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Diabetes Drug May Enhance Activity of Anti-Cancer Vaccines

Researchers at the University of Pennsylvania and McGill University have shown that the widely prescribed diabetes drug metformin can boost the body’s immunological memory and thus increase the potency of anti-cancer vaccines. "We serendipitously discovered that the metabolizing, or burning, of fatty acids by T-cells following the peak of infection is critical to establishing immunological memory," noted lead author Dr. Erika Pearce. "We used metformin, which is known to operate on fatty acid metabolism, to enhance this process, and have shown experimentally in mice that metformin increases T-cell memory, as well as the ensuing protective immunity of an experimental anti-cancer vaccine." "Our findings were unanticipated, but are potentially extremely important and could revolutionize current strategies for both therapeutic and protective vaccines," said senior author Dr. Yongwon Choi. Metformin may also boost the immune response to infection-fighting vaccines. The findings were published online on June 3 in Nature. [Press release] [Nature abstract]

Insomniac Flies May Provide Clues to Human Sleep Disturbances

Scientists at the Washington University School of Medicine have created a line of fruit flies that sleeps for less than one tenth the time of normal fruit flies (one hour versus twelve hours). "Insomnia is a common and debilitating disorder that results in substantial impairments in a person's quality of life, reduces productivity, and increases the risk for psychiatric illness," said senior author Dr. Paul Shaw. "We think this model has clear potential to help us learn more about the causes of insomnia and someday develop ways to test for or treat them in the clinic." Earlier, Dr. Shaw’s lab had been the first to show that fruit flies enter a state of inactivity comparable to sleep. The researchers demonstrated that the flies have periods of inactivity during which greater stimulation is required to rouse them. Like humans, flies deprived of sleep one day will try to make up for it by sleeping more the next day. In the current work, the researchers created the line of “insomniac” flies by selective breeding of flies that naturally exhibited certain insomnia-like signs. These included difficulty in falling asleep under normal circumstances, and sleep that was often interrupted or fragmented. The researchers also used hyper-responsiveness to stimuli as a breeding guide. For example, if researchers turned on a light at night, insomniac flies woke and stayed up the rest of the night, while the healthy flies went back to sleep. The flies that stayed up were added to the breeding pool. Ultimately, this selective breeding resulted in a line of flies that sleeps for only one hour a day. This work will be published in the June 3 issue of the Journal of Neuroscience. [Press release]

New Arenavirus Is Cause of Fatal Fever Outbreak in Africa

Using unbiased high-throughput pyrosequencing, scientists have identified a new arenavirus as the cause of a highly fatal hemorrhagic fever outbreak in Zambia and South Africa in late 2008. At that time, five cases of undiagnosed hemorrhagic fever were recognized in South Africa after air transfer of a critically ill individual from Zambia. The disease was fatal in four of the five cases, including the originally infected individual, the paramedic who attended the patient during air transfer, the nurse who attended the patient in the intensive care unit, and a member of the hospital staff who cleaned the room after the death of the patient. The fifth case, a nurse who attended the paramedic one day before barrier nursing procedures were implemented, received anti-viral treatment (ribavirin) and recovered. The new virus, called Lujo virus after the sites of the outbreaks (Lusaka, Zambia, and Johannesburg, South Africa) is the first new hemorrhagic fever-associated arenavirus from Africa identified in nearly four decades. The virus is distantly related to the Lassa virus, also an arenavirus. The Lujo virus was identified with 72 hours of the receipt of specimens. According to the authors, their findings will enable the development of specific reagents to further investigate the reservoir, geographic distribution, and unusual pathogenicity of the Lujo virus. In addition, their results confirm the utility of unbiased high-throughput pyrosequencing for pathogen discovery and public health. The report of this work was published on May 29 in PLoS Pathology. [Press release] [PLoS Pathology article]

Light-Emitting Organ of Squid Also Senses Light

In addition to their prominent eyes that sense light, some squid have an organ that emits light. This light organ contains symbiotic luminous bacteria that produce light that is used by the squid to avoid predators. The light is believed to make the squid appear as bright as the ocean surface above them and thus obscure them from predators below. Now, researchers at the University of Wisconsin-Madison have obtained evidence that the light-emitting organ also senses light. "Until now, scientists thought that illuminating tissues in the light organ functioned exclusively for the control of the intensity and direction of light output from the organ, with no role in light perception," said lead author Dr. Margaret McFall-Ngai. "Now we show that the E. scolopes squid has additional light-detecting tissue that is an integral component of the light organ." Dr. McFall-Ngai added that "the tissues may perceive environmental light, providing the animal with a mechanism to compare this light with its own light emission." The findings may lead to future studies that provide insight into the mechanisms of controlling and perceiving light. The work was published in the June 2 issue of PNAS. [Press release]

Silver Nanoparticles Show Promise in Preventing Blood Clots

Working with mice, scientists have shown that the injection of silver nanoparticles 1/50,000 the diameter of a human hair can reduce the ability of platelets to clump together by more than 40 percent, with no apparent harmful side effects. The scientists suggested that such an approach might provide a new alternative to aspirin and other anti-platelet agents widely used to prevent blood clots in coronary artery disease, heart attack, and stroke. The authors noted that patients urgently need new anti-clotting agents because traditionally prescribed medications too often cause dangerous bleeding. At the same time, aging of the population, sedentary lifestyle, and spiraling rates of certain diseases have increased the use of these drugs. Researchers are presently seeking treatments that more gently orchestrate the activity of platelets, disk-shaped particles in the blood that can form clots. The nanoparticles "hold immense potential to be promoted as an antiplatelet agent," the researchers noted. "Nanosilver appears to possess dual significant properties critically helpful to the health of mankind—antibacterial and antiplatelet—which together can have unique utilities, for example in coronary stents." This study is scheduled for publication in the June 23 issue of the monthly journal American Chemical Society Nano. [Press release]

Ancient Skeleton Reveals Signs of Leprosy in India in 2000 B.C.

Previously, the earliest widely accepted evidence for leprosy was in Asian texts dated 600 B.C. Now, scientific analysis of an ancient male skeleton has revealed signs of leprosy infection and indicated that leprosy was present in India in 2000 B.C. The presence and patterning of lesions in the skeleton allowed a differential diagnosis for leprosy. These results represent the oldest documented skeletal evidence for the disease. Leprosy is a chronic infectious disease caused by Mycobacterium leprae that still today affects almost 250,000 people worldwide. The timing of first infection, the geographic origin, and the pattern of transmission of the disease are still under investigation. Comparative genomics research has suggested that M. leprae evolved either in East Africa or South Asia during the Late Pleistocene period before spreading to Europe and the rest of the World. The current work was published on May 27 in PLoS One. [PLoS One article]

Common Gene Variants Associated with Testicular Cancer

Testicular cancer is the most common cancer among young men between the ages of 15 and 40 and its incidence in non-Hispanic Caucasian men has doubled in the last 40 years. Researchers have now identified two common gene variants that are associated with increased susceptibility to this disease. This discovery lays the groundwork for genetic tests for susceptibility to testicular cancer which is over 90% curable if detected early. In a genome-wide association study, Dr. Katherine Nathanson, senior author of the report, and collaborators, found that men who have two copies of the common version of the c-KIT ligand (KITLG) gene have a 4.5-fold higher risk of testicular cancer than men who have two copies of the less common or minor version of the gene. Additionally, men with two copies of the common version of variants next to another gene, sprouty 4 (SPRY4), have a 1.48-fold higher risk than men with two copies of the less common version of this gene. "This finding is quite different than those observed in many other genome-wide association studies," Dr. Nathanson said. "In most studies, the increased risk of disease is associated with the less common variant of the gene. In this case, it is the more common variant in Caucasians that is associated with risk. If you carry two copies of the less common variant you are probably at incredibly low risk.” “Our observed strong association is intriguing and may reflect the impact of the genetic effect of KITLG," lead author Dr. Peter Kanetsky noted. "However, since the prevalence of the common variant is so high, it may also reflect other underlying factors required in conjunction with KITLG for disease development. This remains to be determined.” Additionally, the new findings may begin to explain why white men are more often diagnosed with testicular cancer than African American men.

Blue-Light Goggles May Address Sleep Disturbances in Elderly

Scientists have created a blue-light-emitting goggle and shown that it may be effective in addressing fitfulness of sleep in the elderly. In recent years, scientists at Rensselaer Polytechnic Institute’s Lighting Research Center (LRC), and elsewhere, have demonstrated that blue light is the most effective at stimulating the circadian system, when combined with the appropriate light intensity, spatial distribution, timing, and duration. In the current work, a team at the LRC has tested a goggle-like device designed to deliver blue light directly to the eyes to improve sleep quality in older adults. “The study suggests that the light goggles might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders. The next steps are to conduct field studies where we will be testing the effectiveness of this personal light-treatment device on those suffering from circadian-related sleep disorders, while also verifying the acceptance of the device among the test groups,” said Dr. Mariana Figueiro, the lead author of the study published in Chronobiology International. [Press release] [Chronobiology International abstract]

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]

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.

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