Carbon Nanostructures: Elixir or Poison?

Carbon Nanostructures: Elixir or Poison?

  1:15:00 AM    Science Lover

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A Los Alamos National Laboratory toxicologist and a multidisciplinary team of researchers have documented potential cellular damage from "fullerenes" -- soccer-ball-shaped, cage-like molecules composed of 60 carbon atoms. The team also noted that this particular type of damage might hold hope for treatment of Parkinson's disease, Alzheimer's disease, or even cancer.

Los Alamos National Laboratory toxicologist Jun Gao works in his laboratory using a protective fume hood. (Credit: Photo by James R. Rickman)

The research recently appeared in Toxicology and Applied Pharmacology and represents the first-ever observation of this kind for spherical fullerenes, also known as buckyballs, which take their names from the late Buckminster Fuller because they resemble the geodesic dome concept that he popularized.

Engineered carbon nanoparticles, which include fullerenes, are increasing in use worldwide. Each buckyball is a skeletal cage of carbon about the size of a virus. They show potential for creating stronger, lighter structures or acting as tiny delivery mechanisms for designer drugs or antibiotics, among other uses. About four to five tons of carbon nanoparticles are manufactured annually.

"Nanomaterials are the 21st century revolution," said Los Alamos toxicologist Rashi Iyer, the principal research lead and coauthor of the paper. "We are going to have to live with them and deal with them, and the question becomes, 'How are we going to maximize our use of these materials and minimize their impact on us and the environment?'"

Iyer and lead author Jun Gao, also a Los Alamos toxicologist, exposed cultured human skin cells to several distinct types of buckyballs. The differences in the buckyballs lay in the spatial arrangement of short branches of molecules coming off of the main buckyball structure. One buckyball variation, called the "tris" configuration, had three molecular branches off the main structure on one hemisphere; another variation, called the "hexa" configuration, had six branches off the main structure in a roughly symmetrical arrangement; the last type was a plain buckyball.

The researchers found that cells exposed to the tris configuration underwent premature senescence -- what might be described as a state of suspended animation. In other words, the cells did not die as cells normally should, nor did they divide or grow. This arrest of the natural cellular life cycle after exposure to the tris-configured buckyballs may compromise normal organ development, leading to disease within a living organism. In short, the tris buckyballs were toxic to human skin cells.

Moreover, the cells exposed to the tris arrangement caused unique molecular level responses suggesting that tris-fullerenes may potentially interfere with normal immune responses induced by viruses. The team is now pursuing research to determine if cells exposed to this form of fullerenes may be more susceptible to viral infections.

Ironically, the discovery could also lead to a novel treatment strategy for combating several debilitating diseases. In diseases like Parkinson's or Alzheimer's, nerve cells die or degenerate to a nonfunctional state. A mechanism to induce senescence in specific nerve cells could delay or eliminate onset of the diseases. Similarly, a disease like cancer, which spreads and thrives through unregulated replication of cancer cells, might be fought through induced senescence. This strategy could stop the cells from dividing and provide doctors with more time to kill the abnormal cells.

Because of the minute size of nanomaterials, the primary hazard associated with them has been potential inhalation -- similar to the concern over asbestos exposure.

"Already, from a toxicological point of view, this research is useful because it shows that if you have the choice to use a tris- or a hexa-arrangement for an application involving buckyballs, the hexa-arrangement is probably the better choice," said Iyer. "These studies may provide guidance for new nanomaterial design and development."

These results were offshoots from a study (Shreve, Wang, and Iyer) funded to understand the interactions between buckyballs and biological membranes. Los Alamos National Laboratory has taken a proactive role by initiating a nanomaterial bioassessmnet program with the intention of keeping its nanomaterial workers safe while facilitating the discovery of high-function, low-bioimpact nanomaterials with the potential to benefit national security missions. In addition to Gao and Iyer, the LANL program includes Jennifer Hollingsworth, Yi Jiang, Jian Song, Paul Welch, Hsing Lin Wang, Srinivas Iyer, and Gabriel Montaño.

Los Alamos National Laboratory researchers will continue to attempt to understand the potential effects of exposure to nanomaterials in much the same way that Los Alamos was a worldwide leader in understanding the effects of radiation during the Lab's early history. Los Alamos workers using nanomaterials will continue to follow protocols that provide the highest degree of protection from potential exposure.

Meantime, Los Alamos research into nanomaterials provides a cautionary tale for nanomaterial use, as well as early foundations for worker protection. Right now, there are no federal regulations for the use of nanomaterials. Disclosure of use by companies or individuals is voluntary. As nanomaterial use increases, understanding of their potential hazards should also increase.

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Biologists Wake Dormant Viruses and Uncover Mechanism for Survival

Biologists Wake Dormant Viruses and Uncover Mechanism for Survival

  9:44:00 PM    Science Lover

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It is known that viral "squatters" comprise nearly half of our genetic code. These genomic invaders inserted their DNA into our own millions of years ago when they infected our ancestors. But just how we keep them quiet and prevent them from attack was more of a mystery until EPFL researchers revived them.

This shows the functioning of Kap1 protein in mouse embrocation cells. (Credit: Pascal Coderay, pascal@salut.ch)

The reason we survive the presence of these endogenous retroviruses -- viruses that attack and are passed on through germ cells, the cells that give rise to eggs and sperm -- is because something keeps the killers silent. Now, publishing in the journal Nature, Didier Trono and his team from EPFL, in Switzerland, describe the mechanism. Their results provide insights into evolution and suggest potential new therapies in fighting another retrovirus -- HIV.

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Evolutionary Surprise: Eight Percent of Human Genetic Material Comes from a Virus

Evolutionary Surprise: Eight Percent of Human Genetic Material Comes from a Virus

  10:15:00 PM    Science Lover

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About eight percent of human genetic material comes from a virus and not from our ancestors, according to researchers in Japan and the U.S.

A new study shows that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus. (Credit: iStockphoto)

The study, and an accompanying News & Views article by University of Texas at Arlington biology professor Cédric Feschotte, is published in the journal Nature.

The research showed that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus. Feschotte wrote on recent research led by Professor Keizo Tomonaga at Osaka University in Japan. Feschotte said this virally transmitted DNA may be a cause of mutation and psychiatric disorders such as schizophrenia and mood disorders.

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Swine Flu Outbreak Illuminated By Avian Flu Research

Swine Flu Outbreak Illuminated By Avian Flu Research

  9:15:00 PM    Science Lover

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A new study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu pandemic is greater than previously thought. Results also illustrate how the current swine flu outbreak likely came about.

This graphic shows why the Type A virus can't be eradicated.
(Credit: Image courtesy of University of Maryland)

As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However, in research recently published in the Proceedings of the National Academy of Sciences, Associate Professor Daniel Perez from the University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.

"This is similar to the method by which the current swine influenza strain likely formed," said Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project, AICAP. "The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing."

Image via Wikipedia

In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together, Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface avian flu genes from the H9N2 virus. Though it comes from a different strain of avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez's research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.

Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.

When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, they concluded that after an animal-human hybrid influenza virus forms in nature, a human pandemic of this virus is potentially just a few mutations away.

"We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets," Perez said. "We will be doing more research on the current swine flu strain to study its specific genetic mutations."

Perez found that one of the two of the genetic mutations in his lab strain that enabled respiratory transmission between mammals was on the tip of the HA surface protein, one of the sites where human antibodies created in response to current vaccines would bind.

"Because the binding site of the mutant virus is different from the virus upon which the vaccine is modeled, it may mean that current vaccine stocks would not be as effective against the H9N2 mutant strain as previously anticipated," said Perez. "We should keep this in mind when designing vaccines for an avian flu pandemic in humans."

However, scientists cannot predict what the actual mutations will look like if and when they occur in nature, or even which strain of avian influenza will mutate to infect mammals.

"This is just the tip of the iceberg," said Perez. "Many more studies have to be done to see which combinations of mutations cause this type of transmission before we can design the appropriate vaccines."

Perez will be talking this week with the NIH and the CDC to discuss his team's role in researching the current swine flu virus strain. Perez will likely do studies related to vaccine development, virus transmission between humans and animals, and the pathogenesis of the virus.

A virus vaccine is derived from the virus itself. The vaccine consists of virus components or killed viruses that mimic the presence of the virus without causing disease. These prime the body's immune system to recognize and fight against the virus. The immune system produces antibodies against the vaccine that remain in the system until they are needed. If that virus, or in some cases a closely similar one is later introduced into the system, those antibodies attach to viral particles and remove them before they have time to replicate, preventing or lessening symptoms of the virus.

The immune system also retains antibodies to a virus after being infected with it, so humans have general immunity to human strains of avian influenza strains. But humans do not generally have immunity to avian flu strains because they have not been infected by them before. The surface proteins are sufficiently different to escape the human immune response. Avian flu strains are therefore more dangerous for humans because the human immune system cannot recognize the virus or protect against it.

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