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A new polymer on the basis of a trick used by mussels has been developed by the Wageningen PhD student Juan Yang. The polymer should be able to let water-based paint flow better and produce water resistant coatings. Yang will defend her PhD-thesis on 12 January at Wageningen University. Water-based paint is better for humans and the environment compared to paint with chemical solvents. Paint based on water, however, still does not carry the same properties as those based on chemicals. The paint flows differently than traditional alkyd systems for example. Giving a water-based product water-repellent characteristics is also no sinecure. Yang therefore has been looking for a polymer that dissolves in water but creates water resistance after application in her PhD research. She was inspired by the mussel. Being under water, a mussel can still attach itself to surfaces. The mussel does so by first excreting a thread of a specific type of protein from its foot. A reaction then occurs in these proteins, whereby the thread losses the ability to dissolve in water within a minute and becomes strong and tough. Much research already has been done on the chemistry of these proteins because of the adhesion properties, but not so much on the insolubility in water. Yang is unravelling this characteristic in her dissertation Mussel-inspired chemistry and its applications. The Wageningen PhD student was able to create a polymer with this property that reacts in water. One of the requirements for the toughening characteristic of this polymer is the de-acidification of its surroundings. This proof of principle offers a lead of departure for the paint industry to improve water based paints. The effects of the polymer on other paint components, such as pigment and other properties, needs further research. The reactive polymer has the potency for application in other situations. For instance, mussel-inspired chemistry is suitable for the creation of antimicrobial coatings. Explore further: Industry's first use of water-based paint for plastic chassis ICT equipment More information: Juan Yang et al. A clear coat from a water soluble precursor: a bioinspired paint concept, J. Mater. Chem. A (2016). DOI: 10.1039/C5TA09437B

For the first time, researchers at the Stowers Institute have mapped where recombination occurs across the whole genome of the fruit fly Drosophila melanogaster after a single round of meiosis. Their results indicate that separate mechanisms position the two main kinds of recombination events, crossovers and non-crossovers. The findings, which are reported online ahead of print in the journal Genetics, give important insights into the understanding of chromosomes and the mechanisms of inheritance. "It is amazing to me that more than 100 years after the discovery of genetic recombination in flies, we are only starting to understand just how these events are distributed," says R. Scott Hawley, Ph.D., an investigator at the Stowers Institute and senior author of the study. This genetic recombination takes place during a specialized form of cell division called meiosis. During meiosis, the cell copies all its chromosomes, pairs them up, and shuffles sections of genetic material between the arms of the paired or homologous chromosomes. This shuffling can occur one of two ways. In crossover events, large tracts of DNA are exchanged, like two people swapping playing cards. In non-crossover events, smaller pieces of DNA are copied from one arm and pasted onto another, like the crown from the King of Hearts in one player's hand suddenly appearing atop another player's King of Spades. Once the deck is sufficiently shuffled, the cell divides, and then divides again to create four cells, each carrying only one copy of the organism's genome. Recombination ensures that each gamete ends up with a unique copy of every chromosome, but when the process goes awry, it can result in chromosomal abnormalities. For example, improperly placed crossovers or the complete lack of crossovers on chromosome 21 are a major cause of trisomy 21 or Down Syndrome in humans. With one exception, all previous genetic studies of recombination in Drosophila have focused either on a single chromosome arm or on groups of flies pooled together. In this study, the Stowers researchers wanted to determine how both crossovers and non-crossovers are distributed across all five major chromosomal arms of fruit flies. Crossovers are relatively easy to identify because they involve entire chromosomal arms or parts of arms encompassing thousands of base pairs, the A's, C's, T's, and G's that make up DNA. But non-crossovers are tougher to spot, because they only involve a few hundred of those letters. Therefore, Danny Miller, an MD-PhD student at the University of Kansas Medical Center who is conducting his doctoral research in the Hawley lab, had to rely on whole genome sequencing and new computer algorithms to pinpoint the locations of both kinds of events. Miller, lead author of the study, says the project gave him the opportunity to delve into the genetic principles that underlie human health and disease. "I would like to keep doing research as a physician-scientist when I graduate," says Miller, who plans to pursue a specialty in pediatric oncology or pediatric medical genetics. "I want to have a good foundational understanding of genetics. Some people may gloss over these basic questions, instead of looking at the data and trying to answer them." In this study alone, Miller generated a vast amount of data. First, he mated two genetically distinct varieties of fruit flies, known to differ at roughly 500,000 different spots in their genetic code. Miller then sequenced the entire genomes of the resulting 196 progeny and wrote a custom computer program that could scan the 160 million bases of each fruit fly genome for evidence of recombination. The approach identified a total of 541 crossovers and 291 non-crossovers. Unlike crossovers, which are generally distributed over the distal two-thirds of the chromosome arms, the non-crossovers were spread uniformly among the five major chromosome arms. Non-crossovers formed in places where crossovers rarely do, such as near the knotty centromere that ties the arms of chromosomes together. And they popped up close together, in contrast to crossovers that respond to a phenomenon known as interference when they try to form near other crossovers. The researchers discovered that the number of crossovers varied widely not just according to their position along the chromosome arm, but also from chromosome to chromosome. For example, they identified five double crossovers on one arm of chromosome 2—fewer than expected. "The finding gives credence to a certain kind of lore that has circulated in the field—the idea that each of the chromosomal arms was behaving a little differently—but nobody really knew for sure because nobody had looked at each of the arms in the same experiment," says Hawley. "What we found was that each chromosome has its own rules for making sure it gets its crossovers exactly where it wants them." In addition to crossovers and non-crossovers, the researchers also noticed evidence of duplications and deletions caused by the presence of transposons, a special class of genetic elements that can jump from one area in the genome to another. These transposable elements are a serious problem for the meiotic machinery because they can skew the pairing of homologous chromosomes, triggering duplications or deletions of genetic material that affect the viability of an organism. The study identified transposable elements in 1-2 percent of the genome, in line with previous reports.

The feat, reported in the January 15 issue of the journal Science, has already enabled pharma giant Pfizer to proceed with the evaluation of a promising cancer drug candidate that otherwise could not have been made in sufficient quantities. "People from other pharma companies who have seen early drafts of this paper can't get their hands on the supporting information fast enough," said senior investigator Phil S. Baran, the Darlene Shiley Professor of Chemistry at TSRI. "I expect that every company in the business of making drugs will be using this chemistry soon." The technique, known as "strain-release amination," also should enable the easier construction of a variety of molecules besides pharmaceuticals, including molecular probes for basic biology studies, plastics, and other materials made from organic compounds. The project began with Pfizer's request for help in synthesizing a molecule known as bicyclo[1.1.1]pentan-1-amine, which it needed to make the cancer drug candidate. The Baran laboratory frequently collaborates with Pfizer and other pharma companies to solve tough problems in medicinal and process chemistry. Traditional methods of synthesizing bicyclo[1.1.1]pentan-1-amine left much to be desired. "Most of the previously published synthetic routes require three to five steps with toxic reagents and yield only tens of milligrams," said Ryan Gianatassio, a PhD student at TSRI who was co-first author of the study. Pfizer needed kilograms of bicyclo[1.1.1]pentan-1-amine for preclinical studies of its cancer drug candidate, and the company had had to shelve the drug's development until it could make that much of it. "We built a team of expert synthetic chemists to solve this challenging problem, including chemists from Phil Baran's lab and Pfizer's synthetic and process chemistry groups," said Michael R. Collins, a senior principal scientist at the drug company's La Jolla Laboratories. Baran and his team, including Gianatassio and co-first author TSRI Research Associate Justin M. Lopchuk were able to solve the supply problem for this building block, enabling a relatively quick and easy synthesis from a readily available starting compound. "Using our procedure, Pfizer easily produced over 100 grams, and they are now in a position to scale that up further and re-start that delayed drug development program," said Gianatassio. Baran realized that the new method could have much broader applications. Bicyclo[1.1.1]pentan-1-amine is a "spring-loaded" or "strained ring" molecule, in which carbon atoms are arranged in rings at odd angles, with relatively large bond energies. Pharmaceutical chemists know that adding such a structure to a drug molecule sometimes greatly improves the drug's properties: making it more absorbable by the gut, for example, or enabling it to resist breakdown by enzymes in the body so that it works therapeutically for longer periods. The problem has been that, using traditional methods, the insertion of these small structures into larger drug molecules is tricky—so much so that chemists often have had to redesign the entire synthesis around the small added structure. "The way they've been doing it is like decorating a Christmas tree by putting the ornaments in place first and then growing the tree around it," said Baran. "In many cases they just won't pursue that because of the time and labor it would take." Baran and his team showed that they could use their new method to directly append a strained-ring molecule favored by pharmaceutical chemists—propellane, so-called because its structure resembles a propeller—to existing larger drug molecules. "We can make that five-carbon ring structure of propellane click onto a wide range of drug molecules of a type known as secondary amines—we call that a propellerization reaction," said Lopchuck. "In fact, starting with a stock solution of the propellane, we can use high-throughput techniques to quickly elaborate a matrix of amine-containing compounds with the bicyclopentyl moiety, instead of painstakingly synthesizing the compounds one at a time," Collins said. The team went on to demonstrate similar direct modifications using two other strained-ring structures, azetidine and cyclobutane. The TSRI researchers also found that they could use the new method to attach molecules very precisely and selectively to specific amino acids on proteins, thus in principle enabling the creation of new biologic drugs as well as new reagents that would be useful in basic biology research. "This technique opens up a world of chemistry that academic and commercial laboratories have really wanted to look into but couldn't, due to the technical obstacles," said Baran. The supporting, publicly available information on strain-release amination is meant to enable chemists to start using the technique right away. A behind-the-scenes account and high-definition photos of the new reaction setup can be found on the Baran Lab Blog, Open Flask. "This can be considered rapid bench to bedside chemistry because it is fundamental science that will have a positive impact on human medicine in a short period of time," Baran said. Explore further: Scientists find easier, cheaper way to make a sought-after chemical modification to drugs

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Site: www.cemag.us

3D printing techniques have quickly become some of the most widely used tools to rapidly design and build new components. A team of engineers at the University of Bristol has developed a new type of 3D printing that can print composite materials, which are used in many high performance products such as tennis rackets, golf clubs, and airplanes. This technology will soon enable a much greater range of things to be 3D printed at home and at low-cost. The study published in Smart Materials and Structures creates and demonstrates a novel method in which ultrasonic waves are used to carefully position millions of tiny reinforcement fibers as part of the 3D printing process. The fibers are formed into a microscopic reinforcement framework that gives the material strength. This microstructure is then set in place using a focused laser beam, which locally cures the epoxy resin and then prints the object. To achieve this the research team mounted a switchable, focused laser module on the carriage of a standard three-axis 3D printing stage, above the new ultrasonic alignment apparatus. Tom Llewellyn-Jones, a PhD student in advanced composites who developed the system, says, “We have demonstrated that our ultrasonic system can be added cheaply to an off-the-shelf 3D printer, which then turns it into a composite printer.” In the study, a print speed of 20mm/s was achieved, which is similar to conventional additive layer techniques. The researchers have now shown the ability to assemble a plane of fibers into a reinforcement framework. The precise orientation of the fibers can be controlled by switching the ultrasonic standing wave pattern mid-print. This approach allows the realization of complex fibrous architectures within a 3D printed object. The versatile nature of the ultrasonic manipulation technique also enables a wide-range of particle materials, shapes and sizes to be assembled, leading to the creation of a new generation of fibrous reinforced composites that can be 3D printed. Bruce Drinkwater, Professor of Ultrasonics in the Department of Mechanical Engineering, says, “Our work has shown the first example of 3D printing with real-time control over the distribution of an internal microstructure and it demonstrates the potential to produce rapid prototypes with complex microstructural arrangements. This orientation control gives us the ability to produce printed parts with tailored material properties, all without compromising the printing.” Dr. Richard Trask, Reader in Multifunctional Materials in the Department of Aerospace Engineering, adds, “As well as offering reinforcement and improved strength, our method will be useful for a range of smart materials applications, such as printing resin-filled capsules for self-healing materials or piezoelectric particles for energy harvesting.” Release Date: January 18, 2016 Source: University of Bristol

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Site: www.biosciencetechnology.com

Located in southern Tunisia, Tataouine is a desert province located in a region marred by political conflict. In 2009, a team led by Univ. of Bologna’s Prof. Federico Fanti began working to unearth the fossilized remnants of the region’s prehistoric ecosystem. In 2014, researchers discovered the skeleton of an ancient behemoth, a 35-ft long marine crocodile named Machimosaurus rex. Marine crocodiles were thought to have inhabited the seas and coastal regions of the late Jurassic period, approximately 150 million years ago. However, Machimosaurus was dated to 130 million years ago, which coincides with the Cretaceous period. According to the Univ. of Alberta, Machimosaurus’ closest relative lived 30 million years earlier in the ancient seas near what is now England. According to the Univ. of Bologna, Machimosaurus was an ambush predator that occupied a lagoon-like environment, which was located between the inland Saharan regions and the ancient Tethys Ocean. Its skull was around 5.5 ft in length, larger than that of a Tyrannosaurus rex, and it boasted blunt bullet-shaped teeth with wrinkles. Researchers believe the teeth were used to crush the shells of marine turtles. Turtle fossils have been found associated with the crocodile skeleton. Research on their findings was published in Cretaceous Research. In 2015, Fanti and Univ. of Alberta PhD student Tetsuto Miyashita were scheduled to return to Tunisia to excavate the rest of Machimosaurus’ skeleton. While their plans were hindered by political turmoil, they decided to return to the region regardless. In Tunisia’s capital Tunis, the team cleaned the skull for three days and studied it for one. Miyashita commented that it was enough observation to convince the team the specimen was a new species. The team remains hopeful that in the future they’ll make it back to the region to excavate the rest of the skeleton. According to researchers, the find is bringing into question how widespread the Jurassic-Cretaceous extinction was. The researchers believe Machimosaurus’ skeleton supports that the end-Jurassic extinction primarily affected biota in the supercontinent Laurasia.

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