Imaging inflammation in the living brain

Inflammation occurs in the human brain during illnesses such as Alzheimer's disease, Parkinson’s disease, stroke and traumatic brain injury. Now, a research team in Japan has developed a probe that can bind to the pro-inflammatory enzyme cyclooxygenase (COX). The probe, 11C-ketoprofen methyl ester, enables researchers to observe when and where the enzyme is acting in the brains of living animals using positron emission tomography (PET) imaging.

In PET imaging, a radioactive tracer that binds specifically to a specific molecule in the body is injected into a living organism. Images are then taken with a PET scanner, indicating where in the body that tracer is found.

Led by Hirotaka Onoe at the RIKEN Center for Molecular Imaging Science in Kobe, the researchers had previously discovered that 11C-ketoprofen methyl ester could recognize COX, but not which of its two forms. To determine which isoform is responsible for binding their molecular probe, Miho Shukuri, a young member of Onoe’s team, utilized a series of mice lacking the genes for either COX-1 or COX-2. She found that the PET probe could bind to the brains of COX-2-deficient mice, but not to those lacking COX-1. According to the researchers, 11C-ketoprofen methyl ester is therefore the first PET probe that is specific to COX-1 in living animals.

When Shukuri injected bacterial antigens into the brain of rats to induce inflammation, she saw the PET probe build up in the brain within six hours to one day after antigen injection. The levels dropped a week later. Because COX-1 is rapidly activated by brain injury, this may mean that administration of drugs that block COX-1 soon after injury could prevent the progression of brain damage. “COX-1 could therefore be a promising target for the neurodegenerative diseases that exhibit neuro-inflammation,” explains Onoe.

Microglia are immune cells in the brain that proliferate in response to injury, while macrophages are immune cells normally found within the blood that invade the brain after injury. The researchers observed that the injury-induced increase in brain COX-1 seemed to occur within microglia and macrophages (Fig. 1), which also became more numerous in the brain after exposure to bacterial antigens. Other research groups have found COX-1-expressing microglia in diseases such as Alzheimer's disease, Parkinson’s disease and multiple sclerosis. This suggests to Onoe and colleagues that 11C-ketoprofen methyl ester could be used to track the time course and localization of increased COX-1 expression in living organisms, including humans, suffering from diseases linked to neuro-inflammation.

More information: Shukuri, M., et al. In vivo expression of cyclooxygenase-1 in activated microglia and macrophages during neuroinflammation visualized by PET with 11C-ketoprofen methyl ester. The Journal of Nuclear Medicine published online 1 July, 2011 (doi: 10.2967/jnumed.110.084046).

Takashima-Hirano, M., et al. General method for the 11C-labeling of 2-arylpropionic acids and their esters: construction of a PET tracer library for a study of biological events involved in COXs expression. Chemistry 16, 4250–4258 (2010).

Provided by RIKEN (news : web)

Laser pioneer or electrochemist for Nobel?

(AP) -- Americans William Moerner, Allen Bard and Richard Zare could be among the potential candidates when the Nobel Prize in chemistry is announced Wednesday.

Guessing a winner among scores of discoveries in such a broad field as chemistry is notoriously hard but that doesn't stop people from trying.

Recent discoveries are more or less ruled out because Nobel jurors look for research that has stood the test of time. Typically, Nobel winners have received plenty of other awards before they get the call from Stockholm.

Both Zare, a laser chemistry pioneer at Stanford University, and Bard, an electrochemistry expert of the University of Austin, Texas, have been decorated with multiple honors, including the Priestley Award, handed out by the American Chemical Society, and Israel's Wolf Prize.

Bard shared the latter in 2008 with Moerner, of Stanford University, for creating a new field of science: single-molecule spectroscopy and imaging.

Should the chemistry prize committee chose a woman, for a change, American Jacqueline Barton, of the California Institute of Technology, could get the nod for her work on the transport of electrons in DNA.

Only four women have won the chemistry prize since the awards were first handed out in 1901: French scientist Marie Curie (1911), her daughter Irene Joliot-Curie (1935), British chemist Dorothy Crowfoot Hodgkin (1964) and Ada Yonath of Israel (2009).

Other names that routinely pop up in Nobel speculation include Americans Stuart Schreiber and Gerald Crabtree for work that sheds light on how tiny molecules can be used on cell circuits and signaling pathways.

If the prize honors nanotechnology - the science dedicated to building materials from the molecular level - possible winners could include American Charles Lieber, British chemist James Fraser Stoddart or Japan's Sumio Iijima, who discovered carbon nanotubes in 1991.

The Nobel Prize in chemistry announcement will cap this year's science awards.

Immune system researchers Bruce Beutler of the U.S. and Frenchman Jules Hoffmann shared the medicine prize Monday with Canadian-born Ralph Steinman, who died three days before the announcement. U.S.-born scientists Saul Perlmutter, Brian Schmidt and Adam Riess won the physics prize on Tuesday for discovering that the universe is expanding at an accelerating pace.

Last year, the chemistry committee rewarded Japanese scientists Ei-ichi Negishi and Akira Suzuki and American Richard Heck for designing a technique to bind together carbon atoms, a key step in assembling the skeletons of organic compounds used in medicine, agriculture and electronics.

The 10 million kronor (US$1.4 million) Nobel Prizes are handed out every year on Dec. 10, the anniversary of award founder Alfred Nobel's death in 1896.

?2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Advance offers new opportunities in chemistry education, research

Researchers at Oregon State University have created a new, unifying method to describe a basic chemical concept called "electronegativity," first described almost 80 years ago by OSU alumnus Linus Pauling and part of the work that led to his receiving the Nobel Prize.

The new system offers simplicity of understanding that should rewrite high school and college chemistry textbooks around the world, even as it opens important new avenues in materials and chemical research, with possible applications in everything from solar energy to solid state batteries.

The findings were just published in the Journal of the American Chemical Society, in work supported by the National Science Foundation and the U.S. Department of Energy.

"This is a quantum leap forward in understanding basic tendencies in chemical bond formation," said John Wager, a professor of electrical engineering at OSU. "We can now take a concept that college students struggle with and I could explain it to a kindergarten class.

"Even advanced scientists will gain new insights and understanding into the chemical processes they study," Wager said. "Using this system, I could look at various materials being considered for use in new solar energy cells and determine quickly that this one might work, that one doesn't stand a chance."

Electronegativity, as defined by Pauling, is "the power of an atom in a molecule to attract electrons to itself." This concept is useful for explaining why some atoms tend to attract electrons, others share them and some give them away. In the 1930s, Pauling was the first to devise a method for numerically estimating the electronegativity of an atom. Other researchers later developed different approaches.

The new system developed at OSU – the first of its type since the early 1990s - is called an atomic "solid state energy scale." It characterizes electronegativity as the solid state energy of elements in a compound, and shows that electrons simply move from a higher energy to a lower energy.

"This is a remarkably intuitive approach to understanding electronegativity, and yet it's based on data that are absolute, not arbitrary," said Douglas Keszler, an OSU professor of chemistry, co-author on the study and an international expert in materials science research.

"This is already one of the best instruments in my tool box for predicting the properties of new materials and understanding inorganic reactions," Keszler said. "It's not only more accurate and comprehensive, it just offers a simplicity of understanding that is very important."

The electronegativity scale developed by Pauling is among the most widely known of his contributions in studies on the nature of the chemical bond, the work for which he received a Nobel Prize in chemistry.

According to Ram Ravichandran, an electrical engineering student at OSU and co-author of the study, the new approach is based on the study of how the "band gap," a fundamental property of materials, varies for a variety of compounds. This helps to derive an absolute energy reference and a new solid state energy scale, providing a surprisingly simple way to visualize the way materials will interact.

The system could aid research in new semiconductor devices, catalysts, solar cells, light emitting materials and many other uses.

Provided by Oregon State University (news : web)

Biochemists identify how tissue cells detect and perfect

Scientists have discovered how cells detect tissue damage and modify their repair properties accordingly. The findings, published today [6 October] in the journal Developmental Cell, could open up new opportunities for improving tissue repair in patients following illness or surgery.

The Wellcome Trust-funded study, led by biochemists at the University of Bristol, examined the signalling process in damaged tissue cells and identified the cellular mechanisms responsible for activating effective repair.

In healthy adults the majority of tissue cells lie dormant unless challenged by wounding, at which point they sense a change in the molecular environment. Plasma leaking from damaged blood vessels and causes fibroblast cells to migrate into the damaged tissue, contract the wound, and plug the gap by depositing a substance such as collagen, which provides the structural support.

Dr Mark Bass, lead author and Research Fellow in the University's School of Biochemistry, said: "Each of these processes requires the turnover of cellular adhesions, and the challenge has been to determine how cells detect tissue damage and modify their adhesive properties accordingly."

Using atomic force microscopy, the team were able to determine how a molecule sensor, syndecan-4, triggers the uptake and redeployment of adhesive molecules. This novel signalling pathway causes fibroblasts and keratinocytes to migrate in response to the changing tissue architecture and follow the matrix fibres that make up the skin. Such linear migration towards a damage signal allows the cells to arrive at the wound far more efficiently than if activated cells searched randomly about the tissue, and results in a very efficient healing response.

Dr Bass added: "We find that this signalling cascade is essential for efficient healing, this opens up considerable opportunities for improving tissue repair in patients."

More information: The Wellcome Trust-funded study, entitled 'A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis' by Dr Mark Bass is published in the journal Developmental Cell.

Provided by University of Bristol (news : web)

A coating that prevents barnacles forming colonies

It is not necessary for an effective anti-fouling coating to release toxins into the environment. Scientists at the University of Gothenburg have shown that it is instead possible to mix into the coating molecules on which the adult barnacles cannot grow. The result has been published in the scientific journal Biofouling.

Fouling of hulls is a problem for all boat owners, and one of the most difficult organisms to deal with is barnacles. A research group at the Department of Cell and Molecular Biology has therefore studied the biology of barnacles in detail, and focussed on one particularly sensitive stage in the barnacle life cycle.

"When newly matured adult barnacles attempt to penetrate through the coating in order to establish a fixed location to grow, they are extremely sensitive to certain molecules known as 'macrocyclic lactones', which are normally produced by certain bacteria", says Professor Hans-Björne Elwing of the Department of Cell and Molecular Biology at the University of Gothenburg.

A better effect with no toxin released to the environment

When such molecules are mixed into the anti-fouling coating, the treated surface is first colonised by barnacles in the normal way. But as soon as the young barnacles have matured into adults and attempt to establish stronger contact with the surface, they lose contact and probably die. It is also the case that certain brown algae counteract the colonisation by barnacles on the surfaces of leaves in a similar manner.

"Using this discovery, we have managed to create coatings with new binding agents that shut down the release of the macrocyclic lactones into the marine environment. Further, only trace amounts of the macrocyclic lactones are required in the coating to give full effect against barnacles."

The research group has shown through field trials on leisure craft that the addition of macrocyclic lactones can fully replace copper in coatings used on such craft, on both the eastern and the western coasts of Sweden, and for several seasons.

"While it is true that it is only barnacles that are affected by the additive, the growth of algae and similar organisms can be counteracted relatively simply by other methods."

Provided by University of Gothenburg (news : web)