April 2016 - Page 8 of 8 - Science Rocks My World

Researchers Use New Tech to Map Zika Structure and Find Unique ‘Targets’ [Video]

A team of researchers announced in the journal Science that they’ve determined the structure of the Zika virus and found regions where it differs from similar viruses such as West Nile and dengue.

Those differences could potentially explain how the virus is transmitted and how it causes disease, according to Richard Kuhn, who co-led the team and directs the Purdue Institute for Inflammation, Immunology, and Infectious Diseases.

“The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment, used to create an effective vaccine or to improve our ability to diagnose and distinguish Zika infection from that of other related viruses,” says Kuhn. “Determining the structure greatly advances our understanding of Zika—a virus about which little is known. It illuminates the most promising areas for further testing and research to combat infection.”

The Zika virus, a mosquito-borne disease, has recently been associated with a birth defect called microcephaly that causes brain damage and an abnormally small head in babies born to mothers infected during pregnancy. It also has been associated with the autoimmune disease Guillain-Barré syndrome, which can lead to temporary paralysis.

In the majority of infected individuals symptoms are mild and include fever, skin rashes and flulike illness, according to the World Health Organization.

Zika virus transmission has been reported in 33 countries. Of the countries where Zika virus is circulating, 12 have reported an increased incidence of Guillain-Barré syndrome, and Brazil and French Polynesia have reported an increase in microcephaly, according to WHO. In February WHO declared the Zika virus to be “a public health emergency of international concern.”

NEW TECHNOLOGY MADE IT POSSIBLE

“We were able to determine through cryo-electron microscopy the virus structure at a resolution that previously would only have been possible through X-ray crystallography,” says Michael Rossmann, who co-led the team and is a professor of biological sciences at Purdue University. “Since the 1950s X-ray crystallography has been the standard method for determining the structure of viruses, but it requires a relatively large amount of virus, which isn’t always available; it can be very difficult to do, especially for viruses like Zika that have a lipid membrane and don’t organize accurately in a crystal; and it takes a long time.

“Now, we can do it through electron microscopy and view the virus in a more native state. This was unthinkable only a few years ago.”

The team studied a strain of Zika virus isolated from a patient infected during the French Polynesia epidemic and determined the structure to 3.8Å. At this near-atomic resolution key features of the virus structure can be seen and groups of atoms that form specific chemical entities, such as those that represent one of 20 naturally occurring amino acids, can be recognized, Rossmann says.

‘THESE UNIQUE AREAS MAY BE CRUCIAL’

The team found the structure to be very similar to that of other flaviviruses with an RNA genome surrounded by a lipid, or fatty, membrane inside an icosahedral protein shell.

The strong similarity with other flaviviruses was not surprising and is perhaps reassuring in terms of vaccine development already underway, but the subtle structural differences are possibly key, says graduate student Devika Sirohi.

“Most viruses don’t invade the nervous system or the developing fetus due to blood-brain and placental barriers, but the association with improper brain development in fetuses suggest Zika does,” Sirohi adds. “It is not clear how Zika gains access to these cells and infects them, but these areas of structural difference may be involved. These unique areas may be crucial and warrant further investigation.”

The team found that all of the known flavivirus structures differ in the amino acids that surround a glycosylation site in the virus shell. The shell is made up of 180 copies of two different proteins. These, like all proteins, are long chains of amino acids folded into particular structures to create a protein molecule, Rossmann says.

LIKE CANDY FOR HUMAN CELLS

The glycosylation site where Zika virus differs from other flaviviruses protrudes from the surface of the virus. A carbohydrate molecule consisting of various sugars is attached to the viral protein surface at this site.

In many other viruses it has been shown that as the virus projects a glycosylation site outward, an attachment receptor molecule on the surface of a human cell recognizes the sugars and binds to them, Kuhn says.

The virus is like a menacing stranger luring an unsuspecting victim with the offer of sweet candy. The human cell gladly reaches out for the treat and then is caught by the virus, which, once attached, may initiate infection of that cell.

The glycosylation site and surrounding residues on Zika virus may also be involved in attachment to human cells, and the differences in the amino acids between different flaviviruses could signify differences in the kinds of molecules to which the virus can attach and the different human cells it can infect, Rossmann says.

“If this site functions as it does in dengue and is involved in attachment to human cells, it could be a good spot to target an antiviral compound,” Rossmann adds. “If this is the case, perhaps an inhibitor could be designed to block this function and keep the virus from attaching to and infecting human cells.”

The team plans to pursue further testing to evaluate the different regions as targets for treatment and to develop potential therapeutic molecules, Kuhn says.

The National Institutes of Health funded the research, which is published in the journal Science.

Source: Republished from Futurity.org as a derivative work under the Attribution 4.0 International license. Original article posted to Futurity by Elizabeth Gardner-Purdue

Featured Image Credit: Kuhn and Rossmann research groups/Purdue University

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Every Part of this Microprocessor is Open Source

Software source code and hardware designs tend to be closely guarded trade secrets. But researchers recently made the full design of one of their microprocessors available as an open-source system.

Luca Benin, a professor at ETH Zurich involved with the project, says making the system open source maximizes the freedom of other developers to use and change the system. “It will now be possible to build open-source hardware from the ground up.

“In many recent examples of open-source hardware, usage is restricted by exclusive marketing rights and non-competition clauses,” adds Benini. “Our system, however, doesn’t have any strings attached when it comes to licensing.”

The arithmetic instructions that the microprocessor can perform are also open source: The scientists made the processor compatible with an open-source instruction set developed at the University of California in Berkeley.

PERFECT FOR SMARTWATCHES

The new processor is called PULPino and it is designed for battery-powered devices with extremely low energy consumption (PULP stands for ‘parallel ultra low power’).

These could be for chips for small devices, such as smartwatches, sensors for monitoring physiological functions (that can communicate with a heart rate monitor, for instance), or sensors for the Internet of Things.

Benini offers an example from the research currently underway in his lab: “Using the PULPino processor, we are developing a smartwatch equipped with electronics and a micro-camera. It can analyze visual information and use it to determine the user’s whereabouts.

“The idea is that such a smartwatch could one day control something like home electronics.”

puplino_smart_watch-768x383 — Prototype of a smartwatch in Luca Benini’ lab. The prototype above is shown with a commercial processor, not the open-source PULPino. (Credit: ETH Zurich/Frank K. Gürkaynak)

You can download the entire source code, test programs, programming environment, and even the bitstream for the popular ZEDboard for free at www.pulp-platform.org/.

Source: Republished from Futurity.org as a derivative work under the Attribution 4.0 International license. Original article posted to Futurity by Fabio Bergamin-ETH Zurich.

Featured Image Credit: ETH Zurich/Frank K. Gürkaynak

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Scientists turn to 3D printing, digital simulations to treat heart disease

By Erica Cherry Kemmerling, Tufts University

My mother bought her first GPS in the 1990s. A few months later, she came home angry because it had directed her to the wrong side of the city, making her an hour late. “That’s too bad,” I said, and we went on with our lives. We both understood that commercial GPS was a new technology and wasn’t infallible, but one wasted hour was a small price to pay for the 99 percent of driving trips on which it worked correctly. We knew that with further testing and user feedback, GPS technology would continue to improve.

Things would have been different if that technology with a 1 percent failure rate was a pacemaker or artificial valve implanted in my mom’s heart and designed to keep her alive.

But how can we expect technology to improve if a person’s health is at stake? It is unethical to test new medical devices on patients without ample evidence they will work; extensive animal testing, clinical trials and a complicated FDA approval process are necessary before such devices go to market. This means potentially lifesaving treatments can take years to reach patients.

Now, scientists are turning to new tools, including computer simulation and 3D printing, to develop faster, safer ways to test medical devices without installing them in live humans or animals. My lab is working on applying these techniques to heart and vascular diseases. This work has the potential to improve outcomes from the invasive procedures common in treatment today.

Taking measurements inside the body

Vascular disease, my research area, is a very common affliction in the U.S. There are hundreds of techniques for fixing circulatory system problems, including stents (wire cylinders hold blood vessels open), balloon angioplasty (blocked arteries are reopened by pushing obstructions out of the way) and even heart valve replacement.

Before a cardiovascular device or procedure is deemed safe and effective, it must be verified to successfully restore healthy blood flow in the body. It has been shown that the details of blood flow, such as flow speed, direction and pressure, can affect the health of the cells lining the heart and blood vessels. Knowing what the blood flow looks like before being fixed, and what may happen after a procedure or device installation, can help predict the technique’s success.

Properties such as flow speed, direction and pressure are hard to measure in a live human or animal because most measurement techniques require puncturing blood vessels. The few noninvasive methods either give unreliable results or are too slow and expensive to use on every patient. Furthermore, most flow measurements from live animals and humans are not sufficiently detailed to determine whether a procedure will ultimately lead to disease of the walls of the affected blood vessels.

Using computers to model blood flow

To circumvent this problem, scientists can test cardiovascular devices and procedures using simulations and synthetic models. These studies allow far more controlled and extensive flow data collection than would be possible on a live patient. Several research groups, including my own, are currently doing this sort of work, which includes modeling fluid velocity and pressure in blood vessels with computers. This process is called computational fluid dynamics (CFD).

Because every patient’s vascular network is a slightly different shape, there has been a movement to perform patient-specific simulations. That means scanning an individual patient’s blood vessels from medical images and modeling them virtually. By varying the model to simulate a procedure or device implantation, doctors can predict how the patient’s blood flow will change and choose the best possible outcome in advance. For example, CFD has been used to model coronary aneurysms in children and suggest techniques for treating them.

There are many advantages to using this method to predict cardiovascular procedure and device success. First, CFD produces detailed data on blood flow near vessel walls, which are difficult to measure experimentally and yet are critical in determining future vessel health. Also, because CFD can simulate variations in blood vessel shape, physicians can use it to optimize surgery plans without experimenting on the patient. For example, CFD has been used to plan surgery to repair the hearts of babies born with only one working ventricle.

Flow velocity simulation contours in cross-sections of three different vessel geometries after a Fontan procedure, which compensates for a weak heart ventricle in babies. This type of work allows surgeons to plan surgeries. W. Yang, JA Feinstein, AL Marsden, et al., Author provided

CFD can also show how blood flow distributes medication to various organs and tissues: tracking the motion of medication particles injected into a vessel reveals where they reach blood vessel walls.

Simulated blood velocity and medication distribution in a patient-specific aorta model. IA Carr, N Nemoto, SC Shadden, et al., Author provided

However, CFD also has its challenges. Cardiovascular devices are more difficult than surgery to model in a simulation. Also, fluid models often must be coupled to models of arterial wall mechanics and biological factors such as cell responses to hormones to obtain a complete simulation of a device or procedure’s impact.

Using experiments to model blood flow

Some researchers, including my group, have taken modeling beyond computers and have fabricated physical models to study how cardiovascular devices affect blood flow. Now 3D printing technology is advanced enough to build realistic models of human blood vessels, and pulsatile-flow pumps can drive flow through these vessels to mimic the heart’s pumping. Since the vessel models are synthetic, there are no ethical issues associated with puncturing them to take flow measurements.

These real-world models also have the advantage that it is possible to install real cardiovascular devices and use real blood, neither of which can be accomplished with a simulation. For example, a recent study found previously unidentified vortices in blood flow through a curved artery downstream of a stent. However, experiments are slower than CFD, more expensive and generally produce lower-resolution data.

There are still many challenges in using fluid mechanics simulations and experiments to predict the success of cardiovascular procedures and devices. The effect of flow on blood vessel health is closely coupled with the elasticity of blood vessel walls and cell responses to blood chemistry; it is difficult to model all of these factors together. It is also hard to validate model data against real human blood flow since it is so difficult to take measurements in a live patient.

Cross-sectional slices of experimental velocity data in a curved blood vessel model. The waveforms at the top indicate points in the cardiac cycle blood flow waveform. Autumn L. Glenn, Kartik V. Bulusu, Fangjun Shu, Michael W. Plesniak, Author provided

However, simulated blood flow models are already being used in the clinic. For example, the FDA recently approved HeartFlow FFR-CT, a flow simulation software package, to help health care professionals evaluate the severity of coronary artery blockages. As blood flow modeling techniques continue to develop, it is our hope that we can acquire more data on the human circulatory system and the effectiveness of devices with minimal human or animal experimentation.

Erica Cherry Kemmerling, Assistant Professor of Mechanical Engineering, Tufts University

This article was originally published on The Conversation. Read the original article.

Featured Image Credit: Alison Marsden, Author provided

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This is Likely the World’s Only 2D Superconductor

Scientists have determined that two-dimensional boron is a natural low-temperature superconductor. In fact, it may be the only 2D material with such potential.

Theoretical physicist Boris Yakobson and colleagues at Rice University published their calculations that show atomically flat boron is metallic and will transmit electrons with no resistance. The work appears in journal Nano Letters.

The hitch, as with most superconducting materials, is that it loses its resistivity only when very cold, in this case between 10 and 20 kelvins (roughly, minus-430 degrees Fahrenheit). But for making very small superconducting circuits, it might be the only game in town.

The basic phenomenon of superconductivity has been known for more than 100 years, said Evgeni Penev, a research scientist in the Yakobson group, but had not been tested for its presence in atomically flat boron.

“It’s well-known that the material is pretty light because the atomic mass is small,” Penev says. “If it’s metallic too, these are two major prerequisites for superconductivity. That means at low temperatures, electrons can pair up in a kind of dance in the crystal.”

“Lower dimensionality is also helpful,” Yakobson says. “It may be the only, or one of very few, two-dimensional metals. So there are three factors that gave the initial motivation for us to pursue the research. Then we just got more and more excited as we got into it.”

Electrons with opposite momenta and spins effectively become Cooper pairs; they attract each other at low temperatures with the help of lattice vibrations, the so-called “phonons,” and give the material its superconducting properties, Penev explains.

“Superconductivity becomes a manifestation of the macroscopic wave function that describes the whole sample. It’s an amazing phenomenon,” he says.

THE FIRST SAMPLES OF BORON

It wasn’t entirely by chance that the first theoretical paper establishing conductivity in a 2D material appeared at roughly the same time the first samples of the material were made by laboratories in the United States and China. In fact, an earlier paper by the Yakobson group had offered a road map for doing so.

That 2D boron has now been produced is a good thing, according to Yakobson and lead authors Penev and Alex Kutana, a postdoctoral researcher at Rice.

“We’ve been working to characterize boron for years, from cage clusters to nanotubes to planer sheets, but the fact that these papers appeared so close together means these labs can now test our theories,” Yakobson says.

“In principle, this work could have been done three years ago as well,” he adds. “So why didn’t we? Because the material remained hypothetical; okay, theoretically possible, but we didn’t have a good reason to carry it too far.

“But then last fall it became clear from professional meetings and interactions that it can be made. Now those papers are published. When you think it’s coming for real, the next level of exploration becomes more justifiable,” Yakobson says.

Boron atoms can make more than one pattern when coming together as a 2D material, another characteristic predicted by Yakobson and his team that has now come to fruition. These patterns, known as polymorphs, may allow researchers to tune the material’s conductivity “just by picking a selective arrangement of the hexagonal holes,” Penev says.

He also notes boron’s qualities were hinted at when researchers discovered more than a decade ago that magnesium diborite is a high-temperature electron-phonon superconductor.

“People realized a long time ago the superconductivity is due to the boron layer,” Penev says. “The magnesium acts to dope the material by spilling some electrons into the boron layer. In this case, we don’t need them because the 2D boron is already metallic.”

Penev suggests that isolating 2D boron between layers of inert hexagonal boron nitride (aka “white graphene”) might help stabilize its superconducting nature.

The Office of Naval Research and the Department of Energy Office of Basic Energy Sciences supported the research, which was published in the journal Nano Letters.

Source: Republished from Futurity.org as a derivative work under the Attribution 4.0 International license. Original article posted to Futurity by Mike Williams-Rice.

Featured Image Credit: Evgeni Penev/Rice University

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Explainer: What child prodigies have in common with kids with autism

By Joanne Ruthsatz, The Ohio State University.

As a toddler growing up in the 1950s, Richard Wawro threw violent tantrums. Often, he would tap the same piano key for long stretches of time.

When he was three, his parents took him for testing at a nearby hospital. They were told that he was moderately to severely retarded. His family, however, never believed that his IQ was as low as the experts claimed.

A special education teacher began working with Richard when he was six. She introduced him to drawing with crayons, which he took to quickly.

He began filling sketchbooks (and the wallpaper of his Scotland home) with startlingly accurate depictions of cartoon characters like Yogi Bear. When Richard was 12, his artwork astounded a visiting artist who said that his drawings were created “with the precision of a mechanic and the vision of a poet.”

Richard could never read or write well. His speech remained limited. But his involvement with the art world spurred his social development. He participated in dozens of exhibitions and became a well-known artist. His artwork was celebrated by the media and in a documentary, “With Eyes Wide Open.” Both Margaret Thatcher and Pope John Paul II owned Wawro’s originals.

Richard was a savant, an individual with a spike in a particular ability combined with an impairment or disability. In Richard’s case, that underlying condition was autism. Autism is a condition characterized by social and communication challenges, like difficulty making eye contact or making conversation, along with repetitive behaviors or intense interests.

It turns out that many savants have autism. In a 2015 paper, the savant expert Darold Treffert reported that among the congenital savants in his registry, 75 percent had an autism spectrum disorder, a term used to describe a group of disorders with variable symptoms and severity.

Exceptional memory and autism

Not every autistic individual has extraordinary talents.

In fact, autism can be accompanied by serious challenges that last a lifetime (as was also the case for Wawro, whose family handled his daily living needs until he died at age 53).

But when the astounding abilities are there, they are often rooted in extreme memory, excellent attention to detail and passionate interests – traits also linked to autism.

My work has been with child prodigies, those astounding individuals who perform at an adult-professional level in a demanding field before adolescence.

In many ways, prodigies look a lot like savants. They have the same preternatural abilities. They have the same prolific output.

But there’s a key difference between the two. While in savants, these extreme abilities are paired with an underlying impairment or disability, prodigies don’t typically have any such disability.

Still, as I recount in my new book, The Prodigy’s Cousin, I have found the overlap between prodigy and autism to be striking. Even though prodigies are not typically autistic, they have the same excellent memories, extreme attention to detail, and passionate interests linked to autism and autistic savants.

The prodigies’ excellent memories were almost immediately apparent. When I investigated nine prodigies across two studies, each one scored in the 99th percentile for this ability. When this group was expanded to 18 prodigies in a 2014 study, the prodigies’ average working memory score was 140 – north of the 95th percentile.

Early work on autism

Reports linking extreme memory and autism date back to the first published reports of Leo Kanner and Hans Asperger, the two scientists credited with identifying autism as an independent condition in the 1940s.

In his landmark 1943 study, Kanner remarked upon his subjects’ “excellent memory for events of several years before, the phenomenal rote memory for poems and names, and the precise recollection of complex patterns and sequences.”

Memory in autistic kids is complex. mimitalks, married, under grace, CC BY-NC-ND

He included a report of a boy, Donald T., with “an unusual memory for faces and names,” who had memorized “an inordinate number of pictures in a set of Compton’s Encyclopedia.” Another, Charles N., could distinguish between 18 symphonies at age one-and-a-half.

Since Kanner’s time, scientists have found that memory in autism is complex. But in a 2015 study, a team of researchers found that more than half of their 200 autistic subjects had notable memories. Treffert has described excellent memory as “integral” for savants in particular.

Prodigies and autism

As part of my 2012 study, the child prodigies I worked with were given the Autism-Spectrum Quotient, a self-administered test designed to measure autistic traits. On attention to detail, they outscored not only the controls, but also those with an autism spectrum disorder.

Attention to detail is another strength associated with autism. Some have described excellent attention to detail as “a universal feature of the autistic brain.” In 2006, the prominent autism researchers Francesca Happé and Uta Frith concluded that there was strong evidence that autism was associated with superiority on “tasks requiring detail-focused processing.”

Child prodigies are also exceptionally passionate about their area of expertise.

Such passionate interests are closely associated with autism. They are even part of autism’s diagnostic criteria.

This trait has been observed since the early days of autism research. Kanner’s 1943 paper includes a description of Alfred L., a child whose mother noted his tendency toward intense interests. As she put it:

He talks of little else while the interest exists, he frets when he is not able to indulge in it (by seeing it, coming in contact with it, drawing pictures of it), and it is difficult to get his attention because of his preoccupation.

This sort of passion can result in prolific output, as it did for Richard Wawro, who created at least 2,453 pictures in his lifetime.

Why do prodigies have autistic relatives?

The link between prodigy and autism could be even deeper than we think.

Researchers have found that child prodigies often have an autistic relative.hepingting, CC BY-SA

In addition to drawing from a similar well of cognitive abilities, there appears to be a family link between prodigy and autism. In a study I conducted in 2012, more than half of the prodigies investigated had a close autistic relative. In one instance, a prodigy had five autistic relatives.

Another study I conducted with colleagues at The Ohio State University suggests that prodigies and their autistic relatives may even share a genetic link. We found evidence that the prodigies and their autistic relatives both had a mutation on chromosome one not shared by their non-prodigious, non-autistic relatives.

The same traits that are celebrated in prodigies – like their excellent attention to detail and the passionate interests – are often recognized as strengths in the context of autism, too, though sometimes families report that the extreme nature of autistic interests can take a toll on family life.

This is a real challenge, as are other aspects of autism. Figuring out the best way to support those with autism and their families is essential.

But let’s remember the strengths of autism as well as the challenges.

Kimberly Stephens, coauthor of The Prodigy’s Cousin, contributed to this piece.

Joanne Ruthsatz, Assistant Professor of Psychology, The Ohio State University

This article was originally published on The Conversation. Read the original article.

Featured Image Credit: MIke Wawro, CC BY