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Archive - 2011

November 11th

Two Mayo Clinic Studies Focus on High Blood Pressure and Pregnancy

Two studies from the Mayo Clinic presented during the this year’s American Society of Nephrology's Annual Kidney Week (November 8-November 13, 2011) provide new information related to high blood pressure during pregnancy. In one study, Dr. Vesna Garovic and her team examined the potential of a test done mid-pregnancy to predict which women will later develop preeclampsia, a late-pregnancy disorder that is characterized by high blood pressure and excess protein in the urine and that affects 3% to 5% of pregnancies. Left untreated, preeclampsia can lead to serious -- even fatal -- complications for a pregnant woman and her baby. Among a group of 315 patients, 15 developed preeclampsia and 15 developed high blood pressure (but not preeclampsia) during pregnancy. All of the patients who developed preeclampsia tested positive in mid-pregnancy in a test that detects the shedding of certain kidney cells called podocytes in the urine. None of those with only high blood pressure tested positive, and none of 44 women with normal pregnancies tested positive. Therefore, this test is highly accurate for predicting preeclampsia, which could alert clinicians to take steps to safeguard against the condition. In another study, Dr. Garovic's team looked at the long-term health effects of high blood pressure during pregnancy. They identified female residents of Rochester, Minnesota, and the surrounding townships in Olmsted County who delivered between 1976 and 1982. The investigators divided the women into two groups -- those with high blood pressure during pregnancy and those without -- and followed them after they reached 40 years of age to monitor their heart and kidney health. A total of 6,051 mothers delivered between 1976 and1982, and 607 women had high blood pressure at the time while 5,444 did not.

Insight into 100-Year-Old Haber-Bosch Process for Producing Ammonia

For the past 100 years, the Haber-Bosch process has been used to convert atmospheric nitrogen into ammonia, which is essential in the manufacture of fertilizer. Despite the longstanding reliability of the process, scientists have had little understanding of how it actually works. But now a team of chemists, led by Dr. Patrick Holland of the University of Rochester, has gained new insight into how the ammonia is formed. Their findings are published in the November 11, 2011 issue of Science. Dr. Holland calls nitrogen molecules "challenging." While they're abundant in the air around us, which makes them desirable for research and manufacturing, their strong triple bonds are difficult to break, making them highly unreactive. For the last century, the Haber-Bosch process has made use of an iron catalyst at extremely high pressures and high temperatures to break those bonds and produce ammonia, one drop at a time. The question of how this works, though, has not been answered to this day. "The Haber-Bosch process is efficient, but it is hard to understand because the reaction occurs only on a solid catalyst, which is difficult to study directly," said Dr. Holland. "That's why we attempted to break the nitrogen using soluble forms of iron." Dr. Holland and his team, which included Dr. Meghan Rodriguez and Dr. William Brennessel at the University of Rochester and Dr. Eckhard Bill of the Max Planck Institute for Bioinorganic Chemistry in Germany, succeeded in mimicking the process in solution. They discovered that an iron complex combined with potassium was capable of breaking the strong bonds between the nitrogen (N) atoms and forming a complex with an Fe3N2 core, which indicates that three iron (Fe) atoms work together in order to break the N-N bonds.

“1000 Fungal Genomes” Project Funded

With an estimated 1.5 million species, fungi represent one of the largest branches of the Tree of Life. They have an enormous impact on human affairs and ecosystem functioning due to their diverse activities as decomposers and pathogens, and their partnership with host organisms for mutual benefit. To use fungi for the benefit of humankind, an accurate understanding of what exactly they do, how they function, and how they interact in natural and synthetic environments is required. Dr. Jason Stajich, an assistant professor of plant pathology and microbiology at the University of California, Riverside, is a member of an international research team that, in collaboration with the Joint Genome Institute of the U.S. Department of Energy, has embarked on a five-year project to sequence 1000 fungal genomes from across the Fungal Tree of Life. Called the "1000 Fungal Genomes" project, the research endeavor aims to bridge the gap in our understanding of fungal diversity and is one of 41 projects funded through the U.S. Department of Energy's 2012 Community Sequencing Program. The funding awards were announced on November 3, 2011 by the DOE. "The overall plan is to fill in gaps in the Fungal Tree of Life by sequencing at least two species from every known fungal family," said Dr. Stajich, a member of UCR's Institute for Integrative Genome Biology. "Once the data is compiled, the project scientists will make use of the data as a starting point for interpreting how these organisms change and use their environment to make a living." Dr. Stajich is co-leading the Fungal Genomes project with Dr. Joey Spatafora, a professor of botany and plant pathology at Oregon State University.

New Artemisinin-Based Combination Treatment Promising for Malaria

For some time now, artemisinin, derived from a Chinese herb, has been the most powerful treatment available against malaria. To avoid the malaria parasite becoming resistant, the World Health Organization (WHO) strongly recommends combining artemisinin with another anti-malarial drug. But there are different formulations and derivatives, in different combinations, and with dosing schemes. Scientists from the Institute of Tropical Medicine (ITM) carried out a head-to-head comparison of four combination therapies in seven African countries. One combination appeared particularly promising for regions where the risk of re-infection is high. Malaria is caused by several related parasites, of which Plasmodium falciparum is the worst. The parasites have a complicated life cycle, partly in mosquitoes. When an infected mosquito bites a human, parasites are injected with the mosquito saliva into the blood, travel to the liver, where they change form, then infect red blood cells, where they further reproduce. After a few days (depending on the parasite species), the red blood cells burst to release a huge number of new parasites. These bursts cause intense fever, anaemia, and renal problems. Each year, approximately 800,000 people die of malaria. In recent years, the burden of malaria has declined substantially in several sub-Saharan African countries, due to large scale indoor residual spraying of insecticides, massive distribution of insecticide-treated bed nets, and the introduction of artemisinin-based combination treatments, ACTs for short. To treat patients with malaria, the WHO advises each region to choose an ACT based on the local level of resistance to non-artemisinin medicine in the combination. But data on that resistance are scarce.

Cholera Vacccine Prequalified by WHO

Shanchol™, a new oral cholera vaccine developed through the International Vaccine Institute (IVI), an international organization established by the United Nations and based in Seoul, Korea, recently received prequalification from the World Health Organization (WHO). Developed for use in developing countries to protect against life-threatening cholera, Shanchol™ is ready to use in a single-dose vial and is administered orally, which facilitates its implementation in large-scale immunization programs. Shanchol™ is produced by Shantha Biotechnics – part of the Sanofi group - in India where the vaccine has been licensed and sold since 2009. "I am immensely pleased by the news that Shanchol™, a vaccine enabled by IVI, received WHO prequalification," said Dr. Christian Loucq, IVI's new Director General. "This stamp of approval shows that public-private partnerships - such as those among IVI, Vabiotech, Shantha, and Sanofi – are essential for successful vaccine development, particularly in developing vaccines against neglected diseases of the poor like cholera." Certification by WHO of Shanchol™ represents a major milestone as it indicates that the vaccine meets WHO standards of quality, safety, and efficacy, and allows the vaccine to be procured by UN agencies and other international organizations for use in countries around the world. It also accelerates international use of the vaccine because WHO prequalification eliminates the need for country-level market authorization in some countries, which can take years to obtain. WHO prequalification of Shanchol™ is the latest achievement in IVI's mission to develop and introduce innovative, safe, and effective vaccines to protect vulnerable populations in poor countries against deadly diseases including cholera.

November 10th

Mutations in Hereditary Parkinson’s Disease Disrupt System for Disposing of Damaged Mitochondria

Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's Hospital Boston now shows that genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. Findings appear in the November 11, 2011 issue of Cell. Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' peripheries in order to fuel the axons and dendrites that send and receive signals. However, arresting this movement is equally important, says senior investigator Dr. Thomas Schwarz, of Children's F.M. Kirby Neurobiology Center, because it allows mitochondria to be quarantined and destroyed when they go bad. "Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too," Dr. Schwarz says. "It's the equivalent of an environmental disaster in the cell." Studying neurons from fruit flies, rats, and mice, as well as cultured human cells, Dr. Schwarz and colleagues provide the most detailed understanding to date of the effects of the gene mutations, which encode the mutated forms of the proteins Parkin and PINK1. They demonstrate how these proteins interact with proteins responsible for mitochondrial movement -- in particular Miro, which literally hitches a molecular motor onto the organelle. Normally, when mitochondria go bad, PINK1 tags Miro to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion.

Potential New Target for Slowing Spread of Breast Cancer

A new potential target to slow breast cancer tumor progression and metastasis has been identified by a team of researchers led by Dr. Richard Kremer from the Research Institute of the McGill University Health Centre (RI-MUHC). Complications in breast cancer patients are commonly caused by the spread of the disease through metastasis to other parts of the body, most often to the bones and lungs. The new findings, published online on November 7, 2011 in the Journal of Clinical Investigation (JCI), suggest that a specific protein plays a key role in the progression of the disease outside of the initial tumor area. Researchers showed that this particular target, called parathyroid hormone-related protein (PTHrP), present at high levels in cancers, is involved in key stages of breast cancer initiation, progression, and metastatic spread in mice. "We are hoping for a significant effect on the prevention of breast cancer recurrence, growth, and development by using a strategy to decrease the production of that particular protein," says Dr. Richard Kremer, co-director of the Musculoskeletal Axis of the RI-MUHC and a professor in the Department of Medicine at McGill University. To better understand the role of PTHrP in cancer development, researchers eliminated the production of the hormone from mouse breast cells using a strategy called "conditional knockout" and then studied the progression of the tumor. "The results showed that without the presence of PTHrP in the breast, even before the tumor developed, a reduction of 80 to 90 per cent in the growth of the tumor was observed," explains Dr. Kremer. "The removal of this hormone in the breast and breast tumors blocks not only the growth of the tumors, but also its spread to different organs." In order to bring this strategy one step closer to the patient, Dr.

Protein Interactions and Queen Determination in Honey Bees

A honey bee becomes a royal queen or a common worker as a result of the food she receives as a larva. While it has been well established that royal jelly is the diet that makes bees queens, the molecular path from food to queen is still in dispute. However, scientists at Arizona State University, led by Adam Dolezal and Dr. Gro Amdam, together with colleagues at other institutions, have helped reconcile some of the conflicts about bee development and the role of insulin pathways and partner proteins. Their article "IRS and TOR nutrient-signaling pathways act via juvenile hormone to influence honey bee cast fate" has been published in the December 2011 issue of the Journal of Experimental Biology. Central to the dispute within the scientific community about "who would be queen" has been a ground-breaking study published in the journal Nature in 2011 by Japanese scientist Dr. Masaki Kamakura of the Biotechnology Research Center, Toyama Prefectural University. He found that a single protein in royal jelly, called royalactin, activated queen development in larval bees through interaction with an epidermal growth factor receptor (EGFR). Dr. Kamakura's work suggested that insulin signals do not play a role in queen development, despite previous studies suggesting otherwise, including work pioneered with the insulin receptor protein by Dr. Amdam's group. Undeterred by Dr. Kamakura's findings, Dolezal, a doctoral student, and Dr. Amdam, a Pew Biomedical Scholar and professor in ASU's School of Life Sciences, looked for ways to resolve the disparity between the research studies. Amdam's team's first step involved taking control of the insulin receptor's partner protein, IRS, which the insulin receptor relies upon for signaling.

November 9th

Scientists Investigate “Panhandle” Structure of Salmon Virus RNA

A research team at the National Institute of Standards and Technology (NIST) has provided the first look at a genetic structure that may play a critical role in the reproduction of the infectious salmon anemia virus (ISAV), more commonly known as the "fish flu." A scourge in fish farms with a mortality rate as high as 90 percent, ISAV was recently found in wild salmon in the Pacific Northwest for the first time, threatening an already dwindling population and the vast food web it supports. The new research was published online on October 12, 2011 in the Journal of Virology. While there is a vaccine for the virus, it must be administered by injection—a task that is both cumbersome and economically impractical for the aquaculture industry. A drug or vaccine that prevents the spread of the disease by interfering with the virus' ability to replicate its genetic code (contained in eight segments of RNA) would be far more practical for fish farmers and marine biologists to deliver. Dr. Robert Brinson, a NIST scientist working at the Hollings Marine Laboratory (HML) in Charleston, South Carolina, and NIST colleagues Drs. Andrea Szakal and John Marino working at the Institute for Bioscience and Biotechnology Research (IBBR) in Rockville, Maryland, knew from the scientific literature that the family of viruses that includes both the many types of influenza—the causes of yearly human flu outbreaks—and infectious salmon anemia, form "panhandle" structures in their genomic RNA. In human influenza, these panhandles are known to interact with proteins that begin the process of copying and replicating the virus.

Proof-of-Principle for RNAi Treatment of Genetic Bone Disease

Scientists at Penn’s Perelman School of Medicine Center for Research in FOP and Related Disorders have developed a new genetic approach to specifically block the damaged copy of the gene for a rare bone disease, while leaving the normal copy untouched. Lead author Dr. Josef Kaplan, postdoctoral fellow; and senior authors Dr. Eileen M. Shore and Dr. Frederick S. Kaplan, both from the Department of Orthopaedic Surgery, published this new proof-of-principle approach for treating the disease, called FOP, online on October 20, 2011 in Gene Therapy. FOP (fibrodysplasia ossificans progressive) is a rare genetic disorder of progressive extra bone formation for which there is presently no cure. It is caused by a mutation in the gene for ACVR1/ALK2, a bone morphogenetic protein (BMP) receptor that occurs in all classically affected individuals. Individuals who have FOP harbor one normal copy and one damaged copy of the ACVR1/ALK2 gene in each cell. The mutation increases the amount of BMP in cells to greater than normal levels, which initiates the transformation of muscles and cartilage into a disabling second skeleton of bone. Using a special type of RNA molecule engineered to specifically silence the damaged copy of the gene rather than the normal copy -- a process known as RNA interference, or RNAi -- the scientists restored the cellular function caused by the FOP mutation by ridding cells of the mutant ACVR1/ALK2 mRNA. Cells were essentially left with only normal copies of ACVR1/ALK2 mRNA, thus adjusting the protein’s activity to normal, similar to that of cells without the FOP mutation. The human cells used in the experiments were adult stem cells obtained directly from discarded baby teeth donated by FOP patients.