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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="https://www.pbs.org/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>

  

  
      <p>
 Photo Credit:
 <a href="http://commons.wikimedia.org/wiki/File:DNA-molecule2.jpg">
  ynse / Wikimedia Commons
 </a>
</p>
  



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="https://www.pbs.org/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>

  

  
      <p>
 Photo credit: D. Delattre © Bibliothèque de l'Institut de France
</p>
  



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="https://www.pbs.org/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.
 <div class="credit"></div></figcaption>
            </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>

  

  
      <p>
 Photo credit: NASA/JPL-Caltech
</p>
  



Our Solar System May Have Two Undiscovered Planets





  
      <p>
 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.
</p>
  

  
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      <p>
 “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.
</p>
<p>
 “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.
</p>
  

  
      <div class="related"></div>
  

  
      <p>
 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.
</p>
<p>
 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.”
</p>
<p>
 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.”
</p>
  

  
      <div class="newsletter"></div>
  

  
      <p>
 Photo credit: Frances S. Chance/Janelia Farm Research Campus/HHMI/Sandia National Laboratory
</p>
  



Researchers imaged an entire mouse brain to see how a recent encounter with another mouse changed its chemistry.

<p>Studies of mouse brains after they die reveal the chemical traces of their last encounters.</p>

Your Last Moments May Be Imprinted on Your Brain After Death





  
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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>
 
            <figure class="richtext-image full-width"><img alt="Original Title: Aa_FC3_11a.jpg" class="richtext-image full-width" height="451" width="800"
            src="https://www.pbs.org/wgbh/nova/media/images/original-title-aa_fc3_11a_crop-e1490808176135.width-800.jpg"/><figcaption><div class="credit"></div></figcaption>
            </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>

  

  
      <p>
 Photo credit: James Gathany / cdc.gov (public domain)
</p>
  



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





  
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 <p>
  If you spent your last road trip staring queasily at the horizon, chances are you might be one of around 33% of people who suffer from motion sickness.
 </p>
 <p>
  Motion sickness, it turns out, might not just be a matter of willpower and intestinal fortitude. Personal genetics company 23andMe has mined the genomes sequenced from the spit of over 80,000 customers to conduct the first ever
  <a href="http://www.genome.gov/20019523">
   genome-wide association study
  </a>
  of motion sickness. They discovered that variation in certain genes may predispose a person to the dizziness and nausea thought to result from conflicting sensory signals about whether the body is in motion, or standing still.
 </p>
 
            <figure class="richtext-image full-width"><img alt="dizzy_crop" class="richtext-image full-width" height="450" width="800"
            src="https://www.pbs.org/wgbh/nova/media/images/dizzy_crop.width-800.jpg"/><figcaption>
  23andMe found common genetic variations in people who get carsick.
 <div class="credit"></div></figcaption>
            </figure>
            
 <p>
  Using an online questionnaire, participants self-reported how carsick they get from never (a score of zero) to frequently (a score of three). Variations in single bits of genetic code—also known as single nucleotide polymorphisms, or SNPs—in 35 regions of the genome associated with balance, glucose regulation, and eye, ear, and brain development occurred more frequently in people who scored higher on the carsickness scale.
 </p>
 <p>
  The many different kinds of motion sickness make it difficult to draw broad conclusions from a questionnaire that specifically examined carsickness, explained motion sickness expert and University of Minnesota professor of kinesiology Thomas Stoffregen.
 </p>
 <p>
  “People get sick in cars, but they get sick in ships, and they get sick at the movies, and they get sick while they’re playing video games, and they get sick in all kinds of different situations,” he said, adding “the fact that there are some genes that line up with the answers that people gave on these online questionnaires does not, does not, does not in any way imply that the genes are causally related to motion sickness.”
 </p>
 <p>
  From the genetics perspective, Steven McCarroll, assistant professor of genetics at Harvard Medical School, said that there are very few genome wide association studies that have been conducted on this scale–and is optimistic about future studies that take advantage of the databases collected by companies like 23andMe.
 </p>
 <p>
  “When I realized that they had studied this common phenotype in 80,000 people it’s clear that they had a lot of statistical power,” he said. “I think that it’s just tremendously exciting that communities can organize over the internet and bring amazing statistical power to a problem that required really large cohorts to answer a question like this.”
 </p>
 <p>
  The
  <a href="http://www.eurekalert.org/pub_releases/2015-02/e-2su020215.php">
   announcement
  </a>
  of 23andMe’s results—published in the journal Human Molecular Genetics—comes just days after President Obama announced his $215 million Precision Medicine Initiative, which many hope will use the genetic data collected in databases like 23andMe’s to usher in a new age of genetically guided treatment and therapeutic development.
 </p>
</section>

  

  
      <p>
 Photo credit:
 <a href="https://www.flickr.com/photos/areyoumyrik/308908967/in/photolist-5LU1TV-tieSF-9GZkPo-dcAYb-druhJP-7kiuj2-6vx4EG-77rvh-7knoA3-6m4Mwp-5Jr5A-7knotb-7knowy-7knoqw-tiePX-76GzE6-29oiRM-29sFcu-4f1Sq1-fAUHr-6EzpQf-tieNG-5Tfe7t-Jar3A-kxb2s5-9UdxCW-pPeQGL-r7w3U-69vNtQ-MAW5-4v2eM7-7bfYZ4-fvxFc-MpSDi-98yoDw-2tdoEF-dcAzw-6Am9XB-kB7o9-3KL88-6dnmg6-6aXw9e-gs31c-7vMLKw-7jsdJs-9XoqDA-4GiN5a-56jgPv-nchET-mJuPd">
  are you my rik? / Flickr (CC BY-ND 2.0)
 </a>
</p>
  



You May Be Born to Feel Carsick





  
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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"
            src="https://www.pbs.org/wgbh/nova/media/images/heatsink_JNKYJaj.width-800.jpg"/><figcaption>
  Computer processors can throw off a lot of heat, which is often wasted but which can be put to good use.
 <div class="credit"></div></figcaption>
            </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="https://www.pbs.org/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>

  

  
      <p>
 Photo credits:
 <a href="https://www.flickr.com/photos/jstownsley/388362245/">
  J.S. Townsley/Flickr (CC BY-NC-ND)
 </a>
 , Kareem Ahmad
</p>
  



R.A. Becker

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