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May 29th, 2009

Reason for Long, Prime-Numbered Life Cycles in Cicadas

Scientists may have discovered the reason for the long, prime-numbered life cycles (13 and 17 years) in periodical cicadas. A mathematical model used to predict the life cycles of these insects yielded these prime-numbered periods only when the so-called Allee effect was considered. This effect is a general model used to predict evolution that links large numbers of organisms to high survival rates. These results suggest that natural selection during times of low population size has favored the evolution of non-overlapping broods; broods emerging at the same time ultimately drive both populations to extinction. With 13- and 17-year life cycles, two neighboring broods of cicadas co-emerge approximately once every 221 years (13 times 17), greatly limiting the accompanying population crash. As cicadas depend on their overwhelming numbers to ward off predators, a smaller cicada population would result in increased mortality. This work was published online on May 18 in PNAS. [PNAS abstract]

May 28th

Mice with Human Speech Gene Show Suggestive Changes

Mice engineered to carry the humanized version of the FOXP2 gene show changes in brain circuits that have previously been linked to human speech, and the engineered mouse pups show qualitative differences in the ultrasonic vocalizations they use when placed outside the comfort of their mothers' nests. The FOXP2 gene has previously been putatively associated with development of speech in humans. One important difference between humans and chimpanzees are two amino acid substitutions in FOXP2. Those changes became fixed after the human lineage split from chimpanzees and earlier studies have yielded evidence that the gene underwent positive selection. That evolutionary change is thought to reflect selection for some important aspects of speech and language. "Currently, one can only speculate about the role these effects may have played during human evolution," the researchers wrote. "However, since patients that carry one nonfunctional FOXP2 allele show impairments in the timing and sequencing of orofacial movements, one possibility is that the amino acid substitutions in FOXP2 contributed to an increased fine-tuning of motor control necessary for articulation, i.e., the unique human capacity to learn and coordinate the muscle movements in lungs, larynx, tongue, and lips that are necessary for speech. We are confident that concerted studies of mice, humans, and other primates will eventually clarify if this is the case." The authors cautioned that not enough is known about mouse communication to yet read too much into what the current results might mean. The senior author of the report was Dr. Svante Paabo. The work was published in the May 29 issue of Cell.

May 27th

Dystrophin Substitute Shows Promise in Mouse Model of Muscular Dystrophy

Researchers have shown that use of a dystrophin-like molecule with a cell-penetrating tag can effectively repair weakened muscle in a mouse model of Duchenne muscular dystrophy (DMD). Muscular dystrophy causes the muscles in the body to progressively weaken. DMD is the most common and most severe form of childhood muscular dystrophy. About one of 3,500 boys is born with the crippling disease. Symptoms usually begin in children who are 2 to 3 years-old, most are in a wheelchair by age 12, and many who have the disease pass away by their late teens to early 20s. Current treatment, limited to corticosteroids, is minimally effective and can cause serious side effects. DMD is caused by mutation in the gene for the dystrophin protein, which is an important structural component within muscle tissue. In this work, the researchers used the dystrophin-like molecule utrophin, attached to a cell-penetrating tag called TAT. "This unique approach can replace the missing protein without the complexities of gene replacement or stem cell approaches," said Dr. James Ervasti, principal investigator of the study. This new method would not be a cure for muscular dystrophy. Rather, it would be a therapy most likely administered on a regular basis. Dr. Ervasti is hopeful that the therapy can move into human clinical trials within three years. This work was published in the May 26 edition of PLoS Medicine. [Press release] [PLoS Medicine article]

Hormone Addition May Solve Pod Shattering Problem in Oilseed Rape

Experiments in the related plant Arabidopsis suggest that artificial production of the hormone auxin in a specific region of the plant can prevent pod shattering and seed loss in brassica plants such as oilseed rape. Oilseed rape is grown for its tiny black oil-containing seeds, prized for cooking oil and margarines low in saturated fat, and increasingly for biodiesel. The meal that remains after oil extraction is also used as a high protein animal feed. Just before harvest, oilseed rape pods are prone to shatter, causing a 10-25% loss of seeds and up to 70% in some cases. Brassica plants normally disperse their seeds by a pod-shattering mechanism. Although this mechanism is an advantage in nature, it is one of the biggest problems in farming oilseed rape. As well as losing valuable seeds, it results in runaway 'volunteer' seedlings that contaminate the next crop in the rotation cycle. If rape seeds are harvested early to circumvent the problem, immature seeds may be collected which are of an inferior quality. This work is published in the May 28 issue of Nature. [Press release] [Nature abstract]

May 26th

Maturation Chemical May Fight Parasitic Worm Infections

A chemical that causes certain parasitic worms, including hookworms, to pass from the infective larval stage to the feeding larval stage may prove useful in reducing the risk posed by these worms throughout the world. The chemical is dafachronic acid and it sends the necessary signals for the worms to mature from the stage in which they infect a host to the stage in which they start feeding on the host, which is what makes the host sick. In this study, researchers treated hookworm parasites pharmacologically at the infective larval stage with dafachronic acid, causing them to pass into the feeding larval stage outside a host, where they had no food supply and died. Treatment of other infectious species had similar effects. Dr. David Mangelsdorf, the senior author of the study, said that the next step in the research is to screen large libraries of chemicals to search for compounds that behave like dafachronic acid and that could possibly be developed into pesticides that could be spread in high-infection areas. Many infectious nematode larvae live in the soil, often in areas where proper sanitation is lacking. According to the World Health Organization, parasitic nematodes infect about 2 billion people worldwide and severely sicken some 300 million, at least 50 percent of whom are school-age children. This report on dafachronic acid will be available online in PNAS and in an upcoming article in the journal. [Press release]

Folic Acid Consumption May Reduce Risk of Early Preterm Births

Folic acid consumption for a year or more before conception is associated with a 50%–70% decrease in early (but not late) spontaneous preterm births and the longer a woman takes folic acid supplements before becoming pregnant, the lower her risk of a preterm birth. These are the conclusions of researchers reporting recently in PLoS Medicine. The findings are particularly significant because premature babies (born before 37 weeks of completed pregnancy) are more likely to die than full-term babies and many have short- and/or long-term health problems. The severity of these health problems depends on the degree of prematurity—preterm babies born between 34 and 36 weeks of pregnancy rarely develop severe disabilities, but a quarter of babies born before 28 weeks of pregnancy develop serious lasting disabilities and half have learning and behavioral problems. The researchers noted the folic acid consumption itself may not be the causative factor as it may be a marker for a healthier lifestyle in general. Nevertheless, they said, the results suggest that long-term folic acid supplementation before conception is worth investigating further as a potential way to prevent preterm births. [PLoS Medicine article]

May 23rd

Specific Extra Phosphate on Tau Protein Crucial to Alzheimer’s Disease

Scientists have shown that a particular one of the multiple extra phosphates on the abnormal tau protein in Alzheimer’s disease appears to be a principal cause of the disease. "The impact of this study is twofold," said Dr. Hemant Paudel, the senior author of the study. "We can now do brain imaging at the earliest stages of the disease. We don't have to look for many different tau phosphates, just this single phosphate. The possibility of early diagnosis now exists. Second, the enzyme which puts this phosphate on the tau can be targeted by drugs, so therapies can be developed. This discovery gives us, for the first time, a clear direction towards the early diagnosis and treatment of Alzheimer's." Several years ago, it was discovered that tau proteins in normal brains contain only three to four attached phosphates, while abnormal tau proteins in Alzheimer's patients have anywhere from 21 to 25 additional phosphates. Here, Dr. Paudel and his team have shown that the addition of a single phosphate to the serine 202 amino acid within the tau protein is a likely principal culprit in Alzheimer's disease. This work was published in the May 15 issue of the Journal of Biological Chemistry. [Press release] [JBC abstract]

May 22nd

Increased Flu Susceptibility Associated with Arsenic in Well Water—Possible Mexico Connection

Susceptibility to influenza A (H1N1) infection is significantly increased by exposure to low levels of arsenic commonly encountered in contaminated well water. This is the conclusion of researchers who studied the effects of low levels of arsenic in the drinking water of mice. The initial immune response of these mice to influenza A (H1N1) was quite feeble and when the response was made it was too robust and too late. "There was a massive infiltration of immune cells to the lungs and a massive inflammatory response, which led to bleeding and damage in the lung," said Dr. Joshua Hamilton, an author of the study. Morbidity over the course of the infection was significantly higher for the arsenic-exposed mice than for the normal mice. The U.S. Environmental Protection Agency considers 10 parts per billion (ppb) arsenic in drinking water "safe," yet concentrations of 100 ppb and higher are commonly found in well water in regions where arsenic is geologically abundant, including upper New England (Massachusetts, New Hampshire, Maine), Florida, and large parts of the Upper Midwest, the Southwest, and the Rocky Mountains. Respiratory infections with influenza A virus are a worldwide health concern and are responsible for 36,000 deaths annually. The recent outbreak of the influenza A H1N1 substrain ("swine flu"), which is the same virus used in this study, has, to date, killed 72 people in Mexico and 6 in the United States. "One thing that did strike us, when we heard about the recent H1N1 outbreak, is Mexico has large areas of very high arsenic in their well water, including the areas where the flu first cropped up. We don't know that the Mexicans who got the flu were drinking high levels of arsenic, but it's an intriguing notion that this may have contributed," Dr. Hamilton said.

May 21st

Cancer Drugs May Be Useful in Treating Alcoholism

Discovery and functional analysis of a mutant gene (“happyhour”) in fruit flies has led researchers to suggest that certain existing cancer drugs may be effective in treating alcoholism. The mutant “happyhour” gene increases the resistance of the fruit flies to the sedative effects of alcohol. This is similar to the situation in humans where such increased resistance is thought to contribute to the development of alcohol addiction. Studies have indicated that an individual's sensitivity to alcohol intoxication acts as a predictor of future alcoholism, with a link between lower initial response and increased risk of addiction. Here, the researchers showed that the epidermal growth factor (EGF) signaling pathway regulates the fruit fly’s sensitivity to alcohol, and that the normal “happyhour” protein functions as an inhibitor of this pathway. The EGF pathway is best known for its role in cancer, and drugs designed to inhibit the EGF receptor (EGFR), including erlotinib (trade name Tarceva) and gefitinib (trade name Iressa), are FDA-approved for the treatment of non-small cell lung cancer. Here, the researchers showed that fruit flies and mice treated with erlotinib also grow more sensitive to alcohol. In addition, rats given the cancer-fighting drug spontaneously consumed less alcohol when it was freely available to them. The authors concluded that inhibitors of EGFR or components of its signaling pathway are potential pharmacotherapies for alcohol addiction. This work was published in the May 21 online edition of Cell. [Press release] [Cell abstract]

May 20th

Anti-Angiogenesis Genes May Contribute to Low Cancer Rate in Down Syndrome

Researchers have provided evidence that the extra copies of two chromosome 21 genes may be responsible, at least in part, for the extremely low cancer rate in those with Down syndrome. The rate of cancer in Down syndrome individuals is lower than 10 percent of that in the general population. It had been proposed that because Down syndrome individuals have an extra copy of chromosome 21, that there may be one or more cancer-protective genes on this chromosome. The late cancer researcher Dr. Judah Folkman proposed that the extra copy of chromosome 21 may contain a gene that blocks angiogenesis, the development of blood vessels essential for cancer's growth. In the current experiments, scientists showed that a single extra copy of the chromosome 21 gene Dscr1 is sufficient to significantly suppress angiogenesis and tumor growth in mice, as well as angiogenesis in human cells. The team also found that levels of DSCR1 protein are elevated in tissues from people with Down syndrome and in a mouse model of the disease. The extra copy of another chromosome 21 gene, Dyrk1A, also appeared to decrease cells' response to an angiogenesis-promoting protein. "I think there may be four or five genes on chromosome 21 that are necessary for angiogenesis suppression," said Dr. Sandra Ryeom, the senior author of the report. "In huge databases of cancer patients with solid tumors, there are very few with Down syndrome. This suggests that protection from chromosome 21 genes is pretty complete." This research was published online on May 20 in Nature. [Press release] [Nature abstract]