Category for research

Fatty Foods Affect Brain Before Weight

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High amounts of fat in food, such as ice cream, not only affect a person’s stomach but also their brain. Some of the fat travels to the brain, which then causes the brain to send out signals to all of the cells in the body. These signals “tell” the cells to disregard the hormones leptin and insulin, which tell the body to “stop” eating to regulate body weight. When a human eats, these hormones send signals to the body to stop eating once the body is full, but these hormones do not always work when a human eats something enjoyable like “junk” food. Leptin is released to stop the feeling of hunger by fat tissue in the body and insulin slows the desire for food by increasing in the pancreas after detection of blood sugar from a meal.

In a study done at the University of Texas Southwestern Medical Center at Dallas, Dr. Deborah Clegg analyzed what kinds of fats affected the brain in this way. Dr. Clegg believes that the fat actually changed the chemical composition of the brain because the fat is incorporated into the brain. Dr. Clegg performed this study by looking at effects of different fats on the brain of animals after exposure by three different methods: injection directly into the brain, feeding the animal through a stomach tube, and infusion into the carotid artery a few times a day. Palmitic acid and oleic acid were the specific fats used. Palmitic acid is a saturated fatty acid and is found in foods such as butter and beef while oleic acid is an unsaturated fatty acid found in food such as olive oil. The results showed that palmitic acid affected the signaling pathways of the leptin and insulin over about three days while the oleic acid did not affect the hormones. These studies were done on animals but Dr. Clegg believes that the saturated fatty acids will affect a human’s brain in a similar way. In another study with rats, the saturated fats, especially palmitic acid, caused the insulin modulator to localize to the cell membranes in the hypothalamus, which slowed the insulin signaling in the brain. Dr. Clegg hopes to soon determine a way to reverse the effects of the palmitic acid on the brain signaling.

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New Research Finds Novel Uses for Old Drugs

A recent article in C&EN reports that scientists at the University of North Carolina at Chapel Hill School of Medicine and the University of California, San Francisco have developed and experimentally tested a technique to predict new target diseases for existing drugs. The team, led by Bryan L. Roth and Brian K. Shoichet, developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring ligands of disease targets within cells. In their study, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs.

Many of the most successful drugs on the market today are being prescribed for ailments that are quite different from the ones they were originally designed to treat since many drugs have been found to bind to multiple targets. Sometimes these interactions lead to new uses for well established drugs. At other times, they may cause harmful side effects. Either way, knowing about these interactions allows for better use of drugs.

In the new method, drug receptors are not defined by structure or sequence but by the ligands that bind to them. This approach differs from structure-based approaches which usually use a receptor’s crystal structure as a starting point.

“This approach uncovered interactions between drugs and targets that we never could have predicted simply by looking at the chemical structures,” said senior study author Bryan Roth, M.D., Ph.D., professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC. “We may now have a way to predict what side effects are likely to occur from treatment before we even put a drug into clinical testing.” internetchemistry.com

By using a modified version of an already established algorithm used to search gene-sequence databases, compounds were screened against a database of targets, asking how much the compounds looked like the ligands. The team compared 3,665 approved or investigational drugs with hundreds of targets which were defined by their ligands. The researchers predicted thousands of unanticipated interactions and experimentally tested 30 of them. Of these 30, they confirmed 23 of the interactions.

In one case, the team found  that Rescriptor, which inhibits the enzyme HIV reverse transcriptase, also inhibited the histamine H4 receptor. The scientists have linked Rescriptor binding to histamine H4 at physiologically relevant concentrations to some of the painful side effects that the drug has. In another example, the antidepressant Prozac, whose primary target is the serotonin transporter, bound the beta-1 adrenerfic receptor, a G-protein-coupled receptor (GPCR) that usually binds such compounds as epinephrine and norepinephrine.

Roth states that the power of their approach is that it can be used to uncover the real targets of pharmaceutical compounds quickly and efficiently, and will probably lead to a greater understanding of the many molecular targets of each drug. Consequently, this new method will be an important step forward for chemists to design drugs that act on multiple targets.

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Will research journals going web 2.0 really matter?

Cell published their first ‘Article of the Future‘ a couple of weeks ago; arstechnica has a good summary. The format, while new to scientific publishing, utilizes some of the better technologies that have been available on the web for most of the last decade.

It’s great that publishers are making research publications more accessible, especially to those outside the traditional scientific community, but I don’t believe it will impact the day-to-day workflow of most researchers. I, for one, ‘grew up’ with photocopies of papers organized in folders and binders, graduated to printed copies of pdfs (in folders by topic/project), and currently maintain a large DEVONthink database of pdfs, text clipped from articles, notes, etc., as well as assorted paper notebooks. I find RSS access much more useful that a ‘Web 2.0‘ format.

Overall, the broader impact is likely with the publishers as they adopt similar formats to comply with the NIH Public Access Policy, although there are other implications. MIT’s Open-Access Policy is worth reading as is the policy for the University of California system.

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A Natural Lock on Tumor Growth

At the University of California, researchers have been studying RNA interface(RNAi), a naturally occurring system that turns genes on and off, and the proteins drosha and dicer. The research has focused on spacial and temporal regulations of RNAi. Researchers hope that a better understanding of these regulations will help to lead to improved medical applications of controlling the RNAi system. This emerging research is going to be essential in future medical endeavors especially in biomedical applications such as gene therapy.

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Research on drosha and dicer proteins is already being applied to the medical field. According to a study in the New England Journal of Medicine, women who had ovarian tumors with high levels of the proteins Dicer and Drosha survived for an average of 11 years or more, while women who had lower levels survived only a median of around 3 years. Researchers hope that a better understanding of Dicer and Drosha might someday help guide treatment or lead to new types of therapy. These two proteins are essential in RNA interference. In the study, Anil K. Sood, M.D., University of Texas M.D. Anderson Cancer Center, in Houston, and his colleagues looked for Dicer and Drosha in the tissue from 111 women with advanced epithelial ovarian cancer. They found that 60 percent of the cancer tissues had low levels of Dicer, 51 percent had low levels of Drosha, and 39 percent had low levels of both. This study is the largest yet to link RNA interface with any cancer survival rates.

“In the past, people used to think that miRNA might actually promote tumor growth, but there is some emerging thought that some of the miRNAs might keep tumors from growing and actually function as a tumor suppressor,” says Sood, who is an associate professor of cancer biology.

Unfortunately this research does not have immediate application for women with ovarian cancer. However the finding may eventually help doctors to better determine if a patient needs more aggressive treatments.

This new research is causing many biotechnology companies to look at this lock-and-key mechanism as a potential way to fight other diseases. They are working to create new synthetic molecules called small interfering RNAs. These siRNAs are being tested as a way to treat eye disease and age-related macular degeneration.

J. Am. Chem. Soc., 2009. DOI: 10.1021/ja905596t

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Chocoholics Beware: Addiction could be worse than you think…

A recent study by the Scripps Research Institute Committee on the Neurobiology of Addictive Disorders reveals an interesting fact about food addiction. While it has been known that sugary or fatty foods can cause an addiction much like that of heroin or alcohol, Pietro Cottone and his team proves that the “sugar high” isn’t the only reason for the addiction. In fact, in his studies with rats, he found that there is also a negative reinforcement system, much like that found in drug addicts, which can cause feelings of anxiety during a withdrawal of the sugary or fatty foods. This increases the probability for continued addiction. Hypophagia, or under-eating of regular (non-preferred) foods, is common when rats and people are influenced by food addiction. Cottone’s hypothesis involved a non-nutritional explanation for this phenomenon, which is commonly credited to an “energy compensation” theory. The nutritional explanation of hypophagia is that it stems from a “corrective energy homeostasis mechanism which opposes weight gain.”Chocolate.jpg

The study to test this hypothesis was conducted with male Wistar rats that were fed a chow diet (A/I) which was preferred to their regular Chow, and were also offered the choice of a chocolate-flavored chow. The rats were given the regular Chow for 5 days, and then were given the highly preferred sugary chow for 2 days. While they ate roughly the same amount of regular food each day, the rats over-ate the sugary chow, and then under-ate the less-preferable but equally acceptable chow (hypophagia). The group used A/I as well as the sugary chow, which had the same initial levels of energy intake and weight gain, to prove that the rats’ addiction was more than just nutritional. Given their similar caloric value, the rats still preferred and overate the chocolate diet more than the preferred A/I chow.

Ultimately, the group discovered that the rats going through chocolate withdrawal spent more time in corners of a maze, rather than the open parts, illustrating the previously mentioned anxiety effect. They found the anxiety to be attributed to corticotropin-releasing factor (CRF), which is involved in stress-response in the brain (commonly found in drug and alcohol withdrawal cases). This research marks the first time this factor was indicated in a type of food, or chocolate addiction. Could a CRF blocker be the answer to every chocoholic’s addiction? Cottone says yes.

What I found most remarkable about this study was the severity of chocolate or food addiction, and how it could be equated biologically to alcohol or drug addiction. This study suggests that on-and-off dieting could increase addiction and anxiety in withdrawal of that addiction.

PNAS, 2009. DOI: 10.1073/pnas.0908789106

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Don’t Judge a Book by Its Cover … Judge by Its Smell

OldBooksA recently published article in the journal Analytical Chemistry discusses the distinct “aroma” produced by old books and aims to better describe – at the molecular level – that musty smell you encounter in the back rooms of libraries.  Volatile organic compounds (VOCs) are responsible for the odor … hundreds of them.  The exact combination of VOCs results from degradation pathways that are dependent on the original material composition – including the paper source, applied media (e.g. inks) and binding.  The exact composition of the off-gassing VOCs can hold valuable information regarding the condition of the materials and possible ways to aid in preservation.  Unfortunately, most testing methods used to date involve destructive sampling techniques.  The authors of this paper have devised a new approach that involves non-destructive head-space sampling of the emitted VOCs, combined with some advanced statistical analyses (a method termed “material degradomics” … a twist on more popular terms like proteomics or metabolomics).  Although hundreds of potential VOCs can be emitted, the authors focused in on 15 that can be used as markers to track the degradation of paper and help optimize its preservation.  Some of these markers include compounds such as benzaldehyde, nonanal, furfural, acetic acid, hexadecane, and 2-ethylhexanol (among others).

Now we can have a whole new appreciation for those leather-bound books and libraries that smell of rich mahogany (and VOCs)…

Anal. Chem., 2009, 81 (20), pp 8617–8622, DOI: 10.1021/ac9016049.

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New Gene Therapy Technique Provides a Breath of Fresh Air for Lung Donor Recipients

A group of researchers at the University Health Network of Toronto led by Dr. Shaf Keshavjee, developed a novel gene therapy technique that repaired donated lungs deemed too damaged to transplant. The group’s findings, “Functional Repair of Human Donor Lungs by IL-10 Gene Therapy” were published in the October 28, 2009 edition of the journal Science Translational Medicine. Their simple and effective technique could significantly increase the number of available lungs for people desperately in need.

Lungs-close-up-lrgAs it stands, only about 15 percent of lungs donated are usable for transplant. Because doctors injure delicate airways as they try to keep donors alive, or the brain death of the donors causes further damage through massive inflammation of the lung tissue. Lungs that make it to transplantation are still vulnerable to inflammation during the first 72 hours after surgery. Overall, only about 40% of lung transplant recipients survive five years after receiving their new lungs.

The research conducted by the University Health Network’s team focused on saving donated lungs that would otherwise be discarded and, eventually, to improve patient outcomes after transplantation. The most important component of their study is the interleukin-10 gene, IL-10. Among IL-10’s many roles is inhibiting the immune response to infection or foreign materials, like transplanted organs. The research strategy consisted of two parts. The first preserved lungs at normal body temperature in a protective dome called the Toronto XVIVO Lung Perfusion System. The dome continuously pumps oxygen devoid of blood, proteins, and nutrients into the injured lungs to mimic normal body conditions. This made it possible for the injured cells to regenerate themselves. In the second part, researchers injected an adenovirus vector, a common cold virus, along with the IL-10 gene through the windpipe into the lungs. After testing the technique with lungs from pigs and then human donors, the team concluded that the gene therapy significantly improved the ability of the lungs to take in oxygen as well as expel carbon dioxide. The therapy improved blood flow throughout the lungs and lasted for up to 30 days. None of the tested lungs were transplanted into patients; however, future plans include starting clinical trials on humans and testing whether this therapy could protect against post-transplant inflammation.

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Chemical Profile of Decomposition Acquired to Improve Technology for Disasters and Crime

Jones Press Conference-1wFor many years, search dogs have been the standard for the discovery and retrieval of human cadavers in disasters and crimes. The problems with this method are the cost and time it takes to train these search dogs. A device to detect the gases given off of a cadaver would be cheaper and less time consuming than training detection dogs. When a cadaver decomposes, a series of gases are given off over time. In order to develop a device that could detect these gases, experiments had to be performed to discover which gases are given off in different stages of decomposition and also to analyze how the environment affects decomposition in different situations.

Such a device could have been helpful in the search for survivors and cadavers of the earthquake in Indonesia in September. Rescue workers were still searching with detection dogs on the fourth day, and hopes for finding survivors are slim. With a device to detect gases released during decomposition, the search process may have been accelerated.

The first tests were performed on human cadavers, but the human cadavers were not delivered until about two or three days after the person had died. There are certain gases, such as cadaverine and putrescine, that are given off very early in the decomposition process and would therefore be undetected by the time the scientists received the cadavers. Dan Sykes, Ph.D., and student, Sarah A. Jones, from Pennsylvania State University, studied the decomposition of pigs because they display the same stages of decomposition as humans. Sykes and Jones euthanized three pigs and put them into containers that were open at the bottom to allow for insects and air to reach the bodies of the pigs. The gases given off during the decomposition process were collected and analyzed by a solid phase micro extraction (SPME) bundle with polyacrylate fibers. These polyacrylate fibers are polar and are commonly used to collect air samples. Similarly, the gases given off by the body were collected into the fibers. The samples were collected every six to twelve hours over the period of one week and then analyzed using GC-MS. Certain gases, such as indole and putrescine, were not given off until later in the decomposition process, but precursor molecules to these gases were detected, which helped to estimate when the gases would be given off. Using this method, Sykes and Jones were able to create a timeline of decomposition for the pigs, which closely resembles the timeline for the decomposition of a human cadaver. Now that the decomposition timeline has been created, it is possible to begin to set up different scenarios in order to apply the timeline to real life situations of decomposition in disasters and crime scenes.

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Micelles for the Delivery of Nitric Oxide

In the context of cardiovascular medicine, coronary arterial clotting from the fatty build-up from cholesterol is closely related to the control, volume, and coagulation of blood due to cells in the blood vessels. Angioplasty, the technique of mechanically widening an obstructed or dysfunctional blood vessel, is sometimes hampered by poor bodily reaction to a stent. A stent is a man-made ‘tube’ inserted into the blood vessel to prevent a localized blood flow constriction. To prevent the bodily reactions, focus has been placed on local drug delivery with inhibitors of cell growth and muscle contraction.

Nitric oxide has been shown to induce relaxation in cells of the blood vessel and regulate the strength and frequency of motion of the blood vessel muscles. Nitric oxide is difficult to deliver directly to the tissues and advancements in experimentation have been hampered by the rate at which nitric oxide releases into human tissue. Any current product has decomposed much too quickly to be useful as an effective drug. A current theory is to synthesize a molecule to bind nitric oxide to a binding molecule to slow the release of nitric oxide to the amounts needed over an extended time period. For effective treatment, nitric oxide would have to be released over a few weeks. Nitric oxide decomposes in less than fifteen seconds in blood vessel tissue, far too quickly for the treatment to be effective. It is necessary to control the release of nitric oxide into the tissues at a sufficiently slow rate while stabilizing it to last for extended periods of time, as the treatment is expensive and could be harmful with multiple doses every day. This can be achieved by attaching nitric oxide to a stable binding molecule but the size of the binding molecule needs to be sufficiently small to penetrate tissues under mild pressure.

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One of the routes taken by current research (J. Am. Chem. Soc., 2009, 131, 14413–14418) is to encapsulate nitric oxide into a complex of long carbon chains known as micelles. The micelles inhibit the release of nitric oxide by an average of over 50% compared to other molecules. Also, micelles have hydrophobic and hydrophilic properties, meaning that they can interact with solutions that are based of water, like blood, or they can penetrate into tissues with mostly cytosol, the fluid of the inside of cells. The micelle inhibits the release of nitric oxide and can be transported facilely through both blood and tissues, making it an efficient delivery pathway for the release of nitric oxide to inhibit cell growth and muscle movement in blood vessels, protecting stent operation by reducing bodily reaction to the stent.

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Who needs embryonic cells anyway?

An article released in Science last August (Induced Pluripotent Stem Cells Generated from Patients with ALS can be Differentiated into Motor Neurons) prompted Time Magazine to name the discovery the No. 1 Medical Breakthrough of the Year. Collaborators at Harvard University and Columbia University based their research on a previous breakthrough that suggested the feasibility of reprogramming somatic cell nuclei into an undifferentiated state by a process called somatic cell nuclear transfer. While the Obama administration recently reversed the limits Bush had previously imposed on embryonic stem cell research, it is of no consequence to this team of scientists, who opened the door to stem cell research involving skin cells rather than human embryonic cells.

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The motivation for their ground-breaking work is the state of research on ALS, or Lou Gehrig’s disease. Once referred to as an orphan disease, ALS is finally getting the attention it deserves as an incurable and mysterious neurodegenerative disease. The cause of the disease is currently unknown, but a supply of human motor neurons carrying the genes responsible for the disease would be highly beneficial to research and eventual treatment. Unlike other disease research where the affected cells can be removed from patients and examined, obtaining a diseased model of a motor neuron or glial (support) cell is unheard of making investigation of degeneration of the cells very difficult.

The team of scientists used skin cells extracted from two elderly ALS patients and transduced the fibroblasts with four genes previously determined to return cells to an undifferentiated state. This is possible because embryogenesis is not dictated by genetic events; it is actually reversible! Imagine that! From the skin cells, the scientists were able to produce iPS colonies (induced pluripotent stem cells), which are very similar to ES cells in morphology and expression. One success after another, they pressed on in hopes of differentiating these cells into motor neurons and glial cells.

I had the opportunity to work with the team of collaborators at Columbia University two summers ago when they were developing a concrete procedure for the differentiation of mouse and human ES cells into motor neurons. It was with this method that the scientists ultimately created motor neurons from simple skin biopsies. While this research was done on patients who expressed the SOD1 allele (or the gene pinpointed in familial ALS), 90% of ALS cases are sporadic, meaning there is no genetic history of the disease. The research is far from null though; it actually provides great insight into the sporadic form of the disease, which is believed to be caused by a combination of genetic and environmental factors. Once a more stable method of reproduction is determined, this research should have a great impact on research and clinical trials for patients with ALS and other neurodegenerative diseases.

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Maybe you should rethink that all-nighter?

A new study published in Science hints at a connection between sleep (or lack thereof) and the development of Alzheimer’s disease.  In both mice and humans, amyloid-beta peptide levels rose during waking hours, but then fell again upon sleep.  Amyloid-beta plaques (like those found in the brains of Alzheimer’s patients) formed more readily in sleep-deprived mice.  Although certainly not a smoking gun, this research may indicate poor sleep patterns are a risk factor for development of Alzheimer’s disease.

…I think I’ll turn in early tonight…

[via Science/AAAS]

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First images of atomic orbitals

images of the atomic orbitals of a carbon atom

This comes soon after IBM researchers imaged a single molecule using AFM.

To create these images, the researchers used a field-emission electron microscope, or FEEM. They placed a rigid chain of carbon atoms, just tens of atoms long, in a vacuum chamber and streamed 425 volts through the sample. The atom at the tip of the chain emitted electrons onto a surrounding phosphor screen, rendering an image of the electron cloud around the nucleus.

[insidescience via slashdot]

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So mom was right…

broccoli Apparently mom wasn’t trying to torture you with all that broccoli after all. A recent study in Japan stated that

Eating 2.5 ounces a day of broccoli sprouts appeared to reduce the risk of stomach ulcers and probably stomach cancer.

The word “probably” makes me question the validity of their claims. However, they did show that eating broccoli significantly lowered the levels of H. pylori (a bacterium associated with stomach damage and gastric cancer) in those who participated in the study.

So think twice the next time you go to sneak your broccoli under the table for the dog! [Yahoo! Health]

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Don’t count your chickens before they hatch… apparently they can do it for you

chicks A study on chicks has shown that they can also count. Researchers at the University of Padova and University of Trento tested the chicks’ math skills by moving plastic balls behind screens – so as to have three behind one and two behind the other. The researchers had previously found that they prefer to be near groups containing more of the objects.

The chicks still approached the larger of the two groups first, even though they had to rely on memory to work out which screen to choose. –Professor Regolin

So what’s next… algebra? calculus? computational chemistry? Watch out! These cute little guys could be posing a threat to our jobs. [BBC News]

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Northern Lights and a ‘pro’ blogger we know!

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and our very own, Dr. Amanda Grannas, is now a ‘pro’ blogger for the Discovery Channel’s earthlive blog!

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Lifestyle Clues

fingerprintI found a pretty interesting article in C&EN about information that can be obtained from fingerprints.  We know that fingerprints can be used as clues to a person’s identity, and recently researchers have found that they can also be used to discover a person’s drug habits and potentially his or her medical history.  Chemists are reporting that they have discovered ways to detect different types of drugs and their metabolites, such as marijuana, cocaine, etc., in fingerprints.  A team at the University of East Anglia, in England, attached antibodies which recognize drug metabolites to iron oxide magnetic particles, which could be used to dust for fingerprints.  Another antibody was added to fluoresce which will help recognize drugs and metabolites.  Test fingerprints were taken from volunteer drug users at a local clinic and the team was able to successfully identify the drugs in their fingerprints.

I found this article and technique very interesting.  I think that it could have applications in forensic science and even in drug testing at sporting events such as the Olympics.  The article also stated that at some point it will be possible to known a person’s medical history from his or her fingerprint.  This, as well as its drug testing applications, raises some questions about privacy laws.  I think that this technology, if used for the correct purposes and not for exploitation, can be a convenience tool for forensic scientists.

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Duplicating nature in the lab

If you need further justification for research, check out this piece over at wired

But although nature can make a remarkably wide variety of chemicals — far more than the best molecule-making robots — it does not always deliver them in bulk. [wired]

I especially like the conversion of cocaine to an ion-channel blocker found in poison dart frogs. Good stuff!

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A fashionable type of medicine

spidersilknwebA recent CNN.com article describes new and unusual ways of re-growing broken bones and fixing holes in human hearts.  The novel methods involve molecules found in spider silk and the popular waterproof apparel material, Gore-Tex.  At Tufts University, scientists are researching new ways to use spider silk to genetically engineer new bone tissue.  The Department of Biomedical Engineering is trying to utilize the silk’s building-block proteins to create a scaffold material on which new bones or teeth can be grown.  Silk has six times the tensile strength of a steel fiber of equal diameter, but is biocompatible with the human body.  The desired scaffolding material would be used to fill a hole or a break in a tooth or bone.  Tufts scientists plan to take stem cells from elsewhere in the patient’s body to initiate replacement tissue growth.  Silk’s biodegradable nature would allow the scaffold to dissolve over time, much like the soluble stitches used in today’s dentistry.

At Rush University in Indiana, Gore-Tex is being investigated as a viable material to repair holes in the human heart.  Cardiologist Dr. Ziyad Hijazi has shaped the Gore-Tex material into a small umbrella and proposes that it be used to cover a common hole in the upper chamber of the human heart called the Patent Foramen Ovale (PFO).  The PFO is not usually dangerous, but can be for stroke victims.  The Gore-Tex umbrella device, named the Gore-Helex Septal Occluder, has seen success in plugging another type of heart hole.  The PFO hole is suspected to contribute to 40% of strokes in the U.S., so if the device proves successful in coming trials, the new technology could make a big difference in the treatment of stroke patients.

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