Sharper image

first_imgA new microscopy method could enable scientists to generate snapshots of dozens of different biomolecules in a single human cell at once, a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University reported Feb. 2 in Nature Methods.Such images could shed light on complex cellular pathways and potentially lead to new ways to diagnose disease, track its prognosis, or monitor the effectiveness of therapies at a cellular level.Cells often employ dozens or even hundreds of different proteins and RNA molecules to do a complex job. As a result, cellular job sites can resemble a busy construction site, with many different types of cellular workers coming and going. Today’s methods can typically spot at most three or four types of these tiny workers simultaneously. But to truly understand complex cellular functions, it’s important to be able to visualize most or all of those workers at once, said Peng Yin, a core faculty member at the Wyss Institute and assistant professor of systems biology at Harvard Medical School (HMS).“If you can see only a few things at a time, you are missing the big picture,” Yin said.Yin’s team sought a way to take aerial views of job sites that could spot dozens of types of biomolecules that make up large cellular work crews.To capture ultra-sharp images of biomolecules, the team had to overcome laws of physics that had stymied microscopists for most of the last century. When two objects are closer than about 200 nanometers apart — about one five-hundredth the width of a human hair — they cannot be distinguished using a traditional light microscope: The viewer sees a single blurry blob where in reality there are two objects.Since the mid-1990s, scientists have developed several ways to overcome this problem using combinations of specialized optics, special fluorescent proteins, or dyes that tag cellular components.As a graduate student, Ralf Jungmann, now a postdoctoral fellow working with Yin at the Wyss Institute and HMS, helped develop one of those super-resolution methods, called DNA-PAINT. DNA-PAINT can create ultra-sharp snapshots of up to three cellular workers at once by labeling them with different colored dyes.To visualize cellular job sites with crews of dozens of workers, Yin’s team, including Jungmann, Maier Avendano, an HMS graduate student, and Johannes Woehrstein, a postgraduate research fellow at the Wyss Institute, modified DNA-PAINT to create a new method called Exchange-PAINT.How it worksExchange-PAINT relies on the fact that DNA strands with the correct sequence of letters, or nucleotides, bind specifically to partner strands with complementary sequences. The researchers label a biomolecule they want to visualize with a short DNA tag, then add to the solution a partner strand carrying a fluorescent dye that lights up only when the two strands are paired. When the partner strand binds the tagged biomolecule, it lights up, then lets go, causing the biomolecule to “blink” at a precise rate the researchers can control. The researchers use this blinking to obtain ultra-sharp images.They then repeat the process to visualize a second target, a third, and so on. Then they overlay the resulting images to create a composite image in which each biomolecule — each cellular worker — is assigned a different color. This allows them to create false-color images that simultaneously show many types of biomolecules — far more than they could simultaneously visualize by labeling them with different colored dyes. These false-color images allow them to spot enough cellular workers at once to capture the entire scene.Passing the testTo test Exchange-PAINT, the researchers created 10 unique pieces of folded DNA, or DNA origami, that resembled the numerals 0 through 9. These numerals could be resolved with less than 10 nanometers resolution, or one-twentieth of the diffraction limit.The team was able to use Exchange-PAINT to capture clear images of the 10 different types of minuscule DNA origami structures in one image. They also used the method to capture detailed, ultra-sharp images of fixed human cells, with each color tagging an important cellular component — microtubules, mitochondria, Golgi apparatus, or peroxisomes.Yin expects that with further development, the method will be able to visualize dozens of cellular components at once.“Peng’s exciting new imaging work gives biologists an important new tool to understand how multiple cellular components work together in complex pathways,” said Donald Ingber, director of the Wyss Institute. “I expect insights from those experiments to lead to new ways to diagnose and monitor disease.”Ingber is also the Judah Folkman Professor of Vascular Biology at 
Harvard Medical School and Boston Children’s Hospital and professor of bioengineering at Harvard School of Engineering and Applied Sciences.last_img read more

Sick with measles, again

first_imgLast year was the worst for measles in the United States since the country was declared free of the disease in 2000. This year is not off to a promising start. The measles outbreak that began in Disneyland in December has continued to spread, infecting 102 people in 14 states during January, according to the Centers for Disease Control and Prevention (CDC).Why is an illness of our grandparents’ generation suddenly resurgent? Are we on the verge of a measles epidemic? Is the disease here to stay? To find out, the Gazette spoke with Dyann Wirth, the Richard Pearson Strong Professor of Infectious Diseases and chair of the Harvard T.H. Chan School of Public Health’s Department of Immunology and Infectious Diseases.GAZETTE: The CDC’s most recent figure was 102 people infected with measles in 14 states. What’s going on? Isn’t measles something we used to worry about?WIRTH: It’s one of the vaccine success stories. It used to be that children commonly got infectious diseases such as measles, and then recovered and had lifelong immunity. Since the 1960s, we’ve had an effective measles vaccine — a very good vaccine with long-lasting immunity — and, if vaccinated, the vast, vast majority of people develop lifelong immunity.What’s going on is there are susceptible people who have not been vaccinated who have been exposed to measles, which is a highly contagious disease.The current outbreak can be traced to a single individual in California visiting Disneyland. Although measles was eliminated in the United States, there are still countries in the world where measles exists, so importation of measles probably happens quite frequently. But if the individuals exposed are vaccinated, then you don’t have any infection.GAZETTE: So in the past, folks who have had it and come to the U.S. have run into people who have been immunized so it hasn’t spread anywhere, whereas in this case they ran in to people who hadn’t been?WIRTH: Yes, that’s right. There’s a concept of herd immunity: If the vast majority of people are vaccinated from a disease or immune from a disease, then even if a disease is introduced into the community it can’t spread because there’s a very low chance that the virus will enter a susceptible individual. But the more susceptible individuals in a population, the larger the chances an infected person will come in contact with a susceptible person, and that’s how the disease spreads.And it’s highly contagious, so if you’re not immune, then you have a high likelihood that you’ll come down with the disease if you come into contact with it.GAZETTE: Is it contagious through the air?WIRTH: Right. There is aerosol transmission of measles. It can linger in a room after the sick person has left, and it has a long incubation period — seven to 21 days after exposure — in which sick people may not have symptoms, which can exacerbate its spread.GAZETTE: How dangerous is it?WIRTH: It can have serious complications. It makes people very sick. It’s a very unpleasant disease with a high fever and potential neurological problems that can have lifelong effects.GAZETTE: Is it potentially deadly?WIRTH: There is mortality due to measles. It’s not the same kind of mortality you see with Ebola. I would guess most people in this country over 55 or 60 had measles and there’s a very high survival rate, but there are complications that occur at a low frequency compared to something like Ebola, and fatalities at an even lower frequency.GAZETTE: We’ve been hearing about the anti-vaccination movement. Is it your sense that this is essentially what this outbreak is from, or is there some other dynamic going on?WIRTH: I think it would be inappropriate to attribute it to the anti-vaccination movement. But it’s important to realize that most people, including the parents of today’s young children, haven’t known anyone who’s had measles. So the threat seems removed and therefore the incentive to vaccinate against a disease that you’ve never experienced yourself and probably no one in your community has experienced is less.And there were reports — although scientifically without support and eventually retracted — of an association of childhood vaccination with autism. This report has been refuted, retracted, and an Institute of Medicine study looking for any data to support that association came out with there being no basis. Yet this perception still exists and affects the decision of some people about whether they vaccinate their children. Vaccination, of course, is done before children themselves are able to make the decision. This is a decision of parents.GAZETTE: It seems the anti-vaccination movement is made up of people who intentionally decide that they don’t want this for themselves and their children, but often failures of health care are related to poverty, lack of knowledge …WIRTH: And lack of access, right.GAZETTE: Is there some of that going here as well?WIRTH: In the U.S., measles childhood vaccination is required for enrollment into school. In most states, probably all states, it’s given free by the state public health service. By the time of school enrollment, vaccination is a requirement. You need a religious or philosophical exemption to have your unvaccinated child go to public school.GAZETTE: Do you have a sense whether this outbreak is a blip, or is measles here in the U.S. to stay?WIRTH: From what I understand, the vaccination rate is still very high, so I would anticipate that this is not going to continue.According to the CDC, in 2013, there were 11 outbreaks, three of which were more than 20 cases, including one outbreak with 58 cases. In 2014, there were 23 measles outbreaks, including one outbreak of 383 cases in an unvaccinated Amish community in Ohio.Measles is contagious before the individual is symptomatic and therefore transmission can occur before an individual is recognized and quarantined. So the more unvaccinated and unquarantined people that come in contact with the virus, the more you will see this rise, but I don’t expect it to stay in most communities. If there is a situation where a significant proportion of an individual community is unvaccinated, as with the Amish in Ohio, you might see something similar to what was seen in 2014.GAZETTE: When you see a spike within a community, does it — in a way — take care of itself because all those people are now immune?WIRTH: All those people who survived are immune. When I was a child, I had chicken pox and measles and I’m now immune. Of course, in this day and age, getting immunity that way would cause an unnecessary amount of pain and suffering to your child, especially since we have effective vaccines.GAZETTE: With regard to people who choose not to vaccinate their children, are we victims of our own success?WIRTH: Where the threat of the disease is so low that people no longer remember anyone having it, if they think there’s any risk of other complications, you can imagine someone making that decision.So diseases that have largely disappeared — diphtheria, with very high long-term morbidity and mortality; whooping cough [pertussis], with very dramatic pathology — are also diseases where people don’t get vaccinated.As someone who spends my life trying to develop cures for diseases for which there are no vaccines and, in many cases, no effective drugs, I find this incredibly frustrating. Here you have a safe, effective, inexpensive, readily usable, life-saving tool that gives you lifelong protection and people choose not to use it. I find it mind-boggling, but it’s very clear that that is what’s going on.GAZETTE: What is the one thing that the public should know about this?WIRTH: This is a very contagious and potentially dangerous disease, and if you haven’t been vaccinated or you feel your immunity is waning, you should get vaccinated. That is how to prevent yourself and your children from getting measles.If you contrast this to the situation with Ebola, no one is panicking that there’s measles in the United States. There’s not that same kind of fear, but there is a simple, cheap thing you can do to completely protect yourself. And yet, somehow, decisions are being made not to do this.I think demonizing those who don’t vaccinate their children is going to drive them further away. They already have a distrust of the medical establishment. But somehow there needs to be some leadership at the community level. I’m not sure exactly how; maybe the families who’ve been exposed to measles should give testimony about how miserable it is.I also think there’s a somewhat U.S.-centric view, but Disneyland and other places get visitors from all over the world. Other countries do not have the same level of control, don’t have universal vaccination as we do. So there’s risk, even if you don’t leave the borders of the United States.And, according to the CDC, the vast number of people who get measles were unvaccinated. There is the occasional person who is vaccinated and doesn’t develop immunity because of a feature of their immune response, but that’s not something you can predict.last_img read more

Adult female anoa, two calves die at breeding facility in North Sulawesi

first_imgThe North Sulawesi Natural Resources Conservation Agency (BKSDA) has revealed the death of a female anoa ‒ an endangered animal native to Sulawesi ‒ and two baby anoas in March at the government-run Anoa Breeding Centre in Manado, North Sulawesi. The Manado Environment and Forestry Research and Development Agency, which runs the facility, had previously been adamant not to talk about the animals’ death.“A 9.5-year-old anoa named Ana and her unborn calf died on March 7,” North Sulawesi BKSDA head Noel Layuk told The Jakarta Post on Tuesday.Noel said that earlier that day, Ana, who had been pregnant for nine months, was in a healthy condition and had yet to show signs of giving birth.“During a checkup, Ana was still seen lying down and interacting with other anoas. There were no changes in behavior and no signs of fluid that indicated she was going to give birth,” he said.Read also: Where are the anoas? Central Sulawesi’s midget buffaloes no longer in sightThe next morning, Ana and her unborn baby were found dead, with Ana’s body caught in the cage.“She was most likely having difficulty getting her body free and became exhausted, causing shortness of breath leading to death. We estimate that it occurred at night when it was dark and raining so the CCTV could not capture the event,” said Noel.The breeding center reported the death of two anoas to the North Sulawesi BKSDA on March 8.Noel added that another calf had also died.”A newborn to a 10-year-old anoa named Denok had died. It was her third calf,” he said, without further elaboration on the time of death.Read also: Conservation hopes high after third anoa born at breeding centerContacted separately on Tuesday, an officer at the center who refused to be identified, declined to comment about the death of Denok’s newborn and even asked the Post not to expose the incident.The center was established by the Environment and Forestry Ministry in 2015 to help boost the declining population of anoa due to hunting and deforestation.The International Union for Conservation of Nature (IUCN) included the anoa on its red list of endangered species in 1986. The anoa is also a protected species according to the 1990 law on the conservation of natural resources and ecosystems.There are less than 2,500 adult anoas in Sulawesi’s forests, according to IUCN data. Meanwhile, the breeding center has 10 adult anoas ‒ three males and seven females ‒ as well as three calves, which were born in 2017 and 2018. (aly)Topics :last_img read more