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Archive - Jan 2012

Date

January 23rd

New Biochip Measures Glucose in Saliva

For the 26 million Americans with diabetes, drawing blood is the most prevalent way to check glucose levels. It is invasive and at least minimally painful. Researchers at Brown University are working on a new sensor that can check blood sugar levels by measuring glucose concentrations in saliva instead. The technique takes advantage of a convergence of nanotechnology and surface plasmonics, which explores the interaction of electrons and photons. The engineers at Brown etched thousands of plasmonic interferometers onto a fingernail-size biochip and measured the concentration of glucose molecules in water on the chip. Their results showed that the specially designed biochip could detect glucose levels similar to the levels found in human saliva. Glucose in human saliva is typically about 100 times less concentrated than in the blood. “This is proof of concept that plasmonic interferometers can be used to detect molecules in low concentrations, using a footprint that is ten times smaller than a human hair,” said Dr. Domenico Pacifici, assistant professor of engineering and lead author of the paper published online on December 26, 2011 in Nano Letters, a journal of the American Chemical Society. The technique can be used to detect other chemicals or substances, from anthrax to biological compounds, Dr. Pacifici said, “and to detect them all at once, in parallel, using the same chip.” To create the sensor, the researchers carved a slit about 100 nanometers wide and etched two 200 nanometer-wide grooves on either side of the slit. The slit captures incoming photons and confines them. The grooves, meanwhile, scatter the incoming photons, which interact with the free electrons bounding around on the sensor’s metal surface.

January 22nd

Whole Exome Analysis of Rare Disease Reveals Common Mechanism of Hypertension

Analyzing all the genes of dozens of people suffering from a rare form of hypertension, Yale University researchers have discovered a new mechanism that regulates the blood pressure of all humans. The findings by an international research team headed by Yale scientists, published online on January 22, 2012 in the journal Nature, may help explain what goes wrong in the one billion people who suffer from high blood pressure. The study also demonstrates the power of new DNA sequencing methods to find previously unknown disease-causing genes. The team used a technique called whole exome sequencing — an analysis of the makeup of all the genes — to study a rare inherited form of hypertension characterized by excess levels of potassium in the blood. They found mutations in either of two genes that caused the disease in affected members of 41 families suffering from the condition. The two genes interact with one another in a complex that targets other proteins for degradation, and they orchestrate the balance between salt reabsorption and potassium secretion in the kidney. "These genes were not previously suspected to play a role in blood pressure regulation, but if they are lost, the kidney can't put the brakes on salt reabsorption, resulting in hypertension," said Dr. Richard Lifton, Sterling Professor and chair of the Department of Genetics at Yale and senior author of the paper. The mutations had previously been difficult to find because there were very few affected members in each family, so traditional methods to map the genes' locations had been ineffective. "The mutations in one gene were almost all new mutations found in affected patients but not their parents, while mutations in the other gene could be either dominant or recessive. The exome sequencing technology was ideally suited to cutting through these complexities," said Dr.

Study Aids Genetic Understanding of High-Altitude Adaptation

Over many generations, people living in the high-altitude regions of the Andes or on the Tibetan Plateau have adapted to life in low-oxygen conditions. Living with such a distinct and powerful selective pressure has made these populations a textbook example of evolution in action, but exactly how their genes convey a survival advantage remains an open question. Now, a University of Pennsylvania team has made new inroads to answering this question with the first genome-wide study of high-altitude adaptations within the third major population to possess them: the Amhara people of the Ethiopian Highlands. Surprisingly, all three groups’ adaptations appear to involve different genetic mutations, an example of convergent evolution. “These three groups took different genetic approaches to solving the same problem,” said senior author Dr. Sarah Tishkoff, a Penn Integrates Knowledge professor with appointments in the genetics department in Penn’s Perelman School of Medicine and the biology department in the School of Arts and Sciences. In addition to Dr. Tishkoff, the research was led by Dr. Laura B. Scheinfeldt, a research scientist in the genetics department at the Perelman School of Medicine. Other members of the genetics department who contributed to the research are Drs. Sameer Soi, Simon Thompson, Alessia Ranciaro, William Beggs, Charla Lambert, and Joseph P. Jarvis. The Penn team collaborated with Drs. Dawit Wolde Meskel, Dawit Abate, and Gurja Belay of the Department of Biology of Addis Ababa University. Their research was published on January 20, 2012 in the journal Genome Biology. One of the guiding principles behind evolution is natural selection; the more an organism is suited to its environment, the more likely it is to survive and pass on its genes.

Tiny Amounts of Alcohol Dramatically Extend a Worm’s Life Span

Minuscule amounts of ethanol, the type of alcohol found in alcoholic beverages, can more than double the life span of a tiny worm known as Caenorhabditis elegans, which is used frequently as a model in aging studies, UCLA biochemists report. The scientists said they find their discovery difficult to explain. "This finding floored us — it's shocking," said Dr. Steven Clarke, a UCLA professor of chemistry and biochemistry and the senior author of the study, published January 18, 2012 in the online journal PLoS ONE. In humans, alcohol consumption is generally harmful, Dr. Clarke said, and if the worms are given much higher concentrations of ethanol, they experience harmful neurological effects and die, other research has shown. "We used far lower levels, where it may be beneficial," said Dr. Clarke, who studies the biochemistry of aging. The worms, which grow from an egg to an adult in just a few days, are found throughout the world in soil, where they eat bacteria. Dr. Clarke's research team — Paola Castro, Dr. Shilpi Khare, and Dr. Brian Young — studied thousands of these worms during the first hours of their lives, while they were still in a larval stage. The worms normally live for about 15 days and can survive with nothing to eat for roughly 10 to 12 days. "Our finding is that tiny amounts of ethanol can make them survive 20 to 40 days," Dr. Clarke said. Initially, Dr. Clarke's laboratory intended to test the effect of cholesterol on the worms. "Cholesterol is crucial for humans," Dr. Clarke said. "We need it in our membranes, but it can be dangerous in our bloodstream." The scientists fed the worms cholesterol, and the worms lived longer, apparently due to the cholesterol. They had dissolved the cholesterol in ethanol, often used as a solvent, which they diluted 1,000-fold.

Fundamental Discovery in Malaria Parasite’s Protein Targeting

A team of researchers led by Dr. Kasturi Haldar and Dr. Souvik Bhattacharjee of the University of Notre Dame's Center for Rare and Neglected Diseases has made a fundamental discovery in understanding how malaria parasites cause deadly disease. The researchers show how parasites target proteins to the surface of the red blood cell that enables sticking to and blocking blood vessels. Strategies that prevent this host-targeting process will block disease. The research findings appear in the January 20, 2012 edition of the journal Cell. The study was supported by the National Institutes of Health. Malaria is a blood disease that kills nearly 1 million people each year. It is caused by a parasite that infects red cells in the blood. Once inside the cell, the parasite exports proteins beyond its own plasma membrane border into the blood cell. These proteins function as adhesins that help the infected red blood cells stick to the walls of blood vessels in the brain and cause cerebral malaria, a deadly form of the disease that kills over half a million children each year. In all cells, proteins are made in a specialized cell compartment called the endoplasmic reticulum (ER) from where they are delivered to other parts of the cell. Dr. Haldar and Dr. Bhattacharjee and collaborators Dr. Robert Stahelin at the Indiana University School of Medicine- South Bend (who also is an adjunct faculty member in Notre Dame's Department of Chemistry and Biochemistry), and Drs. David and Kaye Speicher at the University of Pennsylvania's Wistar Institute discovered that for host-targeted malaria proteins the very first step is binding to the lipid phosphatidylinositol 3-phosphate, PI(3)P, in the ER. This was surprising for two reasons.

January 20th

“Extinct” Monkey Rediscovered in Borneo

An international team of scientists has found one of the rarest and least known primates in Borneo, Miller's Grizzled Langur, a species which was believed to be extinct or on the verge of extinction. The team's findings, published in the American Journal of Primatology, confirm the continued existence of this endangered monkey and reveal that it lives in an area where it was previously not known to exist. Miller's Grizzled Langur (Presbytis hosei canicrus) is part of the small primate genus Presbytis, found across Borneo, Sumatra, Java, and the Thai-Malay Peninsula. In Borneo, P.h. canicrus is only found in a small corner of the county's north east and its habitat has suffered from fires, human encroachment, and conversion of land for agriculture and mining. The team's expedition took to them to Wehea Forest in East Kalimantan, Borneo, a large 38,000 hectare area of mostly undisturbed rainforest. Wehea contains at least nine known species of non-human primate, including the Bornean orangutan and gibbon. "Discovery of P.h canicrus was a surprise since Wehea Forest lies outside of this monkey's known range. Future research will focus on estimating the population density for P.h. canicrus in Wehea and the surrounding forest," said Dr. Brent Loken, from Simon Fraser University Canada. "Concern that the species may have gone extinct was first raised in 2004, and a search for the monkey during another expedition in 2008 supported the assertion that the situation was dire." By conducting observations at mineral licks where animals congregate and setting up camera traps in several locations, the expedition confirmed that P. h canicrus continues to survive in areas west of its previously recorded geographic range. The resulting photos provide the first solid evidence demonstrating that its geographic range extends farther than previously thought.

January 19th

PLCG2 Mutation Causes Rare Immune Disease

Investigators at the NIH have identified a genetic mutation in three unrelated families that causes a rare immune disorder characterized by excessive and impaired immune function. Symptoms of this condition include immune deficiency, autoimmunity, inflammatory skin disorders, and cold-induced hives, a condition known as cold urticaria. The study was led by Dr. Joshua Milner, in the Laboratory of Allergic Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), and Dr. Daniel Kastner, scientific director at the National Human Genome Research Institute (NHGRI). The work was published online on January 11, 2012 in the New England Journal of Medicine. The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID. "Investigating rare diseases gives researchers more clues about how the healthy immune system functions," says NIAID Director Dr. Anthony S. Fauci. "More importantly, identifying the genetic cause of these disorders opens up possibilities for better disease management and potentially a cure for people who may have spent their entire lives debilitated by severe and unexplained symptoms." The NIH study involved 27 people from three separate families who all suffered from an inherited form of cold urticaria, an allergic disease characterized by the formation of itchy, sometimes painful hives, episodes of fainting and, in certain cases, life-threatening reactions in response to cold temperatures. Blood sample analysis revealed that many patients produced antibodies to their own cells and tissues (autoantibodies), making them more susceptible to developing autoimmune disease.

January 17th

Taste for Fat Has Genetic Basis

Our tongues apparently recognize and have an affinity for fat, according to researchers at Washington University School of Medicine in St. Louis. They have found that variations in a gene can make people more or less sensitive to the taste of fat. The study is the first to identify a human receptor that can taste fat and suggests that some people may be more sensitive to the presence of fat in foods. The study was published online on December 31, 2011 in the Journal of Lipid Research. Investigators found that people with a particular variant of the CD36 gene are far more sensitive to the presence of fat than others. “The ultimate goal is to understand how our perception of fat in food might influence what foods we eat and the quantities of fat that we consume,” says senior investigator Dr. Nada A. Abumrad, the Dr. Robert A. Atkins Professor of Medicine and Obesity Research. “In this study, we’ve found one potential reason for individual variability in how people sense fat. It may be, as was shown recently, that as people consume more fat, they become less sensitive to it, requiring more intake for the same satisfaction. What we will need to determine in the future is whether our ability to detect fat in foods influences our fat intake, which clearly would have an impact on obesity.” People who made more CD36 protein could easily detect the presence of fat. In fact, study subjects who made the most CD36 were eight times more sensitive to the presence of fat than those who made about 50 percent less of the protein. The researchers studied 21 people with a body mass index (BMI) of 30 or more, which is considered to be obese. Some participants had a genetic variant that led to the production of more CD36. Others made much less. And some were in between. Participants were asked to taste solutions from three different cups.

January 16th

Gap-Junction Inhibitors May Prevent Drug-Induced Liver Damage

Rutgers University and Massachusetts General Hospital (MGH) investigators have developed a novel strategy to protect the liver from drug-induced injury and improve associated drug safety. In a report published online on January 15, 2012 in the journal Nature Biotechnology, the team reports that inhibiting a type of cell-to-cell communication can protect against damage caused by liver-toxic drugs such as acetaminophen. "Our findings suggest that this therapy could be a clinically viable strategy for treating patients with drug-induced liver injury," said Dr. Suraj Patel a postdoctoral researcher in the Center for Engineering in Medicine at MGH and the paper's lead author. "This work also has the potential to change the way drugs are developed and formulated, which could improve drug safety by providing medications with reduced risk of liver toxicity." Drug-induced liver injury is the most common cause of acute liver failure in the U.S. and is also the most frequent reason for abandoning drugs early in development or withdrawing them from the market. Liver toxicity limits the development of many therapeutic compounds and presents major challenges to both clinical medicine and to the pharmaceutical industry. Because no pharmaceutical strategies currently exist for preventing drug-induced liver injury, treatment options are limited to discontinuing the offending drug, supportive care, and transplantation for end-stage liver failure. The researchers investigated an approach that targets a liver's gap junctions – hollow multimolecular channels that connect neighboring cells and allow direct communication between coupled cells. In the heart, gap junctions propagate the electrical activity required for synchronized contraction, but their role in the liver has not been well understood.

January 15th

PARP Inhibitors May Prove Useful in Treating Ovarian Cancer

A constellation of defective proteins suspected in causing a malfunction in the body’s ability to repair its own DNA could be the link scientists need to prove a new class of drugs will be effective in treating a broad range of ovarian cancer patients, an Oregon Health & Science University (OHSU) Knight Cancer Institute study has found. These research results, published January 11, 2012 in PLoS ONE, have prompted additional exploration into whether the patient population included in clinical trials for drugs that target the enzyme poly ADP ribose polymerase (PARP) should be expanded. Several forms of cancer are more dependent on PARP for their growth than regular cells, which means that targeting these enzymes when they go haywire is a potentially effective way to treat ovarian cancer. Currently, PARP inhibitors are being tested with patients who have two types of malfunctioning proteins, BRCA1 or BRCA2. But, the OHSU Knight Cancer Institute study of additional proteins, beyond BRCA proteins, suggests that they too are playing a role in driving ovarian cancer. Tapping into the potential of PARP inhibitors could change the dynamics of ovarian cancer treatment. There has not been a substantial increase in treatment options for ovarian cancer in the past two decades, said Dr. Tanja Pejovic, gynecologic oncologist at the OHSU Knight Cancer Institute. Dr. Pejovic, who led the study of these additional defective proteins, added that the results provide evidence that further research into the role of multiple proteins is warranted. Only about 10 to 15 percent of women with ovarian cancer have BRCA 1 or BRCA 2 mutations. Pejovic’s study of 186 patients with nonhereditary cancer found that 41 percent who had an early recurrence of the disease also had abnormal levels of the other proteins tracked.