AÂ Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria â€“ lactobacilli â€“ activates the same ancient signaling pathway in intestinal cells in both insects and mammals.Â It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).
Asma Nusrat, MD
A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliverÂ that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.
This ideaÂ has advanced experimentally, as demonstrated byÂ twoÂ papers from Jones and Neishâ€™s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.
Nusrat told me Friday her team began investigatingÂ annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria areÂ activating the same molecular signals.Â (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)
In aÂ secondÂ Journal of Clinical Investigation paper published this February, NusratÂ and herÂ colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more
Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory and Winship Cancer Institute researchers have found.
The results were published this week in the journalÂ PLOS Pathogens.
The findings suggest imatinib, known commercially as Gleevec, or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cellsÂ in vitro, but provides information on how to dose imatinib for new clinical applications.
â€œWe think that low doses of imatinib are mimicking â€˜emergency hematopoiesis,â€™ a normal early response to infection,â€ says senior author Daniel Kalman, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine.
Imatinib, is an example of a â€œtargeted therapyâ€ against certain types of cancer. It blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.
Imatinib also inhibits normal forms of these enzymes that are found in healthy cells. Several pathogens â€“ both bacteria and viruses â€“ exploit these enzymes as they transit into, through, or out of human cells. Researchers have previously found that imatinib or related drugs can inhibit infection of cells by pathogens that are very different from each other, includingÂ tuberculosis bacteriaÂ andÂ Ebola virus. Read more
Emory’s Max Cooper was celebrated this week in Nature for his discovery of B cells in the 1960s, while working with Robert Good at the University of Minnesota.
Cooper in Good’s laboratory in the 1960s (source: National Library of Medicine)
B cells are immune cells that display antibodies on their surfaces, and can become antibody-secreting plasma cells. Without B cells: no antibodies to protect us against bacteria and viruses. Where B cellsÂ come from, and how they can developÂ such a broad repertoire of antibody tools, was a major puzzle of 20th century immunology, which Cooper contributed toÂ solving. (See the Nature piece to learnÂ why the “B” comes from theÂ name of an organ in chickens.)
The authorsÂ did not mention that Cooper is now at Emory studying lampreys’ immune systems, which are curiouslyÂ different fromÂ those of mammals. The similarities and differences provide insights into the evolution of ourÂ immune systems. In addition, scientists here are exploring whether lamprey’s antibody-like molecules might be turned into anticancer drugs.
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 ScienceÂ 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.
Andrew Gewirtz, PhD
Gewirtzâ€™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 itâ€™s better at fighting a virus? As Gewirtz says in a GSU news release: â€œItâ€™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.â€
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 â€“ 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
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 AEPâ€™s acid-activated snipping can unleash other enzymes that break down brain cellsâ€™ DNA.
Following a hunch that AEP might be involved in neurodegenerative diseases, Yeâ€™s team has discovered that AEP also acts on tau, which forms neurofibrillary tangles in Alzheimerâ€™s disease.
â€œWe were looking for additional substrates for AEP,â€ Ye says. â€œWe knew it was activated by acidosis. And we had readÂ in the literature that the aging brain tends to be more acidic, especially in Alzheimerâ€™s.â€
The findings, published in Nature Medicine in October, point to AEP as a potential target for drugs that could slow the advance of Alzheimerâ€™s, and may also lead to improved diagnostic tools. Read more
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 moleculesÂ that resemble our antibodies in function, but theyÂ look very different at the protein level. The study of lamprey immunityÂ provides hints to how the vertebrate immune system has evolved.
What Abstract Expressionist artist painted this? Jackson Pollock?
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.”
Guest post from Courtney St Clair Ardita, MMGÂ graduate studentÂ andÂ 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
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 â€œstalksâ€ of nerve cells.
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 â€“ 7,8-dihydroxyflavone and deoxygedunin — have shown promise in experimental models of diseases such as stroke and Parkinsonâ€™s disease. They also have been used to tweak learning and memory in animal models.