Syndicate content

Archive

September 26th, 2017

Researchers Identify Possible Biomarker for Diagnosing Chronic Traumatic Encephalopathy (CTE) During Life

A new biomarker (CCL11, a small cytokine) for chronic traumatic encephalopathy (CTE) has been discovered that may allow the disease to be diagnosed during life for the first time. The findings, which were published online on September26, 2017 in PLOS ONE, might also help distinguish CTE from Alzheimer's disease, which often presents with symptoms similar to CTE and also can only be diagnosed post-mortem. The ability to diagnose CTE in living individuals would allow for research into prevention and treatment of the disease. The open-access PLOS ONE article is titled “CCL11 Is Increased in the CNS in Chronic Traumatic Encephalopathy But Not in Alzheimer’s Disease.” Researchers from Boston University School of Medicine (BUSM) and the VA Boston Healthcare System (VABHS) studied the brains of 23 former college and professional football players. They compared them to the brains of 50 non-athletes with Alzheimer's disease and 18 non-athlete controls. The scientists observed that CCL11 levels were normal in the brains of the non-athlete controls and non-athletes with Alzheimer's disease, but were significantly elevated in the brains of individuals with CTE. The rsearchers then compared the degree of elevation of CCL11 to the number of years those individuals played football and found that there was a positive correlation between the CCL11 levels and the number of years played.

Pigeons Better at Multitasking Than Humans in Some Situations; Higher Density of Neurons in Brain May Be Reason

Pigeons are capable of switching between two tasks as quickly as humans – and even more quickly in certain situations. These are the findings of biopsychologists who performed the same behavioral experiments to test birds and humans. The authors hypothesize that the cause of the slight multitasking advantage in birds is their higher neuronal density. Dr. Sara Letzner and Professor Dr. Onur Güntürkün from Ruhr-Universität Bochum published the results in the September 25, 2017 issue of Current Biology, in collaboration with Professor Dr. Christian Beste from the University Hospital Carl Gustav Carus at Technische Universität Dresden. The open-access article is titled “How Birds Outperform Humans in Multi-Component Behavior.” “For a long time, scientists used to believe the mammalian cerebral cortex to be the anatomical cause of cognitive ability; it is made up of six cortical layers,” says Dr. Letzner. In birds, however, such a structure does not exist. “That means the structure of the mammalian cortex cannot be decisive for complex cognitive functions such as multitasking,” continues Dr. Letzner. The pallium of birds does not have any layers comparable to those in the human cortex; but its neurons are more densely packed than in the cerebral cortex in humans: pigeons, for example, have six times as many nerve cells as humans per cubic millimeter of brain. Consequently, the average distance between two neurons in pigeons is fifty per cent shorter than in humans. As the speed at which nerve cell signals are transmitted is the same in both birds and mammals, researchers had assumed that information is processed more quickly in avian brains than in mammalian brains.

Ascorbate Peroxidase Proximity Labeling Used to Identify Promoters of Mitochondria-Endoplasmic Reticulum Contacts; Advance Could Aid Understanding of Certain Neurodegenerative Diseases

Inside every cell is a complex infrastructure of organelles carrying out different functions. Organelles must exchange signals and materials to make the cell operate correctly. New technologies are allowing researchers to see and understand the networks that connect these organelles, allowing the scientists to build maps of the trade routes that exist within a cell. A study to be published in the September 29, 2017 issue of the Journal of Biological Chemistry, and published online on July 31, 2017, reports the use of an emerging method to identify proteins that allows two organelles, the mitochondria and the endoplasmic reticulum, to attach to each other. The open-access JBC article is titled “Ascorbate Peroxidase Proximity Labeling Coupled with Biochemical Fractionation Identifies Promoters of Endoplasmic Reticulum Mitochondrial Contacts.” "Think of [an organelle] like a ferry docking at one site, unloading and loading passengers and cars, and then going to another site and doing the same thing," said Dr. Jeffrey Golden, a professor at Brigham and Women's Hospital and Harvard Medical School who oversaw the work. "Their ability to dock, load, and unload cargo requires guides or ramps of specific width and heights that connect the boat and land or they cannot freely load and unload." Contact points between the endoplasmic reticulum (ER) and mitochondria are those "ramps" and "guides" that enable these contacts. They permit important activities like signaling, exchange of calcium and lipids, and control of mitochondrial physiology. Faulty connections between ER and mitochondria have been implicated in several neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease.

Invitation to ASEMV 2017 Annual Meeting (Exosomes & Microvesicles) in Asilomar, California (October 8-12)

The American Society for Exosomes and Microvesicles (ASEMV) is inviting interested scientists to the ASEMV 2017 meeting, to be held October 8-12, 2017 at the Asilomar Conference Center in California. This center is located on the Monterrey peninsula, just south of San Francisco (www.visitasilomar.com). The meeting will cover the full breadth of the exosome field, from basic cell biology to clinical applications, and follow the ASEMV tradition of inclusion and diversity as participants learn about the latest advances in the field. ASEMV 2017 is a forum for learning the latest discoveries in the field of exosomes, microvesicles, and extracellular RNAs. Over the course of four days at the Asilomar Conference Center, ASEMV 2017 will offer presentations from leading scientists and young researchers. Topics will span the breadth of the extracellular vesicle/RNA field, including the basic sciences, disease research, translation efforts, and clinical applications. Talks will be presented in multiple sessions, beginning at 7 pm on Sunday, October 8, 2017, and concluding at 4 pm on Thursday, October 12, 2017. Poster sessions will run throughout the meeting, with ample time to get to know your colleagues in the field and explore the many opportunities in this rapidly expanding field. Please see the links below.

September 21st

Exosomes May Be Missing Link to Insulin Resistance in Diabetes

Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now. In a paper, published in the journal Cell on September 21, 2017, University of California San Diego School of Medicine researchers identified exosomes — extremely small vesicles or sacs secreted from most cell types — as the missing link. The article is titled “Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity.” “The actions induced by exosomes as they move between tissues are likely to be an underlying cause of intercellular communication causing metabolic derangements of diabetes,” said Jerrold Olefsky, MD, Professor of Medicine in the Division of Endocrinology and Metabolism at UC San Diego School of Medicine and senior author of the paper. “By fluorescently labeling cells, we could see exosomes and the microRNA they carry moving from adipose (fat) tissue through the blood and infiltrating muscle and liver tissues.” During chronic inflammation, the primary tissue to become inflamed is adipose tissue. Forty percent of adipose tissue in obesity is comprised of macrophages — specialized immune cells that promote tissue inflammation. Macrophages in turn create and secrete exosomes. When exosomes get into other tissues, they use the microRNA (miRNA) they carry to induce actions in the recipient cells. The macrophage-secreted miRNAs are on the hunt for messenger RNAs. When the miRNA finds a target in RNA, it binds to it, rendering the messenger RNA inactive. The protein that would have been encoded by the messenger RNA is no longer made. Thus, the miRNAs are a way to inhibit the production of key proteins. A team led by Dr.

Tumor-Associated Macrophages (TAMs) Promote Neuroblastoma by STAT3 Phosphorylation and Up-Regulation of c-MYC

Investigators at the Children's Center for Cancer and Blood Diseases at Children's Hospital Los Angeles have reported new findings about an immune cell - called a tumor-associated macrophage - that promotes cancer instead of fighting it. They have identified the molecular pathway, known as STAT3, as the mechanism the immune cell uses to foster neuroblastoma, a pediatric cancer, and have demonstrated use of a clinically available agent, ruxolitinib, to block the pathway. Results of the study were published online in Oncotarget on September 20, 2017. The article is titled Tumor-Associated Macrophages Promote Neuroblastoma Via STAT3 Phosphorylation and Up-Regulation of c-MYC.” Neuroblastoma is the second most common solid tumor effecting children. Individuals with high-risk disease have a mortality rate of approximately 50 percent. Certain conditions are associated with high-risk disease. High levels of some chemicals involved with inflammation and the presence of an immune cell called a tumor-associated macrophage (TAM) are associated with high-risk disease and lower survival rates. Macrophages are a type of immune cell that typically function to battle disease, not encourage it. "The macrophages are essentially co-opted by the tumor cells to help them grow," said Shahab Asgharzadeh, MD, Director of the Basic and Translational Neuroblastoma program at CHLA and lead investigator of the study. "We're trying to find out more about the mechanisms that enable TAMs to help cancer grow so that we can target the pathways they use and block their pro-tumor effect."

Discovery by Doudna Lab & Collaborators Should Help Improve Accuracy of CRISPR-Cas9 Gene Editing

Scientists at the University of California, Berkeley, and Massachusetts General Hospital have identified a key region within the Cas9 protein that governs how accurately CRISPR-Cas9 homes in on a target DNA sequence, and have tweaked it to produce a hyper-accurate gene editor with the lowest level of off-target cutting to date. The protein domain the researchers identified as a master controller of DNA cutting is an obvious target for re-engineering to improve accuracy even further, the researchers say. This approach should help scientists customize variants of Cas9 - the protein that binds and cuts DNA - to minimize the chance that CRISPR-Cas9 will edit DNA at the wrong place, a key consideration when doing gene therapy in humans. One strategy to achieve improved accuracy is to create mutations in the governing protein domain, called REC3, and see which ones improve accuracy without impacting the efficiency of on-target cutting. "We have found that even minor alterations in the REC3 domain of Cas9 affect the differential between on- and off-target editing, which suggests that this domain is an obvious candidate for in-depth mutagenesis to improve targeting specificity. As an extension of this work, one could perform a more unbiased mutagenesis within REC3 than the targeted mutations we have made," said co-first author Janice Chen, a graduate student in the lab of Dr. Jennifer Doudna, who co-invented the CRISPR-Cas9 gene-editing tool. Co-first authors Chen, Yavuz Dagdas, and Benjamin Kleinstiver, and their colleagues at UC Berkeley, Massachusetts General Hospital, and Harvard University reported their results online on September 20, 2017 in Nature. The article is titled “Enhanced Proofreading Governs CRISPR–Cas9 Targeting Accuracy.” Since 2012, when Dr.

September 19th

PureTech Health Exclusively Licenses Novel Milk-Derived Exosome Technology for Oral Administration of Biologics, Nucleic Acids, and Complex Small Molecules

On September 19, 2017, PureTech Health plc (“PureTech Health” or the “Company”, LSE: PRTC), an advanced, clinical-stage biopharmaceutical company, announced an exclusive licensing agreement with 3P Biotechnologies, Inc., via University of Louisville, for an exosome-based technology (Calix) for the oral administration of biologics, nucleic acids, and complex small molecules. The Calix technology is based on the pioneering research of Ramesh Gupta, PhD, Founder of 3P Biotechnologies, Agnes Brown Duggan Chair in Oncological Research at the James Graham Brown Cancer Center, and Professor in the Department of Pharmacology and Toxicology at University of Louisville. This license, together with additional PureTech Health-generated intellectual property, establishes the company as a leader in the application of milk exosomes for the oral administration of therapeutic molecules. Exosomes, which can contain mixtures of lipids, proteins and nucleic acids, play a critical physiologic role in intercellular communication and the transport of macromolecules between cells and tissues. Mammalian-derived exosomes have attractive potential as vehicles for the administration of a variety of drug payloads, especially nucleic acids, because their natural composition will likely provide superior tolerability over the variety of synthetic polymers currently in use. Previously, exosomes had not been considered viable as vehicles for oral administration of drugs due to their lack of stability under the harsh physiologic conditions associated with transit through the stomach and small intestine. However, the milk-derived exosomes that form the basis for the Calix technology have evolved specifically to accomplish the task of oral transport of complex biological molecules.

Acoustic Microfluidic Device Can Gently and Rapidly Isolate Exosomes from Blood; Isolated Exosomes Can Be Analyzed for Molecular Signatures of Cancer and Other Diseases

Cells secrete nanoscale membraned packets called exosomes that can carry important messages from one part of the body to another. Scientists from MIT and other institutions have now devised a way to intercept these messages, which could be used to diagnose problems such as cancer or fetal abnormalities. Their new device uses a combination of microfluidics and sound waves to isolate these exosomes from blood. The researchers hope to incorporate this technology into a portable device that could analyze patient blood samples for rapid diagnosis, without involving the cumbersome and time-consuming ultracentrifugation method commonly used today. “These exosomes often contain specific molecules that are a signature of certain abnormalities. If you isolate them from blood, you can do biological analysis and see what they reveal,” says Dr. Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and a senior author of the study, which appears in PNAS the week of September 18, 2017. The paper’s senior authors also include Dr. Subra Suresh, President-Designate of Nanyang Technological University in Singapore, MIT’s Vannevar Bush Professor of Engineering Emeritus, and a former Dean of Engineering at MIT; Dr. Tony Jun Huang, a Professor of Mechanical Engineering and Materials Science at Duke University; and Dr. Yoel Sadovsky, Director of the Magee-Women’s Research Institutein Pittsburgh. The paper’s lead author is Duke graduate student Mengxi Wu. The article is titled “Isolation of Exosomes from Whole Blood by Integrating Acoustics and Microfluidics. In 2014, the same team of researchers first reported that they could separate cells by exposing them to sound waves as they flowed through a tiny channel.

Rutgers Researchers Shed Light on Role of Key Fat-Regulating Enzyme in Human Health; Findings May Hold Clues to Obesity, Diabetes, Cancer, And Other Diseases

had already been known that the enzyme known as phosphatidic acid phosphatase plays a crucial role in regulating the amount of fat in the human body. Controlling it is therefore of interest in the fight against obesity. But scientists at Rutgers University-New Brunswick have now found that getting rid of the enzyme entirely can increase the risk of cancer, inflammation, and other ills. Their findings were published online on July 3, 2017 in the Journal of Biological Chemistry. "The goal of our lab is to understand how we can tweak and control this enzyme," said Dr. George M. Carman, Board of Governors Professor in the Department of Food Science in the School of Environmental and Biological Sciences. "For years, we have been trying to find out how to fine-tune the enzyme's activity so it's not too active, and creating too much fat, but it's active enough to keep the body healthy." The JBC article is titled “Yeast PAH1-Encoded Phosphatidate Phosphatase Controls The Expression of CHO1-Encoded Phosphatidylserine Synthase for Membrane Phospholipid Synthesis.” The enzyme was discovered in 1957 and Gil-Soo Han, Research Assistant Professor in the Rutgers Center for Lipid Research, discovered the gene encoding the enzyme in 2006. The enzyme determines whether the body's phosphatidic acid will be used to create storage fat, or to create the lipids in cell membranes. The current study used baker's yeast as a model organism, becausee it also contains the key enzyme. Dr. Han, study lead author, deleted a gene in yeast to eliminate the enzyme. That led to accumulations of phosphatidic acid, with cells making far more membrane lipids than necessary, said Dr. Carman, who founded the center in Rutgers' New Jersey Institute for Food, Nutrition, and Health a decade ago.