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Archive - Aug 2014

August 13th

Varying Acoustic Pressure Used in Moving Different-Sized Drugs Past the Blood-Brain Barrier

A new technique developed by Dr. Elisa Konofagou, professor of biomedical engineering and radiology at Columbia Engineering, has demonstrated for the first time that the size of molecules penetrating the blood-brain barrier (BBB) can be controlled using acoustic pressure—the pressure of an ultrasound beam—to let specific molecules through. The study was published in the July 2014 issue of the Journal of Cerebral Blood Flow & Metabolism. “This is an important breakthrough in getting drugs delivered to specific parts of the brain precisely, non-invasively, and safely, and may help in the treatment of central nervous system diseases like Parkinson’s and Alzheimer’s,” says Dr. Konofagou, whose National Institutes of Health Research Project Grant (R01) funding was just renewed for another four years for an additional $2.22 million. The award is for research to determine the role of the microbubble in controlling both the efficacy and safety of drug safety through the BBB with a specific application for treating Parkinson’s disease. Most small—and all large—molecule drugs do not currently penetrate the blood-brain barrier that sits between the vascular bed and the brain tissue. “As a result,” Dr. Konofagou explains, “all central nervous system diseases remain undertreated at best. For example, we know that Parkinson’s disease would benefit by delivery of therapeutic molecules to the neurons so as to impede their slow death. But because of the virtually impermeable barrier, these drugs can only reach the brain through direct injection and that requires anesthesia and drilling the skull while also increasing the risk of infection and limiting the number of sites of injection.

New Technique for Identifying Epigenetic Markers in Cancer Cells Could Improve Patient Treatment

Scientists have known for decades that cancer can be caused by genetic mutations, but more recently they have discovered that chemical modifications of a gene can also contribute to cancer. These alterations, known as epigenetic modifications, control whether a gene is turned on or off. Analyzing these modifications can provide important clues to the type of tumor a patient has, and how it will respond to different drugs. For example, patients with glioblastoma, a type of brain tumor, respond well to a certain class of drugs known as alkylating agents if the DNA-repair gene MGMT is silenced by epigenetic modification. A team of MIT chemical engineers has now developed a fast, reliable method to detect this type of modification, known as methylation, which could offer a new way to choose the best treatment for individual patients. “It’s pretty difficult to analyze these modifications, which is a need that we’re working on addressing. We’re trying to make this analysis easier and cheaper, particularly in patient samples,” says Dr. Hadley Sikes, the Joseph R. Mares Assistant Professor of Chemical Engineering and the senior author of a paper describing the technique first published online on April 28, 2014 in the journal Analyst. The paper’s lead author is Brandon Heimer, an MIT graduate student in chemical engineering. After sequencing the human genome, scientists turned to the epigenome — the chemical modifications, including methylation, that alter a gene’s function without changing its DNA sequence. In some cancers, the MGMT gene is turned off when methyl groups attach to specific locations in the DNA sequence — namely, cytosine bases that are adjacent to guanine bases. When this happens, proteins bind the methylated bases and effectively silence the gene by blocking it from being copied into RNA.

August 13th

Gene Linked to Huntingtin’s Disease Plays Critical Role in Normal Memory Development

It has been more than 20 years since scientists discovered that mutations in the gene huntingtin cause the devastating progressive neurological condition Huntington’s disease, which involves involuntary movements, emotional disturbance, and cognitive impairment. Surprisingly little, however, has been known about the gene’s role in normal brain activity. Now, a study from The Scripps Research Institute’s (TSRI’s) Florida campus and Columbia University shows it plays a critical role in long-term memory. “We found that huntingtin expression levels are necessary for what is known as long-term synaptic plasticity—the ability of the synapses to grow and change—which is critical to the formation of long-term memory,” said TSRI Assistant Professor Sathyanarayanan V. Puthanveettil, who led the study with Nobel laureate Dr. Eric Kandel of Columbia University. In the study, published online on July 23, 2014 by the journal PLOS ONE, the team identified an equivalent of the human huntingtin protein (image)in the marine snail Aplysia, a widely used animal model in genetic studies, and found that, just like its human counterpart, the protein in Aplysia is widely expressed in neurons throughout the central nervous system. Using cellular models, the scientists studied what is known as the sensory-to-motor neuron synapse of Aplysia—in this case, gill withdrawal, a defensive move that occurs when the animal is disturbed. The study found that the expression of messenger RNAs of huntingtin—messenger RNAs are used to produce proteins from instructions coded in genes—is increased by serotonin, a neurotransmitter released during learning in Aplysia. After knocking down production of the huntingtin protein, neurons failed to function normally.

Australia Results Indicate HPV Vaccine Causes Dramatic Reduction in Genital Warts

In the most comprehensive assessment of its type, UNSW Australia-led research has found that in just four years, the HPV vaccine has resulted in a dramatic drop in genital warts in young Australians from a range of backgrounds, a result that could herald further good news for cervical cancer rates in future. The research, which was done in collaboration with the University of Sydney, is based on national hospital admission rates and shows a similar result in the female indigenous population, which has historically had significantly higher rates of cervical cancer. Genital warts and cervical cancer are both caused by HPV. The work was published online on August 12, 2014 in the Journal of Infectious Diseases. In the four years after the national program for school-aged girls was rolled out in 2007, there was a 90% drop in genital warts for girls aged between 12 and 17, and a 73% decrease for women between 18 and 26 years. The vaccine appeared to have an indirect protective effect among young men between the ages of 18 and 26, with a 38% drop in genital warts even prior to boys being vaccinated at school. "This is a fantastic outcome," says the senior author of the paper, Associate Professor Karen Canfell, from UNSW's Lowy Cancer Research Centre. "This is a condition which can be distressing and embarrassing and most often occurs when people start to become sexually active." The vaccine used in the National HPV Vaccination Program in Australia, Gardasil, provides protection against four strains of HPV. HPV 16 and 18 are implicated in several cancers, particularly cervical cancer. Two other strains, HPV 6 and 11 are associated with 90% of genital warts.

MRSA Colonization Common in Groin and Rectal Areas

Colonization of methicillin-resistant Staphylococcus aureus (MRSA) allows people in the community to unknowingly harbor and spread this life-threatening bacteria. The inside of the front of the nose is where this bacteria is most predominant, but new research shows nearly all colonized individuals have this bacteria living in other body sites. The study was published in Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America. "While people colonized with MRSA may not be sick, the bacteria can become aggressive and lead to infection in the person or others," said Kyle Popovich, M.D., M.S., lead author of the study. Because of the risk of transmission, hospitals have developed infection control and prevention efforts that identify individuals with nasal MRSA colonization. These patients may be placed in isolation or decolonized of MRSA by treating and removing the bacteria from the patient's nose and skin. These strategies have been used to prevent MRSA infections for the patient and to decrease risk of spread of MRSA to other patients. Several states also mandate these MRSA surveillance programs. Researchers collected surveillance swab specimens for nose and other body sites from patients at Stroger Hospital of Cook County within 72 hours of admission from March 2011-April 2012. After analyzing the samples, researchers observed that, following the nose, the rectal and groin areas were frequent sites of colonization of community-associated MRSA. The bacteria were found in these body sites more often in men than in women. "Our findings show that MRSA colonization is not limited to the nose. This may have important implications MRSA surveillance programs nationwide," said Dr. Popovich.

How Spiders Fix Their Webs

Spider silk is light and delicate, while incredibly resilient and tear-resistant. Understanding the structure and way of construction of these threads is a challenge taken up by a research team of Kiel University. The scientists examined five different spider species regarding the adhesion and tensile strength of a particular silk they use to fix the main thread to a surface. As shown in their new study published online on July 16, 2014 in the international Journal of the Royal Society Interface, the scientists found out that the substrate has a particularly significant impact on the silk’s adhesion. The research group led by Professor Stanislav Gorb (Institute of Zoology, Kiel University) has attended to the functional analysis of animal surfaces. Why do a gecko’s feet adhere to a wall? Why does a snake’s skin not fray out while the snake is moving forward? The group’s most recent study object is spider silk: spiders use the so-called safety thread to prevent them from falling, to lower themselves and to build the web’s framework. The threads are fixed to the surface and other threads by means of so-called attachment discs generated by rotating motions of the silk glands and applied in the form of a special lattice pattern. The scientists of Dr. Gorb’s research team investigated how attachment discs adhere to various surfaces. “To this end, we placed the spiders on glass, Teflon, and the leaf of a sycamore maple, and they produced attachment discs on each surface. Subsequently, we performed tensile tests to measure the strength necessary to detach the discs from the substrate,” says the author of the current study, Jonas Wolff.

Gene That Controls Nerve Conduction Velocity Linked to Multiple Sclerosis

A new study published online on August 12, 2014 in The American Journal of Pathology identifies a novel gene that controls nerve conduction velocity. Investigators report that even minor reductions in conduction velocity may aggravate disease in multiple sclerosis (MS) patients and in mice bred for the MS-like condition experimental autoimmune encephalomyelitis (EAE). A strong tool for investigating the pathophysiology of a complex disease is the identification of underlying genetic controls. Multiple genes have been implicated as contributing to the risk of developing MS. Unlike studies that have focused on genetic regulators of inflammation, autoimmunity, demyelination, and neurodegeneration in MS, this study focused on nerve conduction velocity. Investigators found that polymorphisms of the inositol polyphosphate-4-phosphatase, type II (Inpp4b) gene affect the speed of nerve conduction in both mice with EAE and humans with MS. "Impairment of nerve conduction is a common feature in neurodegenerative and neuroinflammatory diseases such as MS. Measurement of evoked potentials (whether visual, motor, or sensory) is widely used for diagnosis and recently also as a prognostic marker for MS," says lead investigator Saleh M. Ibrahim, M.D., Ph.D., of the Department of Dermatology, Venereology, and Allergology of the University of Lubeck (Germany). Using several genomic approaches, the investigators narrowed their search to the genetic region controlling the enzyme inositol-polyphosphate-4-phosphatase II (INPP4B), the product of which helps to regulate the phosphatidyl inositol signaling pathway. Enzymes in this family are involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular communication.

August 12th

Scientists Pinpoint Gene Likely to Promote Certain Childhood Cancers

Researchers at the Children’s Medical Center Research Institute at University of Texas (UT) Southwestern (CRI) have identified a gene that contributes to the development of several childhood cancers, in a study conducted with mice designed to model the human cancers. If the findings prove to be applicable to humans, the research could lead to new strategies for targeting certain childhood cancers at a molecular level. The study was published online on August 11, 2014 in Cancer Cell. “We and others have found that Lin28b (see image of cells stained with anti-Lin28b antibody)– a gene that is normally turned on in fetal but not adult tissues – is expressed in several childhood cancers, including neuroblastoma, Wilms’ tumor, and hepatoblastoma, a type of cancer that accounts for nearly 80 percent of all liver tumors in children,” said Dr. Hao Zhu, a principal investigator at CRI, and Assistant Professor of Pediatrics and Internal Medicine at UT Southwestern Medical Center. “In our study, we found that overproduction of Lin28b specifically causes hepatoblastoma, while blocking Lin28b impairs the cancer’s growth. This opens up the possibility that pediatric liver cancer patients could one day be treated without resorting to chemotherapy.” Lin28b is an attractive therapeutic target in cancer because it is ordinarily only expressed in embryos, so blocking it in children should specifically hinder cancer growth without introducing many side effects. Each year in the United States, 700 children are newly diagnosed with neuroblastoma, 500 with Wilms’ tumor, and 100 with hepatoblastoma. At Children’s Medical Center in Dallas, more than 100 children have been treated for those three types of cancers over the last two years.

August 10th

Venom Gets Good Buzz As Potential Cancer-Fighter at ACS Meeting

Bee, snake, or scorpion venom could form the basis of a new generation of cancer-fighting drugs, scientists will report here in San Francisco today at the National Meeting of the American Chemical Society (ACS), the world's largest scientific society. They scientists have devised a method for targeting venom proteins specifically to malignant cells while sparing healthy ones, which reduces or eliminates side effects that the toxins would otherwise cause. The report was part of the 248th National Meeting of the American Chemical Society (ACS), the world's largest scientific society. The meeting, attended by thousands of scientists, features nearly 12,000 reports on new advances in science and other topics. It is being held here through Thursday. A brand-new video on the research is available at http://www.youtube.com/watch?v=GRsUi5UrH7k&feature=youtu.be. "We have safely used venom toxins in tiny nanometer-sized particles to treat breast cancer and melanoma cells in the laboratory," says Dipanjan Pan, Ph.D., who led the study. "These particles, which are camouflaged from the immune system, take the toxin directly to the cancer cells, sparing normal tissue." Venom from snakes, bees, and scorpions contains proteins and peptides which, when separated from the other components and tested individually, can attach to cancer cell membranes. That activity could potentially block the growth and spread of the disease, other researchers have reported. Dr. Pan and his team say that some of substances found in any of these venoms could be effective anti-tumor agents. But just injecting venoms into a patient would have side effects. Among these could be damage to heart muscle or nerve cells, unwanted clotting or, alternately, bleeding under the skin. So Dr.

How the Woodpecker Avoids Brain Injury Despite High-Speed Impacts via Optimal Anti-Shock Body Structure

Designing structures and devices that protect the body from shock and vibrations during high-velocity impacts is a universal challenge. Scientists and engineers focusing on this challenge might make advances by studying the unique morphology of the woodpecker, whose body functions as an excellent anti-shock structure. The woodpecker's brain can withstand repeated collisions and deceleration of 1200 g during rapid pecking. This anti-shock feature relates to the woodpecker's unique morphology and ability to absorb impact energy. Using computed tomography and the construction of high-precision three-dimensional models of the woodpecker, Chinese scientists explain its anti-shock biomechanical structure in terms of energy distribution and conversion. Their findings, presented in a new study titled "Energy conversion in the woodpecker on successive pecking and its role in anti-shock protection of the brain" and published in the Beijing-based journal SCIENCE CHINA Technological Sciences, could provide guidance in the design of anti-shock devices and structures for humans. To build a sophisticated 3-D model of the woodpecker, scientist Dr. Wu Chengwei and colleagues at the State Key Lab of Structural Analysis for Industrial Equipment, part of the Department of Engineering Mechanics at the Dalian University of Technology in northeastern China, scanned the structure of the woodpecker and replicated it in remarkable detail. "CT scanning technology can be used to obtain the images of internal structures of objects … which is widely used in the medical field and expanded to mechanical modeling of biological tissue," they explain in the study.