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Archive - 2014

January 20th

Hot Pepper Genome Sequenced

An article by Pat Bailey in the January 19 issue of The Davis Enterprise reports on the sequencing of the hot pepper (Capsicum annuum)(image) genome by a large international team, which included scientists from the University of California-Davis and Seoul National University in Korea. The research was published online on January 19, 2014 in an open-access article in Nature Genetics. According to Bailey, the new genome sheds light on the biology of the pepper’s characteristic spiciness, as well as its fruit-ripening and disease-resistance mechanisms. In addition, the genome data reveals new information v ital. for improving the horticultural, nutritional, and medicinal qualities of these peppers, for which the annual global production has grown more than 40-fold in the last two decades and now is greater than $14.4 billion. According to Bailey’s article, the researchers sequenced a hot pepper landrace, or domesticated variety, from the Mexican state of Morelos. The variety, known as Criolo de Morelos 334, has consistently exhibited high levels of disease resistance and has been extensively used in hot-pepper research and breeding. The research team also provided sequencing data for the Perennial and Dempsey cultivated pepper varieties and for the related habanero pepper species (Capsicum chinense). The sequencing also uncovered evidence suggesting that the pungency, or “heat,” of the hot pepper originated through the evolution of new genes by duplication of existing genes and changes in gene expression after the peppers evolved into species. Bailey said that it was already known that pepper pungency was caused by the accumulation of naturally occurring chemicals called capsaicinoids, unique to the Capsicum genus.

Hookworm Genome Decoded; Insights May Aid Development of Therapies

Going barefoot in parts of Africa, Asia, and South America contributes to hookworm infections, which afflict an estimated 700 million of the world's poor. The parasitic worm lives in the soil and enters the body through the feet. By feeding on victims' blood, the worms cause anemia and, in children, stunted growth and learning problems. Now, researchers at Washington University School of Medicine in St. Louis, together with colleagues, have decoded the genome of the hookworm, Necator americanus, finding clues to how it infects and survives in humans and to aid in development of new therapies to combat hookworm disease. The research was published online on January 19, 2014 in an open-access article in Nature Genetics. "We now have a more complete picture of just how this worm invades the body, begins feeding on the blood, and successfully evades the host immune defenses," said senior author Makedonka Mitreva, Ph.D., assistant professor of medicine and of genetics and a member of The Genome Institute at the School of Medicine. "This information will accelerate development of new diagnostic tools and vaccines against the infection." Necator americanus causes about 85 percent of human hookworm infections, which are not usually fatal. However, in pregnant women, the worm can cause severe anemia, leading to maternal deaths and low birth weights that contribute to newborn deaths. The deworming drug albendazole typically is given as part of mass treatment programs in areas with endemic infection, but its repeated and excessive use is leading to treatment failures and drug resistance in some regions, Dr. Mitreva said. Hookworms are common in areas of extreme poverty that lack indoor plumbing. The worm's eggs are excreted in the feces of infected individuals, contaminating the soil.

Sunlight Causes NO to Move from Skin to Circulation, Reducing Heart Attack Risk

Exposing skin to sunlight may help to reduce blood pressure and thus cut the risk of heart attack and stroke, a study published in the Journal of Investigative Dermatology suggests. Research carried out at the Universities of Southampton and Edinburgh shows that sunlight alters levels of the small messenger molecule, nitric oxide (NO) (image) in the skin and blood, reducing blood pressure. Dr. Martin Feelisch, Professor of Experimental Medicine and Integrative Biology at the University of Southampton, comments: "NO along with its breakdown products, known to be abundant in skin, is involved in the regulation of blood pressure. When exposed to sunlight, small amounts of NO are transferred from the skin to the circulation, lowering blood vessel tone; as blood pressure drops, so does the risk of heart attack and stroke." While limiting sunlight exposure is important to prevent skin cancer, the authors of the study, including Dr. Richard Weller of the University of Edinburgh, suggest that minimizing exposure may be disadvantageous by increasing the risk of prevalent conditions related to cardiovascular disease. Cardiovascular disease, often associated with high blood pressure, accounts for 30 per cent of deaths globally each year. Blood pressure and cardiovascular disease are known to vary according to season and latitude, with higher levels observed in winter and in countries farther from the equator, where ultraviolet radiation from the sun is lower. During the study, the skin of 24 healthy individuals was exposed to ultraviolet (UVA) light from tanning lamps for two sessions of 20 minutes each. In one session, the volunteers were exposed to both the UVA rays and the heat of the lamps. In another, the UV rays were blocked so that only the heat of the lamps affected the skin.

New Drug Targets/Epigenetic Changes Found in Cocaine Addiction

Researchers from the Icahn School of Medicine at Mount Sinai in New York have identified a new molecular mechanism by which cocaine alters the brain's reward circuits and causes addiction. Published online in PNAS by Dr. Eric J. Nestler, M.D., Ph.D., and colleagues, the preclinical research reveals how an abundant enzyme and synaptic gene affect a key reward circuit in the brain, changing the ways genes are expressed in the nucleus accumbens. The DNA itself does not change, but its "mark" activates or represses certain genes encoding synaptic proteins within the DNA. The marks indicate epigenetic changes—changes made by enzymes—that alter the activity of the nucleus accumbens. In a mouse model, the research team found that chronic cocaine administration increased levels of an enzyme called PARP-1 or poly(ADP-ribosyl)ation polymerase-1 (image). This increase in PARP-1 leads to an increase in its PAR marks at genes in the nucleus accumbens, contributing to long-term cocaine addiction. Although this is the first time PARP-1 has been linked to cocaine addiction, PARP-1 has been under investigation for cancer treatment. "This discovery provides new leads for the development of anti-addiction medications," said the study's senior author, Dr. Nestler, Nash Family Professor of Neuroscience and Director of the Friedman Brain Institute, at the Icahn School of Medicine at Mount Sinai. Dr. Nestler said that the research team is using PARP to identify other proteins regulated by cocaine. PARP inhibitors may also prove valuable in changing cocaine's addictive power. Kimberly Scobie, Ph.D., the lead investigator and postdoctoral fellow in Dr. Nestler's laboratory, underscored the value of implicating PARP-1 in mediating the brain's reward center.

Illumina’s NextSeq™ 500 Brings Next-Gen Sequencing to the Desktop

In a January 14, 2014 press release, Illumina, Inc. (NASDAQ:ILMN) announced the immediate availability of a transformative addition to its industry-leading next-generation sequencing portfolio with the launch of the NextSeq 500 System. The new sequencer packs high-throughput performance into an affordable desktop form factor, enabling researchers to perform the most popular sequencing applications in less than a day. The NextSeq 500 System is priced at $250,000. “Illumina’s sequencing portfolio is the most comprehensive in the world, and the addition of the NextSeq 500 System furthers this distinction by enabling next-generation sequencing to become an everyday tool,” said Jay Flatley, CEO of Illumina. “The NextSeq 500 was reimagined from the ground up and uses technology breakthroughs in optics, fluidics, and chemistry to bring high-throughput power to the desktop at a significantly reduced cost.” The NextSeq 500 System delivers the power of high-throughput sequencing with the load-and-go simplicity of a desktop sequencer, effectively transforming a broad range of high-throughput applications into affordable, everyday research tools. Its push-button operation delivers a one-day turnaround for a number of popular sequencing applications, including one whole human genome and up to 16 exomes, up to 20 non-invasive prenatal testing samples, up to 20 transcriptomes, up to 48 gene expression samples and up to 96 targeted panels. With its streamlined informatics, sequencing data can be run through a range of open-source or commercial pipelines or instantly transferred, analyzed, and stored securely in BaseSpace® or the new BaseSpace® OnSite for researchers needing an on-premises solution.

New Sequencing System from Illumina May Enable World’s First $1,000 Genomes

In a January 14, 2014 press release, Illumina, Inc. (NASDAQ:ILMN) announced that it had broken the ‘sound barrier’ of human genomics by enabling the $1,000 genome. This achievement is made possible by the Illumina’s new HiSeq X Ten Sequencing System. This platform includes dramatic technology breakthroughs that enable researchers to undertake studies of unprecedented scale by providing the throughput to sequence tens of thousands of human whole genomes in a single year in a single lab. Initial customers for the transformative HiSeq X Ten System include Macrogen, a global next-generation sequencing service organization based in Seoul, South Korea and its CLIA laboratory in Rockville, Maryland, the Broad Institute in Cambridge, Massachusetts, the world’s leading research institute in genomic medicine, and the Garvan Institute of Medical Research in Sydney, Australia, a world leader in biomedical research. “The sequencing capacity and economies of scale of the HiSeq X Ten facility will also allow Garvan to accelerate the introduction of clinical genomics and next-generation medicine in Australia,” said Professor John Mattick, Executive Director of the Garvan Institute of Medical Research. “We expect the HiSeq X Ten to underpin a new phase of collaboration between government, industry, and other medical research stakeholders.” “For the first time, it looks like it will be possible to deliver the $1,000 genome, which is tremendously exciting,” said Dr. Eric Lander, founding director of the Broad Institute and a professor of biology at MIT. “The HiSeq X Ten should give us the ability to analyze complete genomic information from huge sample populations.

January 18th

More Rigid Analogs of ADEPS Have Potent Antibiotic Activity

As concerns about bacterial resistance to antibiotics grow, researchers are racing to find new kinds of drugs to replace ones that are no longer effective. One promising new class of molecules called acyldepsipeptides — ADEPs — kills bacteria in a way that no marketed antibacterial drug does — by altering the pathway through which cells rid themselves of harmful proteins. Now, researchers from Brown University and the Massachusetts Institute of Technology have shown that giving the ADEPs more backbone can dramatically increase their biological potency. By modifying the structure of the ADEPs in ways that make them more rigid, the team prepared new ADEP analogs that are up to 1,200 times more potent than the naturally occurring molecule. A paper describing the research was published online on January 14, 2014 in the Journal of the American Chemical Society. “The work is significant because we have outlined and validated a strategy for the enhancing the potency of this promising class of antibacterial drug leads,” said Dr. Jason Sello, professor of chemistry at Brown and the paper’s senior author. “The molecules that we have synthesized are among the most potent antibacterial agents ever reported in the literature.” ADEPs kill bacteria by a mechanism that is distinct from all clinically available anti-bacterial drugs. They work by binding to a protein in bacterial cells that acts as a “cellular garbage disposal,” as Dr. Sello describes it. This barrel-shaped protein, called ClpP, breaks down proteins that are misfolded or damaged and could be harmful to the cell. However, when ClpP is bound by an ADEP, it’s no longer so selective about the proteins it degrades In essence, the binding by ADEP causes the garbage disposal to run amok and devour healthy proteins throughout the cell. For bacteria, a runaway ClpP is deadly.

Novel Biological Mechanism Relays Electrons Along Hemes in Proteins in Mineral-Breathing Bacteria

Researchers simulating how certain bacteria run electrical current through tiny molecular wires have discovered a secret that nature uses for electron travel. The results are key to understanding how the bacteria do chemistry in the ground, and will help researchers use these bacteria in microbial fuel cells, batteries, or for turning waste into electricity. Within the bacteria's protein-based wire, molecular groups called hemes communicate with each other to allow electrons to hop along the chain like stepping stones. The researchers found that evolution has set the protein up so that, generally, when the electron's drive to hop is high, the heme stepping stones are less tightly connected, like being farther apart; when the drive to hop is low, the hemes are more closely connected, like being closer together. The outcome is an even electron flow along the wire. This is the first time scientists have seen this evolutionary design principle for electron transport, the researchers reported online on January 2, 2014 in PNAS. "We were perplexed at how weak the thermodynamic driving force was between some of these hemes," said geochemist Dr. Kevin Rosso of the Department of Energy's Pacific Northwest National Laboratory. "But it turns out those pairs of hemes are essentially hugging each other. When the driving force is strong between hemes, they are only shaking hands. We've never seen this compensation scheme before, but it seems that the purpose is to allow the protein to transfer electrons with a steady flow along heme wires." Certain bacteria breathe using metal like people use oxygen. In the process, these bacteria steal electrons from carbon and ultimately transfer the electrons to metals or minerals in the ground.

Newly Discovered ATP Receptor Helps Plants Manage Environmental Change, Pests, and Wounds

ATP (adenosine triphosphate) is the main energy source inside a cell and is considered to be the high energy molecule that drives all life processes in animals, including humans. Outside the cell, membrane receptors that attract ATP drive muscle control, neurotransmission, inflammation, and development. Now, researchers at the University of Missouri (MU) have found, for the first time, the same receptor in plants and believe it to be a vital component in the way plants respond to dangers, including pests, environmental changes, and plant wounds. This discovery could lead to herbicides, fertilizers, and insect repellants that naturally work with plants to make them stronger. "Plants don't have ears to hear, fingers to feel, or eyes to see," said Dr. Gary Stacey an investigator in the MU Bond Life Sciences Center and professor of plant sciences in the College of Agriculture, Food and Natural Resources. "Plants use these chemical signals to determine if they are being preyed upon or if an environmental change is occurring that could be detrimental to the plant. We have evidence that when ATP is outside of the cell it is probably a central signal that controls the plant's ability to respond to a whole variety of stresses." Dr. Stacey and fellow researchers, graduate student Jeongmin Choi, and postdoctoral fellow Dr. Kiwamu Tanaka, screened 50,000 plants over two years to identify the ATP receptors. By isolating a key gene in the remaining plants, scientists found the receptor that aids in plant development and helps repair a plant during major events. "We believe that when a plant is wounded, ATP is released into the wound and triggers the gene expressions necessary for repair," Dr. Stacey said.

Bacterium “Breathes” Toxic Metals to Survive, Potential for Industry and Environment

Buried deep in the mud along the banks of a remote salt lake near Yosemite National Park are colonies of bacteria with an unusual property: they breathe a toxic metal to survive. Researchers from the University of Georgia discovered the bacteria on a recent field expedition to Mono Lake (image) in California, and their experiments with this unusual organism show that it may one day become a useful tool for industry and environmental protection. The bacteria use elements that are notoriously poisonous to humans, such as antimony and arsenic, in place of oxygen, an ability that lets them survive buried in the mud of a hot spring in this unique saline soda basin. "Just like humans breathe oxygen, these bacteria respire poisonous elements to survive," said Chris Abin, co-author of a paper describing the research published in the January 7, 2014 issue of Environmental Science & Technology and a doctoral candidate in microbiology. "It is particularly fond of arsenic, but it uses other related elements as well, and we think it may be possible to harness these natural abilities to make useful products out of different elements." Antimony, for example, is a naturally occurring silver-colored metal that is widely used by numerous industries to make plastics, vulcanized rubber, flame retardants, and a host of electronic components including solar cells and LEDs. To make these products, antimony must be converted into antimony trioxide, and this bacterium is capable of producing two very pure types of crystalline antimony trioxide perfectly suited for industry. Traditional chemical methods used to convert antimony ore into antimony trioxide can be expensive, time-consuming, and often create harmful byproducts.