Tag Archives: amyotrophic lateral sclerosis (ALS)

Repairing brain circuits using nanotechnology

A July 30, 2019 news item on Nanowerk announces some neuroscience research (they used animal models) that could prove helpful with neurodegenerative diseases,

Working with mouse and human tissue, Johns Hopkins Medicine researchers report new evidence that a protein pumped out of some — but not all — populations of “helper” cells in the brain, called astrocytes, plays a specific role in directing the formation of connections among neurons needed for learning and forming new memories.

Using mice genetically engineered and bred with fewer such connections, the researchers conducted proof-of-concept experiments that show they could deliver corrective proteins via nanoparticles to replace the missing protein needed for “road repairs” on the defective neural highway.

Since such connective networks are lost or damaged by neurodegenerative diseases such as Alzheimer’s or certain types of intellectual disability, such as Norrie disease, the researchers say their findings advance efforts to regrow and repair the networks and potentially restore normal brain function.

A July 30, 2019 Johns Hopkins University School of Medicine news release (also on EurekAlert) provides more detail about the work (Note: A link has been removed),

“We are looking at the fundamental biology of how astrocytes function, but perhaps have discovered a new target for someday intervening in neurodegenerative diseases with novel therapeutics,” says Jeffrey Rothstein, M.D., Ph.D., the John W. Griffin Director of the Brain Science Institute and professor of neurology at the Johns Hopkins University School of Medicine.

“Although astrocytes appear to all look alike in the brain, we had an inkling that they might have specialized roles in the brain due to regional differences in the brain’s function and because of observed changes in certain diseases,” says Rothstein. “The hope is that learning to harness the individual differences in these distinct populations of astrocytes may allow us to direct brain development or even reverse the effects of certain brain conditions, and our current studies have advanced that hope.”

In the brain, astrocytes are the support cells that act as guides to direct new cells, promote chemical signaling, and clean up byproducts of brain cell metabolism.

Rothstein’s team focused on a particular astrocyte protein, glutamate transporter-1, which previous studies suggested was lost from astrocytes in certain parts of brains with neurodegenerative diseases. Like a biological vacuum cleaner, the protein normally sucks up the chemical “messenger” glutamate from the spaces between neurons after a message is sent to another cell, a step required to end the transmission and prevent toxic levels of glutamate from building up.

When these glutamate transporters disappear from certain parts of the brain — such as the motor cortex and spinal cord in people with amyotrophic lateral sclerosis (ALS) — glutamate hangs around much too long, sending messages that overexcite and kill the cells.

To figure out how the brain decides which cells need the glutamate transporters, Rothstein and colleagues focused on the region of DNA in front of the gene that typically controls the on-off switch needed to manufacture the protein. They genetically engineered mice to glow red in every cell where the gene is activated.

Normally, the glutamate transporter is turned on in all astrocytes. But, by using between 1,000- and 7,000-bit segments of DNA code from the on-off switch for glutamate, all the cells in the brain glowed red, including the neurons. It wasn’t until the researchers tried the largest sequence of an 8,300-bit DNA code from this location that the researchers began to see some selection in red cells. These red cells were all astrocytes but only in certain layers of the brain’s cortex in mice.

Because they could identify these “8.3 red astrocytes,” the researchers thought they might have a specific function different than other astrocytes in the brain. To find out more precisely what these 8.3 red astrocytes do in the brain, the researchers used a cell-sorting machine to separate the red astrocytes from the uncolored ones in mouse brain cortical tissue, and then identified which genes were turned on to much higher than usual levels in the red compared to the uncolored cell populations. The researchers found that the 8.3 red astrocytes turn on high levels of a gene that codes for a different protein known as Norrin.

Rothstein’s team took neurons from normal mouse brains, treated them with Norrin, and found that those neurons grew more of the “branches” — or extensions — used to transmit chemical messages among brain cells. Then, Rothstein says, the researchers looked at the brains of mice engineered to lack Norrin, and saw that these neurons had fewer branches than in healthy mice that made Norrin.

In another set of experiments, the research team took the DNA code for Norrin plus the 8,300 “location” DNA and assembled them into deliverable nanoparticles. When they injected the Norrin nanoparticles into the brains of mice engineered without Norrin, the neurons in these mice began to quickly grow many more branches, a process suggesting repair to neural networks. They repeated these experiments with human neurons too.

Rothstein notes that mutations in the Norrin protein that reduce levels of the protein in people cause Norrie disease — a rare, genetic disorder that can lead to blindness in infancy and intellectual disability. Because the researchers were able to grow new branches for communication, they believe it may one day be possible to use Norrin to treat some types of intellectual disabilities such as Norrie disease.

For their next steps, the researchers are investigating if Norrin can repair connections in the brains of animal models with neurodegenerative diseases, and in preparation for potential success, Miller [sic] and Rothstein have submitted a patent for Norrin.

Here’s a link to and a citation for the paper,

Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin by Sean J. Miller, Thomas Philips, Namho Kim, Raha Dastgheyb, Zhuoxun Chen, Yi-Chun Hsieh, J. Gavin Daigle, Malika Datta, Jeannie Chew, Svetlana Vidensky, Jacqueline T. Pham, Ethan G. Hughes, Michael B. Robinson, Rita Sattler, Raju Tomer, Jung Soo Suk, Dwight E. Bergles, Norman Haughey, Mikhail Pletnikov, Justin Hanes & Jeffrey D. Rothstein. Nature Neuroscience volume 22, pages741–752 (2019) DOI: https://doi.org/10.1038/s41593-019-0366-7 Published: 01 April 2019 Issue Date: May 2019

This paper is behind a paywall.

Stephen Hawking comic updates ‘Stephen Hawking: Riddles of Time & Space’ and adds life story for a tribute issue

Artist: Robert Aragon. Courtesy: TidalWave Productions

It would seem I wasn’t having one of my brighter days today (Feb. 7, 2019) and it took me a while to to decode the messaging about this Stephen Hawking comic book. Briefly, they’ve (TidalWave Productions; Note: The company seems to have more than one name) repackaged an old title (Stephen Hawking: Riddles of Time & Space) and included new material in the form of his life story. After some searching, as best as I can tell, the ‘Tribute’ was originally released sometime in 2018 in a digital version. This latest push for publicity was likely occasioned by the release of a print version.

Here’s more from a February 7, 2019 TidalWave Entertainment/Bluewater Productions news release (received via email),

TidalWave Comics, applauded for illustrated biographies featuring the
famous and infamous who influence our politics, entertainment, and
social justice, is proud to present its newest comic book release this
week. Telling the life story of a world-renowned physicist, cosmologist,
and author Stephen Hawking, “Tribute: Stephen Hawking,” is written
by Michael Lent, Brian McCarthy and Michael Frizell with art by Zach
Bassett. The comic book features a cover by famed artist Robert Aragon.

“Tribute: Stephen Hawking” is out this week in print and digital.
With the passing of English cosmologist, theoretical physicist, and
author, the world has lost one of the greatest scientific minds of the
20th and 21st Centuries. Hawking united the general theory of relativity
with quantum mechanics but may be more known for his rare, early-onset
and slow-progressing battle with Lou Gehrig’s disease. Hawking believed
in the concept of an infinite multiverse. Perhaps he’s watching us
mourn his loss.

Stephen Hawking is one of the most brilliant minds of this century. The
comic explores his brilliance while revealing some surprises.

Hawking’s life has been the subject of several movies, including the
2014 hit, “The Theory of Everything” starring Eddy Redmayne, who
received an Oscar and a Golden Globe for his performance as the
scientist dealing with an early-onset slow-progressing form of Lou
Gehrig’s disease. The comic seeks to add to Hawking’s story.

“I learned a lot from reading the script and doing the research for the
issue.  The very concept of making an engaging comic book where the
protagonist is essentially immobile is a pretty tall order, but I think
the key to us keeping it exciting was being able to get inside his mind
(one of the greatest of our time) and show some of his most abstract
concepts in a visual and dynamic way,” said artist Bassett.

Darren G. Davis, publisher and creative force behind TidalWave, believes
as Bassett does that the visual storytelling model is a good way to tell
the stories of real people. “I was a reluctant reader when I was a
kid. The colorful pages and interesting narrative I found in comic books
drew me in and made me want to read.” In a market crowded with
superheroes, the publisher’s work is embraced by major media outlets,
libraries, and schools.

Michael Frizell, one of TidalWave’s writers and the author of the
Bettie Page comic, enjoys writing for TidalWave’s biography lines
Political Power, Orbit, Female Force, Tribute, and Fame because of the
publisher’s approach to the books. “Darren asks us to focus on the
positive and to dig deep to explore the things that make the subject
tick – the things that drive them,” Frizell said.

In print on Amazon and are available on your e-reader from iTunes,
Kindle, Nook, ComiXology, DriveThru Comics, Google Play, Overdrive,
IVerse, Biblioboard, Madefire, Axis360, Blio, Entitle, EPIC!,
Trajectory, SpinWhiz, Smash Words, Kobo and wherever eBooks are sold.

TidalWave’s recent partnership with Ingram allows them to produce
high-quality books on demand – a boon for the independent publisher. The
comic book will feature a heavy-stock cover and bright, clean colors in
the interior. Ingram works across the full publishing spectrum, aiding
some of the largest names in the business to local indie authors.

Comic book and book stores can order these titles in print at INGRAM.

TidalWave’s biography comic book series has been embraced by the media
and featured on television news outlets including The Today Show and on
CNN. The series has also been featured in many publications such as The
Los Angeles Times, MTV, Time Magazine, and People Magazine.


For more information about the company, visit www.tidalwavecomics.com
 
About TidalWave Comics
TidalWave delivers a multimedia experience unparalleled in the burgeoning graphic fiction and nonfiction marketplace. Dynamic storytelling coupled with groundbreaking art delivers an experience like no other. Stories are told through multiple platforms and genres, gracing the pages of graphic novels, novelizations, engaging audio dramas, cutting-edge film projects, and more. Diversity defines Storm’s offerings in the burgeoning pop culture marketplace, offering fresh voices and innovative storytellers.

As one of the top independent publishers of comic book and graphic novels, TidalWave unites cutting-edge art and engaging stories produced by the publishing industry’s most exciting artists and writers. Its extensive catalog of comic book titles includes the bestsellers “10th Muse” and “The Legend of Isis,” complemented by a line of young adult books and audiobooks. TidalWave’s publishing partnerships include legendary filmmaker Ray Harryhausen (“Wrath of the Titans,” “Sinbad: Rogue of Mars,” “Jason and the Argonauts,” and more), novelists S.E. Hinton (“The Puppy Sister”) and William F. Nolan (“Logan’s Run”), and celebrated actors Vincent Price (“Vincent Price Presents”), and Adam West of 1966’s “Batman” fame (“The Mis-Adventures of Adam West”). TidalWave also publishes a highly-successful line of biographical comics under the titles “Orbit,” “Fame,” “Beyond,” “Tribute,” “Female Force,” and “Political Power.”

Should you happen to operate a comic and/or book store, I have found the Ingram (Content Group) website. Happy ordering!

Democratizing science .. neuroscience that is

What is going on with the neuroscience folks? First it was Montreal Neuro opening up its science  as featured in my January 22, 2016 posting,

The Montreal Neurological Institute (MNI) in Québec, Canada, known informally and widely as Montreal Neuro, has ‘opened’ its science research to the world. David Bruggeman tells the story in a Jan. 21, 2016 posting on his Pasco Phronesis blog (Note: Links have been removed),

The Montreal Neurological Institute (MNI) at McGill University announced that it will be the first academic research institute to become what it calls ‘Open Science.’  As Science is reporting, the MNI will make available all research results and research data at the time of publication.  Additionally it will not seek patents on any of the discoveries made on research at the Institute.

Will this catch on?  I have no idea if this particular combination of open access research data and results with no patents will spread to other university research institutes.  But I do believe that those elements will continue to spread.  More universities and federal agencies are pursuing open access options for research they support.  Elon Musk has opted to not pursue patent litigation for any of Tesla Motors’ patents, and has not pursued patents for SpaceX technology (though it has pursued litigation over patents in rocket technology). …

Whether or not they were inspired by the MNI, the scientists at the University of Washington (UW [state]) have found their own unique way of opening up science. From a March 15, 2018 UW news blog posting (also on EurekAlert) by James Urton, Note: Links have been removed,

Over the past few years, scientists have faced a problem: They often cannot reproduce the results of experiments done by themselves or their peers.

This “replication crisis” plagues fields from medicine to physics, and likely has many causes. But one is undoubtedly the difficulty of sharing the vast amounts of data collected and analyses performed in so-called “big data” studies. The volume and complexity of the information also can make these scientific endeavors unwieldy when it comes time for researchers to share their data and findings with peers and the public.

Researchers at the University of Washington have developed a set of tools to make one critical area of big data research — that of our central nervous system — easier to share. In a paper published online March 5 [2018] in Nature Communications, the UW team describes an open-access browser they developed to display, analyze and share neurological data collected through a type of magnetic resonance imaging study known as diffusion-weighted MRI.

“There has been a lot of talk among researchers about the replication crisis,” said lead author Jason Yeatman. “But we wanted a tool — ready, widely available and easy to use — that would actually help fight the replication crisis.”

Yeatman — who is an assistant professor in the UW Department of Speech & Hearing Sciences and the Institute for Learning & Brain Sciences (I-LABS) — is describing AFQ-Browser. This web browser-based tool, freely available online, is a platform for uploading, visualizing, analyzing and sharing diffusion MRI data in a format that is publicly accessible, improving transparency and data-sharing methods for neurological studies. In addition, since it runs in the web browser, AFQ-Browser is portable — requiring no additional software package or equipment beyond a computer and an internet connection.

“One major barrier to data transparency in neuroscience is that so much data collection, storage and analysis occurs on local computers with special software packages,” said senior author Ariel Rokem, a senior data scientist in the UW eScience Institute. “But using AFQ-Browser, we eliminate those requirements and make uploading, sharing and analyzing diffusion-weighted MRI data a simple, straightforward process.”

Diffusion-weighted MRI measures the movement of fluid in the brain and spinal cord, revealing the structure and function of white-matter tracts. These are the connections of the central nervous system, tissue that are made up primarily of axons that transmit long-range signals between neural circuits. Diffusion MRI research on brain connectivity has fundamentally changed the way neuroscientists understand human brain function: The state, organization and layout of white matter tracts are at the core of cognitive functions such as memory, learning and other capabilities. Data collected using diffusion-weighted MRI can be used to diagnose complex neurological conditions such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Researchers also use diffusion-weighted MRI data to study the neurological underpinnings of conditions such as dyslexia and learning disabilities.

“This is a widely-used technique in neuroscience research, and it is particularly amenable to the benefits that can be gleaned from big data, so it became a logical starting point for developing browser-based, open-access tools for the field,” said Yeatman.

The AFQ-Browser — the AFQ stands for Automated Fiber-tract Quantification — can receive diffusion-weighted MRI data and perform tract analysis for each individual subject. The analyses occur via a remote server, again eliminating technical and financial barriers for researchers. The AFQ-Browser also contains interactive tools to display data for multiple subjects — allowing a researcher to easily visualize how white matter tracts might be similar or different among subjects, identify trends in the data and generate hypotheses for future experiments. Researchers also can insert additional code to analyze the data, as well as save, upload and share data instantly with fellow researchers.

“We wanted this tool to be as generalizable as possible, regardless of research goals,” said Rokem. “In addition, the format is easy for scientists from a variety of backgrounds to use and understand — so that neuroscientists, statisticians and other researchers can collaborate, view data and share methods toward greater reproducibility.”

The idea for the AFQ-Browser came out of a UW course on data visualization, and the researchers worked with several graduate students to develop and perfect the browser. They tested it on existing diffusion-weighted MRI datasets, including research subjects with ALS and MS. In the future, they hope that the AFQ-Browser can be improved to do automated analyses — and possibly even diagnoses — based on diffusion-weighted MRI data.

“AFQ-Browser is really just the start of what could be a number of tools for sharing neuroscience data and experiments,” said Yeatman. “Our goal here is greater reproducibility and transparency, and a more robust scientific process.”

Here are a couple of images the researchers have used to illustrate their work,

AFQ-Browser.Jason Yeatman/Ariel Rokem Courtesy: University of Washington

Depiction of the left hemisphere of the human brain. Colored regions are selected white matter regions that could be measured using diffusion-weighted MRI: Corticospinal tract (orange), arcuate fasciculus (blue) and cingulum (green).Jason Yeatman/Ariel Rokem

You can find an embedded version of the AFQ-Browser here: http://www.washington.edu/news/2018/03/15/democratizing-science-researchers-make-neuroscience-experiments-easier-to-share-reproduce/ (scroll down about 50 – 55% of the way).

As for the paper, here’s a link and a citation,

A browser-based tool for visualization and analysis of diffusion MRI data by Jason D. Yeatman, Adam Richie-Halford, Josh K. Smith, Anisha Keshavan, & Ariel Rokem. Nature Communicationsvolume 9, Article number: 940 (2018) doi:10.1038/s41467-018-03297-7 Published online: 05 March 2018

Fittingly, this paper is open access.