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Archive - 2016

December 28th

Bromodomain Inhibitor Shrinks Testicular Tumors in New Study

Testicular cancer is the most common malignant tumor disease in men between 20 and 40 years of age. It can usually be treated well. In some cases, however, the cancer hardly responds or does not respond at all to treatment. A substance that was originally destined to be an innovative contraceptive is offering new hope in these cases. The experimental drug with the cryptic name JQ1 blocks sperm maturation and was discussed to be a male contraceptive. Instead, it may be suitable for cancer therapy. JQ1 belongs to a new class of drugs (bromodomain inhibitors) with far-reaching abilities: its members fundamentally influence which genes in the cell are active and which are not. The hereditary material DNA is similar to an extremely long strip of Morse code, on which the assembly instructions for the cellular molecules are found. To fit into the cell nuclei, this strip of Morse code is wrapped around small protein balls at regular intervals - the histones. Histones and DNA together resemble a string of pearls. However, the histones do not only play a structural role. They also feature chemical tags - called methyl or acetyl groups. These tags signal to the synthesis machinery in the cell whether the strip of Morse code should be read at this point or not. "JQ1 inhibits those proteins that read these histone marks and thus changes the gene activity in the cell," explains Professor Hubert Schorle from the Institute for Pathology at the University of Bonn in Germany. The cancer cells are very sensitive to these changes: they activate a suicide program, called apoptosis. "In a testicular cancer mouse model, the tumors began to shrink after administering JQ1," explains the lead author of the study, Dr. Sina Jostes.

Experimental Therapy for Prader-Willi Syndrome Shows Promise in Mice

Drugs capable of activating silenced genes improve survival and growth outcomes in a mouse model of Prader-Willi syndrome (PWS), a rare and incurable childhood disease, according to a study funded by the National Institutes of Health (NIH). PWS occurs in 1 in every 15,000 to 25,000 live births, equally affecting boys and girls. The genetic disorder can lead to life-threatening obesity in children. It also can cause physical, intellectual, behavioral and psychiatric symptoms. Genetic information passes to a child in a pair of chromosomes--one from the father and one from the mother. PWS is caused by genetic changes along a section of chromosome 15 called the Prader-Willi critical region. Under normal circumstances, genes in this region are inactive, or silenced, on maternal chromosome 15 but active on paternal chromosome 15. In PWS, however, the critical region on the paternal chromosome either is inactive or missing. Infants with PWS fail to thrive and have altered metabolisms and trouble feeding. However, as they get older, they become compulsive overeaters. In the study, researchers found two drugs, called UNC0638 and UNC0642, capable of activating maternal PWS genes in cells from a patient. They targeted maternal genes because, unlike paternal genes, they are consistently available in PWS patients. The study team then tested UNC0642, which had more favorable pharmacological features, in a mouse model of PWS. These mice grow poorly, like infants with PWS, and do not survive. The experimental drug activated maternal PWS genes, and the treated mice had better growth and weight gain than untreated mice, with 15 percent surviving to adulthood without serious side effects.

December 27th

New Study Sheds Light on the “Gray Zone” of Speciation

There is usually no ambiguity about species delineation when distant lineages are compared. For instance, there is no doubt that dogs and cats belong to two different species. However, such distinction becomes less clear-cut when comparing recently diverged groups of individuals, between which interbreeding is still to some extent possible. This is the paradox of speciation: a gradual, continuous process that ultimately leads to distinct biological entities. New research published online on December 27, 2016 in the open-access journal PLOS Biology from French biologists Camille Roux, Christelle Fraïsse, Jonathan Romiguier, Yoann Anciaux, Nicolas Galtier and Nicolas Bierne (CNRS - University Montpellier) characterizes the ability of populations to interbreed and exchange genes as a function of the level divergence of their genomes. These authors improved existing methods, allowing them to infer the history of speciation by modeling the confounding effect of natural selection, drift, and migration rates, thereby accounting for the differing patterns of variation seen in different parts of the genome. The PLOS Biology article is titled “Shedding Light on the Grey Zone of Speciation along a Continuum of Genomic Divergence.” The new method was applied to a large genomic dataset consisting of 61 pairs of populations or species of animals. Their analysis uncovered a zone of intermediate molecular divergence, between 0.5% and 2% of differences between genomes, in which the transition from one to two species proceeds - the so-called "gray zone of speciation." Pairs of populations/species falling in this zone are typically characterized by a semi-permeable genome: some genes are freely exchanged between populations, but some are blocked and contribute to isolation - the so-called species barriers.

Engineers Create Programmable Silk-Based Materials With Embedded, Pre-Designed Functions; Process Enables Creation of Mechanical Components with Functionality, Such As Surgical Pins That Change Color with Strain

Tufts University engineers have created a new format of solids made from silk protein that can be pre-programmed with biological, chemical, or optical functions, such as mechanical components that change color with strain, deliver drugs, or respond to light, according to a paper published online on December 27, 2016 in PNAS. The article is titled “Directed Self-Assembly of Silk Fibroin into Bulk Materials: Programming Function into Mechanical Forms from the Nano- to Macroscale.” Using a water-based fabrication method based on protein self-assembly, the researchers generated three-dimensional bulk materials out of silk fibroin, the protein that gives silk its durability. Then they manipulated the bulk materials with water-soluble molecules to create multiple solid forms, from the nano- to the micro-scale, that have embedded, pre-designed functions. For example, the researchers created a surgical pin that changes color as it nears its mechanical limits and is about to fail, functional screws that can be heated on demand in response to infrared light, and a biocompatible component that enables the sustained release of bioactive agents, such as enzymes. Although more research is needed, additional applications could include new mechanical components for orthopedics that can be embedded with growth factors or enzymes, a surgical screw that changes color as it reaches its torque limits, hardware such as nuts and bolts that sense and report on the environmental conditions of their surroundings, or household goods that can be remolded or reshaped. Silk's unique crystalline structure makes it one of nature's toughest materials. Fibroin, an insoluble protein found in silk, has a remarkable ability to protect other materials while being fully biocompatible and biodegradable.

Bat Calls Contain Wealth of Discernible Information; Analyzing Some 15,000 Bat Vocalizations, Researchers Identify Speakers, Objectives, and Contexts of Bat Conversations

Bats, like humans, are extremely social mammals. They enjoy an average lifespan of 20-30 years, settle in large colonies, and rely heavily on social interactions for their survival, using vocalizations -- or calls -- for communication. There is very little known about the purpose and content of these noises. A new Tel Aviv University (TAU) study published in Scientific Reports extracts critical information from bat vocalizations to offer a rare, informative look into the world of bat communication. The new research, led by Professor Yossi Yovel of the Department of Zoology at TAU's Faculty of Life Sciences, delves into the veritable cacophony emitted by bats to identify concrete evidence of a socially sophisticated species that learns communication, rather than being born with a fixed set of communication skills. "When you enter a bat cave, you hear a lot of 'gibberish,' a cacophony of aggressive bat noise - but is this merely 'shouting' or is there information amid the noise?" asked Prof. Yovel. "Previous research presumed that most bat communication was based on screaming and shouting. We wanted to know how much information was actually conveyed -- and we wanted to see if we could, in fact, extract that information." The open-access Scientific Reports article was published online on December 22, 2016, and is titled “Everyday Bat Vocalizations Contain Information About Emitter, Addressee, Context, and Behavior.” For the purpose of the research, Mor Taub and Yosef Prat, students in Professor Yovel's lab, recorded the sounds emitted by 22 Egyptian fruit bats in TAU's "bat cave" over the course of 75 days. The authors then assembled a dataset of approximately 15,000 vocalizations, which represented the full vocal repertoire the bats used during the experiment.

Sugar Element of Keratan Sulfate Halts Progress of Emphysema

Using a mouse model, scientists from the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology and a number of other institutes have identified a sugar molecule that reduced the inflammatory response and progress of emphysema, a common component of chronic obstructive pulmonary disease (COPD). According to Naoyuki Taniguchi, Ph.D., the leader of the group, this discovery could lead to the development of drugs based on glycans—biological sugar molecules—for the treatment of diseases such as COPD, which is the fourth leading cause of death worldwide. As part of the research group’s work to explore the roles of sugar molecules in health and disease, they found that keratan sulfate, a large negatively charged saccharide found in the small airway of the lung, is decreased in mice that have been exposed to cigarette smoke. The scientists wondered if this decrease might be associated with the damage that smoking causes to the lung. Dr. Taniguchi says, “We are not absolutely sure of the mechanism through which smoking leads to a reduction in keratan sulfate, but felt that clearly the reduction is important in thinking about glycan-based strategies for combating emphysema and COPD.” They wondered whether the keratan sulfate might be playing a protective role in COPD. To test the hypothesis, they prepared a repeating disaccharide element of keratan sulfate, named L4, and administered it into two mouse models of emphysema—one a model of emphysema triggered by the enzyme elastase, and the other an exacerbation of smoking-induced emphysema triggered by LPS, a toxin found in bacterial cell walls.

2016 Winners of FASEB BioArt Competition Announced

On November 22, 2016, the Federation of American Societies for Experimental Biology (FASEB) was pleased to announce the winners of its fifth annual BioArt competition. This year’s 10 winning images and three videos represent a wide range of research in the biomedical and life sciences, from technology that may aid in recovery from spinal cord injury to a portrait of the New York City skyline “printed” in yeast. Winning entries were unveiled on the FASEB’s web site and will be exhibited at the National Institutes of Health. “It’s so important to seize opportunities to share the wonder of discovery with the public. The BioArt images showcase the beauty of scientific research and are a great place to start the conversation,” said Hudson Freeze, Ph.D., FASEB President. The Image winners are: “Skyline of New York City” created by “printing” nanodroplets of yeast — Michael Shen, Jasmine Temple, Leslie Mitchell, and Jef Boeke, New York University School of Medicine, Nick Phillips, James Chuang, and Jiarui Wang, Johns Hopkins University; “Immune cells battling a urinary tract infection”— Valerie O'Brien, Matthew Joens, Scott J. Hultgren, and James A.J. Fitzpatrick, Washington University in St. Louis; “Nerve cells growing on a nanofiber gel that may aid recovery from spinal cord injury” (image here)—Mark McClendon, Zaida Alvarez Pinto, and Samuel I.

December 26th

Warning of Toxic Algal Blooms Before They Develop

Toxic algae blooms in lakes and reservoirs are highly destructive, resulting in fish kills and toxicity risks to wildlife, livestock -- and even humans. But their development is difficult to predict. Resource managers would like to stop such events in their tracks, before blooms cross a threshold and grow to the point of damaging a body of water. A new study, published online on December 26, 2016 in PNAS, demonstrates that automated monitoring systems that identify "regime shifts" -- such as rapid growth of algae and then depletion of oxygen in the water -- can successfully predict full-scale algae blooms in advance, and help resource managers avert their development. Prior studies indicated that this might be possible, but the researchers have now proven this is so during experiments in an isolated lake in Michigan. The researchers caused an algae bloom in the experimental lake by gradually enriching it with nutrients, similar to the flow of nutrients that might occur in a lake downstream of an agricultural area or city. As they did this, they also closely monitored a nearby un-enriched lake, and a third continuously enriched "reference" lake. Once the gradually enriched experimental lake exceeded pre-set boundaries, the researchers halted the flow of nutrients. They found that algae growth quickly declined, resulting in conditions similar to those in the un-enriched lake. Meanwhile, a large algae bloom formed in the continuously enriched lake. "Our system detected early warnings more than two weeks prior to the bloom," said University of Virginia environmental scientist Michael Pace, Ph.D., who led the study. "In the experiment where nutrient inputs were cut off when early warnings occurred, the algae bloom was reversed.

Key Protein May Have Salutary Effects in Neurodegenerative Diseases, Such As Parkinson’s, Huntington’s, Alzheimer’s, and ALS

New details learned about a key cellular protein could lead to treatments for neurodegenerative diseases, such as Parkinson's, Huntington's, Alzheimer's, and amyotrophic lateral sclerosis (ALS). At their root, these disorders are triggered by misbehaving proteins in the brain. The proteins misfold and accumulate in neurons, inflicting damage and eventually killing the cells. In a new study, researchers in the laboratory of Steven Finkbeiner, M.D., Ph.D., at the Gladstone Institutes used a different protein, Nrf2, to restore levels of the disease-causing proteins to a normal, healthy range, thereby preventing cell death. The researchers tested Nrf2 in two models of Parkinson's disease: cells with mutations in the proteins LRRK2 and α-synuclein. By activating Nrf2, the researchers turned on several "house-cleaning" mechanisms in the cell to remove excess LRRK2 and α-synuclein. "Nrf2 coordinates a whole program of gene expression, but we didn't know how important it was for regulating protein levels until now," explained first author Gaia Skibinski, Ph.D., a staff research scientist at Gladstone. "Overexpressing Nrf2 in cellular models of Parkinson's disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we've found." In the study, published in the early online edition of PNAS, the scientists used both rat neurons and human neurons created from induced pluripotent stem cells. They then programmed the neurons to express Nrf2 and either mutant LRRK2 or α-synuclein. Using a one-of-a-kind robotic microscope developed by the Finkbeiner laboratory, the researchers tagged and tracked individual neurons over time to monitor their protein levels and overall health. They took thousands of images of the cells over the course of a week, measuring the development and demise of each one.