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Archive - Nov 2016

November 30th

Sleep Apnea Promotes Release of Circulating Exosomes That Can Increase Tumor Growth

A team of researchers from the University of Chicago and the University of Barcelona has found that intermittent hypoxia, or an irregular lack of air experienced by people with sleep apnea, can increase tumor growth by promoting the release of circulating exosomes. Their results were published in the November 2016 issue of the journal CHEST. The article is titled “Tumor Cell Malignant Properties Are Enhanced by Circulating Exosomes in Sleep Apnea.” Obstructive sleep apnea has been associated with increased incidence of cancer and mortality. In order to better understand the connection between the two, investigators took a detailed look at lung cancer tumor cell growth in mice. Half of the mice experienced regular breathing patterns, while the other half were exposed to intermittent hypoxia (IH) to simulate sleep apnea. The team found that exosomes released in the mice exposed to IH enhanced the malignant properties of the lung cancer cells. Exosomes are microscopic spheres that transport proteins, lipids, mRNAs, and miRNAs between cells, similar to courier messengers delivering packages. They play a central role in cell-to-cell communication and are involved in promoting cancer cell growth and metastasis. "Exosomes are currently under intense investigation since they have been implicated in the modulation of a wide range of malignant processes," explained lead investigator David Gozal, M.D., M.B.A., Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois. "Hypoxia can increase exosomal release and selectively modify exosome contents such as to enhance tumor proliferation and angiogenesis.

EphA2 Identified As Elusive Functional Signaling Receptor for Progranulin; Finding May Aid Advances in Cancer & Neurodegenerative Disease Studies

Progranulin is produced and secreted by most cells in the body. From skin to immune cells, brain to bone marrow cells, progranulin plays a key role in maintaining normal cellular function. In cancer, too much progranulin makes tumors (particularly prostate carcinomas) more aggressive and metastatic, whereas, in neurodegenerative diseases, too little progranulin is associated with disease onset and progression. Until now, studying progranulin has been tricky as the progranulin receptor that communicates biological information to the cell's signaling machinery has remained elusive for decades. Now, researchers at Thomas Jefferson University's Sidney Kimmel Cancer Center have discovered a cell-surface receptor highly expressed by cancerous and brain cells that directly and tightly binds progranulin. Importantly, the researchers also showed that this binding activates a cellular program that makes cancer cells more aggressive. The results were published online on November 30, 2016 in The Journal of Cell Biology. The article is titled “EphA2 Is a Functional Receptor for the Growth Factor Progranulin." "Identifying the functional signaling receptor for progranulin will help us understand how this molecule functions in cancer and whether pharmacologically targeting it will slow the progression of a number of cancers," says Renato V. Iozzo, M.D., Ph.D., Gonzalo E. Aponte Professor and Deputy Chair of the Department of Pathology, Anatomy & Cell Biology at Thomas Jefferson University and researcher at the Sidney Kimmel Cancer Center at Jefferson.

Study Reveals Key Role of mRNA's “Fifth Nucleotide” in Sex Determination in Fruit Flies

A team of scientists led by researchers at the University of Birmingham has shown how a common mRNA modification, N6-methyladenosine (m6A), regulates gene expression to determine the sex of fruit flies. The function of m6A, an mRNA modification known as the “fifth nucleotide,” has long been a mystery. But a new study, published online on November 30, 2016 in Nature, has revealed that m6A plays a key role in the regulation of the Sex-lethal (Sxl) gene, which controls sex determination of the fruit fly Drosophila. The Nature article is titled “m6A Potentiates Sxl Alternative pre-mRNA Splicing for Robust Drosophila Sex Determination.” Sxl is a “switch gene,” meaning that Drosophila sex is determined by whether or not Sxl protein is made. The Sxl gene is transcribed into mRNA in both males and females, but through a process called “alternative splicing” only the female mRNA can be made into a functional protein. Alternative splicing is a widespread mechanism of gene expression and occurs in almost all human genes, allowing the synthesis of many more proteins than would be expected from the 20,000 protein-coding genes in our genome. The new study shows that m6A mediates this process for Sxl in Drosophila, ultimately determining whether a fly develops as male or female. The new findings offer an important insight into a classic textbook example of an essential and widely studied process. “Despite sex determination being so fundamental, nature has found many ways of determining sex,” says Dr. Matthias Soller from the School of Biosciences at the University of Birmingham and lead author on the paper. “Our study suggests that m6A-mediated adjustment of gene expression might be an ancient yet unexplored mechanism for the development of this diversity.” The collaboration began after co-author Dr.

Each Animal Species Hosts Unique Microbial Community and Benefits from It, Study Suggests

Each animal species hosts its own, unique community of microbes that can significantly improve its health and fitness. That is the implication of a laboratory study that investigated four different animal groups and their associated microbiota. The research found that each species within the group has a distinctive microbial community. Additional experiments with two of the groups - one mammal and one insect - demonstrated that individuals possessing their natural microbiota digested food more efficiently and had greater survival than those that were implanted with the microbial communities of closely related species. "Previous research has tended to concentrate on the negative effects of microbes. In this case, we are showing that whole communities of microbes have positive effects as well," said Vanderbilt graduate student Andrew Brooks, co-first author of the study. The paper describing the study's results is titled "Phylosymbiosis: Relationships and Functional Effects of Microbial Communities across Host Evolutionary History" and it was published online on November 18, 2016 in PLOS Biology. "We coined the term phylosymbiosis a couple of years ago to denote the fact that evolution can act on host species and change their microbial communities," said Seth Bordenstein, Ph.D., Associate Professor of Biological Sciences and Pathology, Microbiology, and Immunology at Vanderbilt University, who directed the study. Postdoctoral researcher Dr. Kevin Kohl and Robert Brucker at Harvard University were other co-first authors, and another participant, Edward Van Opstal, is a graduate student at Vanderbilt. All animals teem with thousands of different species of microbes collectively called the microbiome.

Fiber Optic pH Probe May Aid Breast Cancer Surgery

University of Adelaide researchers have developed an optical fiber probe that distinguishes breast cancer tissue from normal tissue - potentially allowing surgeons to be much more precise when removing breast cancer. The device could help prevent follow-up surgery, currently needed for 15-20% of breast cancer surgery patients where all the cancer is not removed. In an article published online on November 30, 2016 in the journal Cancer Research, researchers at the University of Adelaide in the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), the Institute for Photonics and Advanced Sensing, and the Schools of Physical Sciences and Medicine, describe how the optical probe works by detecting the difference in pH between the two types of tissue. The article is titled “Cancer Detection in Human Tissue Samples Using a Fiber-Tip pH Probe.” The research was carried out in collaboration with the Breast, Endocrine and Surgical Oncology Unit at the Royal Adelaide Hospital. "We have designed and tested a fiber-tip pH probe that has very high sensitivity for differentiating between healthy and cancerous tissue with an extremely simple - so far experimental - setup that is fully portable," says project leader Dr. Erik Schartner, postdoctoral researcher at the CNBP at the University of Adelaide. "Because it is cost-effective to do measurements in this manner compared to many other medical technologies, we see a clear scope for this technology in operating theaters." Current surgical techniques to remove cancer lack a reliable method to identify the tissue type during surgery, relying on the experience and judgement of the surgeon to decide on how much tissue to remove. Because of this, surgeons often perform “cavity shaving,” which can result in the removal of excessive healthy tissue.

Nanotechnology “Green” Approach May Have Impact on Liver Cancer; Photothermic Therapy Using Gold Nanoparticles Coated with Gum Arabic Shows Promise

According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or to transplant the entire organ. However, an international study led by University of Missouri (MU) School of Medicine researchers has proven that a new, minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and in vitro human cells. "The limitations when treating most forms of cancer involve collateral damage to healthy cells near tumor sites," said Kattesh Katti (photo), Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study. "For more than a decade we have studied the use of nanotechnology to test whether targeted treatments would reduce or eliminate damage to nearby healthy cells. Of particular interest has been the use of green nanotechnology approaches pioneered here at MU that use natural chemical compounds from plants." The study was conducted in the United States and Egypt, and it involved the use of gold nanoparticles encapsulated by a protective stabilizer called gum Arabic. The nanoparticles were introduced to the livers of mice intravenously and were heated with a laser through a process known as photothermal therapy. "Gum Arabic is a natural gum made of the hardened sap from acacia trees," said Dr. Katti, who also serves as director of the MU Institute of Green Nanotechnology and is the Margaret Proctor Mulligan Distinguished Professor of Medical Research at the MU School of Medicine. "It is FDA-approved for human consumption and is primarily used in the food industry as an additive.

November 29th

Platypus Venom May Hold Clues to Fighting Type 2 Diabetes

Australian researchers have discovered remarkable evolutionary changes to insulin regulation in two of the nation's most iconic native animal species - the platypus and the echidna - which could pave the way for new treatments for type 2 diabetes in humans. The findings, published online on November 29, 2016 in the Nature journal Scientific Reports, reveal that the same hormone produced in the gut of the platypus to regulate blood glucose is also surprisingly produced in its venom. The research is led by Professor Frank Grutzner at the University of Adelaide and Associate Professor Briony Forbes at Flinders University. The open-access article is titled “Monotreme Glucagon-Like Peptide 1 in Venom Gut—One Gene, Two Vdery Different Functions.” The hormone, known as glucagon-like peptide-1 (GLP-1), is normally secreted in the gut of both humans and animals, stimulating the release of insulin to lower blood glucose. But GLP-1 typically degrades within minutes. In people with type 2 diabetes, the short stimulus triggered by GLP-1 isn't sufficient to maintain a proper blood sugar balance. As a result, medication that includes a longer-lasting form of the hormone is needed to help provide an extended release of insulin. "Our research team has discovered that monotremes - our iconic platypus and echidna - have evolved changes in the hormone GLP-1 that make it resistant to the rapid degradation normally seen in humans," says co-lead author Professor Frank Grutzner, from the University of Adelaide's School of Biological Sciences and the Robinson Research Institute. "We've found that GLP-1 is degraded in monotremes by a completely different mechanism.

Rockefeller’s Elaine Fuchs Recognized for “Stellar Record” of Research Accomplishments in Skin Diseases and Cancer Stem Cells, and of Mentoring Other Women in Science

Elaine Fuchs, Ph.D., Head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development at The Rockefeller University has won the 2016 Vanderbilt Prize in Biomedical Science for her innovative use of reverse genetics to understand skin diseases and cancer stem cells. The prize honors women scientists with a “stellar record” of research accomplishments who have also made significant contributions to mentoring other women in science. Dr. Fuchs will receive the prize on March 30, 2017. Dr. Fuchs is the second Rockefeller recipient to receive the Vanderbilt Prize. In 2012, it was awarded to Dr. Titia de Lange for her research on telomeres, the protective ends of chromosomes. Dr. Fuchs is highly regarded for her studies using reverse genetics to understand the biological basis of normal and abnormal skin development and function. Among her important research discoveries are the identification and characterization of skin stem cells and the elucidation of the molecular mechanisms underlying their ability to produce the epidermis, hair follicles, and sweat and oil glands. She has also defined how the normal biology of skin stem cells is deregulated in skin cancers and other hyperproliferative disorders of the skin. Her work has implications for skin-related diseases, particularly cancers, genetic diseases and proinflammatory disorders. Dr. Fuchs majored in chemistry at the University of Illinois, and earned her Ph.D. in biochemistry from Princeton University. She was a postdoctoral fellow at the Massachusetts Institute of Technology, and was recruited by the University of Chicago as the first woman faculty member in biochemistry. Dr. Fuchs joined Rockefeller University in 2002. Dr.

Mena Protein Biomarker Could Help Guide Cancer Therapy for Triple-Negative Breast Cancer

MIT biologists have identified a new biomarker that can reveal whether patients with a particularly aggressive type of breast cancer will be helped by paclitaxel (commercially known as Taxol), one of the drugs most commonly used to treat this cancer. The findings could offer doctors a new way to choose drugs for this type of breast cancer, known as “triple-negative” because it lacks the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2 protein. The biomarker, a protein called Mena, has previously been shown to help cancer cells spread through the body. The researchers also showed that combining paclitaxel with another drug that interferes with Mena’s effects can kill the cells much more effectively than paclitaxel alone. “Drugs that target that pathway restore paclitaxel sensitivity to cells expressing Mena,” says Dr. Frank Gertler, an MIT Professor of Biology and a member of the Koch Institute for Integrative Cancer Research. “The study also suggests that, during the course of treatment, it might be worth monitoring the level of Mena. If the levels begin to increase, it might suggest that switching to another type of therapy could be useful.” Dr. Gertler is the senior author of the study, which was published online on November 3, 2016 in the journal Molecular Cancer Therapeutics. The article is titled “Mena Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer.” Dr. Madeleine Oudin, a Koch Institute postdoc, is the paper’s lead author. The Mena protein is known to interact with a cell’s cytoskeleton in ways that help the cell to become mobile.

Ants Transmit Chemical Signals by Mouth-to-Mouth Sharing of Liquids

Liquids shared mouth-to-mouth by social insects contain proteins and small molecules that can influence the development and organization of their colonies, according to new findings published online on November 29, 2016 in eLife. The article is titled “Oral Transfer of Chemical Cues, Growth Proteins and Hormones in Social Insects.” The study, from the University of Lausanne, Switzerland, suggests that Florida carpenter ants can collectively influence their communities by shifting the cocktail of proteins, hormones, and other small molecules that they pass mouth-to-mouth to one another and their young through a process called trophallaxis. "Food is passed to every adult and developing ant by trophallaxis. This creates a network of interactions linking every member of the colony," says senior author Laurent Keller, Ph.D., Professor in the Department of Ecology and Evolution. "A lot of researchers consider trophallaxis only as a means of food-sharing," adds Professor Richard Benton of the Center for Integrative Genomics, also a senior author of the study. "But trophallaxis occurs in other contexts, such as when an ant is reunited with a nest-mate after isolation. We therefore wanted to see if the fluid exchanged by trophallaxis contains molecules that allow ants to pass other chemical messages to each other, and not just food." To answer this question, the team, led by first author and postdoctoral researcher Dr. Adria LeBoeuf, analyzed fluid from pairs of ants engaged in trophallaxis. Surprisingly, they identified a large number of proteins that appear to be involved in regulating the growth of ants, along with high levels of juvenile hormone, an important regulator of insect development, reproduction, and behavior.