Gold nanoparticles help earlier diagnosis of liver cancer

A new diagnostic technique can spot tumor-like masses as small as 5 millimeters in the liver. Gold nanoparticles with a polyelectrolyte coating can make smaller tumors more visible through X-ray scatter imaging, enabling earlier diagnosis. Credit: Rose-Petruck lab, Brown University

Hepatocellular carcinoma is the most common cancer to strike the liver. More than 500,000 people worldwide, concentrated in sub-Saharan Africa and Southeast Asia, are diagnosed with it yearly. Most of those afflicted die within six months.

A big obstacle to treatment of liver cancer is the lack of early diagnosis. Current techniques, including ultrasound, CT and MRI scans, spot tumors only when they have grown to about 5 centimeters in diameter. By that time, the cancer is especially aggressive, resisting chemotherapy and difficult to remove surgically.

Now a research team led by Brown University reports some promising results for earlier diagnosis. In lab tests, the team used gold nanoparticles ringed by a charged polymer coating and an X-ray scatter imaging technique to spot tumor-like masses as small as 5 millimeters. The approach, detailed in the American Chemical Society journal Nano Letters, marks the first time that metal nanoparticles have been used as agents to enhance X-ray scattering signals to image tumor-like masses.

"What we're doing is not a screening method," said Christoph Rose-Petruck, professor of chemistry at Brown University and corresponding author on the paper. "But in a routine exam, with people who have risk factors, such as certain types of hepatitis, we can use this technique to see a tumor that is just a few millimeters in diameter, which, in terms of size, is a factor of 10 smaller."

The team took gold nanoparticles of 10 and 50 nanometers in diameter and ringed them with a pair of 1-nanometer polyelectrolyte coatings. The coating gave the nanoparticles a charge, which increased the chances that they would be engulfed by the cancerous cells. Once engulfed, the team used X-ray scatter imaging to detect the gold nanoparticles within the malignant cells. In lab tests, the nontoxic gold nanoparticles made up just 0.0006 percent of the cell's volume, yet the nanoparticles had enough critical mass to be detected by the X-ray scatter imaging device.

"We have shown that even with these small numbers, we can distinguish these [tumor] cells," Rose-Petruck said.

The next step for the researchers is on the clinical side. Beginning this summer, the group will attach a cancer-targeting antibody to the nanoparticle vehicle to search for liver tumors in mice. The antibody that will be used was developed by Jack Wands, director of the Liver Research Center at Rhode Island Hospital and professor of medical science at the Warren Alpert Medical School of Brown University.

"We have developed a monoclonal antibody that targets a cell surface protein highly expressed on liver cancer cells," Wands said. "We plan to couple the antibody to the gold nanoparticles in an attempt to detect the growth of early tumors in the liver by X-ray imaging."

The researchers say the X-ray scatter imaging method could be used to detect nanoparticle assemblies in other organs. "The idea should be that if you can figure out to get that [nanoparticle] to specific sites in the body, you can figure out how to image it," said Danielle Rand, a second-year graduate student in chemistry and the first author on the paper.

Provided by Brown University (news : web)

Researchers clarify properties of 'confined' water within single-walled carbon nanotube pores

This global temperature-diameter (T-D) phase diagram of water inside SWCNTs shows that, depending on the water content, hollow or filled ice will form. On the right, hollow- and filled-ice nanotubes can be calculated at low temperature for SWCNTs with diameters indicated with (a) and (b) in the lower portion of the phase diagram. Credit: Yutaka Maniwa

Water and ice may not be among the first things that come to mind when you think about single-walled carbon nanotubes (SWCNTs), but a Japan-based research team hoping to get a clearer understanding of the phase behavior of confined water in the cylindrical pores of carbon nanotubes zeroed in on confined water's properties and made some surprising discoveries.

The team, from Tokyo Metropolitan University, Nagoya University, Japan Science and Technology Agency, and National Institute of Advanced Industrial Science and Technology, describes their findings in the American Institute of Physics' Journal of Chemical Physics.

Although carbon nanotubes consist of hydrophobic (water repelling) graphene sheets, experimental studies on SWCNTs show that water can indeed be confined in open-ended carbon nanotubes.

This discovery gives us a deeper understanding of the properties of nanoconfined water within the pores of SWCNTs, which is a key to the future of nanoscience. It's anticipated that nanoconfined water within carbon nanotubes can open the door to the development of a variety of nifty new nanothings—nanofiltration systems, molecular nanovalves, molecular water pumps, nanoscale power cells, and even nanoscale ferroelectric devices.

"When materials are confined at the atomic scale they exhibit unusual properties not otherwise observed, due to the so-called 'nanoconfinement effect.' In geology, for example, nanoconfined water provides the driving force for frost heaves in soil, and also for the swelling of clay minerals," explains Yutaka Maniwa, a professor in the Department of Physics at Tokyo Metropolitan University. "We experimentally studied this type of effect for water using SWCNTs."

Water within SWCNTs in the range of 1.68 to 2.40 nanometers undergoes a wet-dry type of transition when temperature is decreased. And the team discovered that when SWCNTs are extremely narrow, the water inside forms tubule ices that are quite different from any bulk ices known so far. Strikingly, their melting point rises as the SWCNT diameter decreases—contrary to that of bulk water inside a large-diameter capillary. In fact, tubule ice occurred even at room temperature inside SWCNTs.

"We extended our studies to the larger diameter SWCNTs up to 2.40 nanometers and successfully proposed a global phase behavior of water," says Maniwa. "This phase diagram (See Figure) covers a crossover from microscopic to macroscopic regions. In the macroscopic region, a novel wet-dry transition was newly explored at low temperature."

Results such as these contribute to a greater understanding of fundamental science because nanoconfined water exists and plays a vital role everywhere on Earth—including our bodies. "Understanding the nanoconfined effect on the properties of materials is also crucial to develop new devices, such as proton-conducting membranes and nanofiltration," Maniwa notes.

Next up, the team plans to investigate the physical properties of confined waterdiscovered so far inside SWCNTs (such as dielectricity and proton conduction). They will pursue this to obtain a better understanding of the molecular structure and transport properties in biological systems.

Provided by American Institute of Physics

Organisms that stick to the lower structures of ships increase fuel consumption and costs of maintenance substantially. Currently, the organisms are killed with toxic biocides, but these chemicals need to be removed to protect our environment. Researchers are trying to develop environmentally friendly anti-biofouling technologies, such as nano-structured surfaces that make organisms fall off when the ships move.

Organisms, such as algae and barnacles, sticking to the lower structure of ships are increasing the required propulsive power. It is estimated that ships’ fuel consumption could be reduced by up to forty percent by removing thoseorganisms. Erosive systems containing biocides are mainly used for this purpose. However, the use of eco-friendly alternatives such as silicon based fouling release coatings, nearly all enhanced with an oil additive, have increased lately. Researchers at GE Global Research Center in the U.S. have shown that organisms react differently to the various silicone fouling release coatings, andcoating type crossed with oil type is very important when it comes to establishing an organism’s attachment strength magnitude.

However, there is a need for improved eco-friendly alternatives and researchers are working on solutions. For example, scientists at the University of Gothenburg in Sweden have developed what they call a “low emission” approach where avermectins, a class of antibiotics, are included. Only very small amounts are released, since the substances in the coating are tightly associated with the binding matrix agent. The scientists found that 1mg avermectin/gr coating very effectively hindered adult barnacles from colonization, but a similar coating did not disturb barnacle larvae. The reason is that the barnacles first encounter the avermectin when they try to stick tighter to the surface and the avermectin then make them detach. This principle was named post settlement inhibition (PSI) because this coating only seems to influence adult barnacle growth.

Another innovation that neither involves toxic substances currently used nor nanoparticles, has been developed by researchers connected to the European Commission-funded project AMBIO (Advanced Nanostructured Surfaces for the Control of Biofouling). Their coating technology that can replace the toxic biocides technology is instead based on nano-pattering. Molecules within their innovative paint will arrange themselves in a chequeboard pattern were hydrophobic nanosized points are combined with hydrophilic nanosized points. This texture makes it very hard for algae and barnacles to hold on to the surface and the water’s friction will remove them.

Although a coating alternative that do not release any toxic substances into the environment appears to be the safest choice, the AMBIO coating technology will first be studied extensively in a real world setting to make sure it has the right properties, for example that it can last five years on ships, before it can become commercially available.

Source: Youris.com (news : web)

“Self-organization” of nano-devices: Magnetic molecules (green) arrange on a carbon nanotube (black) to build an electronic component Credit: Photo: C. Grupe, KIT

Magnetic storage media such as hard drives have revolutionized the handling of information: We are used to dealing with huge quantities of magnetically stored data while relying on highly sensitive electronic components. And hope to further increase data capacities through ever smaller components. Together with experts from Grenoble and Strasbourg, researchers of KIT's Institute of Nanotechnology (INT) have 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 Materiaux 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 inorganic 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 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.

Scientists find simple way to produce graphene

Amartya Chakrabarti holds up a sample of graphene produced via the dry-ice method. Credit: Scott Walstrom, Northern Illinois University

The focus of intense scientific research in recent years, graphene is a two-dimensional material, comprised of a single layer of carbon atoms arranged in ahexagonal lattice. It is the strongest material ever measured and has other remarkable qualities, including high electron mobility, a property that elevates its potential for use in high-speed nano-scale devices of the future.

In a June communication to the Journal of Materials Chemistry, the NIU researchers report on a new method that converts carbon dioxide directly into few-layer graphene (less than 10 atoms in thickness) by burning pure magnesium metal in dry ice.

"It is scientifically proven that burning magnesium metal in carbon dioxide produces carbon, but the formation of this carbon with few-layer graphene as the major product has neither been identified nor proven as such until our current report," said Narayan Hosmane, a professor of chemistry and biochemistry who leads the NIU research group.

"The synthetic process can be used to potentially produce few-layer graphene in large quantities," he said. "Up until now, graphene has been synthesized by various methods utilizing hazardous chemicals and tedious techniques. This new method is simple, green and cost-effective."

Hosmane said his research group initially set out to produce single-wall carbon nanotubes. "Instead, we isolated few-layer graphene," he said. "It surprised us all."

"It's a very simple technique that's been done by scientists before," added Amartya Chakrabarti, first author of the communication to the Journal of Materials Chemistry and an NIU post-doctoral research associate in chemistry and biochemistry. "But nobody actually closely examined the structure of the carbon that had been produced."

More information: http://pubs.rsc.or … m/c1jm11227a

Provided by Northern Illinois University

Microbiologists Discover How Cavity-Causing Microbes Invade Heart

Posted by Biomechanism 

Scientists have discovered the tool that bacteria normally found in our mouths use to invade heart tissue, causing a dangerous and sometimes lethal infection of the heart known as endocarditis. The work raises the possibility of creating a screening tool – perhaps a swab of the cheek, or a spit test – to gauge a dental patient’s vulnerability to the condition.

The identification of the protein that allows Streptococcus mutans to gain a foothold in heart tissue is reported in the June issue of Infection and Immunity by microbiologists at the University of Rochester Medical Center.

S. mutans invading a human coronary artery endothelial cell.

S. mutans is a bacterium best known for causing cavities. The bacteria reside in dental plaque – an architecturally sophisticated goo composed of an elaborate molecular matrix created by S. mutans that allows the bacteria to inhabit and thrive in our oral cavity. There, they churn out acid that erodes our teeth.

Normally, S. mutans confines its mischief to the mouth, but sometimes, particularly after a dental procedure or even after a vigorous bout of flossing, the bacteria enter the bloodstream. There, the immune system usually destroys them, but occasionally – within just a few seconds – they travel to the heart and colonize its tissue, especially heart valves. The bacteria can cause endocarditis – inflammation of heart valves – which can be deadly. Infection by S. mutans is a leading cause of the condition.

“When I first learned that S. mutans sometimes can live in the heart, I asked myself: Why in the world are these bacteria, which normally live in the mouth, in the heart? I was intrigued. And I began investigating how they get there and survive there,” said Jacqueline Abranches, Ph.D., a microbiologist and the corresponding author of the study.

Abranches and her team at the University’s Center for Oral Biology discovered that a collagen-binding protein known as CNM gives S. mutans its ability to invade heart tissue. In laboratory experiments, scientists found that strains with CNM are able to invade heart cells, and strains without CNM are not.

When the team knocked out the gene for CNM in strains where it’s normally present, the bacteria were unable to invade heart tissue. Without CNM, the bacteria simply couldn’t gain a foothold; their ability to adhere was about one-tenth of what it was with CNM.

The team also studied the response of wax worms to the various strains of S. mutans. They found that strains without CNM were rarely lethal to the worms, while strains with the protein were lethal 90 percent of the time. Then, when Abranches’ team knocked out CNM in those strains, they were no longer lethal – those worms thrived.

Jacqueline Abranches, Ph.D., flanked by technician James Miller (left) and graduate student Alejandro Aviles-Reyes. The three are holding cultures of S. mutans.

The work may someday enable doctors to prevent S. mutans from invading heart tissue. Even sooner, though, since some strains of S. mutans have CNM and others do not, the research may enable doctors to gauge a patient’s vulnerability to a heart infection caused by the bacteria.

Abranches has identified five specific strains of S. mutans that carry the CNM protein, out of more than three dozen strains examined. CNM is not found in the most common type of S. mutans found in people, type C, but is present in rarer types of S. mutans, including types E and F.

“It may be that CNM can serve as a biomarker of the most virulent strains of S. mutans,” said Abranches, a research assistant professor in the Department of Microbiology and Immunology. “When patients with cardiac problems go to the dentist, perhaps those patients will be screened to see if they carry the protein. If they do, the dentist might treat them more aggressively with preventive antibiotics, for example.”

Until more research is done and a screening or preventive tool is in place, Abranches says the usual advice for good oral health still stands for everyone.

“No matter what types of bacteria a person has in his or her mouth, they should do the same things to maintain good oral health. They should brush and floss their teeth regularly – the smaller the number of S. mutans in your mouth, the healthier you’ll be. Use a fluoride rinse before you go to bed at night. And eat a healthy diet, keeping sugar to a minimum,” added Abranches.

Abranches presented the work at a recent conference on the “oral microbiome” hosted by the University’s Center for Oral Biology. The center is part of the Medical Center’s Eastman Institute for Oral Health, a world leader in research and post-doctoral education in general and pediatric dentistry, orthodontics, periodontics, prosthodontics, and oral surgery.

____________________

Additional authors of the study include laboratory technician James Miller; former technician Alaina Martinez; Patricia Simpson-Haidaris, Ph.D., associate professor of Medicine; Robert Burne, Ph.D., of the University of Florida; and Abranches’ husband, Jose Lemos, Ph.D., of the Center for Oral Biology, who is also assistant professor in the Department of Microbiology and Immunology. The work was funded by the American Heart Association.

Exhumation of Shakespeare to determine cause of death and drug test

 Other Sciences / Archaeology & Fossils 
(PhysOrg.com) -- Director of the Institute for Human Evolution, anthropologist Francis Thackeray has formally petitioned the Church of England to allow him to exhume the body of William Shakespeare in order to determine the cause of his death.

Thackeray is best known for his controversial suggestion nearly a decade ago which pointed to the possibility that Shakespeare had been a regular cannabis smoker. Utilizing forensic techniques, Thackeray examined 24 pipes which had been discovered in Shakespeare’s garden and determined that they had been used to smoke the drug.

Citing that even after 400 years, Shakespeare is still one of the most famous people in history, Thackeray hopes to be able to end the question of how he died and establish a health history. With new state-of-the-art computer equipment he hopes to create a three dimensional reconstruction of Shakespeare. The hope is to be able to determine the kind of life he led, any diseases of medical conditions he may have suffered from and what ultimately caused his death.

The new technology, nondestructive analysis, will not require the remains to be moved but will instead scan the bones. They are also hoping to collect DNA from Shakespeare and his wife and sister, all who are buried at Holy Trinity Church.

Thackeray also hopes to find evidence to back his controversial claims years ago regarding Shakespeare’s marijuana smoking. Examining the teeth could provide the evidence they need. If they are able to discover grooves between the incisor and canine teeth, it could show them he was chewing on a pipe.

This plan however goes against the final wishes of Shakespeare himself who had the following words engraved on his tomb: “Good frend for Jesus sake forebeare, To dig the dust encloased heare, Bleste be the man that spares thes stones, And curst be he that moves my bones.”

The Church of England denies that any requests have been made to exhume Shakespeare’s body but Thackeray and his team hopes to gain approval in time to be able to make the determination before the 400th anniversary of his death in 2016.

© 2010 PhysOrg.com

"Exhumation of Shakespeare to determine cause of death and drug test." June 27th, 2011.http://www.physorg.com/news/2011-06-exhumation-shakespeare-death-drug.html

Posted by
Robert Karl Stonjek

Advances in delivery of therapeutic genes to treat brain tumors

Advances in delivery of therapeutic genes to treat brain tumors

 Genetics 

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies is an authoritative peer-reviewed journal published monthly in print and online that presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Credit: © Mary Ann Liebert Inc., publishers

Novel tools and methods for delivering therapeutic genes to cells in the central nervous system hold great promise for the development of new treatments to combat incurable neurologic diseases. Five of the most exciting developments in this rapidly advancing field are presented in a series of articles in the June issue of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc.

A review article by Betley and Sternson, "Adeno-Associated Viral Vectors for Mapping, Monitoring, and Manipulating Neural Circuits," highlights the latest genetic tools that are enabling cell type-specific delivery of transgenes for studying the structure and function of neuronal circuits.

Ryu et al. report on the successful use of stem cells derived from human umbilical cord blood to deliver a novel therapeutic gene—interleukin-12—to the brain for long-term anti-tumor activity against gliomas, a deadly type of brain tumor. Their innovative strategy is presented in the research report "Gene Therapy of Intracranial Glioma Using Interleukin 12-Secreting Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells."

"High-Density Lipoprotein Facilitates In Vivo Delivery of α-Tocopherol-Conjugated Short-Interfering RNA to the Brain" by Uno et al. describes a combination strategy for dramatically improved delivery of siRNAs to the brain to silence genes involved in neurological disease.

Loss of the neurotrophic factor GDNF contributes to the development of neuropathic pain caused by trauma or neurodegenerative disease. Shi et al. present data to support this link and demonstrate the potential to replace GDNF via intramuscular gene delivery in the article "Glial Cell Line-Derived Neurotrophic Factor Gene Transfer Exerts Protective Effect on Axons in Sciatic Nerve Following Constriction-Induced Peripheral Nerve Injury."

The use of adenoviral vectors as carriers of therapeutic genes to the cerebrospinal fluid has the potential to enable long-term gene expression for the treatment of neurological diseases. In the brief report "Intrathecal Injection of Helper-Dependent Adenoviral Vectors Results in Long-Term Transgene Expression in Neuroependymal Cells and Neurons" Dindot et al. describe the successful use of adenoviral vectors to transduce neuronal cells.

"Treating neurologic diseases with traditional biologic products such as therapeutic proteins has been challenging due to limited access. The use of vectors helps to overcome these barriers," says James M. Wilson, MD, PhD, Editor-in-Chief, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

More information: The articles are available free online at www.liebertpub.com/hum

Provided by Mary Ann Liebert, Inc.

"Advances in delivery of therapeutic genes to treat brain tumors." June 27th, 2011.http://medicalxpress.com/news/2011-06-advances-delivery-therapeutic-genes-brain.html

Posted by
Robert Karl Stonjek

Ocean Currents Speed Melting of Antarctic Ice: A Major Glacier Is Undermined from Below

Scientists aboard the Nathaniel B. Palmer visited the Amundsen Sea region in 2009 to study oceanic changes. (Credit: Frank Nitsche, Lamont-Doherty Earth Observatory)

Science Daily  — Stronger ocean currents beneath West Antarctica's Pine Island Glacier Ice Shelf are eroding the ice from below, speeding the melting of the glacier as a whole, according to a new study in Nature Geoscience. A growing cavity beneath the ice shelf has allowed more warm water to melt the ice, the researchers say -- a process that feeds back into the ongoing rise in global sea levels. The glacier is currently sliding into the sea at a clip of four kilometers (2.5 miles) a year, while its ice shelf is melting at about 80 cubic kilometers a year -- 50 percent faster than it was in the early 1990s -- the paper estimates.

"More warm water from the deep ocean is entering the cavity beneath the ice shelf, and it is warmest where the ice is thickest," said study's lead author, Stan Jacobs, an oceanographer at Columbia University's Lamont-Doherty Earth Observatory.

In 2009, Jacobs and an international team of scientists sailed to the Amundsen Sea aboard the icebreaking ship Nathaniel B. Palmer to study the region's thinning ice shelves -- floating tongues of ice where landbound glaciers meet the sea. One goal was to study oceanic changes near the Pine Island Glacier Ice Shelf, which they had visited in an earlier expedition, in 1994. The researchers found that in 15 years, melting beneath the ice shelf had risen by about 50 percent. Although regional ocean temperatures had also warmed slightly, by 0.2 degrees C or so, that was not enough to account for the jump.

The local geology offered one explanation. On the same cruise, a group led by Adrian Jenkins, a researcher at British Antarctic Survey and study co-author, sent a robot submarine beneath the ice shelf, revealing an underwater ridge. The researchers surmised that the ridge had once slowed the glacier like a giant retaining wall. When the receding glacier detached from the ridge, sometime before the 1970s, the warm deep water gained access to deeper parts of the glacier. Over time, the inner cavity grew, more warm deep water flowed in, more melt water flowed out, and the ice thinned. With less friction between the ice shelf and seafloor, the landbound glacier behind it accelerated its slide into the sea. Other glaciers in the Amundsen region have also thinned or widened, including Thwaites Glacier and the much larger Getz Ice Shelf.

One day, near the southern edge of Pine Island Glacier Ice Shelf, the researchers directly observed the strength of the melting process as they watched frigid, seawater appear to boil on the surface like a kettle on the stove. To Jacobs, it suggested that deep water, buoyed by added fresh glacial melt, was rising to the surface in a process called upwelling. Jacobs had never witnessed upwelling first hand, but colleagues had described something similar in the fjords of Greenland, where summer runoff and melting glacier fronts can also drive buoyant plumes to the sea surface.

In recent decades, researchers have found evidence that Antarctica is getting windier, and this may also help explain the changes in ocean circulation. Stronger circumpolar winds would tend to push sea ice and surface water north, says Jacobs. That in turn, would allow more warm water from the deep ocean to upwell onto the Amundsen Sea's continental shelf and into its ice shelf cavities.

Pine Island Glacier, among other ice streams in Antarctica, is being closely watched for its potential to redraw coastlines worldwide. Global sea levels are currently rising at about 3 millimeters (.12 inches) a year. By one estimate, the total collapse of Pine Island Glacier and its tributaries could raise sea level by 24 centimeters (9 inches).

The paper adds important and timely insights about oceanic changes in the region, says Eric Rignot, a professor at University of California at Irvine and a senior research scientist at NASA's Jet Propulsion Laboratory. "The main reason the glaciers are thinning in this region, we think, is the presence of warm waters," he said. "Warm waters did not get there because the ocean warmed up, but because of subtle changes in ocean circulation. Ocean circulation is key. This study reinforces this concept."

The study received funding from the US National Science Foundation and the UK National Environment Research Council

Generating 'Green' Electricity: Waste Heat Converted to Electricity Using New Alloy

During a small-scale laboratory demonstration, University of Minnesota researchers showed how their new material can spontaneously produce electricity when the temperature is raised a small amount. Pictured (from left) are aerospace engineering and mechanics professor Richard James, PhD student Yintao Song and post-doctoral researchers Kanwal Bhatti and Vijay Srivastava. (Credit: Image courtesy of University of Minnesota)

Science Daily  — University of Minnesota engineering researchers in the College of Science and Engineering have recently discovered a new alloy material that converts heat directly into electricity. This revolutionary energy conversion method is in the early stages of development, but it could have a wide-sweeping impact on creating environmentally friendly electricity from waste heat sources.

"This research is very promising because it presents an entirely new method for energy conversion that's never been done before," said University of Minnesota aerospace engineering and mechanics professor Richard James, who led the research team."It's also the ultimate 'green' way to create electricity because it uses waste heat to create electricity with no carbon dioxide."Researchers say the material could be used to capture waste heat from a car's exhaust that would heat the material and produce electricity for charging the battery in a hybrid car. Other possible future uses include capturing rejected heat from industrial and power plants or temperature differences in the ocean to create electricity. The research team is looking into possible commercialisation of the technology.To create the material, the research team combined elements at the atomic level to create a new multiferroic alloy, Ni₄₅Co₅Mn₄₀Sn₁₀. Multiferroic materials combine unusual elastic, magnetic and electric properties. The alloy Ni₄₅Co₅Mn₄₀Sn₁₀ achieves multiferroism by undergoing a highly reversible phase transformation where one solid turns into another solid. During this phase transformation, the alloy undergoes changes in its magnetic properties that are exploited in the energy conversion device.During a small-scale demonstration in a University of Minnesota lab, the new material created by the researchers begins as a non-magnetic material, then suddenly becomes strongly magnetic when the temperature is raised a small amount. When this happens, the material absorbs heat and spontaneously produces electricity in a surrounding coil. Some of this heat energy is lost in a process called hysteresis. A critical discovery of the team is a systematic way to minimize hysteresis in phase transformations. The team's research was recently published in the first issue of the new scientific journalAdvanced Energy Materials.

Watch a short research video of the new material suddenly become magnetic when heated:http://z.umn.edu/conversionvideo.

In addition to Professor James, other members of the research team include University of Minnesota aerospace engineering and mechanics post-doctoral researchers Vijay Srivastava and Kanwal Bhatti, and Ph.D. student Yintao Song. The team is also working with University of Minnesota chemical engineering and materials science professor Christopher Leighton to create a thin film of the material that could be used, for example, to convert some of the waste heat from computers into electricity.

"This research crosses all boundaries of science and engineering," James said. "It includes engineering, physics, materials, chemistry, mathematics and more. It has required all of us within the university's College of Science and Engineering to work together to think in new ways."

Funding for early research on the alloy came from a Multidisciplinary University Research Initiative (MURI) grant from the U.S. Office of Naval Research (involving other universities including the California Institute of Technology, Rutgers University, University of Washington and University of Maryland), and research grants from the U.S. Air Force and the National Science Foundation. The research is also tentatively funded by a small seed grant from the University of Minnesota's Initiative for Renewable Energy and the Environment.

Genome Editing -- A Next Step in Genetic Therapy -- Corrects Hemophilia in Animals

Scientists have treated the blood clotting disorder hemophilia in mice by using genome editing that hones in on the precise location of mutated DNA. (Credit: © Rodolfo Clix / Fotolia)

Science Daily — Using an innovative gene therapy technique called genome editing that hones in on the precise location of mutated DNA, scientists have treated the blood clotting disorder hemophilia in mice. This is the first time that genome editing, which precisely targets and repairs a genetic defect, has been done in a living animal and achieved clinically meaningful results.

As such, it represents an important step forward in the decades-long scientific progression of gene therapy -- developing treatments by correcting a disease-causing DNA sequence. In this new study, researchers used two versions of a genetically engineered virus (adeno-associated virus, or AAV) -- one carrying enzymes that cut DNA in an exact spot and one carrying a replacement gene to be copied into the DNA sequence. All of this occurred in the liver cells of living mice.

"Our research raises the possibility that genome editing can correct a genetic defect at a clinically meaningful level after in vivo delivery of the zinc finger nucleases," said the study leader, Katherine A. High, M.D., a hematologist and gene therapy expert at The Children's Hospital of Philadelphia. High, a Howard Hughes Medical Institute Investigator, directs the Center for Cellular and Molecular Therapeutics at Children's Hospital, and has investigated gene therapy for hemophilia for more than a decade.

The study appeared online in Nature.

High's research, a collaboration with scientists at Sangamo BioSciences, Inc., makes use of genetically engineered enzymes called zinc finger nucleases (ZFNs) that act as molecular word processors, editing mutated sequences of DNA. Scientists have learned how to design ZFNs custom-matched to a specific gene location. ZFNs specific for the factor 9 gene (F9) were designed and used in conjunction with a DNA sequence that restored normal gene function lost in hemophilia.

By precisely targeting a specific site along a chromosome, ZFNs have an advantage over conventional gene therapy techniques that may randomly deliver a replacement gene into an unfavorable location, bypassing normal biological regulatory components controlling the gene. This imprecise targeting carries a risk of "insertional mutagenesis," in which the corrective gene causes an unexpected alteration, such as triggering leukemia.

In hemophilia, an inherited single-gene mutation impairs a patient's ability to produce a blood-clotting protein, leading to spontaneous, sometimes life-threatening bleeding episodes. The two major forms of the disease, which occurs almost solely in males, are hemophilia A and hemophilia B, caused respectively by a lack of clotting factor VIII and clotting factor IX. Patients are treated with frequent infusions of clotting proteins, which are expensive and sometimes stimulate the body to produce antibodies that negate the benefits of treatment.

In the current study, the researchers used genetic engineering to produce mice with hemophilia B, modeling the disease in people. Before treatment, the mice had no detectable levels of clotting factor IX.

Previous studies by other researchers had shown that ZFNs could accomplish genome editing in cultured stem cells that were then injected into mice to treat sickle cell disease. However, this ex vivo approach is not feasible for many human genetic diseases, which affect whole organ systems. Therefore the current study tested whether genome editing was effective when directly performed in vivo (in a living animal).

High and colleagues designed two versions of a vector, or gene delivery vehicle, using adeno-associated virus (AAV). One AAV vector carried ZFNs to perform the editing, the other delivered a correctly functioning version of the F9 gene. Because different mutations in the same gene may cause hemophilia, the process replaced seven different coding sequences, covering 95 percent of the disease-carrying mutations in hemophilia B.

The researchers injected mice with the gene therapy vector, which was designed to travel to the liver -- where clotting factors are produced. The mice that received the ZFN/gene combination then produced enough clotting factor to reduce blood clotting times to nearly normal levels. Control mice receiving vectors lacking the ZFNs or the F9 minigene had no significant improvements in circulating factor or in clotting times.

The improvements persisted over the eight months of the study, and showed no toxic effects on growth, weight gain or liver function, clues that the treatment was well-tolerated.

"We established a proof of concept that we can perform genome editing in vivo, to produce stable and clinically meaningful results," said High. "We need to perform further studies to translate this finding into safe, effective treatments for hemophilia and other single-gene diseases in humans, but this is a promising strategy for gene therapy." She continued, "The clinical translation of genetic therapies from mouse models to humans has been a lengthy process, nearly two decades, but we are now seeing positive results in a range of diseases from inherited retinal disorders to hemophilia. In vivo genome editing will require time to mature as a therapeutic, but it represents the next goal in the development of genetic therapies."

Support for this work came from the National Institutes of Health and the Howard Hughes Medical Institute. High's co-authors were from The Children's Hospital of Philadelphia, the University of Pennsylvania, and Sangamo BioSciences, Inc. of Richmond, Calif

Premature Aging Caused by Some HIV Drugs, Study Shows

Science Daily  — A class of anti-retroviral drugs commonly used to treat HIV, particularly in Africa and low income countries, can cause premature aging, according to research published June 26 in the journal Nature Genetics. The study shows that the drugs damage DNA in the patient's mitochondria -- the 'batteries' which power their cells.

Nucleoside analogue reverse-transcriptase inhibitors (NRTIs) -- of which the most well known is Zidovudine, also known as AZT -- were the first class of drug developed to treat HIV. They were a major breakthrough in the treatment of the disease, greatly extending lifespan and leading the condition to be seen as a chronic, rather than terminal, condition.The findings may explain why HIV-infected people treated with antiretroviral drugs sometimes show advanced signs of frailty and age-associated diseases such as cardiovascular disease and dementia at an early age.In high income countries, such as Europe and North America, the older NRTIs are used less commonly now due to concerns over toxicity and side-effects when taken over a long period of time. However, as they are now off-licence and hence relatively cheap, the drugs have proved to be an important lifeline for people infected with HIV in Africa and low income countries.Professor Patrick Chinnery, a Wellcome Senior Fellow in Clinical Science from the Institute of Genetic Medicine at Newcastle University, says: "HIV clinics were seeing patients who had otherwise been successfully treated but who showed signs of being much older than their years. This was a real mystery. But colleagues recognised many similarities with patients affected by mitochondrial diseases -- conditions that affect energy production in our cells -- and referred them to our clinic."Mitochondria are the 'batteries' in our cells which provide them with the energy to carry out their functions. During natural human aging, these mitochondria acquire mutations, though it is unclear whether these mutations are a cause of aging or a consequence.In an attempt to understand what was happening at a cellular level, Professor Chinnery and colleagues studied muscle cells from HIV-infected adults, some of whom had previously been given NRTIs.

The researchers found that patients who had been treated with NRTIs -- even as long ago as a decade previously -- had damaged mitochondria which resembled that of a healthy aged person.

"The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors," explains Professor Chinnery. "We believe that these HIV drugs accelerate the rate at which these errors build up. So over the space of, say, ten years, a person's mitochondrial DNA may have accumulated the same amount of errors as a person who has naturally aged twenty or thirty years. What is surprising, though, is that patients who came off the medication many years ago may still be vulnerable to these changes."

Co-author and HIV specialist, Dr Brendan Payne, a Medical Research Council fellow from the Department of Infection and Tropical Medicine at the Royal Victoria Infirmary, Newcastle, believes that despite the side effects caused by NRTIs, they are still important drugs and the risks are relative.

"These drugs may not be perfect, but we must remember that when they were introduced they gave people an extra ten or twenty years when they would otherwise have died," he says. "In Africa, where the HIV epidemic has hit hardest and where more expensive medications are not an option, they are an absolute necessity."

Professor Chinnery and colleagues are now looking at ways to repair or stall some of the damage caused by the medication and believe that focusing on exercise -- which appears to have a beneficial effect on patients with mitochondrial diseases -- may help.

The study was funded by the Medical Research Council, the British Infection Society, the Newcastle Healthcare Charity, the UK NIHR Biomedical Research Centre for Aging and Age-related Disease and the Wellcome Trust