Koch Foundation

Draper





  
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 <p>
  Over a decade ago, the Human Genome Project deciphered the “human instruction book” of our DNA, but how cells develop vastly different functions using the same genetic instructional text has remained largely a mystery.
 </p>
 <p>
  As of yesterday, it became a bit less mysterious. A massive NIH consortium called the Roadmap Epigenomics Program published eight papers in the journal Nature which report on their efforts to map epigenetic modifications, or the changes to DNA that don’t alter its code. These subtle modifications make genes more or less likely to be expressed, and the collection of epigenetic modifications is called the epigenome.
 </p>
 
            <figure class="richtext-image full-width"><img alt="DNA-molecule" class="richtext-image full-width" height="450" width="800"
            src="/wgbh/nova/media/images/dna-molecule.width-800.jpg"/><figcaption>
  A handful of new studies provide epigenetic roadmaps to understanding the human genome in action.
 <div class="credit"></div></figcaption>
            </figure>
            
 <p>
  One of the eight studies
  <a href="http://www.nature.com/nature/journal/v518/n7539/full/nature14248.html#f2">
   mapped over 100 epigenomes
  </a>
  characterizing every epigenetic modification occurring in human tissue cells. “These 111 reference epigenome maps are essentially a vocabulary book that helps us decipher each DNA segment in distinct cell and tissue types,” Roadmap researcher Bing Ren, a professor of cellular and molecular medicine at the University of California, San Diego, said in
  <a href="http://www.nih.gov/news/health/feb2015/niehs-18.htm">
   a news release
  </a>
  . “These maps are like snapshots of the human genome in action.”
 </p>
 <p>
  This kind of mapping has challenged the field because of the huge amount of data needed to make sense of the chaotic arrangements of genes and their regulators. “The genome hasn’t nicely arranged the regulatory elements to be cheek by jowl with the elements they regulate,” Broad Institute director
  <a href="http://www.nytimes.com/2015/02/19/health/scientists-shed-light-on-circuits-that-control-genes.html">
   Eric Lander told Gina Kolata
  </a>
  at The New York Times. “It can be very hard to figure out which regulator lines up with which genes.”
 </p>
 <p>
  Here’s how Lander described the detective process used to Kolata:
 </p>
 <blockquote>
  <p>
   If you knew when service on the Red Line was disrupted and when various employees were late for work, you might be able to infer which employees lived on the Red Line, he said. Likewise, when a genetic circuit was shut down, certain genes would be turned off. That would indicate that those genes were connected, like the employees who were late to work when the Red Line shut down.
  </p>
 </blockquote>
 <p>
  Diseases can be linked to epigenetic variations as well. For example, another of the eight papers published yesterday
  <a href="http://www.nature.com/nature/journal/v518/n7539/full/nature14252.html">
   proposed
  </a>
  that the roots of Alzheimer’s disease lie in immune cell genetic dysfunction and epigenetic alterations in brain cells.
 </p>
 <p>
  Creating an epigenetic road map is a huge step, but it’s just a first step. As Collins wrote in 2001 when the human genome had been mostly mapped, “This is not even the beginning of the end. But it may be the end of the beginning.”
 </p>
</section>
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 Photo Credit:
 <a href="http://commons.wikimedia.org/wiki/File:DNA-molecule2.jpg">
  ynse / Wikimedia Commons
 </a>
</p></div>
  



In Once-Mysterious Epigenome, Scientists Find What Turns Genes On





  
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 <p>
  After two millennia, scientists wielding X-rays have finally revealed the text of an ancient library long thought to be unreadable.
 </p>
 <p>
  Blasted by the volcanic eruption of Mount Vesuvius that also demolished Pompeii in 79 CE, the library in Herculaneum, which contained around 1,800 rolled papyrus scrolls, has tantalized classical scholars since archaeologists first unearthed it in 1752. While many of the scrolls did not burn, they were carbonized, locking pages of ancient text into fragile tubes resembling the charcoal remnants of a campfire.
 </p>
 
            <figure class="richtext-image full-width"><img alt="SAMSUNG DIGITAL CAMERA" class="richtext-image full-width" height="448" width="800"
            src="/wgbh/nova/media/images/charred-scroll.width-800.jpg"/><figcaption>
  Scientists peered inside this fragile scroll using a special X-ray technique.
 <div class="credit"></div></figcaption>
            </figure>
            
 <p>
  Previous attempts to read the scrolls that may once have belonged to Julius Ceasar’s father-in-law have been highly damaging, chastening future would-be readers. But yesterday, an international team of scientists, led by Vito Mocella of the Institute for Microelectronics and Microsystems in Naples, Italy, and Emmanuel Brun of the European Synchotron, announced that that X-ray phase contrast tomography enabled them to read the text layered inside the scrolls without ever having to unroll them. The technique can detect differences in how similar materials—such as ancient ink and papyrus—bend light. They published their results in the journal Nature.
 </p>
 <p>
  Richard Van Noorden, reporting for Nature News, explained the technique:
 </p>
 <blockquote>
  <p>
   This is used in medicine to image the structures of soft tissues that do not absorb x-rays well, such as those in the brain, lungs and breast. It works by detecting contrast in how materials refract, rather than absorb, X-rays. Inside the Herculaneum scrolls, the inked letters are raised some 0.1 millimetres above the surface of the papyrus. That tiny bump was enough for Mocella’s team to make out the ink using coherent beams of X-rays from the European Synchrotron Radiation Facility in Grenoble, France.
  </p>
 </blockquote>
 <p>
  From those bumps, the team could read a number of Greek letters and even a few words. Mocella and Brun admit that there are several limitations to using X-ray phase contrast tomography to read ancient text, including how to decide which direction to read words that may be folded or upside down.
 </p>
 <p>
  But it does show promise, they said. “While our first experiments have revealed only small segments of writing and are in need of further refinement,” the authors wrote, once the technique has been perfected, “the imaging of an entire papyrus scroll should not require more than a few hours.”
 </p>
</section>
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 Photo credit: D. Delattre © Bibliothèque de l'Institut de France
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X-ray Vision Unveils Hidden Text in Vesuvius-Blasted Papyrus





  
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 <p>
  On the outer reaches of our solar system, well past Neptune and Pluto, lurk dozens of asteroids and possible minor planets, dimly lit by the faint glow of our sun. Last week, that strange place got even stranger.
 </p>
 <p>
  On January 13, scientists from the University of Madrid and the University of Cambridge announced that the eccentricities of some of the farthest objects might be explained by the gravitational pull of two large bodies—in other words, undiscovered planets.
 </p>
 
            <figure class="richtext-image full-width"><img alt="ETNOS jpl caltech image" class="richtext-image full-width" height="449" width="800"
            src="/wgbh/nova/media/images/etnos-jpl-caltech-image-e1421874263232.width-800.jpg"/><figcaption>
  New calculations suggest that two undiscovered planets may lurk at the edge of our solar system.
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            </figure>
            
 <p>
  The team faces an uphill battle to add them to our solar system’s familiar roster. David Wilson, writing for Astrobites, urges caution:
 </p>
 <blockquote>
  <p>
   The calculations suggesting the existence of unseen planets is based on observations of only 13 KBOs [Kuiper Belt Objects], few enough that the clustering could be down to simple chance. If future observations find many more KBOs that don’t fit the pattern, then the case for missing planets will disappear. If, on the other hand, they do match what has already been seen, then their behaviour could be used to narrow down the locations of the unseen super-Earths, giving future astronomers the information they need to find them.
  </p>
 </blockquote>
 <p>
  The authors of the study—who published their results in two papers, one just this month, and an earlier one in September, in the Monthly Notices of the Royal Astronomical Society—agree that their conclusions are limited by a small sample size, but conclude their earlier paper with the argument that “the same trends are found for asteroids and comets,” and their results are unlikely to be due to Neptune’s gravitational pull or to observational bias.
 </p>
 <p>
  Fortunately, this all may be sorted out by the New Horizons spacecraft, which is scheduled to buzz Pluto this summer. The data it beams back could shed light on these mysterious gravitational forces.
 </p>
</section>
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 Photo credit: NASA/JPL-Caltech
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Our Solar System May Have Two Undiscovered Planets





  
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 <p>
  Scientists have reinvented the technology that makes analyzing crime scene DNA and diagnosing infectious diseases possible—for 1/500
  <sup>
   th
  </sup>
  the cost.
 </p>
 <p>
  Today, we can distinguish human genetic material at crime scenes and detect the DNA of infectious agents in blood using a reliable, heat-dependent process called PCR. The catch is that PCR equipment usually runs into the multiple thousands of dollars—a significant barrier in resource-limited settings.
 </p>
 <p>
  So scientists at the University of California, Santa Barbara designed a system that combines the wasted heat from an over-clocked computer with the imaging capacity of a mobile phone. It works just like regular PCR, but “for a fraction of the cost,” writes Faye Walker, an author of the study. Scientists eager to convert their PCs and phones to PCR machines can find
  <a href="http://pubs.acs.org/doi/full/10.1021/ac5022419">
   the how-to guide
  </a>
  published by members of Tom Soh’s lab in September’s issue of Analytical Chemistry.
 </p>
 
            <figure class="richtext-image full-width"><img alt="heatsink" class="richtext-image full-width" height="450" width="800"
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  Computer processors can throw off a lot of heat, which is often wasted but which can be put to good use.
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            </figure>
            
 <p>
  “I think the cost effectiveness, particularly, is going to be a very attractive feature,” said Susan Montgomery, the epidemiology team lead of the Parasitic Diseases Branch at the CDC. “The equipment that’s needed for the way PCR is done in laboratories now is expensive.”
 </p>
 <p>
  PCR works by mixing a miniscule amount of DNA with chemicals and running it through cycles of heating and cooling on a machine called a thermal cycler to copy the DNA billions of times. This amplification increases the amount of DNA to levels that, when mixed with fluorescent dyes, can be seen under UV light.
 </p>
 <p>
  Kareem Ahmad, another author on the study, first considered harnessing a PC’s heat for biomedical research four and a half years into his PCR-intensive PhD. Ahmad had built a PC at home to watch movies and noticed the computer’s fan whirring loudly while he watched Netflix. When he checked the computer’s internal temperature, he saw it approaching 70˚ C. He remembers thinking, “I wonder if it could be hot enough to do PCR?”
 </p>
 <p>
  Ahmad found inexpensive software online that could cycle the internal temperature of a computer, just like a PCR machine. The next day, he decided to run a PCR experiment using the computer instead of a thermal cycler as the heat source. “The second time I did that experiment, it worked, which was unlike every other project I had worked on up until that point,” Ahmad said.
 </p>
 
            <figure class="richtext-image full-width"><img alt="heat-sink-pcr" class="richtext-image full-width" height="449" width="800"
            src="/wgbh/nova/media/images/heat-sink-pcr1.width-800.jpg"/><figcaption>
  A closeup of Kareem Ahmad's heat-sink PCR thermocycler
 <div class="credit"></div></figcaption>
            </figure>
            
 <p>
  Over the next two years, the PC-Phone-PCR (P3) system evolved until it eventually included a camera phone outfitted with a special filter and tubes pre-loaded with the necessary chemicals and fluorescent dye. Ahmad—who graduated with his PhD six months after the initial experiments—handed off the work to Faye Walker, “who did an excellent job of putting it across the finish line,” he said.
 </p>
 <p>
  Using the final P3 product, the scientists in the lab could detect parasites in human blood by adding blood to the pre-loaded tubes, boiling them briefly, placing them in the computer’s heat sink, cycling the computer’s temperature, and—under UV or blue light—using the camera to detect the presence of the now-fluorescing parasite DNA. They then used the same computer that provided the heat source to analyze the photos and determine which tubes contained blood positive for parasite infection.
 </p>
 <p>
  “I’m almost kicking myself for not coming up with it sooner, because it seems like—once you realize it—it seems like such a simple, obvious thing,” Ahmad said.
 </p>
 <p>
  “I love the idea of making things with what you have, that solve problems that you have in the field,” said Dr. Darvin Scott Smith, chief of infectious disease and geographic medicine at Kaiser Permanente. Smith would like to see this technology tested in environments where the scientists anticipate it being used and eventually see it tested on multiple diseases.
 </p>
 <p>
  Montgomery, the CDC epidemiologist, added that field-testing the P3 system, “will go a long way, I think, to pushing the argument forward that this is something that could be used in a disease control setting.”
 </p>
 <p>
  Ahmad hopes the P3 system’s practicality will make it widely adoptable. “To me, what’s cool about this technology is that it’s not actually that sophisticated, and it’s not something that is beyond the reach of most people,” he said. “It’s something that’s almost democratic.”
 </p>
</section>
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 Photo credits:
 <a href="https://www.flickr.com/photos/jstownsley/388362245/">
  J.S. Townsley/Flickr (CC BY-NC-ND)
 </a>
 , Kareem Ahmad
</p></div>
  



Bioengineers Hack PCs and Phones to be Cheap Disease Detectors





  
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</p>
<p>
 It was, perhaps, inevitable. Once we gained the ability to modify the DNA of an organism, it was only a matter of time before we turned that technology on ourselves and our offspring.
</p>
<p>
 Now, Chinese scientists have edited the genome of a human embryo. Their work was
 <a href="http://link.springer.com/article/10.1007/s13238-015-0153-5/fulltext.html">
  quietly published
 </a>
 late last week, on a Saturday, in the little-known, open-access journal
 <i>
  Protein &amp; Cell
 </i>
 , an unusual way to introduce a first-of-its-kind study.
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 Typically, such results usually appear in the pages of a handful of respected journals like
 <i>
  Science
 </i>
 or
 <i>
  Nature
 </i>
 and are surrounded by a flurry of publicity. The lead researcher, Junjui Huang of Sun Yat-sen University in Guangzhou, attempted to publish in several journals but was turned down out of ethical concerns. David Cyranoski and Sara Reardon unearthed the paper and brought it to wider attention in
 <a href="http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378">
  an article
 </a>
 they published late yesterday in
 <i>
  Nature
 </i>
 ’s news section.
</p>
<p>
 The journals may also have balked at the mediocrity of the science itself. “It came up with relatively non-break through results,” says George Church, a professor at Harvard University. It was “a fairly technical paper that didn’t provide any brand new insights.”
</p>
<p>
 “Ethically, it is of huge significance,” says Arthur Caplan, a professor of bioethics at New York University. “The paper is much more interesting as an ethics paper than it is as a science paper. The science isn’t going to be impacted in any way by the appearance of this paper.”
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      <div class="rich-text"><h2>
 Familiar Methods, Unfamiliar Sources
</h2>
<p>
 Much of the paper’s experimental method retraces well-trodden ground. The team used the CRISPR-Cas9 genome editing technique, a relatively new but powerful and widely-used method that allows scientists to modify genes more rapidly than before. Though the molecular machinery was first demonstrated as an editing technique in 2012, scientists have quickly become adept at wielding it, to the point where researchers at various levels—from undergraduates to tenured professors—are using it in labs around the world.
</p>
<p>
 The Chinese team’s target was the gene responsible for β-thalassaemia, an inherited blood disorder that can lead to severe anemia. In that sense, they were on the right path. “I think there’s tremendous promise in genome editing for blood disorders, and other disorders, but particularly blood disorders,” says Dr. Daniel Bauer, a professor and blood disorder researcher at the Harvard Stem Cell Institute. But, he adds, this and other disorders could be corrected by altering a person’s blood stem cells. In that case, “one wouldn’t necessarily need to modify the germ line to have a benefit in this kind of blood disorder,” he says. Dr. Suneet Agarwal, an assistant professor at the Harvard Medical School who studies gene therapy and bone marrow disorders, agrees. “I don’t think it’s safe to try and achieve a clinical cure with this type of technology. We already know that it has a long way to go in terms of its development.”
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 Huang and his team said they collected embryos with the mutation from a nearby fertility clinic, according to Cyranoski and Reardon’s reporting, though little else is known about how they were created or obtained, Caplan points out. The researchers chose to modify
 <a href="http://humrep.oxfordjournals.org/content/27/suppl_1/i22.full.pdf">
  tripronuclear zygotes
 </a>
 , which are single-celled embryos that have an additional set of chromosomes. Humans, having two copies of each chromosome, are diploid. So while a triploid embryo may develop for several days or weeks, it ultimately has an extremely low chance of survival.
</p>
<p>
 Using tripronuclear zygotes allowed the researchers to study whether their edits took hold and how they affected early development. Since the embryos were unable to develop into viable fetuses, it provided the team with a modicum of ethical cover. But it also prevented them from saying anything about the viability of the modified embryos.
</p>
<p>
 Even then, the results weren’t promising. The researchers started out with 86 embryos, but just 71 made it to the end of the study. Of those, 54 were tested, and the team discovered that only 28 had successfully been modified. Worse, the CRISPR scissors missed their target often enough to be worrying. Two of the six embryos Huang’s team sequenced for off-target mutations were found to contain mistaken edits.
</p>
<h2>
 Ethical Concerns
</h2>
<p>
 Despite the fact that the embryos weren’t viable, many scientists are concerned that Huang and his group plowed ahead before the rest of the community had arrived at a consensus on how to proceed. Back in the 1970s, when researchers first discovered how to splice new bits of DNA into a genome, a technology known as recombinant DNA, they held a conference at Asilomar in California in 1975 to hash out a number of guidelines. In January of this year, scientists met in Napa, California, to do the same for genome editing. They identified a number of guidelines, including calling for a moratorium on any modifications to the earliest phases of development, known as the germline.
</p>
<p>
 “When you cross the germline bright line, you’re also opening the door to eugenic reasons—improvement, enhancement—not just disease,” Caplan says. The scientific community, he adds, hasn’t “even talked about that very much.”
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 “The paper is much more interesting as an ethics paper than it is as a science paper.”
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 Modifying the germline is ethically debatable, possibly perilous, but also potentially powerful. With current gene therapies, clinicians must modify every targeted cell in the body, which could number in the trillions. But in a zygote, the stage at which the Chinese group worked, they only have to modify one. As the embryo divides, every subsequent cell should retain the modifications. But if the editing technique fails to cut in the right place, as it did in several of the Chinese group’s modified embryos, every cell will also carry unintended edits, potentially introducing new, deleterious mutations. Furthermore, in the Chinese study, not every cell in the tested embryos contained the modifications. That kind of defeats the purpose of editing the germline.
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      <div class="rich-text"><p>
 Still, Church thinks this sort of experimentation should be happening, just at a more careful pace. “I’m one of the advocates of going forward cautiously,” he says. “This is one of the experiments I’m sure everybody would like to see.” Though there weren’t any breakthrough results—if the Chinese group had succeeded, Church points out, their work would certainly have been considered “more important”—he does see some value from their work. “It’s important for other safety and efficacy steps, and they even mention ways that you could improve the efficiency and specificity in the future.”
</p>
<p>
 Kevin Esvelt, a technology development fellow at Harvard’s Wyss Institute, thinks this study could help put the brakes on any fast-movers in the field. “It’s a basic first step that provides a nice cautionary tale warning against clinical attempts any time soon.”
</p>
<p>
 Despite many scientists’ reservations, this research isn’t likely to stop. Huang is hoping to refine his technique, Nature reports, either by tweaking his CRISPR-Cas9 system or using another gene editing technique like TALENs, which is more accurate and should lead to fewer off-target mutations. Furthermore, Huang’s group is not alone, Cyranoski and Reardon report. Four other groups in China are rumored to be working on editing human embryos.
</p>
<p>
 To give the scientific community and the general public more time to consider the issue, Caplan thinks we should ask researchers to stop voluntarily. “I think we should have a moratorium,” he says. “Journals should not accept papers right now.”
</p>
<p>
 “This experiment stirs attention to the fact that we need to have both national and international discussions about how to proceed, if at all,” Caplan adds. “But if we’re going to do it, we don’t do it by publishing a meaningless experiment in a third-tier journal. That’s not the way to begin.”
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 Image credit: Yorgos Nikas/Wellcome Images (CC BY-NC-ND)
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<p>Chinese scientists used the CRISPR-Cas9 editing technique to alter the genome of a “nonviable” human embryo.</p>

Scientists Genetically Modify Human Embryos





  
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 <p>
  The fight against mosquito-borne diseases and growing insecticide resistance may have gained a new weapon—the mosquitoes themselves. That is, if the FDA approves modifications to their genome.
 </p>
 <p>
  Painful viral infections like dengue fever and chikungunya—which causes such severe contortions that the name translates to “that which bends over”—are both transmitted by mosquitoes. Last year, the first cases of chikungunya transmitted in the Americas were reported in the Caribbean, and dengue epidemics have been occurring in Puerto Rico since the 1960s.
 </p>
 
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            </figure>
            
 <p>
  Beyond managing the pain, fevers, and other symptoms,there are no treatments or vaccines for either dengue or chikungunya, and insecticide use is increasingly unsuccessful at combating the spread of these diseases;
  <em>
   Aedes aegypti
  </em>
  mosquitoes, the species that carry both diseases, are now able to evade four of the six insecticides leveled against them, according to the Associated Press.
 </p>
 <p>
  Now, British biotech firm Oxitec is proposing to kill mosquitoes in the Florida Keys from the inside, out. They have developed a strain of genetically modified mosquitoes that possess a mélange of genes from the herpes simplex virus, E. coli bacteria, cabbage, and coral. When the mutated males breed with wild-type females in the general mosquito population, the larvae that result die, reducing the number of disease-transmitting adults in the following generation.
 </p>
 <p>
  In tests conducted outside of the U.S., Oxitec’s strategy has diminished mosquito populations. One peer-reviewed study published in Nature Biotechnology demonstrated that mating a wild-type female with a modified male mosquito in the lab killed over 96% of the offspring. When 3.3 million modified mosquitoes were released in the Cayman Islands, they reduced mosquito populations by 80% compared to areas with no genetically modified mosquitoes, according to a commentary published in 2012 which wasn’t subject to peer review.
 </p>
 <p>
  Although at the time Oxitec apparently ran into trouble for not obtaining the necessary consent for these trials,
  <a href="http://www.nature.com/nbt/journal/v29/n1/full/nbt0111-9a.html" target="_blank">
   Nidhi Subbaraman reported for Nature Biotechnology News
  </a>
  that “William Petrie, director of the MRCU in the Cayman Islands, says the sterile transgenic mosquito release technique is head and shoulders above the population control methods currently in place there.”
 </p>
 <p>
  Support for genetically modified mosquitoes being released in Florida though, remains tenuous. “I think the science is fine, they definitely can kill mosquitoes, but the GMO issue still sticks as something of a thorny issue for the general public,” Phil Lounibos—who studies mosquito control at the Florida Medical Entomology Laboratory—
  <a href="http://hosted.ap.org/dynamic/stories/U/US_MODIFIED_MOSQUITOES_ABRIDGED?SITE=AP&amp;SECTION=HOME&amp;TEMPLATE=DEFAULT&amp;CTIME=2015-01-25-12-58-28" target="_blank">
   told Jennifer Kay of the Associated Press.
  </a>
 </p>
 <p>
  This is not the first proposal to prevent the spread of deadly mosquito-borne diseases by genetically modifying the vectors. In July 2014,
  <a href="http://www.pbs.org/wgbh/nova/next/evolution/crispr-gene-drives/" target="_blank">
   Tim De Chant and Eleanor Nelsen reported for NOVA Next
  </a>
  that the newly developed CRISPR-Cas9 gene editing system could be used to drive killer mutations through populations of mosquitoes—wiping them out. However, George Church, a professor of genetics at Harvard Medical School and co-author of the proposal, urged caution.
 </p>
 <p>
  “I think we need to be cautious with all new technologies, especially all new technologies that are messing with nature in some way or another. But there’s also a risk of doing nothing,” Church told De Chant and Nelsen. “We have a population of 7 billion people. You have to deal with the environmental consequences of that.”
 </p>
</section>
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 Photo credit: James Gathany / cdc.gov (public domain)
</p></div>
  



Mosquito-Borne Diseases to Be Fought by Modified Mosquitoes in Florida





  
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 Ever close your eyes and have an image burned into your retina? Our brains may do the same thing after we die.
</p>
<p>
 Scientists have developed a technique that can recreate a 3D map of the cells that were firing in a mouse’s brain a few hours before it died, giving them a high-resolution picture of what was going on in the mouse’s head during life—in this case, when it met a member of the opposite sex. The team of researchers published their results yesterday in the journal Cell Reports.
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 “The work mapping these circuits in the whole mouse brain is quite heroic,” wrote Rafael Yuste in an email. Yuste, professor of biological sciences and neuroscience at Columbia University and a leader of the Brain Activity Map Project that inspired Obama’s BRAIN initiative, was not involved in the study. He cautions that it’s a less than ideal technique since the mouse must be sacrificed in the process—mice won’t sit still long enough for a noninvasive MRI scan.
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 “We can take normal mice and have them do complex tasks such as social behavior, and then look throughout the whole brain and identify brain regions that were activated—at cellular resolution,” said Pavel Osten, professor at Cold Spring Harbor Laboratory and the senior investigator on the study.
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 Using mice modified so their neurons glow green when they fire, the researchers found that, even before any mating or aggression behaviors, the brain regions associated with reproductive behavior, sexual behavior, and aggression light up when a male mouse meets a female mouse. But when a male mouse meets another male mouse, brain regions that control defensive behavior—in addition to the ones that control sexual behavior and aggression—glow.
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 Osten’s new methodology, which improves on one he originally published in 2012, automates several different laboratory techniques formerly done by hand, which in this study allowed the researchers to create a map of brain activation from the earliest moments of sensing another animal to the sex-specific behavioral inclinations that evoked. He hopes that it will eventually be able to shed light on how diseases and pharmaceuticals change connections in the brain. Until now, Osten said, “That comparison in animals hasn’t really been possible at all at this kind of unbiased scale.”
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 Yuste wrote that detecting fluorescent markers of brain activity after death represents “a step towards future techniques for the full blown mapping of neuronal activity in living brains in real time.”
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 Photo credit: Frances S. Chance/Janelia Farm Research Campus/HHMI/Sandia National Laboratory
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<p>Studies of mouse brains after they die reveal the chemical traces of their last encounters.</p>

R.A. Becker