Carbon black nanoparticles can cause cell death, inflammation in lungs, researchers find

 Researchers from the University of Iowa Roy J. and Lucille A. Carver College of Medicine have found that inhaled carbon black nanoparticles create a double source of inflammation in the lungs.

Their findings were published online in the April 27 edition of the Journal of Biological Chemistry. Martha Monick, Ph.D., UI professor of internal medicine, was lead author of the paper which outlined the results.

Monick said researchers expected to find one level of inflammation when cells were exposed to carbon black nanoparticles. They were surprised, however, to find that nanoparticles activated a special inflammatory process and killed cells in a way that further increased inflammation. She said the research showed that the intake of carbon black nanoparticles from sources such as diesel fuel or printer ink caused an initial inflammatory response in lung cells. The surprising results came when the team discovered that these nanoparticles killed macrophages -- immune cells in the lungs responsible for cleaning up and attacking infections -- in a way that also increases inflammation.

"Apoptosis is one way cells die in which all the contents stay in the cell, the cell just keeps shrinking onto itself and the surrounding tissue is protected," Monick said. "We thought that was what was happening with the carbon nanoparticles; we were wrong. A different process called pyroptosis was occurring, causing the cells to burst and spill their contents."

That, she said, can cause a secondary inflammatory response.

Monick cautioned that the doses of carbon black nanoparticles used in the study were much more concentrated than the amounts to which a person might typically be exposed.

"This doesn't mean that walking through a cloud of diesel exhaust will hurt your lungs," she said. "It does show that we may have an environmental exposure that could contribute to inflammation in the lung."

The study was a collaborative project involving researchers in the Department of Internal Medicine in the UI Carver College of Medicine and the Department of Chemistry in the College of Liberal Arts and Sciences. In addition to Monick, a key contributor to the research was Vicki Grassian, Ph.D., UI professor of chemistry who holds the F. Wendell Miller Professorship.

The research team also included Anna C. Reisetter, Linda Powers, and Amit Gupta from internal medicine and Larissa V. Stebounova, and Jonas Baltrusaitis in chemistry.

The study was funded in part by a grant from the National Institutes of Health.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Iowa Health Care, via EurekAlert!, a service of AAAS.

Journal Reference:

A. C. Reisetter, L. V. Stebounova, J. Baltrusaitis, L. Powers, A. Gupta, V. H. Grassian, M. M. Monick. Induction of inflammasome dependent pyroptosis by carbon black nanoparticles. Journal of Biological Chemistry, 2011; DOI: 10.1074/jbc.M111.238519

Disease-Causing Compound Found in Air Clogged with Smoke from Cigarettes, Fires or Pollution

Inhaling cigarette smoke or smoggy air is clearly not great for your health. And exposure to various kinds of smoke has been associated with cardiovascular disease, rheumatoid arthritis and cataracts.

Researchers have now pinpointed a compound common in disparate forms of smoke that might explain some of the frequent ills associated with it. The findings are described in a new paper published online May 16 in the Proceedings of the National Academy of Sciences.

"We found isocyanic acid in a number of places, from air in downtown Los Angeles and air downwind of a Colorado wildfire, to cigarette smoke," Jim Roberts, a chemist at NOAA's Earth System Research Laboratory and co-author of the new study, said in a prepared statement. Isocyanic acid—abbreviated as HNCO—is a substance known to act in the body along disease-related pathways through a process known as protein carbamylation.

Although the new study did not look specifically at how ambient HNCO might be affecting people's health, the researchers note that it makes sense that it would have easy access into the human body's innards. "It dissolves readily in water, which means that humans can be exposed directly if it gets into eyes or lungs," Roberts said.

This is the first time that HNCO had been measured in ambient air, the researchers report. To get specific readings, the team used a negative-ion proton-transfer chemical ionization mass spectrometer.

Roberts and his colleagues measured high concentrations of the compound in the air in Boulder, Colo., during last year's Fourmile Canyon fire and in the smoggy city of Los Angeles, finding that both had about 200 parts per billion HNCO. Previous findings have indicated that levels higher than one part per billion in the ambient air might have negative impacts on human health. The high levels in L.A. are likely an unintended consequence of efforts to curb nitrogen emissions from diesel trucks. These so-called urea-selective catalytic reduction systems scrub out nitrogen but create HNCO as a byproduct, the researchers report.

In addition to these significant concerns for people living here in the U.S., the risks might be greater for the many people in the developing world who use open-fire stoves, or cook stoves. A lab test of burning biomass produced concentrations of 600 parts per billion when measured close to the flames. "There are literally billions of people in the world who burn biomass for cooking and heating," Roberts said. "If these indoor fires release similar levels of isocyanic acid as the fires we studied in the laboratories, families could be exposed to high levels of the chemical."

The team underscored the need for further research into how HNCO might be affecting human health—especially with the prevalence of biomass-based stoves and the prediction for more wild fires due to climate change. "We may be facing a future of higher amounts of HNCO in the atmosphere," Roberts said. And although that might be bad news for human health, Roberts noted that at least "it is fortunate that now we can measure it."

Image courtesy of iStockphoto/plherrera

View the original article here

New method of unreeling cocoons could extend silk industry beyond Asia

The development and successful testing of a method for unreeling the strands of silk in wild silkworm cocoons could clear the way for establishment of new silk industries not only in Asia but also in vast areas of Africa and South America. The report appears in ACS' journal Biomacromolecules.

Fritz Vollrath, Tom Gheysens and colleagues explain that silk is made by unraveling— or unreeling — the fine, soft thread from cocoons of silkmoths. The practice began as far back as 3500 BC in ancient China, where silk was the fabric of royalty. Today, most silk comes from cocoons of the domesticated Mulberry silkworm (bred from a species native to Asia) because they are easy to unreel into long continuous strands. The cocoons formed by "wild" species are too tough for this process, so harsher methods are sometimes used. However, these methods damage the strands, producing a poor-quality silk. To overcome this challenge to the widespread commercial use of wild cocoons, the researchers developed a new way to loosen the strands without damaging them.

The group found that the surfaces of wild cocoons were coated with a mineral layer and that removing this layer ("demineralizing") made it easy to unreel the cocoons into long continuous strands with commercial reeling equipment. These strands were just as long and strong as those from Mulberry silkworm cocoons. The researchers say that the new method could expand the silk industry to new areas of the world where wild silkworms thrive.

More information: Demineralization enables reeling of Wild Silkmoth cocoons, Biomacromolecules, Just Accepted Manuscript, DOI: 10.1021/bm2003362

Abstract
Wild Silkmoth cocoons are difficult or impossible to reel under conditions that work well for cocoons of the Mulberry silkmoth, Bombyx mori. Here we report evidence that this is caused by mineral reinforcement of wild silkmoth cocoons and that washing these minerals out allows for the reeling of commercial lengths of good quality fibers with implications for the development of the ‘wild silk’ industry. We show that in the Lasiocampid silkmoth Gonometa postica, the mineral is whewellite (calcium oxalate monohydrate). Evidence is presented that its selective removal by ethylenediaminetetraacetic acid (EDTA) leaves the gum substantially intact preventing collapse and entanglement of the network of fibroin brins, enabling wet reeling. Therefore this method clearly differs from the standard “degumming” and should be referred to as “demineralizing”. Mechanical testing shows that such preparation results in reeled silks with markedly improved breaking load and extension to break by avoiding the damage produced by the rather harsh degumming, carding or dry reeling methods currently in use.

Provided by American Chemical Society (news : web)

Dynamics of crucial protein 'switch' revealed

Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders.

The article was deemed a "Paper of the Week" by and will be on the cover of the Journal of Biological Chemistry. It is scheduled for publication May 20 and now available online.

"This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB.

The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways.

Errors in cell signaling are responsible for diseases such as diabetes, cancer and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers.

The project involved an ongoing collaboration between Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr. and colleagues at UCSD, pioneers in the development and application of hydrogen/deuterium exchange mass spectrometry (DXMS) technology. Compared with other protein-analysis techniques, DXMS is especially good at studying the structural motion of proteins.

Using this novel approach, the investigators were able to reveal, in fine detail, that cAMP interacts with its two known binding sites on Epac2 in a sequential fashion and that binding of cAMP changes the shape of the protein in a very specific way – switching on its activity by exposing further signaling interaction sites on Epac2.

"DXMS analysis has proved to be an amazingly powerful approach, alone or in combination with other techniques, in figuring out how proteins work as molecular machines, changing their shapes – or morphing – in the normal course of their function," said Woods. "This will be of great use in the identification and development of therapeutic drugs that target these protein motions."

Provided by University of Texas Medical Branch at Galveston (news : web)