HIV virions attached to cell membrane

Waiting to escape their tethers (another Best Image winner from Postdoc Research Symposium)

Spider fibers in smooth muscle cells

Beta-tubulin looks hairy

Happy birthday, spinal cord neurons

White candles mark neurons' birthdays in contest-winning image

HIV virions attached to cell membrane

The third winner of the Best Image contest from the Postdoctoral Research Symposium, from postdoc Joshua Strauss in electron microscopist Elizabeth Wright’s lab.

Strauss explains:

Tetherin is a host cell factor that mechanically links HIV-1 to the plasma membrane. This is the first time anyone has imaged tethered HIV-1 by cryo-electron tomography. In doing so, we were able to learn about the length and arrangement of the tethers.

Note: Tetherin also studied by Paul Spearman + colleagues.Joshua_Strauss_OPE_Image

Cryo-electron tomography is an imaging technique which enables scientists to look at biological specimens in a “native-like” (frozen hydrated) state, without the chemical fixatives or heavy metal stains typically used for conventional electron microscopy.

The 3D reconstruction was manually segmented to highlight the different viral and cellular components: HIV-1 virions (lavender), mature conical-cores (aqua blue), immature Gag lattice (pink), plasma membrane (peach), rod-like tethers (sea green).

Posted on by Quinn Eastman in Immunology Leave a comment

Spider fibers in smooth muscle cells

This image submitted by Thalita Abrahao won second place at the Postdoctoral Research Symposium Thursday. Abrahao, a postdoc in Kathy Griendling’s lab, is studying vesicle trafficking in vascular smooth muscle cells.

Thalita Abrahao -- Kathy Griendling lab

Thalita Abrahao — Kathy Griendling lab

Griendling’s lab has been looking into how the enzyme Nox4 and its partner Poldip2 are involved in cell migration, and Abrahao was investigating if vascular smooth muscle cells that have less Poldip2 have changes in protein processing.

Here, green represents beta-tubulin, a protein making up fine-looking fibers (microtubules) extending through the cell. Purple represents Sec23, part of the process of vesicle trafficking and protein secretion. White indicates when beta-tubulin and Sec23 are both present. Orange marks DNA in the nucleus.

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Happy birthday, spinal cord neurons

Congratulations to JoAnna Anderson, postdoctoral fellow in Francisco Alvarez’ lab, for winning the Best Image contest, part of the Postdoctoral Research Symposium taking place Thursday. We will have explanations of the second and third place images Thursday and Friday.

The brief description of Anderson’s image is: “EdU birthdating of V1 inhibitory interneurons in the postnatal day 5 lumbar spinal cord.” But how did all those colors get in there and what do they mean? Alvarez explains:

The work is about finding the times of neurogenesis of the many inhibitory neurons that pattern motor output in the ventral horn of the spinal cord, so that our muscles contract in a coordinated manner to achieve the desired movements.

For example, when one muscle contracts, the muscle with the opposite action on the same joint will be inhibited. Anderson and her fellow postdoc Andre Rivard have been studying the development of the V1 neurons that carry out this inhibition.

AndersonJoAnnaThe image shows a slice of a 5 day old mouse’s spinal cord, and we can see individual cells. Some of the neurons are producing fluorescent proteins: one of the proteins is red, the other is green, and where both proteins are present, a yellow or orange color can be seen. The red and the green colors are indicators for two genes, Engrailed-1 and FoxP2, respectively, both of which regulate neurons’ development.

In addition, the white spots at the top come from EdU (5-ethynyl-2’-deoxyuridine), a chemical that impersonates a building block of DNA well enough to get incorporated into cells when they are dividing. It is helpful to remember that neurons are cells that have stopped dividing. Giving embryos a pulse of EdU is a way to mark the point at which progenitor cells mature and become neurons.

By repeating the experiment at different dates, the researchers can see that FoxP2 positive green cells are generated after the FoxP2 negative red cells. Both types of cells are derived from the same progenitors, but in different cell cycles. Read more

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Moving urology beyond the PSA test

The PSA (prostate specific antigen) blood test has been criticized for years for driving men to seek biopsies and then definitive treatment for slow-growing cancers that may not pose a danger.

At the recent AUA meeting in New Orleans, urologist Martin Sanda presented results from research on tests that could allow the urology field to move beyond the PSA test as it is now. The upcoming issue of Winship magazine’s cover story will have more on this topic.

Martin Sanda, MD is director of Winship Cancer Institute’s Prostate Cancer Program and chair of urology at Emory University School of Medicine

Right now, only about a sixth of men who have a biopsy based on the results of a PSA test have something that doctors agree should be called a cancer (a tumor with a Gleason score of seven or higher).

Sanda described studies on a urine test that could double that specificity, possibly eliminating unnecessary biopsies for many men. Read more

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Really? I had a heart attack?

A recent Harvard study, published in Circulation, found a surprising level of inconsistency between what medical records say about whether people had a heart attack and what they report themselves in surveys.

About a quarter of Medicare patients who said in a survey that they previously had a heart attack have no record of having any heart-related hospital admission. Conversely, about one-third of patients who, according to Medicare, experienced a heart attack said they hadn’t.

This finding is consistent with an Emory study from cardiologists Neal Dickert and Habib Samady, in which participants in a clinical trial were interviewed just a couple days after the initial procedure. The trial was testing a “post-conditioning” modification of angioplasty+stenting performed during treatment for a heart attack. Just over half (55 percent) of the participants initially remembered being asked to participate when asked. Read more

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Test of megadose vitamin D in intubated critical care patients

Whether dietary supplementation with vitamin D is beneficial, in terms of preventing disease, has been controversial. However, vitamin D has been reported to increase immune cells’ production of microbe-fighting proteins. That’s why Emory doctors have been testing whether high doses of vitamin D could be helpful for critical care patients, who need to ward off infections.

The results of a small-scale clinical trial, presented in Denver this week at the American Thoracic Society meeting, suggest that high doses of vitamin D could decrease the length of hospital stays in critically ill patients with respiratory failure. Read more

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A few links for BEINGS2015

Several well-known authors, scientists and bioethicists are in downtown Atlanta’s Tabernacle for the #BEINGS2015 conference. Paul Wolpe and the Center for Ethics have been central to organizing the event, and several Emory biomedical and genetics researchers will be involved in shaping the consensus documents that will emerge.

I won’t attempt to summarize the ongoing discussion at this point; with biotechnology, it is difficult to draw a circle around certain topics and say “we’re going to focus on this, but not this” and today was a good example. The border between existing agricultural biotechnology and new organisms seems hard to define.

Three interesting relevant links:

The National Academy of Sciences is launching an effort to guide decision making on human gene editing technologies such as Cas9/CRISPR

Collection of scientists’ comments on human gene editing and Cas9/CRISPR in Nature Biotechnology

Nature Chem Bio paper on engineered yeast that “paves way for home brew heroin”. Interesting role of FBI in overseeing this emerging area, and note that full production of opiates in yeast may look close, but is still not yet possible.

 

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Spotlight on liver fibrosis

For a May explainer, we’d like to spotlight liver fibrosis. Two recent papers from Emory research teams in the journal Hepatology focus on this process.

Liver fibrosis is an accumulation of scar tissue and proteins outside cells that occurs as a result of chronic damage to the liver. It involves inflammation and immune cells, as well as activation of a type of cell in the liver (hepatic stellate cells), which usually stores fat and vitamin A. Fibrosis and cirrhosis are not the same. Think of it this way: cirrhosis is the late stage of the disease, but fibrosis is how someone can get there.

The liver has a remarkable, even mythical, ability to regenerate, but there is a long list of ways that someone can injure this most vital organ. Quickly – take too much acetaminophen (the most common cause of acute liver failure in the United States). More slowly – develop a hepatitis C infection. Drink large quantities of alcohol. Or something with more subtle effects: consume a diet high in sugar, which can lead to fatty liver. The relationship between fatty liver and more serious liver disease is currently under investigation.

One of the Hepatology papers comes at liver fibrosis from a malaria angle. Patrice Mimche, Tracey Lamb and colleagues show the involvement of EphB2 tyrosine kinase, a signaling molecule not previously known to be involved in liver fibrosis.

Malaria parasites have a complex life cycle, growing in the liver and then in the blood. Lamb says an important part of her paper was the finding that in mouse malaria infection, EphB2 is activated during the blood stage on immune cells infiltrating into the liver. EphB2 (an active drug discovery target) may be acting as a tissue-specific adhesion molecule, she says.

Read more

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Education is a life preserver, after heart attack

For the last decade, cardiology researchers have been collecting detailed information on the patients who come through Emory’s catheterization labs. The density of data (close to 7000 people) can make it possible to achieve some insights about mortality in American society.

Cardiology research fellow Salim Hayek, MD, presented some provocative findings yesterday in a poster competition at the American College of Physicians meeting in Boston. He has been working with Arshed Quyyumi, MD and colleagues at Emory’s Clinical Cardiovascular Research Institute.

Their analysis shows “college education as a discrete indicator of socioeconomic status was an independent predictor of survival.”

A key thing to remember when looking at this data is that most of the people in the cath lab at a given moment are not actually having a heart attack — just 13 percent are. (Abstract/poster available upon request). However, there’s enough suspicion or history of heart disease for doctors to take a look inside; most of them have hypertension and coronary artery disease, and many have had a heart attack in the past. The group is mostly men, average age 63. Read more

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Six beautiful images — choose your favorites

WoodruffMatthew1

Matthew Woodruff — Bali Pulendran lab

ImageJ=1.48g unit=micron

Kenneth Myers — James Zheng lab

Joshua_Strauss_OPE_Image

Joshua Strauss — Elizabeth Wright lab

AndersonJoAnna

JoAnna Anderson — Francisco Alvarez lab

AlexTamas

Alexey Tamas — Charles Searles lab

Emory’s Office of Postdoctoral Education is holding a Best Image contest. The deadline to vote is this Thursday, April 30. You can look at these beautiful images (and guess exactly what they are, based on what lab they come from), but to VOTE, you need to go to the OPE site.

This is part of the run up to their Postdoctoral Research Symposium at the end of May.

(Hat tip to Ashley Freeman in Dept of Medicine!)

Read more

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