Transforming Ambulances to Trains to Repair the Brain

Imagine your brain as a giant system of metro rail lines with trains constantly zipping through. Now imagine an earthquake crumbles many of the lines; obviously we’re talking about some sort of brain damage here such as trauma or Alzheimer’s disease. In the real world, ambulances, fire trucks and eventually construction vehicles appear on the scene to clean up the mess and get the whole system back on track.

Your brain has analogous cells as well called glial cells that appear on the scene to repair damaged neurons. But now imagine that the entire emergency response system of New York shows up for damaged lines in Queens and then refuse to get out of the way once the job is done. Sure, the damage may be somewhat repaired, but the vehicles are blocking the paths.

This is sort of what happens with glial scarring. The glial cells that support healthy neurons build up on a damaged site and don’t let any more trains pass. But researchers at Penn State hope they have found a solution. They have demonstrated the ability to convert ambulances and police cars to rail trains, freeing up the transportation system once more.

The researchers accomplished this feat using genetic engineering techniques, introducing a retrovirus to glial cells to deliver a protein called NeuroD1, which is known to be important in the formation of nerve cells in the hippocampus area of adult brains. They hypothesized that expressing NeuroD1 protein into the reactive glial cells at the injury site might help to generate new neurons — just as it does in the hippocampus.

In one test, the team showed that the retrovirus could coax glial cells into becoming functional neural cells in adult mice. What’s more, they found that two types of glial cells can be converted into both excitatory and inhibitory neurons, which is important for proper brain function. While some neurons in your brain are excitatory, passing signals on to their neighbors, others are inhibitory, telling them to calm the hell down.

In a second test, the team showed that the same could be done in adult mouse models of Alzheimer’s disease, even when the mice were 14 months old, which is 60 in human years. “Therefore, the conversion technology that we have demonstrated in the brains of mice potentially may be used to regenerate functional neurons in people with Alzheimer’s disease,” said Gong Chen, a professor of biology, the Verne M. Willaman Chair in Life Sciences at Penn State, and the leader of the research team.

Finally, Chen and his colleagues showed that the same technique could work for human glial cells in a laboratory experiment. “Within 3 weeks after expression of the NeuroD1 protein, we saw in the microscope that human glial cells were reinventing themselves: they changed their shape from flat sheet-like glial cells into normal-looking neurons with axon and dendritic branches,” Chen said. The scientists further tested the function of these newly converted human neurons and found that, indeed, they were capable of both releasing and responding to neurotransmitters.

 

“Our dream is to develop this in vivo conversion method into a useful therapy to treat people suffering from neural injury or neurological disorders,” Chen said. “Our passionate motivation for this research is the idea that an Alzheimer’s patient, who for a long time was not able to remember things, could start to have new memories after regenerating new neurons as a result of our in vivo conversion method, and that a stroke victim who could not even move his legs might start to walk again.”

Of course, caveats abound for projects like this. Just because something works in a mouse model does not mean it will work in an actual human brain. And even if it does, the potential side effects are numerous. And even converting excess glial cells into active neural cells likely can’t repair all of the damage done by debilitating diseases.

Can transformed glial cells actually integrate into the existing neural network harmoniously? Can they even be transformed at all? This is just a first step, and most first steps lead to nowhere. But still, it’s a cool and exciting first step nonetheless.

The paper, “In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model,” was published in the journal Cell by Chen and his colleagues Ziyuan Guo, Lei Zhang, Zheng Wu, Yuchen Chen, and Fan Wang, all from Penn State.

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The Duck-Billed Platypus of the Plant World

Amborella

Amborella

Flowering plants are pretty important. Besides giving us a way to try to make amends for acting like less civilized versions of ourselves while in a state of extreme inebriation, they also provide the plants responsible for creating the opportunity to get to that inebriated state to begin with. That, and they pretty much provide all of the fruits and vegetables we consume on a daily basis. So yeah, you might say they’re pretty important.

Interestingly enough, the fossil record shows that flowering plants didn’t make an appearance on this planet until about 200 million years ago. But once they did, the proliferated extremely quickly, covering the globe and diversifying into the more than 300,000 species prospering today. That’s roses, corn, cherries, apples, dandelions – you name it.

new_caledoniaIn a recent issue of Science, researchers report on the genome sequencing of one of the more interesting lineages still alive and kicking. Amborella trichopoda is a shrub that grows in one place and one place only – the bustling metropolis that is New Caledonia. What makes Amborella interesting is that it split from the evolutionary tree of flowering plants not long after they appeared at all.

It’s sort of like the duck-billed platypus of the flowering kingdom. It’s still technically a flower, but it’s quite different from many of its distant cousins because of how long ago it branched away into a new evolutionary direction.

Reading the shrub’s DNA has given researchers a possible insight into how flowering plants evolved in the first place. They believe now that it all started with a gene-doubling event. In other words, a few of our flowers’ ancient ancestors accidentally and suddenly created cells with a whole lot of extra copies of genes. And that situation is exactly what you need for an explosion in evolution.

If you have a gene that codes for the chloroplasts that convert sunlight into energy and it gets horribly mutated, what happens? It breaks down and the plant dies. But what happens if there are two of those genes? Even if one is broken, the other can pick up the slack and keep the organism alive. That gives the genetic duplicates the freedom to mutate and change into weird and exciting new forms without putting the plant at risk. And eventually at least a few of those mutating genes will become something new and useful, like, for example, the pistols and pollen of a flowering plant.

Genome doubling may offer an explanation for the apparently abrupt proliferation of new species of flowering plants in fossil records dating to the Cretaceous period,” said Claude dePamphilis, professor of biology at Penn State, the overall principal investigator for the project, and the corresponding author for the paper. “Generations of scientists have worked to solve this puzzle, known as Darwin’s “abominable mystery.”

The paper, “The Amborella Genome and the Evolution of Flowering Plants,” was published in Science by dePamphilis and a whole host of other researchers from many other institutions, including Penn State University, the University at Buffalo, the University of Florida, the University of Georgia, and the University of California-Riverside.

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Powering a Pacemaker with the Heart it Keeps in Rhythm

The implant contains a flexible piezoelectric film and a tiny rechargeable battery. (Credit: John Rogers, University of Illinois)

The implant contains a flexible piezoelectric film and a tiny rechargeable battery. (Credit: John Rogers, University of Illinois)

It’s beginning to become pretty apparent to me that Yonggang Huang of Northwestern University and John Rogers of the University of Illinois are two of the biggest science rock stars in the Big Ten. And when you put the two of them together in collaboration, amazing things will soon follow. The duo have a longstanding collaboration that researchers flexible electronics.

Take, for example, my post from 2011 about stick-on “tattoos” that are basically fully functioning, wireless computer chips just 40 micrometers thick that stick to human skin without any sort of adhesive. These could act as an EEG or EMG sensor to monitor nerve and muscle activity, or a sensor to monitor brain waves, sleeping patterns and other brain functions. Current methods require sticky gel pads to be placed all over the body with long, clunky wires attached to computers and power sources. But the new electronic tattoos have all of that built in. You could walk around all day, sleep on your sofa and go for a run without even noticing that you’re wearing medical devices.

Or there’s my post from 2012 on similarly thin electronic strips with all the wiring embedded that dissolve away completely in the presence of water. The possibilities are endless. Medical implants – sensors or thermal therapeutic devices, for example – could simply vanish once they are no longer needed. Environmental sensors could be deployed without the need to retrieve them ever. Hell, cell phones could disintegrate away into thin air once the next model gets released.

Or the post from 2013 on radically new camera lenses that integrate many cameras on a spherical surface much like a bug’s eye to create a wide field of vision. Again, flexible electronics that can conform to the shape of a sphere were integral to the project.

Well, they’re at it again, folks, this time with some piezoelectric magic.

Piezo comes from the Greek word for pressure, while electric means exactly what you think it is. So these materials are able to generate electricity through the pressures exerted on them and the deformations those pressures cause. There are a lot of projects out there trying to harness energy from wearable electronics embedded in your shoes or clothing, so that natural everyday movements could charge electronic devices.

But for their new project, Huang and Rogers went for something even more intrinsic to your everyday life – the beating of a human heart.

The duo have now demonstrated a thin-film, all-in-one electronic device that can adhere to the surface of a heart and generate electricity from its constant beating. Such a device could power pacemakers, defibrillators and heart-rate monitors naturally and reliably and reduce or eliminate the need for batteries.

You could see this sort of advance coming by looking at their previous work. Thin film electronics, biocompatible materials, adhesive films—it all adds up to implantable microdevices. In their study, the team attached their prototype to the hearts, lungs, and diaphragms of living animals and produced enough electricity to charge a 3.8-volt battery.

“This work is a great demonstration of engineers working with doctors and taking advantage of the natural properties of a beating heart,” Huang said. “We envision this device being used to power a pacemaker with the energy coming right from the heart.”

With a proof-of-concept in the bag, the pair are now working to optimize different design layouts of the stretchable mechanical energy harvester to facilitate its easy use. This is step one toward having everything mentioned above actually available in humans.

So stay tuned.

The paper, “Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm,” was published in the Proceedings of the National Academy of Sciences by Huang and Rogers, and, of course, an entire slew of brilliant team members.

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Seeing the Forrest for the Batshit

?????????????????????????????????????????????????Just time for a quickie this morning, partly because I’m busy and partly because there’s not a ton to say about this particular interesting tidbit.

What do you do when fruit bats start spreading a deadly virus in rural populations of developing nations that kills in more than 70 percent of cases and has no cure nor vaccine? The immediate answer might be to kill all the fruit bats. No bats equals no viral spread.

But you might also consider planting some trees.

After going door-to-door in affected areas of Bangladesh, using GPS-assisted data collection and satellite remote sensing, researchers noticed a glaring trend; people who lived in deforested areas were the only ones getting sick.

The reason?

In areas with a lot of trees and thus a lot of fruit, the fruit bats didn’t need to find their food in human villages. Thus if they’re not flying around the villages, they’re not defecating into common sap collection jars and other food-gathering tools.

First of all, gross. Aren’t you glad you live in a place where you don’t have to worry about bats shitting in your food? And second of all, goddamnitthatsgross.

“The immediate reaction may be to get rid of the bats,” said Micah Hahn, who received her joint PhD in epidemiology and environment and resources from the University of Wisconsin, and is now working on a joint post-doctoral fellowship with the Centers for Disease Control in Fort Collins, Colo. and the National Center for Atmospheric Research in Boulder, Colo., “so we won’t have Nipah virus, but bats are important as seed spreaders for forest regeneration, they eat a lot of different fruits and fly long distances. The presence of bats alone is not a risk factor; there are villages with bats but that haven’t had Nipah virus cases. This is not just about having bats, the disease risk is a result of humans changing the landscape in ways that create opportunities for human-wildlife interactions.”

The study, “The Role of Landscape Composition and Configuration on Pteropus giganteus Roosting Ecology and Nipah Virus Spillover Risk in Bangladesh,” was published in the American Journal of Tropical Medicine and Hygiene by first author Hahn.

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Messing with a Spud’s Glycemic Index

chipsAnybody who has worried about cutting carbs or sticking to a South Beach diet has probably heard of the term glycemic index. In short, it’s a scale that indicates how quickly eating a specific type of food will raise your blood sugar levels.

If you’re an athlete, you want that blood sugar spike to fuel your competition. If you’re dieting, you want to avoid that rush because excess sugar will quickly be stored as fat if you don’t use it immediately and you’ll be hungry again very quickly. And if you’re a diabetic, the sugar rush can kill you.

There’s not much left to do but avoid certain foods like highly processed carbohydrates and simple starches. That is, unless you’re a kick-ass food scientist.

Take Srinivas Janaswamy from Purdue University, for example. He’s figured out a way to embed different kinds of molecules within a simple starch lattice.

A simple starch is little more than a handful of glucose (sugar) molecules linked together in a certain pattern—a pattern that creates holes. Janaswamy has shown that he can insert different molecules inside of these natural holes, changing the way the starch is digested without actually changing the chemistry of the starch itself.

Sort of like sticking a bunch of fruit inside of a Jello mold; you don’t change the Jello at all but the bits get trapped and go along for the ride.

So far he’s shown that adding certain molecules can slow down the digestion of a potato starch, which in theory could stop the common food from causing blood sugar spikes. But he’s also going further and showing that you can embed just about anything from antioxidants to vitamins to flavor molecules. Sounds like the first step to a healthy potato chip that tastes like chocolate to me!

There is one catch, of course, and that is that the process has only been shown to work in vitro. For those of you lacking in your Latin, that phrase means that it hasn’t been tested inside of an actual stomach yet, only outside of an organism in a dish or beaker somewhere. Only time will tell if the method works inside of an actual stomach.

The paper, “Encapsulation altered starch digestion: Toward developing starch-based delivery systems,” was published in the journal Carbohydrate Polymers by Janaswarmy and Janaswarmy alone.

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Maybe Pot Needs a Minimum Legal Age, Too

exploredti-tractsAfter being mostly legalized in Washington and Colorado, marijuana is becoming a trendier news topic with every passing day. And when a topic is trending in the 24-hour news cycle, you can be sure that scientific studies are soon to follow. What greater influence on those who award the grants is there?

One common argument for the legalization of pot is that it isn’t harmful to human health; or at the very least, not as harmful as alcohol, a substance that was only illegal for a brief, dark period in human history in a very backward corner of the globe.

Whether or not the substance is addictive is, to me at least, an open question. A website from the NIH reports that marijuana is addictive to about 9 percent of users, raising to 17 percent in teenage users and 25-50 percent in daily users. Then again, they also report the “withdrawal” symptoms of irritability, sleeplessness, anxiety and drug craving, all of which my wife exhibits after a couple of days without chocolate and seem less of a problem than someone going through caffeine withdrawal.

But I’m not here to make judgments or assumptions; I’m just here to report the facts. According to a recent study from Northwestern University, there is at least one health concern that might be worth taking into account when decriminalizing this controlled substance, and that’s age.White_Matter_Fiber_Architecture_Slideshow_full

As many studies have shown, at least some of the wiring in the human brain continues to develop well into the early 20s. We are born with a massive number of jumbled connections that slowly get either strengthened or pruned as we experience the world around us. Sufficed to say, those experiences have an impact on how our wiring takes shape and the ability for it to change years later down the line. So introducing any type of chemical that might affect how these wires are crossed is an issue well worth considering.

In the new study, researchers looked at the brains of 97 individuals who partook in daily THC doses in their late teens or early twenties for several years, but had since stopped the habit. They used fMRI machines to trace the connections made deep within the brain’s white matter.

A thin layer of neurons at the surface of the brain called the cortex is where most of the actual computation is going on at any given time. Called grey matter, these brain cells are responsible for seeing, hearing, memory, emotions, speech, decision making, and self-control, to name a few, and consume 95 percent of the oxygen that is sent to your noggin.

By contrast, white matter mostly makes up the interior of your brain and acts more or less as connections between the different areas on the surface. They make crucial communication pathways between your emotional center, decision-making center and muscle control functions, for example. How else are you going to binge eat after watching the Red Wedding for a tenth time?

It is these wires or connections that the researchers mapped out. And what they found was that those who had previously used marijuana on a daily basis had distinctly different white matter patterns than those who did not. What’s more, those changes bore a striking resemblance to disparities found in those suffering from schizophrenia—a condition whose strength of affliction has been linked to marijuana use in previous studies. It has also been linked to a poor working memory, which predicts poor academic performance and everyday functioning.

Now, of course, this study is not definitive. What if the marijuana users had these subtle differences in brain wiring before they started smoking? What if these differences are actually part of the reason they started in the first place? Or maybe there’s some other confounding factor that links the dozens of subjects together?

Some sort of long-term longitudinal study would be need to tease out the exact implications, meaning they’d have to map a lot of people’s brain before they started smoking as well as years afterward and compare them to similar controls. And who knows? Maybe that might be possible if more states legalize the practice.

But for now, if I were a neuroscience graduate student studying in Colorado or Washington, I know exactly what study I’d be proposing for my thesis.

The study, “Cannabis-Related Working Memory Deficits and Associated Subcortical Morphological Differences in Healthy Individuals and Schizophrenia Subjects,” was published in the journal Schizophrenia Bulletin by senior co-author John G. Csernansky, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital.

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Self-Healing Engineered Muscle Grown in the Laboratory

Long, colorful strands of engineered muscle fiber have been stained to observe growth after implantation into a mouse.

Long, colorful strands of engineered muscle fiber have been stained to observe growth after implantation into a mouse.

Biomedical engineers have grown living skeletal muscle that looks a lot like the real thing. It contracts powerfully and rapidly, integrates into mice quickly, and for the first time, demonstrates the ability to heal itself both inside the laboratory and inside an animal.

The study conducted at Duke University tested the bioengineered muscle by literally watching it through a window on the back of living mouse. The novel technique allowed for real-time monitoring of the muscle’s integration and maturation inside a living, walking animal.

Both the lab-grown muscle and experimental techniques are important steps toward growing viable muscle for studying diseases and treating injuries, said Nenad Bursac, associate professor of biomedical engineering at Duke.

This series of images shows the destruction and subsequent recovery of engineered muscle fibers that had been exposed to a toxin found in snake venom. This marks the first time engineered muscle has been shown to repair itself after implantation into a living animal.

This series of images shows the destruction and subsequent recovery of engineered muscle fibers that had been exposed to a toxin found in snake venom. This marks the first time engineered muscle has been shown to repair itself after implantation into a living animal.

The results appear the week of March 25 in the Proceedings of the National Academy of Sciences Early Edition.

“The muscle we have made represents an important advance for the field,” Bursac said. “It’s the first time engineered muscle has been created that contracts as strongly as native neonatal skeletal muscle.”

Through years of perfecting their techniques, a team led by Bursac and graduate student Mark Juhas discovered that preparing better muscle requires two things — well-developed contractile muscle fibers and a pool of muscle stem cells, known as satellite cells.

Every muscle has satellite cells on reserve, ready to activate upon injury and begin the regeneration process. The key to the team’s success was successfully creating the microenvironments — called niches — where these stem cells await their call to duty.

This series of images shows the progress  of veins slowly growing into implanted engineered muscle fibers.

This series of images shows the progress of veins slowly growing into implanted engineered muscle fibers.

“Simply implanting satellite cells or less-developed muscle doesn’t work as well,” said Juhas. “The well-developed muscle we made provides niches for satellite cells to live in, and, when needed, to restore the robust musculature and its function.”

To put their muscle to the test, the engineers ran it through a gauntlet of trials in the laboratory. By stimulating it with electric pulses, they measured its contractile strength, showing that it was more than 10 times stronger than any previous engineered muscles. They damaged it with a toxin found in snake venom to prove that the satellite cells could activate, multiply and successfully heal the injured muscle fibers.

Then they moved it out of a dish and into a mouse.

With the help of Greg Palmer, an assistant professor of radiation oncology in the Duke University School of Medicine, the team inserted their lab-grown muscle into a small chamber placed on the backs of live mice. The chamber was then covered by a glass panel. Every two days for two weeks, Juhas imaged the implanted muscles through the window to check on their progress.

By genetically modifying the muscle fibers to produce fluorescent flashes during calcium spikes — which cause muscle to contract — the researchers could watch the flashes become brighter as the muscle grew stronger.

“We could see and measure in real time how blood vessels grew into the implanted muscle fibers, maturing toward equaling the strength of its native counterpart,” said Juhas.

The engineers are now beginning work to see if their biomimetic muscle can be used to repair actual muscle injuries and disease.

“Can it vascularize, innervate and repair the damaged muscle’s function?” asked Bursac. “That is what we will be working on for the next several years.”

This work was supported by a National Science Foundation Graduate Research Fellowship and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR055226).

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“Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo.” Juhas, M., Engelmayr, Jr., G.C., Fontanella, A.N., Palmer, G.M., Bursac, N. PNAS Early Edition, March, 2014. DOI: 10.1073/pnas.1402723111

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