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Fatal Infections of Mountain Gorillas Linked to Human Contact

In a study published in the April 2011 issue of the journal Emerging Infectious Diseases, an international team of researchers report that a virus that causes respiratory disease in humans infected and contributed to the deaths of mountain gorillas in Virunga National Park in Africa. This finding raises questions about the safety of ecotourism for endangered species. The study was conducted by scientists at Columbia University's Center for Infection and Immunity (CII), Roche 454 Life Sciences, the UC Davis Wildlife Health Center, and the Mountain Gorilla Veterinary Project, a US-based non-profit organization. Mountain gorillas (Gorilla beringei beringei) live primarily in Rwanda, Uganda, and the Democratic Republic of Congo in Bwindi Impenetrable National Park and Virunga National Park, which houses about a third of the world's remaining gorilla population. Despite international efforts to protect this endangered species, there are currently fewer than 800 living mountain gorillas in the world. Now, this study, which focuses on an outbreak of respiratory disease in the Hirwa group of mountain gorillas in 2009, suggests that these animals may also be susceptible to human pathogens. Infectious diseases, especially respiratory ones, are the second leading cause of sudden deaths among mountain gorillas, after poaching. Growing ecotourism has increased interactions between humans and wild animals living in these parks, intensifying the chance for disease transmission. While ecotourism has heightened awareness of the need to safeguard endangered species, world travel also has the potential to quickly spread disease. Local authorities have recently tried to reduce animals' exposure to potentially harmful pathogens by limiting the number of tourists visiting wildlife parks and requiring visitors to wear protective masks.

Yellow Dye Extends Life, Slows Disease in Worms

Basic Yellow 1, a dye used in neuroscience laboratories around the world to detect damaged protein in Alzheimer's disease, turns out to be a wonder drug for nematode worms. In a study appearing in the March 30, online edition of Nature, the dye, also known as Thioflavin T (ThT) extended lifespan in healthy nematode worms by more than 50 percent and slowed the disease process in worms bred to mimic aspects of Alzheimer's. The research, conducted at the Buck Institute for Research on Aging, could open new ways to intervene in aging and age-related disease. The study highlights a process called protein homeostasis – the ability of an organism to maintain the proper structure and balance of its proteins, which are the building blocks of life. Genetic studies have long indicated that protein homeostasis is a major contributor to longevity in complex animals. Many degenerative diseases have been linked to a breakdown in the process. Buck faculty member Dr. Gordon Lithgow, who led the research, said this study points to the use of compounds to support protein homeostasis, something that ThT, did as the worms aged. ThT works as a marker of neurodegenerative diseases because it binds amyloid plaques – the toxic aggregated protein fragments associated with Alzheimer's. In the nematodes ThT's ability to not only bind, but also slow the clumping of toxic protein fragments, may be key to the compound's ability to extend lifespan, according to Dr. Lithgow. "We have been looking for compounds that slow aging for more than ten years and ThT is the best we have seen so far," said Dr. Lithgow. "But more exciting is the discovery that ThT so dramatically improves nematode models of disease-related pathology as well," said Dr.

Hidden Elm Population May Hold Genes to Combat Dutch Elm Disease

Two U.S. Department of Agriculture (USDA) scientists may have discovered "the map to El Dorado" for the American elm—a previously hidden population of elms that may carry genes for resistance to Dutch elm disease. The disease kills individual branches and eventually the entire tree within one to several years. It has been accepted for 80 years that American elms (Ulmus americana) are tetraploids, trees with four copies of each chromosome. But there have also been persistent but dismissed rumors of trees that had fewer copies—triploids, which have three copies of chromosomes, or diploids, which have two copies. Now botanist Alan T. Whittemore and geneticist Richard T. Olsen with USDA's Agricultural Research Service (ARS) have proven beyond question that diploid American elms exist as a subset of elms in the wild. Their findings will be published in the April 2011 edition of the American Journal of Botany and were released online on March 30, 2011. Whittemore and Olsen work at the U.S. National Arboretum operated by ARS in Washington, D.C. American elms once lined the country's streets and dominated eastern forests until they succumbed by the millions after Dutch elm disease arrived in the United States in 1931. Yet elms are still one of the most important tree crops for the $4.7 billion-a-year nursery industry, especially since the introduction of a very few new trees with some tolerance to the disease. American elms remain popular because of their stately beauty, their rapid leaf litter decay, and their ability to stand up to city air pollution. It was one of the disease-tolerant elm trees—Jefferson, released jointly by ARS and the National Park Service in 2005—that put Whittemore and Olsen on the trail of the diploid. "Jefferson is a triploid.

Mystery of 22nd Amino Acid Production Is Solved

The most recently discovered amino acid, pyrrolysine, is produced by a series of just three chemical reactions with a single precursor – the amino acid lysine, according to new research. Scientists at Ohio State University used mass spectrometry and a series of experiments to discover how cells make the amino acid, a process that until now had been unknown. They confirmed that pyrrolysine is made from enzymatic reactions with two lysine molecules – a surprising finding, given that some portions of its structure suggested to researchers that it might have more complex origins. The research is published in the March 31 issue of the journal Nature. Pyrrolysine is rare and so far is known to exist in about a dozen organisms. But its discovery in 2002 as a genetically encoded amino acid in methane-producing microbes raised new questions about the evolution of the genetic code. Pyrrolysine is among 22 amino acids that are used to create proteins from the information stored in genes. Proteins are essential to all life and perform most of the work inside cells. This information about how pyrrolysine is produced – its biosynthetic pathway – offers a more complete understanding of how amino acids are made. And because of its rarity, this molecule is emerging as a handy tool for manipulating proteins in biomedical research. With its production mechanism identified, scientists can use that information to devise ways to mass-produce similar or identical synthetic molecules for a variety of research purposes. The Ohio State scientists had a genuine "ah-ha" moment over the course of the study. As part of their experimentation, they combined lysine with one other amino acid and some enzymes and expected this to produce what is called an intermediate – essentially, a piece of an amino acid that is generated in the biosynthesis process.

Scientists Seek to Selectively Starve Kidney Cancer Cells

Researchers at the University of Texas Southwestern Medical Center have discovered genetic pathways to selectively starve kidney cancer cells. Two separate studies indicate that both rare and common cases of kidney cancer may be susceptible to a new class of drugs that inhibits cancer cells from generating the energy needed to survive. In one study, available online and scheduled for the May 5 issue of the journal Oncogene, researchers found that inactivating the gene von Hippel-Lindau (VHL) in mice blocked cells from using oxygen to provide energy to the cell, forcing them to use another method of energy generation, namely glycolysis – the conversion of glucose to lactic acid. Because the VHL gene is inactive in about 90 percent of clear-cell renal cell carcinomas, the most common type of kidney cancer in humans, the study provides a rationale for the evaluation of glycolytic inhibitors in fighting kidney cancer, said Dr. James Brugarolas, assistant professor of internal medicine and developmental biology and the study's senior author. "It would be expected to kill cancer cells preferentially and spare most normal cells that would still have mitochondrial respiration to rely on," said Dr. Brugarolas. An estimated 58,000 new cases of kidney cancer were reported in the U.S. in 2010, and 13,040 died of the disease. Based on incidence of this cancer from 2005 to 2007, 1 in 67 people will be diagnosed with cancer of the kidney or renal pelvis during his or her lifetime. The study also revealed that the effect of VHL loss was mediated by hypoxia-inducible factors (HIF), a family of proteins that binds to specific DNA sequences and responds to decreases in oxygen, known as hypoxia. "We discovered that simultaneous inactivation of HIF rescued the mice from the effects of VHL inactivation," Dr. Brugarolas said.

54 Beneficial Compounds Found in Pure Maple Syrup

University of Rhode Island researcher Dr. Navindra Seeram has discovered 34 new beneficial compounds in pure maple syrup and confirmed that 20 compounds discovered last year in preliminary research play a key role in human health. On March 30, 2011, at the 241st American Chemical Society's National Meeting in Anaheim, California, the URI assistant pharmacy professor told scientists from around the world that his URI team has now isolated and identified 54 beneficial compounds in pure maple syrup from Quebec, five of which have never been seen in nature. "I continue to say that nature is the best chemist, and that maple syrup is becoming a champion food when it comes to the number and variety of beneficial compounds found in it," Dr. Seeram said. "It's important to note that in our laboratory research we found that several of these compounds possess anti-oxidant and anti-inflammatory properties, which have been shown to fight cancer, diabetes, and bacterial illnesses." These discoveries of new molecules from nature can also provide chemists with leads that could prompt synthesis of medications that could be used to fight fatal diseases, Dr. Seeram said. "We know that the compounds are anti-inflammatory agents and that inflammation has been implicated in several chronic diseases, such as heart disease, diabetes, certain types of cancers and neurodegenerative diseases, such as Alzheimer's," Dr. Seeram said. As part of his diabetes research, Dr. Seeram has collaborated with Dr. Chong Lee, professor of nutrition and food sciences in URI's College of the Environment and Life Sciences. The scientists have found that maple syrup phenolics, the beneficial anti-oxidant compounds, inhibit two carbohydrate hydrolyzing enzymes that are relevant to Type 2 diabetes management. The irony of finding a potential anti-diabetes compound in a sweetener is not lost on Dr. Seeram.

Scientists Sequence Protein from 600,000-Year-Old Mammoth

Researchers from the University of York and Manchester have successfully extracted protein from the bones of a 600,000-year-old mammoth, paving the way for the identification of ancient fossils. Using an ultra-high resolution mass spectrometer, bio-archaeologists were able to produce a near complete collagen sequence for the West Runton Elephant, a Steppe Mammoth skeleton which was discovered in cliffs in Norfolk, UK, in 1990. The remarkable 85 percent complete skeleton - the most complete example of its species ever found in the world - is preserved by the Norfolk Museums and Archaeology Service in Norwich. Bio-archaeologist Professor Matthew Collins, from the University of York’s Department of Archaeology, said: “The time depth is absolutely remarkable. Until several years ago we did not believe we would find any collagen in a skeleton of this age, even if it was as well-preserved as the West Runton Elephant. We believe protein lasts in a useful form ten times as long as DNA which is normally only useful in discoveries of up to 100,000 years old in Northern Europe. The implications are that we can use collagen sequencing to look at very old extinct animals. It also means we can look through old sites and identify remains from tiny fragments of bone.” Dr Mike Buckley, from the Faculty of Life Sciences at the University of Manchester, said: “What is truly fascinating is that this fundamentally important protein, which is one of the most abundant proteins in most (vertebrate) animals, is an ideal target for obtaining long lost genetic information." The collagen sequencing was carried out at the Centre for Excellence in Mass Spectrometry at the University of York and it is arguably the oldest protein ever sequenced; short peptides (chains of amino acids) have controversially been reported from dinosaur fossils.

Nanobioconjugate Targets Deadly Breast Cancer Cells

Throwing stones at castle walls is one way to attack an enemy, but sneaking inside makes the target much more vulnerable. Researchers at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute have employed a similar strategy using a mouse model to target important mechanisms inside the most challenging breast cancer cells. Earlier studies at Cedars-Sinai found a similar approach effective in attacking malignant brain tumor targets. Unlike other drugs that target cancer cells from outside and often injure normal cells as a side effect, this therapy consists of multiple drugs chemically bonded to a "transport vehicle." The drugs bypass healthy cells, accumulate inside tumor cells and attack molecular targets that enable cancer cells to grow and spread. Studies using a mouse model show this highly targeted approach, using combinations of drugs, to be more effective than standard treatment methods. This research targeted HER2-positive breast cancer – a type that, due to a genetic mutation, makes excessive amounts of a protein that promotes the growth of cancer cells. HER2-positive breast cancers tend to be more aggressive and less responsive to treatment than other breast cancers. One commonly used antitumor drug, trastuzumab (Herceptin®), is sometimes beneficial, but with advantages and disadvantages. It is an antibody to the HER2 antigen, which means it naturally seeks out this protein in cancers. But its effectiveness as a treatment usually is limited because in 66 to 88 percent of patients, the tumors become resistant within the first year of treatment. Herceptin also can injure normal organs it contacts. The researchers reported in their recent studies, published in the February 19, 2011 issue of Cancer Research, that the new drug carried multiple molecular components, each with a distinct role.

Irish Hare Threatened

Researchers at Queen’s University Belfast in Northern Ireland have issued a stark warning about the future of the Irish hare and the threat it faces from the European ‘brown’ hare, which has set up home in Mid-Ulster and West Tyrone. Dr. Neil Reid from Quercus (Queen’s University’s Centre for Biodiversity and Conservation Science), said: “In March 2011, the Northern Ireland Assembly voted to outlaw hare coursing in Northern Ireland to protect the future of the Irish hare. But our native hare remains vulnerable to another serious threat – that of the invading European hare.” European hares are found in Britain and continental Europe, but they have been highly successful in invading many countries beyond their native range in south-west Europe and parts of Asia. There have been many studies on their impact on native species. Dr. Reid reviewed these studies to get a clearer picture of how much of a threat the invading species might be to the Irish hare. The study, published in the March 2011 issue of the international journal Biological Invasions, suggested that European hares exhibit strong competition for habitat space and food resources with native species, most notably other hare species. It also warns that disease and parasite transmission and climate change may give the invading European hare an edge over the native species. Dr. Reid added: “The Irish hare represents an evolutionary unique lineage, which is restricted to Ireland where it has been present since before the last glacial maximum, making it one of our few native mammal species. Hence, it has been isolated for 30,000-60,000 years.

Apoptosis-Targeted Drug May Prove Useful in Multiple Cancers

Researchers at the University of Michigan Comprehensive Cancer Center have developed a new drug called AT-406 with potential to treat multiple types of cancer. A study published online on March 28, 2011, in the Journal of Medicinal Chemistry showed that AT-406 effectively targets proteins that block normal cell death from occurring. Blocking these proteins caused tumor cells to die, while not harming normal cells. The researchers believe the drug could potentially be used alone or in combination with other treatments. The normal cell death process, called apoptosis, is what keeps normal cells in check. When apoptosis is disrupted, cells reproduce uncontrollably, which is a hallmark of human cancer. "Removing key apoptosis blockades in tumor cells is a completely new cancer therapeutic approach and could have benefit for the treatment of many types of human tumors," said study senior author Dr. Shaomeng Wang, Warner-Lambert/Parke-Davis Professor in Medicine and director of the Cancer Drug Discovery Program at the U-M Comprehensive Cancer Center. Dr. Wang's laboratory has been pursuing new cancer treatments aimed at this cell death pathway since 2003. His team designed and made AT-406 and tested it in the laboratory in 2006. The small-molecule drug homes in directly on the proteins – called inhibitor of apoptosis proteins or IAPs – that block cell death. The researchers found that AT-406 destroyed these proteins in cancer cells. Meanwhile, the drug had little to no effect on normal cells. In animal models, the drug shrank tumors but caused few side effects. The drug is designed to be taken by mouth, which researchers say will make it easier than traditional intravenous chemotherapies to administer.

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