Why Do Flowers Do The Thing They Do?

I wish you all a Merry Christmas!

It’s a tremendous Trilobite Tuesday! 

When most of us think about trilobites, we imagine rather small creatures that inhabited the ancient seas. Indeed, most members of the more than 25,000 scientifically recognized trilobite species were less that three inches in length. Occasionally, however, paleontologists encounter a megafauna where, due to a variety of circumstances, the trilobite species were huge. One of these megafaunas can be found near the small Portuguese town of Arouca where the 450 million year-old Valongo formation produces prodigious numbers of exceptionally large Ordovician-age trilobites, such as this 41 cm Hungioides bohemicus. Other trilobite magafaunas appear sporadically around the globe, including Cambrian locations in Morocco and Devonian outcrops in Nevada.

Meet many more trilobites on the Museum website.

Manufacturing Dopamine in the Brain with Gene Therapy

Parkinson’s patients who take the drug levodopa, or L-Dopa, are inevitably disappointed. At first, during a “honeymoon” period, their symptoms (which include tremors and balance problems) are brought under control. But over time the drug becomes less effective. They may also need ultrahigh doses, and some start spending hours a day in a state of near-frozen paralysis.

A biotech company called Voyager Therapeutics now thinks it can extend the effects of L-Dopa by using a surprising approach: gene therapy. The company, based in Cambridge, Massachusetts, is testing the idea in Parkinson’s patients who’ve agreed to undergo brain surgery and an injection of new DNA.

Parkinson’s occurs when dopamine-making neurons in the brain start dying, causing movement symptoms that afflicted boxing champ Muhammad Ali and actor Michael J. Fox, whose charitable foundation has helped pay for the development of Voyager’s experimental treatment.

The cause of Parkinson’s isn’t well understood, but the reason the drug wears off is. It’s because the brain also starts losing an enzyme known as aromatic L-amino acid decarboxylase, or AADC, that is needed to convert L-Dopa into dopamine.

Voyager’s strategy, which it has begun trying on patients in a small study, is to inject viruses carrying the gene for AADC into the brain, an approach it thinks can “turn back the clock” so that L-Dopa starts working again in advanced Parkinson’s patients as it did in their honeymoon periods.

Videos of patients before and after taking L-Dopa make it obvious why they’d want the drug to work at a lower dose. In the ‘off’ state, people move in slow motion. Touching one’s nose takes an effort. In an ‘on’ state, when the drug is working, they’re shaky, but not nearly so severely disabled.

“They do well at first but then respond very erratically to L-Dopa,” says Krystof Bankiewicz, the University of California scientist who came up with the gene-therapy plan and is a cofounder of Voyager. “This trial is to restore the enzyme and allow them to be awakened, or ‘on,’ for a longer period of time.”

Voyager was formed in 2013 and later went public, raising about $86 million. The company is part of a wave of biotechs that have been able to raise money for gene therapy, a technology that is starting to pay off: after three decades of research, a few products are reaching the market.

Unlike conventional drug studies, those involving gene therapy often come with very high expectations that the treatment will work. That’s because it corrects DNA errors for which the exact biological consequences are known. Genzyme, a unit of the European drug manufacturer Sanofi, paid Voyager $65 million and promised hundreds of millions more in order to sell any treatments it develops in Europe and Asia.

“We’re working with 60 years of dopamine pharmacology,” says Steven Paul, Voyager’s CEO, and formerly an executive at the drug giant Eli Lilly. “If we can get the gene to the right tissue at the right time, it would be surprising if it didn’t work.”

But those are big ifs. In fact, the concept for the Parkinson’s gene therapy dates to 1986, when Bankiewicz first determined that too little AADC was the reason L-Dopa stops working. He thought gene therapy might be a way to fix that, but it wasn’t until 20 years later that he was able to test the idea in 10 patients, in a study run by UCSF.

In that trial, Bankiewicz says, the gene delivery wasn’t as successful as anticipated. Not enough brain cells were updated with the new genetic information, which is shuttled into them by viruses injected into the brain. Patients seemed to improve, but not by much.

Even though the treatment didn’t work as planned, that early study highlighted one edge Voyager’s approach has over others. It is possible to tag AADC with a marker chemical, so doctors can actually see it working inside patients’ brains. In fact, ongoing production of the dopamine-making enzyme is still visible in the brains of the UCSF patients several years later.

It is possible to tag AADC with a marker chemical, so doctors can actually see it working inside patients’ brains. Image Source: MIT Technology Review.

In some past studies of gene therapy, by contrast, doctors had to wait until patients died to find out whether the treatment had been delivered correctly. “This is a one-and-done treatment,” says Paul. “And anatomically, it tells us if we got it in the right place.”

A new trial under way, this one being carried out by Voyager, is designed to get much higher levels of DNA into patients’ brains in hopes of achieving better results. To do that, Bankiewicz developed a system to inject the gene-laden viral particles through pressurized tubes while a patient lies inside an MRI scanner. That way, the surgeon can see the putamen, the brain region where the DNA is meant to end up, and make sure it’s covered by the treatment.

There are other gene therapies for Parkinson’s disease planned or in testing. A trial developed at the National Institutes of Health seeks to add a growth factor and regenerate cells. A European company, Oxford BioMedica, is trying to replace dopamine.

Altogether, as of this year, there were 48 clinical trials under way of gene or cell replacement in the brain and nervous system, according to the Alliance for Regenerative Medicine, a trade group. The nervous system is the fourth most common target for this style of experimental treatment, after cancer, heart disease, and infections.

Voyager’s staff is enthusiastic about a study participant they call “patient number 6,” whom they’ve been tracking for several months—ever since he got the treatment. Before the gene therapy, he was on a high dose of L-Dopa but still spent six hours a day in an “off” state. Now he’s off only two hours a day and takes less of the drug.

That patient got the highest dose of DNA yet, covering the largest brain area. That is part of what makes Voyager think higher doses should prove effective. “I believe that previous failure of gene-therapy trials in Parkinson’s was due to suboptimal delivery,” says Bankiewicz.

Image Credit: L.A. JOHNSON

Source: MIT Technology Review (by Antonio Regalado)

Dive deep into Episode 05 of #ShelfLife to discover the various technologies that have helped humans map the sky around us for eons. 

From sundials to mega-powered modern telescopes, tools for stargazing allow us to understand the universe—and our place within it. Season 2 begins on November 1. 

Quote from Sau Lan Wu, scientist who discovered the #higgsboson. More quotes like this one to inspire you in my I Love Science Journal coming to stores in March. Preorder now on Amazon! #ilovescience #womeninscience #scientificliteracy

It is imperfection - not perfection - that is the end result of the program written into that formidably complex engine that is the human brain, and of the influences exerted upon us by the environment and whoever takes care of us during the long years of physical, psychological and intellectual development.

Rita Levi-Montalcini

Image Credit: Hammersmith Hospital in London

(via neuromorphogenesis)

Giant Artwork Reflects The Gorgeous Complexity of The Human Brain

The new work at The Franklin Institute may be the most complex and detailed artistic depiction of the brain ever.

Your brain has approximately 86 billion neurons joined together through some 100 trillion connections, giving rise to a complex biological machine capable of pulling off amazing feats. Yet it’s difficult to truly grasp the sophistication of this interconnected web of cells.

Now, a new work of art based on actual scientific data provides a glimpse into this complexity.

The 8-by-12-foot gold panel, depicting a sagittal slice of the human brain, blends hand drawing and multiple human brain datasets from several universities. The work was created by Greg Dunn, a neuroscientist-turned-artist, and Brian Edwards, a physicist at the University of Pennsylvania, and goes on display at The Franklin Institute in Philadelphia. 

“The human brain is insanely complicated,” Dunn said. “Rather than being told that your brain has 80 billion neurons, you can see with your own eyes what the activity of 500,000 of them looks like, and that has a much greater capacity to make an emotional impact than does a factoid in a book someplace.”

To reflect the neural activity within the brain, Dunn and Edwards have developed a technique called micro-etching: They paint the neurons by making microscopic ridges on a reflective sheet in such a way that they catch and reflect light from certain angles. When the light source moves in relation to the gold panel, the image appears to be animated, as if waves of activity are sweeping through it.

First, the visual cortex at the back of the brain lights up, then light propagates to the rest of the brain, gleaming and dimming in various regions — just as neurons would signal inside a real brain when you look at a piece of art.

That’s the idea behind the name of Dunn and Edwards’ piece: “Self Reflected.” It’s basically an animated painting of your brain perceiving itself in an animated painting.

To make the artwork resemble a real brain as closely as possible, the artists used actual MRI scans and human brain maps, but the datasets were not detailed enough. “There were a lot of holes to fill in,” Dunn said. Several students working with the duo explored scientific literature to figure out what types of neurons are in a given brain region, what they look like and what they are connected to. Then the artists drew each neuron.

Dunn and Edwards then used data from DTI scans — a special type of imaging that maps bundles of white matter connecting different regions of the brain. This completed the picture, and the results were scanned into a computer. Using photolithography, the artists etched the image onto a panel covered with gold leaf.

“A lot of times in science and engineering, we take a complex object and distill it down to its bare essential components, and study that component really well” Edwards said. But when it comes to the brain, understanding one neuron is very different from understanding how billions of neurons work together and give rise to consciousness.

“Of course, we can’t explain consciousness through an art piece, but we can give a sense of the fact that it is more complicated than just a few neurons,” he added.

The artists hope their work will inspire people, even professional neuroscientists, “to take a moment and remember that our brains are absolutely insanely beautiful and they are buzzing with activity every instant of our lives,” Dunn said. “Everybody takes it for granted, but we have, at the very core of our being, the most complex machine in the entire universe.”

Image 1: A computer image of “Self Reflected,” an etching of a human brain created by artists Greg Dunn and Brian Edwards.

Image 2: A close-up of the cerebellum in the finished work.

Image 3: A close-up of the motor cortex in the finished work.

Image 4: This is what “Self Reflected” looks like when it’s illuminated with all white light.

Image 5: Pons and brainstem close up.

Image 6: Putkinje neurons - color encodes reflective position in microetching.

Image 7: Primary visual cortex in the calcarine fissure.

Image 8: Basal ganglia and connected circuitry.

Image 9: Parietal cortex.

Image 10: Cerebellum.

Credit for all Images: Greg Dunn - “Self Reflected”

Source: The Huffington Post (by Bahar Gholipour)

For those poorly informed (educated) who insist that vaccines are just the same as catching the illness…. This is just one example of why that is not true.

Breakthrough for vaccine research: Mucosa forms special immunological memory

If a vaccine is to protect the intestines and other mucous membranes in the body, it also needs to be given through the mucosa, for example as a nasal spray or a liquid that is drunk. The mucosa forms a unique immunological antibody memory that does not occur if the vaccine is given by injection. This has been shown by a new study from Sahlgrenska Academy published in Nature Communications.                                

Immunological memory is the secret to human protection against various diseases and the success of vaccines. It allows our immune system to quickly recognize and neutralize threats. “The largest part of the immune system is in our mucosa. Even so, we understand less about how immunological memory protects us there than we do about protection in the rest of the body. Some have even suggested that a typical immune memory function does not exist in the mucosa,” says Mats Bemark, associate professor of immunology at Sahlgrenska Academy, University of Gothenburg.

After extensive work, the research team at Sahlgrenska Academy can now show that this assumption is completely wrong.

Mats Bemark et al. Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization, Nature Communications (2016). DOI: 10.1038/ncomms12698

This new drug is as strong as morphine, but without the side effects

Incredible pain relief – without the addiction.

Scientists have developed a new drug that could be a safer alternative to morphine for medical use. The researchers found that engineered variants of endomorphin, a naturally occurring chemical in the body, are as strong as morphine when it comes to killing pain.

On top of that, the medication doesn’t produce any of the unwanted side effects that come with opium-based drugs – such as being extremely addictive. At this point, the findings only relate to tests in rats, but it’s a promising start to what could be a powerful and less problematic painkiller.

Opioid pain medications are commonly used to treat severe and chronic pain, but in addition to their habit-forming qualities, patients also build up a tolerance to them over time. Hand in hand with their addictiveness, this can makes higher doses – and overdoses in drug abuse situations – dangerous. Overdoses can cause motor impairment and potentially fatal respiratory depression, resulting in thousands of deaths in the US every year.