New method to monitor early sign of oxidative stress that triggers cancer

Washington, Sept 12 (ANI): Scientists from University of Michigan have developed a new method to monitor early sign of oxidative stress that triggers cancer spread.

Lead researcher Kate Carroll suggests that being able to monitor a marker of oxidative stress that is associated with the activation of tumor cell growth pathways, particularly at an early stage, and then tailor treatments accordingly would allow for more targeted studies and might improve the odds of success with antioxidants and pro-oxidants.

The new method detects sulfenic acid in proteins-a tip off to early oxidative stress and to a specific protein modification associated with cell growth pathways.

Sulfenic acid is produced when a particular oxidant, hydrogen peroxide, reacts with the protein building block cysteine. But because the chemical modification involved is so small and transient, it has been difficult to detect.

To get around that problem, Carroll and Seo used a chemical probe that “traps” sulfenic acid and tags it for recognition by an antibody.

The antibody is labeled with a fluorescent dye that glows when observed with a fluorescence microscope.

The researchers then used the method to assess sulfenic acid levels as a marker of oxidative stress in several systems, including a panel of breast cancer cell lines.

“For each line, we saw a very distinct pattern of sulfenic acid modifications,” indicating different oxidative stress levels and hinting at differences in the underlying molecular events associated with tumor growth,” said Carroll, assistant professor of chemistry and a research assistant professor in the Life Sciences Institute.

“Whether the patterns we see will correlate with response to antioxidant treatment or other therapies that modulate oxidative stress level remains to be seen, but now we at least have a way to investigate that question,” the expert added.

The study appears in Proceedings of the National Academy of Sciences. (ANI)

Men with high levels of bone lead 6 times more likely to die from heart disease

Washington, Sept 10 (ANI): Men with high levels of lead in bones are six times more likely to die from heart disease, according to a new study.

Researchers from the Harvard School of Public Health (HSPH) and the University of Michigan School of Public Health found that bone lead was associated with a higher risk of death from all causes, particularly from cardiovascular disease.

“The findings with bone lead are dramatic,” said Marc Weisskopf, assistant professor of environmental and occupational epidemiology at HSPH and lead author of the study.

“It is the first time we have had a biomarker of cumulative exposure to lead and the strong findings suggest that, even in an era when current exposures are low, past exposures to lead represent an important predictor of cardiovascular death, with important public health implications worldwide,” he added.

During the study, the researchers examined 868 participants in the Department of Veterans Affairs Normative Aging Study, a study of aging in men that began in 1963. Blood lead and bone lead were analyzed using X-ray fluorescence.

The results showed that the risk of death from cardiovascular disease was almost six times higher in men with the highest levels of bone lead compared to men with the lowest levels.

The risk of death from all causes was 2.5 times higher in men with the highest levels of lead compared to those with the lowest levels.

According to the authors, there are a number of mechanisms, such as increased oxidative stress, by which lead exposure may result in cardiovascular mortality.

They also note that, in addition to high blood pressure, exposure to lead has been associated with widened pulse-pressure (an indicator of arterial stiffening) and heart disease.

Given that bone lead may be a better biomarker of cumulative lead exposure than blood lead, it may be the best predictor of chronic disease from exposure to lead in the environment.

The study appears in journal Circulation. (ANI)

High-performance, low-cost green LEDs to brighten up the future

Washington, September 6 (ANI): A scientist is aiming to develop a high-performance, low-cost green LED (Light-emitting diode).

According to Christian Wetzel, professor of physics and the Wellfleet Professor of Future Chips at Rensselaer Polytechnic Institute (RPI), “Going green means different things to different people. For companies, going green means making a profit by selling equipment and services that allow one’s customers to be more efficient and reduce costs.”

“I’m doing both of those, but I’m also trying to make an LED that literally shines green light,” he said.

First discovered in the 1920s, LEDs are semiconductors that convert electricity into light.

When switched on, swarms of electrons pass through the semiconductor material and fall from an area with surplus electrons into an area with a shortage of electrons.

As they fall, the electrons jump to a lower orbital and release small amounts of energy. This energy is realized as photons – the most basic unit of light.

Unlike conventional light bulbs, LEDs produce almost no heat.

The color of light produced by LEDs depends on the type of semiconductor material it contains.

“We have high-performance red LEDs, we have high-performance blue LEDs, and if we paired them with a high-performance green LED we would be able to produce every color visible to the human eye – including true white,” said Wetzel.

“Every computer monitor and television produces its picture by using red, blue, and green. That means developing a high-performance green LED would likely lead to a new generation of high-performance, energy-efficient display devices,” he added.

“The problem, however, is that green LEDs are much more difficult to create than I, or anyone else, imagined,” he explained.

Simple preliminary attempts to create green LEDs, by merely adding more indium (In) to the gallium nitride (GaN) materials that composed blue LEDs, were unsuccessful.

The resulting green LEDs just weren’t strong or bright enough to stand toe-to-toe with red or blue.

Wetzel and his research group have been working to tweak precisely how to add more indium, and how to grow the structure more carefully into a device, with the goal of boosting the strength and light output of green LEDs.

“They’re endeavoring, he said, to close the green gap,” said Wetzel.

Once they overcome the challenge of developing efficient green LEDs, Wetzel envisions LED technology will quickly evolve from its current applications in signs and small displays and grow into a universally adopted, globally used replacement for traditional light bulbs and compact fluorescence tubes. (ANI)

New X-ray technique reveals buried image in N. C. Wyeth’s painting

Washington, August 20 (ANI): A new X-ray imaging technique has for the first time in a century revealed unprecedented details of a painting hidden beneath another painting by famed American illustrator Newell Convers Wyeth, who is regarded as the greatest American illustrator of the 20th century.

While making a presentation at the 238th National Meeting of the American Chemical Society (ACS) on Wednesday, Dr. Jennifer Mass said that the non-destructive look-beneath-the-surface method could reveal hidden images in hundreds of Old Master paintings, and other prized works of art.

In the study paper, the researcher noted that many great artists re-used canvases or covered paintings with other paintings, in order to save money on materials or to let the colours and shapes of a prior composition influence the next one.

Art historians believe that several of Wyeth’s most valued illustrations have been lost from view in that way, and one of them, depicting a dramatic fist fight, was published in a 1919 Everybody’s Magazine article titled ‘The Mildest Mannered Man’.

X-ray techniques previously used by other scientists suggested that Wyeth had covered the fight scene with another painting called ‘Family Portrait’, but they had not shown the the true image except in black and white reproductions.

The new instrument, called a confocal X-ray fluorescence microscope, was developed at the Cornell High Energy Synchrotron Source (CHESS) national X-ray facility.

The instrument reveals minute details in hidden paintings without removing paint samples. It shoots X-ray beams into a painting and then collects fluorescent X-ray “signals” given off by the chemicals in the various paint layers.

Scientists can link each signal to specific paint pigments.

In addition to revealing the original image, the method is providing new information on Wyeth’s materials and methods.

The same technique may ultimately reveal hidden images in paintings by other famed artists, the researchers say. (ANI)

Scientists use titanium dioxide nanoparticles to kill cancer cells, sparing healthy ones

Washington, August 20 (ANI): Scientists in America have developed a way to target brain cancer cells using inorganic titanium dioxide nanoparticles bonded to soft biological material.

This achievement is a result of the joint efforts of scientists from the U.S. Department of Energy’s (DOE) and the University of Chicago’s Brain Tumor Center.

Thousands of people die from malignant brain tumours every year, and the tumors are resistant to conventional therapies.

The researchers say that their nano-bio technology may eventually provide an alternative form of therapy, which targets only cancer cells and does not affect normal living tissue.

“It is a real example of how nano and biological interfacing can be used for biomedical application. We chose brain cancer because of its difficulty in treatment and its unique receptors,” said scientist Elena Rozhkova with the DOE’s Argonne National Laboratory.

The novel approach relies upon a two-pronged approach.

The researchers describe titanium dioxide as a versatile photoreactive nanomaterial that can be bonded with biomolecules.

When linked to an antibody, they say, nanoparticles recognize and bind specifically to cancer cells.

When focused visible light is shined onto the affected region, the researchers add, the localized titanium dioxide reacts to the light by creating free oxygen radicals that interact with the mitochondria in the cancer cells.

Mitochondria act as cellular energy plants, and when free radicals interfere with their biochemical pathways, mitochondria receive a signal to start cell death.

“The significance of this work lies in our ability to effectively target nanoparticles to specific cell surface receptors expressed on brain cancer cells,” said Dr. Maciej S. Lesniak, Director of Neurosurgical Oncology at University of Chicago Brain Tumor Center.

“In so doing, we have overcome a major limitation involving the application of nanoparticles in medicine, namely the potential of these agents to distribute throughout the body. We are now in a position to develop this exciting technology in preclinical models of brain tumours, with the hope of one day employing this new technology in patients,” Lesniak added.

Using X-ray fluorescence microscopy at Argonne’s Advanced Photon Source, the researchers have also found that the tumours’ invadopodia, actin-rich micron scale protrusions that allow the cancer to invade surrounding healthy cells, can be also attacked by the titanium dioxide.

The researchers have thus far carried out tests on cells in a laboratory setting, but animal testing is planned for the next phase.

Results show an almost 100 percent cancer cell toxicity rate after six hours of illumination, and 80 percent after 48 hours.

Also, since the antibody only targets the cancer cells, surrounding healthy cells are not affected, unlike other cancer treatments such as chemotherapy and radiotherapy.

Rozhkova said that a proof of concept is demonstrated, and other cancers can be treated as well using different targeting molecules.

The expert, however, admits that the research is presently in the early stages. (ANI)

Scientists develop microscope capable of ‘super-resolution’ video imaging

Washington, May 5 (ANI): A team of scientists at the University of Georgia (UGA), US, has developed a microscope that is capable of live imaging at double the resolution of fluorescence microscopy using structured illumination.

The fluorescence microscope has allowed a generation of scientists to study the properties of proteins inside cells.

Yet, as human capacity for discovery has zoomed to the nanoscale, fluorescence microscopy has struggled to keep up.

The laws of physics have limited the resolution of fluorescence microscopy, whereby a fluorescent marker is used to distinguish specific proteins, to about 200 nanometers.

At this resolution significant detail is lost about the activity within a cell.

Now, the increased resolution by structured illumination is an engineering feat that will help scientists learn more about cell behavior and study mechanisms important for human disease.

“Our understanding of what is going on inside cells and our ability to manipulate them has advanced so much that it has become more and more important to see them at a better resolution,” said UGA engineer Peter Kner.

Kner built the structured illumination microscope with colleagues at the University of California, San Francisco.

This work follows on at least a decade of research building on the nearly fifty-year history of fluorescence microscopy.

The technology has been a multi-disciplinary springboard of optical engineering, chemistry and biology, in which the disciplines have all contributed to visualizing fluorescent dyes attached to proteins, advancing our understanding of cellular activity.

The importance of fluorescence microscopy was recently recognized with the 2008 Nobel Prize for Chemistry, which was awarded for the development of the green fluorescent protein (GFP), which has played a crucial role in our identification and understanding of proteins.

“What we’ve done is develop a much faster system that allows you to look at live cells expressing GFP, which is a very powerful tool for labeling inside the cell,” Kner explained.

“It would be difficult to overstate the importance of bio-imaging to ongoing research in human health,” said Dale Threadgill, director of the UGA Faculty of Engineering.

“The ability to shine a light on the leading-edge of scientific discovery will define the route to entirely new regimens of health management at the intersections of science and engineering, and Dr. Kner has joined a distinguished cadre at UGA to continue working at that interface,” he added. (ANI)

Nanotechnology may help fight HIV infection

London, May 4 (ANI): Biomedical engineers at Yale University have found a new method that may help stop HIV infection in future-a safe measure to deliver potentially therapeutic RNAs into vaginal cells using nanoparticles.

Led by Mark Saltzman, the researchers believe that similar particles could be used to make topical creams containing anti-HIV RNAs.
The team wanted to find a better way to deliver short interfering RNAs (siRNAs) into vaginal cells that might come into contact with HIV.

These short snippets of RNA can be designed to repress specific genes, and siRNAs against HIV genes have been shown to stop the virus reproducing in humanized mice.

Usually, siRNAs are transferred into cells by attaching them to lipids, which is expensive and can be toxic, reports Nature.

In the new study, however, the scientists instead found a surprisingly simple way to pack thousands of siRNAs into nano-sized bits of a biodegradable and biocompatible plastic that is already approved for medical uses.

Such nanoparticles could then be incorporated into a vaginal gel, which could be applied by women before sex to help prevent infection.

“It’s surprising that you can load as much siRNA as you can into particles like this. It wasn’t obvious that it would work,” said Saltzman.

For developing the new method, the team first mixed the siRNA molecules with spermidine – a natural condensing agent, which formed the siRNA into clumps that were later encapsulated in porous plastic particles 100 nanometres across.

Some siRNAs are known to stop the HIV virus replicating, and thus the researchers tested this delivery technique in mice using siRNA that ‘silences’ or prevents the production of a green fluorescent protein (EGFP).

After transferring the loaded nanoparticles into the vaginas of female mice engineered to produce EGFP, the team could easily see how well their ‘medicine’ worked by checking if the vaginal cells stopped fluorescing.

The nanoparticle-delivery system silenced fluorescence just as well as a traditional lipid delivery system.

But, the researchers found that the lipid-treated mice developed signs of vaginal irritation, whereas those given the nanoparticles did not.

The nanoparticles also did a good job of spreading siRNA around – deep into vaginal tissue and into the uterus – and released their cargo slowly over a month.

And now, Saltzman is testing his nanoparticles against the monkey version of HIV, and says it “looks good”. But there’s still a long way to go.

“The challenge is to show it works against disease,” he said.

The study is published in Nature Materials. (ANI)

Amnis Receives Broad Patent Coverage for Diagnostic Cell Imaging

SEATTLE, April 20 /PRNewswire/ — Amnis Corporation, a manufacturer of
advanced cell imaging systems, announced today that it has received U.S.
patent 7,522,758. The patent, entitled Blood and Cell Analysis Using an
Imaging Flow Cytometer, broadly covers diagnostic uses of multispectral cell
imaging in flow or on slides and expands the company’s intellectual property
estate to 32 issued U.S. patents plus multiple foreign counterparts.

“Amnis’ ImageStream(R) platform was designed to achieve tremendous speed and
high fluorescence sensitivity while providing rich diagnostic information in
the form of multiple images per cell,” remarked William Ortyn, Amnis’
co-founder and Chief Operations Officer. “With its ability to image hundreds
of thousands of cells in minutes, directly in flow, ImageStream combines the
diagnostic strengths of high resolution microscopy and flow cytometry in a
single platform,” added Ortyn.

“Our technology is a natural fit for the minimally-invasive diagnostic
analysis of cells in bodily fluids. ImageStream enables the identification and
functional analysis of even extremely rare cells that are indicative of
disease, such as circulating tumor cells,” said David Basiji, Ph.D., Amnis’
President and Chief Executive Officer. Basiji added, “We are actively
collaborating with our clinical partners on the development of diagnostic
applications and are pleased that we now have broad intellectual property in
multiple diagnostic areas.”

About Amnis: Amnis Corporation, headquartered in Seattle, WA, develops,
manufactures and markets instrumentation for high speed cell imaging for
research and diagnostic markets.

SOURCE Amnis Corporation

David Basiji, President and Chief Executive Officer of Amnis Corporation,
+1-206-374-7000, fax, +1-206-576-6895, marketing@amnis.com

Electronic biological chips bring ultra-portable detectors closer to reality

Washington, January 16 (ANI): A new study has raised Penn State researchers’ hopes for the development of a handheld device that will recognize and immediately report on a wide variety of environmental or medical compounds.

The researchers say that a method that incorporates a mixture of biologically tagged nanowires onto integrated circuit chips can help develop an ultra-portable device of this kind.

“Probably one of the most important things for connecting to the circuit is to place the wires accurately. We need to control spatial placement on the chip with less than a micron of accuracy,” says Theresa S. Mayer, professor of electrical engineering and director of Penn State’s Nanofabrication Laboratory.

The researchers say that using standard chip manufacturing would help place each type of nanowire on the board in a separate operation, and then using their bottom-up method would help place three different types of DNA-coated wires where they are wanted, with an error rate of less than one percent.

“This approach can be used to simultaneously detect different pathogens or diseases based on their nucleic acid signatures,” says Christine D. Keating, associate professor of chemistry.

“Device components such as nanowires can be synthesized from many different materials and even coated with biological molecules prior to assembling them onto a chip,” the researchers note in the journal Science.

They add that positioning the nanowires accurately is still difficult using conventional methods.

According to them, their assembly method can be helpful in placing specific nanowires in assigned areas.

The team begin with a chip with tiny rectangular depressions in the places they wish to place the nanowires, and then apply an electrical field between electrodes that define the area where they want the nanowires to assemble.

The researchers inject a mixture of the tagged nanowires and a liquid over the top of the chip. The nanowires are attracted to the area with an electric field and they fall into the proper tiny wells.

“We do not need microfluidic channels to control where each nanowire type goes. We can run the solution over the whole chip and its wires will only attach where they are supposed to attach. This is important for scale-up,” says Mayer.

The researchers later move the electric field and position the next tagged nanowires.

Though the different tagged wires in the current proof-of-concept experiment were placed in rows, the researchers say that they could be placed in a variety of configurations.

Once the wires are in place, they can be made into a variety of devices like resonators or field effect transistors, which can be used to detect nucleic acid targets.

The researchers believe that their assembly method is extremely flexible, capable of placing a variety of conducting and non-conducting wires with a wide array of coatings.

“The eventual idea would be to extend the method to more nanowire types, such as different DNA sequences or even proteins, and move from fluorescence to real-time electrical detection on the chip,” says Keating. (ANI)