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Archive - Jul 2015

July 23rd

Dolphin Study Suggests That a Saturated Fat (Heptadecanoic Acid) May Lead to Reversal of Pre-Diabetes in Humans; Finding Hints That Move Away from Whole Fat Dairy Products May Play Role in Global Diabetes Epidemic

For decades, the public has been told to avoid foods high in saturated fats and cholesterol. A new study, led by the National Marine Mammal Foundation (NMMF) and published in online on July 22, 2015 in the open-access journal PLOS ONE, reports that a saturated fat, called heptadecanoic acid, may help reverse prediabetes in humans. NMMF research discovered that bottlenose dolphins can readily switch in and out of diabetes-like states, and that dolphins - including those in the wild - can develop metabolic syndrome, a subclinical condition called prediabetes in humans. "To better understand what may be a driver for metabolic syndrome in dolphins, we started exploring their diet, which is primarily fish," said Dr. Stephanie Venn-Watson, Director of the NMMF's Translational Medicine and Research Program and the study's lead author. Because of the popularity of fish-based omega-3 fatty acids as a human health supplement, NMMF's team started by assessing fatty acid blood levels in 49 dolphins, as well as in their dietary fish. "We were surprised to find that among the 55 fatty acids studied, the saturated fat heptadecanoic acid appeared to have had the most beneficial impact on dolphin metabolism," said Dr. Venn-Watson. "Dolphins with higher levels of heptadecanoic acid in their blood had lower insulin and triglycerides." The study also showed that while some fish have high levels of heptadecanoic acid, other fish types had none. Six dolphins with low heptadecanoic acid were then fed fish high in this fatty acid. Within six months on the new diet, indicators of metabolic syndrome in dolphins, including elevated insulin, glucose, and triglycerides normalized. Key to this surprising outcome was reversal of high ferritin, an underlying precursor to metabolic syndrome.

CRISPR/Cas9 Gene Editing Technology Used to Reverse Inversions Causing Hemophilia A Defect in Patient-Specific Stem Cells; This Success Points Way to Possible Cure

For the first time, chromosomal defects responsible for hemophilia have been corrected in patient-specific induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 nucleases for gene editing. The scientific report of this possibly life-saving advance is titled “Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9.” It published online on July 23, 2015 in Cell Stem Cell. Sufferers of hemophilia live in a perpetual state of stress and anxiety: their joints wear down prematurely and they have bleeding episodes that feel as if they will never end. Their bodies lack the ability to make the clotting factor responsible for the coagulation of blood so any cut or bruise can turn into an emergency without immediate treatment. Hemophilia A occurs in approximately 1 in 5,000 male births and almost half of severe cases are caused by identified “chromosomal inversions.” In a chromosomal inversion, the order of a sequence of base pairs on the chromosome is reversed so that a gene containing the inversion is not expressed properly. In chromosomal inversions in hemophilia A, the sufferer cannot express the blood coagulation factor VIII (F8) gene, and therefore lacks the protein (factor VIII) that causes blood to clot in healthy people. A Korean team, led by Director of the Center for Genome Engineering Dr. Jin-Soo Kim, Institute for Basic Science (IBS), and Professor Dong-Wook Kim at Yonsei University, has experimented with hemophilia-A-patient-derived induced pluripotent stem cells (iPSCs) and hemophilia mice and found a way to correct the hemophilia-A-causioning inversions and repair the clotting factor deficiency that causes hemophilia A.

Ginkgo Bioworks Raises $45 Million; Boston-Based Synthetic Biology Start-Up Designs Organisms to Produce Flavors, Fragrances, Cosmetics, and Sweeteners; Plans to Expand into Pharmaceuticals and Probiotics

Ginkgo Bioworks, an organism design company, today (July 23, 2015)announced that it has raised $45 million in an oversubscribed Series B round. Viking Global, a firm managing more than $30 billion in capital, led the round along with previous investors including OS Fund, Y Combinator and Felicis Ventures. The new funds will be used to expand into new categories such as pharmaceuticals, cosmetics, and probiotics, as well as hire additional employees and build out Bioworks 2, the next generation of Ginkgo’s robotic Foundry. “Ginkgo Bioworks was our first-ever biotech investment and was part of the Y Combinator class of 2014,” said Sam Altman, President at Y Combinator. “Synthetic biology is one of the fastest growing areas of tech right now and Ginkgo is leading the category. We're excited to invest again in the company." Ginkgo Bioworks is at the intersection of industrial design and biology, delivering designer organisms built to specification for customers. The company specializes in engineering microbes to produce cultured ingredients such as flavors, fragrances, cosmetics, and sweeteners. The company’s foundry, Bioworks1, employs proprietary software and robotics to streamline the design, construction, and testing of engineered organisms. “This new financing allows us to further expand into real-world products in the nutrition, health, and consumer goods sectors, as well as add to our world-class team of engineers and designers,” said Jason Kelly, Co-Founder, Ginkgo Bioworks. “We’re excited to have top investors like Viking, OS Fund, Y Combinator, and Felicis to support our efforts and continued growth.” Ginkgo currently has more than 20 organism design contracts with customers, including Fortune 500 companies.

New Drug (CHK1 Inhibitor) Could Enhance Chemotherapy Effects, First Clinical Trials Scheduled in Lung and Pancreatic Cancer Patients

A new drug that blocks cancer's escape route from chemotherapy could be used to treat deadly lung and pancreatic cancers, new research reports. Scientists have shown in human cancer cells and in mice that the drug, which was discovered at The Institute of Cancer Research in London, boosts the effectiveness of conventional chemotherapy. The drug, known as CCT245737, is scheduled to begin first-in-human clinical trials in patients with lung and pancreatic cancers - two cancers with low survival rates that continue to resist currently available treatments. CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The new study was published online on July 22, 2015 the journal Oncotarget, and was funded by Cancer Research UK and Sareum Limited. The article is titled “The Clinical Development Candidate CCT245737 Is an Orally Active CHK1 Inhibitor with Preclinical Activity in RAS Mutant NSCLC and Eµ-MYC Driven B-cell Lymphoma.” The research, conducted at The Institute of Cancer Research (ICR) in collaboration with colleagues at the drug discovery company Sareum and at Newcastle University, shows the effectiveness of a new class of drugs called CHK1 inhibitors that can be delivered orally to patients. Most chemotherapies work by damaging the DNA of rapidly dividing cells. But in response, cancer cells activate a molecule called CHK1 that delays cell division and gives cancer cells time to repair their damaged DNA. Scientists hoped that blocking CHK1 could stop cancer cells from repairing DNA damage and prevent them from becoming resistant to the cell-killing effects of chemotherapy. Researchers developed techniques to assess the method of action of CCT245737 in human cancer cell lines, and demonstrated that it potently blocked the molecule CHK1.

July 22nd

Kiwi Genome Sequenced; Much Evidence for Adaptation to Nocturnal Behavior Noted: Loss of Color Vision, Heightened Sense of Smell, Low Metabolic Rate

The kiwi bird's unique nocturnal behavior is linked to some altered genes that eliminate color vision and others that modify its sense of smell, according to the first kiwi genome published in the open-access journal Genome Biology. Kiwis are endangered, ground-dwelling birds endemic to New Zealand. They are the smallest and only nocturnal representatives of the ratites - a group of flightless birds that includes the ostrich and the emu. Kiwis are also unusual in that they have a highly developed sense of smell, low metabolic rate, and enormous eggs in relation to body size. However, the genetic adaptations that underpin their unique traits have so far not been well understood. A team of researchers sequenced the genomes of two North Island brown kiwi. Not only was the kiwi genome found to be one of the largest bird genomes sequenced to date, but the team also identified evolutionary changes in its genome that help explain the bird's unique adaptations to nocturnality - a behavior found in under 3% of all bird species. Lead author Dr. Diana Le Duc from the University of Leipzig and the Max Planck Institute for Evolutionary Anthropology, Germany, said: "We've seen for the first time that kiwi lack color vision, and that their olfactory receptors can probably detect a larger range of odors which may be essential for their night-time foraging. These adaptations seem to have happened around 35 million years ago, soon after their arrival in New Zealand, probably as a consequence of their nocturnal lifestyle." The kiwi gene coding for the protein responsible for black-and-white vision, rhodopsin, was found to be similar to the corresponding gene in other vertebrates. However, the team identified mutations in the green-and-blue vision receptor genes, which could render blue and green color vision absent in the kiwi.

Antisense Morpholino Drug May Be Effective Against Deadly Marburg Virus; Current Human Fatality Rate Is 90%

An experimental drug that protected monkeys from the deadly Marburg virus appears to have potential for treating people who have been exposed to the virus, according to a study published in the July 23, 2015 issue of The New England Journal of Medicine. The article is titled “AVI-7288 for Marburg Virus in Nonhuman Primates and Humans.” Marburg virus is closely related to Ebola virus and, as Ebola, also causes a severe hemorrhagic fever. The research was jointly conducted by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the biotechnology firm Sarepta Therapeutics, Inc., using a compound known as AVI-7288. Taken together, the results of efficacy testing conducted in nonhuman primates and safety testing performed in a Phase I clinical trial suggest that AVI-7288 has the potential to be used to treat Marburg virus infection in humans when administered post-exposure, according to the authors. Case fatality rates associated with Marburg virus have been reported to be nearly 90 percent and the virus is deemed a potential "Category A" bioterrorism agent by the Centers for Disease Control and Prevention. No licensed vaccine or therapy is currently available for Marburg virus infection. For over a decade, USAMRIID and Sarepta have been collaborating to develop and test a class of antisense compounds known as phosphorodiamidate morpholino oligomers (or PMOs), according to senior author and USAMRIID Science Director Sina Bavari, Ph.D. Antisense drugs are designed to enter cells and eliminate viruses by preventing their replication, Dr. Bavari explained. The drugs act by blocking the translation of critical viral genetic sequences, preventing a key viral protein from being made, and giving the infected host time to mount an immune response and clear the virus.

More Birds Develop Darker Plumage on Smaller Islands; Genetic Link Between Melanism and Aggression Has Previously Been Shown in Mammals and Fish; Darker Plumage May Give Birds Aggression-Based Mating Advantage in Smaller Territories

Animal populations on islands tend to develop unusual traits over time, becoming big (like Galapagos tortoises) or small (like extinct dwarf elephants), or losing the ability to fly (as the flightless parrots of New Zealand). One less-studied pattern of evolution on islands is the tendency for animal populations to develop "melanism"--that is, dark or black coloration. Dr. J. Albert Uy and Dr. Luis Vargas-Castro of the University of Miami found an ideal species in which to study this phenomenon: the chestnut-bellied monarch (Monarcha castaneiventris) flycatcher, a bird found in the Solomon Islands. Most of these birds have the chestnut belly suggested by their name, but in the subspecies found in the Russell Islands, a few all-black birds coexist with the chestnut-bellied majority. After visiting 13 islands of varying sizes to survey their chestnut-bellied monarch populations, Dr. Uy and Dr. Vargas-Castro confirm, in a new paper published online on July 22, 2015 in an open-access article in The Auk: Ornithological Advances, that island size predicts the frequency of melanic birds, with populations on smaller islands including more dark individuals. The article is titled “Island Size Predicts the Frequency of Melanic Birds in the Color-Polymorphic Flycatcher Monarcha castaneiventris of the Solomon Islands." Because the pattern is repeated on island after island, it is very unlikely to have developed through random chance; instead, dark coloration most likely provides some sort of benefit to birds on small islands. Studies in mammals and fish have found a genetic link between melanism and aggressive behavior, and Dr. Uy and Dr. Vargas-Castro speculate that the limited space available on smaller islands makes competition for breeding territories more intense, giving an advantage to the most aggressive individuals.

High Levels of Fumarate May Play Prominent Role in Diabetic Kidney Disease; As Measurable Metabolite in Urine, Compound Could Prove Useful New Biomarker

Tapping the potential of metabolomics, an emerging field focused on the chemical processes of metabolism, researchers at the University of California (UC), San Diego School of Medicine have identified a new and pivotal player in diabetic kidney disease. The study, published online on July 22, 2015 in the Journal of the American Society of Nephrology, also clarifies a central mechanism of action in diabetic kidney disease that is generating considerable excitement among researchers and the biopharmaceutical community. The mechanism, involving the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX) proteins NOX1 and NOX4 is now the subject of a phase II clinical trial for the treatment of diabetic kidney disease. "Our study further illuminates the role of NOX proteins, in particular NOX4, in mediating diabetes-associated kidney dysfunction and identifies fumarate, a product of the TCA (tricarboxylic acid) and urea cycles, as a key link in the metabolic pathways underlying diabetic kidney disease," said senior author Kumar Sharma, M.D., a Professor of Medicine and Director of the Center for Renal Translational Medicine at UC San Diego School of Medicine. By pinpointing fumarate, Dr. Sharma added, the research team has also discovered a new, and potentially better, biomarker for diagnosing and monitoring chronic diabetic kidney disease. Young-Hyun You, Ph.D., a project scientist in the Center for Renal Translational Medicine, was first author on the study. The article is titled “Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease.” Diabetic kidney disease is the leading cause of end-stage kidney disease, the eighth leading cause of death in the United States and a major risk factor for cardiovascular disease.

100-Year-Old Theory for Origin of Mysterious “Hair Ice” Is Confirmed; Specific Fungus Is Key; Physics, Chemistry, and Biolgy Converge to Solve Riddle of Evanescent Frozen Beauty

You may have never seen or heard of it, but hair ice - a type of ice that has the shape of fine, silky hairs and resembles white candy floss - is remarkable. It grows on the rotten branches of certain trees when the weather conditions are just right, usually during humid winter nights when the air temperature drops slightly below 0°C. Now, a team of scientists in Germany and Switzerland has identified the missing ingredient that gives hair ice its peculiar shape: namely the fungus Exidiopsis effusa. The research was published online today (July 22, 2015) in Biogeosciences, an open-access journal of the European Geosciences Union (EGU). The article is titled “Evidence for Biological Shaping of Hair Ice.” "When we saw hair ice for the first time on a forest walk, we were surprised by its beauty," says Dr. Christian Mätzler from the Institute of Applied Physics at the University of Bern in Switzerland. "Sparked by curiosity, we started investigating this phenomenon, at first using simple tests, such as letting hair ice melt in our hands until it melted completely." Then Dr. Mätzler, a physicist, joined forces with a chemist (Dr. Diana Hofmann) and a biologist (Dr. Gisela Preuß) in Germany. Inspired by earlier work, and by photographs of hair ice sent in from various countries, the team performed a set of experiments to figure out just what conditions are needed to grow this type of ice and what its properties are. In the process, they confirmed a 100-year-old theory for the origin of hair ice. Dr. Alfred Wegener, of tectonic-plate fameand originator of the Continental Drift theory, was the first to study hair ice. In 1918, he noticed a whitish cobwebby coating on the surface of hair-ice-bearing wood, which his assistant identified as fungus mycelium - the mass of thin threads from where mushrooms grow. Dr.

Ultra-Brief-Pulse Electroshock Effective for Severe Depression with Far Fewer Cognitive Side Effects Than Standard Electroshock

Electroconvulsive therapy (ECT) remains one of the most effective treatments for severe depression, but new University of New South Wales (UNSW) research shows ultra-brief pulse stimulation is almost as effective as standard ECT, with far fewer cognitive side effects. The study, published online in the Journal of Clinical Psychiatry, is the first systematic review to examine the effectiveness and cognitive effects of standard ECT treatment, brief pulse stimulation, versus the newer treatment, known as ultra-brief pulse right unilateral (RUL) ECT. It comes after previous trials had shown conflicting results. The latest study reviewed six international ECT studies comprising 689 patients with a median age of 50 years old. The study found that, while standard ECT was slightly more effective for treating depression and required one fewer treatment, this came at a cost with significantly more cognitive side effects. "This new treatment, which is slowly coming into clinical practice in Australia, is one of the most significant developments in the clinical treatment of severe depression in the past two decades," according to UNSW Professor of Psychiatry Dr. Colleen Loo. "Our analysis of the existing trial data showed that ultra-brief stimulation significantly lessened the potential for the destruction of memories formed prior to ECT, reduced the difficulty of recalling and learning new information after ECT, and was almost as effective as the standard ECT treatment," Professor Loo said. The article is titled "A Systematic Review and Meta-Analysis of Brief Versus Ultrabrief Right Unilateral Electroconvulsive Therapy for Depression." ECT delivers a finely controlled electric current to the brain's prefrontal cortex, an area that is underactive in people with depression.