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Archive - Jan 2015

January 30th

Obama Proposes $215 Million “Precision Medicine Initiative,” A Massive Personalized Medicine and DNA Sequencing Effort; Obama Calls It “Greatest Opportunity for Medical Breakthroughs That We Have Ever Seen” (2012 Nobelist's Comments Added)

by BioQuick Editor & Publisher Michael D. O'Neill (http://www.bioquicknews.com/node/34)

Shortly after 11 am EST on Friday, January 30, 2015, United States President Barack Obama announced his $215 million proposed “precision medicine initiative.” This is a massive personalized medicine effort centered on the use of next-generation DNA sequencing that Obama said represents the “greatest opportunity for medical breakthroughs that we have ever seen." It will enable physicians to administer the “right treatment at the right time, every time, to the right person." "The time is right to unleash new wave of medicine," Obama said. A jointly authored commentary on the proposed initiative, from NIH Director Dr. Francis Collins (M.D., Ph,D.) and National Cancer Institute (NCI) Director Dr. Harold Varmus (Ph.D), is posted on the New England Journal of Medicine web site (http://www.nejm.org/doi/full/10.1056/NEJMp1500523). Please also see links to related popular press articles provided below. Dr. Collins is a former Director of the National Human Genome Research Institute, leader of the Human Genome Project, and longtime physician-scientist-researcher, whose numerous seminal discoveries include identification of the gene for cystic fibrosis. Dr. Varmus is co-winner of the 1989 Nobel Prize for Physiology or Medicine for discovery of the cellular origin of retroviral oncogenes. Dr. Varmus is also a former President of Memorial Sloan-Kettering Caner Center (MSKCC) and former Director the NIH.

January 29th

Novel Study of Dopamine-Releasing Neurons in Forebrain May Impact Understanding of Schizophrenia, Parkinson’s, and Many Diseases Involving Movement Disorder

Scientists studying hatchling zebrafish fish have made a new advance in in understanding the brain chemical dopamine that influences movement. The team from the University of Leicester (UK) Department of Biology has examined the transparent hatchling zebrafish to gain new insights into the working of neurons in areas of the brain that are normally difficult to access. As a result, they have discovered, for the first time, both when and why the particular cells in the brain that affect movement are active. The new study was published recently online in an open-access article in Current Biology and will appear the February 2015 print issue of Current Biology. Senior author Dr. Jonathan McDearmid said, “Our research is aimed at understanding how dopamine, a neurochemical secreted by nerve cells (neurons) in the brain, influences neuronal networks in the spinal cord that control motor behaviour. “Our understanding of dopamine function is largely derived from the study of dopamine-releasing neurons that are located within the midbrain, a structure located near to the base of the brain. However, vertebrates, including humans, also possess a cluster of dopamine-containing neurons in the forebrain. Unlike their midbrain counterparts, these neurons extend projections to the spinal cord, a region that is dedicated to the production of motor behaviors (such as walking and swimming). We know relatively little about the role this forebrain population plays in regulating behaviour: the main aim of our study was to address this problem.” The Leicester team was able to overcome this problem by examining hatchling zebrafish which are transparent and lack bone tissue, which makes the brain accessible to study.

Young Scientist Wins Prestigious Friedrich Miescher Prize for Work on Cas9 “Genetic Scissors” Tool

Martin Jinek, Ph.D., a professor in the Department of Biochemistry at the University of Zurich has won the Friedrich Miescher Prize, which carries 20,000 Swiss francs (CHF) in prize money,according to a January 29, 2015 press release from the University of Zurich. The award is the highest accolade for budding researchers in biochemistry in Switzerland. The Swiss Society for Molecular and Cellular Biosciences has awarded this year’s Friedrich Miescher Prize to 35-year-old Dr. Jinek in recognition of his work on the microbial defense system and the genetic engineering tool CRISPR-Cas9. The biochemist from the Czech Republic helped make the protein Cas9 an essential tool in genetic engineering. The molecule serves as a versatile pair of scissors to process the genetic material of animal or plant cells. Cas9 can be used to cut out, add, activate, or suppress genes as and when required. The application became a permanent feature in research labs in no time at all. Dr. Jinek studied at Trinity College (Cambridge University) and completed a doctorate in Heidelberg. He moved to the University of Zurich from the University of Berkeley in the United States two years ago. “The university’s good reputation and the outstanding research environment were key factors in the move to Switzerland,” says Dr. Jinek. Meanwhile, he has already been awarded a prestigious ERC grant worth millions from the European Research Council and won the John Kendrew Prize from the European Molecular Biology Laboratory in Heidelberg. The Friedrich Miescher Prize is Switzerland’s top accolade for outstanding achievements in biochemistry. The prize-winners must be younger than 40, hold Swiss citizenship or have conducted their research in Switzerland.

High Salt Intake Accelerates Chronic Kidney Disease by Activating Renin-Angiotensin Axis

In addition to affecting blood pressure, high salt intake can promote kidney function decline in patients with chronic kidney disease. A study appearing in online on January 29,2015 in the Journal of the American Society of Nephrology (JASN) reveals that the effects of salt consumption on the kidneys are mediated at least in part by brain-kidney interactions. The findings suggest new strategies for protecting patients' kidney health. While it is known that salt intake can contribute to the progression of chronic kidney disease, the mechanisms involved are unclear. Fan Fan Hou, M.D., Ph.D., Wei Cao, M.D., and Aiqing Li, Ph.D. (Southern Medical University, in Guangzhou, China) wondered whether interactions between the kidneys and the brain might be involved. Their research team studied the brain-kidney connections in rats with kidney disease. The investigators found that salt intake accelerated kidney scarring in the animals by activating a brain-kidney connection called the renin-angiotensin axis that interlinks the damaged kidney and brain by afferent and efferent sympathetic nerves. Targeting these nerves reduced salt-induced kidney scarring. "These findings provide novel targets to fill a therapeutic void in preventing relentless progression of chronic kidney disease," said Dr. Hou. The investigators noted that kidney scarring, or fibrosis, is the final common pathway for most categories of chronic kidney disease and culminates in kidney failure. Additional co-authors of the study included Liangliang Wang, M.D.; Zhanmei Zhou, M.B.B.S.; Zhengxiu Su, M.Med.; Wei Bin, M.B.B.S.; and Christopher Wilcox, M.D., Ph.D. The article was entitled "A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression."

Crucial Protective Role Observed for Farnesoid-X Receptor in Cholestatic Liver Injury

The farnesoid-X receptor (FXR) (image), also known as the chief regulator of bile acid metabolism, is thought to play a role in some hepatobiliary and gastrointestinal disorders. In a study published online on January 11, 2015 in The American Journal of Pathology, researchers demonstrated dysfunctional intestinal FXR-signaling in a rat model of cholestatic liver injury, accompanied by intestinal bacterial translocation (BTL) and increased permeability and inflammation. Notably, a highly potent, selective FXR agonist, obeticholic acid (INT-747), counteracted these effects, suggesting a potential new therapeutic avenue for liver disease. FXR has been recognized as a key transcription-regulator in hepatic and intestinal bile metabolism. “In experimental cholestasis, FXR-agonism improves ileal barrier function by attenuating intestinal inflammation leading to reduced bacterial translocation, demonstrating a crucial protective role for FXR in the gut-liver axis,” said lead investigator Len Verbeke, M.D., Ph.D., of the Division of Liver and Biliopancreatic Disorders at University Hospitals Leuven, KU Leuven-University of Leuven, Belgium. The experimental model used generated cholestatic liver injury in rats (cholestasis refers to a condition in which the flow of bile is blocked). In one experiment, 51 rats underwent ligation of the common bile duct (BDL) and were then treated with vehicle, 5 mg/kg ursodeoxycholic acid (UDCA), or 5 mg/kg of the FXR agonist INT-747 by gavage every two days for 10 days after surgery. UDCA is a bile acid similar in molecular structure to INT-747, which lacks FXR-agonizing properties. INT-747 is a semisynthetic bile acid derivative that is a first-in-class FXR agonist.

January 28th

Preventing Inflammation in Obese Fat Tissue Could Be Key to Preventing Type 2 Diabetes; Interleukin-33 Acts to Boost Treg Populations in Fat Tissue, Halting the Development of Type 2 diabetes, or Even Reversing the Disease in Preclinical Models Preventing

Preventing inflammation in obese fat tissue may hold the key to preventing or even reversing type 2 diabetes, new research has found. RScientists from Melbourne's Walter and Eliza Hall Institute in Australia, with colleagues from the RIKEN Institute in Japan, found they could “reverse” type 2 diabetes in laboratory models by dampening the inflammatory response in fat tissue. Dr. Ajith Vasanthakumar, Dr. Axel Kallies, and colleagues from the institutes discovered that specialized immune cells, called regulatory T cells (Tregs), played a key role in controlling inflammation in fat tissue and maintaining insulin sensitivity. The findings were published online on Jnuary 19, 2015 in Nature Immunology. More than 850,000 Australians are estimated to have type 2 diabetes, which is the most common type of diabetes, and its prevalence is rising. The disease is strongly linked with 'lifestyle' factors, such as being overweight or having high blood pressure. Long-term complications of type 2 diabetes include kidney, eye, and heart disease, and there is no cure. People with type 2 diabetes have reduced sensitivity to insulin, a hormone that normally triggers uptake of glucose by cells, and their cells no longer respond to insulin appropriately. This decrease in insulin sensitivity is thought to be a result of long-term, low-level inflammation of fat tissue in people who are obese. Dr. Vasanthakumar said Tregs acted as the guardians of the immune system, preventing the immune response from getting out-of-hand and attacking the body's own tissues. "When Treg numbers are reduced, inflammatory diseases such as diabetes and rheumatoid arthritis can occur," he said.

Easter Island Decline Began Prior to Arrival of Europeans

Long before the Europeans arrived on Easter Island in 1722, the native Polynesian culture known as Rapa Nui showed signs of demographic decline. However, the catalyst has long been debated in the scientific community. Was environmental degradation the cause, or could a political revolution or an epidemic of disease be to blame? A new study by a group of international researchers, including Universty of Caifornia (UC) UC Santa Barbara’s Dr. Oliver Chadwick, offers a different explanation and helps to clarify the chronological framework. The investigators expected to find that changes coincided with the arrival of the Europeans, but their work shows instead that the demise of the Rapa Nui culture began prior to that. Their findings are published in the January 27, 2015 issue of PNAS. "In the current Easter Island debate, one side says the Rapa Nui decimated their environment and killed themselves off," said Dr. Chadwick, a professor in UC Santa Barbara's Department of Geography and the Environmental Studies Program. "The other side says it had nothing to do with cultural behavior, that it was the Europeans who brought disease that killed the Rapa Nui. Our results show that there is some of both going on, but the important point is that we show evidence of some communities being abandoned prior to European contact." Dr. Chadwick joined archaeologists Dr. Christopher Stevenson of Virginia Commonwealth University, Dr. Cedric Puleston of UC Davis and Dr. Thegn Ladefoged of the University of Auckland, New Zealand in examining six agriculture sites used by the island's statue-building inhabitants. The research focused mainly on the three sites for which the scientists had information on climate, soil chemistry, and land use trends, as determined by an analysis of obsidian spear points.

January 27th

Pollinator Declines Place Millions at Risk of Malnutrition

Each year, millions of deaths result from diseases transmitted by insects. A new study shows that more than half the people in some developing countries could become newly at risk for malnutrition if crop-pollinating animals -- like bees -- continue to decline. Despite popular reports that pollinators are crucial for human nutritional health, no scientific studies have actually tested this claim -- until now. The new research by scientists at the University of Vermont (UVM) and Harvard University has, for the first time, connected what people actually eat in four developing countries to the pollination requirements of the crops that provide their food and nutrients. "The take-home is: pollinator declines can really matter to human health, with quite scary numbers for vitamin A deficiencies, for example," says UVM scientist Dr. Taylor Ricketts who co-led the new study, "which can lead to blindness and increase death rates for some diseases, including malaria." It's not just plummeting populations of bees. Scientists around the world have observed a worrisome decline of many pollinator species, threatening the world's food supply. Recent studies have shown that these pollinators are responsible for up to forty percent of the world's supply of nutrients. The new research takes the next step. It shows that in some populations -- like parts of Mozambique that the team studied, where many children and mothers are barely able to meet their needs for micronutrients, especially vitamin A -- the disappearance of pollinators could push as many as 56 percent of people over the edge into malnutrition. The study, "Do Pollinators Contribute to Nutritional Health?" was led by Drs. Alicia Ellis and Dr. Ricketts at UVM's Gund Institute for Ecological Economics and by Dr.Samuel Myers at the Harvard School of Public Health.

Newly Identified Plant Compounds Disrupt the Unique-to-Insects Juvenile Hormone Complex Receptor; Compounds Effectively and Safely Target Yellow-Fever Mosquitoes, Promise Similar Success Against Wide Range of Insect Pests & Disease Carriers

Each year, millions of deaths result from diseases transmitted by insects. Insects are also responsible for major economic losses, worth billions of dollars annually, by damaging crops and stored agricultural products. Many currently available insecticides present environmental and health risks. Further, insects develop resistance to existing insecticides, complicating pest-control strategies. The need to develop novel effective insecticides is therefore urgent. Enter "insect-specific growth regulators," which, as their name suggests, are compounds that regulate the growth of insects. They represent attractive pest-control agents because they pose no health risk to humans and are also environmentally safe. One hormone in insects, called juvenile hormone, is a particularly attractive target for insect growth regulators because this hormone exists only in insects. Juvenile hormone plays key roles in insect development, reproduction, and other physiological functions. An international team of scientists, including an entomologist at the University of California, Riverside (UCR), has investigated in detail how juvenile hormone acts and has devised a method to prevent its working. The researchers, led in the United States by Dr. Alexander Raikhel, a Distinguished Professor of Entomology at UCR, discovered potent compounds in plants that counteract the action of juvenile hormone. These compounds, called juvenile hormone antagonists (JHANs), make up plants' innate resistance mechanism against insect herbivores. In collaboration with Korean scientists, Dr. Raikhel's lab screened 1,651 plant species and chose active JHANs from these plants. They then identified five JHANs from two plants that are effective in causing mortality of yellow fever mosquito larvae, specifically by retarding the development of ovaries.

Nanoparticles That Effectively Deliver Charge-Neutral Oligonucleotide Analog Drugs into Cells

Therapeutic oligonucleotide analogs represent a new and promising family of drugs that act on nucleic acid targets such as RNA or DNA; however, their effectiveness has been limited due to difficulty crossing the cell membrane. A new delivery approach based on cell-penetrating peptide nanoparticles can efficiently transport charge-neutral oligonucleotide analogs into cells, as reported online on January 16, 2015 in an open-access article in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. In the article, entitled "Peptide Nanoparticle Delivery of Charge-Neutral Splice-Switching Morpholino Oligonucleotides," Dr. Peter Järver form the Medical Research Council (MRC) on the Cambridge Biomedical Campus (UK) and coauthors also from the Cambridge Biomedical Campus (U.K.), and also from Karolinska University Hospital (Huddinge, Sweden), Stockholm University (Sweden), Alexandria University (Egypt), and University of Oxford (UK), note that while delivery systems exist to facilitate cell entry of negatively charged oligonucleotide drugs, these approaches are not effective for charge-neutral oligonucleotide analogs. The authors describe lipid-functionalized peptides that form a complex with charge-neutral morpholino oligonucleotides, enabling them to cross into cells and retain their biological activity. "The exploitation of phosphorodiamidate morpholinos represents an exciting approach to treating a number of therapeutic targets," says Nucleic Acid Therapeutics Executive Editor Graham C. Parker, Ph.D., The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, Michigan, an who was not involved in the research.