Researchers have shown that the use of near-infrared (NIR) biospectroscopy to detect indicators of changes in oxidative stress levels in blood plasma may be a useful approach to the early identification of Alzheimer’s disease (AD). The procedure is minimally invasive, rapid, and relatively inexpensive. There is currently no accepted laboratory test for diagnosing AD. Diagnosis is based solely on a patient’s medical history and neurological examination, is labor-intensive and expensive, and is often inconclusive in early stages of the illness. The availability of a biologic marker (in this case, a chemical signature of indicators of oxidative stress levels) that reliably differentiates AD from normal aging and other dementing conditions would represent a major achievement in the management of this common neurodegenerative disorder. In differentiating AD patients from the normal elderly control group, the NIR biospectroscopy approach achieved a sensitivity of 80% and specificity of 77%. “These results demonstrate the potential for NIR biospectroscopy to differentiate mild, and possibly pre-clinical, Alzheimer’s disease from normal aging with high accuracy,” said Dr. Hyman Schipper, senior author of the study. “We are very encouraged by these data and look forward to testing this potential diagnostic tool in larger-scale studies.” This work was published in the June issue of the Journal of Alzheimer’s Disease. [Press release 1] [Press release 2] [June issue of JAD]
Targeted Nanoparticles May Improve on Whole-Body Chemotherapy
Researchers using nanoparticles with attached molecules of folic acid and containing the widely-used anti-cancer drug taxol have shown that it may be possible to target cancer cells specifically and thus avoid the multiple side effects that are seen with toxic whole-body chemotherapies such as taxol. The specificity is built upon cancer cells’ high consumption of folic acid. In addition to taxol, the nanoparticles contain a fluorescent dye and an iron oxide magnetic core. Thus, the location of the nanoparticles within cells and the body can be detected with optical imaging and magnetic resonance imaging. This allows the physician to see how the tumor is responding to the treatment. The nanoparticles can also be engineered without the drug and used as imaging (contrast) agents for cancer. If there is no cancer, the biodegradable nanoparticles will not bind to the tissue and will be eliminated by the liver. The iron oxide core will be utilized as regular iron in the body. “What’s unique about our work is that the nanoparticle has a dual role, as a diagnostic and therapeutic agent, in a biodegradable and biocompatible vehicle,” said Dr. J. Manuel Perez, senior author of the report. This research, by scientists at the University of Central Florida and the Memorial Sloan-Kettering Cancer Center, was published in the journal Small. [Press release] [Small abstract]
Electronic Nose May Sniff Out Early Kidney Disease
Scientists may have discovered an ingenious way to detect chronic renal failure (CRF) at its earliest and most treatable stages. The method would involve the electronic detection of volatile molecules found in the breath of those with developing kidney disease, but not in the breath of those without kidney disease. The promise of this approach was supported by experiments in rats where an “electronic nose” was used to detect 27 volatile organic compounds that appear in the breath of rats with no kidney function, but not in the breath of rats with normal kidney function. The “electronic nose” is based on a technology in which a semi-conductive random network of single-walled carbon nanotubes and insulating nonpolymeric organic materials provides arrays of chemically sensitive resistive vapor detectors. The results presented in this study raise expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, the researchers said, noting that the tests could detect patients with early disease, when it is possible to control blood pressure and protein intake to slow disease progression. The researchers pointed out that the blood and urine tests now used to diagnose CRF can be inaccurate and may come out “normal” even when patients have lost 75 percent of their kidney function. The most reliable test, a kidney biopsy, is invasive and may result in infections and bleeding. Doctors have long hoped for better tests for early detection of kidney disease. The current research was reported in the May 26 issue of the American Chemical Society journal ACS Nano. [ACS Nano abstract]
Microchannel Device Could Trap Cancer Cells
Scientists at Northwestern University have developed a novel method that can be used to separate metastatic cancer cells from normal cells. They have proposed that the method could be used to create a “cancer trap” using implantable and biodegradable materials. A device they have currently developed illustrates the method. The device takes advantage of a physical principle called ratcheting and is a very tiny system of microfluidic channels for cell locomotion. Each channel is less than a tenth of a millimeter wide. Asymmetric obstacles inside these channels direct cell movement along a preferred direction. To sort metastatic cancer cells from normal cells, the scientists took advantage of the cells’ different shapes and mobility characteristics. Migrating cancer cells tend to be rounder and broader, while normal epithelial cells are long and thin with long protrusions on the ends. The researchers designed a channel with “spikes” (rachets) coming out at 45-degree angles from the walls, alternating on opposite sides of the channel. This pattern funnels cancer cells in one direction, while at the same time directing normal cells in the opposite direction. The researchers showed that a device with a number of these channels leading to a central reservoir, like spokes on a wheel, worked just as well at separating cancer and non-cancerous cells. A stack of these radially arranged ratchet channels could be used to create a “cancer trap,” the researches suggested. “When implanted next to a tumor, the particles [stack of rachet channels] would guide cancer cells, but not normal cells, inward to the reservoir, where they would be trapped,” said Dr. Bartosz Grzybowski, the paper’s senior author.
Huntington Disease Clue Discovered
Researchers have demonstrated that mutated huntingtin protein, but not normal huntingtin, activates a neuron-specific protein (JNK3) which inhibits fast axonal transport, a system used to shuttle proteins from the nerve cell body, where they are made, to the synaptic terminals, where they are needed. This discovery might help explain the curious nervous system specificity of Huntington disease, even though the huntingtin protein is expressed in other parts of the body. “Inhibition of neuronal transport is enough to explain what is happening in Huntington’s,” asserted Dr. Scott Brady, senior author of the report. Loss of delivery of materials to the synaptic terminals results in loss of transmission of signals from the neuron. Loss of signal transmission causes the neurons to begin to die back, leading to reduced transmissions, more dying back, and eventual neuronal cell death. This mechanism might also explain the late onset of the disease, Dr. Brady said. Activation of JNK3 reduces transport, but does not eliminate it. Young neurons have a robust transport system, but transport gradually declines with age. “If you take a hit when you’re very young, you still are making more and transporting more proteins in each neuron than you need,” Dr. Brady said. “But as you get older and older, the neuron produces and transports less. Each hit diminishes the system further. Eventually, the neuron falls below the threshold needed to maintain cell health.” This work was reported online on June 14 in Nature Neuroscience. [Press release] [Nature Neuroscience article]
Tiny Bacterium in Ancient Ice May Hold Clues to Extraterrestrial Life
A novel species of ultramicrobacterium has been isolated from a 120,000-year-old, 3042-meter-deep Greenland glacier ice core by researchers at Pennsylvania State University. The scientists have provisionally called the new species Herminiimonas glaciei and suggested that it may hold clues to possible life forms on other planets. “These extremely cold environments are the best analogues of possible extraterrestrial habitats,” said Dr. Jennifer Loveland-Curtze, lead author of the report. “The exceptionally low temperatures can preserve cells and nucleic acids for even millions of years. H. glaciei is one of just a handful of officially described ultra-small species and the only one so far from the Greenland ice sheet; studying these bacteria can provide insights into how cells can survive and even grow under extremely harsh conditions, such as temperatures down to -56˚C, little oxygen, low nutrients, high pressure, and limited space.” The small size of H. glaciei probably helped it to survive in the liquid veins among ice crystals and the thin liquid film on their surfaces. Small cell size is considered to be advantageous for more efficient nutrient uptake, protection against predators, and occupation of micro-niches, and it has been shown that ultramicrobacteria are dominant in many soil and marine environments. This report was published in the June issue of the International Journal of Systematic and Evolutionary Microbiology. [Press release] [IJSEM abstract]
New Target for Treatment of Macular Degeneration
A new target for the diagnosis and treatment of age-related macular degeneration (AMD) has been identified by an international scientific team. The researchers demonstrated that blocking the activity of a protein called CCR3 can reduce the abnormal blood vessel growth that leads to macular degeneration. Furthermore, targeting this new protein may prove to be safer and more effective than the current treatment for the disease, which is directed at a protein called VEGF. The researchers detected the presence of CCR3 in eye tissue from humans with AMD, but not in eye tissue from individuals of similar age who did not have the disease. When CCR3 activity was blocked in model systems, either with drugs or through genetic engineering, the researchers saw a decrease in the generation of abnormal blood vessels. Drugs targeting CCR3 were significantly more effective than those targeting VEGF, implying that targeting of CCR3 could represent a new therapy for the two-thirds of patients who do not respond to current treatment. AMD affects 30 to 50 million people around the world, and that number is expected to double in the next decade as the “baby boomer” generation ages. The discovery of the role of CCR3 may enable physicians to catch the disease at its earliest stages, before blood vessels have fully infiltrated and destroyed the central portion of the retina, an area known as the macula, to cause vision loss. “An exciting implication of this study was that the CCR3 protein could be detected in early abnormal blood vessel growth, giving us the opportunity to prevent structural damage to the retina and preserve vision,” said Dr. Mary Elizabeth Hartnett, one of the study authors.
Key Gene Identified in Deadliest Breast Cancer
Scientists have identified a key gene in the pathogenesis of inflammatory breast cancer (IBC), which is the most lethal form of primary breast cancer, often striking women in the prime of life and causing death within 18 to 24 months. The disease-related gene is eIF4GI, a translation initiation factor. Researchers found that this gene is overexpressed in the majority of IBC patients and enables the formation of small, highly mobile clusters of cells (tumor emboli) that are responsible for the rapid metastasis that makes IBC such an effective killer. “The tragedy of IBC is that it is often misdiagnosed and misclassified,” said Dr. Robert Schneider, senior author of the report. “Rather than presenting as a “typical” lump, IBC looks like an inflammation of the breast and is frequently mistaken for an infection. Physicians often prescribe antibiotics, losing valuable time for treating this fast-moving killer.” He noted that while IBC accounts for just several percent of all breast cancer cases, it takes a disproportionately high toll in mortality and has an incidence that is 50 percent higher in African American women. He added that there has been little progress in treating IBC over the past two decades, and there are no drugs specifically for this form of cancer. The new findings on eIF4GI could lead to the identification of new approaches, therapies, and a new class of drugs to target and treat IBC. This would be a critical development in the fight against IBC, which responds poorly to chemotherapy, radiation, or any other current treatments for breast cancer, Dr. Schneider noted. This research, conducted by scientists at New York University and George Washington University, was reported online in Nature Cell Biology on June 14.
Potential Target for Gout Treatment Is Identified
Researchers at Johns Hopkins and the University of Texas-Houston have shown that a gene, located in a chromosome 4 region statistically associated with gout, is functionally associated with the disease. The gene is ABCG2 (ATP-binding cassette, subfamily G, 2) and the researchers showed that it is a previously unidentified urate efflux transporter. The researchers further showed that the native ABCG2 protein is located in the brush border membrane of proximal kidney tubule cells where it mediates renal urate secretion. Introduction of a common SNP mutation into the gene resulted in 53% reduced urate transport rates in an experimental model. Data from a population-based study supports the fact that this particular SNP is a causal variant in the gout-associated region on chromosome 4. The authors also said that their data indicates that this common casual variant is responsible for at least 10 percent of all gout cases in whites. Noting that gout affects approximately 3 million people in the United States and that present treatments are often insufficient, the researchers suggested that ABCG2 represents an attractive drug target. This work was published online on June 8 in PNAS. Gout is a disease hallmarked by elevated levels of uric acid in the bloodstream. In this condition, crystals of monosodium urate, a uric acid salt, are deposited on the articular cartilage of joints, tendons, and surrounding tissues. The disease is marked by transient painful attacks of acute arthritis initiated by crystallization of urates within and about the joints, and can eventually lead to chronic gouty arthritis and the deposition of masses of urates in joints and other sites. [PNAS abstract]
Unique “Snow Roots” Found in Mountain Plant
In a remote region of the Russian Caucasus Mountains, a previously unknown and entirely unique form of plant root has been discovered. The root belongs to the small alpine plant Corydalis conorhiza and, unlike normal roots that grow into the soil, these roots extend upward, against gravity, through layers of snow. Given this novel behavior, the scientists have termed them “snow roots.” “This is a completely new discovery,” said Dr. Johannes Cornelissen, the senior author of the study. “Snow roots are thus far unknown and a spectacular evolutionary phenomenon.” The team made its discovery high up in the Caucasus Mountains, where the ground remains covered in snow for much of the year. As the snow melted at the height of summer, the scientists noted that C. conorhiza plants were surrounded by a network of above-ground roots, stretching uphill and to each side for around 50 cm. During the spring and perhaps also winter, these roots extend into the surrounding snow and during the summer they die and decompose, which may explain how they had remained undiscovered. C. conorhiza also possesses normal roots which anchor the plant to the ground and take up nutrients such as phosphorus and nitrogen. Cornelissen’s team hypothesized that the additional snow roots allow C. conorhiza to take nitrogen directly from the snow. Many mountain plants take up nitrogen from melted snow soaking into the ground only after snow melt. However, an impenetrable ice crust prevents C. conorhiza from doing this, and therefore the plant is forced to depend upon the snow roots. Further study confirmed that the snow roots are anatomically very different from normal soil roots, and that they are specifically adapted for the fast uptake and transport of nitrogen. This work was published online on June 4 in Ecology Letters.