Emory researchers led by neurologist Manuel Yepes, MD have identified a protein released by neurons while the brain is recovering from a stroke. The results were published online today in Journal of Neuroscience.
The protein, called urokinase-type plasminogen activator or uPA, has been approved by the FDA to dissolve blood clots in the lungs. It has been tested in clinical trials in some countries as a treatment for acute stroke.
The Emory team’s findings suggest that in stroke, uPA’s benefits may extend beyond the time when doctors’ principal goal is dissolving the blood clot that is depriving the brain of blood.
Instead, uPA appears to help brain cells recover from the injuries induced by loss of blood flow. Treating mice with uPA after an experimental stroke can improve their recovery of motor function, the researchers found.
Geneticist Joe Cubells is doing some monumental work re-examining a Chinese study of folic acid supplementation during pregnancy and its impact on autism risk. He is also the Medical Director at the Emory Autism Center. Please see SFARI to check it out.
Biomedical engineer Yonggang Ke‘s “DNA origami” artwork appears on the cover of Nature Methods, as part of a celebration of the journal’s 10th anniversary. Ke designed self-assembling DNA strands that would form a cylinder and a ring structure, let them assemble, and obtained images with transmission electron microscopy. The height of the final image is 120 nanometers, smaller than the wavelengths of visible light and about the size of an influenza or HIV virion.
Methylation, an epigenetic modification to DNA, can be thought of as a highlighting pen applied to DNA’s text, adding information but not changing the actual letters of the text.
Are you still with me on the metaphors? If so, consider this wrinkle. (If not, more explanation here.)
Emory geneticist Peng Jin and his colleagues have been a key part of the discovery in the last few years that methylation comes in several colors. His lab has been mapping where 5-hydroxymethylcytosine or 5hmC appears in the genome and inferring how it functions. 5-hmC is particularly abundant in the brain.
Methylation, in the form of 5-methylcytosine or 5mC, is both a control button for turning genes off and a sign of their off state. 5hmC looks like 5mC, except it has an extra oxygen. That could be a tag for a removal, or a signal that a gene is poised to be turned on.
Two recent papers on this topic:
Please recall that an enriched environment (exercise and mental stimulation) is good for learning and memory, for young and old. In the journal Genomics, Jin and his team show that exposing mice to an enriched environment — a running wheel and a variety of toys — leads to a 60 percent reduction in 5hmC in the hippocampus, a region of the brain critical for learning and memory. The changes in 5hmC were concentrated in genes having to do with axon guidance. Hat tip to the all-things-epigenetic site Epigenie.
In Genes and Development, structural biologist Xiaodong Cheng and colleagues demonstrate that two regulatory proteins that bind DNA (Egr1 and WT1) respond primarily to oxidation of their target sequences rather than methylation. These proteins like plain old C and 5mC equally, but they don’t like 5hmC or other oxidized forms of 5mC. “Gene activity could plausibly be controlled on a much finer scale by these modifications than simply ‘on or ‘off’,” the authors write.
What conferences like the HIV + Aging meeting recently held by Emory in Decatur offer the visiting writer: anecdotes that illustrate issues of clinical care.
To illustrate her point that assumptions about who is likely to develop a new HIV infection may lead doctors to miss possible diagnoses, keynote speaker Amy Justice from Yale described a patient who was seen last year at Yale-New Haven Hospital.
A 60 year old man reported fatigue and had lost 40 pounds over the course of a year. Despite those symptoms, and the discovery of fungal and viral infections commonly linked to HIV/AIDS, it took nine months before a HIV test was performed on the patient, a delay Justice deplored.
Sex and substance abuse do not end at age 50, she said, citing data showing that the risk of HIV transmission can be greater among older adults, and that substance abuse is more likely among adults who are HIV positive compared to those who are HIV negative.
Justice also highlighted the issue of polypharmacy (interactions between prescription drugs at the same time), a concern even in people who are not living with HIV. Common blood pressure medications taken by older adults to prevent heart disease have been suspected of increasing the risk for falls. That’s a problem especially for people living with HIV, because HIV infection has been linked to weakened bone. Read more
You may have been hearing about the advent of Big Data: truckloads of information coming from cell phones, satellites, microscopes, and perhaps someday, wearable health monitoring devices.
At Emory, specialists in biomedical informatics have been in the forefront of efforts to design software that will allow scientists to learn from these mountains of data. Fusheng Wang was recently named as co-PI on a five-year $5 million National Science Foundation grant to create MIDAS (Middleware for Data-Intensive Analytics and Science), part of the NSF’s Data Infrastructure Building Blocks program. For this grant, the team consists of seven institutions: Indiana University (lead — Geoffrey Fox), Arizona State, Emory, Kansas, Rutgers, Utah and Virginia Tech.
Wang also recently received a NSF Career award in this same area.
The MIDAS project addresses major data challenges in seven different communities: biomolecular simulations, network and computational social science, epidemiology, computer vision, spatial geographical information systems, remote sensing for polar science, and pathology informatics. Wang is responsible for pathology informatics and geospatial, gathering requirements from those communities and implementing the spatial query and parts of the image analysis library. The libraries are supposed to be interoperable across a range of computing systems including clouds, clusters and supercomputers. The project includes a plan to develop a open online course (MOOC), according to the NSF.
From left: RSPH dean Jim Curran, First Lady Jeannette Kagame, HIV/AIDS researcher Susan Allen, Vice Provost Philip Wainwright
Most of the discussion, when Rwanda’s First Lady Jeannette Kagame recently visited Emory, was not about HIV vaccines, and rightly so. It was about how far Rwanda has come as a country since the 1994 genocide [videos of author Philip Gourevitch discussing Rwanda].
Still, while introducing the First Lady and thanking her for her support of HIV/AIDS research in Rwanda, Susan Allen mentioned a clinical trial for a HIV vaccine that began last year in Rwanda, Kenya and the United Kingdom and is now wrapping up the vaccination phase. Her colleague in Kigali, Etienne Karita, is one of the principal investigators.
The vaccine uses replicating Sendai virus, which causes respiratory tract illness in rodents but not in humans, as a vector to deliver the HIV gag gene. The trial combines this vaccine, administered intranasally, in various configurations with an adenovirus-based vaccine. This is the first time that Sendai virus is being used in a HIV vaccine.
As IAVI Report’s Regina McEnery explains, researchers hope the Sendai vector might recruit targeted immune responses to mucosal tissues and provide an edge to the immune system when it is subsequently challenged by HIV.
In a future post, we plan to provide an additional update on HIV vaccine research, focusing on GeoVax and (separate, for comparison) a planned large-scale followup to the landmark RV144 Thai trial.
Cardiac cell therapy sounds like a promising idea: use the patients’ own cells to enhance healing or even regenerate the damaged heart muscle. Doctors have taken up the promise, testing it in clinical trials involving thousands of patients. But a basic problem facing the field is this: naked cells don’t appear to stay in the heart or stay alive for long enough to provide a sustained benefit.
Three labs at Emory have published papers in the last year addressing this problem. All describe some kind of supportive biomaterials, consisting of capsules or a gel, which help cells stay put and stay alive, in experiments where recovery from a heart attack is modeled in rodents.
The most recent comes from cardiologist Young-sup Yoon and colleagues, in ACS Nano. The first author is Kiwon Ban, a senior postdoc in Yoon’s laboratory. Ban and his team use self-assembling peptides, developed in collaboration with biomaterials engineer Ho-wook Jun at UAB (see figure). The peptides form a gel that both physically keeps cardiac muscle cells in the heart and eases their integration into the heart tissue over a period of weeks. As Katie Bourzac explains in Chemical & Engineering News:
One peptide acts like a natural protein that adheres to cells and promotes cell survival. The second peptide is readily broken down by a protease. The team designed the gel so that when it is implanted, it begins to degrade a bit, allowing cells from the body to migrate in. Eventually the gel should disintegrate completely as the heart tissue builds its own extracellular matrix. This particular gel has already performed well as a support for other kinds of cells grown from stem cells, including pancreatic and muscle cells.
We thought it may be useful to readers to be able to compare and contrast these papers in chart form. Read more