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Archive - Mar 2017

March 3rd

Why Giant Pandas Are Black and White

The scientists who uncovered why zebras have black and white stripes (to repel biting flies), took the coloration question to giant pandas in a study published on February 28, 2017 in the journal Behavioral Ecology. The study, a collaboration between the University of California (UC), Davis, and California State University (CSU), Long Beach, determined that the giant panda's distinct black-and-white markings have two functions: camouflage and communication. "Understanding why the giant panda has such striking coloration has been a long-standing problem in biology that has been difficult to tackle because virtually no other mammal has this appearance, making analogies difficult," said lead author Tim Caro, a professor in the UC Davis Department of Wildlife, Fish and Conservation Biology. "The breakthrough in the study was treating each part of the body as an independent area." This enabled the team to compare different regions of fur across the giant panda's body to the dark and light coloring of 195 other carnivore species and 39 bear subspecies, to which it is related. Then they tried to match the darkness of these regions to various ecological and behavioral variables to determine their function. Through these comparisons, the study found that most of the panda - its face, neck, belly, rump -- is white to help it hide in snowy habitats. The arms and legs are black, helping it to hide in shade. The scientists suggest that this dual coloration stems from its poor diet of bamboo and inability to digest a broader variety of plants. This means it can never store enough fat to go dormant during the winter, as do some bears. So it has to be active year-round, traveling across long distances and habitat types that range from snowy mountains to tropical forests.

“Red Hair” Gene Variant May Underlie Association Between Melanoma & Parkinson's Disease

A gene variant that produces red hair and fair skin in humans and in mice, and which increases the risk of the dangerous skin cancer melanoma, may also contribute to the known association between melanoma and Parkinson's disease. In a paper appearing in the March 2017 issue of Annals of Neurology and previously published online (January 23, 2017), Massachusetts General Hospital (MGH) investigators report that mice carrying the red-hair variant of the melanocortin 1 receptor (MC1R) gene have reduced production of the neurotransmitter dopamine in the substantia nigra [the brain structure in which dopamine-producing neurons are destroyed in Parkinson's disease (PD)] and are more susceptible to toxins known to damage those neurons. "This study is the first to show direct influences of the melanoma-linked MC1R gene on dopaminergic neurons in the brain and may provide evidence for targeting MC1R as a novel therapeutic strategy for PD," says Xiqun Chen, M.D., Ph.D., of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), lead and corresponding author of the report. "It also forms a foundation for further interdisciplinary investigations into the dual role of this gene in tumorigenesis within melanocytes (the pigment cells in which melanoma develops) and the degeneration of dopaminergic neurons, improving our understanding of why and how melanoma and Parkinson's disease are linked." Inherited variants of the MC1R gene determine skin pigmentation, with the most common form leading to greater production of the darker pigment called eumelanin and the red-hair-associated variant, which inactivates the gene's function, increasing production of the lighter pigment called pheomelanin.

New Technique Removes Cause of Allergic Asthma: IgE Antibodies Immuno-Adsorbed on Sepharose Column

Allergies are the most common cause of asthma. The immune system over-reacts to harmless substances such as birch or grass pollen, for example, forming immunoglobulin E antibodies (IgE). Together with the inflammatory cells in the skin and mucous membranes (the "mast cells"), IgE antibodies are responsible for certain allergic diseases, such as asthma and hay fever, for example, and are also partly responsible for the development of neurodermatitis. Scientists from MedUni Vienna have now successfully developed a technique for suctioning the IgE antibodies out of the blood, thereby significantly improving the quality of life for people who suffer from severe allergic asthma. The "IgEnio" column was developed for this purpose. This one-way adsorber, which has been specifically developed for treating IgE-related diseases, reduces the plasma IgE level by running the patient's blood through a "column" that traps the IgE antibodies – by means of Sepharose beads carrying IgE-binding proteins. These beads bind IgE in the column, thereby adsorbing the antibodies as the blood flows through during "dialysis." There is also a similar absorber for IgG antibodies, for treating autoimmune diseases. In the first study conducted with IgEnio, the MedUni Vienna researchers at the Institute of Pathophysiology and Allergy Research, led by Dr. Rudolf Valenta and lead author Dr. Christian Lupinek, Dr. Kurt Derfler from the Division of Nephrology and Dialysis (Department of Medicine III), and Dr. Ventzislav Petkov from the Division of Pulmonology (Department of Medicine II), were able to show that this absorption technique brings about a significant improvement in the quality of life for sufferers during the pollen season – even those with a greatly elevated IgE levels. The technique removes approximately 80% of the IgE antibodies.

Sickle Cell Disease: Remission of Signs of Disease in First Patient in World Treated with Gene Therapy; NEJM Publishes Case Study; Patient Treated with LentiGlobin Drug Product Is Free from Severe Symptoms & Has Resumed Normal Activities

On March 1, 2017. Bluebird Bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, announced publication in the New England Journal of Medicine of positive results of a case study on Patient 1204, the first patient with severe sickle cell disease (SCD) to be treated with gene therapy. The NEJM article is titled ““Gene Therapy in a Patient with Sickle Cell Disease.” This patient, who was 13 years old at the time of treatment, was treated with LentiGlobin drug product in the HGB-205 clinical study conducted in Necker Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. The data in the publication reflects 15 months of follow-up. A brief summary of this patient’s outcomes with 21 months of follow-up was presented at the 58th American Society of Hematology Annual Meeting in December 2016. “We have managed this patient at Necker for more than 10 years, and standard treatments were not able to control his SCD symptoms. He had to receive blood transfusions every month to prevent severe pain crises,” said Professor Marina Cavazzana, M.D., Ph.D., principal investigator of this study and Professor of Hematology at Paris Descartes University, Head of the Department of Biotherapy Hospital, the clinical research center of Biotherapy at Necker Enfants Malades - Greater Paris University Hospital, AP-HP and INSERM, and of the Lymphohematopoiesis Laboratory, Imagine Institute of Genetic Diseases, Paris, France.

March 2nd

Powerful & Flexible Software (CRISPETa) Developed for Designing Quick & Easy CRISPR Deletion Experiments

Until recently, genomics was a “read-only” science. But scientists, led by Dr. Rory Johnson at the University of Bern and the Centre for Genomic Regulation in Barcelona, Spain, have now developed a tool for quick and easy deletion of DNA in living cells. This software will boost efforts to understand the vast regions of non-coding DNA, or “Dark Matter,” in our DNA and may lead to discovery of new disease-causing genes and potential new drugs. Genomics is the field of research studying how our genome, or entire DNA sequence, specifies a human being, and how errors in this sequence give rise to diseases. Genomics was recently a “read-only” endeavor: researchers used powerful technology to read genome sequences and their regulatory layers. However, until recently, there was no way to edit or delete DNA for either basic research objectives, or for potential therapeutic interventions. Just a few years ago, this outlook changed dramatically with the discovery of a revolutionary technique for editing genomes: “CRISPR-Cas9.” CRISPR-Cas9 is a molecular tool composed of two simple components: a molecular barcode, called “sgRNA,” which is designed by the researcher to recognize one precise location in the genome; and a protein, Cas9, that binds to a structured loop in the sgRNA. By introducing these two units, researchers may perform a wide range of operations on specific pieces of genomic DNA, from introducing small mutations, to regulating gene activity, to tagging the DNA with small sequences. Until recently, most studies employing CRISPR-Cas9 were aimed at silencing protein-coding genes, the best-studied part of our genome. However, 99% of our genome consists of DNA that does not encode any protein.

Intestinal Bacteria of Irritable Bowel Syndrome (IBS) Patients Alter Gut & Brain Function in Mice; Finding May Lead to New Microbiota-Directed Therapies for GI Upset & Brain Disorders

Research from McMaster University and the University of Waterloo, both in Canada, has found that bacteria in the gut impact both intestinal and behavioral symptoms in patients suffering from irritable bowel syndrome (IBS), a finding which could lead to new microbiota-directed treatments. The new study, published in the March 1, 2017 issue of Science Translational Medicine, was led by researchers from the Farncombe Family Digestive Health Research Institute at McMaster--Drs. Premysl Bercik and Stephen Collins--in collaboration with researchers from the University of Waterloo. The article is titled “Transplantation of Fecal Microbiota from Patients with Irritable Bowel Syndrome Alters Gut Function and Behavior in Recipient Mice.” IBS is the most common gastrointestinal disorder in the world. It affects the large intestine and patients suffer from abdominal pain and altered bowel habits like diarrhea and constipation, which are often accompanied by chronic anxiety or depression. Current treatments aimed at improving symptoms have limited efficacy because the underlying causes are unknown. The goal of the study was to explore whether fecal microbiota from human IBS patients with diarrhea have the ability to influence gut and brain function in recipient mice. Using fecal transplants, researchers transferred microbiota from IBS patients with or without anxiety into germ-free mice. The mice went on to develop changes both in intestinal function and behavior reminiscent of the donor IBS patients, compared to mice that were transplanted with microbiota from healthy individuals.

Scientists Create Artificial Mouse “Embryo” from Stem Cells

Scientists at the University of Cambridge in the UK have managed to create a structure resembling a mouse embryo in culture, using two types of stem cells - the body's “master cells” - and a 3D scaffold on which the cells can grow. Understanding the very early stages of embryo development is of interest because this knowledge may help explain why more than two out of three human pregnancies fail at this time. Once a mammalian egg has been fertilized by a sperm, it divides multiple times to generate a small, free-floating ball of stem cells. The particular stem cells that will eventually make the future body, the embryonic stem cells (ESCs), cluster together inside the embryo towards one end: this stage of development is known as the blastocyst. The other two types of stem cell in the blastocyst are the extra-embryonic trophoblast stem cells (TSCs), which will form the placenta; and the primitive endoderm stem cells that will form the so-called yolk sac, ensuring that the fetus's organs develop properly and providing essential nutrients. Previous attempts to grow embryo-like structures using only ESCs have had limited success. This is because early embryo development requires the different types of cell to coordinate closely with each other. Now, however, in a study published online on March 2, 2017 in Science, University of Cambridge researchers describe how, using a combination of genetically-modified mouse ESCs and TSCs, together with a 3D scaffold known as an extracellular matrix (ECM), they were able to grow a structure capable of assembling itself and whose development and architecture very closely resembled the natural mouse embryo.

Humans Found to Have Three Times More Brown Fat Than Previously Thought; Obesity & Diabetes Drugs That Activate Brown Fat May Be More Effective Than Initially Believed; Creatine Clearance Shown to Affect Brown Fat Activity

Compared to white fat, brown body fat burns through energy at an extraordinary rate. However, until now the proportion of brown fat in humans was thought to be quite small. Now a study conducted by researchers at the Technical University of Munich (TUM) in Germany has shown: The quantity of brown fat in humans is three times greater than previously known. As a consequence, new obesity and diabetes drugs that activate brown adipose tissue are expected to be more effective. For the study, published in the Journal of Nuclear Medicine, nearly 3,000 PET scans of 1,644 patients were analyzed. PET is an acronym for positron emission tomography, a method widely used in oncology. PET scans enable the visualization of metabolic activity in the body. Because a tumor often has a different energy metabolism than healthy tissue, PET scans can be used to demonstrate the presence of metastases. "A byproduct of PET scans is that they allow us to see active brown adipose tissue," said Dr .Tobias Fromme from the Else-Kröner-Fresenius Center at the TUM. “Brown adipose tissue absorbs lots of sugar, and we can observe this activity through the scans." For example, it is conceivable that a drug could reduce excessive blood sugar levels in diabetics by increasing the activity of the brown fat. Similarly, it is conceivable that patients with obesity could use the high rate of energy combustion through brown fat to melt away their excess weight -- at least to a certain extent. "In any event, the outlook for the efficacy of drugs in brown adipose tissue can be adjusted upwards," said the researcher. The analysis of the PET scans also revealed that some groups of persons have an easier time activating their brown fat than others, or even have more of it in the first place.

March 1st

Exosome-Mediated Intercellular Communication Is Implicated in Activation of Hepatic Stellate Cells for Liver Fibrosis in Hepatitis C Virus Infection

Hepatitis C virus (HCV)-associated liver fibrosis is a critical step for end-stage liver disease progression in chronic HCV infection. Fibrogenic pathways in the liver are principally regulated by activation of hepatic stellate cells (HSC). The mechanism underlying the liver fibrosis associated with chronic HCV infection has heretofore been poorly understood. Now, scientists at St. Louis University in Missouri have conducted experiments indicating that microRNA-19a (miR-19a) is carried by exosomes from HCV-infected hepatocytes to HSC, where the miR-19a activates the HSC to produce liver fibrosis. In the HSC, miR-19a targets SOCS3, which in turn activates the STAT3-mediated transforming growth factor-beta (TGF-beta) signaling pathway and enhances fibrosis marker genes. The authors state that “Our results implicated a novel mechanism of exosome-mediated intercellular communication in the activation of HSC for liver fibrosis in HCV infection.” These results were published in the March 2017 issue of the Journal of Virology. The article is titled “Exosome-Mediated Intercellular Communication between Hepatitis C Virus-Infected Hepatocytes and Hepatic Stellate Cells.”

[Journal of Virology abstract]

Scientists Reveal Core Genes Involved in Immunity of Honey Bees

A core set of genes involved in the responses of honey bees to multiple diseases caused by viruses and parasites has been identified by an international team of researchers. The findings provide a better-defined starting point for future studies of honey-bee health, and may help scientists and beekeepers breed honey bees that are more resilient to stress. "In the past decade, honey-bee populations have experienced severe and persistent losses across the Northern Hemisphere, mainly due to the effects of pathogens, such as fungi and viruses," said Dr. Vincent Doublet, postdoctoral research fellow, University of Exeter (UK). "The genes that we identified offer new possibilities for the generation of honey-bee stocks that are resistant to these pathogens." According to the researchers, recent advances in DNA sequencing have prompted numerous investigations of the genes involved in honey-bee responses to pathogens. Yet, until now, this vast quantity of data has been too cumbersome and idiosyncratic to reveal overarching patterns in honey-bee immunity. "While many studies have used genomic approaches to understand how bees respond to viruses and parasites, it has been difficult to compare across these studies to find the core genes and pathways that help the bee fight off stressors," said Distinguished Professor of Entomology Christina Grozinger, Penn State.