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Archive - Dec 15, 2014

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Scientists Create “Green” Process to Reduce Waste from Molecular Switches; Significant Advance for Nanotechnology Solves Decades-Long Problem

Dartmouth researchers have found a solution using visible light to reduce waste produced in chemically activated molecular switches, opening the way for industrial applications of nanotechnology ranging from anti-cancer drug delivery to LCD displays and molecular motors. The study was published online on September 15, 2014 in the Journal of the American Chemical Society. Chemically activated molecular switches are molecules that can shift controllably between two stable states and that can be reversibly switched -- like a light switch -- to turn different functions "on" and "off." For example, light-activated switches can fine-tune anti-cancer drugs, so they target only cancer cells and not healthy ones, thereby eliminating the side effects of chemotherapy. But such switches typically generate waste and side products that are problematic. One way of making these processes cleaner is by using light energy, similar to how photosynthesis operates in nature. In their experiments, the researchers show that a merocyanine-based photoacid derivative can effectively be used in a switching process that is fast, efficient, and forms no wastes. "We address a bottleneck that's been hampering the field for decades -- what to do with the accumulated salts and side products when activating such switches," says co-author Dr. Ivan Aprahamian, an associate professor of chemistry. "Acids, bases, and other compounds need to be constantly added to the mix to make sure the system can be switched, but within a few cycles there is so much waste that it interferes with the switching process. We found a neat solution by coupling an efficient photoacid to our chemically activated hydrazone switch. We showed the system can be efficiently modulated more than 100 times with no accumulation of waste or degradation.

Pattern of 48 Long Noncoding RNAs Is Novel Prognostic Marker in Older Patients with Acute Myeloid Leukemia (AML)

A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) describes a novel marker that may help doctors choose the least toxic, most effective treatment for many older patients with acute myeloid leukemia (AML). AML occurs mainly in older patients and has a three-year survival rate of just 5 to 15 percent. The researchers investigated patterns of molecules called long noncoding RNAs (lncRNAs), a class of RNA molecules more than 200 nucleotide units long that are involved in regulating genes. The researchers examined the abundance, or expression, of lncRNAs in patients who were 60 years and older and who had cytogenetically normal (CN) AML. The study was published online on December 15, 2014 in PNAS..“We have identified a pattern of 48 lncRNAs that predicted both response to standard chemotherapy and overall survival in older CN-AML patients,” says first author Ramiro Garzon, M.D., associate professor of internal medicine at Ohio State. “Patients in the favorable group had a high probability of responding to standard chemotherapy, while those in the unfavorable group generally responded poorly to the treatment and had worse overall survival,” he says. These findings are important for several reasons, says principal investigator Clara D. Bloomfield (photo), M.D., Distinguished University Professor, Ohio State University Cancer Scholar and holder of the William Greenville Pace III Endowed Chair in Cancer Research.

Sex and Relatedness Mediate Intensity of Egg Cannibalism by Ant Larvae

To the casual observer, the colonies of social insects like bees and ants appear to be harmonious societies where individuals work together for the common good. But appearances can be deceiving. In fact, individuals within nests compete over crucial determinants of fitness such as reproductive dominance and production of male eggs. The intensity of competition often depends on the level of kinship between colony members. This is because selfish individuals lose indirect fitness when their behavior harms close relatives. A new study by Dr. Eva Schultner and colleagues from the Universities of Helsinki, St. Andrews, and Oxford reveals that in ants, such social conflict occurs even among the youngest colony members: the eggs and developing larvae. In behavioral experiments conducted at Tvärminne Zoological Station in Finland, ant larvae acted selfishly by cannibalizing eggs, but levels of cannibalism were lower when relatedness among brood was high. In addition, male larvae engaged in cannibalism more often than female larvae. Using evolutionary modeling, the researchers show that cannibalism is predicted to evolve when it carries a benefit to the cannibal (for example in the form of increased survival), and that the costs of consuming kin influence the intensity of cannibalism behavior. Differences in cannibalism benefits for male and female larvae on the other hand may be responsible for higher levels of cannibalism in males. By exploring the evolutionary causes and consequences of selfish larvae behavior, the study published in The American Naturalist sheds new light on the evolutionary constraints of competition in social insect colonies, and demonstrates how in complex societies, even the youngest individuals are potential players in social conflict.

RNA-Binding Musashi Proteins Implicated in Regulation of Cancer

A new study from MIT and collaborating institutions implicates a family of RNA-binding proteins in the regulation of cancer, particularly in a subtype of breast cancer. These proteins, known as Musashi proteins, can force cells into a state associated with increased proliferation. Biologists have previously found that this kind of transformation, which often occurs in cancer cells as well as during embryonic development, is controlled by transcription factors — proteins that turn genes on and off. However, the new MIT research reveals that RNA-binding proteins also play an important role. Human cells have about 500 different RNA-binding proteins, which influence gene expression by regulating messenger RNA, the molecule that carries DNA’s instructions to the rest of the cell. “Recent discoveries show that there’s a lot of RNA-processing that happens in human cells and mammalian cells in general,” says Dr. Yarden Katz, a recent MIT Ph.D. recipient and one of the lead authors of the new paper. “RNA is processed at several points within the cell, and this gives opportunities for RNA-binding proteins to regulate RNA at each point. We’re very interested in trying to understand this unexplored class of RNA-binding proteins and how they regulate cell-state transitions.” Dr. Feifei Li of China Agricultural University is also a lead author of the paper, which was published online on November 7, 2014 in an open-access article in eLife. Senior authors of the paper are MIT biology professors Dr. Christopher Burge and Dr. Rudolf Jaenisch, and Dr. Zhengquan Yu of China Agricultural University. Until this study, scientists knew very little about the functions of Musashi proteins. These RNA-binding proteins have traditionally been used to identify neural stem cells, in which they are very abundant.

Scientist Discover On-Off Switch for Key Stem Cell Gene (Sox2)

Consider the relationship between between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome - the controller - directs when a particular gene - the pilot - can perform its prescribed function. A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal. "We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published online December 15, 2014 in Genes & Development. "Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Dr. Mitchell. Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome make some people more likely to develop certain diseases.