German cockroaches (image), which are found throughout many human settlements, have apparently evolved an aversion to glucose in order to avoid roach poisons that often contain this ingredient. In a study published in the May 24, 2013 issue of Science, North Carolina State (NC State) University entomologists describe the neural mechanism behind the aversion to glucose, the simple sugar that is a popular ingredient in roach-bait poisons. Glucose now sets off bitter receptors in cockroach taste buds, causing cockroaches to avoid foods that bring on this taste-bud reaction. This aversion has a genetic basis and it eventually spreads to offspring, resulting in increasingly large groups of cockroaches that reject glucose and any baits made with it. In normal German cockroaches, glucose elicits activity in sugar gustatory receptor neurons, which react when exposed to sugars like glucose and fructose – components of corn syrup, a common roach-bait ingredient. Generally, roaches have a sweet tooth for these sugars. “We don’t know if glucose actually tastes bitter to glucose-averse roaches, but we do know that glucose triggers the bitter receptor neurons that would be triggered by caffeine or other bitter compounds,” says Dr. Coby Schal, the Blanton J. Whitmire Distinguished Professor of Entomology at NC State and the corresponding author of the paper. “That causes the glucose-averse roach to close its mouth and run away from glucose in tests.” In the study, the researchers conducted tests on the roach tongue, the paired mouth appendages called paraglossae. The tests showed the unexpected electrophysiological reactions that glucose stimulates both sugar and bitter receptor neurons, confirming behavioral tests that showed roaches quickly fleeing from glucose when presented with it. But it’s not just a sugar aversion.
In a pioneering, first-of-its-kind-in-the-world operation, an international team of surgeons at Children's Hospital of Illinois created and transplanted a windpipe into a 32-month-old Korean toddler born with a rare, fatal, congenital abnormality in which her trachea failed to develop. During the revolutionary operation, the surgical team implanted a tissue-engineered stem cell based artificial windpipe in Hannah Warren, who had spent her entire life living in a neonatal intensive care unit in a hospital in Seoul, South Korea. Unable to breathe, talk, swallow, eat or drink on her own since birth, Hannah would have died without a trachea transplant. The groundbreaking, nine-hour operation took place at Children’s Hospital of Illinois, part of the OSF Saint Francis Medical Center, in Peoria, Illinois, on April 9, 2013. It is the first time a child has received a tissue-engineered, bioartificial trachea, which was made using non-absorbable nanofibers and stem cells from her own bone marrow. Because no donor organ was used, the remarkable procedure virtually eliminates the chance of her immune system rejecting the transplant. It is expected that in the coming months, Hannah will be able to return home with her family and lead a normal life. “The most amazing thing, which for a little girl is a miracle, is that this transplant has not only saved her life, but it will eventually enable her to eat, drink and swallow, even talk, just like any other normal child,” said Dr. Paolo Macchiarini, Professor of Regenerative Surgery at the Karolinska Institutet, Stockholm, Sweden and lead surgeon in the case.
Ruhr-University Bochum’s (RUB’s) medics in Germany have succeeded in treating cerebral palsy with autologous cord blood. Following a cardiac arrest with severe brain damage, a 2.5-year-old boy had been in a persistent vegetative state – with minimal chances of survival. Just two months after treatment with the cord blood containing stem cells, the symptoms improved significantly; over the following months, the child learned to speak simple sentences and to move. “Our findings, along with those from a Korean study, dispel the long-held doubts about the effectiveness of the new therapy,” says Dr. Arne Jensen of the Campus Clinic Gynecology. Together with his colleague Professor Dr. Eckard Hamelmann of the Department of Pediatrics at the Catholic Hospital Bochum (University Clinic of the RUB), he reports on the case in an open-access article in 2013 issue of the journal “Case Reports in Transplantation.” At the end of November 2008, the child suffered from cardiac arrest with severe brain damage and was subsequently in a persistent vegetative state with his body paralyzed. Up to now, there has been no treatment for the cause of what is known as infantile cerebral palsy. “In their desperate situation, the parents searched the literature for alternative therapies,” Dr. Jensen explains. “They contacted us and asked about the possibilities of using their son’s cord blood, frozen at his birth.” Nine weeks after the brain damage, on 27 January 2009, the doctors administered the prepared blood intravenously. They studied the progress of recovery at 2, 5, 12, 24, 30, and 40 months after the insult. Usually, the chances of survival after such severe brain damage and more than 25 minutes duration of resuscitation are six per cent.
In an age when microbial pathogens are growing increasingly resistant to the conventional antibiotics used to tamp down infection, a team of Wisconsin scientists has synthesized a potent new class of compounds capable of curbing the bacteria that cause staph infections. Writing online on May 6, 2013 in the Journal of the American Chemical Society, a group led by University of Wisconsin-Madison chemistry Professor Helen Blackwell describes agents that effectively interfere with the "quorum sensing" behavior of Staphylococcus aureus (image), a bacterium at the root of a host of human infections ranging from acne to life-threatening conditions such as pneumonia, toxic shock syndrome, and sepsis. "It's a whole new world for us," says Dr. Blackwell, whose group identified peptide-based signaling molecules that effectively outcompete the native molecules the bacterium uses to communicate and activate the genes that cause disease. Bacteria employ quorum sensing to assess their population density and coordinate certain behaviors. They do so through the use of pheromone-like chemicals, which bind to receptors either in the bacterial cell or on its surface and tell it if there are enough companion bacteria around to switch on genes that perform certain functions. In the case of Staphylococcus aureus, quorum sensing activates toxin production, manifesting disease in the host.Interfering with bacterial quorum sensing to stymie disease is considered a promising new antibiotic strategy, says Dr. Blackwell. Staph, she adds, is an excellent target as the bacterium is not only a prevalent pathogen, but some strains, notably methicillin-resistant Staphylococcus aureus or MRSA, have developed resistance to commonly used antibiotics such as penicillin and its derivatives. The new compounds synthesized by Dr.
Researchers have pinpointed a catalytic trigger for the onset of Alzheimer’s disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons in the brain. For the first time, scientists at Cambridge’s Department of Chemistry have been able to map in detail the pathway that generates “aberrant” forms of proteins that are at the root of neurodegenerative conditions such as Alzheimer’s. They believe the breakthrough is a vital step closer to increased capabilities for earlier diagnosis of neurological disorders such as Alzheimer’s and Parkinson’s, and opens up possibilities for a new generation of targeted drugs, as scientists say they have uncovered the earliest stages of the development of Alzheimer’s that drugs could possibly target. The study, published online on May 20, 2013 in PNAS, is a milestone in the long-term research established in Cambridge by Professor Christopher Dobson and his colleagues, following the realization by Dr. Dobson of the underlying nature of protein ‘misfolding’ and its connection with disease over 15 years ago. The research is likely to have a central role to play in diagnostic and drug development for dementia-related diseases, which are increasingly prevalent and damaging as populations live longer. “There are no disease-modifying therapies for Alzheimer’s and dementia at the moment, only limited treatment for symptoms. We have to solve what happens at the molecular level before we can progress and have real impact,” said Dr Tuomas Knowles, lead author of the study and long-time collaborator of Professor Dobson’s. “We’ve now established the pathway that shows how the toxic species that cause cell death, the oligomers, are formed.
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes. The breakthrough study, conducted by Ph.D. student Sean Humphrey and Professor David James from Sydney’s Garvan Institute of Medical Research, was published online on May 16, 2013 in Cell Metabolism. First discovered in 1921, the insulin hormone plays a very important role in the body because it helps us lower blood sugar after a meal, by enabling the movement of sugar from the blood into cells. Until now, although scientists have understood the purpose of insulin at a broad level, they have struggled to understand exactly how it achieves its task. Sophisticted analytical devices called mass spectrometers now provide the tool that has been missing – the means of looking into the vastly complex molecular maze that exists in every single cell in the human body. These powerful devices have opened up a field known as ‘proteomics,’ the study of proteins on a very large scale. Proteins represent the working parts of cells, using energy to perform essential functions such as muscle contraction, heartbeat, or even memory. Each cell houses multiple copies of between 10,000 and 12,000 protein types, which communicate with each other using various methods, the most common of which is a process known as ‘phosphorylation.’ Phosphate molecules are deliberately added to proteins in order to convey information, or else change the protein’s function. Each of the protein types in a cell has up to 20 potential ‘phosphorylation sites,’ regions to which a phosphate molecule can be added. This pushes the total number of possible cell states from one moment to the next into the billions.
Dr. Gerald Zon’s latest blog post in “Zone in with Zon—What’s Trending in Nucleic Acid Research,” (http://zon.trilinkbiotech.com/) was posted on May 20, 2013. It features Dr. Zon’s analysis of meat and fish adulteration around the world, based on DNA analyses. Dr. Zon takes the reader on a sobering gastronomical journey from horsemeat to sushi to game meat to rats disguised as mutton in this DNA-based discussion. Dr. Zon is an eminent nucleic acid chemist and Director of Business Development at TriLink BioTechnologies in San Diego, California. [Zon blog post]
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer cells into normal cells that die as scheduled. One way that cancer cells thrive is by inhibiting a process that would cause them to die on a regular cycle that is subject to strict programming. This study in cells, led by Ohio State University researchers, found that a compound in certain plant-based foods, called apigenin, could stop breast cancer cells from inhibiting their own death. Much of what is known about the health benefits of nutrients is based on epidemiological studies that show strong positive relationships between eating specific foods and better health outcomes, especially reduced heart disease. But how the actual molecules within these healthful foods work in the body is still a mystery in many cases, and particularly with foods linked to lower risk for cancer. Parsley, celery, and chamomile tea are the most common sources of apigenin, but it is found in many fruits and vegetables. The researchers also showed in this work that apigenin binds with an estimated 160 proteins in the human body, suggesting that other nutrients linked to health benefits – called "nutraceuticals" – might have similar far-reaching effects. In contrast, most pharmaceutical drugs target a single molecule. "We know we need to eat healthfully, but in most cases we don't know the actual mechanistic reasons for why we need to do that," said Dr. Andrea Doseff, associate professor of internal medicine and molecular genetics at Ohio State and a co-lead author of the study. "We see here that the beneficial effect on health is attributed to this dietary nutrient affecting many proteins.
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Northwestern University scientists have shown that a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock. In a study of the common fruit fly, the researchers found the gene, called Ataxin-2, keeps the clock responsible for sleeping and waking on a 24-hour rhythm. Without the gene, the rhythm of the fruit fly's sleep-wake cycle is disturbed, making waking up on a regular schedule difficult for the fly. The discovery is particularly interesting because mutations in the human Ataxin-2 gene are known to cause a rare disorder called spinocerebellar ataxia (SCA) and also contribute to amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. People with SCA suffer from sleep abnormalities before other symptoms of the disease appear. This study linking the Ataxin-2 gene with abnormalities in the sleep-wake cycle could help pinpoint what is causing these neurodegenerative diseases as well as provide a deeper understanding of the human sleep-wake cycle. The findings were published online on May 17. 2013 in Science. Ravi Allada, M.D., professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences, and Dr. Chunghun Lim, a postdoctoral fellow in his lab, are authors of the paper. Period (per) is a well-studied gene in fruit flies that encodes a protein, called PER, which regulates circadian rhythm. Drs. Allada and Lim discovered that Ataxin-2 helps activate translation of PER RNA into PER protein, a key step in making the circadian clock run properly. "It's possible that Ataxin-2's function as an activator of protein translation may be central to understanding how, when you mutate the gene and disrupt its function, it may be causing or contributing to diseases such as ALS or spinocerebellar ataxia," Dr. Allada said.
The sixth annual Personalized Medicine Conference (6.0) organized by San Francisco State University will focus on the amazing technological challenges and advances of “next-generation sequencing,” examining the very latest approaches and how they are leading to profound changes in our understanding of basic biological questions and to more efficacious and cost-effective therapies. The conference is entitled, “Next-Generation Sequencing for Targeted Therapeutics.” Featured speakers include Kimberly J. Popovits, Chairman of the Board, Chief Executive Officer & President of Genomic Health; Dr. Mark Sliwkowski, Distinguished Staff Scientist at Genentech; Professor Atul Butte of Stanford University; and Dr. Carl Borrebaeck, Professor & Chair of Immunotechnology and Director of CREATE Health at Lund University in Sweden. The conference will take place at the South San Francisco Conference Center (http://www.ssfconf.com/directions-top) from 8:00 am to 5:30 pm on Thursday, May 30, 2013, with a reception to follow. Those wishing to attend are urged to register as soon as possible (http://personalizedmedicine.sfsu.edu/register.html). For additional information, to help sponsor the event, or to inquire about special academic rates, contact dnamed@sfsu.edu. The conference organizers, including Michael Goldman, Ph.D., Professor and Chair of San Francisco State’s Department of Biology, noted that with the price of sequencing a complete human genome falling into the $1,000 range, stunning advances are sure to come over the next few years. It is likely that a detailed genome sequence will soon be part of a routine medical history, allowing unprecedented precision in diagnosis and treatment. The DNA and RNA signatures of both complex, common diseases and rare, elusive conditions will yield their secrets.
