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Superoxide May Help Birds Navigate

The molecule superoxide, normally thought of as toxic and cell-damaging, may be crucial to a migrating bird’s sense of direction according to researchers from the University of Illinois and Goethe University. The researchers proposed that superoxide interacts with a molecule called cryptochrome to help provide birds with a sense of geomagnetism. Cryptochrome is a blue-light photoreceptor found in plants and in the eyes of birds and other animals, including humans. The senior author of the current research, Dr. Klaus Schulten, was the first to propose (in 2000) that cryptochrome was a key component of birds' geomagnetic sense, a proposal that was later corroborated by experimental evidence. Dr. Schulten made this prediction after he and his colleagues discovered that magnetic fields can influence chemical reactions if the reactions occur quickly enough to be governed by pure quantum mechanics. “Prior to our work, it was thought that this was impossible because magnetic fields interact so weakly with molecules," he said. The rapid chemical reactions involve electron transfers, Dr. Schulten said, "which result in freely tumbling spins of electrons. These spins behave like an axial compass. Changes in the electromagnetic field, such as those experienced by a bird changing direction in flight, appear to alter this biochemical compass in the eye, allowing the bird to see how its direction corresponds to north or south." Dr. Schulten noted that “other researchers had found that cryptochrome, acting through its own molecular spins, recruits a reaction partner that operates at so-called zero spin. They suggested that molecular oxygen is that partner.

Sagebrush Recognizes Self, Warns of Danger

Researchers have shown that sagebrush plants that receive volatile cues from genetically identical cuttings accumulate less natural damage (e.g., from grasshoppers) than do plants receiving cues from non-self cuttings. Based on their results, the authors, Dr. Richard Karban of the University of California-Davis and Dr. Kaori Shiojiri of Kyoto University, concluded that volatile communication is required to coordinate systemic processes such as induced resistance, and that plants respond more effectively to self than non-self cues. They noted that this self/non-self discrimination did not require physical contact and suggested that it is a necessary first step towards possible kin recognition and kin selection. In earlier research, Dr. Karban had found that “volatile cues are required for communication among branches within an individual sagebrush plant. This observation suggests that communication between individuals may be a by-product of a volatile communication system that allows plants to integrate their own systemic physiological processes.” The current research appears in the June issue of Ecology Letters. [UC Davis press release] [Ecologoy Letters abstract]

Scat DNA Testing Permits Accurate Counting of Tigers

A study describing the successful application of fecal DNA testing to the accurate counting of tigers has been published by scientists from the Wildlife Conservation Society (WCS) and collaborating institutions. By testing the DNA in individual samples of tiger scat in a particular area, the scientists were able to obtain unique DNA signatures for particular tigers and use these data in computer models to estimate the tiger population in the area. "This study is a breakthrough in the science of counting tiger numbers, which is a key yardstick for measuring conservation success," said noted tiger scientist Dr. Ullas Karanth of the WCS, and an author of the study. "The technique will allow researchers to establish baseline numbers on tiger populations in places where they have never been able to accurately count them before." The study took place in India's Bandipur Reserve in Karnataka, a long-term WCS research site in the Western Ghats that supports a high abundance of tigers. Researchers collected 58 tiger scats following rigorous protocols, then identified individual animals through their DNA. Tiger populations were then estimated using sophisticated computer models. These results were validated against camera trap data, where individual tigers are photographed automatically and identified by their unique stripe patterns. Camera-trapping is considered the gold standard in tiger population estimation, but is impractical in several areas where tiger densities are low or field conditions too rugged. "We see genetic sampling as a valuable additional tool for estimating tiger abundance in places like the Russian Far East, Sunderban mangrove swamps, and dense rainforests of Southeast Asia where camera trapping might be impractical due to various environmental and logistical constraints," said Dr. Karanth.

New Approach to Anti-Anxiety Medication

Benzodiazepines (e.g., Valium) are fast-acting, effective anti-anxiety agents. However, they have side effects (sedation, tolerance development, and withdrawal symptoms) that can make them problematic for long-term use. Consequently, there is a need for medications that retain the rapid anti-anxiety effects of benzodiazepines, but lack their unfavorable side effects. Researchers have recently shown that a molecule called XBD173 might fill this bill. XBD173 is known to bind to the translocator protein (18 kD), formerly known as peripheral or mitochondrial benzodiazepine receptor. This translocator protein is believed to favor the production of certain neurosteroids that are potent positive modulators of GABA type A receptors that mediate the effects of the inhibitory neurotransmitter GABA in the mammalian nervous system. These neurosteroids produce pronounced anti-anxiety effects in animal models and their levels are reduced during panic attacks in humans with panic disorder. In the current work, the authors showed that XBD173 enhanced GABAergic neurotransmission and counteracted induced panic attacks in rodents, in the absence of sedation and tolerance development. XBD173 also exerted anti-panic activity in humans, and, in contrast to benzodiazepines, did not cause sedation and withdrawal symptoms. Therefore, the authors concluded that ligands of the translocator protein (18 kD) are promising candidates for fast-acting anti-anxiety drugs with less severe side effects than benzodiazepines. This work was published online on June 18 in Science Express. [Science abstract]

Merkel Cells Linked to Light-Touch Sensation

Scientists have demonstrated that the sensation of light touch, such as that which allows one to feel the fine texture of materials or lets the blind read Braille, depends on the activity of the long-mysterious Merkel cells, which are present in high numbers on our fingertips and lips. These cells form complexes with nerve fibers, and while these complexes are known to respond to light touches to the skin, the specific role of the Merkel cells has been controversial. The topic has been debated for more than 100 years, since the cells were first described in 1875 by German scientist Friedrich Merkel, who himself first proposed the link with light-touch sensation. The key to the current conclusive demonstration of the link was work with a transcription factor gene called Atoh1. When this gene was conditionally knocked out in the body skin and foot pads of mice, the resulting knockouts had no Merkel cells in these areas. The skin of these knockout mice did not show the same neurological responses to light touch that normal skin does, suggesting that Merkel cells enable their connecting neurons to resolve fine spatial details, the authors reported. "To our knowledge, Atoh1 is the first gene shown to be necessary for the specification of Merkel cells," the authors noted. "We don't know how any mammalian touch receptor works," added Dr. Ellen Lumpkin, of the Baylor College of Medicine, and a senior author on the report. "What genes allow them to function as light or painful touch receptors? This project gives us the experimental handle with which to start to dissect the genetic basis of touch." Among the other authors on the report were Dr. Huda Zoghbi and Dr. Stephen Maricich. This work was reported in the June 19 issue of Science. [Press release]

Bacteria Can Anticipate Events and Prepare for Them

Through evolution, bacteria and other microorganisms can “learn” to anticipate a future environmental event and prepare for it, according to recent research from the Weizmann Institute, Tel Aviv University, and Harvard Medical School. The research findings showed that certain microorganisms' genetic networks are hard-wired to "foresee" what comes next in a normally predictable sequence of events and to begin responding to the new state of affairs before its onset. This is analogous to classical Pavlovian conditioning. As an example, E. coli bacteria, which normally cruise harmlessly down the human digestive tract, encounter a number of different environments on their way. In particular, they find that one type of sugar, lactose, is invariably followed by a second sugar, maltose, soon afterward. The research team checked the bacterium's genetic response to lactose, and found that, in addition to the genes that enable it to digest lactose, the gene network for utilizing maltose was partially activated. When the researchers switched the order of the sugars, giving the bacteria maltose first, there was no corresponding activation of lactose genes, implying that bacteria have naturally "learned" to get ready for maltose following lactose. In addition, when E. coli were raised in an environment containing the first sugar, lactose, but not the follow-up with maltose, the bacteria evolved, after several months, to stop activating their maltose genes at the taste of lactose, only turning them on when maltose was actually available. Senior author Dr. Yitzhak Pilpel and his team believe that genetic conditioned responses may be a widespread means of evolutionary adaptation that enhances survival in many organisms, and may also take place in the cells of higher organisms, including humans.

Triumphant Return of the Large Blue Butterfly

An upcoming report in Science celebrates the 25-year effort to restore the large blue butterfly (Maculinea arion) in the UK, where it reached extinction in 1979. Meticulous research showed that the extinction was caused by a subtle change in habitat that disrupted the unusual life cycle of this spectacular butterfly. Previously, the extinction had been attributed to the work of overzealous collectors. Adult M. arion females lay their eggs on thyme flowers in the summer. After hatching, the caterpillars stay very small and many eventually fall to the ground. They secrete chemicals that attract red ants and fool them into thinking the caterpillars are ant grubs. The ants then carry the tiny caterpillars into their underground nests. In most cases, only caterpillars that have landed in the nest of one particular ant species, Myrmica sabuleti, will survive to adulthood. The caterpillars' secretions are a sufficiently close match to those of M. sabuleti grubs that the ants never discover that they have been duped, and instead continue to protect the caterpillars for 10 months even though they are feeding on the ants' own brood. In early June, the caterpillars form a chrysalis near the colony entrance and then emerge to crawl aboveground two weeks later as butterflies. Using laboriously collected field data, lead author Dr. Jeremy Thomas and his coauthors explored the possible factors that could be causing the butterflies’ decline. They realized that the grass in the butterflies' habitat had grown too long, as farmers had gradually stopped grazing their livestock on these hillsides and a viral infection had killed many of the wild rabbits in the 1950s. The soil on these overgrown grasslands was therefore too cool to support adequate numbers of M. sabuleti ants.

Blood Test Detects Marker for Human Aging

Levels of a well-known tumor suppressor protein, p16INK4a, increase sharply with age in most mammalian tissues, and these increases contribute to an age-induced functional decline of certain self-renewing compartments. Researchers at the University of North Carolina have now shown that p16INK4 can be detected in peripheral blood T-lymphocytes (PBTL) and that its expression levels are strongly correlated with an individual's chronological age and, in fact, increase exponentially with age. In addition, increased expression levels of p16INK4a were independently associated with certain behaviors (tobacco use and physical inactivity) known to accelerate human aging. p16INK4a levels were also associated with a biomarker of human frailty. The authors said that the data suggest that p16INK4 expression in PBTL is an easily measured, peripheral blood biomarker of molecular age. "This is a major step toward a practical tool to clinically determine a person's actual molecular, as opposed to just their chronological, age," said Dr. Norman Sharpless, the senior author of the study. "Although we don't know whether this test is a good reflection of cellular age in all types of human tissues, we believe it is a first step toward a better understanding of issues like the suitability of organs for transplantation, how well patients are likely to recover after surgery, or the future toxicity of chemotherapy for cancer patients," he added. This work was published online ahead of pring in Aging Cell. [Press release] [Aging Cell abstract]

Spectroscopy Technology May Detect Early Alzheimer’s

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]

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