Next Week I’ll Give A Presentation On The Researchers Night At Eötvös Loránd University, Hungary

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)

Solidification of liquid Gallium 

Gallium is a chemical element with symbol Ga and atomic number 31. Gallium is a soft, silvery metal, and elemental gallium is a brittle solid at low temperatures, and melts at 29.76 °C (85.57 °F) (slightly above room temperature). Elemental gallium is not found in nature, but it is easily obtained by smelting.

Gallium metal expands by 3.1% when it solidifies, and therefore storage in either glass or metal containers are avoided, due to the possibility of container rupture with freezing. Gallium shares the higher-density liquid state with only a few materials, like water, silicon,germanium, bismuth, and plutonium.

Giffed by: rudescience  From: This video

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

Maryam Mirzakhani was an Iranian mathematician and a professor of mathematics at Stanford University. She was the first-ever female winner of the prestigious Fields Medal prize and the first Iranian to be honoured with the award.

Mirzakhani was born in Tehran, Iran. She attended Farzanegan School, which was part of the National Organization for Development of Exceptional Talents. In both 1994 and 1995 she won the International Mathematical Olympiads for high-school students. In the 1995 International Mathematical Olympiad, she became the first Iranian student to achieve a perfect score and to win two gold medals.

Mirzakhani continued her education at Sharif University of Technology in Tehran, where she earned a BSc in Mathematics. After this, she undertook a  a Ph.D. from Harvard University. She worked under the supervision of the Fields Medalist Curtis T. McMullen, and her dissertation focused on Simple Geodesics on Hyperbolic Surfaces and Volume of the Moduli Space of Curves. She had a unique way of working, and “would spend hours on the floor with supersized canvases of paper, sketching out ideas, drawing diagrams and formulae, often leading Anahita [her daughter] to say, “Oh, Mommy is painting again!” Mirzankhani said that “I don’t have any particular recipe [for developing new proofs] … It is like being lost in a jungle and trying to use all the knowledge that you can gather to come up with some new tricks, and with some luck you might find a way out.”

From 2004 to 2008 she was a Clay Mathematics Institute Research Fellow and an assistant professor at Princeton University. She then became a professor at Stanford University where she specialized in theoretical mathematics including moduli spaces, Teichmüller theory, hyperbolic geometry, Ergodic theory and symplectic geometry.” 

In 2014, Mirzakhani was awarded the Fields Medal prize for her work on complex geometry and dynamic systems, becoming the first-ever female winner and the first Iranian to be honoured with the award. During her lifetime, she won a number of awards including the 2009 Blumenthal Award for the Advancement of Research in Pure Mathematics and the 2013 Satter Prize of the American Mathematical Society. She worked up until her death in 2017, and was still producing amazing mathematics during her battle with cancer over the last few years.

Sources here, here, here, here and here

Superconducting Bismuth Is Real, and It's Forcing Us to Rethink the Nature of Superconductivity

A Nobel Prize-winning theory has been challenged.

Bismuth is one of the weirdest-looking elements on the Periodic Table, but its internal properties just got even stranger. Scientists have discovered that at a fraction of a degree above absolute zero (-273.15°C), bismuth becomes a superconductor - a material that can conduct electricity without resistance.

According to the current theory of superconductivity, that doesn’t make a whole lot of sense, because for 40 years now, scientists have assumed that superconducting materials must be abundant in free-flowing mobile electrons. But in bismuth, there’s just one mobile electron for every 100,000 atoms.

“In general, compounds that exhibit superconductivity have roughly one mobile electron per atom,” Srinivasan Ramakrishnan from the Tata Institute of Fundamental Research in India explained to Chemistry World.

“However, in bismuth, one mobile electron is shared by 100,000 atoms – since [the] carrier density is so small, people did not believe bismuth will superconduct.”

Continue Reading.

Scientists are pretty sure that deep inside the moon, there’s water

While Earth’s surface cracks and spouts fire, the moon’s surface, for as long as we’ve known it, has been quiet. 

The youngest sign of volcanic activity scientists have found on the moon’s surface is 18 million years old.

But the traces of that long-ago volcanic activity could help scientists crack an enduring mystery: How much water is on the moon?

A study published Monday in Nature Geoscience suggests it may be more than we thought. Read more (7/24/17)

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For #WorldBeeDay, here’s a look at the chemistry behind the honey some bees produce: https://ift.tt/2GV5qtq https://ift.tt/2LJpsIe

Physicists Have Created a New Form of Hydrogen

The most abundant element in the Universe just got interesting.

As the element that makes up 75 percent of all the mass in the Universe, and more than 90 percent of all the atoms, we’re all pretty well acquainted with hydrogen.

But the simplest and most abundant element in the Universe still has some tricks up its sleeve, because physicists have just created a never-before-seen form of hydrogen - negatively charged hydrogen clusters.

To understand what negatively charged hydrogen clusters are, you first have to wrap your head around their far more common counterparts - positively charged hydrogen clusters.

Positively charged hydrogen clusters are pretty much exactly what they sound like - positively charged clusters of a few or many hydrogen molecules.

Known simply as hydrogen ion clusters, they form at very low temperatures, and can contain as many as 100 individual atoms.

Physicists confirmed the existence of hydrogen ion clusters some 40 years ago, and while a negative counterpart to these clusters boasting large numbers of atoms were theorised, no one could figure out how to create one.

But that didn’t stop a team of physicists led by Michael Renzler from the University of Innsbruck in Austria from giving it a shot.

Continue Reading.

Antibiotic resistance discovered in the guts of ancient mummies

The gut bacteria inside 1000-year-old mummies from the Inca Empire are resistant to most of today’s antibiotics, even though we only discovered these drugs within the last 100 years.

“At first we were very surprised,” Tasha Santiago-Rodriguez of California Polytechnic State University in San Louis Opisbo, told the Annual Meeting of the American Society for Microbiology last month.

Her team studied the DNA within the guts of three Incan mummies dating back to between the 10th and 14thcenturies and six mummified people from Italy, from between the 15th and 18th centuries. They found an array of genes that have the potential to resist almost all modern antibiotics, including penicillin, vancomycin and tetracycline.

These ancient genes were largely in microbes whose resistance is problematic today, including Enteroccocus bacteria that can infect wounds and cause urinary tract infections. But they found that many other species, including some harmless ones, carried some of these resistant genes too.

Enterococcus enigma

“When you think about it, almost all these antibiotics are naturally produced, so it makes sense to find antibiotic genes as well,” says Santiago-Rodriguez.

Their finding shows that genes that can confer resistance to antibiotics were relatively widespread hundreds of years before Alexander Fleming discovered penicillin in 1928. “It’s ridiculous to think evolution of antibiotic resistance began when penicillin was discovered,” said team-member Raul Cano, also at California Polytechnic State University, at the meeting while discussing the findings. “It’s been going on for 2 billion years.”

These genes existed long before antibiotics became common, but it is our overuse of these drugs in both people and livestock that caused the superbug resistance to explode worldwide, said Cano.

“This is exciting data,” says Adam Roberts, who studies antibiotic resistance genes at University College London. While it is already well known that antibiotic resistance occurred naturally before people started using antibiotics, this study shows that resistance genes were already within the human gut long before we started using these drugs, he says.

“It begs the question of what was selecting for these genes at this time? Was it the natural production of antibiotics by other bacteria, or were there other, as yet unknown forces at play?” asks Roberts.