Max Planck and a mouse whisker

One-whiskered rodent helps scientists get clear picture of a healthy brain

Mice at Max Planck Institute get a shave, save for one whisker.

And then scientist watch what the mouse does with that one whisker.

Marcel Oberlander

“We have these two little platforms with a gap between them, and we see how long it takes for the mouse to jump the gap. To figure it out, it uses its whiskers as it’s primary sense, like we use our fingertips,” explained researcher Marcel Oberlander. “We increase the gap. It fails. It returns. We do this at a certain age after its birth and see what changes.”

Each whisker is controlled by a well-defined region in the brain, he said.

“In the brain of a rodent, there are function units, with a couple of thousands of neurons that process the information coming from the whiskers,” said researcher Hanno Meyer. “Thus, you have a system of 10,000 neurons, and we are looking at how (the system) is built and organized.

“Once we know how the neurons work, then we are able to analyze what goes on when it is diseased.”

Only one whisker

How can a one-whiskered mouse be compared to a human? “A mouse has a cortex,” Meyer said. “It can learn. It can exhibit disturbed behavior. It can solve tasks. Jumping the gap is kind of like giving a human a little pinch, and gives us some idea of how the brain works.”

Obviously, mapping out all those neurons in the mouse’s brain is going to be a bit time consuming.

“There are billions of neurons, each with 5,000 connections, and we want to find all those connections. That’s quite a process,” Oberlander said.

To help them do this, the scientists use a machine called the microtome, which slices a mouse’s brain into several hundred slices. Then, the slices are stained and put under a confocal microscope where high resolution scans are made of several hundred tiles of that slice. Then the tiles are stitched together using special software, so that a whole picture of the slice can be made and all the neurons identified and analyzed.

Then, they will scan the brain of a mouse afflicted with Alzheimer’s and note the differences.

The researchers also make living brain records of the activity of the neuron, using the patch clamp technique.

(They work with Dr. Bert Sakmann, the 1991 Nobel Laureate in Medicine and inaugural scientific director of the Max Planck Florida Institute. With German physicist Erwin Neher, Sakmann used the patch-clamp technique to establish the existence of sets of ion channels in cell membranes, some permitting the flow of only positive ions, while others pass only negatively charged ions. Once they established that, they examined a range of cellular functions, eventually discovering the role that ion channels play in a variety of diseases.)

Meyer explains how to make those records: “You take a glass pipette with a single opening and put it on an electrode, which is advanced into the brain and records the activity on a graph that will show the firing spikes of a single neuron. When it fires a spike all the neurons to it are either inhibited or excited.”

The purpose of this research is to provide scientists with a clear picture of a healthy, functioning brain, so that they can understand degenerative neurological diseases like Alzheimer’s.

written for Palm2Jupiter

Discover Local Artists: Segall and Sagui

JF Gallery presents “The Muses Are Heard (and They’re Loud),” an exhibition of the work of Liz Ghitta Segall and James Sagui, starting February 24.

Liz Segall and Jim Sagui

JF Gallery in West Palm Beach is presenting “The Muses Are Heard (and They’re Loud),” an exhibition of the work of Liz Ghitta Segall and James Sagui, a married couple who work and create together, February 24 through March 24.

There is no escaping the sound (sometimes a low, carefree humming, sometimes a noisy, nagging whining) of the Muses that pass between them at any given moment whether it be over morning coffee at home or across the parking courtyard that separates their two studios in the Northwood section of West Palm Beach, they say.

This particular exhibition showcases new work from each which was inspired by the other. For example: Segall found herself using her husband’s woodshop materials — walnut stain for furniture — in her paintings and Sagui discovered a link in his line figure drawings not too dissimilar to his wife’s sketches.

"Madrigal #1" by Liz Segall is an oil-on-wood, 24 by 48 inches, priced at $3,200
James Sagui's "XXY," metal & gold leafed, 7 by 9 by 25 inches, $4,500 each.

JF GALLERY is at 3901 S. Dixie Highway in West Palm Beach. The opening night reception is on Thursday, Feb. 24 from 6-9 p.m.  Gallery hours are 10 a.m. to 5 p.m. Tuesday through Saturday. For information, call (561) 478-8281.

Robotic varmints

Robots that help scientist understand biological principles

Salamander
Salamander

There’s the wiggly robot developed by a team from Ecole Polytechnique Fédérale de Lausanne.

It’s based on the salamander’s spinal column and, directed by a lab top, it swims, crawls, changes speed and directions­, giving scientists information about locomotion.

The Waalbot, developed by a team from the NanoRobotics Lab, Carnegie Mellon University, is like a synthetic gecko with dry adhesives on the bottom of its “feet.”  This robot walks up walls.

Waalbot

And then there’s RoboFly, a project that Axel Borst, Ph.D., director of Max Planck Institute of Neurobiology, introduced to his audience last month during his talk, “From the Cockpit of a Fly: How Visual Information is Processed.”

RoboFly, as well as the other robots, will eventually go where humans won’t (or can’t). But, really, that’s just a byproduct, because their real contribution is to help scientists understand biological principles.

RoboFly

Here’s a little background on Max Planck Institute, which received almost $190 million in state and local money in return for a promise to hire 135 employees. It has operated at its temporary Jupiter campus at Florida Atlantic University since 2008, while waiting for its 100,000 square-foot facility to be finished sometime in 2012, and, currently has a staff of 45.

A neuroscience company headquarted in Munich, its 80 institutes focus on a variety of fields. Borst, from Munich, specializes in neurobiology. Since he’s interested in how motion information from changing retinal images is computed and guides the fly in flight, his research is centered on two types of flies: the big fly and the fruit fly.  In addition, Borst serves as an advisor here in Jupiter (see the sidebar on the one-whiskered mouse).

Dr. Borst

How the fly sees and moves helps us understand how the brain works and how visual motion is processed in the brain, Borst said.

“As neuroscientists, we’d like to understand how the brain works. That would answer philosophical questions: How do we perceive the world? What makes our personality? How should we teach children? How can we help cure diseases of the brain?”

We do know that the brain’s volume is 1.3 litres and it contains a trillion neurons, he said, and we can assign function to different areas of the brain and we know that behind the visual cortex is where vision is processed.

Through MRIs, scientists have learned a lot in the last 20 years, he added. “A scanner subject is given a task and his or her activity is recorded. But an MRI’s resolution is one cubic millimeter, so we can’t assign the function of different parts of the brain.

“The connection between single neurons and what we see on the MRI is what we are missing. In between is the circuitry, and we don’t understand that.

“In computers, for example, we understand the chips but what we don’t have is the circuit diagram that makes up the function of the chip.”

And since, Max Planck scientists want to understand the brain at that level, they studied the neurons and their connections so that they could figure out the “circuit diagram.”

While the brain volume is 1.3 litre, the fruit fly brain is much smaller – .0000001 litre. Human brains have trillions of neurons while a fruit fly has 100,000, but the volume per neuron is the same, he said.

“The fly brain is just as complex, but has fewer neurons.  This is why I picked the fly.

“Each of the facets of its eye can be regarded as a single pixel. Each facet looks at a neighboring point and they form an image like we do with a single lens.”

When the fly is buzzing around, it’s hard to catch. That’s because it’s relying on optic flow information, Borst explained.

“Moving forward to the tree, imagine that the world is expanding away from where you are heading. The images are shifting as you move forward.  You can describe this image by a vector field where you indicate the motion of each pixel.  Image pixels that you are heading to seem to be moving slowly, and at your sides, moving fast, like you are going down a lane. That’s optic flow, and it depends on how you move, and when you rotate, it moves in the opposite direction.

“Flies use that to navigate through the environment. We do that as well. If I tell you to walk straight with your eyes closed, you couldn’t.  But if you look at an image of a rollercoaster, you just see it and you can experience it, without being on it.

“The brain area where neurons respond to optic flow, it’s like those 3D movies. In flies, we call it the cockpit of the eye.”

Researchers study the optic flow by filling neurons with dyes and using electrodes to make intracellular recordings, looking at connectivity and the properties of the lobula plate cells and the descending neurons.

“Just like the human, neighboring points always are processed by neighboring points, and, in the fly, the lobula plate creates the map,” he said.

Local motion vectors are calculated from local changes in retinal brightness. From the resulting optic flow, course control parameters are extracted.

“Following this motion is computed by a mechanism that does sequence detection.  You get directional information: vertical, horizontal and rotation,” he said.

“We copied the circuit, and made a computer simulation.”

Now back to his team’s creation, RoboFly, the flying robot whose flight trajectory is controlled by visual stimuli.

So, asked Borst, “Why not build an artificial eye? And we started the RoboFly project.

“We decided to buy a commercially available platform (it looks like a gyrocopter) and we mounted a camera with two wide-angle lenses, and then we followed that by parallel chips that would implement the locomotion detecting followed by the lobula plate network. We still fly it with remote control, but we plan to close the loop and unleash it to see what it does.”

RoboFly is an opportunity to test the function of the circuit and to see if it works the way he think it works as well as to give insight as to why the neurons are wired up the way they are, he said. And the technical application for autonomous robots is to send them where people don’t want to go. “So if you have the robot, an autonomous regulation mechanism that avoids collisions and stabilizes even with a gust of wind, it can send me the images and fly back.”

Written for palm2jupiter

Plants for pain relief

Scripps scientist, Dr. Laura Bohn, talks about discovering substances that might bring pain relief.

Other than the poppy…

Pain, like death and taxes, is part of the human condition. Can’t escape it. So, it’s no surprise that humans figured out how to make drugs (from the opium poppy) for pain relief, centuries ago – and it’s been a valued commodity, ever since.

Laura Bohn

So explained Scripps Florida associate professor, Laura Bohn, Ph.D., as she embarked on her presentation, “Taking the Pain out of Drug Discovery,” at January’s Front Lines of Hope Discussion Series. Bohn investigates G protein-coupled receptors, which are critical to how patients respond to various drugs, including those used for the treatment of pain.

By 1805, she recounted, Wilhelm Adam Serturner isolated a component of opium and started pharmaceutical manufacturing. There are many derivatives: morphine, heroine, oxycodone, Percocet, and the synthetic, methadone. However, like all valuable assets, opiate narcotics do come with a price tag.

Its worse side effects are dependence, addiction and overdose, but there are others to contend with. Because, morphine, for example, affects the entire body. It offers sedation and euphoria; it induces an itching sensation, may cause respiratory failure, and, since it also affects the gut, constipation.

What if, asks Bohn, we could just turn on the receptors for pain relief, and turn off those other receptors?

The receptors are the targets where the drug acts on the cell. They traverse the cell membrane, she explained.  So, when a person takes the drug, it’s able to get into the cell, change the cell’s shape and lead to the recruitment of proteins in the cell.

Bohn’s lab works on beta arrestins, a protein that determines how drugs act at the receptors, turning them on or off.

“To determine the effect, many years ago, we generated mice that lacked the protein of beta arrestin-2, and we gave them morphine. What we found is that we got the pain relief, but not tolerance, physical dependence, constipation and respiratory problems.

“So we know that we can have signaling for pain relief, in the brain, but in the gut, we can have it turned off for constipation.

“Over time, though, it gums up the works and you become tolerant to the drug. But it doesn’t happen in the gut. We believe that beta arrestin doesn’t work on that gear.

“So, what if we could make drugs that activate the receptor without recruiting beta arrestin-2?

“That’s the motivation of our drug discovery.

Salvia

A component in one of the drug candidates was derived from Salvia Mexican Mint, and scientists made a drug that did that, but it is not good in solution, because it’s not stable, she said. “We just started a start up getting the compound ready for clinical trials.

“We can have pain relief without the side effect of constipation? Very soon, and without fear of addition or overdose,” she said.

Relating to the neurotransmitter serotonin, there are many good therapies (antidepressants) that have lousy side affects, she continued, showing an illustration of a neuron in the brain releasing serotonin. “In a normal state, we have enough to maintain a good mood, and it is taken up by the transporter.

“On the other side, the receptor is blocked and we get all those serotonins in the receptors.

Serotonin neuron

“Why block serotonin uptake? Why not make something that targets the serotonin 2a receptor?”

If you make an agonist (a chemical that binds to a receptor, and triggers a response by that cell.), you end up with a hallucinogenic compound, like LSD, psilocybin, endogenous tryptamines.

And some of the serotonin metabolites can cause hallucination.

If you have too much serotonin, you have side affects, and as levels increase, you have hallucinations and ultimately coma and death from serotonin syndrome.

“So question is, can we refine serotonin therapies by fine-tuning serotonin receptors? We don’t want too much or too little. It’s got to be normal. Can we identify the gears that make up the machine that the serotonin receptor 2a responds to?

“Its very early, but we have found two signaling pathways,” she said.

Pinwheel Jasmine

Another new avenue in drug discovery is a compound derived from pinwheel jasmine. “When we tested it in mice, we found it was an analgesic. It’s not an opioid, and it doesn’t have any side effects.  This may represent a new class of pain medications. We haven’t found a target for it yet.”

Written for Palm2Jupiter

Finding ways to fight cancer

Scripps Florida scientists look for new ways to fight breast cancer

Scripps receives philanthropic support from Frenchman’s Creek Women for Cancer Research

Here’s a sobering thought.  For men, chances of developing prostate cancer are one out of two. For women, chances of developing cancer are one in three, with breast cancer being the biggest culprit.

In 2009, in the United States, 175,000 women got breast cancer, and 45,000 died of the disease. 190,000 men got prostate cancer, and 40,000 died of the disease.

But there are survivors: 2.5 million women have survived breast cancer; 2 million men have survived prostate cancer. Those successes came about because of medical advancements in the last 30 years, when the survival rate was 70 percent for women and 67 percent for men. Those rates are now 88 percent for women and 90 percent for men.

Cancer research, like that done at Scripps, helps. And it needs funding.  Most money that funds research comes from the National Institute of Health, but the funding rates dropped two-thirds since 2000.  To help take up the slack, Frenchman’s Creek Women for Cancer Research has raised more than $400,000 to support three cancer research  fellows in cancer biology at Scripps.

Working with Howard Petrie and Kendall Nettles, the fellows have made inroads in advancing research in the role of the immune system in cancer and the impact of steroid hormones, and how notch3, a key regulatory protein and known cause of cancer, contributes to the development or progression of cancer.

In January, Scripps professors gave a presentation to those donors, updating them on their research activities and 2010 achievements.

To give an overview on research to help those 30 percent of patients with estrogen-receptor positive breast cancer who are resistant to the drug, Tamoxifen, Howard Petrie, Ph.D., professor in the division of immunology at Scripps’ Department of Cancer Biology, spoke about the roll in biology and cancer of the notch3 gene and the proteins that are encoded by them.

The notch protein sits like a trigger and penetrates the cell membrane, he said. “On the outside, notch has a bunch of repeats (of amino acids). On the inside there’s also a lineup of some repeats with different functions. Both the inside part and the outside part of notch interact with specific types of proteins.”

When the outside part is connected to a specific protein, the inside part is cleaved and released within the cell, then enters the cell nucleus and binds with DNA.

“Notch is a master mediator of how genes encode proteins,” he said. “When this process, though, goes awry, it leads to cancer.”

All multi-cellular animals have one or more notch genes. Humans have four. Notch1 protein has clearly defined roles in biology and cancer in a wide variety of tissues, including the mammary and prostate.

But, not much is known about notch3, he said. “What we do know is that it’s implicated in cancer.  Despite its importance in biology and the obvious links to cancer, we don’t know that much about it, nor do we know how to correct its function when it goes awry.

Scripps researchers have developed a genetic resource for understanding the function of notch3, showing its structure. “What we did was replace the intracellular piece with a bacterial enzyme not found in mammals, and that allows us to encode notch3 that has that enzyme and specifically identify it in the animal.

“We don’t understand that much about notch3, but we have screened the chemical libraries and identified 51 drugs that activate the notch pathway (the process where both parts of notch are activated).

“These are small chemical compounds, when put on the stem cell, activate the notch3 pathway. In other words, we can see which cells attach to which cell in the notch3 protein.”

In 2010. Scripps professors wrote a manuscript citing women’s cancer research.  “Our research has shown that two proteins encoded by the Notch family of genes, both of which are implicated in cancer, have distinct and non-overlapping functions, and thus are unlikely to be targeted by the same drug regimens,” he said.

In clinical endocrine therapy (therapies that deal with hormones), Tamoxifen treatment blocks the estrogen signals and that’s the most effective treatment for patients with ER (estrogen receptor) positive breast cancer. However, some of those tumors are resistant to treatment and metastasize.

Possible strategies to solve this: To find biomarkers (a biomarker is anything that can be used as an indicator of a particular disease state) that can predict which cancer will be Tamoxifen-resistant so that doctors can use other strategies to treat those kinds of cancers. And to find drugs that can kill cancers that Tamoxifen missed.

Kendall Nettles, Ph.D. an associate professor in he Department of Cancer Biology, is working to make new types of estrogen therapy. Current therapies block growth of estrogen, he said, which is good because estrogen promotes growth of breast cancer, but estrogen is also anti-inflammatory. Ju-Li Luo, (Ph.D., assistant professor in the Department of Cancer Biology) discovered that inflammation can be associated with cancer production, Nettles added.

Tamoxifen works by wrapping around the estrogen receptor, replacing the estrogen, and changing the shape of the receptor and its activity. Then the receptor can interact with different proteins with an end result of turning off the growth of cancer.

“The drug Tamoxifen blocks both estrogen and its anti-inflammatory properties, and we’d like to find drugs that will block tumor growth and inflammation and that will be a new way to prevent treatment-resistant cancer,” he said.

Last fall, Scripps scientists published a study in Nature Chemical Biology on their findings that in working with the molecular systems that recognize the hormone estrogen, that as protein receptors change shape, ligands can adapt to that change, binding productively to both active and inactive structures.

Nettles is excited by the possibility of working with an ensemble of ligand arrangements, combining one with anti-inflammatory properties (which plays a role in cancer) and with another that blocks tumor growth – potentially doubling the effectiveness of the treatment.  Nettles said, “If ligand dynamics turn out to be a general feature of small molecule signaling, our findings could transform our approach to finding improved cancer therapies.”

Discover Local Artists: International artists

American International Fine Art Fair through Feb. 13

Thought to have some fun at the American International Fine Art Fair by looking for narratives — what the visual works of art have to say, so to speak, and, dealers enjoyed playing along.

Boy and Girl, $7,500.

Above is a scarf, part of Whitford Fine Art’s collection. A young man approaches a young woman straight on. Her dog is trying to keep him away, because it does not want to share its mistress’s affection. The young lady faces her viewers, and appears uninterested, but her right foot is turned toward him , she is about to turn, (don’t you think?), and face her beau.

Art historian Gabriel Toso,  a representative of Whitford, said, that’s possible, but maybe the young man was bringing her flowers, because he was sorry for something that he’d done…

… In truth,  Zika and Lida Ascher, famous textile designers in the 40s and 50s (even the Queen of England wore dresses made with their fabrics, he said, adding ladies knew how to dress in those days), asked some well-known artists to collaborate by creating designs. Then the scarves were sold, worn, and enjoyed. Some, though, were preserved. Like this one, “The Lovers Boy and Girl,” which was designed by Andre Derain.

Barry Friedman was showing some of Wendell Castle’s chairs. This one, a table and chair looked very soft, for wood — it’s made of Peruvian walnut. And comfortable, too, a Friedman representative said.

Wendell Castle, $90,000.

Very organic, it looks like it took root and just started to grow. The grains are lovely, too. How much weight would it hold, since the seat looks to extend from the base of the table? 650 pounds, Friedman said without blinking.  He admitted he just made up that number for fun, but added the chair was very sturdy, and it could handle an elephant…

Stone Fossils, $48,500.

These natural stone fossil murals were at the fair last year but this year, one is hung in the sushi bar — don’t you love it? These, though, are not on the menu — they might be kinghtia escaena…

These fossils are unearthed, extracted by hand from a quarry in the Northwest, and are exhibited by Eostone.

Below are two examples of works by Australian Aborigine artists; they come with stories freely. They are shown at Leslie Smith Gallery and researcher Robbert Hovenberg pointed out that the one directly below shows patterns of animal tracks and baskets.

Australian Aborigine Art
Australian Aborigine Art

And this one, directly above, looks somewhat like a map. Before the Aborigines were rounded up, they would make these map-like designs of the desert, a watering hole or some important part of their cosmos. At birth, an Aborigine would have a custodial site (like a watering hole) and the snake would come down from dream time, and curl up around the watering hole, and that presented a clear image to that Aborigine so that he could find the spot again.

This one looks like a bird’s eye view of sand dunes.

Over a period of time, these spiritual symbols morphed into geometric designs, as the Aborigines transferred their talents from a drawing on a “canvas” comprised of their skin or part of their environment to expressing themselves through art with paint on canvas. Often, Hovenberg said, the background would be black, because they used to draw these symbols on their skin. Or red, because they drew them in the sand or on stone.

And this changeover from the spirit world to the artistic world is a fairly new development, he said. Three of the artists, for example, walked out of the wilderness in the 1980s, naked, and having lived all their lives as hunter-gatherers…

The fair continues through February 13. Hours are noon until 7 p.m., and until 6 p.m. on the 13th. It is held at the Palm Beach County Convention Center, 650 Okeechobee Blvd., West Palm Beach. A one-day pass costs $15.

Discover Local Artists: at the NAWA Exhibit

Northwood University’s Jeanette Hare Art Gallery presents works by members of the National Association of Women Artists (NAWA), February 4 through March 25.

Northwood University’s Jeanette Hare Art Gallery presents works by members of the National Association of Women Artists (NAWA), February 4 through March 25. with an opening reception, Thursday, Feb. 25 from 3-4 p.m.

"Atlantic Avenue Reflections," by Emalee Andre is 24 by 20 inches, framed photography. $350.
Emalee And

Thirty NAWA members will be showing 51 works in the show.

“My paintings are usually layered with different images,” said Emalee Andre of Palm Beach Gardens.. “So during a walk down Atlantic Avenue one morning I saw this reflection in

Lori Baer

a shop window and immediately snapped the picture to capture that same kind of look in a photograph.”

Said Lore Baer: “The welding process requires such intense concentration and focus that it takes me to a different world, where I can be someone I never knew I was. I have tried to express that feeling in this sculpture.”

"Grounded," by Lore Baer, is a 38-by-14-by-32 inch sculpture. $7,500.
"Everywhere Poppies," by Lynn Morgan, is a 20-by-28-inch pastel. $650.
Lynn Morgan

“This painting was based on many vistas I saw on a painting trip to Southwestern France this past June,” said Lynn Morgan. “The poppies were in bloom everywhere and were irresistible to paint.”

Baer and Morgan are also Palm Beach Gardens residents.

The Northwood University Jeannette Hare Art Gallery is located at 2600 N. Military Trail, West Palm Beach, Florida (It is located on the first floor of Northwood’s Turner Education Center.) Gallery hours are 9 to 6 p.m., Monday through Friday; and noon to 6 p.m. Saturday and Sunday.
For further information relating to the exhibit, please call Northwood University’s Cultural Arts office at (561) 478-5532 or (800) 458-8325 or e-mail mccreery@northwood.edu.