It's elemental: Paper celebrates discovery of iodine

George Luther, Maxwell P. and Mildred H. Harrington Professor at UD, is one of 11 internationally recognized co-authors on a paper commemorating 200 years of iodine research. The paper appeared on Friday, Dec. 2, in Angewandte Chemie, one of the prime chemistry journals in the world.

Most of us think of iodine as a liquid that comes in a little brown bottle to help heal cuts or as something that gets mixed in with table salt to prevent goiter. But the element that appears as number 53 in the periodic table was actually discovered during the Napoleonic Wars when French chemist Bernard Courtois was searching for an alternative to wood ashes as a feedstock for the production of saltpeter. Today, iodine has applications ranging from pharmaceuticals to semiconductors.

The element plays a role in a broad range of fields, including materials, medicine and physiology, atmospheric chemistry, geochemistry and marine chemistry. The latter is where Luther's expertise was called upon for the article. His section provides an overview of iodine and its major chemical forms in the marine environment.

"Iodine is incorporated into diatoms and other algae in the surface ocean," Luther says. "Upon death, some plankton sink to the sediments, and iodine is enriched in the sediments and their porewaters. There is also some release of gaseous iodine to the atmosphere from algal and plant sources. Weathering of the continents adds some iodine to the ocean via rivers to maintain the balance of about 0.45 micromolar total iodine that is in the ocean."

Apparently, Luther doesn't have to worry about running out of research opportunities any time soon. The authors conclude that in the ocean, the iodide–iodate transformation still offers challenges to biological and chemical oceanographers. At the same time, the biogenic, evolutionary origin of the high iodine levels encountered in marine sediments requires more research efforts.

However, the man who discovered iodine two centuries ago did not fare so well. Despite the scientific significance of his discovery and the growing commercial interest in iodine, Courtois did not capitalize on his discovery. He died in poverty on Sept. 27, 1838, at the age of 62. Iodine production from seaweed quickly became a major economic activity in the coastal regions of Europe, and others went on to benefit from his finding.

More information: Commemorating Two Centuries of Iodine Research: An Interdisciplinary Overview of Current Research” appeared on Friday, Dec. 2, in Angewandte Chemie., Frithjof C. Küpper, et al.

Provided by University of Delaware (news : web)

Elusive ultrafine indoor air contaminants yield to NIST analysis

Monitoring such tiny particles was made possible by NIST advances in measurement capabilities. Measurements were carried out in weeks of experiments at a 340-square-meter (1,500-square-feet) test house on the NIST campus in Gaithersburg, Md. The researchers used the data to develop a model for predicting changes in the size and distribution of so-called ultrafine particles (technically, particles smaller than 100 nanometers) discharged by tools, appliances and other sources.

The measurements and model will further efforts to explain the dynamics of ultrafine particles, an area of growing interest among environmental and health researchers. They also will advance work to develop accurate and reliable methods for determining how changes in heating and cooling systems, often done to reduce energy consumption, will affect indoor environments.

"If we can understand and predict the dynamics of these extremely small indoor air contaminants, designers and equipment manufacturers can avoid potential negative impacts on the environment inside homes and buildings and may even devise ways to improve conditions and save energy at the same time," explains NIST engineer Andrew Persily.

Utrafine particles are produced naturally—by forest fires and volcanoes, for example—as well as by internal combustion engines, power plants and many other human-made sources. Although ever present in outdoor and indoor environments, ultrafine particles have eluded detection, and are not subject to federal or state air quality standards. However, particles with nanoscale dimensions have been associated with a variety of human health problems—especially heart, lung and blood disorders.

Because we spend most of our time indoors, however, the bulk of human exposure to ultrafine particles occurs in homes and buildings. Typically, releases of the tiny particles occur in periodic bursts—during cooking or hair drying, perhaps—but airborne concentrations during these episodes can greatly exceed outdoor levels, according to the NIST team.

The researchers measured the airborne concentrations of ultrafine particles at regular intervals after they were emitted by gas and electric stoves, candles, hair dryers and power tools. With their recently enhanced capabilities, the team could measure particles about four times smaller than in previous studies of indoor air contaminants.

Tests were conducted with the house central fan either on or off, which made a major difference in the behavior of ultrafine particles. With the fan off, these very small particles collide with each other and coagulate—or combine—during the first 2.5 minutes following a blast of ultrafine particles from an appliance or tool. In the process, they form successively larger particles, decreasing airborne concentrations of particles. As particles grow larger, they tend to settle on surfaces more quickly.

With the central fan recirculating air, ultrafine particles tend, in roughly equal proportions, to coagulate or settle on surfaces. Under both fan conditions, ventilation accounted for the removal of no more than about 5 percent of ultrafine particles.

Tests also revealed that for many indoor sources, such as stovetop cooking with gas, more than 90 percent of the particles emitted were smaller than 10 nanometers. In turn, emissions of smaller particles result in higher airborne concentrations that dissipate primarily through coagulation.

More information: *D. Rim, L. Wallace, A. Persily and J. Choi, Evolution of ultrafine particle size distributions following indoor episodic releases: Relative importance of coagulation, deposition and ventilation. Aerosol Science and Technology. Posted online Nov. 15, 2011. DOI 10.1080/02786826.2011.639317. Available online at www.tandfonline.com/action/showAxaArticles?journalCode=uast20

Provided by National Institute of Standards and Technology (news : web)

Scientists elevate little-studied cellular mechanism to potential drug target

The study was published December 11, 2011, in an advance online edition of the journal Nature Chemical Biology.

"With this paper, we've elevated protein sulfenylation from a marker of oxidative stress to a bona fide reversible post translational modification that plays a key regulatory role during cell signaling," said Kate Carroll, a Scripps Research associate professor who led the study. "The sulfenyl modification is the new kid on the block."

During periods of cellular stress, caused by factors such as exposure to UV radiation or chronic disease states like cancer, the level of highly reactive oxygen-containing molecules can increase, resulting in inappropriate modification of proteins and cell damage. In sulfenylation, one oxidant, hydrogen peroxide, functions as a messenger that can activate cell proliferation through oxidation of cysteine residues in signaling proteins, producing sulfenic acid. Cysteine, an amino acid (natural protein building block), is highly oxidant sensitive.

Conventional wisdom has long held that if hydrogen peroxide does exist in the cell at any appreciable level, it represents a disease state, not a regulatory event. The new study shows that sulfenylation is actually a positive protein modification, and that it's required for signaling through the pathway, a validation of a long-held belief in some scientific circles that hydrogen peroxide functions as a general signaling molecule, not an oxidative "bad boy" to be eliminated at all costs.

A New Chemical Probe

To explore the process, Carroll and her colleagues developed a highly selective chemical probe -- known as DYn-2 -- with the ability to detect minute differences in sulfenylation rates within the cell.

With the new probe, the team was able to show that a key signaling protein, epidermal growth factor receptor (EGFR), is directly modified by hydrogen peroxide at a critical active site cysteine, stimulating its tyrosine kinase activity.

The technology described in the new paper is unique, Carroll said, because it allows scientists to trap and detect these modifications in situ, without interfering with the redox balance of the cell. "Probing cysteine oxidation in a cell lysate is like looking for a needle in a haystack," she said, "our new approach preserves labile sulfenyl modifications and avoids protein oxidation artifacts that arise during cell homogenization."

As with phosphorylation, future studies on sulfenylation will delve into the exciting discovery of new enzymes, new signaling processes, and new mechanisms of regulation.

Another broad impact of these findings, Carroll said, is to open up an entirely new mechanism to exploit for the development of therapeutics, particularly in cancer. "It should influence the design of inhibitors that target oxidant-sensitive cysteine residues in the future," she said.

More information: "Peroxide-dependent Sulfenylation of the EGFR Catalytic Site Enhances Kinase Activity," Candice E. Paulsen et al., Nature Chemical Biology (2011).

Provided by The Scripps Research Institute (news : web)

Closing in on an ulcer- and cancer-causing bacterium

Writing in a Journal of Biological Chemistry "Paper of the Week," the scientists say the information they have obtained about the pathogen's clever employment of acid neutralizers may inform those who are designing new drugs to blunt H. pylori's effects across the globe.

H. pylori are the only bacteria known to thrive in the human stomach. It remains unclear how the pathogens are transmitted, although researchers suspect they could be spread through contaminated food or water. The damage the bacteria do to the mucous coating of the gut allows stomach acid to eat away at the sensitive organ lining, causing ulcers.

Although more than half of the world's population has the infection, for reasons still not quite understood most never develop ulcers. In fact, existing antibiotics can cure 80 to 90 percent of ulcers caused by the pathogen. However, H. pylori over the years have become increasingly resistant to antibiotics. Some experts have attributed that resistance to the fact that doctors are quick to prescribe antibiotics to kill it even when patients show no symptoms.

"There is a pressing need to develop new drugs and alternative strategies to fight against H. pylori infection before the prevalence of antibiotic resistance gets out of hand," says Ivan Fong, the lead author on the JBC paper and a graduate student at the Chinese University of Hong Kong whose research is focused on the biochemical makeup of protein complexes that assist in H. pylori's survival.

Ivan Fong, a graduate student at the Chinese University of Hong Kong, studies the biochemical makeup of protein complexes that assist in H. pylori's survival. Kam-Bo Wong is a professor at the institution and oversaw Fong's recent project. Credit: Chinese University of Hong Kong

It's the pathogen's ability to persist within the acid bath in the human stomach that has made it such a successful, albeit harmful, vector, says Fong. "The key is its use of an enzyme called urease to neutralize gastric acid," he explains.

H. pylori produce urease to spur the breakdown of urea, a naturally occurring chemical in the body, so that urea can release ammonia and make the gut an environment in which the pathogens can thrive. But, unlike most other enzymes, urease doesn't start doing its job immediately after being produced by the bacterium; instead, two nickel ions have to be delivered to it, and then the enzyme can mature, so to speak, and thus allow H. pylori to begin their damaging work.

"As the survival of H. pylori depends on active urease, this is a life-or-death issue for the pathogen to ensure nickel ions are delivered to the urease," says Kam-Bo Wong, a professor who oversaw the project at the institution.

It's not entirely clear how H. pylori make sure that urease can mature and then neutralize the surrounding acid. But Wong's team focused on four proteins that they suspect are helpers: UreE, UreF, UreG and UreH.

Using X-ray crystallography, "which essentially performs the function of a molecular microscope to visualize proteins with atomic resolution," Fong explains, the team took snapshots of UreF and UreH. What they saw was that UreH morphs the shape of UreF to enable UreF to recruit a third player, UreG, to form the UreF-UreH-UreG complex. In other words, the three proteins hook up to collectively deliver nickel ions to the right place on urease. Once the nickel ions are in place, they serve like a flint to ignite the breakdown of urea into ammonia, which then neutralizes the stomach acids.

"So, now we have a better understanding of how the machine can assemble itself, as if a skillful mechanic were there for the job, and deliver the nickel ions," says Fong.

Importantly, the team also discovered that disrupting the formation of the crafty UreF-UreH-UreG complex does, in fact, inhibit the synthesis of active urease. They hope that the information they've obtained about the molecular structures of UreF and UreH will help in the design of drugs that will essentially muck up the works of the molecular machine.

"As active urease is the key to survival of H. pylori, designing drugs that target this complex may well be a viable strategy to eradicate the pathogen," says Wong.

More information: The abstract for the paper, titled "Assembly of the preactivation complex for urease maturation in Helicobacter pylori: Crystal Structure of the UreF/UreH complex," is available at http://www.jbc.org … 830.abstract

Provided by American Society for Biochemistry and Molecular Biology