Overcoming cardiac pacemaker "source-sink mismatch"

Instead of complication-prone electronic cardiac pacemakers, biomedical engineers at Georgia Tech and Emory envision the creation of “biological Read more

Hope Clinic part of push to optimize HIV vaccine components

Ten years ago, the results of the RV144 trial– conducted in Thailand with the help of the US Army -- re-energized the HIV vaccine field, which had been down in the Read more

Invasive cancer cells marked by distinctive mutations

What does it take to be a leader – of cancer cells? Adam Marcus and colleagues at Winship Cancer Institute are back, with an analysis of mutations that drive metastatic behavior among groups of lung cancer cells. The findings were published this week on the cover of Journal of Cell Science, and suggest pharmacological strategies to intervene against or prevent metastasis. Marcus and former graduate student Jessica Konen previously developed a technique for selectively labeling “leader” Read more

Neuro

Alzheimer’s drug discovery: looking under the right ROCK

Developing drugs that can change the progression of Alzheimer’s disease is a huge challenge. In the last few years, more than one pharmaceutical firm have abandoned clinical programs in Alzheimer’s that once looked promising. Still, Emory and Scripps scientists have found an approach that deserves a second look and more investigation.

One straightforward drug strategy against Alzheimer’s is to turn down the brain’s production of beta-amyloid, the key component of the disease’s characteristic plaques. A toxic fragment of a protein found in healthy brains, beta-amyloid accumulates in the brains of people affected by the disease.

The enzyme that determines how much beta-amyloid brain cells generate is called BACE (beta-secretase or beta-site APP cleaving enzyme). Yet finding drugs that inhibit that elusive enzyme has been far from straightforward.

Now researchers  have identified a way to shut down production of beta-amyloid by diverting BACE to a different part of the cell and inhibiting its activity. The results were published this week in Journal of Neuroscience. Read more

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A discriminative stimulus

You may remember Highlights magazine from when you were a kid (or parent). Highlights has a feature where readers have to spot the differences between two similar pictures.

NEDA

Dopamine gets a lot of press, and cocaine addiction research has generally focused more on dopamine. (What is “the molecule behind all our most sinful behaviors and secret cravings?”) Norepinephrine is usually described more prosaically, as a hormone related to attention, stress and blood pressure regulation. Lowering norepinephrine levels does not stop animals from giving themselves a steady stream of cocaine, but it does inhibit their tendency to try to get it after a break or exposure to relapse triggers.

What is the difference between these two important brain communication chemicals, dopamine and norepinephrine? Look closely.

The answer is: just one oxygen atom. But it’s enough to mean http://www.magliettedacalcioit.com that the two neurotransmitters use different receptors and dominate different groups of neurons in the brain.

An area of medicine where that subtle difference is crucial is drug abuse. Geneticist David Weinshenker is an expert on the enzyme that converts dopamine into norepinephrine: dopamine beta-hydroxylase or DBH. He and his lab have been exploring whether medications that inhibit DBH could be used to help treat cocaine addiction. Read more

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Blood pressure meds + PTSD

The connection between stress and blood pressure seems like common sense. Of course experiencing stress — like a narrow miss in morning traffic or dealing with a stubborn, whiny child — raises someone’s blood pressure.

Try reversing the cause-and-effect relationship: not from brain to body, but instead from body to brain. Could medication for controlling blood pressure moderate the effects of severe stress, and thus aid in controlling PTSD symptoms or in preventing the development of PTSD after trauma?

That was the intriguing implication arising from a 2012 paper from Grady Trauma Project investigators led by psychiatrist Kerry Ressler (lab at Yerkes, supported by HHMI).

They had found that traumatized civilians who take either of two classes of common blood pressure medications tend to have less severe post-traumatic stress symptoms. In particular, individuals taking ACE inhibitors (angiotensin converting enzyme) or ARBs (angiotensin receptor blockers) tended to have lower levels of hyperarousal and intrusive thoughts, and this effect was not observed with other blood pressure medications.

This was one of those observational findings that needs to be tested in an active way: “OK, people who are already taking more X experience less severe symptoms. But can we actually use X as an intervention?”

In mice, it seems to work. Read more

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Growth factor mimics promote recovery after nerve injury

Peripheral nerve injury ranges from chronic irritation like carpal tunnel syndrome to violent trauma. Severe nerve injury can leave patients with lifelong disabilities. Even if nerves regenerate, functional recovery is often poor, because of problems with regeneration of axons, the signal-carrying “stalks” of nerve cells.Figure4.axons

Cell biologist Art English and his colleagues have shown that compounds identified by pathologist Keqiang Ye can promote axon regeneration when mice have injured peripheral nerves. The growth Cheap NFL Jerseys factor-mimicking compounds not only stimulate axons to regenerate twice as quickly (see figure), but also promote the restoration of connections between nerve and muscle. The results were published in September in PNAS.

Ye previously identified compounds that activate the same signals as the neuron growth factor BDNF (brain-derived neurotrophic factor). These compounds – 7,8-dihydroxyflavone and deoxygedunin — have shown promise in experimental models of diseases such as stroke and Parkinson’s disease. They also have been used to tweak learning and memory in animal models.

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Depression imaging test cited as real deal

Tired of hearing neuroscience, and brain imaging in particular, dismissed as trendy and overblown?

In this Sunday’s review section of the New York Times, Nobel Prize winner Eric Kandel cited research by Emory psychiatrist Helen Mayberg and colleagues (published in JAMA Psychiatry) as a good example of research with potential for substantive impact for the treatment of mental illness:

 In a recent study of people with depression, Professor Mayberg gave each person one of two types of treatment: cognitive behavioral therapy, a form of psychotherapy that trains people to view their feelings in more positive terms, or an antidepressant medication. She http://www.raybani.com/ found that people who started with below-average baseline activity in the right anterior insula responded well to cognitive behavioral therapy, but not to the antidepressant. People with above-average activity responded to the antidepressant, but not to cognitive behavioral therapy. Thus, Professor Mayberg found that she could predict a depressed person’s response to specific treatments from the baseline activity in the right anterior insula.

These results show us four very important things about the biology of mental disorders. First, the neural circuits disturbed by psychiatric disorders are likely to be very complex. Second, we can identify specific, measurable markers of a mental disorder, and those biomarkers can predict the outcome of two different treatments: psychotherapy and medication. Third, psychotherapy is a biological treatment, a brain therapy. It produces lasting, detectable physical changes in our brain, much as learning does. And fourth, the effects of psychotherapy can be studied empirically…

National Institutes of Mental Health director Thomas Insel also has commented on the technique’s clinical potential.

“For the treatment of mental disorders, brain imaging Ray Ban outlet remains primarily a research tool, yet these results demonstrate how it may be on the cusp of aiding in clinical decision-making,” Insel said in a NIMH press release earlier this summer.

In addition, author David Dobbs and blogger Neurocritic both delve into the details of Mayberg’s work.

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Dynamic functional connectivity

How can neuroscientists tell that distant parts of the brain are talking to each other?

They can look for a physical connection, like neurons that carry signals between the two. They could probe the brain with electricity. However, to keep the brain intact and examine cheap oakley function in a living person or animal, a less invasive approach may be in order.

Looking for functional connectivity has grown in popularity in recent years. This is a way of analyzing fMRI (functional magnetic resonance imaging) scans, which measure activity in the brain by looking at changes in blood oxygen. If two regions of the brain “light up” at the same time, and do so in a consistent enough pattern, that indicates that those two regions are connected.*

Functional connectivity networks

Shella Keilholz and her colleagues have been looking at functional connectivity data very closely, and how the apparent connections fluctuate over short time periods. This newer form of analysis is called “dynamic” or “time-varying” functional connectivity. Functional connectivity analyses can be performed while the person or animal in the scanner is at rest, not doing anything complicated.

“Even if you’re lying in the scanner daydreaming, your mind is jumping around,” she says. “But the way neuroscientists usually average fMRI data over several minutes means losing lots of information.”

Keilholz is part of the Wallace H Coulter Department of Biomedical Engineering at Georgia Tech and Emory. She participated in a workshop at the most recent Human Brain Mapping meeting in Seattle devoted to the topic. She says neuroscientists have already started using dynamic functional connectivity to detect differences in the brain’s network properties in schizophrenia. However, some of that information may be noise. Skeptical tests have shown that head motion or breathing can push scientists into inferring connections that aren’t really there. For dynamic analysis especially, preprocessing can lead to apparent correlations between two randomly matched signals.

“I got into this field as a skeptic,” she says. “Several years ago, I didn’t believe functional connectivity really reflects coordinated brain activity.”

Now Keilholz and her colleagues have shown for the first time that dynamic functional connectivity data is “grounded”, because it is linked with changes in electrical signals within the brain. The results were published in July in the journal NeuroImage. The first author is graduate student Garth Thompson. Read more

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Manipulating neurons with light

Welcome to a feature of Lab Land we hope to have on a regular basis! It’s where we explain a word or phrase that is a hot topic of discussion in the science online world and particularly relevant to research going on at Emory.

Optogenetics allows researchers to stimulate specific brain cells with light. It involves introducing light-sensitive proteins from algae into the brain cells of mice, and then using a fiber optic cable to apply a laser signal to the relevant region of the brain.

Optogenetics is a leap beyond previous genetic engineering techniques that made it possible to turn on (or delete) a gene by feeding a mouse some extraneous chemical, such as the antibiotic tetracycline or the anti-hormone tamoxifen. Instead of wondering how long it takes that chemical to make its way into the brain, scientists can literally flick a switch and see near-instantaneous and localized effects. Read more

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Fragile X clinical trials: this is not the end

A clinical trial testing a therapy for children with fragile X syndrome is closing down, after the sponsoring company announced that the drug, called arbaclofen, was not meeting its goals.

Readers of Emory Health magazine may remember Samuel McKinnon, an arbaclofen study participant who was featured in a 2012 article and video (below).

“We were surprised,” Samuel’s mother Wendy told us Monday. “But we knew going in that there were no guarantees.”

She reports that Samuel has made significant progress in the last couple of years. He likes playing and talking with the family’s new puppy, Biscuit. Samuel’s language skills have Ray Ban outlet blossomed and he will be headed to second grade this fall. But it’s hard to say whether that’s mainly because of the experimental drug or because Samuel has been continuing to grow and work hard in school and in therapy, she says.

A sizable fraction of patients in the study appeared to benefit from the drug, just not the majority of them, says Emory genetics chair Steve Warren.

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ScienceSeeker honors Anna’s story

The story of Anna Sumner’s extraordinary experience — disabling chronic sleepiness, leading to scientific discovery and treatment at Emory — has been told in several places, among them the Wall Street Journal and the Today Show.

One of the most extensive and elegant approaches, in our opinion, was science journalist Virginia Hughes‘ post “Re-Awakenings,” originally written for the group blog Last Word on Nothing. (Hughes is now part of National Geographic’s Phenomena quartet of bloggers.) Yesterday “Re-Awakenings” won some recognition, receiving the “Post of the Year” award from ScienceSeeker, a community square for science blogging.

Note: We here at Emory Health Now are still learning about the thriving world of science blogging, but Scientific American’s blog impresario cheap oakley sunglasses Bora Zivkovic calls ScienceSeeker “the main portal for collecting, connecting and filtering science writing online.” The judges for the awards were Fraser Cain, Maggie Koerth-Baker, and Maryn McKenna.

In addition, the most recent issue of Emory Medicine has a feature on Anna’s story, and neurologist David Rye, who leads the Emory team who treated Anna, has his own take in the June issue of Discover magazine.

 

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Where does learning to touch more sensitively “live” in the brain?

When someone’s sense of touch becomes more acute through training, the brain itself changes. Using functional magnetic resonance imaging (fMRI), researchers have devised ways to see which areas of the brain become more active.

Surprisingly, the changes in activity appear in parts of the Cheap Oakleys brain thought to be responsible for decision-making, rather than the “somatosensory” regions involved in processing touch signals from the fingers.

The results were reported Tuesday in the Journal of Neuroscience.

Participants were asked to discriminate between three-dot patterns, while the horizontal offset became less and less.

Participants were asked to discriminate between three-dot patterns, while the horizontal offset became less and less.

Sighted college undergraduates were trained to discriminate between patterns of raised dots with their fingers. After several sessions, the threshold of differences study participants could detect became much smaller. They could detect differences of less than 0.2 millimeters, when they had started out only being able to detect 1 millimeter changes.

“It is a task that resembles reading braille, and it tests for the same kind of fine level discrimination needed to read braille,” says Krish Sathian, MD, PhD, professor of neurology, rehabilitation medicine, and psychology at Emory University.

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