Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Emory researchers see investigating 3q29 deletion as a way of unraveling schizophrenia’s biological and genetic Read more

B cells off the rails early in lupus

Emory scientists could discern that in people with SLE, signals driving expansion and activation are present at an earlier stage of B cell differentiation than previously Read more

Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

Department of Pathology and Laboratory Medicine

Breaking the rules: flagellin vs rotavirus

Flagellin is a bacterial protein that activates the innate immune system. Its name comes from flagella, the whips many bacteria use to propel themselves.

On Thursday, a team of researchers led by immunologist Andrew Gewirtz reported in Science that treatment with flagellin can prevent or cure rotavirus infection in animals. Rotavirus infection is one of the most common causes of severe diarrhea and is a major cause of death for children in developing countries.

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Andrew Gewirtz, PhD

Gewirtz’s lab is now at Georgia State, but he and his colleagues initiated this research while at Emory and several co-authors are affliliated with Emory, including immunologist Ifor Williams.

These findings are remarkable for several reasons. One is: give the immune system something from bacteria, and it’s better at fighting a virus? As Gewirtz says in a GSU news release: “It’s analogous to equipping an NFL defense with baseball bats. Blatant violation of all the rules but yet, at least in this case, very effective.”

For me, what was most surprising about this paper was that treatment with flagellin, or immune signaling proteins activated by flagellin, can get mice with severely impaired immune systems – no T cells or B cells at all — to evict rotavirus. These are mice that have to be reared under special conditions because they are vulnerable to other infections. Interferons, well-known antiviral signaling molecules, are also not involved in resisting or evicting rotavirus infection, the researchers found. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Acidity of aging leads to new Alzheimer’s drug target

Pathologist Keqiang Ye and his colleagues have been studying the functions of an enzyme called AEP, or asparagine endopeptidase, in the brain. AEP is activated by acidic conditions, such as those induced by stroke or seizure.

AEP is a protease. That means it acts as a pair of scissors, snipping pieces off other proteins. In 2008, his laboratory published a paper in Molecular Cell describing how AEP’s acid-activated snipping can unleash other enzymes that break down brain cells’ DNA.

Following a hunch that AEP might be involved in neurodegenerative diseases, Ye’s team has discovered that AEP also acts on tau, which forms neurofibrillary tangles in Alzheimer’s disease.

“We were looking for additional substrates for AEP,” Ye says. “We knew it was activated by acidosis. And we had read in the literature that the aging brain tends to be more acidic, especially in Alzheimer’s.”

The findings, published in Nature Medicine in October, point to AEP as a potential target for drugs that could slow the advance of Alzheimer’s, and may also lead to improved diagnostic tools. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Alternative antibody architecture

This complex diagram, showing the gene segments that encode lamprey variable lymphocyte receptors, comes from a recent PNAS paper published by Emory’s Max Cooper and his colleagues along with collaborators from Germany led by Thomas Boehm. Lampreys have molecules that resemble our antibodies in function, but they look very different at the protein level. The study of lamprey immunity provides hints to how the vertebrate immune system has evolved.
PNAS-2014-Das-1415580111_Page_4

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BioArt: amyloid in the heart

What Abstract Expressionist artist painted this? Jackson Pollock?LewisW2013

Actually, the photo depicts amyloid plaques, a frequent topic in the context of Alzheimer’s disease. Pathologist William Lewis‘ photo reminds us that amyloid can also appear in the heart.

Amyloidosis of the heart is a set of complex diseases caused by the accumulation of cellular proteins that form an amyloid plaque. Although http://www.oakleyonorder.com/ amyloidosis was described more than 100 years ago, the causative proteins were not identified until recent chemical analyses were conducted. This image shows an amyloid plaque stained with Congo red stain and viewed through a polarized lens. The optical properties of the amyloid-forming protein cause it to appear green, while other matrix materials within the plaque appear as orange and blue.

The photo, which was one of the winners of the FASEB (Federation of American Societies for Experimental Biology) 2013 BioArt competition, was featured on NIH director Francis Collins’ blog this week.

Lewis, who studies the effects of antiretroviral drugs on the cardiovascular system in his laboratory, reports that he came across the amyloid tissue sample as part of his duties as director of cardiovascular pathology: “It was beautiful.”

Posted on by Quinn Eastman in Heart Leave a comment

How beneficial bacteria talk to intestinal cells

Guest post from Courtney St Clair Ardita, MMG graduate student and co-author of the paper described. Happy Halloween!

In the past, reactive oxygen species were viewed as harmful byproducts of breathing oxygen, something that aerobic organisms just have to cope with to survive. Not any more. Scientists have been finding situations in humans and animals where cells create reactive oxygen species (ROS) as signals that play important parts in keeping the body healthy.

One example is when commensal or good bacteria in the gut cause the cells that line the inside of the intestines to produce ROS. Here, ROS production helps repair wounds in the intestinal lining and keeps the environment in the gut healthy. This phenomenon is not unique to human intestines. It occurs in organisms as primitive as fruit flies and nematodes, so it could be an evolutionarily ancient response. Examples of deliberately created and beneficial ROS can also be found in plants, sea urchins and amoebas.

Researchers led by Emory pathologist Andrew Neish have taken these findings a step further and identified the cellular components responsible for producing ROS upon encountering bacteria. Postdoctoral fellow Rheinallt Jones is first author on the paper that was recently published in The EMBO Journal. 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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