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Archive - Apr 17, 2015

Mutual Gaze Between Dogs & Humans Drives Neural Feedback Loop Based on Oxytocin, Same Hormone That Strengthens Human Mother-Child Bonding Through Mutual Gaze

A new study suggests that dogs and humans may have tapped into an instinctual bonding mechanism that originally evolved to reinforce the strongest biological bonds -- those between parent and offspring. In work reported in an open-access article published in the April 17, 2015 issue of Science, Dr. Miho Nagasawa from both Azabu University (Kanagawa, Japan) and Jichi Medical University (Tochigi, Japan) and colleagues from those institutions, as well as from the University of Tokyo, demonstrated that the hormone oxytocin, which spikes in both human and canine brains when the species interact, operates in a neural feedback loop that likely strengthened the bonds between man and his “best friend” for millennia. The researchers show that mutual gaze between the two -- an oxytocin-driven bonding mechanism known to strengthen emotional ties between human mothers and their infants -- helps to regulate the bonds between dogs and their owners as well. Because wolves don’t have this same response, even when they’ve been raised by humans, Dr. Nagasawa and colleagues suggest that this particular social bonding mechanism co-evolved in both dogs and humans over the course of the animals’ domestication. The researchers put dogs into a room with their owners, documenting every interaction between the two species, such as talking, touching, and gazing, for 30 minutes. They then measured oxytocin levels in the dogs’ and owners’ urine and discovered that increased eye contact between dogs and their owners had driven up levels of oxytocin in the brains of both species. In a second experiment, the researchers sprayed oxytocin directly into the noses of certain dogs and placed them in a room with their owners and some strangers. Female dogs responded to the treatment by increasing the amount of time they gazed at their owners.

Microbiome of Remote Amazonian Indians 40 Percent More Diverse Than That of Those in Industrialized Countries

A multicenter team of U.S. and Venezuelan scientists, led by researchers from the New York University (NYU) Langone Medical Center, has discovered the most diverse collection of bodily bacteria yet in humans among an isolated tribe of Yanomami Indians in the remote Amazonian jungles of southern Venezuela. By comparison, the microbiome of people living in industrialized countries is about 40 percent less diverse, the scientists estimate. The team reports its findings online on April 17, 2015 in an open-access article in Science Advances. The results, the researchers say, suggest a link between modern antibiotics and industrialized diets, and greatly reduced diversity of the human microbiome--the trillions of bacteria that live in and on the body and are increasingly seen as vital to our health. The Yanomami villagers of this study, who have subsisted by hunting and gathering for hundreds of generations, are believed to have lived in total seclusion from the outside world until 2009 when they were first contacted by a medical expedition. Among a rare population of people unexposed to modern antibiotics, the villagers offer a unique window onto the human microbiome. "We have found unprecedented diversity in fecal, skin, and oral samples collected from the Yanomami villagers," says Maria Dominguez-Bello, Ph.D., Associate Professor of Medicine at NYU Langone Medical Center and the senior author of the study. "Our results bolster a growing body of data suggesting a link between, on the one hand, decreased bacterial diversity, industrialized diets, and modern antibiotics, and on the other, immunological and metabolic diseases--such as obesity, asthma, allergies, and diabetes, which have dramatically increased since the 1970s," notes Dr. Dominguez-Bello.

Circulating Lung Cancer DNA Can Provide Vital “Liquid Biopsy” for EGFR Mutations When Tumor Tissue Is Not Accessible

Cancer DNA circulating in the bloodstream of lung cancer patients can provide doctors with vital mutation information that can help optimize treatment when tumor tissue is not available, an international group of researchers has reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland, April 15-18, 2015. The results have important implications for the use of cancer therapies that target specific cancer mutations, explains Dr. Martin Reck from the Department of Thoracic Oncology at Lung Clinic Grosshansdorf, Germany, who presented the findings at the conference. The title of Dr. Reck’s presentation was “Investigating the Utility of Circulating-Free Tumor-Derived DNA (ctDNA) in Plasma for the Detection of Epidermal Growth Factor Receptor (EGFR) Mutation Status in European and Japanese Patients with Advanced Non-Small-Cell Lung Cancer.” Testing for the presence of these mutations in the tumor itself is not always possible, however studies have suggested that DNA from the tumor that circulates in the bloodstream of patients may provide similar information. The large international ASSESS study aimed to compare the ability of blood testing to detect EGFR mutations with the more standard method of testing the tumor itself. "We were really asking a question on behalf of patients," Dr. Reck said: "Is there a valid test that can identify an EGFR mutation and give me the opportunity for superior treatment, even if my lung tumor is not accessible for bronchoscopy or CT-guided biopsy? And, are the results of this blood test in agreement with the results of the 'gold-standard' tissue test?" Overall, the study included 1,162 matched tissue and blood samples.

Exosomes Secreted by Human iPSC-Derived Mesenchymal Stem Cells Reduce Limb Ischemia by Promoting Angiogenesis; May Represent Novel Treatment for Ischemic Diseases

Patient-specific induced pluripotent stem cells (iPSCs) are attractive because they can be an abundant source of cells that can be used for cell therapy without posing the risk of immune rejection. Studies have showed that iPSCs-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effects. Recently, most studies have indicated that stem cells exert their therapeutic effect mainly through a paracrine mechanism other than transdifferentiation, and exosomes have emerged as an important paracrine factor for influencing stem cells to reprogram injured cells. The objective of the current study by scientists in China was to evaluate whether exosomes derived from iMSCs (iMSCs-Exo) possess the ability to attenuate limb ischemia and promote angiogenesis after transplantation into limbs of mice suffering from femoral artery excision. The report of this study was published online on April 10, 2015 in an open-access article in Stem Cell Research & Therapy. The article was titled “Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Attenuate Limb Ischemia by Promoting Angiogenesis.” In the work, human iPSCs (iPS-S-01, C1P33, and PCKDSF001C1) were used to differentiate into iMSCs in a modified one-step method. iMSCs were characterized by flow cytometry and multipotent differentiation potential analysis. Ultrafiltration combined purification method was used to isolate iMSCs-Exo; while transmission electron microscopy and Western blotting were used to identify iMSCs-Exo. After establishment of mouse hind-limb ischemia with excision of the femoral artery and iMSCs-Exo injection, blood perfusion was monitored at days 0, 7, 14, and 21; microvessel density in ischemic muscle was also analyzed.

New Anti-Cancer Therapy Uses Exosomes to Deliver Drug to Entire Tumor

The Korea Advanced Institute of Science and Technology’s (KAIST’s) Department of Bio and Brain Engineering Professor Ji-Ho Park and his team in South Korea has successfully developed a new, highly efficacious anti-cancer nanotechnology by delivering anti-cancer drugs uniformly to an entire tumor via exosomes. Their research results were published online in Nano Letters on March 31, 2015. To treat inoperable tumors, anti-cancer medicine is commonly used. However, efficient drug delivery to tumor cells is often difficult, treating an entire tumor with drugs even more so. Using the existing drug delivery systems, including nanotechnology, a drug can be delivered only to tumor cells near blood vessels, leaving cells at the heart of a tumor intact. Because most drugs are injected into the bloodstream, tumor recurrence post medication is frequent. Therefore, the team used liposomes that can fuse to the cell membrane and enter the cell. Once inside liposomes the drug can travel into the bloodstream, enter tumor cells near blood vessels, where they are loaded to exosomes, which are naturally occurring nanoparticles in the body. Because exosomes can travel between cells, the drug can be delivered efficiently into inner cells of the tumor. Exosomes, which are secreted by cells that exist in the tumor microenvironment, are known to have an important role in tumor progression and metastasis because they transfer biological materials between cells. The research team started the investigation recognizing the possibility of delivering the anti-cancer drug to the entire tumor using exosomes. The team injected the light-sensitive, anti-cancer drug using their new delivery technique into experimental mice. The researchers applied light to the tumor site to activate the anti-cancer treatment and analyzed a tissue sample.

Liquid Biopsy for Solid Tumors, Based on Analyzing Exosomes from Blood, Will Be Tested at Thomas Jefferson University in Collaboration with Exosome Sciences

On April 1, 2015, Thomas Jefferson University in Philadelphia announced a partnership with Exosome Sciences Inc. (http://www.exosomesciences.com/), near Princeton, New Jersey, to evaluate a novel, exosome-based liquid biopsy platform that might offer clinicians new and actionable information about a patient's cancer as the disease progresses and changes via a simple blood test. "The term 'liquid biopsy' describes the fact that a simple blood sample can contain many tumor-derived molecules and even tumor cells enabling molecular analyses similar to those possible in tumor tissue samples," says Ulrich Rodeck, M.D., Ph.D., Professor of Dermatology, Cutaneous Biology, and Radiation Oncology at Jefferson and co-lead investigator of the study. Jefferson is a leader in liquid biopsies for cancer. Massimo Cristofanilli, M.D., Director of the Jefferson Breast Care Center at the Sidney Kimmel Cancer Center discovered in 2004 that a blood test could help to predict the prognosis of women with breast cancer. This study established that the number of circulating tumor cells in a blood sample can give doctors a quick and minimally invasive snapshot of whether a patient is likely to respond to treatment or not. In addition to circulating tumor cells, the blood also contains free-floating cancer DNA, providing researchers with an option to access treatment-relevant gene alterations in blood samples. The new partnership between Exosome Sciences Inc. and a Jefferson team led by Dr. Rodeck, and Adam Luginbuhl, M.D., Assistant Professor of Otolaryngology Head and Neck Surgery, will focus on exosomes as a novel liquid biopsy platform.

Trials Demonstrate Benefits of Endovascular Stroke Therapy in “Resounding Fashion,” NEJM Editorial States

Anthony J. Furlan, M.D., Chairman of Neurology and Co-Director of the Neurological Institute at University Hospitals (UH) Case Medical Center and Case Western Reserve University School of Medicine, who writes an accompanying editorial for five studies about endovascular stroke therapy published simultaneously on April 17, 2015 in the New England Journal of Medicine, says these randomized clinical trials represent a breakthrough in showing the benefits of endovascular therapy for acute ischemic strokes. "Now even endovascular skeptics will be convinced," Dr. Furlan writes. His editorial, entitled “Endovascular Stroke Therapy: It's About Time,” states that these trials demonstrate the therapy is highly beneficial in a "resounding fashion." The studies compared endovascular therapy - administration of an intravenous clot-busting agent (tPA) followed by device removal of a clot blocking a brain artery - with the clot-busting agent IV tPA alone for the treatment of ischemic stroke. Dr. Furlan says that these new studies should settle any lingering uncertainties that have existed over endovascular therapy (also known as intra-arterial therapy), especially since three studies in 2013 indicated the therapy was no more effective than IV tPA alone. He attributes the difference in results in the new studies to three factors: superior surgical technology resulting in faster, more complete clearage of the blockage; heightened awareness of decreasing the amount of time between patient arrival in the emergency department to the start of the endovascular procedure, and improved neuroimaging criteria for selecting patients most likely to benefit from the therapy. Dr. Furlan says these studies represent a paradigm shift reminiscent of the introduction of the clot-busting therapy IV tPA in the 1990s.

Scientist Establish Genetic Cause of Life-Threatening “Brisket” Lung Disease Affecting Cattle Grazing at High Altitude; Discovery May Also Shed Light on Certain Human Lung Diseases

Vanderbilt University researchers have found a genetic mutation that causes pulmonary hypertension in cattle grazed at high altitude, and which leads to a life-threatening condition called brisket disease. Their findings, reported online on April 15, 2015 in an open-access article in Nature Communications, may shed light on human lung disease, in particular, the mechanism behind non-familial pulmonary hypertension in patients with conditions such as emphysema and pulmonary fibrosis. "A genetic variant in cattle might tell us why some humans get into trouble at sea level and at altitude," said first author John H. Newman, M.D., the Elsa S. Hanigan Professor of Pulmonary Medicine at Vanderbilt University Medical Center. When the lung experiences low oxygen, or hypoxia, the blood vessels of the lung constrict. Over time in continued hypoxic conditions, these vessels become muscularized, resulting in pulmonary hypertension, high blood pressure in the blood vessels of the lung. Lowland cattle can develop pulmonary hypertension after being at high altitude over a period of six months to a year. Brisket disease, or right heart failure, develops when the heart fails to pump against the high pulmonary blood pressure. If these animals are not brought to lower altitudes, they will die. Brisket disease costs millions of dollars of loss each year in the Rocky Mountains, where the herds graze. Fifteen years ago, Dr. Newman, James Loyd, M.D., Rudy W. Jacobson Professor of Pulmonary Medicine, and colleagues identified the genetic basis for familial pulmonary hypertension in humans, mutations in a gene called BMPR2 (bone morphogenic protein receptor type 2). "I was sitting in our conference room after we had found the BMPR2 gene in humans and I thought, well, we should be able to find the brisket gene in cattle using the same strategy," Dr. Newman said.

“Revolutionary Leap Forward in Artificial Photosynthesis”—With Combined Nanowire/Bacteria Hybrid Technology, Chemicals and Fuels Can Be Produced in a Totally Renewable Way

A potentially game-changing breakthrough in artificial photosynthesis has been achieved with the development of a system that can capture carbon dioxide emissions before they are vented into the atmosphere and then, powered by solar energy, convert that carbon dioxide into valuable chemical products, including biodegradable plastics, pharmaceutical drugs, and even liquid fuels. Scientists with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have created a hybrid system of semiconducting nanowires and bacteria that mimics the natural photosynthetic process by which plants use the energy in sunlight to synthesize carbohydrates from carbon dioxide and water. However, this new artificial photosynthetic system synthesizes the combination of carbon dioxide and water into acetate, the most common building block today for biosynthesis. "We believe our system is a revolutionary leap forward in the field of artificial photosynthesis," says Dr. Peidong Yang, a chemist with Berkeley Lab's Materials Sciences Division and one of the leaders of this study. "Our system has the potential to fundamentally change the chemical and oil industry in that we can produce chemicals and fuels in a totally renewable way, rather than extracting them from deep below the ground." Dr. Yang, who also holds appointments with UC Berkeley and the Kavli Energy NanoSciences Institute (Kavli-ENSI) at Berkeley, is one of three corresponding authors of a paper describing this research that was published online on April 7, 2015 the journal Nano Letters.