Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Visualizing retrograde flow

This month’s intriguing image is a set of videos produced by cell biologist James Zheng’s laboratory. Looking at this video of a cell can be mesmerizing. The edges of the cell appear to be flowing inward, like a waterfall. Zheng explains that this is a phenomenon called “actin retrograde flow.”

Actin is a very abundant protein found in animals, plants and fungi that forms filaments, making up the cell’s internal skeleton. What we are seeing with retrograde flow is that molecules of actin are being added to one end of the filaments while coming loose from the other end.Actin

Zheng’s laboratory is studying a protein called cofilin, which disassembles actin filaments. Using a technique called CALI (chromophore-assisted laser inactivation) the scientists http://www.troakley.com/ used a laser to blast cofilin, inactivating it. This is why, partway through the loop, after the word CALI appears, the flow slows down. Postdoctoral fellow Eric Vitriol is the lead author on a paper in Molecular Biology of the Cell that includes these videos.

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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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Gene duplication leads to obesity in childhood syndrome

A team of researchers has discovered a genetic syndrome that causes childhood obesity, intellectual disability and seizures. The syndrome comes from an “unbalanced” chromosomal translocation: affected individuals have additional copies of genes from one chromosome and fewer copies of genes from another.

The results were published this week in Proceedings of the National Academy of Sciences, Early Edition.

Katie Rudd, PhD, assistant professor of human http://www.raybanoutletes.com/ genetics at Emory University School of Medicine, is senior author of the paper. Research specialist Ian Goldlust, now a graduate student in the NIH-Oxford-Cambridge Scholars Program, is the first author. Co-authors include investigators from around the USA and Australia.

Rudd’s team was able to connect the contribution of one gene, GNB3, among many involved in the translocation, to the obesity aspect of the syndrome. Her lab created a mouse model with an extra copy of the GNB3 gene and found that the mice are obese. The mice are on average 6 percent (males) or 10 percent (females) heavier.

Rudd says her work was greatly assisted by collaboration with the Unique Rare Chromosome Disorder Support Group, a UK-based charity. Within Unique, a few parents had together found that their children had translocations involving the same chromosomes and similar symptoms. They contacted Rudd and helped her find additional affected families. Her study includes seven unrelated patients.

“It really was a group effort, and Unique was the linchpin,” she says. “Managing to find seven families with exactly the same rare translocation would have been extremely difficult otherwise.”

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Molecular beacons shine path to cardiac muscle repair

Pure cardiac muscle cells, ready to transplant into a patient affected by heart disease.

That’s a goal for many cardiology researchers working with stem cells. Having a pure population of cardiac muscle cells is essential for avoiding tumor formation after transplantation, but has been technically challenging.

CardioMBs

Fluorescent beacons that distinguish cardiac muscle cells

Researchers at Emory and Georgia Tech have developed a method for Cheap Oakleys purifying cardiac muscle cells from stem cell cultures using molecular beacons.

Molecular beacons are tiny “instruments” that become fluorescent only when they find cells that have turned on certain genes. In this case, they target instructions to make a type of myosin, a protein found in cardiac muscle cells.

Doctors could use purified cardiac muscle cells to heal damaged areas of the heart in patients affected by heart attack and heart failure. In addition, the molecular beacons technique http://www.lependart.com could have broad applications across regenerative medicine, because it could be used with other types of cells produced from stem cell cultures, such as brain cells or insulin-producing islet cells.

The results are published in the journal Circulation.

“Often, we want to generate a particular cell population from stem cells for introduction into patients,” says co-senior author Young-sup Yoon, MD, PhD, professor of medicine (cardiology) and director of stem cell biology at Emory University School of Medicine. “But the desired cells often lack a readily accessible surface marker, or that marker is not specific enough, as is the case for cardiac muscle cells. This technique could allow us to purify almost any type of cell.”

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Mix-and-match immune regulators

Go check out the article on the Emory Office of Technology Transfer’s site on Jacques Galipeau and the artificial chimeric immune stimulators he’s invented. He and his colleagues take one immune regulatory molecule, GM-CSF, and stick it onto others, creating a series of potent immune stimulants he calls “fusokines.” According to Galipeau, one of them turns antibody-producing B cells into The Hulk. Another is like a five hour energy drink.

These super-stimulants may be especially ray ban outlet effective in the realm of cancer, where the immune system is not responding to a stealthy threat. But in dealing with autoimmune diseases such as multiple sclerosis or inflammatory bowel disease, it is more necessary to rein in over-enthusiastic immune cells. Galipeau has devised a fusokine that apparently reprograms cells into being more orderly.

 

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Exception from informed consent: what patients say

Informed consent is a basic principle of clinical research. Doctors are required to make sure that patients understand what’s involved with experimental treatments, and patients should only participate if they provide consent.

However, an important area of clinical research takes place outside of this general rule, because some life-threatening conditions – seizures, traumatic brain injury and cardiac arrest, as examples — make it impossible for the patient to learn about a clinical trial and make a decision about whether to participate. The urgency of treatment can also mean that seeking proxy consent from a relative is impractical.

A recent editorial in USA Today highlights this area of research, called EFIC (exception from informed consent). The author, Katherine Chretien from George Washington University, cites research from Emory investigators Neal Dickert and Rebecca Pentz.

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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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The creeping edges of cells: lamellipodia

Lamellipodia with red box
This month’s Image feature highlights lamellipodia, the thin sheet-like regions at the leading edges of migrating cells. Lamellipodia act as tiny creeping motors that pull the cell forward.

To help visualize lamellipodia, Adriana Simionescu-Bankston, a graduate student in Grace Pavlath’s lab, provided us with this photo of muscle cells. The red box shows an example of lamellipodia. Notice the edge of the cell, where the green color is more intense.

The green color comes from FITC-phalloidin, which stains F-actin, the Ray Ban outlet filaments that make up a large part of the cells’ internal skeleton. (Phalloidin is an actin-binding toxin originally isolated from death cap mushrooms, and FITC is what makes it green.) The blue color comes from DAPI, a dye that stains the DNA in the nucleus.

Simionescu-Bankston and Pavlath recently published a paper in the journal Developmental Biology, examining the function of a protein called Bin3 in muscle development and regeneration. They found that Bin3 appears to regulate lamellipodia formation; in mice that lack Bin3, muscle cells have fewer lamellipodia and the muscle tissues regenerate slower after injury. Bin3 is also important in the eye, since the “knockout” mice develop cataracts soon after birth.

 

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Lampreys hint at origin of ancient immune cells

Lamprey slideStudying lampreys allows biologists to envision the evolutionary past, because they represent an early offshoot of the evolutionary tree, before sharks and fish. Despite their inconspicuous appearance, lampreys have a sophisticated immune system with three types of white blood cell that resemble our B and T cells, researchers have discovered.

Scientists at Emory University School of Medicine and the Max Planck Institute of Immunology and Epigenetics in Freiburg have identified a type of white blood cell in lampreys analogous to the “gamma delta T cells” found in mammals, birds and fish. Gamma delta T cells have specialized roles defending the integrity of the skin and intestines, among other functions.

The results are published in the journal Nature. The finding follows an earlier study showing that cells resembling two main types of white blood cells, B cells and T cells, are present in lampreys.

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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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