Thursday, June 30, 2011

Scientists a step closer to understanding 'natural antifreeze' molecules

Scientists have made an important step forward in their understanding of cryoprotectants -- compounds that act as natural 'antifreeze' to protect drugs, food and tissues stored at sub-zero temperatures.

Researchers from the Universities of Leeds and Illinois, and Columbia University in New York, studied a particular type of cryoprotectants known as osmolytes. They found that small osmolyte molecules are better at protecting proteins than larger ones.

The findings, published in Proceedings of the National Academy of Sciences, could help scientists develop better storage techniques for a range of materials, including human reproductive tissue used in IVF.

Biological systems can usually only operate within a small range of temperatures. If they get too hot or too cold, the molecules within the system can become damaged (denatured), which affects their structure and stops them from functioning.

But certain species of fish, reptiles and amphibians can survive for months below freezing by entering into a kind of suspended animation. They are able to survive these extreme conditions thanks to osmolytes -- small molecules within their blood that act like antifreeze -preventing damage to their vital organs.

These properties have made osmolytes attractive to scientists. They are used widely in the storage and testing of drugs and other pharmaceuticals; in food production; and to store human tissue like egg and sperm cells at very low temperatures (below -40oC) for a long period of time.

"If you put something like human tissue straight in the freezer, ice crystals start to grow in the freezing water and solutes -- solid particles dissolved in the water -- get forced out into the remaining liquid.

This can result in unwanted high concentrations of solutes, such as salt, which can be very damaging to the tissue," said Dr Lorna Dougan from the University of Leeds, who led the study. "The addition of cryoprotectants, such as glycerol, lowers the freezing temperature of water and prevents crystallisation by producing a 'syrupy' semi-solid state. The challenge is to know which cryoprotectant molecule to use and how much of it is necessary.

"We want to get this right so that we recover as much of the biological material as possible after re-thawing. This has massive cost implications, particularly for the pharmaceutical industry because at present they lose a large proportion of their viable drug every time they freeze it."

Dr Dougan and her team tested a range of different osmolytes to find out which ones are most effective at protecting the 3D structure of a protein. They used an atomic force microscope to unravel a test protein in a range of different osmolyte environments to find out which ones were most protective. They discovered that smaller molecules, such as glycerol, are more effective than larger ones like sorbitol and sucrose.

Dr Dougan said: "We've been able to show that if you want to really stabilise a protein, it makes sense to use small protecting osmolytes. We hope to use this discovery and future research to develop a simple set of rules that will allow scientists and industry to use the best process parameters for their system and in doing so dramatically increase the amount of material they recover from the freeze-thaw cycle."

The research was funded by the UK Engineering and Physical Sciences Research Council, the US National Institutes of Health and the China National Basic Research Program.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Leeds.

Journal Reference:

L. Dougan, G. Z. Genchev, H. Lu, J. M. Fernandez. Probing osmolyte participation in the unfolding transition state of a protein. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1101934108

Self-assembling electronic nano-components

Magnetic storage media such as hard drives have revolutionized the handling of information: huge quantities of data are magnetically stored while relying on highly sensitive electronic components. And data capacities are expected to increase further through ever smaller components. Together with experts from Grenoble and Strasbourg, researchers of KIT's Institute of Nanotechnology (INT) have now developed a nano-component based on a mechanism observed in nature.

What if the very tininess of a component prevented one from designing the necessary tools for its manufacture? One possibility could be to "teach" the individual parts to self-assemble into the desired product. For fabrication of an electronic nano-device, a team of INT researchers headed by Mario Ruben adopted a trick from nature: Synthetic adhesives were applied to magnetic molecules in such a way that the latter docked on to the proper positions on a nanotube without any intervention. In nature, green leaves grow through a similar self-organizing process without any impetus from subordinate mechanisms. The adoption of such principles to the manufacture of electronic components is a paradigm shift, a novelty.

The nano-switch was developed by a European team of scientists from Centre National de la Recherche Scientifique (CNRS) in Grenoble, Institut de Physique et Chimie des Matériaux at the University of Strasbourg, and KIT's INT. It is one of the invention's particular features that, unlike the conventional electronic components, the new component does not consist of materials such as metals, alloys or oxides but entirely of soft materials such as carbon nanotubes and molecules.

Terbium, the only magnetic metal atom that is used in the device, is embedded in organic material. Terbium reacts highly sensitively to external magnetic fields. Information as to how this atom aligns along such magnetic fields is efficiently passed on to the current flowing through the nanotube. The Grenoble CNRS research group headed by Dr. Wolfgang Wernsdorfer succeeded in electrically reading out the magnetism in the environment of the nano-component. The demonstrated possibility of addressing electrically single magnetic molecules opens a completely new world to spintronics, where memory, logic and possibly quantum logic may be integrated.

The function of the spintronic nano-device is described in the July issue of Nature Materials (DOI number: 10.1038/Nmat3050)for low temperatures of approximately one degree Kelvin, which is -272 degrees Celsius. Efforts are taken by the team of researchers to further increase the component's working temperature in the near future.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by Karlsruhe Institute of Technology.

Journal Reference:

M. Urdampilleta, S. Klyatskaya, J-P. Cleuziou, M. Ruben, W. Wernsdorfer. Supramolecular spin valves. Nature Materials, 2011; DOI: 10.1038/nmat3050

Astronomers reach for the stars to discover new cancer therapy

ScienceDaily (June 25, 2011) — Astronomers' research on celestial bodies may have an impact on the human body.

Ohio State University astronomers are working with medical physicists and radiation oncologists to develop a potential new radiation treatment -- one that is intended to be tougher on tumors, but gentler on healthy tissue.

In studying how chemical elements emit and absorb radiation inside stars and around black holes, the astronomers discovered that heavy metals such as iron emit low-energy electrons when exposed to X-rays at specific energies.

Their discovery raises the possibility that implants made from certain heavy elements could enable doctors to obliterate tumors with low-energy electrons, while exposing healthy tissue to much less radiation than is possible today. Similar implants could enhance medical diagnostic imaging.

On June 24, at the International Symposium on Molecular Spectroscopy, Ohio State University senior research scientist Sultana Nahar announces the team's computer simulations of the elements gold and platinum, and the design of a prototype device that generates X-rays at key frequencies.

Their simulations suggest that hitting a single gold or platinum atom with a small dose of X-rays at a narrow range of frequencies -- equal to roughly one tenth of the broad spectrum of X-ray radiation frequencies -- produces a flood of more than 20 low-energy electrons.

"As astronomers, we apply basic physics and chemistry to understand what's happening in stars. We're very excited to apply the same knowledge to potentially treat cancer," Nahar said.

"We believe that nanoparticles embedded in tumors can absorb X-rays efficiently at particular frequencies, resulting in electron ejections that can kill malignant cells," she continued. "From X-ray spectroscopy, we can predict those energies and which atoms or molecules are likely to be most effective."

Nahar and Anil Pradhan, professor of astronomy at Ohio State, discovered that particular frequencies of X-rays cause the electrons in heavy metal atoms to vibrate and break free from their orbits around the nucleus, creating what amounts to an electrically charged gas, or plasma, around the atoms at the nanometer scale.

They have thus dubbed their medical concept Resonant Nano-Plasma Theranostics (RNPT) -- the latter word a merger of "therapy" and "diagnostics."

"From a basic physics point of view, the use of radiation in medicine is highly indiscriminate," Pradhan added. "Really, there has been no fundamental advance in X-ray production since the 1890s, when Roentgen invented the X-ray tube, which produces X-rays over a very wide range."

No fundamental advance, that is, until now.

"Together with long-time collaborator and medical physicist Yan Yu from Thomas Jefferson University Medical College, we've developed the RNPT methodology, which we hope will have far-reaching consequences for X-ray imaging and radiation therapy," Pradhan said.

He explained why metals such as gold or platinum display this behavior, and how hospitals can take advantage of it. The basic physics, he said, has been well understood since the 1920s.

Physicists have long known that electrons orbit the nuclei of atoms at different distances, some close to the nucleus and some farther away. When one of the close-in electrons is lost, a far-out electron may drop in to take its place, which releases energy. This is called the Auger effect, which was discovered in 1922.

Often the energy is strong enough to kick out a second electron, called an Auger electron. The same process could also result in the emission of light particles, or photons, at specific energies or frequencies, the most prominent of which are called K-alpha X-rays.

The astronomers believe that K-alpha X-ray frequencies kick the close-in electrons out of heavy metal atoms such as platinum, causing many far-out electrons to fall in, and many more electrons to be kicked out. These free Auger electrons are low in energy but great in number, and could feasibly bombard nearby malignant cells and shatter their DNA.

While typical therapeutic X-ray machines such as CT scanners generate full-spectrum X-rays, hospitals could employ RNPT using only K-alpha X-rays, which would greatly reduce a patient's radiation exposure.

That's the function of the proof-of-principle device that the team has constructed. Though the working tabletop prototype needs to be further developed, these first experiments show that the Auger effect can be used to deliver specific frequencies of X-ray radiation to heavy metal nanoparticles embedded in diseased tissue for imaging or therapy.

Gold and Platinum are only the first two elements that the team is studying in detail for the application of the RNPT methodology. Both metals are safe to use in the body. Platinum is already used in the chemotherapy drug cisplatin, where it helps deliver the drug by binding to malignant DNA.

"This work could eventually lead to a combination of radiation therapy with chemotherapy using platinum as the active agent," Pradhan said.

Cancer therapy is new territory for the astronomers. Together with Yu, they came upon the idea for RNPT when they were trying to understand the abundance of different chemical elements inside stars.

Their goal at the time was to help astronomers understand what different stars are made of, based on how radiation flows through them and emanates from them.

Astronomers already have several methods for doing this, but their results vary widely. By simulating how different elements behave when exposed to the radiation inside stars, Nahar and Pradhan hope to help astronomers determine precisely what our sun is made of.

Even for a profession as mathematically rigorous as astronomy, Nahar and Pradhan's undertaking is staggeringly large. They must calculate how every possible atom contained in a star will react to every possible wavelength of energy. They rely on the Ohio Supercomputer Center for these calculations and simulations; in fact, their research team has ranked among the biggest users of computational resources ever since the center's establishment more than two decades ago.

The simulations have started to pay off, in an astrophysical sense. They have revealed that previous observations and calculations of chemical abundances of the sun may in fact be off by as much as 50 percent.

Even more surprising to the astronomers were the results for simulating the radiation absorption by heavy metal atoms, such as iron. Iron plays the dominant role in controlling radiation flow through stars, but it is also observed in some black hole environments, where K-alpha X-rays can be detected from Earth.

"That's when we realized that the implications went way beyond atomic astrophysics," Pradhan said. "X-rays are used all the time in radiation treatments and imaging, and so are heavy metals -- just not in this way. If we could target heavy metal nanoparticles to certain sites in the body, X-ray imaging and therapy could be more powerful, reduce radiation exposure, and be much more precise."

Leading a multi-disciplinary team, Nahar, Pradhan, and Yu are working with several colleagues in the departments of radiation oncology at Ohio State and Thomas Jefferson University Medical College to further explore these medical applications.

The Ohio State collaborators include Russell Pitzer, professor emeritus of chemistry, Enam Chowdhury, senior research associate in physics, and Sara Lim, a graduate student in biophysics. They also worked with Kaile Li and Jian Wang, assistant professors in radiation oncology; former postdoctoral researchers Max Montenegro (now of the Pontificia Universidad Católica de Chile), and Chiranjib Sur (now of the high-performance computing group of IBM's India Software Lab); and graduate student Mike Mrozik in chemical physics.

This research was funded by a Large Interdisciplinary Grant award from Ohio State, and computational resources were provided by the Ohio Supercomputer Center.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ohio State University. The original article was written by Pam Frost Gorder.

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.

Probing the secrets of the ryegrasses: Chemists design a route for synthesis of loline alkaloids

Loline alkaloids protect plants from attack by insects and have other interesting features that have yet to be studied in detail. Chemists from Ludwig-Maximilians-Universitaet in Munich have developed a method for the effective synthesis of these compounds, which will facilitate further investigations in biology and medicine.

Chemists from Ludwig-Maximilians-Universitaet in Munich led by Professor Dirk Trauner have developed a concise and efficient method for the synthesis of the alkaloid loline and related compounds.

Loline alkaloids are a biologically interesting group of natural products, which have unusual physicochemical and pharmacological characteristics, but are as of yet poorly understood. They are produced by fungal symbionts that infect weeds and forage grasses, and act as deterrents of insects and other herbivores.

Some of the agents synthesized by endophytic fungi are toxic to grazing animals, producing a syndrome known as the staggers. Indeed, such toxic weeds (commonly called ryegrass or cockle) were much feared in antiquity and are mentioned both by Virgil and in the New Testament.

Lolines however are comparatively innocuous to mammalian herbivores, and might therefore be of some therapeutic use. The loline alkaloid temuline has attracted particular attention in another context because it can strongly bind carbon dioxide.

Lolines are relatively small molecules and have a fairly simple structure, but chemical synthesis of the compounds has proven to be quite challenging. "Our synthetic route is highly efficient and, with a maximum of 10 steps, very short," says Dirk Trauner, who led the project. "It will allow us to make these compounds in sufficient quantities to enable their various aspects to be investigated in detail. We should then be able to dissect the complex network of interactions of the plants and their fungal parasites with insects and bacteria. We now plan to use our synthetic material to identify the receptor for loline alkaloids."

The project was carried out in the Center for Integrated Protein Science Munich (CIPSM), an LMU Cluster of Excellence.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Ludwig-Maximilians-Universitaet Muenchen (LMU).

Journal Reference:

Mesut Cakmak, Peter Mayer, Dirk Trauner. An efficient synthesis of loline alkaloids. Nature Chemistry, 2011; DOI: 10.1038/nchem.1072

Wednesday, June 29, 2011

Evonik has reduced its specific energy-related greenhouse gas emissions by sixteen percent compared to 2004

Evonik Industries has significantly improved its CO2 efficiency. The Group has been able to reduce its specific energy-related greenhouse gas emissions in chemical production by sixteen percent; compared to the previous year, the improvement in 2010 was a full three percent. This is highlighted in the company’s 2010 Corporate Responsibility Report, which was recently presented in Brussels. This success means that Evonik has moved another step closer to its self-imposed goal of reducing the specific energy-related greenhouse gases of its chemical activities to twenty percent below the level of 2004 by 2014.

60 percent of CO2 emissions in 2010 were energy-related and 40 percent related to chemical processes. Absolute emissions of greenhouse gases increased to 9.14 million metric tons CO2 equivalents in 2010, a rise of 11 percent over the previous year (2009: 8.23). At the same time, specific emissions, i.e. emissions relative to output, declined by 3 percent. Accordingly, Evonik has successfully detached its production growth from rising emissions. “Our significantly increased energy efficiency is making an important contribution to climate protection" says Klaus Engel, the Chairman of the Evonik Executive Board.

With the global economy regaining momentum, the Group returned to operating its chemical production facilities at full capacity in 2010, in many cases with optimized efficiency. A number of efficiency enhancement measures contributed to the reduction of specific greenhouse gas emissions.  These included the start-up of a new cogeneration power plant in Antwerp (Belgium) and a more efficient installation for thermal incineration of exhaust gases from the production of the feed additive methionine. In addition, Evonik initiated selective energy-saving programs at its site in Rheinfelden (Germany). During the 2010 financial year, Evonik invested a total of 36 million Euro in environmental protection for its chemical business activities.

“We want to be successful as a supplier of competitive products and technologies that also make a contribution to sustainability. At the same time, we want to be a responsible, reliable and fair partner for our customers, employees and society and meet the demands made by our shareholders,” noted CEO Klaus Engel.

Evonik invested some €338 million in research and development in 2010. The Group pursued about 500 different projects, of which approximately 100 focused on resource efficiency.

The Corporate Responsibility (CR) efforts of Evonik provide answers for challenges of the future, such as resource efficiency. Says Christine Anders, Head of CR at Evonik: “Corporate Responsibility is an integral part of our business and we plan to keep fine-tuning our CR strategy in 2011.” With its three dimensions of Business, Employees, and Processes, the CR strategy is a fixed component of the corporate strategy, providing support and new impulses.  In 2010, the Group identified important sustainability topics as part of so-called materiality analyses and intensified its dialog with stakeholders.

The Evonik Corporate Responsibility Report 2010 for the first time met the requirements for the highest application level A+ of the Global Reporting Initiative (GRI). GRI is the internationally recognized standard for comprehensive sustainability reporting and confirmed the A+ reporting level for Evonik. Large parts of the report underwent a business audit by an auditing firm.


SABIC wins VNCI Responsible Care Award for 2011

 SABIC has won the Responsible Care award for 2011. The announcement was made during the annual meeting of the Dutch Chemical Industry Federation (Vereniging van de Nederlandse Chemische Industrie (VNCI)) in The Hague. The company was chosen to receive the award because of its efforts to render the transportation of hazardous substances as safe as possible. SABIC has implemented a number of safety policies which go above and beyond the statutory and regulatory provisions. In addition, SABIC also actively involves its suppliers in safety improvements throughout the logistics chain.

Two tangible examples of this are the Rail Safety Policy and the Responsible Care requirement for our haulers. The judging panel decided that by introducing this new safety policy, SABIC has proved itself to be an excellent example of how to implement transport safety. In the view of the panel of experts and also the general public, who were able to cast their vote for the first time, SABIC has set the standard with this safety policy.

Among other things, the Rail Safety Policy prescribes that the company only uses carriages fitted with crash buffers. The use of this safety feature ensures that the impact of a collision on the tank is smaller, thereby reducing the risk of a disaster. In addition, under the Rail Safety Policy the carriages used are no more than 20 years old. This is also beneficial in terms of transport safety. SABIC was presented with a trophy to mark the occasion and is now in the running for the European Responsible Care award.

The Responsible Care program is a global initiative introduced by the chemical industry which aims to continuously improve companies’ performance in the field of safety, health, the environment and sustainability. On April 1 of this year, SABIC became the first company in the industry to call for its haulers to commit to Responsible Care. For this purpose, SABIC concluded three-year contracts with its road haulers to reinforce the company’s commitment to safety and sustainability throughout the entire logistics chain. This emphasizes the importance of implementing measures in an efficient manner and of openly discussing not only the successes but also the failures. It is also important to work with the authorities and organizations in order to develop, attain and also to exceed safety standards.

Huub Meessen, Vice President for Europe, says that he is “proud that SABIC’s revolutionary safety vision has been rewarded with the presentation of this Responsible Care award. I hope that our initiatives contribute to new standards being put in place within the chemical industry which will then further increase safety during the transportation of hazardous substances.”

The Responsible Care award will bring the VNCI Responsible Care right into the spotlight. The industry association has been bestowing this award on the most prominent and inspiring candidate since 1999. This year there were nine entries and for the first time in the award’s history the public was able to have its say in an online poll. The independent Responsible Care judging panel, which consisted of representatives from the government, MVO Nederland and the chemical industry, took the result of the online vote into account in its final decision. AkzoNobel and Nyrstar, who were both nominated alongside SABIC, received an honorable mention.


Brenntag achieves strategic market entry in China

 Brenntag signed a purchase agreement to acquire 100% of Zhong Yung (International) Chemical Ltd. Deal closing for the first tranche is expected in the 3rd quarter of this year. Brenntag will hold a majority stake of 51% and will acquire the remaining stake in 2016. Entering into a joint venture for five years gives Brenntag the opportunity to use the experience and know-how of Zhong Yung and its management team to establish a solid business platform for Brenntag in China.

“This transaction strengthens Brenntag’s growth strategy in the Asia-Pacific region. This acquisition is a strategic investment for Brenntag in China and also a first step through which Brenntag demonstrates full commitment to build a solid distribution network in China. We are continuing to look for further opportunities to support our growth in Asia Pacific.” says Brenntag’s COO and designated CEO Steve Holland.

Henri Néjade, President of Brenntag Asia Pacific, highlights: “It is a significant milestone in Brenntag’s Asian business development following the successful acquisition of EAC Industrial Ingredients in 2010. We are delighted to team up with Zhong Yung because it opens the opportunity for further growth in China. Zhong Yung is a major chemical distributor with about 2,000 customers, more than 100 suppliers and has an excellent infrastructure including laboratories, blending and storage capabilities.”


Linde to build largest air separation plant in Indonesia

PT. Linde Indonesia, a member of The Linde Group, announced that it had entered into a long term industrial gases supply scheme agreement with PT. KRAKATAU POSCO (PT.KP).

PT. KRAKATAU POSCO, a joint venture between POSCO and Krakatau Steel, is building a three million tonnes per annum (mtpa) steelworks in the first phase in the Cilegon area, located about 100 km west of Jakarta. PT.KP's new plant will be the first integrated steelworks in Southeast Asia and is targeted to be onstream by the end of 2013.

To support the gases requirements of PT.KP’s new  steel plant, Linde will invest about IDR 1 trillion (about EUR 88 million) to install a new air separation plant at Cilegon which is capable of producing approximately 2,000 tons per day (tpd) of oxygen.  In addition to meeting the 1,680 tpd oxygen requirement of PT.KP’s new steelworks, Linde’s new plant, which will be commissioned by October 2013, will also produce liquid products to meet the growing demand for industrial gases in West Java.

Mr Sanjiv Lamba, Member of the Executive Board of Linde AG, and Regional Business Unit Head for Linde South & East Asia, said, "The Linde Group is keen to expand our business in Indonesia, one of the fastest growing economies in this region. Our decision to invest and build what will be Indonesia’s largest air separation plant, and also Linde’s largest investment in Indonesia to date, demonstrates our continued commitment to support our valuable customer PT.KP in its growth plans, and also meet future demand and market opportunities going forward," Mr Lamba added.

Mr Darren Webster, President Director of PT. Linde Indonesia said, "The signing of this long term supply scheme contract is a major milestone for Linde in Indonesia. Our new air separation plant will produce more than 3,000 tpd of oxygen, nitrogen and argon, and will enable us to significantly increase our production capacity and enhance our ability to serve the fast growing West Java area," Mr Webster noted.


Tuesday, June 28, 2011

Cell's power generator depends on long-sought protein: 50-year search for calcium channel ends

Mitochondria, those battery-pack organelles that fuel the energy of almost every living cell, have an insatiable appetite for calcium. Whether in a dish or a living organism, the mitochondria of most organisms eagerly absorb this chemical compound. Because calcium levels link to many essential biological processes—not to mention conditions such as neurological disease and diabetes—scientists have been working for half a century to identify the molecular pathway that enables these processes.

After decades of failed effort that relied on classic biochemistry and membrane purification, Vamsi Mootha, HMS associate professor of systems biology, and colleagues have discovered, through a combination of digital database mining and laboratory assays, the linchpin protein that drives mitochondria's calcium machinery.

"This channel has been studied extensively using physiology and biophysics, yet its molecular identity has remained elusive," said Mootha, who also has appointments at Massachusetts General Hospital and at Broad Institute. "But thanks to the Human Genome Project, freely downloadable genomic databases, and a few tricks -- we were able to get to the bottom of it."

These findings will appear online June 19 in Nature.

The results build on work from Vamsi and his group over the past decade. In 2008, he and his team published a near-comprehensive protein inventory, or proteome, of human and mouse . This inventory, called MitoCarta, consisted of just over 1,000 proteins, most of which had no known function.

In a September 2010 paper, Mootha's group described using the MitoCarta inventory to identify the first protein specifically required for mitochondrial calcium uptake. Their strategy was simple. They knew that mitochondria from humans and Trypanosomes (a parasitical organism), but not baker's yeast, are capable of absorbing large amounts of calcium. By simply overlapping the mitochondrial protein profiles of these three organisms, the group could spotlight roughly 50 proteins out of the 1,000 that might be involved with calcium channeling. They found that one protein, which they dubbed MICU1, is essential for calcium uptake.

"That was an significant advance for the field," says Mootha. "We showed that MICU1 was required for calcium uptake, but because it did not span the membrane, we doubted it was the central component of the channel. But what it provided us with was live bait to then go and find the bigger fish."

Traditionally, researchers used standard laboratory methods for such a fishing exhibition, such as attaching biochemical hooks to the protein, casting it into the cell's cytoplasm, then reeling it back in the hope that another, related protein will have bitten. But MICU1's function as a regulator of a membrane channel made this technically prohibitive. Instead, graduate student Joshua Baughman and postdoctoral researcher Fabiana Perocchi went fishing in publicly available genomic databases.

With MICU1 as their point of reference, they scoured those databases that measure whole genome RNA and protein expression, as well as an additional database containing genomic information for 500 species, and looked for proteins whose activity profile mirrored MICU1's. A single anonymous protein with no known function stood out. The researchers named it MCU, short for "mitochondrial calcium uniporter."

To confirm that MCU is central to mitochondria's calcium absorption, the team collaborated with Alnylam Pharmaceuticals, a company that leverages a laboratory tool called RNAi in order to selectively knock out genes in both cells and live animals. Using one of the company's platforms, the researchers deactivated MCU in the livers of mice. While the mice displayed no immediate reaction, the mitochondria in their liver tissue lost the capacity to absorb calcium.

This basic science finding may prove relevant in certain human diseases. "We've known for decades now that neurons in the brains of people suffering from neurodegenerative disease are often marked by mitochondrial calcium overload," said Mootha, an expert on rare mitochondrial diseases who sees patients at Massachusetts General Hospital when he's not in the lab.

"We also know that the secretion of many hormones, like insulin, are triggered by calcium spikes in the cell's cytoplasm. By clearing cytosolic , mitochondria can shape these signals. Scientists studying the nexus of energy metabolism and cellular signaling will be particularly interested in MICU1 and MCU. It's still very early, but they could prove to be valuable drug targets for a variety of diseases – ranging from ischemic injury and neurodegeneration to diabetes."

More information: "Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter" Nature, online publication June 19, 2011.

Provided by Harvard Medical School (news : web)

Turning off cancer's growth signals


One hallmark of cancer cells is uncontrollable growth, provoked by inappropriate signals that instruct the cells to keep dividing. Researchers at MIT and Brigham and Women’s Hospital have now identified a new way to shut off one of the proteins that spreads those signals — a receptor known as HER3.

Drugs that interfere with HER3’s better-known cousins, EGFR and HER2, have already proven effective in treating many types of cancer, and early-stage clinical trials are underway with antibodies directed against HER3. HER3 is of great interest to cancer biologists because it is commonly involved in two of the deadliest forms of the disease, ovarian and pancreatic cancer, says MIT Professor Linda Griffith, who led the research team with Harvard Stem Cell Institute and Brigham and Women’s cardiologist Richard Lee.

The study, published online May 26 in the , resulted from a serendipitous finding in a regenerative-medicine project. Co-first author Luis Alvarez, who earned his PhD from MIT during a three-year leave from the Army, was interested in regenerative medicine because he knew many soldiers who had been wounded in Iraq and Afghanistan.

While looking for ways to promote bone regrowth, Alvarez developed a series of paired proteins that the researchers thought might promote interactions between growth receptors such as HER3 and EGFR to control growth and differentiation.

Alvarez’s proteins had some impact on regeneration, but the researchers also noticed that in some cases, they appeared to shut off cell growth and migration. Alvarez and others in Griffith’s lab decided to see what would happen if they treated cancer cells with the protein. To their surprise, they found that the cells stopping growing, and in some cases died.

“It was not something we were expecting to see — you don’t expect to shut off a receptor with something that normally activates it — but in retrospect it seemed obvious to try this approach for HER3,” says Griffith, the School of Engineering Professor of Innovative Teaching in MIT’s Department of Biological Engineering and director of the Center for Gynepathology Research. “We pursued it only because we had people in the lab working with cancer cells, and we thought, ‘Since it had these effects in stem cells, let’s just try this in tumor cells, and see if something interesting happens.’”

Targeting vulnerability

Around the same time, Griffith developed a personal interest in this family of cell receptors: She was diagnosed with a form of breast cancer that often overexpresses the receptor EGFR.

EGFR has received much attention from biologists — the drugs Erbitux, Iressa and Tarceva all target it — but not all cancers that overexpress the EGFR respond to targeted therapies. The first highly successful targeted chemotherapy, Herceptin, goes after another member of the family, the HER2 receptor.

The new MIT protein targets a specific vulnerability of HER3: To convey its growth-stimulating signals to the rest of the cell, HER3 must pair up with another receptor, usually HER2.

The new protein, which consists of a fused pair of neuregulin molecules, disrupts that pairing. Single molecules of neuregulin normally stimulate the HER3 receptor, promoting cell growth and differentiation. However, when the paired neuregulin is given to cells, it binds together two adjacent HER3 receptors, preventing them from interacting with the receptors they need to send their signals.

The researchers tested the molecule in six different types of that overexpress HER3, and found that it effectively shut off growth in all of them, including a cell type that is resistant to drugs that target .

Mark Moasser, a professor of oncology at the University of California at San Francisco, described the new technique as clever and elegant, adding that more experiments are needed to determine if it will be effective in living organisms. “Based on the mechanism, it has potential, and it lays the groundwork for a lot of future work,” says Moasser, who was not involved in this study.

The MIT and Brigham and Women’s team is now working on a new version of the molecule that would be more suited to tests in living animals. They plan to undertake such testing soon under the leadership of Steven Jay, a joint MIT/Brigham and Women’s postdoc and co-first author of the new paper. MIT postdoc Elma Kurtagic and graduate student Seymour de Picciotto are also first authors of the paper.
This story is republished courtesy of MIT News (, a popular site that covers news about MIT research, innovation and teaching.

More information: Paper online: … 093.abstract

Provided by Massachusetts Institute of Technology (news : web)

Scientists discover new component of key growth-regulating signaling pathway

Researchers in the lab of Whitehead Institute Member David Sabatini have identified a new substrate of the mammalian target of rapamycin (mTOR) kinase, called Grb10, by using a two-pronged approach of mass spectrometry and kinase specificity profiling.

“These results show that mTOR participates in most key cellular processes, consisting with its established role in common diseases like diabetes, cancer, and neurodegeneration” says Sabatini, who is also a Howard Hughes Medical Institute (HHMI) investigator and a professor of biology at MIT.

The research is published in the June 10 issue of Science.

The Grb10 protein was known to interact with insulin receptors and to inhibit the ability of cells to respond to insulin. By identifying the relationship between Grb10 and mTOR, Peggy Hsu, a former graduate student in the Sabatini lab and first author of the Science paper, was able to show that Grb10 is important for mTOR to inhibit signaling downstream of extracellular growth factors like insulin. This provides researchers with a more detailed understanding of the function of mTOR, especially in the context of cancer, and opens up new areas for mTOR research.

“These results show that mTOR participates in most key cellular processes, consisting with its established role in common diseases like diabetes, cancer, and neurodegeneration” says Whitehead Member David Sabatini.

The role of mTOR in nutrient sensing and regulation of cell growth has been conserved from yeast to worms, flies, and mice.  In humans, it is also important in overall organismal nutrient metabolism and organism size; dysregulation of mTOR has been linked to diabetes and some cancers. Despite its biological and medical importance—drugs that inhibit mTOR are used to treat certain cancers and to suppress the immune system to prevent transplant rejections—little is actually known about the substrates that mTOR targets or the precise manner in which it affects multiple cellular processes.

Hsu, who is now finishing her medical degree at Harvard Medical School, says that until recently, the search for mTOR substrates has been non-systematic and hamstrung by rapamycin’s limited inhibition of mTOR. With the advent of new mTOR inhibitors that target mTOR directly, including the inhibitor Torin1 that Hsu used in her work, researchers are now able to get a more complete picture of what mTOR regulates.

According to Hsu, use of these new mTOR inhibitors in conjuction with and the specificity profiling method will transform both future and current mTOR research.

“I think this will open up different areas of potential exploration,” says Hsu, who worked closely with the labs of Michael Yaffe at MIT and Jarrod Marto at Harvard Medical School. “I hope this work allows other reseachers to make a connection very quickly by looking through our data, and to basically say, ‘Aha! I thought mTOR would be involved in process X. And now maybe I have a way to study it.’ ”

More information: “The mTOR-Regulated Phosphoproteome Reveals a Mechanism of mTORC1-Mediated Inhibition of Growth Factor Signaling” Science, June 10, 2011

Provided by Whitehead Institute for Biomedical Research (news : web)

Researchers find new clues about protein linked to Parkinson's disease

Researchers at the Keck School of Medicine of the University of Southern California (USC) have uncovered structural clues about the protein linked to Parkinson's disease (PD), which ultimately could lead to finding a cure for the degenerative neurological disorder.

The alpha-synuclein (?-synuclein) protein is commonly found in the healthy human brain even though its function is not clear. The protein has been the subject of substantial Parkinson's research, however, because it is a major component in the protein clumps found in PD cases.

Unlike most proteins, which are typically rigid and occur in one definitive form, the alpha-synuclein protein can fold and change its structure. Researchers Tobias S. Ulmer, Ph.D. and Sowmya Bekshe Lokappa, Ph.D. at the Keck School-affiliated Zilkha Neurogenetic Institute have determined that the energy difference between two particular alpha-synuclein structures is less than previously speculated.

Their study, to be published in the June 17 issue of The Journal of Biological Chemistry, is the first to quantify that energy difference, 1.2±0.4 kcal/mol.

"We're trying to understand the mechanisms of protein folding and misfolding," said Ulmer, the study's principal investigator and an assistant professor in the Department of Biochemistry and Molecular Biology at the Zilkha Neurogenetic Institute. "Then we can say why something is going wrong, which is essential to treating neurodegenerative disorders like Parkinson's."

If proteins misfold, they are repaired or they break down. However, when alpha-synuclein misfolds it aggregates and becomes toxic to surrounding nerve cells, Ulmer said. Understanding its folding and finding what causes aberrant folding is therefore key to determining the root cause of the disorder, he added.

To put the discovery into perspective, Ulmer compared the energy that researchers thought was needed to change the protein's structure to hurricane-force winds and the actual energy required to a light summer breeze. The experiments were conducted in 2010, measuring the energy of elongated and broken helix forms of alpha-synuclein through circular dichroism spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry.

"There may be a continuous interconversion between folded alpha-synuclein structural states that might contribute to its pathological misfolding," said Lokappa, a post-doctoral research associate at the Center for Craniofacial Molecular Biology at USC and the study's co-author. "But we need to have even better insight into the mechanisms of folding and misfolding to explain what's going wrong in the brain."

The paper is the sixth in a series of studies that Ulmer has published on .

Parkinson's is a neurological disorder that has no cure or determined cause. It is a slow-progressing degenerative disease that most commonly affects motor function. According to the National Parkinson Foundation, the disorder is the second-most common neurodegenerative disease after Alzheimer's, affecting 1 million people in the United States and some 4 million worldwide.

More information: … 4/21450.full

Provided by University of Southern California (news : web)

Monday, June 27, 2011

'Artificial leaf' moves closer to reality


An important step toward realizing the dream of an inexpensive and simple "artificial leaf," a device to harness solar energy by splitting water molecules, has been accomplished by two separate teams of researchers at MIT. Both teams produced devices that combine a standard silicon solar cell with a catalyst developed three years ago by professor Daniel Nocera. When submerged in water and exposed to sunlight, the devices cause bubbles of oxygen to separate out of the water.

The next step to producing a full, usable , explains Nocera, the Henry Dreyfus Professor of Energy and professor of , will be to integrate the final ingredient: an additional to bubble out the water’s hydrogen atoms. In the current devices, hydrogen atoms are simply dissociated into the solution as loose protons and electrons. If a catalyst could produce fully formed hydrogen molecules (H2), the molecules could be used to generate electricity or to make fuel for vehicles. Realization of that step, Nocera says, will be the subject of a forthcoming paper.

The reports by the two teams were published in the journals Energy & Environmental Science on May 12, and the Proceedings of the National Academy of Sciences on June 6. Nocera encouraged two different teams to work on the project so that each could bring their special expertise to addressing the problem, and says the fact that both succeeded “speaks to the versatility of the catalyst system.”

Ultimately, Nocera wants to produce a low-cost device that could be used where electricity is unavailable or unreliable. It would consist of a glass container full of water, with a solar cell with the catalysts on its two sides attached to a divider separating the container into two sections. When exposed to the sun, the electrified catalysts would produce two streams of — hydrogen on one side, on the other — which could be collected in two tanks, and later recombined through a fuel cell or other device to generate electricity when needed.

“These papers are really important, to show that the catalyst works” when bonded to silicon to make a single device, Nocera says, thus enabling a unit that combines the functions of collecting and converting it to storable fuel. Silicon is an Earth-abundant and relatively inexpensive material that is widely used and well understood, and the materials used for the catalyst — cobalt and phosphorus — are also abundant and inexpensive.

Putting it together

Marrying the technologies of silicon solar cells with the catalyst material — dubbed Co-Pi for cobalt phosphate — was no trivial matter, explains Tonio Buonassisi, the SMA Assistant Professor of Mechanical Engineering and Manufacturing, who was a co-author of the PNAS paper. That’s because the splitting of water by the catalyst creates a “very aggressive” chemical environment that would tend to rapidly degrade the silicon, destroying the device as it operates, he says.

In order to overcome this, both teams had to find ways to protect the silicon surface, while at the same time allowing it to receive the incoming sunlight and to interact with the catalyst.

Professor of Electrical Engineering Vladimir Bulović, who led the other team, says his team's approach was to form the Co-Pi material on the surface of the silicon cell, by first evaporating a layer of pure cobalt metal onto the cell electrode, and then exposing it to a phosphate buffer solution under an electrical charge to transform it into the Co-Pi catalyst. By using the layer of Co-Pi, now firmly bonded to the surface, “we were able to passivate the surface,” says Elizabeth Young, a postdoc who was the lead author of the E&ES paper — in other words, it acts as a protective barrier that keeps the silicon from degrading in water.

“Most people have been staying away from silicon for water oxidation, because it forms silicon dioxide” when exposed to water, which is an insulator that would hinder the electrical conductivity of the material, says Ronny Costi, a postdoc on Bulović’s team. “We had to find a way of solving that problem,” which they did by using the cobalt coating.

Buonassisi’s team used a different approach, coating the silicon with a protective layer. “We did it by putting a thin film of indium tin oxide on top,” explains Joep Pijpers, a postdoc who was the lead author of the PNAS paper. Using its expertise in the design of silicon devices, that team then concentrated on matching the current output of the solar cell as closely as possible to the current consumption by the (catalyzed) water-splitting reaction. The system still needs to be optimized, Pijpers says, to improve the efficiency by a factor of 10 to bring it to a range comparable to conventional solar cells.

“It’s really not trivial, integrating a low-cost, high-performance silicon device with the Co-Pi,” Buonassisi says. “There’s a substantial amount of innovation in both device processing and architecture.”

Both teams had to add an extra power source to the system, because the voltage produced by a single-junction silicon cell is not high enough to use for powering the water-splitting catalyst. In later versions, two or three silicon solar cells will be used in series to provide the needed voltage without the need for any extra power source, the researchers say.

One interesting aspect of these collaborations, says postdoc Mark Winkler, who worked with Buonassisi’s team, was that “materials scientists and chemists had to learn to talk to each other.” That’s trickier than it may sound, he explains, because the two disciplines, even when talking about the same phenomena, tend to use different terminology and even different ways of measuring and displaying certain characteristics.

Portable power?

Nocera’s ultimate goal is to produce an “artificial leaf” so simple and so inexpensive that it could be made widely available to the billions of people in the world who lack access to adequate, reliable sources of electricity. What’s needed to accomplish that, in addition to stepping up the voltage, is the addition of a second catalyst material to the other side of the silicon cell, Nocera says.

Although the two approaches to bonding the catalyst with a cell appear to produce functioning, stable devices, so far they have only been tested over periods of a few days. The expectation is that they will be stable for long periods, but accelerated aging tests will need to be performed to confirm this.

Rajeshwar Krishnan, Distinguished University Professor of Chemistry and Biochemistry at the University of Texas at Arlington, says it remains to be seen “whether this ‘self-healing’ catalyst would hold up to several hours of current flow … under rather harsh oxidative conditions.” But he adds that these papers “certainly move the science forward. The state of the science in water photo-oxidation uses rather expensive noble metal oxides,” whereas this work uses Earth-abundant, low-cost materials. He adds that while there is still no good storage or distribution system in place for hydrogen, “it is likely that the solar photon-to-hydrogen technology will ultimately see the light of day — for transportation applications — with the hydrogen internal combustion engine.”

Meanwhile, Nocera has founded a company called Sun Catalytix, which will initially be producing a first-generation system based on the Co-Pi catalyst material, connected by wires to conventional, separate .

The “leaf” system, by contrast, is “still a science project,” Nocera says. “We haven’t even gotten to what I would call an engineering design.” He hopes, however, that the artificial leaf could become a reality within three years.

Bulović’s team was funded partly by the Chesonis Family Foundation and the National Science Foundation. Buonassisi’s team had support from the Netherlands Organization for Scientific Research (NOW-FOM), the National Science Foundation and the Chesonis Family Foundation. Nocera’s work was funded by the Chesonis Family Foundation, the Air Force Office of Scientific Research and the National Science Foundation.
This story is republished courtesy of MIT News (, a popular site that covers news about MIT research, innovation and teaching.

Provided by Massachusetts Institute of Technology (news : web)

Do steaks make you big?

Adjusting the intake of high protein foods like meat, eggs and milk products could determine whether you become a rugby player or marathon runner and may help you lose weight, according to new research published this month in the Journal of Biological Chemistry.

Dr. Stefan Broer, head of the molecular nutrition group in the ANU College of Medicine, Biology and Environment at The Australian National University, said the study by a group of ANU and Sydney researchers could potentially lead to the development of new weight-loss drugs.

“When it comes to controlling your , everybody thinks about reducing sugar and fat. But we also eat a lot of so we wanted to find out how it influences your body weight,” he said.

To investigate the problem, the team generated mice that could not digest protein as well as a normal mouse and measured a wide variety of physiological and physical properties.

“During digestion, your stomach and intestine breaks down protein into smaller subunits called amino acids,” Dr. Broer said.

“So we focused on mice that could not transport amino acids from the intestine into the cells of the body and therefore could not properly process proteins.

“One of the first things we noticed was that the animals were quite a bit smaller in size than normal mice, which suggests that eating more protein can increase our body size and possibly our sporting potential in the long term.

“When we gave these mice diets of different protein content, we found that they could not control their body weight, losing up to 20% in a couple of days. This indicates that varying protein intake in the short term affects our body weight.”

Dr. Broer said the study also revealed an influence of protein in our nutrition on insulin release, which controls the metabolism of sugar and fat in our bodies.

“This could explain some of the weight loss observed in the animals on different diets because we found that on a high protein diet a significant loss of fat occurred.

“This information may have potential in the future development of weight loss treatments.”

Provided by Australian National University

Evidence of a natural origin for banned drug that plumps up livestock

There may be a natural solution to the mystery of how small amounts of a banned drug that disrupts thyroid function and plumps up livestock gets into their bodies — and the bodies of humans, scientists are reporting. Their study, which appears in ACS' Journal of Agricultural and Food Chemistry, reports the first evidence that the substance can form naturally in feed and food.

Julie Vanden Bussche and colleagues explain that thiouracil is a drug that increases the weight of by making them retain water. Some regulatory agencies have banned its use because the extra weight cheats consumers, who buy water for the price of meat, and because of potential adverse health effects. To keep an eye on compliance, government agencies test animals for thiouracil. For example, both the U.S. Department of Agriculture and the European Union Reference Laboratories developed sensitive tests to detect thiouracil. Perhaps because these tests are so sensitive, the drug is now showing up often but at low levels — levels that are lower than expected if the animals were purposely doped. Hence, some scientists speculated that thiouracil may also have a natural origin. To settle the controversy, the researchers analyzed livestock feed and other food for the presence of thiouracil.

They found that plants in the family called Brassicaceae — which includes cruciferous vegetables, such as broccoli and cauliflower, and other plants, such as rapeseed and feeding cabbage, that are used as animal feed — had small amounts of thiouracil in them naturally. "To the best of our knowledge this study is the first to report the presence of naturally occurring thiouracil in and samples, hereby elucidating and acknowledging a natural origin for the low-level residues detected in urine of various species," say the researchers.

More information: “Feed or Food Responsible for the Presence of Low-Level Thiouracil in Urine of Livestock and Humans?” J. Agric. Food Chem., 2011, 59 (10), pp 5786–5792 DOI: 10.1021/jf200556x

In recent years, questions have been raised on the possible semi-endogenous status of the alleged xenobiotic thyreostatic drug thiouracil; thiouracil has been detected in the urine of various animals (livestock and domesticated) at concentrations between 1 and 10 µg L–1 and also in human urine. Although several studies suggest Brassicaceae-derived feed as potential origin, no traces of thiouracil have been detected in feed so far. Therefore, the aim of this study was to elucidate the origin of thiouracil in the urine of livestock and humans. To this purpose various Brassicaceae feed and food sources (e.g., rapeseed, rapeseed coarse meal, cabbage, cauliflower, broccoli) were investigated for the presence of thiouracil. In addition, the impact of the Brassicaceae-related ß-thioglucosidase enzyme was evaluated. This myrosinase enzyme appeared to be crucial, because without its catalyzed hydrolysis no thiouracil could be detected in the various Brassicaceae-derived samples. Therefore, a sample pretreatment with incorporated enzymatic hydrolysis was developed after ensuring the quality performance of the extracted myrosinase mixture with a single-point glucose assay. Upon enzymatic hydrolysis and LC-MS2 analysis, thiouracil was successfully detected in samples of traditional rapeseed, rapeseed-‘00’ variety coarse meal (values of erucic acid <2% and glucosinolates <25 µmol g–1), and rapeseed cake at 1.5, 1.6, and 0.4 µg kg–1, respectively. As for the food samples, broccoli and cauliflower displayed thiouracil concentrations of 6.0 and <1.0 µg kg–1, respectively. To the best of the authors' knowledge this study is the first to report the presence of naturally occurring thiouracil in feed and food samples. Future research should investigate the pathway of thiouracil formation and identify its possible precursors.

Provided by American Chemical Society (news : web)

Sunday, June 26, 2011

Creating a material that mimics dolphin skin amongst new scheme's research collaborations

Researchers from Imperial College London and University College London are planning to develop a new material that mimics dolphin skin, so that water can flow more efficiently down pipes, in one of seven early-stage projects that will receive support from a new scheme announced today.

The Kick-Start scheme aims to advance engineering research and promote collaborations between the two universities. They have distributed one hundred thousand pounds in seed funding among projects that also include an initiative to make power plants that use from waste more sustainable. The seed funding will help teams to establish their collaborative projects and pursue further funding to get their research to the next level. The scheme is an initiative of the Faculty of Engineering at Imperial and the School of the Built Environment, Engineering and Mathematical and Physical Sciences at UCL.

Professor Jeff Magee, Principal of the Faculty of Engineering at Imperial, says:

“From improving the way that water is managed to enhancing the way that energy is generated, this scheme provides vital seed funding to get some innovative projects off the ground. We think our wealth of outstanding researchers, the close proximity of both institutions and the complementary areas of research at both universities will make it easier for these collaborations to work well. I look forward to seeing how these projects have evolved in the next few years.”

Two of the new scheme’s projects are:

Super-smooth pipes

Many arid countries around the world such as Australia and Libya rely on vast pipeline networks to transport water to areas where it is scarce. However, the resistance between the pipe walls and the flowing water causes friction, which means that huge amounts of energy has to be used to pump the large volume of water to its destination.

To address this, Dr. Michael Templeton, from the Department of Civil and Environmental Engineering at Imperial, and Dr Andrew Wills, from the Department of Chemistry at UCL, aim to develop a new material that reduces this friction. They plan to mimic the special chemical properties and physical structure at the microscopic level of some of the most slippery surfaces in nature. One of the surfaces that they are exploring is dolphin .

Chemicals combine with tiny bumps on the animal’s skin to reduce the friction between the Dolphin and the water that it is swimming through. Similarly, the new material could have nanoscopic bumps, which will control the water flow, making it run more easily over the surface. It will also be coated with water repellent chemicals that will reduce the friction between water particles and pipe surface.

The expectation is that the new material will be in a form that could be applied to the inside of pipes, either as a material that lines the pipes or as a spray.

The team believe that there may also be applications for this material in other industries that require long-distance transport of fluids, such as the oil and gas industry.

Improving the sustainability of power plants that generate energy from waste

Making power plants that burn waste to produce energy more sustainable and efficient will be the focus of the project run by Professor Chris Cheeseman, from the Department of Civil and Environmental Engineering at Imperial, and Dr. Julia Stegemann, from the Department of Civil, Environmental and Geomatic Engineering at UCL.

These power plants burn waste that cannot be recycled by any other means. The heat generated from the combustion process is used to create steam, which powers a turbine to generate electricity. The plants can also produce hot water that can be distributed to local communities.

Currently, there is significant public opposition in the UK to the construction of new plants, which are called “Energy from Waste Plants”, because they are seen as environmentally unfriendly, emitting CO2 and other pollutants into the atmosphere. As a result, the UK lags significantly behind many other European countries, with 24 Energy from Waste Plants, in contrast to others such as France, which has around 130.

The researchers believe that these have the potential to make a significant contribution to energy supply in the UK. Current estimates have shown that about 10 percent of the UK’s energy requirements could come from waste, which could provide a secure source of energy for the country.

The researchers have received seed funding to kick-start a wide ranging project, which will involve stakeholders such as community groups and Energy from Waste Service providers.

They will investigate new ways to extract resources from the residues at the end of the combustion process, which include metals such as steel, aluminium and tin. The researchers will also investigate ways in which the energy generated from the process can be used more efficiently. This could include exporting excess heat, generated from the plant, to local communities.

The team will develop new methodologies for characterising the types of waste going into these facilities. Knowing more about the type of waste that is being combusted will enable the researchers to calculate how much comes from renewable sources such as plant material, which is called biomass. Knowing the percentage of biomass used in the combustion process will enable Energy from Waste companies to charge more for their energy because it comes from a sustainable resource.

The team will also carry out research that aims to understand and resolve the public concerns and planning issues associated with developing new energy from waste infrastructure.

Provided by Imperial College London (news : web)

New evidence backs up claim of dinosaur soft tissue find

 In a new study, biochemist James San Antonio and colleagues offer evidence to support the claims by Mary Higby Schweitzer back in 2005, that she and her colleagues had unearthed a soft tissue specimen that belonged to a Tyrannosaurus rex. Roundly criticized by many in the science community, the specimen, discovered inside a femur fragment, has yet to be proven to be anything else. Now, in a paper published on PLoS ONE, San Antonio and his colleagues (including Mary Schweitzer) claim they’ve found a plausible explanation for the survival of soft dinosaur material after some 68 million years.

The team focused on bits of found in the remains, which are a group of proteins found in the flesh and bones of animals; it grows in a triple helix, which when it winds together, is known as a microfibril. When thousands of microfibril wind together, as they often do, they are known as microfibrils.

After carefully studying 11 fragments of collagen recovered from the T. rex bone and then comparing them to similar fragments in modern rat and human collagen, the team discovered that the found fragments all came from the same innermost part of the fibrils that make up microfibrils. San Antononio likens them to tiny fibers that sit at the very innermost part of a very thick strong rope.
In their paper, the research team suggests that because they were so tightly wound, the microfibrils could have survived over millions of years. They also note that the specimens also contained very few amino acids, which are very susceptible to decay.

To back up her claims, or to quiet the naysayers, Schweitzer points out that if the found were actually contaminants from other more recent organisms, as some have claimed, there should have been more randomness to the collagen, instead of the strict uniformity that was found. She also notes that two other labs have corroborated her results.
The unfortunate side story to all the research done so far though, including these latest findings, is that thus far there is no way to definitively prove whether the soft tissue found inside that T. rex bone was in fact a remnant from its original owner, or something that came after. Thus, claims from both those supporting the idea that dinosaur tissue could have survived for millions of years, and those that think it’s nonsense, are likely to continue.

More information: San Antonio JD, Schweitzer MH, Jensen ST, Kalluri R, Buckley M, et al. (2011) Dinosaur Peptides Suggest Mechanisms of Protein Survival. PLoS ONE 6(6): e20381. doi:10.1371/journal.pone.0020381

Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

? 2010

What makes a plant a plant?

Although scientists have been able to sequence the genomes of many organisms, they still lack a context for associating the proteins encoded in genes with specific biological processes. To better understand the genetics underlying plant physiology and ecology—especially in regard to photosynthesis—a team of researchers including Carnegie's Arthur Grossman identified a list of proteins encoded in the genomes of plants and green algae, but not in the genomes of organisms that don't generate energy through photosynthesis. Their work will be published June 17 in the Journal of Biological Chemistry.

Using advanced computational tools to analyze the genomes of 28 different plants and photosynthetic , Grossman and his colleagues at the University of California in Los Angeles and the Joint Institute of the Department of Energy were able to identify 597 proteins encoded on plant and green algal genomes, but that are not present in non-photosynthetic organisms. They call this suite of proteins the GreenCut.

Interestingly, of the 597 GreenCut proteins, 286 have known functions, while the remaining 311 have not been associated with a specific biological process and are called "unknowns."

The majority of the GreenCut proteins, 52 percent, have been localized in a cellular organelle called the chloroplast--the compartment where photosynthesis takes place. It is widely accepted that chloroplasts originated from photosynthetic, single-celled bacteria called cyanobacteria, which were engulfed by a more complex, non-photosynthetic cell more than 1.5 billion years ago. While the relationship between the two organisms was originally symbiotic, over evolutionary time the cyanobacterium transferred most of its information to the nucleus of the host organism, losing its ability to live independent of its partner.

"This genetically-reduced cyanobacterium, which is now termed a chloroplast, has maintained its ability to perform photosynthesis and certain other essential metabolic functions, such as the synthesis of amino acids and fats. The processes that take place in the chloroplast must also be tightly integrated with metabolic processes that occur in other parts the cell outside of the chloroplast," Grossman explained.

While recent evidence suggests that many of the unknowns of the GreenCut are associated with photosynthetic function, not all GreenCut proteins are located in the chloroplast. But since they are unique to photosynthetic organisms and highly conserved throughout plants and other photosynthetic organisms, it is likely that they are critical for other plant-specific processes. Possible functions could be associated with regulation of metabolism, control of DNA transcription, and the functioning of other cellular organelles, including the energy producing mitochondria and the house-cleaning peroxisomes.

Expanding this work, Grossman and his colleagues found that many GreenCut proteins have been maintained in ancient cyanobacteria, red algae, and other single-celled algae called diatoms. Comparison of GreenCut proteins among various organisms is opening windows for discoveries about the roles that these proteins play in photosynthetic cells, the evolution of chloroplasts, and how photosynthetic cells might be tailored for survival under different environmental conditions.

Provided by Carnegie Institution

Baking powder for environmentally friendly hydrogen storage

Hydrogen is under consideration as a promising energy carrier for a future sustainable energy economy. However, practicable solutions for the easy and safe storage of hydrogen are still being sought. Despite some progress, no generally applicable solutions that meet the requirements of industry have been found to date. In the journal Angewandte Chemie Matthias Beller and his team at the Leibnitz Institute for Catalysis (Rostock, Germany) have now introduced a new approach to hydrogen storage that is based on simple salts of formic acid and carbonic acid.

Practical must take up and give off hydrogen at standard pressure and room temperature, accommodate a large amount of hydrogen in as little space as possible, and release it rapidly and on-demand. tanks store hydrogen in a relatively manageable volume but are very heavy and expensive, as well as operating only at or far too slowly. In addition to organic hydrogen storage materials, such as methane and methanol, researchers have been interested in formic acid (HCO2H) and its salts, known as formates, for the generation of hydrogen. A fundamental problem with the use of these storage materials is the separation of the carbon dioxide formed when the hydrogen is released.

The team from Rostock has now successfully used a special ruthenium catalyst that catalyzes both the release and uptake of hydrogen to establish a reversible, CO2-free hydrogen storage cycle. In this system, hydrogen is released from nontoxic formates and the resulting CO2 captured in the form of bicarbonates. Bicarbonates are a component of many natural stones and are also commonly used as baking powder or sherbet (, NaHCO3).

“Our new concept has a number of advantages,” says Beller, “in comparison to CO2, solid bicarbonate is easy to handle and is very soluble in water. The resulting bicarbonate solution can be catalytically converted to a formate solution under much milder conditions than those required for the reactions to form methane or methanol.” In addition, the harmless solid could easily be stored and transported. Retrieval of the hydrogen occurs at room temperature or even lower. Says Beller, “Most important is that a closed carbon cycle is now possible because the resulting bicarbonate can simply be loaded up with hydrogen again.”

More information: Matthias Beller, CO2-"Neutral" Hydrogen Storage Based on Bicarbonates and Formates, Angewandte Chemie International Edition, … ie.201101995

Provided by Wiley (news : web)

Saturday, June 25, 2011

Powerful computers, experiments provide insights into ion's behavior near interfaces

 From renewable energy sources to pharmaceuticals, iodide ions are a common actor, and now, thanks to scientists at Pacific Northwest National Laboratory, the ion's behavior can be better predicted. By considering electrons' subtler choices about where to reside, Dr. Chris Mundy and Dr. Marcel Baer showed the negatively charged iodine ion congregates at the air-water interface. However, the ions gather at a lower concentration than previously predicted.

The team obtained answers about the iodide ion's choices to be at the surface or under bulk solvation, surrounded by liquid, using the laws of quantum mechanics in conjunction with Newton's to describe the evolution of aqueous electrolytes, or .  The aforementioned calculations were extensive and required the use of leadership-class computers through the Department of Energy's INCITE award. Previous studies relied on empirical potentials, which are simpler mathematical models of molecular motion that do not explicitly consider .

Understanding the nature of ions where air and water meet and at similar interfaces could change how we conduct basic energy research, climate studies, and biological investigations. However, the fundamentals of an ion's propensity to be present at an interface and the important interactions that wrap ions in liquid are still not understood. This research sheds new light on the effects of ions in the vicinity of hydrophobic environments.

"Our work shows where some models may fail and where you may have to take into account the more subtle effects of when performing calculations," said Mundy, the physical chemist who co-authored the study.

It begins with large polarizable anions, negatively charged particles where the electrons slosh back and forth around the atom's central core in response to nearby electric fields produced by the motion of surrounding water molecules. The new conventional wisdom since 2002 is that these ions can exist in significant population at the air-water interface.  The now nearly universally accepted results were pioneered by Dr. Liem Dang at PNNL and independently by Profs. Jungwirth and Tobias at the University of California at Irvine. These studies were done using empirical potentials in conjunction with a parameterized model for how electrons respond to different charged environments, namely polarization.

"Simply put, electric fields felt by an ion at the interface are different than those felt in the bulk of the liquid," said Mundy.

The earlier results have influenced a generation of both experimental and theoretical studies dedicated to understanding this phenomenon.  Although there is now a consensus regarding ions at interfaces Mundy and Baer wanted to understand the precise interactions that drive ions to the air-water interface. 

To understand how ions adsorb onto surfaces and provide the more accurate data to scientific models, the researchers integrated experimental research, theory, and leadership-class computing. The researchers performed extensive density functional theory calculations to mathematically represent the electrons and ions and determine their interactions.

To justify the computationally expensive calculations, the team compared the detailed structure of iodide in water to extended x-ray fine structure experiments conducted by John Fulton at PNNL. Results of this joint theoretical and experimental study suggested that quantum mechanical models reproduced the local solvation structure of iodide more accurately than the models based on empirical polarizable interaction potentials, known as multipole expansions.  Here, a multipole expansion breaks down a complicated arrangement of charges into concepts, such as a monopole, dipole, etc., and is a good description when you are looking at charges from far away.

"Multipole expansions are good from far, but far from good," said Mundy. When it comes to the movement of the electrons and where electrons from different atoms overlap, the expansions don't provide the precise answers scientists need.

This study took advantage of the synergy between computational and experimental science. "Our result would not mean anything without the experimental results," said Baer, a Linus Pauling Distinguished Postdoctoral Fellow at PNNL. "It would just be another number with no weight."

The researchers continue to combine electronic structure, statistical mechanics, and leadership-class computing to assist in understanding the effects of iodide and other . This research will be continued by Mundy at PNNL and by Baer for the rest of his stay at PNNL and when he returns to Europe.

More information: Baer MD and CJ Mundy. 2011. "Toward an Understanding of the Specific Ion Effect Using Density Functional Theory." Journal of Physical Chemistry Letters 2, 1088-1093. DOI: 10.1021/jz200333b

Provided by Pacific Northwest National Laboratory (news : web)

Chemistry never sounded this good

( -- By now, the word is out at UCLA that undergraduates in Neil Garg's organic chemistry course produce clever, creative music videos as an extra-credit assignment. The bigger secret may be just how much chemistry they learn by doing so, as none of them are chemistry majors and most admit they didn't like chemistry when the class started.

It's a little too soon to say which will be this year's sensation. A strong candidate is "We're Yours" by the Gargonauts — Rachel Stafford-Lewis, Myan Pham, Ali Lanewala and Jordan Halfman — which achieves the desired trifecta of excellent in a video that sounds and looks great. But unlike last year, when one video, "Chemistry Jock" — which has become the gold standard of the genre, with 38,000 YouTube views and many fans — ran away from the competition, this year's field is much deeper.

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This quarter, 250 produced 87 videos. The most notable ones also include "Let It Be" by John Boles and Edgar Gonzalez and "Forget That" by Alex Jaksha, Sean Nguyen, Kevin Nishida and Nakia Sarad. This video is not supported by your browser at this time.

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"When I am doing the problem sets or taking a test, I find myself singing the various chemistry songs that people wrote and it helps me remember all the details," said Stafford-Lewis, a sophomore majoring in microbiology, immunology and molecular genetics. Rewriting lyrics helped her to learn the chemistry, she added.

"I catch myself randomly singing the lyrics while I'm walking through the halls and just kind of laugh," said Gonzalez, a sophomore physiological science major. "It's crazy, because up until this point, I had hated chem. I remember when I first signed up for the class I was afraid, but I soon realized I had a great professor. I can honestly say that professor Neil Garg has not only made it a fun class, but he made me care about learning chemistry. You can tell how much he cares about his students by the time and effort he puts into his lectures. He always had a dozen or so pieces of computer paper on which he wrote his lecture notes.

"Making the music video was really fun, and a great way to get out of my comfort zone and at the same time learn some chemistry. I would recommend this course as long as professor Neil Garg is teaching it."

Pham, a second-year pre-med history major, agreed, saying, "Making this video motivated me to do better in the class. This is my favorite chemistry course by far. It's a lot of thinking and solving problems; I've learned a lot. Sometimes we forget that learning should be a fun experience."

Pham added that she's "never been superbly great in chemistry" and "it's always been a little hard" for her, although you'd never suspect that watching her sing "We're Yours."

The lyrics to "We're Yours" include:

Well, I got this chem equation and it's getting pretty hazy
Palladium on carbon and ethanol, that's crazy
With hydrogen molecules, I don't know what to do
But then Garg showed me cat. hydrogenation
Breaking alkenes, what a sensation
Syn addition of hydrogens, it's reduction ...

I've been spendin' way too long on this one chem equation
Ozone and DMS, I'm filled with frustration
Alkenes and double bonded O's, please get rid of my woes
I looked at Garg's answer and it all made sense somehow
You split the alkene and add oxygen to each now
You've got two molecules, with carbonyls, wow!

Boles and Gonzalez turned for inspiration to the Beatles, whose "Let It Be" was, of course, a huge hit long before they were born. One of their verses is:

SN2 electrophiles: primary carbon not tertiary
Lone pairs show nucleophilicity
Use polar aprotic solvent
Tosylates and halides, they will leave
Inversion of stereochemistry

Boles, a life sciences major, like many of Garg's students, said, "I looked forward to class with Professor Garg. He turned a class of potential hours of memorization and confusion into a series of intricate logic games with organic molecules. I had a great time with my buddy Edgar making the movie. As I studied for the final, at least twice in my head I've sung a part of our song or a part of another song from last year. Putting the exceptions and rules of thumb to music helps me remember concepts like solvation and which solvent causes which reaction."

Halfman, a second-year psychobiology major, called the course "an awesome experience" and said, "I've never had a professor so qualified in all aspects to teach a class." He added, "After spending so much time learning so many different reactions, a chance to use that knowledge creatively was a very welcome break."

The students uniformly agreed that making the videos was great fun.

"We had a great time shooting our video," Stafford-Lewis said, adding that she and her creative partners knew early on that "we were going for a different feel" from the rap music videos that dominated Garg's class last year.

"Organic chemistry is as difficult as you make it," she said, noting that Garg "does help to make it more interesting and entertaining than I ever thought possible."

Most of the students who take this course "come in with little or no interest in organic chemistry," Garg admitted. They don't end the course that way, though. Last year, only 5 percent started the course with a high interest in organic chemistry, but by the end of the 10 weeks, most of the students said they had a high interest.

Why does Garg offer students this optional extra-credit assignment?

"The majority of the Chem 14D students are hooked on technology, such as the Internet and YouTube," Garg said. "Rather than fighting this, I designed the assignment to take advantage of the students' strengths and interests. I didn't realize at the outset that so many students would create spectacular videos. When you consider the clever lyrics about and the high quality of the video editing and the audio, the TA's and I were extremely impressed by how amazingly creative UCLA's south campus students are.

"Don't believe anyone who says creativity is mostly in the humanities and arts; the evidence otherwise is right in these videos. And for all the time the students put into creating these videos, we give them some extra credit, but not much."

Yannick Goeb and Kimberly Bui, who starred with Justin Banaga in "Chemistry Jock," are fans of "O-Chem Toolbox," sung with stellar vocals by Michelle Azurin, joined by Daniel Brenners, Frank Choe and Mike Dai.

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If your musical taste runs more to Lady Gaga, you might enjoy "Bond This Way," starring Natalie Green, Storm Hagen, Megan Johnson and Kylie Wilson and directed by Brian Tan.

Garg's course website has all these and more. Garg called this year's class "Chem 14D Jedi," and many of the videos picked up this "Star Wars" theme, in which the students strive to become "Chemistry Jedis."

Provided by University of California

Spotlight on dynamic operation of enzymes

 Our world is unique in that living organisms can undergo complex chemical reactions quickly and precisely, and sequence them together. But how can proteins integral to life effectively hasten these reactions? Researchers from France provide new insight into how enzymes actually work. The study is presented in the journal PLoS Biology.

Scientists from the Institut des Sciences du Végétal (IVS) at the Centre National de la Recherche Scientifique (CNRS) in France, in cooperation with colleagues from the Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (LCBPT), the Institut de Biochimie et Biophysique Moléculaire et Cellulaire (IBBMC) and the Laboratoire de Cristallographie et RMN Biologique, investigated the binding of a compound with therapeutic properties to its biological target.

Experts say specific macromolecules catalyse biochemical reactions and can be reused many times. The question, however, is if these proteins can speed up the reactions. What researchers know is that the enzyme must first recognise the substrate, which then comes into contact with certain chemical groups specific to it and is later transformed. The substrate is then favoured by the chemical environment that is established, and is linked to the deformations of molecular groups physically close to each other in space, according to the researchers.

So the macromolecular assembly reaches an ephemeral state that is highly reactive. Experts define this as the 'transition state'. What results is that the biochemical reaction is accelerated by a factor of several hundred billion.

Research from the 1950s unveiled the 'induced adjustment' model that had the substrate involved in changing the enzyme's form. Here, the small compound initially interacts with the enzyme, and this interaction triggers the conformational change of the macromolecule, which in turn enables the substrate's transformation.

In this latest study, the researchers used a therapeutic target enzyme, investigating a small compound mimicking the substrate that could bind strongly to the enzyme, and blocking its activity and exhibiting antibiotic, antineoplastic and herbicidal properties.

The team says an 'induced adjustment' stage is required to ensure the efficient binding of the compound to the target enzyme. In a nutshell, it is the tiny compound that brings about the conformational modification once attached to the enzyme.

By deriving the resolution of the fine structure of this enzyme from the Arabidopsis thaliana plant, the researchers effectively illustrated the interactions and conformations of each of the enzyme and substrate, at each stage of the reaction.

A hydrogen bond is formed, stabilising the enzyme-substrate complex in the transition state. This enables the enzymatic hydrolysis reaction to be carried out efficiently.

Thanks to their results, the researchers say this model can be used on all forms of the , especially those found in bacteria, which are targeted by antibiotics. The data also show the mechanism of how a therapeutic molecule can bind to its target, making it 'unbind' from it, and thus extending the drug's effect beyond the actual treatment, they say.

The results of this study can contribute to researchers' efforts to develop or improve the pharmacological properties of drug candidates.

More information: Fieulaine, S., et al. (2011) Trapping conformational states along ligand-binding dynamics of peptide deformylase: the impact of induced fit on enzyme catalysis. PLoS Biology. DOI:10.1371/journal.pbio.1001066

Provided by CORDIS

New insights on an old polymer material, Nafion, will enable design of better batteries

Designing new materials depends upon understanding the properties of today's materials. One such material, Nafion, is a polymer that efficiently conducts ions (a polymer electrolyte) and water through its nanostructure, making it important for many energy-related industrial applications, including in fuel cells, organic batteries, and reverse-osmosis water purification. But since Nafion was invented 50 years ago, scientists have only been able to speculate about how to build new materials because they have not been able to see details on how the molecules come together and work within Nafion.

Now, two Virginia Tech research groups have combined forces to devise a way to measure Nafion's internal structure and, in the process, have discovered how to manipulate this structure to enhance the material's applications.

The research is published in the June 19 issue of in the Letters article, "Linear coupling of alignment with transport in a electrolyte membrane," by Jing Li, Jong Keun Park, Robert B. Moore, and Louis A. Madsen, all with the chemistry department in the College of Science and the Macromolecules and Interfaces Institute at Virginia Tech.

Nafion is made up of that combine the non-stick and tough nature of Teflon with the conductive properties of an acid, such as battery acid. A network of tiny channels, nanometers in size, carries water or ions quickly through the polymer. "But, due to the irregular structure of Nafion, scientists have not been able to get reliable information about its properties using most standard analysis tools, such as ," said Madsen, assistant professor of physical, polymer, and .

Madsen and Moore, professor of physical and polymer chemistry; Madsen's post-doctoral associate Jing Li; and Moore's Ph.D. student Jong Keun Park, of Korea, were able to use (NMR)to measure , and a combination of NMR and X-ray scattering to measure molecular alignment within Nafion. "We were looking at water molecules inside Nafion as internal reporters of structure and efficiency of conduction," said Madsen. "The new feature we discovered is the locally aligned aggregates of polymer molecules in the material. The molecules align like strands of dry spaghetti lined up in a box. We can measure the speed (diffusion) of the water molecules and the direction they travel within those structures, which relates strongly to the alignment of the polymer molecule strands."

The researchers observed that the alignment of the channels influenced the speed and preferential direction of water motion. And a startlingly clear picture presented itself when the scientists stretched the Nafion and measured its structure and water motion.

"Stretching drastically influences the degree of alignment," said Madsen. "So the molecules move faster along the direction of the stretch, and in a very predictable way. These materials actually share some properties with liquid crystals -- molecules that line up with each other and are used in every LCD television, projector, and screen."

These relationships have not been previously recognized in a , Madsen said.

The ability to observe motion and direction, and understand what is happening within Nafion, has implications for using the material in new ways, and for designing new materials, the researchers write in the Nature Materials article. Ion-based applications could include actuator devices such as artificial muscles, organic batteries, and more energy efficient fuel cells. A water-based application would be improved reverse osmosis membranes for water purification.

Madsen and Moore started this collaborative project shortly after they arrived at Virginia Tech (Madsen in 2006, Moore in 2007), and they are furthering their work together by investigating new polymeric materials using their unique combination of analysis techniques.

"Alignment provides for a better flow of the molecules through the polymer," Madsen said.

Provided by Virginia Tech (news : web)