Blocking 'oh-glick-nack' may improve long-term memory

Progress toward finding such a blocker for the sugar — with the appropriately malicious-sounding name "oh-glick-nack" — was the topic of a report here today at the 243rd National Meeting & Exposition of the American Chemical Society (ACS).

Linda Hsieh-Wilson, Ph.D., explained that the sugar is not table sugar (sucrose), but one of many other substances produced in the body's cells that qualify as sugars from a chemical standpoint. Named O-linked beta-N-acetylglucosamine — or "O-GlcNAc" — it helps in orchestrating health and disease at their origins, inside the billions of cells that make up the body. O-GlcNAc does so by attaching to proteins that allow substances to pass in and out of the nucleus of cells, for instance, and helping decide whether certain genes are turned on or off. In doing so, O-GlcNAc sends signals that may be at the basis of cancer, diabetes, Alzheimer's disease and other disorders. Research suggests, for instance, that proteins loaded up with too much O-GlcNAc can't function normally.

At the ACS meeting, Hsieh-Wilson described how research in her lab at the California Institute of Technology and Howard Hughes Medical Institute implicate O-GlcNAc in memory loss and cancer. The research emerged from Hsieh-Wilson's use of advanced lab tools for probing a body process that involves attachment of sugars like O-GlcNAc to proteins. Called protein glycosylation, it helps nerves and other cells communicate with each other in ways that keep the body coordinated and healthy. When O-GlcNAc is attached to a protein, that binding process is known as O-GlcNAc glycosylation.

Hsieh-Wilson's team screened the entire mammalian brain for all O-GlcNAc-glycosylated proteins, using a new process that her laboratory developed. They identified more than 200 proteins bearing O-GlcNAc attachments or tags, many for the first time. The research was done in mice, stand-ins for humans in research that cannot be done on people. Some of the proteins carrying O-GlcNAc were involved in regulating processes like drug addiction and securing long-term storage of memories.

O-GlcNAc's effects on one particular protein, CREB, got the scientists' attention. CREB is a key substance that turns on and regulates the activity of genes. Many of the genes in cells are inactive at any given moment. Substances like CREB, termed transcription factors, turn genes on. Hsieh-Wilson found that when O-GlcNAc attached to CREB, CREB's ability to turn on genes was impaired. When the researchers blocked O-GlcNAc from binding CREB, the mice developed long-term memories faster than normal mice.

Could blocking O-GlcNAc boost long-term memory in humans?

"We're far from understanding what happens in humans," Hsieh-Wilson emphasized. "Completely blocking O-GlcNAc might not be desirable. Do you really want to sustain all memories long-term, even of events that are best forgotten? How would blocking the sugar from binding to other proteins affect other body processes? There are a lot of unanswered questions. Nevertheless, this research could eventually lead to ways to improve memory."

In a related study, Hsieh-Wilson found that O-GlcNAc interacted with another protein in ways that encourage the growth of cancer cells, suggesting that blocking its attachment might protect against cancer or slow the growth of cancer. And indeed, in mouse experiments, blocking O-GlcNAc resulted in much smaller tumors.

Again, a treatment for humans based on this discovery is far in the future, but the study singles out O-GlcNAc as a potential new target for developing anti-cancer drugs.

More information: Abstract
Understanding the remarkable complexity of the brain on a molecular, cellular and systems level is one of the major challenges in science. The principles and tools of chemistry, when combined with biology, can be used to gain new insights into the molecules and interactions involved in cellular communication and memory storage. We will describe the synergistic application of chemistry and biology to explore the structure and function of carbohydrates and their impact in various biological contexts, including neuronal communication, long-term memory and cancer.

Provided by American Chemical Society (news : web)

Soft memory device opens door to new biocompatible electronics

 Researchers from North Carolina State University have developed a memory device that is soft and functions well in wet environments -- opening the door to a new generation of biocompatible electronic devices.

"We've created a memory device with the physical properties of Jell-O," says Dr. Michael Dickey, an assistant professor of chemical and biomolecular engineering at NC State and co-author of a paper describing the research.

Conventional electronics are typically made of rigid, brittle materials and don't function well in a wet environment. "Our memory device is soft and pliable, and functions extremely well in wet environments -- similar to the human brain," Dickey says.

Prototypes of the device have not yet been optimized to hold significant amounts of memory, but work well in environments that would be hostile to traditional electronics. The devices are made using a liquid alloy of gallium and indium metals set into water-based gels, similar to gels used in biological research.

The device's ability to function in wet environments, and the biocompatibility of the gels, mean that this technology holds promise for interfacing electronics with biological systems -- such as cells, enzymes or tissue. "These properties may be used for biological sensors or for medical monitoring," Dickey says.

The device functions much like so-called "memristors," which are vaunted as a possible next-generation memory technology. The individual components of the "mushy" memory device have two states: one that conducts electricity and one that does not. These two states can be used to represent the 1s and 0s used in binary language. Most conventional electronics use electrons to create these 1s and 0s in computer chips. The mushy memory device uses charged molecules called ions to do the same thing.

In each of the memory device's circuits, the metal alloy is the circuit's electrode and sits on either side of a conductive piece of gel. When the alloy electrode is exposed to a positive charge it creates an oxidized skin that makes it resistive to electricity. We'll call that the 0. When the electrode is exposed to a negative charge, the oxidized skin disappears, and it becomes conducive to electricity. We'll call that the 1.

Normally, whenever a negative charge is applied to one side of the electrode, the positive charge would move to the other side and create another oxidized skin -- meaning the electrode would always be resistive. To solve that problem, the researchers "doped" one side of the gel slab with a polymer that prevents the formation of a stable oxidized skin. That way one electrode is always conducive -- giving the device the 1s and 0s it needs for electronic memory.

The paper was published online July 4 by Advanced Materials. The paper was co-authored by NC State Ph.D. students Hyung-Jun Koo and Ju-Hee So, and NC State INVISTA Professor of Chemical and Biomolecular Engineering Orlin Velev. The research was supported by the National Science Foundation and the U.S. Department of Energy.

NC State's Department of Chemical and Biomolecular Engineering is part of the university's College of Engineering.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by North Carolina State University.

Journal Reference:

Hyung-Jun Koo, Ju-Hee So, Michael D. Dickey, Orlin D. Velev. Towards All-Soft Matter Circuits: Prototypes of Quasi-Liquid Devices with Memristor Characteristics. Advanced Materials, 2011; DOI: 10.1002/adma.201101257

Subatomic quantum memory in diamond demonstrated

Physicists working at the University of California, Santa Barbara and the University of Konstanz in Germany have developed a breakthrough in the use of diamond in quantum physics, marking an important step toward quantum computing. The results are reported in this week's online edition of Nature Physics.

The physicists were able to coax the fragile quantum information contained within a single electron in diamond to move into an adjacent single nitrogen nucleus, and then back again using on-chip wiring.

"This ability is potentially useful to create an atomic-scale memory element in a quantum computer based on diamond, since the subatomic nuclear states are more isolated from destructive interactions with the outside world," said David Awschalom, senior author. Awschalom is director of UCSB's Center for Spintronics & Quantum Computation, professor of physics, electrical and computer engineering, and the Peter J. Clarke director of the California NanoSystems Institute.

Awschalom said the discovery shows the high-fidelity operation of a quantum mechanical gate at the atomic level, enabling the transfer of full quantum information to and from one electron spin and a single nuclear spin at room temperature. The process is scalable, and opens the door to new solid-state quantum device development.

Scientists have recently shown that it is possible to synthesize thousands of these single electron states with beams of nitrogen atoms, intentionally creating defects to trap the single electrons. "What makes this demonstration particularly exciting is that a nitrogen atom is a part of the defect itself, meaning that these sub-atomic memory elements automatically scale with the number of logical bits in the quantum computer," said lead author Greg Fuchs, a postdoctoral fellow at UCSB.

Rather than using logical elements like transistors to manipulate digital states like "0" or "1," a quantum computer needs logical elements capable of manipulating quantum states that may be "0" and "1" at the same time. Even at ambient temperature, these defects in diamond can do exactly that, and have recently become a leading candidate to form a quantum version of a transistor.

However, there are still major challenges to building a diamond-based quantum computer. One of these is finding a method to store quantum information in a scalable way. Unlike a conventional computer, where the memory and the processor are in two different physical locations, in this case they are integrated together, bit-for-bit.

"We knew that the nitrogen nuclear spin would be a good choice for a scalable quantum memory -- it was already there," said Fuchs. "The hard part was to transfer the state quickly, before it is lost to decoherence."

Awschalom explained: "A key breakthrough was to use a unique property of quantum physics -- that two quantum objects can, under special conditions, become mixed to form a new composite object." By mixing the quantum spin state of the electrons in the defect with the spin state of the nitrogen nucleus for a brief time -- less than 100 billionths of a second -- information that was originally encoded in the electrons is passed to the nucleus.

"The result is an extremely fast transfer of the quantum information to the long-lived nuclear spin, which could further enhance our capabilities to correct for errors during a quantum computation," said co-author Guido Burkard, a theoretical physicist at the University of Konstanz, who developed a model to understand the storage process.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of California - Santa Barbara, via EurekAlert!, a service of AAAS.

Journal Reference:

G. D. Fuchs, G. Burkard, P. V. Klimov, D. D. Awschalom. A quantum memory intrinsic to single nitrogen–vacancy centres in diamond. Nature Physics, 2011; DOI: 10.1038/nphys2026

Chemist investigates material for next-generation computer memory

Investigating the building blocks for next-generation computer memory has earned a University of Houston (UH) chemist his third Tier One research award.

Vassiliy Lubchenko, an assistant professor of chemistry at UH, was recently selected as a 2011 Alfred P. Sloan Research Fellow for his achievements and potential to contribute substantially to his field. Drawn from 54 colleges and universities in the United States and Canada, this year's 118 fellows are early-career scientists and scholars. Lubchenko is one of four winners in Texas. Each will receive a $50,000 fellowship in support of original research and education in science, technology, engineering, mathematics and economic performance.

As a theoretical physical chemist, Lubchenko takes raw data from researchers in a lab and uses mathematical and computer modeling to explain existing measurements and predict what will occur in future experiments and other systems. Amorphous semiconductors, for example, are something he is studying for their applications in phase-change computer memory, which is a potential successor of flash memory.

"One can control the conductivity and reflectivity of phase-change materials – and hence encode information – by varying the speed of cooling a melted material and forcing it to either crystallize or to form a glassy solid," Lubchenko said. "Glass transition is one of the most important, yet least understood, branches of modern physical chemistry. Semiconductor glasses exhibit many unique anomalies whose explanation has evaded researchers for decades. My findings show these anomalies are not a generic consequence of disorder, but instead can be traced to how these solids form from the corresponding liquid."

An important component of his research is to predict the structure and glass-forming ability of specific substances. This task is inaccessible to computer technology, but Lubchenko's technique applies a combination of analytical theories and computational modeling that singles out the most important aspects of the liquid dynamics and electronic motions that precede the glass transition and are amenable to mathematical treatment.

Another area of Lubchenko's research involves protein aggregation, a process thought to be responsible for many degenerative diseases, such as sickle cell anemia or Alzheimer's. His work may make it easier to make protein crystals, which could help in the treatment of such diseases.

"Vas' Sloan award, his third Tier One award since 2008, is recognition by his peers that he tackles and solves tough research problems," said David Hoffman, professor and chair of the chemistry department in the College of Natural Sciences and Mathematics at UH. "We are very proud of his accomplishments and feel fortunate to have him as a colleague."

Provided by University of Houston (news : web)