| From: donpat | 3/20/2006 8:32:55 AM | | | | | | Big Problems From Small Avian Flu Mutations
20 March 2006
As the H5N1 time-bomb continues to tick away, the World Health Organization (WHO), its resources stretched to the limit, is trying to plan containment measures and identify a possible vaccine to stem a possible pandemic. While the 100 deaths and 177 documented cases of the avian influenza virus may seem modest, the WHO says that with each new case comes the possibility of the virus mutating into a form that is transmissible from human-to-human. Once this happens, say experts, there will be few, if any, places on Earth where anyone can escape the deadly virus. But researchers are hopeful that a newly developed technology, the glycan microarray, will at least be able to quickly identify new strains of the virus that have the potential to make that critical mutation.
"With continued outbreaks of the H5N1 virus in poultry and wild birds, further human cases are likely," said Ian Wilson, a Scripps Research professor and head of the laboratory that conducted the work on the glycan microarray. "The potential for the emergence of a human-adapted H5 virus, either by re-assortment or mutation, is a clear threat to public health worldwide."
Wilson's lab has been conducting experiments to observe the kind of mutation needed for the H5N1 virus to become transmissible from human-to-human. So far the researchers have examined one strain called A/Vietnam/1203/2004 (Viet04), which was sourced from a 10-year-old Vietnamese boy who died from the infection in 2004. Researchers say that the Viet04 virus is one of the most pathogenic H5N1 viruses studied to date. When they observed the virus, researchers found that the hemagglutinin (the agent responsible for binding the virus to the cell being infected) structure from Viet04 was closely linked to the 1918 virus HA, which caused 50 million deaths worldwide.
The new findings, reported in Science, were made possible using a newly developed microarray technology comprised of hundreds of microscopic assay sites on a single small surface. Using the microarray technology, researchers concluded that only minor mutations are needed for the binding site preference of the avian virus to switch from receptors in the intestinal tract of birds to the respiratory tract of humans. The researchers wrote that these mutations are already: "known in [some human influenza] viruses to increase binding for these receptors."
Receptor specificity for the influenza virus is determined by the glycoprotein hemagglutinin (HA) on the surface of the virus. These viral HAs bind to host cell receptors containing complex glycans-carbohydrates that in turn contain terminal sialic acids. Avian viruses mostly bind to 2-3 linked sialic acids on receptors of intestinal epithelial cells, while human viruses are usually specific for the 2-6 linkage on the epithelial cells of the lungs and upper respiratory tract. These exchanges allow the virus and host membranes to fuse, so that viral genetic material can be transferred to the cell.
The lack of a jump from a 2-3 to a 2-6 receptor is the major reason why human-to-human transmission following avian-to-human infection has not occurred. But the researchers also made careful note that their study is presuming only a single route for the virus to adapt, and that there are likely many as yet "unidentified mutations" that could surface. Alternate routes may allow the virus to switch receptor specificity and make the necessary jump from human-to-human, since "once a foothold in a new host species is made, the virus HA can optimize its specificity to the new host."
"Our recombinant approach to the structural analysis of the Viet04 virus showed that when we inserted HA mutations that had already been shown to shift receptor preference in H3 HAs to the human respiratory tract, the mutations increased receptor preference of the Viet04 HA towards specific human glycans that could serve as receptors on lung epithelial cells," Wilson explained. "The effect of these mutations on the Viet04 HA increases the likelihood of binding to and infection of susceptible epithelial cells."
Although the study seems only to reinforce previous gloomy avian flu predictions, the use of the glycan microarray technology is actually a positive step toward identifying new active virus strains in the field. "This technology allows researchers to assay hundreds of varieties in a single experiment," said Jeremy M. Berg, the director of the National Institute of General Medical Sciences. "The glycan microarray offers a detailed picture of viral receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza, and could prove invaluable in the early identification of emerging viruses that could cause new epidemics."
Source: Scripps Research Institute
scienceagogo.com |
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| From: donpat | 3/20/2006 8:41:01 AM | | | | | | N95 masks
[Snip]
The government bought 4.5 million standard masks for about 10 cents each. Ontario nurses say the masks are inadequate protection against avian flu, and the government needs to buy N95 surgical masks at about 10 times the cost.
Nurses demanded and received N95 masks three years ago during Toronto's SARS outbreak.
ctv.ca |
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| To: donpat who wrote (36) | 3/21/2006 9:39:37 AM | | From: donpat | | | | James Baker designs nanoparticles to guide drugs directly into cancer cells, which could lead to far safer treatments.
March/April 2006
Nanomedicine
By Kevin Bullis
This article is the second in a series of 10 stories we're running over two weeks, covering today's most significant (and just plain cool) emerging technologies. It's part of our annual "10 Emerging Technologies" report, which appears in the March/April print issue of Technology Review.
The treatment begins with an injection of an unremarkable-looking clear fluid. Invisible inside, however, are particles precisely engineered to slip past barriers such as blood vessel walls, latch onto cancer cells, and trick the cells into engulfing them as if they were food. These Trojan particles flag the cells with a fluorescent dye and simultaneously destroy them with a drug.
Developed by University of Michigan physician and researcher James Baker, these multipurpose nanoparticles -- which should be ready for patient trials later this year -- are at the leading edge of a nanotechnology-based medical revolution. Such methodically designed nanoparticles have the potential to transfigure the diagnosis and treatment of not only cancer but virtually any disease. Already, researchers are working on inexpensive tests that could distinguish a case of the sniffles from the early symptoms of a bioterror attack, as well as treatments for disorders ranging from rheumatoid arthritis to cystic fibrosis. The molecular finesse of nanotechnology, Baker says, makes it possible to "find things like tumor cells or inflammatory cells and get into them and change them directly."
[To view an illustration of nanoparticles delivering a drug, click here. technologyreview.com ]
Cancer therapies may be the first nanomedicines to take off. Treatments that deliver drugs to the neighborhood of cancer cells in nanoscale capsules have recently become available for breast and ovarian cancers and for Kaposi's sarcoma. The next generation of treatments, not yet approved, improves the drugs by delivering them inside individual cancer cells. This generation also boasts multifunction particles such as Baker's; in experiments reported last June, Baker's particles slowed and even killed human tumors grown in mice far more efficiently than conventional chemotherapy.
"The field is dramatically expanding," says Piotr Grodzinski, program director of the National Cancer Institute's Alliance for Nanotechnology in Cancer. "It's not an evolutionary technology; it's a disruptive technology that can address the problems which former approaches couldn't."
The heart of Baker's approach is a highly branched molecule called a dendrimer. Each dendrimer has more than a hundred molecular "hooks" on its surface. To five or six of these, Baker connects folic-acid molecules. Because folic acid is a vitamin, most cells in the body have proteins on their surfaces that bind to it. But many cancer cells have significantly more of these receptors than normal cells. Baker links an anticancer drug to other branches of the dendrimer; when cancer cells ingest the folic acid, they consume the deadly drugs as well.
The approach is versatile. Baker has laden the dendrimers with molecules that glow under MRI scans, which can reveal the location of a cancer. And he can hook different targeting molecules and drugs to the dendrimers to treat a variety of tumors. He plans to begin human trials later this year, potentially on ovarian or head and neck cancer.
Mauro Ferrari, a professor of internal medicine, engineering, and materials science at Ohio State University, is hopeful about what Baker's work could mean for cancer patients. "What Jim is doing is very important," he says. "It is part of the second wave of approaches to targeted therapeutics, which I think will have tremendous acceleration of progress in the years to come."
To hasten development of nano-based therapies, the NCI alliance has committed $144.3 million to nanotech-related projects, funding seven centers of excellence for cancer nanotechnology and 12 projects to develop diagnostics and treatments, including Baker's.
Baker has already begun work on a modular system in which dendrimers adorned with different drugs, imaging agents, or cancer-targeting molecules could be "zipped together." Ultimately, doctors might be able to create personalized combinations of nanomedicines by simply mixing the contents of vials of dendrimers.
Such a system is at least 10 years away from routine use, but Baker's basic design could be approved for use in patients in as little as five years. That kind of rapid progress is a huge part of what excites doctors and researchers about nanotechnology's medical potential. "It will completely revolutionize large branches of medicine," says Ferrari.
technologyreview.com |
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| To: donpat who wrote (1167) | 3/22/2006 1:14:28 AM | | From: worksinjammies | | | | One doesn't even need to hold this stock to hope for that very outcome....how many stocks can you say that about....I'm still bitter about not getting on board in the .20-.30 range when you first led me here!! lol
All kidding aside, their latest press release sounded pretty encouraging.
Regards, WIJ |
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| From: donpat | 3/22/2006 8:13:14 AM | | | | | | Organizing Gold Nanoparticles with DNA
[Off topic....maybe....one never knows!]
Nanotechnology : March 22, 2006
Tiny billionth-of-a-meter sized clusters of gold atoms — gold “nanoparticles” — are being widely studied by scientists. They have many useful potential applications, from carriers for cancer-treatment drugs to digital data storage. But many of these applications, particularly those in electronics, require that the nanoparticles form ordered arrays that can be hard to achieve. At Arizona State University (ASU), researchers have discovered that grids made of DNA strands are excellent templates for neatly organizing gold nanoparticles.
“The collective properties of nanoparticles are heavily dependent on how the particles are grouped. Achieving an even spacing between the particles is particularly important, but can be difficult,” said the study’s lead scientist, ASU chemist Hao Yan. “However, when deposited onto a DNA grid the particles fall neatly into patterns with little effort on our part.”
[Diagram caption]
(a) The two-tile system that forms the DNA nanogrids. Tile A is blue and tile B is orange. The numbers indicate the complementary “sticky” ends that allow the tiles to adhere together, with 1 pairing with 1´ ?and so on. The red strand on tile A is A15. (b) The DNA nanogrid, showing the A15 strand on each A tile. (c) Gold nanoparticles on the DNA grids. The zigzagged black lines surrounding the nanoparticles represent T15 strands. Credit: Hao Yan
Yan and his research group used gold nanoparticles that were five nanometers in diameter. Rather than being bare, the particles were coated with a layer of DNA “pieces,” called “T15 sequences,” which radiated from the particles’ surfaces like arms. The scientists then deposited the particles onto lattices formed by two types of cross-shaped DNA “tiles”, “A” tiles and “B” tiles, that bind together in an alternating fashion to form the DNA grid.
At regular intervals, each A tile contained a short single strand (called an “A15” strand) that protruded out of the tile surface. These strands served as tethering points for the T15-coated nanoparticles, allowing the particles to stick to the DNA surface, a bit like DNA-nanoparticle “Velcro.”
This configuration caused the nanoparticles to “self assemble” into a square pattern — each particle sitting on one A tile — with a nearly constant particle-particle distance of about 38 nanometers. The group confirmed this using an atomic force microscope, a very powerful imaging device.
However, this result, while welcomed by the scientists, wasn’t exactly what they expected.
“We were pleased that the gold nanoparticles formed a very regular square pattern, but it wasn’t quite the pattern we thought we’d see,” said Yan. “If you picture nine DNA tiles forming a square, we predicted that five particles would be organized on the square — one on each corner and one in the middle. But the pattern we observed lacked that middle particle.”
The scientists guess that this is due to the T15 sequence layer, which effectively increases the diameter of each nanoparticle and, moreover, makes each particle highly negatively charged. As a result, the nanoparticles repel each other if they are too close together, which limits the minimum particle-particle distance. Therefore, a particle located at the center of the square would violate this limit.
In future research, Yan and may try to use this organization method to form more complex nanoparticle arrays, such as denser patterns or patterns of different shapes, by altering the particles’ DNA coating.
Citation: “Periodic Square-Like Gold Nanoparticle Arrays Templated by Self-Assembled 2D DNA Nanogrids on a Surface,” Nano Lett., Vol. 6, No. 2, 248-251 (2006)
pubs.acs.org
by Laura Mgrdichian, Copyright 2006 PhysOrg.com
physorg.com |
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