Oxidative stress ain't about free radicals, it's about sulfur

Dean Jones says: don't worry about free radicals. Worry about the oxidized form of sulfur-containing amino acids, such as cystine, a useful biomarker for cardiovascular risk.

When genes forget to forget

In ancient Greek mythology, the souls of the dead were made to drink from the river Lethe, so that they would forget their past lives. Something analogous happens to genes at the very beginning of life. Photo of one- and two-cell mouse embryos courtesy of Todd Macfarlan at NICHD.

Proteomics making fantastic routine

The once fantastic is becoming routine, and here's an example. Protein mass spectrometry is like Wonkavision. The Emory Integrated Proteomics Core will split a sample into many pieces, send it through space, and reconstruct it on the computer, so that scientists can figure out what's in there.

Ancient protein flexibility may drive ‘new’ functions

A mechanism by which stress hormones inhibit the immune system, which appeared to be relatively new in evolution, may actually be hundreds of millions of years old.

A protein called the glucocorticoid receptor or GR, which responds to the stress hormone cortisol, can take on two different forms to bind DNA: one for activating gene activity, and one for repressing it. In a paper published Dec. 28 in PNAS, scientists show how evolutionary fine-tuning has obscured the origin of GR’s ability to adopt different shapes.

“What this highlights is how proteins that end up evolving new functions had those capacities, because of their flexibility, at the beginning of their evolutionary history,” says lead author Eric Ortlund, PhD, associate professor of biochemistry at Emory University School of Medicine.

GR is part of a family of steroid receptor proteins that control cells’ responses to hormones such as estrogen, testosterone and aldosterone. Our genomes contain separate genes encoding each one. Scientists think that this family evolved by gene duplication, branch by branch, from a single ancestor present in primitive vertebrates. Read more

Posted on by Quinn Eastman in Heart, Immunology Leave a comment

Grady Trauma Project — DICER link to PTSD plus depression

Violence and trauma are certainly not gifts, but scientifically, the Grady Trauma Project keeps on giving, even after co-director Kerry Ressler’s 2015 move to Massachusetts. Research at Emory on the neurobiology of post-traumatic stress disorder (PTSD) continues. This Nature Communications paper, published in December with VA-based psychiatrist Aliza Wingo as lead author, is an example.

Three interesting things about this paper:

  1. The focus on PTSD co-occurring with depression. As the authors note, several studies looking at traumatized individuals found PTSD and depression together more often than they were present separately. This was true of Atlanta inner city residents in the Grady Trauma Project, veterans and survivors of the 2001 World Trade Center attack.
  2. DICER: the gene whose activity is turned down in blood samples from people with PTSD plus depression. Its name evokes one of the three Fates in Greek mythology, Atropos, who cuts the thread of life. DICER is at the center of a cellular network of regulation, because it is part of the machinery that generates regulatory micro-RNAs.
  3. The findings recapitulate work in mouse models of stress and its effects on the brain, with a connection to the many-tentacled Wnt signaling/adhesion protein beta-catenin.

Some past posts on the Grady Trauma Project’s scientific fruits follow. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

IgG4-related means mysterious

Emory rheumatologist Arezou Khosroshahi was the lead author on a differential diagnosis case report in New England Journal of Medicine published in October, which describes an example of IgG4-related disease. This autoimmune condition’s name was agreed upon only recently, at an international conference she co-directed in 2011.

This review calls IgG4-related disease an “orphan disease with many faces.” It sounds like each case has the potential to be an episode of House. As Khosroshahi explains:

“Most patients undergo invasive procedures for resection or biopsy of the affected organ to exclude other conditions. Unfortunately, most of those patients get dismissed by the clinicians, given the good news that their disease was not malignancy. Many of them have recurrence of the condition in other organs after a few months or years.”

Arezou Khosroshahi, MD

Rheumatologist Arezou Khosroshahi, MD

In the case report, a woman was admitted to Massachusetts General Hospital, because of shoulder and abdominal pain and an accumulation of fluid around her lungs. Surgeons removed a softball-sized mass from her right lung. The mass did not appear to be cancerous, but instead seemed to be the result of some kind of fibrous inflammation, and the patient was treated with antibiotics. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Looking back – Lab Land Top 10 posts in 2015

Happy New Year, and thank you for reading Emory Lab Land. Here are the top ten posts during 2015, according to Google Analytics. I pledge to bring you more quirky and insightful research, striking images and explanations of hard-to-grasp concepts in 2016.

  1. Hypersomnia update: beyond subject one [post is from summer of 2014, reflects long tail/lasting interest from hypersomnia community]
  2. Anticancer drug strategy: making cells choke on copper
  3. Microbiome enthusiasm at Emory
  4. The unsweetened option [Not about iced tea, but about low-sugar diet and fatty liver disease]
  5. Fragile X regulation is a finely tuned machine
  6. Stem cell/cardiology researcher Hee Cheol Cho joins Emory
  7. There will be micro particles (in stored blood)
  8. Hypersomnia update: clarithromycin study
  9. Gabbing about GABA — implications for hypersomnia treatments
  10. Nudging physician behavior on antibiotic orders
Posted on by Quinn Eastman in Uncategorized Leave a comment

Emory labs on LabTV

This summer, video producers from the web site LabTV came to two laboratories at Emory. We are pleased to highlight the first crop of documentary-style videos.

LabTV features hundreds of young researchers from universities and institutes around the United States, who tell the public about themselves and their research. The videos include childhood photos and explanations from the scientists about what they do and what motivates them. Screen Shot 2015-12-18 at 9.14.51 AM

The two Emory labs are: Malu Tansey’s lab in the Department of Physiology, which studies the intersection of neuroscience and immunology, focusing on neurodegenerative disease, and Mike Davis’ lab in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, which is developing regenerative approaches and technologies for heart disease in adults and children. Read more

Posted on by Quinn Eastman in Heart, Immunology, Neuro Leave a comment

‘Mountain of data’ on flu vaccine responses

Bali Pulendran’s lab at Emory Vaccine Center teamed up with UCSD researchers and recently published a huge analysis of immune responses after seasonal flu vaccination (Immunity is making it available free this week, no subscription needed). Hundreds of volunteers at the Vaccine Center’s Hope Clinic took part in this study.

Note — this study looked at antibody responses to flu vaccines, but didn’t assess protection: whether study participants actually became sick with flu or not.

Our write-up is hereImmunity’s preview, from the Karolinska Institute’s Petter Brodin, is here, Cell Press’s press release is here.

Three points we wanted to call attention to:

*Long-lasting antibodies A surprising finding was how the “molecular signatures” that predict the strength of the immune response a few weeks after vaccination did not predict how long anti-flu antibodies stayed around. Instead, a separate set of signatures predicted the durability of antibody levels.

These distinct signatures may be connected with how plasma cells, responsible for antibody production, need to find homes in the bone marrow. That sounds like the process highlighted by Eun-Hyung Lee and colleagues in an Immunity paper published in July. In bone marrow samples from middle-aged volunteers, her team had found antibody-secreting cells that survive from childhood infections.

*Interfering (?) activation of NK cells/monocytes in elderly While the researchers found people older than 65 tended to have weaker antibody responses to vaccination, there were common elements of molecular signatures that predicted strong antibody responses in younger and older volunteers. However, elderly volunteers tended to have stronger signatures from immune cells that are not directly involved in producing antibodies (monocytes and ‘natural killer’ cells), both at baseline and after vaccination.

From the discussion: “This indicates a potential connection between the baseline state of the immune system in the elderly and reduced responsiveness to vaccination.” Additional comments on this from Shane Crotty in Brad Fikes’ article for the Union Tribune.

*The mountain of data from this and similar studies is available for use by other researchers on the web site ImmPort.

Posted on by Quinn Eastman in Immunology Leave a comment

Metagenomics explainer

A term we heard a bunch at the Emory Microbiome Symposium in November was “metagenomics”. Time for an explainer, with some help from Emory geneticist Tim Read.

Nature Reviews Microbiology defines metagenomics as “genomic analysis of microbial DNA that is extracted directly from communities in environmental samples.”

This technology — genomics on a huge scale — enables a survey of the different microorganisms present in a specific environment, such as water or soil, to be carried out. Metagenomics is also emerging as a tool for clinical diagnosis of infectious diseases.

Read notes that the term specifically refers to “shotgun” sequencing of environmental DNA.

“The shotgun approach is to randomly sample small pieces of the DNA in the tube, no matter which organism they came from,” he says. “The output is a mélange of different genes from bacteria, viruses, fungi, plants and humans.  The data is fascinating but the analysis is daunting.” Read more

Posted on by Quinn Eastman in Uncategorized 1 Comment

Autoimmune gene link for subtype of juvenile arthritis

Geneticist Sampath Prahalad and the families he works with were part of this recent PNAS paper, which probes genetic risk factors for systemic juvenile idiopathic arthritis.

There are several subtypes of juvenile arthritis, and sJIA (systemic juvenile idiopathic arthritis) sounds especially painful because of its inflammatory symptoms: daily spiking fever and skin rashes in addition to joint pain.

The international team of investigators assembled what they report as the largest collection of sJIA patients (close to 1000) and identified HLA-DRB1*11 as a genetic risk factor for sJIA.

HLA-DRB1 alleles have also been linked to autoimmune diseases such as multiple sclerosis, type I diabetes and (adult) rheumatoid arthritis. The finding strengthens the case for trying existing medications that target T cell activation in sJIA. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Chasing invasive cancer cells and more at #ASCB15

Earlier today, we posted a notice on Eurekalert for a Sunday, December 13 presentation by graduate student Jessica Konen at the American Society for Cell Biology meeting in San Diego.

Her research, performed with Adam Marcus at Winship Cancer Institute, was the topic of a video that recently won first prize in a contest sponsored by the Association of American Medical Colleges. This was our video team’s first use of the “fast hand on whiteboard” effect, and a lot of fun to make. The video’s strength grows out of the footage Konen and Marcus have of cancer cells migrating in culture. Check it out, if you haven’t already.

Poster presentations at the 2015 ASCB meeting can be found by searching this PDF. A few Emory-centric highlights:

*Chelsey Ruppersburg and Criss Hartzell’s work on the “nimbus”, a torus-shaped structure enriched in proteins needed to build the cell’s primary cilium

*Anita Corbett on how Emory students have a strong record of attaining their own NIH research funding

*Additional work by Adam Marcus’ lab on the tumor suppressor gene LKB1 and how its loss drives lung cancer cells to take on a “unique amoeboid morphology”

*Research from David Katz’s lab on the “epigenetic eraser” LSD1 (lysine-specific demethylase) and its function in neurons and neurodegeneration Read more

Posted on by Quinn Eastman in Cancer, Neuro Leave a comment

The secrets of a new Alzheimer’s secretase

The title of Keqiang Ye’s recent Nature Communications paper contains a provocative name for an enzyme: delta-secretase.

Just from its name, one can tell that a secretase is involved in secreting something. In this case, that something is beta-amyloid, the toxic protein fragment that tends to accumulate in the brains of people with Alzheimer’s disease.

Aficionados of Alzheimer’s research may be familiar with other secretases. Gamma-secretase was the target of some once-promising drugs that failed in clinical trials, partly because they also inhibit Notch signaling, important for development and differentiation in several tissues. Now beta-secretase inhibitors are entering Alzheimer’s clinical trials, with similar concerns about side effects.

Now, many Alzheimer’s researchers have studied gamma- and beta-secretase, but a review of the literature reveals that so far, only Ye and his colleagues have used the term delta-secretase.

This enzyme previously was called AEP, for asparagine endopeptidase. AEP appears to increase activity in the brain with aging and cleaves APP (amyloid precursor protein) in a way that makes it easier for the real bad guy, beta-secretase, to produce bad beta-amyloid.* At Alzforum, Jessica Shugart describes the enzyme this way:

Like a doting mother, AEP cuts APP into bite-sized portions for toddler BACE1 [beta-secretase] to chew on, facilitating an increase in beta-amyloid production. Read more

Posted on by Quinn Eastman in Neuro Leave a comment
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