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Archive - Jan 11, 2017

Exosome Release from Tumor Cells Promoted by PKM2 Phosphorylation of Synaptosome-Associated Protein 23

In a study published online on January 9, 2017 in Nature Communications, a research team led by Dr. Ke Zen and Dr. Chen-Yu Zhang from Nanjing University in China reports that pyruvate kinase type M2 (PKM2) promotes tumor cell exosome release through phosphorylating synaptosome-associated protein 23 (SNAP-23). The open-access article is titled “Pyruvate Kinase Type M2 Promotes Tumour Cell Exosome Release Via Phosphorylating Synaptosome-Associated Protein 23.” As a mechanism to communicate with the microenvironment, tumor cells actively release large numbers of microvesicles (MVs), particularly exosomes. These tumor-released MVs, which are abundant in the body fluids of patients with cancer, play a critical role in promoting tumor growth and progression. The mechanism underlying the active exocytosis of exosomes by tumor cells, however, remains incompletely understood. It has been reported that cellular exocytosis activity is increased during tumorigenesis, but the molecular basis to switch on the exocytosis process in tumor cells has not been identified. In the present study, the Nanjing University team showed that PKM2, an enzyme involved in the tumor cell's reliance on aerobic glycolysis (Warburg effect), plays a critical role in promoting the release of exosomes from the tumor cell. Specifically, the researchers identify SNAP-23, which controls the dock and release of secretory granules or exosome-containing multivesicular bodies (MVBs), is a substrate of PKM2 in tumor cells. During exocytosis, phosphorylated PKM2 is recruited to secretory granules or MVBs near cell membranes where it associates with SNAP-23 and phosphorylates SNAP-23 at Ser95, leading to upregulation of exocytosis in tumor cells.

Genetic Opposites Attract When Chimps Choose Mates

When it comes to hookups in the animal world, casual sex is common among chimpanzees. In our closest animal relatives both males and females mate with multiple partners. But when taking the plunge into parenthood, they're more selective than it seems. A study appearing online on January 11, 2017 in the journal Royal Society Open Science reveals that chimps are more likely to reproduce with mates whose genetic makeup differs most from their own. The open-access article is titled “Chimpanzees Breed with Genetically Dissimilar Mates.” Many animals avoid breeding with parents, siblings, and other close relatives, said first author Kara Walker, Ph.D., a postdoctoral Associate in Evolutionary Anthropology at Duke University. But chimpanzees are unusual in that even among nonrelatives and virtual strangers they can tell genetically similar mates from more distant ones. The researchers aren't sure yet exactly how the chimps make this discrimination, but it might be a best guess based on appearance, smell, or sound, said senior author Anne Pusey, Ph.D., Professor of Evolutionary Anthropology at Duke. Researchers took DNA samples from the feces of roughly 150 adult chimpanzees in Gombe National Park, Tanzania, and analyzed eight to eleven variable sites across the genome. From these, they were able to estimate the genetic similarity between every possible male-female pair. In chimpanzees, as in other animals, only some sexual encounters lead to offspring. When the researchers compared pairs that produced infants with those that didn't, they found that females conceived with sires that were less similar to them than the average male. Chimps are somehow able to distinguish degrees of genetic similarity among unfamiliar mates many steps removed from them in their family tree, the study shows.

Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis & Anti-TB Host Defense

University of Texas (UT) Southwestern Medical Center researchers have identified a protein that is central to the immune system’s ability to recognize and destroy the bacterium responsible for the global tuberculosis (TB) epidemic. The new finding, reported in the January 11, 2017 issue of Cell Host & Microbe, could someday lead to the development of immunity-based therapies to treat tuberculosis – which typically takes months to eradicate and has become increasingly resistant to antibiotics – by strengthening this immune pathway, said Dr. Michael Shiloh, Assistant Professor of Internal Medicine and Microbiology. The article is titled “The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-Tuberculous Host Defense.” According to the World Health Organization, TB is a top infectious disease killer worldwide and is estimated to have infected 9.5 million people and caused 1.5 million deaths in 2014. That year, tuberculosis surpassed HIV as the world’s most lethal infection. “The protein Smurf1 functions in specialized white blood cells called macrophages in both mice and humans, thereby suggesting a conserved evolutionary pathway,” said Dr. Shiloh, co-senior author of the study along with Dr. Beth Levine, Director of the University’s Center for Autophagy Research. In 2011, UT Southwestern researchers in Dr. Levine’s laboratory identified the protein Smurf1 as important for the elimination of viruses and damaged mitochondria from cells via a cellular housekeeping process called autophagy. Dr. Levine is also a Professor of Internal Medicine and Microbiology; a Howard Hughes Medical Institute Investigator; and holder of the Charles Cameron Sprague Distinguished Chair in Biomedical Science.

New Transplant Technique Restores Vision in Mice; “Results Are a Proof of Concept for Using iPSC-Derived Retinal Tissue to Treat Retinal Degeneration”

Retinal degeneration is largely a hereditary disease that is characterized by the death of photoreceptors--the light-sensitive neurons in the eye--which eventually leads to blindness. While many have attempted to treat the disease through retinal transplants, and some have shown that transplanting graft photoreceptors to the host without substantial integration can rescue retinal function, until now, no one has conclusively succeeded in transplanting photoreceptors that functionally connect to host cells and send visual signals to the host retina and brain. The research team led by Masayo Takahashi, Ph.D., of the RIKEN Center for Developmental Biology in Japan, studied this problem using a mouse model for end-stage retinal degeneration in which the outer nuclear layer of the retina is completely missing. This is an important issue because in clinical practice this type of therapy would most likely target end-stage retinas in which the photoreceptors are dead and the next neurons up the chain do not have any input. The Takahashi group has recently shown that 3D retinal sheets derived from mouse embryonic stem cells develop normal structure connectivity. "Using this method was a key point," explains first author Michiko Mandai, Ph.D. "Transplanting retinal tissue instead of simply using photoreceptor cells allowed the development of more mature, organized morphology, which likely led to better responses to light." The new results were published in the January 10, 2017 issue of Stem Cell Reports. The open-access article is titled “iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice.” (iPSC stands for induced pluripotent stem cells).

UW-Madison Launches $1 Million Microbiome Initiative

We are not alone. Each of us carries a wide array of microbial species that outnumber our cells tenfold. Recent studies have shown that the complement of microorganisms, the microbiome, is an important determinant of human health and disease. The microbiomes of other animals, plants, soil, bodies of water, and the atmosphere play similarly important roles. Our understanding of the diversity and roles of these microbiomes is limited, a fact that led the White House Office of Science and Technology Policy to launch the National Microbiome Initiative last year. Stakeholders, including the University of Wisconsin (UW)–Madison, have responded with new commitments to develop a comprehensive understanding of microbiomes across all ecosystems. A new UW–Madison Microbiome Initiative comes with $1 million in grant funding administered by the vice chancellor for research and graduate education to support interdisciplinary research, infrastructure, and research community enhancements related to the microbiome. “Microbiome science has the potential to revolutionize areas such as health care, agriculture, biomanufacturing, environmental management, and more,” says Marsha Mailick (photo), Ph.D., UW–Madison’s Vice Chancellor for Research and Graduate Education. “The potential of microbiome research is enormous — it could create revolutionary technologies. By providing seed funding for microbiome projects at UW–Madison, we hope to position our faculty to be more competitive when applying for federal funding for their research in this area.” “Microbes influence our everyday existence in immeasurable ways. They are master chemists who have provided us with the air that we breathe.

Nanotechnology Used to Deliver Gene-Silencing RNAs to Plants to Offer Significant Crop Protection Against Viruses

Researchers at the University of Surrey (UK) and University of Queensland (Australia) have developed a revolutionary new crop protection technique which offers an environmentally-friendly alternative to genetically-modified crops and chemical pesticides. The breakthrough research, published online on January 9, 2017 in Nature Plants, could have huge benefits for agriculture and positively impact communities around the world. Plant pests and pathogens are estimated to reduce global crop yields by 30 to 40 per cent a year, constraining global food security. At the same time, the need for higher production, regulatory demands, pesticide resistance, and concern about global warming driving the spread of disease all mean there is a growing need for new approaches to crop protection. The researchers have found that by combining clay nanoparticles with designer “RNAs” (molecules with essential roles in gene biology), it is possible to silence certain genes within plants. The spray the scientists have developed -- known as BioClay -- has been shown to give plants virus protection for at least 20 days following a single application. When sprayed with BioClay, the plant “thinks” it is being attacked by a disease or pest insect and responds by protecting itself. The latest research overcomes the instability of “naked” RNAs sprayed on plants, which has previously prevented these molecules from being used effectively for virus protection. By loading the agents on to clay nanoparticles, they do not wash off, enabling them to be released over an extended period of time before degrading. The BioClay technology, which is based on nanoparticles used in the development of human drug treatments, has a number of advantages over existing chemical-based pesticides.