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Archive - Feb 2015

February 10th

Novel, First-in-Class “Smart” insulin Automatically Adjusts Blood Sugar in Diabetic Mouse Model

For patients with type 1 diabetes (T1D), the burden of constantly monitoring their blood sugar and judging when and how much insulin to self-inject, is bad enough. Even worse, a miscalculation or lapse in regimen can cause blood sugar levels to rise too high (hyperglycemia), potentially leading to heart disease, blindness, and other long-term complications, or to plummet too low (hypoglycemia), which, in the worst cases, can result in coma or even death. To mitigate the dangers inherent to insulin dosing, a University of Utah biochemist and fellow scientists have created Ins-PBA-F, a long-lasting "smart" insulin that self-activates when blood sugar soars. Tests In mouse models for T1D show that one injection works for a minimum of 14 hours, during which time, Ins-PBA-F can repeatedly and automatically lower blood sugar levels after mice are given amounts of sugar comparable to what they would consume at meal-time. Ins-PBA-F acts more quickly, and is better at lowering blood sugar, than long-acting insulin detimir, marketed as LEVIMIR. In fact, the speed and kinetics of touching down to safe blood glucose levels are identical in diabetic mouse models treated with Ins-PBA-F and in healthy mice whose blood sugar is regulated by their own insulin. A study showing these findings was published online on February 9, 2015 in PNAS. The title of this article is, “Glucose-Responsive Insulin Activity by Covalent Modification with Aliphatic Phenylboronic Acid Conjugates.” "This is an important advance in insulin therapy," says co-first author Danny Chou, Ph.D., USTAR Investigator and Assistant Professor of Biochemistry at the University of Utah. "Our insulin derivative appears to control blood sugar better than anything that is available to diabetes patients right now." Dr.

February 10th

New York Times Features Article on Human Geneticist Mary-Claire King (2-10-2015)

BioQuick friend and legendary human geneticist Mary-Claire King, Ph.D. is featured in an article on page D3, above the fold, in today's (2-10-2015) New York Times / Science Times. Dr. King is enormously and widely respected for her brilliant body of work in the areas of breast and ovarian cancer genetics, as well as in other key areas of human genetics.[Check BQ Obama story for more on King./Q&A format] She is also highly regarded for her efforts in the area of human rights. Dr. King is very possibly a future Nobel Prize winner for her breast and ovarian cancer genetics work, particularly for her vast amount of work in support of the ultimate identifications of the BRCA1 and BRCA2 genes. That BRCA work has completely transformed how these grievous cancers of the breast and of the ovary are dealt with. Dr. King won the 2014 Lasker Award that is often a prelude to the Nobel Prize. She is a past President of the American Society of Human Genetics (ASHG) and the winner of innumerable prestigious honors and awards over her long and singular career. Currently, Dr. King is Professor of Genome Sciences and Medical Genetics at the University of Washington in Seattle. Dr. King is viewed particularly favorably by BioQuick News because she has been kind enough to give Editor & Publisher Mike O'Neill two very important quotes even though she was certainly extremely busy with other much more important work at the times. The first Dr. King quote was for a story I was doing on Elizabeth Blackburn, telomeres, and telomerase. Dr. Blackburn would, about one year later, win the 2009 Nobel Prize for Physiology or Medicine for her seminal work in this crucial area of telomeres and telomerase. I simply asked Dr. King and she very quickly provided me with a very nice quote for which I was very, very grateful.

“The Walking Dead” Parasitoid Fungus Attacks Ant, Takes Over Brain, Forces Ant to Move to an Environment Ideal for Fungal Growth; Then and Only Then, Fungus Kills Ant

There are several species of ants known as “zombie ants,” one of which is targeted and infected by a parasitoid fungus called Ophiocordyceps unilateralis. This fungus takes over an ant’s brain and controls its actions so that it does what’s best for the fungus before it eventually kills the ant. “Unlike parasites, like mosquitoes, which benefit by getting food or nutrients from a host without killing it, parasitoids eventually kill the host,” explains Dr. Conrad Labandeira, Curator of fossil arthropods and a researcher at the Smithsonian’s National Museum of Natural History. Here’s what happens. An ant is going about its normal life, when suddenly the parasitoid fungus attacks the ant’s brain and essentially turns that ant into the walking dead. “This type of fungus needs a particular ant as a host to complete its life cycle,” Dr. Labandeira says. “The fungus starts out as airborne spores. When a spore lands on an ant, it lodges itself into its head through an exposed part of the ant’s exoskeleton. The fungus then infiltrates and targets the ant’s brain, taking control of the ant in what’s called ‘zombification.’” Once the fungus takes over the ant’s brain, it makes the ant leave its colony and head for a leaf that provides the ideal conditions for the fungus to grow. The ant crawls under the leaf and goes into a “death grip”—biting down very hard on the major veins of the leaf and eventually hangs attached to the leaf as a carcass. “As the ant clenches to the underside of the leaf, the fungus slowly feeds on it. When the fungus finishes growing, it eventually kills the ant and releases its spores,” Dr. Labandeira says.

Discovery of Regulatory Mechanisms Controlling Circadian Rhythms, These Enable Molecular Communication between Environmental Signals and Signals Controlling Internal Clock to Optimize Photosynthetic and Metabolic Processes

Researchers in the Department of Physiology, Genetics, and Microbiology of the University of Alicante (UA) in Spain and in the Biological Sciences Division of the University of California, San Diego (UCSD) have recently published an article in PNAS, which draws conclusions on the circadian rhythms. This is the name by which the internal clock is known that exists in animals and plants and allows them to adapt to the conditions, which are extremely diverse and changing in some geographical areas. The cycles of light and dark (day and night) are extremely important for species and for life activity on earth. Thus, most organisms have internal clocks. The PNAS paper reports the discovery of regulatory mechanisms that allow molecular communication between environmental signals and those controlling the internal clock to optimize photosynthetic and metabolic processes. Cyanobacteria were pioneers in developing an internal clock to adapt themselves and even to anticipate the cycles of light and darkness. In order to carry out this study, scientists have worked with the model organism in which more molecular details are known about the circadian clock, which is the cyanobacterium Synechococcus elongatus PCC7942, used in laboratories around the world. Cyanobacteria are organisms that created the planet's oxygen atmosphere and enabled life as we currently understand it. These bacteria perform, more efficiently than plants, the same type of photosynthesis, by consuming CO2, and thus have enormous evolutionary and ecological importance, and a great biotechnological potential. Thus, one practical application of the study may be the production of a more affordable biofuel. This work connects the research lines of a University of Alicante group and another from San Diego, respectively led by geneticists Dr.

Scientists Find New Cellular Pathway Defect in Cystinosis

Scientists at The Scripps Research Institute (TSRI) in La Jolla, California, have identified a new cellular pathway that is affected in cystinosis, a rare genetic disorder that can result in eye and kidney damage. The findings, published recently by the journal EMBO Molecular Medicine, could eventually lead to new drug treatments for reducing or preventing the onset of renal failure in patients. “Life expectancy for infantile and juvenile forms of the disease is only 20 to 30 years, even in treated patients,” said Dr. Sergio Catz, an Associate Professor at TSRI. “Clearly, there is a need for additional treatment approaches.” Cystinosis is a so-called lysosomal storage disease, a class of genetically inherited disorders. These conditions are caused by dysfunction of lysosomes, sacs within cells that digest old or unused proteins and other macromolecules. Dr. Catz notes that lysosomes are the recycling centers of cells; when they don’t work properly, a toxic buildup of undigested material can result, and eventually lead to cell degeneration. Patients with cystinosis lack a protein called cystinosin, which is necessary for transporting the amino acid cystine out of the lysosome. Cystine accumulation leads to the formation of crystals in cells that can damage tissues and organs, especially the eyes and kidneys. Cystinosis is normally treated with a drug called cysteamine, which reacts with cystine to form other molecules that can be moved out of the lysosome via other transporter proteins. Doctors have long noticed, however, that while cysteamine successfully reduces cystine buildup in cells, it only lessens kidney damage in some, but not all, patients. This has led researchers to suspect that the disease disrupts more than one crucial cellular pathway.

UCSF-Led Study Shows Why Some Targeted Cancer Drugs Lose Effectiveness; YAP Protein Is Crucial; Use of shRNA to Tamp Done Activity of 5,000 Proteins, One-by-One, in Lung Cancer Cells, Powers Investigation

A protein called YAP, which drives the growth of organs during development and regulates their size in adulthood, plays a key role in the emergence of resistance to targeted cancer therapies, according to a new study led by University of California-San Francisco (UCSF) researchers. By precisely identifying the mechanism by which elevated levels of YAP promote the survival of cancer cells, the new work points the way to combination therapies that may overcome resistance to individual targeted drugs, the scientists said. Though cancer drugs aimed at specific genetic mutations have had some success in recent years, most patients who have a good initial response eventually develop resistance to these therapies, most likely because cancer cells engage alternative survival mechanisms that lie outside the biological pathways targeted by the drugs. Though oncologists have the option of switching to a different targeted drug after resistance takes hold, many cancer researchers believe that a better strategy would be to forestall cancer cells’ eventual escape routes by using customized combinations of targeted drugs at the outset of therapy. “Instead of trying to figure out why patients have developed resistance after it has emerged, we need to decipher what survival tactic tumor cells will be most dependent on when they are challenged with targeted therapy,” said the senior author of the study, Trever Bivona (http://cancer.ucsf.edu/people/profiles/bivona_trever.3308), M.D., Ph.D., UCSF Assistant Professor of Medicine and a member of the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC) (http://cancer.ucsf.edu/).

February 9th

With Google Glass App, Scientists Can Analyze Plant's Health in Seconds

Scientists from UCLA’s California NanoSystems Institute have developed a Google Glass app that, when paired with a handheld device, enables the wearer to quickly analyze the health of a plant without damaging it. The app analyzes the concentration of chlorophyll, the substance in plants responsible for converting sunlight into energy. Reduced chlorophyll production in plants can indicate degradation of water, soil or air quality. One current method for measuring chlorophyll concentration requires removing some of the plant’s leaves, dissolving them in a chemical solvent, and then performing the chemical analysis. With the new system, leaves are examined and then left functional and intact. The research, led by Dr. Aydogan Ozcan, Associate Director of the UCLA California NanoSystems Institute and Chancellor’s Professor of Electrical Engineering and Bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, was published online by the Royal Society of Chemistry journal Lab on a Chip. The system developed by Dr. Ozcan’s lab uses an image captured by the Google Glass camera to measure the chlorophyll’s light absorption in the green part of the optical spectrum. The main body of the handheld illuminator unit can be produced using 3-D printing and it runs on three AAA batteries; with a small circuit board added, it can be assembled for less than $30. Held behind the leaf, facing the Glass wearer, the illuminator emits light that enhances the leaf’s transmission image contrast, indoors or out, regardless of environmental lighting conditions.

Attention Retina Specialists! You Might Want to Hang Your Shingles Up Down Deep; Unusual Ocean-Dwelling Crustacean Has 32 Retinas, 16 in Each Eye; Those Choosing New Crustacean Specialty Can Reduce Their Patient Loads to 2-4 Patients Per Week

Tiny and transparent, the marine crustacean Paraphronima gracilis sees the world through two large eyes that envelop its head like a high-tech space helmet. Now, a new study of this amphipod—a close relative of the sand hopper—reveals that it has 32 different retinas, the light-sensitive parts of its eyes. “We have never seen the retina split up this way in any other arthropod eye, not in insects, not in crustaceans, or other animals with a compound eye,” explains Jamie Baldwin Fergus (http://invertebrates.si.edu/baldwin-fergus.htm), Ph.D., Peter Buck Postdoctoral Fellow at the Smithsonian’s National Museum of Natural History, and lead author of a detailed study of this eye published online on January 15, 2015 in Current Biology. “This eye design has not been described previously and its function is unknown,” said Dr. Fergus. In addition to Dr. Fergus, Karen Osborn (http://invertebrates.si.edu/staff/osborn.cfm), Ph.D., of the Smithsonian’s National Museum of Natural History, and Sonke Johnsen (http://sites.biology.duke.edu/johnsenlab/), Ph.D., of Duke University are also co-authors of the Current Biology paper. Living at depths of 150 to 500 meters off the coast of California, P. gracilis inhabits an environment that is totally dark to the human eye. As it swims, its eyes are positioned upward, looking for prey, transparent creatures called siphonophores, swimming above. In most compound eyes, the retina is a single continuous pigmented sheet. The 32 retinas in the eyes of P. gracilis appear as a series of tiny orange upside-down pyramids neatly arranged in two rows on either side of the animal’s head. Light travels to each retina through a row of transparent facets called ommatidia that cover the eye, collecting light that is channeled through guide tissue similar to fiber optic cables.

Birds Excel at Keeping Warm in Winter: Feathers, Oil, and a Counter-Current Heat Exchange System Are Key; Altering the Single Leg They Stand On, Flocking, and Roosting Close Together Also Help

Many of you might well be interested in a story posted on January 30, 2015 in Smithsonian Science. The story posed and answered the question of how tiny little birds manage to survive and stay warm during bitterly cold winter weather. The article was entitled, “Keeping Warm in Winter is for the Birds.” It was authored by John Gibbons, the Press Secretary for Science at the Smithsonian Institution. Gibbons is also the media contact for the Smithsonian’s Museum Conservation Institute (MCI) (http://www.si.edu/mci/). His story on birds coping with winter appeared, specifically, in Smithsonian Science’s Research News/Conservation Biology section. The entire story, along with some gorgeous images of different birds dealing with cold weather can be viewed at http://smithsonianscience.org/2015/01/keeping-warm-winter-birds/. The Smithsonian Science site (http://smithsonianscience.org/) offers a continuously updated source of fascinating stories on a wide range science and biology topics. According to Smithsonian Science, John Gibbons has over ten years of experience in publicizing research and science. From giant panda babies to 3D scanning of museum collections, Gibbons has shared Smithsonian discoveries with the world. He is most happy when his passions for ornithology and journalism combine, making him the go-to man for the latest in Smithsonian bird research. Much of the most current Gibbons bird story is provided below. “You watch the weather forecast, gear up with hat, coat, scarf and gloves, but you still get cold after just a short time in the snow and wind. If it’s such a challenge for humans to stay warm outside, how do birds―especially the little delicate guys like chickadees and titmice―survive the single-digit temperatures and whipping winds of winter?

Using Optical Tweezers and Custom Microfluidic Chips, Young Swedish Scientist Demonstrates Glycolysis-Related Oscillations in Single, Isolated Cells; Brenner's Vision Finally Being Realized

A better understanding of the way metabolism works may, in the long run, make it easier to find new medicines for diseases such as diabetes. By combining different methods taken from physics, the freshly-minted Ph.D. researcher Anna-Karin Gustavsson, of the University of Gothenberg, Sweden, has been able to study metabolism in individual cells. The objective of these research studies is to see what cells do when there are changes in their environment. In her work, Dr. Gustavsson has created a specially designed microfluidic chip containing channels through which different solutions are able to flow. With the aid of optical tweezers, a highly focused laser beam, she captures individual cells for placing at the point where the channels intersect. This intersection between the channels is where the cells' immediate environment can change very rapidly. “By using a microscope, I have been able to monitor what the cells do when there are changes in their environment. I discovered that the concentration of molecules in the metabolism of individual cells while these [cells] are breaking down sugars could, under specific conditions, be made to rock; i.e., oscillate.” Up to this moment, it had never been possible to achieve the monitoring of oscillations in individual cells, despite there being many publications describing attempts to do this in high-ranking journals. “The ability to confirm that this [does indeed] take place in individual, isolated cells is something new,” says Dr. Gustavsson, who, together with her colleagues has also produced a mathematical model for the behavior of the cells during glycolysis, the process whereby sugars are broken down in our cells to create energy. In both human cells and yeast cells, which are the focus of Dr.