Engineered botulism toxins could have broader role in medicine

ScienceDaily (Nov. 30, 2011) — The most poisonous substance on Earth -- already used medically in small doses to treat certain nerve disorders and facial wrinkles -- could be re-engineered for an expanded role in helping millions of people with rheumatoid arthritis, asthma, psoriasis and other diseases, scientists are reporting. Their study appears in ACS' journal Biochemistry.

Edwin Chapman and colleagues explain that toxins, or poisons, produced by Clostridium botulinum bacteria, cause of a rare but severe form of food poisoning, are the most powerful toxins known to science. Doctors can inject small doses, however, to block the release of the neurotransmitters, or chemical messengers, that transmit signals from one nerve cell to another. The toxins break down a protein in nerve cells that mediates the release of neurotransmitters, disrupting nerve signals that cause pain, muscle spasms and other symptoms in certain diseases. That protein exists not just in nerve cells, but in other cells in the human body. However, these non-nerve cells lack the receptors needed for the botulinum toxins to enter and work. Chapman's group sought to expand the potential use of the botulinum toxins by hooking it to a molecule that can attach to receptors on other cells.

Their laboratory experiments showed that these engineered botulinum toxins do work in non-nerve cells, blocking the release of a protein from immune cells linked to inflammation, which is the underlying driving force behind a range of diseases. Such botulinum toxin therapy holds potential in a range of chronic inflammatory diseases and perhaps other conditions, which could expand the role of these materials in medicine.

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by American Chemical Society.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Felix L. Yeh, Yiming Zhu, William H. Tepp, Eric A. Johnson, Paul J. Bertics, Edwin R. Chapman. Retargeted Clostridial Neurotoxins as Novel Agents for Treating Chronic Diseases. Biochemistry, 2011; 50 (48): 10419 DOI: 10.1021/bi201490t

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

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Read More

New switch could improve electronics

ScienceDaily (Dec. 1, 2011) — Researchers at the University of Pittsburgh have invented a new type of electronic switch that performs electronic logic functions within a single molecule. The incorporation of such single-molecule elements could enable smaller, faster, and more energy-efficient electronics. The research findings, supported by a $1 million grant from the W.M. Keck Foundation, were published online in the Nov. 14 issue of Nano Letters.

"This new switch is superior to existing single-molecule concepts," said Hrvoje Petek, principal investigator and professor of physics and chemistry in the Kenneth P. Dietrich School of Arts and Sciences and codirector of the Petersen Institute for NanoScience and Engineering (PINSE) at Pitt. "We are learning how to reduce electronic circuit elements to single molecules for a new generation of enhanced and more sustainable technologies."

The switch was discovered by experimenting with the rotation of a triangular cluster of three metal atoms held together by a nitrogen atom, which is enclosed entirely within a cage made up entirely of carbon atoms. Petek and his team found that the metal clusters encapsulated within a hollow carbon cage could rotate between several structures under the stimulation of electrons. This rotation changes the molecule's ability to conduct an electric current, thereby switching among multiple logic states without changing the spherical shape of the carbon cage. Petek says this concept also protects the molecule so it can function without influence from outside chemicals.

Because of their constant spherical shape, the prototype molecular switches can be integrated as atom-like building blocks the size of one nanometer (100,000 times smaller than the diameter of a human hair) into massively parallel computing architectures.

The prototype was demonstrated using an Sc3N@C80 molecule sandwiched between two electrodes consisting of an atomically flat copper oxide substrate and an atomically sharp tungsten tip. By applying a voltage pulse, the equilateral triangle-shaped Sc3N could be rotated predictably among six logic states.

The research was led by Petek in collaboration with chemists at the Leibnitz Institute for Solid State Research in Dresden, Germany, and theoreticians at the University of Science and Technology of China in Hefei, People's Republic of China. The experiments were performed by postdoctoral researcher Tian Huang and research assistant professor Min Feng, both in Pitt's Department of Physics and Astronomy.

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Pittsburgh.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Tian Huang, Jin Zhao, Min Feng, Alexey A. Popov, Shangfeng Yang, Lothar Dunsch, Hrvoje Petek. A Molecular Switch Based on Current-Driven Rotation of an Encapsulated Cluster within a Fullerene Cage. Nano Letters, 2011; : 111123145903006 DOI: 10.1021/nl2028409

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.

View the original article here

Read More

Natural killer cells could be key to anthrax defense

ScienceDaily (Oct. 27, 2011) — One of the things that makes inhalational anthrax so worrisome for biodefense experts is how quickly a relatively small number of inhaled anthrax spores can turn into a lethal infection. By the time an anthrax victim realizes he or she has something worse than the flu and seeks treatment, it's often too late; even the most powerful antibiotics may be no help against the spreading bacteria and the potent toxins they generate.

Now, though, University of Texas Medical Branch at Galveston researchers have found new allies for the fight against anthrax. Known as natural killer cells, they're a part of the immune system normally associated with eliminating tumor cells and cells infected by viruses. But natural killer cells also attack bacteria -- including anthrax, according to the UTMB group.

"People become ill so suddenly from inhalational anthrax that there isn't time for a T cell response, the more traditional cellular immune response," said UTMB assistant professor Janice Endsley, lead author of a paper now online in the journal Infection and Immunity. "NK cells can do a lot of the same things, and they can do them immediately."

In test-tube experiments, a collaborative team led by Endsley and Professor Johnny Peterson profiled the NK cell response to anthrax, documenting how NK cells successfully detected and killed cells that had been infected by anthrax, destroying the bacteria inside the cells along with them. Surprisingly, they found that NK cells were also able to detect and kill anthrax bacteria outside of human cells.

"Somehow these NK cells were able to recognize that there was something hostile there, and they actually caused the death of these bacteria," Endsley said.

In further experiments, the group compared the anthrax infection responses of normal mice and mice that were given a treatment to remove NK cells from the body. All the mice died with equal rapidity when given a large dose of anthrax spores, but the non-treated (NK cell-intact) mice had much lower levels of bacteria in their blood. "This is a significant finding," Endsley said. "Growth of bacteria in the bloodstream is an important part of the disease process."

The next step, according to Endsley, is to apply an existing NK cell-augmentation technique (many have already been developed for cancer research) to mice, in an attempt to see if the more numerous and active NK cells can protect them from anthrax. Even if the augmented NK cells don't provide enough protection by themselves, they could give a crucial boost in combination with antibiotic treatment.

"We may not be able to completely control something just by modulating the immune response," Endsley said. "But if we can complement antibiotic effects and improve the efficiency of antibiotics, that would be of value as well."

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Texas Medical Branch at Galveston.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

C. M. Gonzales, C. B. Williams, V. E. Calderon, M. B. Huante, S. T. Moen, V. L. Popov, W. B. Baze, J. W. Peterson, J. J. Endsley. Antibacterial Role for Natural Killer Cells in Host Defense to Bacillus Anthracis. Infection and Immunity, 2011; DOI: 10.1128/IAI.05439-11

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

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Read More

Snakes with big hearts may help yours: Fatty acids involved in python heart growth could benefit diseased human heart

ScienceDaily (Oct. 27, 2011) — Identification of three fatty acids involved in the extreme growth of Burmese pythons' hearts following large meals could prove beneficial in treating diseased human hearts, according to research co-authored by a University of Alabama scientist and publishing in the Oct. 28 issue of Science.

Growth of the human heart can be beneficial when resulting from exercise -- a type of growth known as physiological cardiac hypertrophy -- but damaging when triggered by disease -- growth known as pathological hypertrophy. The new research shows a potential avenue by which to make the unhealthy heart growth more like the healthy version.

"We may later be able to turn the tables, in a sense, in the processes involved in pathological hypertrophy by administering a combination of fatty acids that occur in very high concentrations in the blood of digesting pythons," said Dr. Stephen Secor, associate professor of biological sciences at UA and one of the paper's co-authors. "This could trigger, perhaps, something more akin to the physiological form of hypertrophy."

The research, conducted in collaboration with multiple researchers at the University of Colorado working in the lab of Dr. Leslie Leinwand, identified three fatty acids, myristic acid, palmitic acid and palmitoleic acid, for their roles in the snakes' healthy heart growths following a meal.

Researchers took these fatty acids from feasting pythons and infused them into fasting pythons. Afterward, those fasting pythons underwent heart-rate growths similar to that of the feasting pythons. In a similar fashion, the researchers were able to induce comparable heart-rate growths in rats, indicating that the fatty acids have a similar effect on the mammalian heart.

The paper, whose lead author was Dr. Cecilia Riquelme of the University of Colorado, also showed that the pythons' heart growth was a result of the individual heart cells growing in size, rather than multiplying in number.

By studying gene expression in the python hearts -- which genes are turned on following feasting -- the research, Secor said, shows that the changes the pythons' hearts undergo is more like the positive changes seen in a marathon runner rather than the types of changes seen in a diseased, or genetically altered, heart.

"Cyclists, marathon runners, rowers, swimmers, they tend to have larger hearts," Secor said. "It's the heart working harder to move blood through it. The term is 'volume overload,' in reference to more blood being pumped to tissues. In response, the heart's chambers get larger, and more blood is pushed out with every contraction, resulting in increased cardiac performance."

However, the time-frame of this increased heart performance of a python blows away even the most physically-fit distance runner, Secor said.

"Instead of experiencing elevated cardiac performance for several hours with running, the Burmese python is maintaining heightened cardiac output for five to six days, non-stop, while digesting their large meal."

Another interesting finding of the research, Secor said, is even with the increased volume of triglycerides circulating in the snakes after feeding, those lipids are not remaining within the snakes' hearts or vascular systems after the completion of digestion.

"The python hearts are using the circulating lipids to fuel the increase in performance."

Traditionally, mice have been the preferred animal model used to study the genetic heart disease known as hypertrophic cardiomyopathy, characterized by heart growth and contractile dysfunction. However, the snakes' unusual physiological responses render them more insightful models, in some cases, Secor said.

Pythons are infrequent feeders, sometimes eating only once or twice a year in the wild. When they do eat, they undergo extreme physiologic and metabolic changes that include increases in the size of the heart, along with the liver, pancreas, small intestine and kidney. Three days after a feeding, a python's heart mass can increase as much as 40 percent, before reverting to its pre-meal size once digestion is completed, Secor said.

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Alabama in Tuscaloosa.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Cecilia A. Riquelme, Jason A. Magida, Brooke C. Harrison, Christopher E. Wall, Thomas G. Marr, Stephen M. Secor, Leslie A. Leinwand. Fatty Acids Identified in the Burmese Python Promote Beneficial Cardiac Growth. Science, 2011; 334 (6055): 528-531 DOI: 10.1126/science.1210558

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

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Read More

Highly efficient oxygen catalyst found: Rechargeable batteries and hydrogen-fuel production could benefit

ScienceDaily (Oct. 28, 2011) — A team of researchers at MIT has found one of the most effective catalysts ever discovered for splitting oxygen atoms from water molecules -- a key reaction for advanced energy-storage systems, including electrolyzers, to produce hydrogen fuel and rechargeable batteries. This new catalyst liberates oxygen at more than 10 times the rate of the best previously known catalyst of its type.

The new compound, composed of cobalt, iron and oxygen with other metals, splits oxygen from water (called the Oxygen Evolution Reaction, or OER) at a rate at least an order of magnitude higher than the compound currently considered the gold standard for such reactions, the team says. The compound's high level of activity was predicted from a systematic experimental study that looked at the catalytic activity of 10 known compounds.

The team, which includes materials science and engineering graduate student Jin Suntivich, mechanical engineering graduate student Kevin J. May and professor Yang Shao-Horn, published their results in Science on Oct. 28.

The scientists found that reactivity depended on a specific characteristic: the configuration of the outermost electron of transition metal ions. They were able to use this information to predict the high reactivity of the new compound -- which they then confirmed in lab tests.

"We not only identified a fundamental principle" that governs the OER activity of different compounds, "but also we actually found this new compound" based on that principle, says Shao-Horn, the Gail E. Kendall (1978) Associate Professor of Mechanical Engineering and Materials Science and Engineering.

Many other groups have been searching for more efficient catalysts to speed the splitting of water into hydrogen and oxygen. This reaction is key to the production of hydrogen as a fuel to be used in cars; the operation of some rechargeable batteries, including zinc-air batteries; and to generate electricity in devices called fuel cells. Two catalysts are needed for such a reaction -- one that liberates the hydrogen atoms, and another for the oxygen atoms -- but the oxygen reaction has been the limiting factor in such systems.

Other groups, including one led by MIT's Daniel Nocera, have focused on similar catalysts that can operate -- in a so-called "artificial leaf" -- at low cost in ordinary water. But such reactions can occur with higher efficiency in alkaline solutions, which are required for the best previously known catalyst, iridium oxide, as well as for this new compound.

Shao-Horn and her collaborators are now working with Nocera, integrating their catalyst with his artificial leaf to produce a self-contained system to generate hydrogen and oxygen when placed in an alkaline solution. They will also be exploring different configurations of the catalyst material to better understand the mechanisms involved. Their initial tests used a powder form of the catalyst; now they plan to try thin films to better understand the reactions.

In addition, even though they have already found the highest rate of activity yet seen, they plan to continue searching for even more efficient catalyst materials. "It's our belief that there may be others with even higher activity," Shao-Horn says.

Jens Norskov, a professor of chemical engineering at Stanford University and director of the Suncat Center for Interface Science and Catalysis there, who was not involved in this work, says, "I find this an extremely interesting 'rational design' approach to finding new catalysts for a very important and demanding problem."

The research, which was done in collaboration with visiting professor Hubert A. Gasteiger (currently a professor at the Technische Universität München in Germany) and professor John B. Goodenough from the University of Texas at Austin, was supported by the U.S. Department of Energy's Hydrogen Initiative, the National Science Foundation, the Toyota Motor Corporation and the Chesonis Foundation.

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Massachusetts Institute of Technology. The original article was written by David L. Chandler, MIT News Office.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

J. Suntivich, K. J. May, H. A. Gasteiger, J. B. Goodenough, Y. Shao-Horn. A Perovskite Oxide Optimized for Oxygen Evolution Catalysis from Molecular Orbital Principles. Science, 2011; DOI: 10.1126/science.1212858

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.

View the original article here

Read More