Jet lag pill that slows down body clock to help you ‘catch up’ one step closer

Scientists are one step closer to developing a jet lag pill that could relieve millions of long-haul passengers from sleepless nights and mid-afternoon drowsiness.

Using automated screening techniques developed by pharmaceutical companies to find new drugs, researchers from UC San Diego and three other research institutions have discovered a molecule with the most potent effects ever seen on the biological clock.

Dubbed “longdaysin,” for its ability to dramatically slow down the biological clock, the new compound could pave the way for a host of new drugs to treat severe sleep disorders or quickly reset the biological clocks of jet-lagged travelers who regularly travel across multiple time zones.

The researchers demonstrated the dramatic effects of longdaysin by lengthening the biological clocks of larval zebra fish by more than 10 hours.

“Theoretically, longdaysin or a compound like it could be used to correct sleep disorders such as the genetic disorder Familial Advanced Sleep syndrome, which is characterized by a clock that”s running too fast,” said Steve Kay, dean of UCSD’s Division of Biological Sciences, who headed the research team.

“A compound that makes the clock slow down or speed up can also be used to phase-shift the clock—in other words, to bump or reset the hands of the clock. This would help your body catch up when it is jet lagged or reset it to a normal day-night cycle when it has been thrown out of phase by shift work.”

Biologists in Kay”s laboratory and the nearby Genomics Institute of the Novartis Research Foundation, led by Tsuyoshi Hirota, the first author of the paper, discovered longdaysin by screening thousands of compounds with a robot that tested the reaction of each compound with a line of human bone cancer cells that the researchers genetically modified so they could see visually the changes in the cells” circadian rhythms.

This was done in the cells by attaching a clock gene to a luciferase gene used by fireflies to glow at night, so that the cells glowed when the biological clock was activated.

The robot screened more than 120,000 potential compounds from a chemical library into individual micro-titer wells—a system used by drug companies called high-throughput screening—and automatically singled out those molecules found to have the biggest effects on the biological clock.

Once Kay’s group had isolated longdaysin, they turned to biological chemists in Peter Schultz’s laboratory at The Scripps Research Institute to characterize the molecule and figure out how it lengthened the biological clock.

That analysis showed that three separate protein kinases were responsible for the dramatic effect of longdaysin, one of which, CK1alpha, had previously been ignored by chronobiology researchers.

The researchers then showed that longdaysin had the same effect of lengthening the biological clock in mouse tissue samples and in zebrafish larvae that carried luciferase genes attached to their clock genes.

Kay’s research team plans to test longdaysin on mice in the near future, but their goal isn’t to develop longdaysin into a drug. “Longdaysin is not as potent as we would like,” he adds. “This will be a tool for research.”

The article is published in the open access journal PLoS Biology. (ANI)

Reference:

Hirota T, Lee JW, Lewis WG, Zhang EE, Breton G, et al. (2010) High-Throughput Chemical Screen Identifies a Novel Potent Modulator of Cellular Circadian Rhythms and Reveals CKI? as a Clock Regulatory Kinase. PLoS Biol 8(12): e1000559. doi:10.1371/journal.pbio.1000559

Disclaimer: Bioscholar is not intended to provide medical advice, diagnosis or treatment. The articles are based on peer reviewed research, and discoveries/products mentioned in the articles may not be approved by the regulatory bodies.

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Shining new light on air pollutants using entangled porous frameworks

ScienceDaily (Jan. 26, 2011) — Certain types of pollution monitoring may soon become considerably easier. A group of researchers centered at Kyoto University has shown in a recent Nature Communications paper that a newly-formulated entangled framework of porous crystals (porous coordination polymers, or PCPs) can not only capture a variety of common air pollutants, but that the mixtures then glow in specific, easily-detected colors.

Lead author for the paper was Dr. Yohei Takashima.

Until now, chemical sensors have generally needed to be custom-designed to recognize specific compounds, and a separate transmission mechanism was required in order to "see" that a particular molecule had indeed been successfully captured.

"We have created what amount to be interlocking jungle-gyms, that move relative to each other and are therefore able to capture molecules of varying sizes," explained Dr. Shuhei Furukawa of Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS).

This naphthalenediimide-based PCP, known as NDI, expands and contracts to confine air-born volatile organic compounds (VOCs) such as benzene, toluene, xylene, anisole, and iodobenzene, which are common pollutants in the lower atmosphere.

"When exposed to ultraviolet light, the NDI-VOC interaction luminesces in an unusually wide range of colors, sufficiently intense to be observed even with the naked eye," elaborated iCeMS Professor and deputy director, Susumu Kitagawa.

These findings, including contributions from Dr. Virginia Martínez Martínez at the Universidad del País Vasco in Bilbao, open the door to the development of a new range of portable, solid-state pollution detectors, and possibly even new types of light sources.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Institute for Integrated Cell-Material Sciences, Kyoto University, via EurekAlert!, a service of AAAS.

Journal Reference:

Yohei Takashima, Virginia Martínez Martínez, Shuhei Furukawa, Mio Kondo, Satoru Shimomura, Hiromitsu Uehara, Masashi Nakahama, Kunihisa Sugimoto, Susumu Kitagawa. Molecular decoding using luminescence from an entangled porous framework. Nature Communications, 2011; 2 (1): 168 DOI: 10.1038/ncomms1170

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Van-der-Waals force up close: Physicists take new look at the atom

ScienceDaily (Jan. 26, 2011) — Measuring the attractive forces between atoms and surfaces with unprecedented precision, University of Arizona physicists have produced data that could refine our understanding of the structure of atoms and improve nanotechnology.

The discovery has been published in the journal Physical Review Letters.

Van der Waals forces are fundamental for chemistry, biology and physics. However, they are among the weakest known chemical interactions, so they are notoriously hard to study. This force is so weak that it is hard to notice in everyday life. But delve into the world of micro-machines and nano-robots, and you will feel the force -- everywhere.

"If you make your components small enough, eventually this van-der-Waals potential starts to become the dominant interaction," said Vincent Lonij, a graduate student in the UA department of physics who led the research as part of his doctoral thesis.

"If you make tiny, tiny gears for a nano-robot, for example, those gears just stick together and grind to a halt. We want to better understand how this force works."

To study the van-der-Waals force, Lonij and his co-workers Will Holmgren, Cathy Klauss and associate professor of physics Alex Cronin designed a sophisticated experimental setup that can measure the interactions between single atoms and a surface. The physicists take advantage of quantum mechanics, which states that atoms can be studied and described both as particles and as waves.

"We shoot a beam of atoms through a grating, sort of like a micro-scale picket fence," Lonij explained. "As the atoms pass through the grating, they interact with the surface of the grating bars, and we can measure that interaction."

As the atoms pass through the slits in the grating, the van-der-Waals force attracts them to the bars separating the slits. Depending on how strong the interaction, it changes the atom's trajectory, just like a beam of light is bent when it passes through water or a prism.

A wave passing through the middle of the slit does so relatively unencumbered. On the other hand, if an atom wave passes close by the slit's edges, it interacts with the surface and skips a bit ahead, "out of phase," as physicists say.

"After the atoms pass through the grating, we detect how much the waves are out of phase, which tells us how strong the van-der-Waals potential was when the atoms interacted with the surface."

Mysterious as it seems, without the van-der-Waals force, life would be impossible. For example, it helps the proteins that make up our bodies to fold into the complex structures that enable them to go about their highly specialized jobs.

Unlike magnetic attraction, which affects only metals or matter carrying an electric current, van-der-Waals forces make anything stick to anything, provided the two are extremely close to each other. Because the force is so weak, its action doesn't range beyond the scale of atoms -- which is precisely the reason why there is no evidence of such a force in our everyday world and why we leave it to physicists such as Lonij to unravel its secrets.

Initially, he was driven simply by curiosity, Lonij said. When he started his project, he didn't know it would lead to a new way of measuring the forces between atoms and surfaces that may change the way physicists think about atoms.

And with a smile, he added, "I thought it would be fitting to study this force, since I am from the Netherlands; Mr. van der Waals was Dutch, too."

In addition to proving that core electrons contribute to the van-der-Waals potential, Lonij and his group made another important discovery.

Physicists around the world who are studying the structure of the atom are striving for benchmarks that enable them to test their theories about how atoms work and interact. "Our measurements of atom-surface potentials can serve as such benchmarks," Lonij explained. "We can now test atomic theory in a new way."

Studying how atoms interact is difficult because they are not simply tiny balls. Instead, they are what physicists call many-body systems. "An atom consists of a whole bunch of other particles, electrons, neutrons, protons, and so forth," Lonij said.

Even though the atom as a whole holds no net electric charge, the different charged particles moving around in its interior are what create the van-der-Waals force in the first place.

"What happens is that the electrons, which hold all the negative charge, and the protons, which hold all the positive charge, are not always in the same places. So you can have tiny little differences in charge that are fluctuating very fast. If you put a charge close to a surface, you induce an image charge. In a highly simplified way, you could say the atom is attracted to its own reflection."

To physicists, who prefer things neat and clean and tractable with razor-sharp mathematics, such a system, made up from many smaller particles zooming around each other, is difficult to pin down. To add to the complication, most surfaces are not clean. As Lonij puts it, "Comparing such a dirty system to theory is a big challenge, but we figured out a way to do it anyway."

"A big criticism of this type of work always was, 'well, you're measuring this atom-surface potential, but you don't know what the surface looks like so you don't know what you're really measuring.'"

To eliminate this problem, Lonij's team used different types of atoms and looked at how each interacted with the same surface.

"Our technique gives you the ratio of potentials directly without ever knowing the potential for either of the two atoms," he said. "When I started five years ago, the uncertainty in these types of measurements was 20 percent. We brought it down to two percent."

The most significant discovery was that an atom's inner electrons, orbiting the nucleus at a closer range than the atom's outer electrons, influence the way the atom interacts with the surface.

"We show that these core electrons contribute to the atom-surface potential," Lonij said, "which was only known in theory until now. This is the first experimental demonstration that core electrons affect atom-surface potentials."

"But what is perhaps more important," he added, "is that you can also turn it around. We now know that the core electrons affect atom-surface potentials. We also know that these core electrons are hard to calculate in atomic theory. So we can use measurements of atom-surface potentials to make the theory better: The theory of the atom."

Story Source:

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

Journal Reference:

Vincent Lonij, Catherine Klauss, William Holmgren, Alexander Cronin. Atom Diffraction Reveals the Impact of Atomic Core Electrons on Atom-Surface Potentials. Physical Review Letters, 2010; 105 (23) DOI: 10.1103/PhysRevLett.105.233202

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

'Green' chemistry extraction method developed for hot capsicum fruit

ScienceDaily (Jan. 26, 2011) — Plant pigments are an important source of non-toxic compounds for use as food or cosmetic coloring agents. In addition to their known nutritional value, the red pigments in Capsicum (chile pepper) are important as sources of non-toxic red dyes; the red pigments are added to many processed foods and cosmetics to enhance their appearance. Certain varieties of Capsicum annuum can be "extracted' to isolate red-colored xanthophylls, an important economical source of red pigments that can replace carcinogenic synthetic red dyes.

Until now, the common method for extracting red pigments from dried fruit of Capsicum has used hexane as the extraction solvent. A noteworthy new research study from New Mexico State University presents a process for efficient extraction of these red pigments using "green chemistry." The method recovers 85% or greater of the pigmented carotenoids from dried Capsicum and reduces the hazardous waste and environmental risks associated with traditional extraction methods.

In New Mexico, the economic value of a chile crop includes the value of the fruit harvested as a fresh green product and a dried red product often harvested later in the season. Current extraction processes are limiting; red pigment can only be recovered from American paprika varieties or other mild cultivars. According to a team of researchers from the Department of Plant and Environmental Sciences at New Mexico State University, if extraction of the red pigments could be achieved separate from the capsaicinoids, then a wider range of red-fruited cultivars could be used, including those with important values as fresh green crops.

The scientists created a "green chemical" method that generates an oleoresin from dried Capsicum fruit with virtually the same carotene and xanthophyll composition as the hexane extraction method. The report appears in HortScience. Mary A. O'Connell, corresponding author of the study, explained; "If alternative and environmentally sound, "green" extraction protocols could be developed to replace the use of hexane as a solvent for oleoresin production. This would improve the environmental risks for the isolation of red pigments from Capsicum fruit."

The "green" extraction method includes a process that separates the pigments from the capsaicinoids, an important step which the researchers say increases the flexibility of the process to allow a variety of red Capsicum fruit to be used easily for pigment production. The authors noted that this step in the process is critical, as it allows the pigment industry and Capsicum farmers to use virtually any variety of chile regardless of heat level for pigment production. "Pungent chiles with high American Spice Trade Association (ASTA) values could be grown for either food/spice uses or pigment production," they remarked.

The researchers added that since growers may rely on mechanical harvest of chiles in the future, contamination of the red fruit with stems and leaves may become higher with mechanical harvesting than in hand harvesting. They observed that the type of supercritical fluid extraction method presented in this study provides an advantage for red fruit harvests mixed with leaf material because it reduces the amount of chlorophyll that contaminates the carotenoid pigment extracts as compared with a hexane extract.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by American Society for Horticultural Science, via EurekAlert!, a service of AAAS.

Journal Reference:

Richard D. Richins, Laura Hernandez, Barry Dungan, Shane Hambly, F. Omar Holguin, and Mary A. O'Connell. A 'Green' Extraction Protocol to Recover Red Pigments from Hot Capsicum Fruit. HortScience, 2010; 45: 1084-1087 [link]

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

First study of dispersants in Gulf spill suggests a prolonged deepwater fate

ScienceDaily (Jan. 26, 2011) — To combat last year's Deepwater Horizon oil spill, nearly 800,000 gallons of chemical dispersant were injected directly into the oil and gas flow coming out of the wellhead nearly one mile deep in the Gulf of Mexico. Now, as scientists begin to assess how well the strategy worked at breaking up oil droplets, Woods Hole Oceanographic Institution (WHOI) chemist Elizabeth B. Kujawinski and her colleagues report that a major component of the dispersant itself was contained within an oil-gas-laden plume in the deep ocean and had still not degraded some three months after it was applied.

While the results suggest the dispersant did mingle with the oil and gas flowing from the mile-deep wellhead, they also raise questions about what impact the deep-water residue of oil and dispersant -- which some say has its own toxic effects -- might have had on environment and marine life in the Gulf.

"This study gives our colleagues the first environmental data on the fate of dispersants in the spill," said Kujawinski, who led a team that also included scientists from UC Santa Barbara. "These data will form the basis of toxicity studies and modeling studies that can assess the efficacy and impact of the dispersants.

"We don't know if the dispersant broke up the oil," she added. "We found that it didn't go away, and that was somewhat surprising."

The study, which appears online Jan. 26 in the American Chemical Society (ACS) journal Environmental Science &Technology, is the first peer-reviewed research to be published on the dispersant applied to the Gulf spill and the first data in general on deep application of a dispersant, according to ACS and Kujawinski. Some previous studies had indicated that dispersants applied to surface oil spills can help prevent surface slicks from endangering marshes and coastlines.

Kujawinski and her colleagues found one of the dispersant's key components, called DOSS (dioctyl sodium sulfosuccinate), was present in May and June -- in parts-per-million concentrations--in the plume from the spill more than 3,000 feet deep. The plume carried its mixture of oil, natural gas and dispersant in a southwest direction, and DOSS was detected there at lower (parts-per-billion) concentrations in September.

Using a new, highly sensitive chromatographic technique that she and WHOI colleague Melissa C. Kido Soule developed, Kujawinski reports those concentrations of DOSS indicate that little or no biodegradation of the dispersant substance had occurred. The deep-water levels suggested any decrease in the compound could be attributed to normal, predictable dilution. They found further evidence that the substance did not mix with the 1.4 million gallons of dispersant applied at the ocean surface and appeared to have become trapped in deepwater plumes of oil and natural gas reported previously by other WHOI scientists and members of this research team. The team also found a striking relationship between DOSS levels and levels of methane, which further supports their assertion that DOSS became trapped in the subsurface.

Though the study was not aimed at assessing the possible toxicity of the lingering mixture -- Kujawinski said she would "be hard pressed to say it was toxic" -- it nevertheless warrants toxicity studies into possible effects on corals and deep-water fish such as tuna, she said. The EPA and others have already begun or are planning such research, she added.

David Valentine of UC Santa Barbara and a co-investigator in the study, said, "This work provides a first glimpse at the fate and reactivity of chemical dispersants applied in the deep ocean. By knowing how the dispersant was distributed in the deep ocean, we can begin to assess the subsurface biological exposure, and ultimately what effects the dispersant might have had."

"The results indicate that an important component of the chemical dispersant injected into the oil in the deep ocean remained there, and resisted rapid biodegradation," said Valentine, whose team collected the samples for Kujawinski's laboratory analysis. "This knowledge will ultimately help us to understand the efficacy of the dispersant application, as well as the biological effects."

Kujawinski and Valentine were joined in the study by Soule and Krista Longnecker of WHOI, Angela K. Boysen a summer student at WHOI, and Molly C. Redmond of UC Santa Barbara. The work was funded by WHOI and the National Science Foundation. The instrumentation was funded by the National Science Foundation and the Gordon and Betty Moore Foundation.

In Kujawinski's technique, the target molecule was extracted from Gulf water samples with a cartridge that isolates the DOSS molecule. She and her colleagues then observed the molecule through a mass spectrometer, ultimately calculating its concentration levels in the oil and gas plume. This method is 1,000 times more sensitive than that used by the EPA and could be used to monitor this molecule for longer time periods over longer distances from the wellhead, she said.

"With this method, we were able to tell how much [dispersant] was there and where it went," Kujawinski said. She and her colleagues detected DOSS up to around 200 miles from the wellhead two to three months after the deep-water injection took place, indicating the mixture was not biodegrading rapidly.

"Over 290,000 kg, or 640,000 pounds, of DOSS was injected into the deep ocean from April to July," she said. "That's a staggering amount, especially when you consider that this compound comprises only 10% of the total dispersant that was added."

Kujawinski cautioned that "we can't be alarmist" about the possible implications of the lingering dispersant. Concentrations considered "toxic" are at least 1,000 times greater than those observed by Kujawinski and her colleagues, she said. But because relatively little is known about the potential effects of this type of dispersant/hydrocarbon combination in the deep ocean, she added, "We need toxicity studies."

"The decision to use chemical dispersants at the sea floor was a classic choice between bad and worse," Valentine said. "And while we have provided needed insight into the fate and transport of the dispersant we still don't know just how serious the threat is; the deep ocean is a sensitive ecosystem unaccustomed to chemical irruptions like this, and there is a lot we don't understand about this cold, dark world."

"The good news is that the dispersant stayed in the deep ocean after it was first applied," Kujawinski says. "The bad news is that it stayed in the deep ocean and did not degrade."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Woods Hole Oceanographic Institution.

Journal Reference:

Elizabeth B. Kujawinski, Melissa C. Kido Soule, David L. Valentine, Angela K. Boysen, Krista Longnecker, Molly C. Redmond. Fate of Dispersants Associated with the Deepwater Horizon Oil Spill. Environmental Science & Technology, 2011; : 110126010225058 DOI: 10.1021/es103838p

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.