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New Lung Cell Type Identified; Finding May Lead to New, Non-Traditional Approaches to Treating Pneumonia and Chronic Lung Diseases

A recent study has identified a new lung cell type that is implicated in the body's innate immune defense against the bacteria Streptococcus pneumoniae--one of the leading causes of pneumonia worldwide. The findings, which were published online on September 18, 2017 in the Journal of Clinical Investigation, may lead to new, non-traditional approaches in the fight against pneumonia and chronic lung diseases. The article is titled “Expression of Piwi Protein MIWI2 Defines a Distinct Population of Multiciliated cells.” There are two classifications of cells in the human body: germ cells that are used to make sperm and eggs and somatic cells that make up every other cell in the body including lung cells. There are widespread differences between germ cells and somatic cells underscoring their markedly different roles in human biology. It was previously thought that the MIWI2 gene was only expressed in male germ cells as part of a family of genes that ensure the proper development of sperm. However, researchers at Boston University School of Medicine (BUSM) have discovered that, not only is the same gene expressed in somatic cells in the body, but it also marks a distinct population of multi-ciliated cells that line the upper airways of the lung. "These ciliated cells have hair-like projections that function to sweep mucus and other foreign material out of the lung. However, what sets this new population of ciliated cells apart is that they express the MIWI2 protein and in this report, were found to have a specialized role in controlling lung infection," explains corresponding author Matthew Jones, PhD, Assistant Professor of Medicine at BUSM.

BOOK REVIEW—"Ebola: The Natural and Human History of a Deadly Virus”

The objective of David Quammen’s book, “Ebola: The Natural and Human History of a Deadly Virus” (published October 20, 2014) is stated clearly in the introduction section as “to place the 2014 West Africa outbreak […] within a broader context that makes sense of those mysteries and their partial solutions. My offering here is merely a partial view of the history and science of Ebola” (Quammen, p. 2). Quammen then continues to explain that he did not have a traumatizing experience of losing his loved ones as many have, but did travel through “Ebola habitat” and became very close friends with two men who experienced the horrible realities of the Ebola virus. Quammen uses anecdotes to educate his readers regarding the Ebola virus and similar viruses, such as the Marburg virus for example. In the beginning of the book, Quammen tells about the outbreak in the village of Mayibout 2 in Gabon, Africa, where 18 people mysteriously acquired an illness and quickly died. The original victim had eaten a chimpanzee that was found dead and rotting in the forest, and was then prepared traditionally to eat. Because chimps suffer from the virus and die quickly, as do humans infected with Ebola virus, neither we nor the chimps are the reservoir host. Finding the reservoir host is a great interest of many scientists and public health officials around the world. Another strategy Quammen used to explain the Ebola virus outbreak was comparing it with outbreaks of the Marburg virus, which causes a very similar disease that was recognized about nine years before Ebola. Both viruses are filamentous, lethal RNA viruses and appeared “twisty” to scientists in the labs. Ebola virus had many outbreaks throughout the years starting in 1976. Many research experiments were conducted, most of which were unsuccessful, attempting to isolate the Ebola virus.

Dogs’ Social Skills Linked to Oxytocin Sensitivity

The tendency of dogs to seek contact with their owners is associated with genetic variations in sensitivity for the hormone oxytocin, according to a new study from Linköping University, Sweden. The results have been published in Hormones and Behavior and contribute to our knowledge of how dogs have changed during their development from wolf to household pet. The article is titled “Intranasal Oxytocin and a Polymorphism in the Oxytocin Receptor Gene Are Associated with Human-Directed Social Behavior in Golden Retriever Dogs.” During their domestication from their wild ancestor the wolf to the pets we have today, dogs have developed a unique ability to work together with humans. One aspect of this is their willingness to “ask for help” when faced with a problem that seems to be too difficult. There are, however, large differences between breeds, and between dogs of the same breed. A research group in Linköping, led by Professor Per Jensen, has discovered a possible explanation of why dogs differ in their willingness to collaborate with humans. The researchers suspected that the hormone oxytocin was involved. It is well-known that oxytocin plays a role in social relationships between individuals, in both humans and animals. The effect of oxytocin depends on the function of the structure that it binds to, the receptor, in the cell. Previous studies have suggested, among other things, that differences in dogs’ ability to communicate are associated with variations in the genetic material located close to the gene that codes for the oxytocin receptor. The researchers in the present study examined 60 golden retrievers as they attempted to solve a previously insoluble problem. “The first step was to teach the dogs to open a lid, and in this way, get hold of a treat.

Aethlon Medical Is Awarded $300K NCI Government Contract to Develop Device Strategy for Isolating Oncosomes and Non-Malignant Exosomes

Aethlon Medical, Inc. (Nasdaq: AEMD), a therapeutic technology company focused on unmet needs in global health and biodefense, announced, on September 14, 2017, that the National Cancer Institute (NCI) has awarded the Company a government contract (number HHSN261201700022C). The title of this SBIR Topic 359 Phase I contract is "Device Strategy for Selective Isolation of Oncosomes and Non-Malignant Exosomes." The NCI Phase I contract period runs from September 15, 2017 and runs through June 14, 2018. The total amount of the firm fixed price contract is $299,250. The contract calls for two subcontractors to work with the Company. The subcontractors under Aethlon Medical on the contract are University of Pittsburgh and Massachusetts General Hospital. Aethlon Medical is investigating the potential use of the Aethlon Hemopurifier® to reduce the presence of circulating tumor-derived exosomes (oncosomes), which contribute to cancer progression. The Hemopurifier® is currently being advanced to treat life-threatening viral infections under an FDA designated Expedited Access Pathway (EAP) program. The Company is also engaged in the advancement of exosomal biomarkers to diagnose and monitor cancer and other disease conditions. Aethlon Medical is focused on addressing unmet needs in global health and biodefense. The Aethlon Hemopurifier® was designed to reduce the presence of life-threatening viral pathogens from the circulatory system of infected individuals. The technology provides a first-line candidate defense against viruses that are not addressed with approved therapies, including a broad-spectrum of naturally occurring pandemic threats and agents of bioterrorism.

Evidence for Lack of Anti-Viral Argonaute2 Proteins in Vertebrates

Insects and plants have an important ancient defense mechanism that helps them to fight viruses. This is encoded in their DNA. Scientists have long assumed that vertebrates - including humans - also had this same mechanism. But researchers at KU Leuven (University of Leuven), Belgium, have found that vertebrates have lost this particular asset in the course of their evolution. The possibilities encoded in our DNA are expressed via RNA. Conversely, RNA interference (RNAi) can also suppress the expression of a specific gene. Insects and plants use this RNAi mechanism to defend themselves against viruses, among other things. With a little help, insects and plants can even be made resistant to certain diseases through this RNAi mechanism. Examples include so-called genetically modified crops. It seems only logical to assume, then, that humans can be protected against specific diseases in a similar way. However, past experiments to this effect have proven to be a challenge. Researchers from the Animal Physiology and Neurobiology unit at KU Leuven have now shown why this is the case. The research was published online on August 23, 2017 in Scientific Reports. The open-access article is titled “The Evolution of Animal Argonautes: Evidence for the Absence of Antiviral AGO Argonautes in Vertebrates.” KU Leuven researcher Dr. Niels Wynant studied Argonaute proteins, which play an important role in the RNAi process. "In a first stage, we compared the DNA of more than 40 living organisms from various important animal groups. It's the first time that such a diverse group was studied. It didn't take us long to find the Argonaute proteins in these organisms. We also discovered the existence of three distinct types of Argonautes, each with a specific biological role," Dr. Wynant explains.

$11.6 Million NIH Grant Will Finance Studies of Possible Role of Exosomes in Heart Repair and Regeneration

The incidence of heart disease is on the rise, and new therapeutic strategies are needed. Approaches based on stem cells, which can potentially preserve or even regenerate heart muscle cells damaged by ischemia - a hallmark of heart disease - are especially promising. Now, thanks to an $11.6-Million Program Project Grant (PPG) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number P01HL134608, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) are poised to explore new possibilities in stem-cell-based treatments for heart repair and regeneration. According to a release dated September 13, 2017, the project is aimed specifically at better understanding the regenerative capabilities of stem-cell-derived microvesicles known as exosomes. The Principal Investigator on the new award is Raj Kishore, PhD, Professor of Pharmacology and Medicine and Director of the Stem Cell Therapy Program in the Center for Translational Medicine at LKSOM. According to Dr. Kishore, exosomes offer an exciting opportunity to develop a cell-free approach to stem cell-based therapy for heart disease. "Previous attempts at stem cell therapy for heart disease did not work as hoped," Dr. Kishore said. "In many cases, the stem cells themselves were injured by inflammation in the heart following injection or were not functioning optimally, having been weakened from disease, such as diabetes, or age." Exosomes differ from stem cells in that they are not actually cells. Rather, they are tiny packages, roughly 50-150 nanometers in diameter, which are secreted by stem cells and taken up by neighboring tissue cells. They can carry stem cell-specific small RNAs, proteins, and other cargo that mimic stem cell functions once released inside cells, giving them beneficial properties.

Study Highlights Possible Key Role of TOMM40 Gene Variant in Alzheimer’s Disease

The notorious genetic marker of Alzheimer's disease and other forms of dementia, ApoE4, may not be a lone wolf. Researchers from the University of Southern California (USC) and the University of Manchester have found that another gene, TOMM40 (image depicts TOMM40 protein), complicates the picture. Although ApoE4 plays a greater role in some types of aging-related memory ability, TOMM40 may pose an even greater risk for other types. TOMM40 and APOE genes are neighbors, adjacent to each other on chromosome 19, and they are sometimes used as proxies for one another in genetic studies. At times, scientific research has focused chiefly on one APOE variant, ApoE4, as the No. 1 suspect behind Alzheimer's and dementia-related memory decline. The literature also considers the more common variant of APOE, ApoE3, neutral in risk for Alzheimer's disease. USC researchers believe their new findings raise a significant research question: Has TOMM40 been misunderstood as a sidekick to ApoE4 when it is really a mastermind, particularly when ApoE3 is present? "Typically, ApoE4 has been considered the strongest known genetic risk factor for cognitive decline, memory decline, Alzheimer's disease, or dementia-related onset," said Dr. T. Em Arpawong, the study's lead author and a post-doctoral fellow in the USC Dornsife College of Letters, Arts and Sciences Department of Psychology. "Although prior studies have found some variants of this other gene TOMM40 may heighten the risk for Alzheimer's disease, our study found that a TOMM40 variant was actually more influential than ApoE4 on the decline in immediate memory - the ability to hold onto new information." Studies have shown that the influence of genes associated with memory and cognitive decline intensifies with age.

Caloric Restriction Slows Epigenetic Drift and Slower Epigenetic Drift May Be Mechanism Underlying Extended Lifespan

Almost a century ago, scientists discovered that cutting calorie intake could dramatically extend lifespan in certain animal species. Despite numerous studies since, however, researchers have been unable to explain precisely why. Now, investigators at the Lewis Katz School of Medicine at Temple University (LKSOM) have broken past that barrier. In new work published online on September 14, 2017 in Nature Communications, they are the first to show that the speed at which the epigenome changes with age is associated with lifespan across species and that calorie restriction slows this process of change, potentially explaining its effects on longevity. The article is titled “Caloric Restriction Delays Age-Related Methylation Drift.” "Our study shows that epigenetic drift, which is characterized by gains and losses in DNA methylation in the genome over time, occurs more rapidly in mice than in monkeys, and more rapidly in monkeys than in humans," explains Jean-Pierre Issa, MD, Director of the Fels Institute for Cancer Research at LKSOM, and senior investigator on the new study. The findings help to explain why mice live only about two to three years on average, rhesus monkeys about 25 years, and humans 70 or 80 years. Chemical modifications such as DNA methylation control mammalian genes, serving as bookmarks for when a gene should be used - a phenomenon known as epigenetics. "Methylation patterns drift steadily throughout life, with methylation increasing in some areas of the genome, and decreasing in others," says Dr. Issa. Previous studies had shown that these changes occur with age, but whether they were also related to lifespan was unknown.Dr. Issa's team made its discovery after first examining methylation patterns on DNA in blood collected from individuals of different ages for each of three species - mouse, monkey, and human.

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.

Researchers Find a Possible New Treatment for Aggressive Triple-Receptor-Negative Breast Cancer; New Inhibitor of Cancer Stem-Like Cells Brings New Hope

Scientists from the cluster of excellence BIOSS Centre for Biological Signaling Studies at the University of Freiburg and the Freiburg University Medical Center in Germany have shown that inhibiting the epigenetic regulator KDM4 might offer a potential novel treatment option for breast cancer patients. They used a newly established cell model that enables scientists to isolate cancer stem cells directly from patient tumor. Using this special culture system, they were able to test potential new cancer drugs. One of these, a novel inhibitor of the epigenetic regulator KDM4, co-developed in the lab of Professor Roland Schüle, showed promising results. The researchers published their work online on September 7, 2017 in Cancer Research. The article is titled “KDM4 Inhibition Targets Breast Cancer Stem-Like Cells.” Although the prognosis for breast cancer has been steadily improving in the last decades, patients with triple-receptor-negative breast cancer form a subgroup who receive a considerably worse prognosis in most cases. Roughly 15 percent of all breast cancer patients have triple-receptor-negative breast cancer, which lacks markers for a targeted therapy. In the last few years, a bulk of data pointing to a small population of cells in tumors that maintain tumor growth, are particularly resistant to chemotherapy, are responsible for relapses, and develop metastases. These cells, named cancer stem-like cells, share many characteristics with the body’s normal stem cells. Due to their cancer-driving behavior, researchers have been focusing more and more on targeting these cells. However, there are currently only a few models available to study the biology of cancer stem cells.

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