The University of California, Irvine reports that scientists from the University of Queensland were able to perform surgical holes on a cell located in Southern California laboratory. The collaborative effort between UC Irvine, UC San Diego and the University of Queensland employed the RoboLase software.

To read more about what happened, go here...

The researchers incorporated the key molecules - called small interfering RNAs (siRNAs) into fat-like particles that protect them from attack by digestive enzymes in the blood.

These enzymes normally degrade RNA molecules in cells or the circulation.

Not only did this increase the stability when injected into mice, it also reduced the dose needed for therapeutic effect.

Previous studies suggested that the amounts of siRNA needed to achieve a therapeutic effect in people far exceed safe levels of exposure...

...Professor Roger Williams, consultant hepatologist at University College London, agreed that a human application was a long way off.

But he said potentially the therapy might benefit patients who did not respond to current anti-viral drugs, or those who carried the virus without showing any symptoms.

More at Sirna Therapeutics...

From the press release:

The paper describes how the UB scientists used gene-nanoparticle complexes to activate adult brain stem/progenitor cells in vivo, demonstrating that it may be possible to "turn on" these otherwise idle cells as effective replacements for those destroyed by neurodegenerative diseases, such as Parkinson's.

In addition to delivering therapeutic genes to repair malfunctioning brain cells, the nanoparticles also provide promising models for studying the genetic mechanisms of brain disease...

The UB researchers make their nanoparticles from hybrid, organically modified silica (ORMOSIL), the structure and composition of which allow for the development of an extensive library of tailored nanoparticles to target gene therapies for different tissues and cell types.

A key advantage of the UB team's nanoparticle is its surface functionality, which allows it to be targeted to specific cells, explained Dhruba J. Bharali, Ph.D., a co-author on the paper and post-doctoral associate in the UB Department of Chemistry and UB's Institute for Lasers, Photonics and Biophotonics.

While they are easier and faster to produce, non-viral vectors typically suffer from very low expression and efficacy rates, especially in vivo.

"This is the first time that a non-viral vector has demonstrated efficacy in vivo at levels comparable to a viral vector," Bharali said.

In the UB experiments, targeted dopamine neurons -- which degenerate in Parkinson's disease, for example -- took up and expressed a fluorescent marker gene, demonstrating the ability of nanoparticle technology to deliver effectively genes to specific types of cells in the brain.

Using a new optical fiber in vivo imaging technique (CellviZio developed by Mauna Kea Technologies of Paris), the UB researchers were able to observe the brain cells expressing genes without having to sacrifice the animal.

The press release...

The Institute for Lasers, Photonics and Biophotonics at the University at Buffalo...

The mutation in the dystrophin gene causes the progressive deterioration of skeletal muscles seen in people with MD. But the mutation affects cardiac muscle, too. Many people with Duchenne muscular dystrophy die in their 20s from heart failure caused by cardiomyopathy, a gradual weakening of the heart muscle. Heart failure is the second leading cause of death in DMD.

The chemical sealant that protected hearts in dystrophic mice from damage is called poloxamer 188. According to Joseph M. Metzger, Ph.D., the U-M scientist who directed the research, poloxamer 188 can insert itself into small holes in cell membranes just like "a finger in a dike".

The U-M study will be published July 17 in Nature as an advance online publication.

The study is important because it is the first to show what happens to heart muscle cells called myocytes in the absence of dystrophin, and the first study to demonstrate a new, promising approach to repair the damage. The study's authors emphasize, however, that several years of additional animal research will be required before the treatment could be tested in human patients.

"Most people think of the heart as a pump," explains Metzger, a professor of molecular and integrative physiology and of internal medicine in the U-M Medical School. "They say their heart is failing, because it's not pumping hard enough. That can be true, but another major problem is poor function during the relaxation phase when the heart fills with incoming blood. In our study, we found that cardiac myocytes in dystrophin-deficient mice don't relax and lengthen as readily as cardiac myocytes in normal mice. They are stiffer than normal heart muscle cells, and vulnerable to damage when stretched.

"That's where poloxamer 188 comes in," Metzger adds. "It assists the heart to be more compliant during the relaxation phase--allowing more blood to flow into the heart. We demonstrated this effect at the level of individual heart muscle cells, and it turned out to be true at the organ level, also."

More details of this fascinating research...

The BBC coverage...

For the first time ever, using "laser tweezers," the mechanical properties of an individual fiber in a blood clot have been determined by researchers at the University of Pennsylvania School of Medicine. Their work, led by John W. Weisel, PhD, Professor of Cell and Developmental Biology at Penn, and published in this week's early online edition of the Proceedings of the National Academy of Sciences, provides a basis for understanding how the elasticity of the whole clot arises.

Clots are a three-dimensional network of fibrin fibers, stabilized by another protein called factor XIIIa. A blood clot needs to have the right degree of stiffness and plasticity to stem the flow of blood when tissue is damaged, yet be digestible enough by enzymes in the blood so that it does not block blood-flow and cause heart attacks and strokes.

Weisel and colleagues developed a novel way to measure the elasticity of individual fibrin fibers in clots-with and without the factor XIIIa stabilization. They used "laser tweezers"-essentially a laser-beam focused on a microscopic bead 'handle' attached to the fibers-to pull in different directions on the fiber.

The investigators found that the fibers, which are long and very thin, bend much more easily than they stretch, suggesting that clots deform in flowing blood or under other stresses primarily by the bending of their fibers.

Weisel likens the structure of a clot composed of fibrin fibers to a microscopic version of a bridge and its many struts. "Knowing the mechanical properties of each strut, an engineer can extrapolate the properties of the entire bridge," he explains. "To measure the stiffness of a fiber, we used light to apply a tiny force to it and observed it bend in a light microscope, just as an engineer would measure the stiffness of a beam on a macroscopic scale. The mechanical properties of blood clots have been measured for many years, so now we can develop models to relate individual fiber and whole clot properties to understand mechanisms that can yield clots that have vastly different properties."

He states that these findings have relevance for many areas: materials science, polymer chemistry, biophysics, protein biochemistry, and hematology. "We present the first determination of the microscopic mechanical properties of any polymer of this sort," says Weisel...

The press release...

The idea of "caged compounds" has been around for some 30 years. In the current application, the team attached a light-sensitive molecule called a chromophore to a bioactive molecule called an effector through a single covalent bond that inactivates the bioactive molecule. Exposing the caged compound to light releases the effector in its active form.

"It's analogous to placing an animal in a cage to restrict its activity," said Dore, "but the term 'cage' is really a misnomer because we are not actually placing a molecule inside of a molecule."

The team developed a caged anisomycin compound that can be activated by exposure to ultraviolet light or an infrared laser beam. (Anisomycin is an antibiotic that inhibits protein synthesis.) The new chromophore, called Bhc, is the only one sensitive enough to light that it can mediate light-induced protein synthesis inhibition in a living system.

While previous studies have focused on releasing molecules that activate biological events, little has been done in the area of regulating the inhibition of biological processes.

"Ultimately, we want to understand the role local protein synthesis plays in biological systems such as neurons," said Schuman. "When and where in the neuron is protein synthesis used to bring about changes? How does protein synthesis regulate synaptic strength and axonal outgrowth? These are questions we'd like to answer."

Another example of a process the new method can help clarify involves the role of protein synthesis in the development of an organism. Since stem cells in humans, for example, differentiate into skin, brain and muscle cells, among many others, researchers want to know the controlling mechanisms for how these cells are chosen for their specific roles.

"If we had a way to selectively abolish protein synthesis in subcellular compartments and observe the effects, then we could infer the role of local protein synthesis in development," said Dore.

Generally speaking, there are few research tools available that are location-specific, so the new method adds a potentially powerful tool for scientists. Often, manipulations are carried out on all parts of a sample, but researchers have learned that much of biological function is dependent on the specific location of a particular event.

While the new caged compound and its photoreactive properties may never be used for anything as complex as drug delivery, it may well serve a purpose in studying such areas as memory, brain function and even Alzheimer's Disease.

"Our technique will enable scientists to conduct experiments aimed at understanding the mechanisms of learning and memory at the molecular and cellular level," said Dore.

The technique could also be used in drug discovery and development, though it is much more likely to be used in advancing knowledge about biological systems.

Press release from the University of Georgia...

Inovio reports on how the therapy is thought to work in concert with bleomycin chemo:

Two decades ago researchers discovered that briefly applying an electric field to a living cell causes a transient permeability in the cell's outer membrane. This permeation is manifest by the appearance of pores across the membrane. After the field is discontinued, the pores close within minutes without significant damage to the exposed cells and with the therapeutic molecules trapped inside the target cells. The phenomenon is known as electroporation from the words electric and pore. Electroporation Therapy has significant potential for the delivery of large molecules into cells...

Bleomycin is a well-established anti-cancer drug which is approved for use in humans in most countries of the world. When administered conventionally by injection or infusion it is not particularly effective in the treatment of malignant tumors. However, when a patient is treated with Bleomycin (intratumorally or systemically) and the tumor is exposed to electroporation, the efficacy of the drug is increased significantly. In vitro, electroporation has been shown to enhance tumor cell killing up to 5,000-fold. This increase in efficacy is based on the ability of electroporation to form temporary "pores" in the cell membrane, which allows Bleomycin to efficiently enter the cell. When the pores close again within seconds or minutes, the drug is trapped inside the cell and acts catalytically to destroy the cancer cell's nucleic acids. Inovio has shown that tumors injected with bleomycin retain the drug in their cells much longer when electroporated, compared with non-electroporated tumors.

The goal of chemotherapy is to kill cancer cells with high efficiency, while keeping toxic side effects as low as possible. The enhancement of Bleomycin efficacy by electroporation allows to use relatively low doses of the drug locally, thus reducing the side effects to the point of no concern. Inovio's standard treatment dose is 1 unit of Bleomycin per cm3 of tumor. For most tumors this dose will be well below the dose which would be given during conventional treatment, and well below the recommended maximal lifetime dose of 400 units.

Bleomycin has proven to be the most effective drug in combination with electroporation. Among over 20 chemotherapeutic drugs tested in a broad variety of tumors, with and without electroporation, the combination of Bleomycin and electroporation was consistently more effective than any other drug or drug-electroporation combination.

Inovio believes that its electroporation technology one day might also be used for a wide variety of other uses such as DNA delivery for gene therapy or DNA vaccinations, for ex vivo applications, for transdermal delivery for cosmetics, dermatology, and many other uses.

More at Inovio...

The laws of physics combine with the mutual attraction of two proteins to create the honeycomb pattern of fruit fly eyes, say molecular biologists at Washington University School of Medicine in St. Louis. This same combination of forces forms the delicate filtering structures of the mammalian kidney.

The findings, reported in the June issue of Developmental Cell, provide a new understanding of how individual cells find their niche during organ development. They also mean that the fruit fly eye can now become a fast, inexpensive system for gaining insight into how kidneys develop in mammals and why development sometimes goes awry.

"We've challenged scientists who study the development of organs such as eyes and kidneys to think about physics," says Ross Cagan, Ph.D., associate professor of molecular biology and pharmacology. "In the developing fruit fly eye, we found that cells change shape and move into their proper placement because they want to minimize the free energy of the system."

Just as molecules of oil floating in water will gather together to exclude water molecules, cells with "sticky" molecules on their surface will gather together in clumps to exclude "non-sticky" cells during organ development. This property of cell adhesion has been previously proposed as a key to moving different cell types into the right positions as developing organs change from an immature, disorganized state to a mature, functional state.

More in the press release...

Ever wonder how cells divide and position themselves within the tissue? A new program is available for download that is "demonstrating cell division, cell movement and growth in the crypt of intestinal epithelium."

Download your the 30-day free trial package here. Then it's a hefty $280.00.

The simulation, called AgentCell, has possible applications in cancer research, drug development and combating bioterrorism. Other simulations of biological systems are limited to the molecular level, the single-cell level or the level of bacterial populations. AgentCell can simultaneously simulate activity on all three scales, something its creators believe no other software can do.

"With AgentCell we can simulate the behavior of entire populations of cells as they sense their environment, respond to stimuli and move in a three-dimensional world," said Thierry Emonet, a Research Scientist in Philippe Cluzel's laboratory at the University of Chicago's Institute for Biophysical Dynamics.

Emonet and his colleagues have verified the accuracy of AgentCell in biological experiments. AgentCell now enables scientists rapidly to run test experiments on the computer, saving them valuable time in the laboratory later...

AgentCell will be used to tackle a major goal in single-cell biology today: to document the connection between internal biochemical fluctuations and cellular behavior. "The belief is that these fluctuations are going to be reflected in the behavior of the cell as shown experimentally by John Spudich and Daniel Koshland in 1976," Emonet said. They may even reveal why cells sometimes act as individuals and sometimes as part of a community...

Each digital cell in AgentCell is a virtual Escherichia coli, a single-celled bacterium, which is equipped with all the virtual components necessary to search for food. These digital E. coli contain their own chemotaxis system, which transmits the biochemical signals responsible for cellular locomotion. They also have flagella, the whiplike appendages that cells use for propulsion, and the motors to drive them.

Emonet and his associates have designed their digital bacterial system in modules, so that additional components may be added later.

What's more is that the AgentCell computer code is going to be an open source project, and available for download right here.