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New research links specific inherited genetic differences (alterations) to an increased risk for eye (uveal) melanoma, a rare form of melanoma that arises from pigment cells that determine eye color. Roughly 2,500 people are diagnosed with uveal melanoma in the United States annually. Previous clinical data suggests uveal melanoma is more common in Caucasians and individuals with light eye coloration; however, the genetic mechanisms underlying this cancer's development were largely unknown. In this new study -- co-authored by ophthalmologic pathologist and cancer geneticist Mohamed Abdel-Rahman, M.D., Ph.D., of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and cancer geneticist Tomas Kirchhoff, Ph.D., of the Perlmutter Cancer Center of NYU School of Medicine - scientists report the first evidence of a strong association between genes linked to eye color and development of uveal melanoma. Reported data suggests that inherited genetic factors associated with eye and skin pigmentation could increase a person's risk for uveal melanoma. Abdel-Rahman, Kirchhoff and team report their findings in the medical journal Scientific Reports. "This is a very important discovery that will guide future research efforts to explore the interactions of these pigmentary genes with other genetic and environmental risk factors in cancers not linked to sun exposure, such as eye melanoma. This could provide a paradigm shift in the field. Our study suggests that in eye melanoma the pigmentation difference may play a direct cancer-driving role, not related to sunlight protection," says Abdel-Rahman. Unlike other solid tumors, there has been limited progress in understanding the contribution of genetic risk factors to the development of uveal melanoma, researchers say, primarily due to the absence of comprehensive genetic data from patients as the large sample cohorts for this rare cancer type have not been available for research. To overcome these limitations, researchers analyzed samples from more than 270 patients with uveal melanoma, most of whom were treated at Ohio State. Because there is a known clinical connection between eye melanoma and skin cancer, in this study researchers sought to determine whether there were commonly shared genetic factors between both diseases, as the inherited genetic risk of skin melanoma has been more extensively explored in previous medical literature. The team analyzed 29 inherited genetic mutations previously linked with skin melanoma to determine if there was an associated risk of uveal melanoma. This analysis revealed that five genetic mutations were significantly associated with uveal melanoma risk. The three most significant genetic associations occurred in a genetic region that determines eye color. "Genetic susceptibility to uveal melanoma has been traditionally thought to be restricted only to a small groups of patients with family history. Now our strong data shows the presence of novel genetic risk factors associated with this disease in a general population of uveal melanoma patients," says Kirchhoff. "But this data is also important because it indicates -- for the first time -- that there is a shared genetic susceptibility to both skin and uveal melanoma mediated by genetic determination of eye color. This knowledge may have direct implications in the deeper molecular understanding of both diseases," adds Kirchhoff. Researchers expect the data presented in this study to fuel the formation of large national and international research consortiums to conduct comprehensive, systematic analysis of inherited (germline) genome data in large cohorts of uveal melanoma patients. "This type of collaboration is critically needed to dissect additional modifying genetic risk factors that may be uveal melanoma specific. This has important consequences not only for the prevention or early diagnosis of the disease but potentially for more improved therapies for at-risk patients," says Kirchhoff. "Federal funding will be crucial to support research of rare cancers such as eye melanoma as it is likely, as shown in this study, that the impact of such research will extend across the different cancer types," adds Abdel-Rahman.
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Paul Sutter is an astrophysicist at The Ohio State University and the chief scientist at COSI Science Center. Sutter is also host of the podcasts Ask a Spaceman and RealSpace, and the YouTube series Space In Your Face. Sutter contributed this article to Space.com's Expert Voices: Op-Ed & Insights. To paraphrase Galileo, "The book of nature is written in mathematical characters." The language that physicists and astronomers use to describe the natural world around us and the vast cosmos above us is just that — mathematics. It's through theoretical equations, data analysis number-crunching, and hardcore computer simulations that scientists pry open nature's secrets from her jealous hands. [Images: The World's Most Beautiful Equations] Mathematics is a fantastic tool, revealing more about the universe than we could've ever dreamt when the first scientists started applying rigorous methods to their natural philosophy. But that blessing is also a curse. Mathematics, the language that proves so adept at describing nature, is not the easiest language to translate into, say, plain English. That difficulty — the same difficulty in translating from any language into another — is at the root of much of the distrust some people have of astronomers and scientific findings. It's nothing new, unfortunately — just ask Galileo how much trouble he had. Scientists have an undeserved reputation for being poor communicators, but this couldn't be further from the truth. A healthy fraction of a scientist's day is filled with communication: coordinating work with colleagues and students, writing papers and grant proposals, preparing and giving talks at conferences and workshops, and teaching. How else is a scientist supposed to convince their fellows that they've hit upon the Next Great Idea if those results aren't communicated clearly? [Scientists Should Learn to Talk to Kids] Scientists are some of the strongest and most eloquent communicators you'll ever meet — when they're speaking their "native" language of mathematics and jargon. Jargon words are just shorthand expressions for complex topics, and any profession, from physicists to bakers, use it. It's just that bakers aren't usually called upon to report their findings to the public. And many scientists are up to the challenge of translating their findings into non-jargon English, but there's a problem: there's no good reason for them to do it. The priorities for a scientist in our current academic system are, in order: 1) get grants, 2) write papers, and 3) anything else. That "anything else" includes teaching, serving on committees, refereeing papers, and — in the tiny fraction of time leftover — engage with the broader community. Oh, and maybe spend some time with their families. If you've ever wondered why most scientists don't go to the trouble of communicating their work with the public, there's your reason: there's no incentive for them to do it. There aren't any rewards, and there certainly isn't any money. When a scientist does engage with the public, say, by giving a public lecture or visiting a classroom, by and large they are doing it in their spare-spare-spare time, and doing it because they enjoy it. So we (and "we" here means both scientists and the public) have a problem: the knowledge that scientists gain about the natural world stays relatively locked up within the scientific community, the scientists have no incentive to share it more broadly, and the public grows ever more distrustful of scientists. That reduces science funding opportunities, which means researchers have to work even harder to get grants, which means they have even less time for outreach …. We need to break this cycle. Society needs to be scientifically literate to function, and scientists need public support to continue being scientists. This is where storytelling comes in. Stories are powerful. They resonate with us on a human level in a way that bare numbers can't. And there are many creative ways to tell stories. Usually scientists are nervous to tell stories based on science — they are, after all, trained to be as precise and exacting as possible. Fortunately, there are many talented people around the world who are experts at telling stories — artists. Such as dancers. Yes, dance. People moving their bodies to music. Dance is a natural "language" for interpreting and representing physical concepts: the way a dancer thinks about the world, in terms of transfers of momentum and flows of energy, isn't much different from a physicist. Endeavors like the popular "Dance Your Ph.D." program or a project I'm involved with, "Song of the Stars," take advantage of that natural connection. In "Song of the Stars," the dances reflect themes from astrophysical phenomena. We've all been wowed by Hubble images, but it's something completely different to be immersed in the formation of the first stars or to witness a companion being pulled into a black hole, as only dance can express. To have astronomy brought down to Earth and be brought to life. To explore and share astrophysical phenomena in new and creative ways. To interpret the motions of gas and the play of complex forces using only the movement of the human body. To be told a story in a way that emotionally connects with us. And there are so many wonderful stories to tell about the universe, stories revealed by the scientific process but not usually exposed to the public in a way that they can appreciate and enjoy. [Do Science and Art Share a Source? - Café Panel Chat ] "Song of the Stars" is a blending of astronomy and dance to tell the life stories of the stars above. From the first revolution of light more than 13 billion years ago in a dark universe, to a galactic collision that sparks a new generation, to the loss of a companion into a black hole, to a spectacular supernova that sends one last message across the universe. Dance pieces depicting these scenarios are interwoven with narration that conveys the science and gives the audience enough information to fully appreciate the creative work of the artists. I'm continually fascinated by the ever-unfolding mysteries that the universe presents to us, and I want to share those mysteries with anyone I can. This is why I started working with Seven Dance Company to create "Song of the Stars." By sharing what I know with dancers and choreographers, we're working together to translate mathematics and jargon into new languages and use those new languages to tell stories that connect with us in different, emotional ways. This process sacrifices technical details, which is fine. I'm trying to communicate intuition, not information. If an audience wants reams of complex text and mathematics, they're already well-served. Most people may not realize the beauty and drama that plays out in the heavens above, because it's never been shared with them in a way that makes them care. Many people are immediately "turned off" by science or space concepts. But maybe dance can reach them. Maybe other artistic expressions can communicate to them. Maybe if science is shared with them in a way that they can appreciate and enjoy, we can break the cycle of distrust. Maybe if science knowledge is presented in new ways — away from meaningless soundbites or contextless data points — audiences can gain an understanding of, and an appreciation for, what scientists do. And maybe those audiences can gain an appetite for more. We're all curious; it is part of what makes us human. If that curiosity can be awakened — or reawakened — maybe the next time scientists beg the public for money they won't be immediately dismissed. Maybe the next time a research group publishes a new result, it's met with joy and fascination from all corners of society. Maybe a kid who never realized he or she could be a scientist pushes toward a new career. The point of combining science with the arts isn't to necessarily dictate what the artist creates, but rather to explore a shared experience and find the common ground between the disciplines. The point is to inspire artists and to bring science to new audiences who wouldn't normally be interested in the topics. To reveal and revel in what science truly is: an expression of our shared human curiosity, expressed in the language of mathematics, but translated to make it enjoyable by everyone. "Song of the Stars" is supported by a Kickstarter campaign. Learn more by listening to the episode "What's the point in talking about science?" on the Ask A Spaceman podcast, available on iTunes and on the Web at http://www.askaspaceman.com. Ask your own question on Twitter using #AskASpaceman or by following Paul @PaulMattSutter and facebook.com/PaulMattSutter. Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Space.com. Do Not Fear Failure, The Lessons are Important (Op-Ed) Copyright 2016 SPACE.com, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
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Large amounts of copper are toxic to people and to most living cells. But our immune systems use some copper to fend off bacteria that could make us sick. More copper in the environment leads to more bacteria, including E. coli, that develop a genetic resistance. And that could pose an increased infection risk for people, said Jason Slot, who directed a new copper-resistance study and is assistant professor of plant pathology at The Ohio State University. Today, copper is widely used, including in animal feed and to make hospital equipment - areas that could be particularly conducive to bacteria developing even greater resistance, Slot said. Under the pressure of "copper stress," bacteria have traded DNA that enabled some to outlive the threat, said Slot, who specializes in fungal evolutionary genomics. And over centuries, the genes that lead to copper resistance have bonded, forging an especially tough opponent for the heavy metal, a cluster scientists call the "copper homeostasis and silver resistance island," or CHASRI. Slot and his colleagues created a molecular clock, using bacterial samples collected over time and evolutionary analysis to trace the history of copper resistance. The team studied changes in bacteria and compared those to human use of copper. Their work suggests there were repeated episodes of genetic diversification within bacteria that appear to correspond to peaks in copper production. The study appears in the journal Genome Biology and Evolution. Slot, an evolutionary biologist, first became interested in copper resistance when he learned that the genes involved weren't evolving in the way scientists would expect. "This may have arisen at the time that humans started using a lot of copper - in the Bronze Age," Slot said. He and his collaborators speculate that the original resistance might have started in milk fermented in a copper-alloy vessel, or in the gut of an animal in a high-copper environment. From then on, human use of copper has likely contributed to bacteria with a stronger armor against it. For instance, "About 2,000 years ago Romans were pumping a ton of copper dust into the environment," Slot said. Ice cores from Greenland have supported this theory, showing likely high copper emissions during the time. Today, copper is widely used in industry, including in farming, where the metal is added to feed to fatten up animals. And in recent years, there's been a movement toward using copper more in medical settings because of its antibacterial properties, Slot said. "You're enticing the bacteria in the environment to develop a mechanism that evades your immune system," Slot said. "I think overuse of anything is a bad idea, but it's really hard for people not to overuse the few weapons that we have."
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Researchers at The Ohio State University have found a way to light up a common cancer drug so they can see where the chemo goes and how long it takes to get there. They've devised an organic technique for creating this scientific guiding star and in doing so have opened up a new frontier in their field. Previous efforts have been limited by dyes that faded quickly and by toxic elements, particularly metals. A study published this week in the journal Nature Nanotechnology highlighted two novel accomplishments. First, the researchers created a luminescent molecule, called a peptide and made up of two amino acids. Then they hitched that light to the cancer medication so that it revealed the chemo's arrival within cells. "This is very important for personalized medicine. We really want to see what's going on when we give chemo drugs and this work paves the way for the exciting endeavor," said Dr. Mingjun Zhang, the biomedical engineering professor who led the study. Biomedical engineers strive to find techniques that behave naturally within the body and leave without doing harm. This research holds promise for doing just that because the peptide is one that should easily coexist with human cells and leave as harmlessly as it entered. "You can combine your drug with this luminescent vehicle," Zhang said of the tiny fluorescent particle devised in his lab. "Composed of natural amino acids, the nanoparticle is inherently biocompatible. Our biological machines can easily take care of it." This work was done in petri dishes in Zhang's lab and work in animals is currently underway. In the body or tissue of an animal or person, scientists would watch the fluorescent signal with an optical detection system, he said. Zhang and his colleagues sandwiched their peptide to a common chemotherapy drug so that its light was hidden until the two elements peeled apart upon entering the cells. Zhang was particularly delighted to see that the blue peptide, which can be seen under ultraviolet light, maintained its luminescence for extended periods of time. Previous work to track drugs using organic dyes has been hampered by their tendency to fade with time. "You can label it and you can attach it to a drug and see where the drug goes and when it is released," Zhang said. And it could be that the biomedical advance can give patients and their doctors information on how well and how quickly a medication is working for them. "Maybe for some people a drug is taking effect in a few minutes and for somebody else it's hours and for somebody else it never takes effect," Zhang said. The research team used doxorubicin, a widely used chemotherapy drug, for their lab work, but the discovery could apply to different types of treatments. Better understanding of the complex interplay of cells and drugs is critical to development of treatments that are finely tuned for individual patients. The Ohio State work builds on research that earned a trio of scientists the 2008 Nobel Prize in Chemistry. Their work on green fluorescent protein found in jelly fish led to the discovery that scientists could illuminate cellular-level activity that had previously been cloaked in mystery. Explore further: Next generation biomarker detects tumour cells and delivers anti-cancer drugs More information: Zhen Fan et al. Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release, Nature Nanotechnology (2016). DOI: 10.1038/nnano.2015.312
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The search for such targeted drug delivery options for chemotherapy and other treatments inspired a team of researchers from the University of Science and Technology of China and The Ohio State University to develop a new way to package two or more ingredients into a single capsule. If the ingredients must be mixed for the drug to work, doctors could trigger the mixing in targeted area of the body, boosting drug efficiency while reducing side effects. The researchers report their method for multi-ingredient encapsulation and triggered mixing in a new paper in the journal Applied Physics Letters. While the work has shown promise because it allows the researcher to produce micro capsules, they have not yet used the technique to encapsulate cancer treatments. If such capsules can be made, they will have to prove safe and effective in clinical trials before becoming widely available to treat cancer. "One of the limitations of chemotherapy is that less than 5 percent of the drugs typically get to the tumor, while the rest can be absorbed by other organs," said Ronald Xu, a professor in biomedical engineering at The Ohio State University in Columbus, Ohio. One possible way to address the problem could be to make the drugs non-toxic when injected into the body and trigger mixing that would produce a toxic product only near the tumor site. For such drugs to work on a large scale, there must be a way to quickly, controllably, and cost-effectively produce capsules with two or more active ingredients. If the drugs are to be injected and spread through the body via the bloodstream, the capsules should also be small. Xu and his colleagues from the University of Science and Technology of China developed a device that can produce tiny capsules approximately 100 microns across (about the size of a speck of dust) with multiple inner ingredients. Ting Si, the first author on the paper and an expert in fluid mechanics, also developed mathematical models that show the relationship between process parameters, like flow rate and needle diameter, and the size of the final capsules. The models were used to achieve the designated capsule sizes. The device works by funneling different ingredients through two inner needles. The inner needles run parallel to each other and are both enclosed in a larger outer needle, which contains an ingredient for making the outer shell of the capsule. As all the ingredients exit the needles through a single nozzle, a high-speed gas forces the liquids into a narrow stream that breaks up into individual droplets. An electric field stabilizes the flow so that uniform droplets are created. Depending on the relative flow rates, each droplet may contain two or more smaller inner droplets made from the ingredients in the inner needles. The researchers tested their device with colored paraffin wax - red in one needle and blue in the other. The outer shell was made from sodium alginate - a material extracted from seaweed that turned gelatinous when the droplets fell into a calcium chloride solution. Depending on the experimental conditions, the team was able to produce between 1,000 to 100,000 capsules per second, and nearly 100 percent of the inner liquids were incorporated into the capsules without any waste. Once encapsulated, the two colors of wax did not mix, because of surface tension, but the team demonstrated that they could force the red and blue wax to merge by vibrating the capsules. The team also demonstrated that they could release the inner droplets by dissolving the outer shell. The key features of the new device are its high efficiency and yield, and the fact that the size of the droplets can be uniformly controlled, Xu said. By further fine-tuning the device's operation Xu predicts that the team could make capsules that are 3-5 microns across, about the size of a red blood cell. The process can also be easily scaled up by building an array of nozzles and could be modified to encapsulate 3 or more active ingredients by adding additional inner needles. While Xu and his colleagues were motivated by drug delivery, their device might also find wider use in a range of applications that require controlled reactions, such as regenerative medicine, and nuclear and chemical engineering, Xu said. Explore further: Fabrication of new elastic 'soft capsule' using nano-sized flakes More information: "Steady cone-jet mode in compound-fluidic electro-flow focusing for fabricating multicompartment microcapsules," is authored by Ting Si, Chuansheng Yin, Peng Gao, Guangbin Li, Hang Ding, Xiaoming He, Bin Xie and Ronald X. Xu. It will be published in the journal Applied Physics Letters on January 11, 2016. DOI: 10.1063/1.4939632