovered challenges this concept. We found another player – acetylation – in the process.”
In their experiments, Chin and his team looked at how cells respond to type 1 interferon, a protein produced in response to a viral infection or other immune trigger. The researchers found that type 1 interferon receptors, which are found in every cell in the body, call up cytoplasmic CREB-binding protein, or CBP, to move up to the cell surface. CPB acetylates these receptors. That, in turn, sparks a biochemical cascade that attracts more proteins to create a complex called ISGF3. To activate this protein complex, Chin found, acetylation is required. Once that occurs, the complex travels to the cell nucleus to switch on anti-viral or tumor-suppressing genes.
The discovery of the acetylation of cytokine receptors marks a milestone in the study of signal transduction, the process of how cells receive and respond to chemical messages.
Many diseases, such as diabetes, cancer and heart disease, occur when signal transduction goes awry. That is why some drugs either inhibit or amplify signaling inside cells by targeting tyrosine phosphorylation. By showing that another chemical process is critical to signal transduction, Chin’s findings may explain why some anti-cancer or anti-viral drugs do not work for everyone. The findings provide an important new target for therapies that fight cancer and viral infectious diseases.
The Brown research team also included Xiaoli Tang, Jin-Song Gao, and Ying-jie Guan, all post-doctoral research associates in Chin’s Rhode Island Hospital laboratory. Bharat Ramratnam, associate professor of medicine at Brown, also assisted with the research along with Katya McLane, a scientist with Upstate/Chemicon International Inc.
The National Cancer Institute funded the work.
Note: This story has been adapted from material provided by Brown University.

Fausto Intilla
www.oloscience.com

New Telomere Discovery Could Help Explain Why Cancer Cells Never Stop Dividing

Source:

http://www.sciencedaily.com/releases/2007/10/071004143131.htm

Science Daily — A group working at the Swiss Institute for Experimental Cancer Research (ISREC) in collaboration with the University of Pavia has discovered that telomeres, the repeated DNA-protein complexes at the end of chromosomes that progressively shorten every time a cell divides, also contain RNA.

This discovery, published in Science Express, calls into question our understanding of how telomeres function, and may provide a new avenue of attack for stopping telomere renewal in cancer cells.
Inside the cell nucleus, all our genetic information is located on twisted, double stranded molecules of DNA which are packaged into chromosomes. At the end of these chromosomes are telomeres, zones of repeated chains of DNA that are often compared to the plastic tips on shoelaces because they prevent chromosomes from fraying, and thus genetic information from getting scrambled when cells divide.
The telomere is like a cellular clock, because every time a cell divides, the telomere shortens. After a cell has grown and divided a few dozen times, the telomeres turn on an alarm system that prevents further division. If this clock doesn't function right, cells either end up with damaged chromosomes or they become "immortal" and continue dividing endlessly -- either way it's bad news and leads to cancer or disease. Understanding how telomeres function, and how this function can potentially be manipulated, is thus extremely important.
The DNA in the chromosome acts like a sort of instruction manual for the cell. Genetic information is transcribed into segments of RNA that then go out into the cell and carry out a variety of tasks such as making proteins, catalyzing chemical reactions, or fulfilling structural roles. It was thought that telomeres were "silent" -- that their DNA was not transcribed into strands of RNA. The researchers have turned this theory on its head by discovering telomeric RNA and showing that this RNA is transcribed from DNA on the telomere.
Why is this important" In embryonic cells (and some stem cells), an enzyme called telomerase rebuilds the telomere so that the cells can keep dividing. Over time, this telomerase dwindles and eventually the telomere shortens and the cell becomes inactive. In cancer cells, the telomerase enzyme keeps rebuilding telomeres long past the cell's normal lifetime. The cells become "immortal", endlessly dividing, resulting in a tumor. Researchers estimate that telomere maintenance activity occurs in about 90% of human cancers. But the mechanism by which this maintenance takes place is not well understood. The researchers discovered that the RNA in the telomere is regulated by a protein in the telomerase enzyme. Their discovery may thus uncover key elements of telomere function.
"It's too early to give yet a definitive answer," to whether this could lead to new cancer therapies, notes Joachim Lingner, senior author on the paper. "But the experiments published in the paper suggest that telomeric RNA may provide a new target to attack telomere function in cancer cells to stop their growth."
Joachim Lingner is an Associate Professor at the EPFL (Ecole Polytechnique Fédérale de Lausanne). Funding for this research was provided in part by the Swiss National Science Foundation NCCR "Frontiers in Genetics".
Article: "Telomeric Repeat Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends"
Note: This story has been adapted from material provided by Ecole Polytechnique Fédérale de Lausanne.

Fausto Intilla

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Sizing Cells Up: Researchers Pinpoint When A Cell Is Ready To Reproduce

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http://www.blogger.com/post-create.g?blogID=4305283407805626298

Science Daily — For more than 100 years, scientists have tried to figure out the cell size problem: How does a cell know when it is big enough to divide?

In research conducted in budding yeast (Saccharomyces cerevisiae), scientists at Rockefeller University have now identified the cellular event that marks the moment when a cell knows it is big enough to commit to cell division and spawn genetic replicas of itself. The findings provide a precise and quantitative framework for studying the possible mechanisms that allow cells to monitor and sense their size.
During the first phase of the cell cycle, known as G1, budding yeast grows and begins to form a bud; in the final stage, the cell splits into two — one bigger than the other. Although researchers have identified several key proteins that regulate and play a role in coordinating cell growth and division during G1, they have not been able to get to the core mechanism that senses whether a cell possesses enough resources to divide. Scientists needed a way to organize and confidently sort out molecular candidates involved in cell size control from those that played other roles.
Graduate student Stefano Di Talia, a biophysicist, and postdoc Jan Skotheim, an applied mathematician, provided just that. Working with Eric Siggia, head of the Laboratory of Theoretical Condensed Matter Physics, and Fred Cross, head of the Laboratory of Yeast Molecular Genetics, Di Talia and Skotheim showed that a unique cellular event, the exiting of the protein Whi5 from the nucleus, separates G1 into two independent steps: one controlled by a sizer (T1) and one controlled by a timer (T2). T1 begins when the mother and daughter cells have completely separated from each other; T2 starts in G1 once Whi5 has exited the nucleus and lasts until the new daughter cell forms its own bud.
“You need some way to know how big you are,” says first author Di Talia, whose work appears in the August 23 issue of Nature. “This precise quantitative framework allows us to narrow down the possibility of events that are involved in size control.”
By measuring the sizes of budding yeast and how long they spend in G1 and in T1, Di Talia saw that daughter cells, which are much smaller than their mother cells, need to spend more time in T1 growing. Once daughter cells reach the required size for division, they spend as much time as their mothers in T2, subsequently replicating their DNA and producing daughter cells of their own. Di Talia and his colleagues used genetics to show that a different medley of proteins coordinate cell growth and division during T1 and T2, a crucial finding highlighting that these two parts of G1 are independent from each other and are regulated by different mechanisms.
“If we continue to identify the molecular events that change how T1 is regulated,” says Di Talia, “we can really hope to get to the core of what the size-sensing machinery is.”
Nature 448(7156): 947-951 (August 23, 2007)
Note: This story has been adapted from material provided by Rockefeller University.

Fausto Intilla

www.oloscience.com