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February 26th, 2016

Ultra-Thin Patterned Graphene Sheets, Inspired by Moths’ Eyes, May Help Power Future Smart Technologies, Nanotextured Sheets Absorb 95% of Incident Light

New research published online on February 26, 2016 in Science Advances has shown how graphene can be manipulated to create the most light-absorbent material for its weight, to date. This nanometer-thin material will enable future applications such as “smart wallpaper”that could generate electricity from waste light or heat, and power a host of applications within the growing “internet of things.” Using a technique known as nanotexturing, which involves growing graphene around a textured metallic surface, researchers from the University of Surrey's Advanced Technology Institute took inspiration from nature to create ultra-thin graphene sheets designed to more effectively capture light. Just one atom thick, graphene is very strong, but traditionally inefficient at light absorption. To combat this, the team used the nano-patterning to localize light into the narrow spaces between the textured surface, enhancing the amount of light absorbed by the material by approximately 90%. The open-access Science Advances article is titled “Ultra-Broadband Light Trapping Using Nanotextured Decoupled Graphene Multilayers.” "Nature has evolved simple, yet powerful,adaptations, from which we have taken inspiration in order to answer challenges of future technologies," explained Professor Ravi Silva, Head of the Advanced Technology Institute. "Moths' eyes have microscopic patterning that allows them to see in the dimmest conditions. These work by channelling light towards the middle of the eye, with the added benefit of eliminating reflections, which would otherwise alert predators of their location. We have used the same technique to make an amazingly thin, efficient, light-absorbent material by patterning graphene in a similar fashion."

Cryo-Electron Microscopy Analysis of Coronavirus Spike Protein May Point Way to Effective Vaccine Strategies

High-resolution cryo-electron microscopy and supercomputing have now made it possible to analyze, in detail, the infection mechanisms of coronaviruses. These viruses are notorious for attacking the respiratory tract of humans and animals. A research team that included scientists from the University of Washington (UW), the Pasteur Institute, and the University of Utrecht has obtained an atomic model of a coronavirus spike protein that promotes entry into cells. Analysis of the model is providing ideas for specific vaccine strategies. The study results are outlined in a study published online in Nature on February 8, 2016. David Veesler, UW Assistant Professor of Biochemistry, headed the project. The article is titled “Cryo-Electron Microscopy Structure of a Coronavirus Spike Glycoprotein Trimer.” Coronaviruses, with their crowns of spikes, are responsible for almost a third of mild, cold-like symptoms and atypical pneumonia worldwide, Dr. Veesler explained. But deadly forms of coronaviruses emerged in the form of SARS-CoV (severe acute respiratory syndrome coronavirus) in 2002 and of MERS-CoV (Middle East respiratory syndrome coronavirus) in 2012 with fatality rates between 10 percent and 37 percent. These outbreaks of deadly pneumonia showed that coronaviruses can be transmitted from various animals to people. Currently, only six coronaviruses are known to infect people, but many coronaviruses naturally infect animals. The recent deadly outbreaks resulted from coronaviruses overcoming the species barrier. This suggests that other new, emerging coronavirus with pandemic potential are likely to emerge. There are presently no approved vaccines or antiviral treatments against SARS-CoV or MERS-CoV.

Elevated Levels of Certain GEF Proteins Associated with Shorter Progression-Free Survival in Metastatic Colorectal Cancer

Researchers at University of California (UC), San Diego School of Medicine and Moores Cancer Center, together with colleagues in Spain and Germany, have unraveled how elevated levels of particular proteins in cancer cells trigger hyperactivity in other proteins, fueling the growth and spread of a variety of cancers. The findings are published in the February 26, 2016 online publication of Scientific Reports. The open-access article is titled “Prognostic Impact of Modulators of G proteins in Circulating Tumor Cells from Patients with Metastatic Colorectal Cancer.” Specifically, the international team, led by senior author Pradipta Ghosh, MD, Associate Professor at UC San Diego School of Medicine, found that increased levels of expression of some members of a protein family called guanine nucleotide exchange factors (GEFs) triggered unsuspected hyperactivation of G proteins and subsequent progression or metastasis of cancer. The discovery suggests GEFs offer a new and more precise indicator of disease state and prognosis. "We found that elevated expression of each GEF is associated with a shorter progression-free survival in patients with metastatic colorectal cancer," said Dr. Ghosh. "The GEFs fared better as prognostic markers than two well-known markers of cancer progression and the clustering of all GEFs together improved the predictive accuracy of each individual family member." In recent years, circulating tumor cells (CTCs), which are shed from primary tumors into the bloodstream and act as seeds for new tumors taking root in other parts of the body, have become a prognostic and predictive biomarker. The presence of CTCs is used to monitor the efficacy of therapies and to detect early signs of metastasis. But counting CTCs in the bloodstream has limited utility, said Dr. Ghosh.

Preventing the Unfolding of Proteins: Covalently Bonded Polymers Can Theoretically Stabilize Small Proteins

When the body loses its ability to fold proteins into the correct shapes, the result can be irreversible and tragic. The accumulation of unfolded or misfolded proteins in the brain causes many devastating neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s disease). In order to maintain their functions, structural proteins and engineered, protein-based materials need to avoid unfolding even under large mechanical stresses. Scientists, therefore, are exploring ways to design proteins that can survive extreme mechanical insults. Now, Northwestern Engineering's Sinan Keten has theoretically demonstrated that small proteins can be reinforced with covalently bonded polymers against mechanical unfolding. His computational model illustrates strategies for using this polymer conjugation to prevent proteins from rapidly unfolding even when stretched or pulled. "If you apply a stress to a protein, we know it will start to unfold," said Dr. Keten, Assistant Professor of Mechanical, Civil, and Environmental Engineering at Northwestern. "Given that proteins are subject to mechanical forces in the body and in all applications, it will be useful to reinforce them in this way." Dr. Keten's research is featured on the cover of the February issue of the journal ACS Nano. Elizabeth DeBenedictis, a Ph.D. student in Keten's lab, and Elham Hamed, Ph.D., a former postdoctoral fellow in Keten's lab, are the paper's first authors. DeBenedictis also created the diagram that was used for the journal's cover image. The ACS Nano article is titled “Mechanical Reinforcement of Proteins with Polymer Conjugation.”

Non-Integrating Viral Vector Delivers Chemotherapy-Sensitizing Gene to Pancreatic Cancer Cells

A novel HIV-based lentiviral vector can introduce a gene to pancreatic tumor cells that makes them more sensitive to the chemotherapeutic drug gemcitabine, without integrating into cellular DNA. This integrase-defective lentiviral delivery system greatly reduces the risk of insertional mutagenesis and replication-competent lentivirus production, as described in a new study published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The full article is available free to read on the Human Gene Therapy website until March 31, 2016. The article, titled "Initial Characterization of Integrase-Defective Lentiviral Vectors for Pancreatic Cancer Gene Therapy," ( is part of a special issue of Human Gene Therapy focusing on advances in gene and cell therapy research in France. The issue has been coordinated by guest editors Nathalie Cartier, M.D., Director of Research, INSERM, Paris, and President, European Society of Gene and Cell Therapy (ESGCT), and Pierre Cordelier, Ph.D., Senior Researcher, INSERM, Toulouse, France, and President, French Society of Cell and Gene Therapy (SFTCG). The special issue will be distributed at the SFTCG meeting, March 9-11, in Marseilles, France. In the referenced article, Naima Hanoun, Marion Gayral, Adeline Pointreau, Louis Buscail, and Pierre Cordelier, of INSERM (Toulouse), Université Toulouse III-Paul Sabatier, and CHU Toulouse-Rangueil, present work demonstrating that an integrase-deficient lentiviral vector can deliver the gene that codes for the DCK protein to pancreatic adenocarcinoma-derived cells in the laboratory with high efficacy. These cells are typically very resistant to gene transfer. Deficiency of DCK protein is commonly associated with resistance to anti-cancer chemotherapy.

E. coli Bacteria Engineered to Produce Morphine Precursor; Approach May Make Pain-Killer Production More Efficient & Less Costly, with Minimal Risk of Unregulated Use

Japanese bioengineers have tweaked Escherichia coli genes so that the bacteria pump out thebaine, a morphine precursor that can be modified to make painkillers. The genetically modified E. coli produces 300 times more thebaine with minimal risk of unregulated use compared to a recently developed method involving yeast. "Morphine has a complex molecular structure; [and] because of this, the production of morphine and similar painkillers is expensive and time-consuming," said study author Fumihiko Sato, Ph.D., of Kyoto University in Japan. "But with our E. coli, we were able to yield 2.1 milligrams of thebaine in a matter of days from roughly 20 grams of sugar, as opposed to 0.0064 mg with yeast." Morphine is extracted from poppy sap in a process that results in opiates such as thebaine and codeine. Other synthetic biologists have recently engineered the yeast genome so that it produces opiate alkaloids from sugar. There were ethical concerns with this approach, however, including a risk that the pain-killing molecules could be produced easily and in unregulated ways, provided that one has access to the necessary yeast strain. With E. coli, Dr. Sato says that such production risk is insignificant. "Four strains of genetically modified E. coli are necessary to turn sugar into thebaine," explains Dr. Sato. "E. coli are more difficult to manage and require expertise in handling. This should serve as a deterrent to unregulated production." In 2011, Dr. Sato and colleagues engineered E. coli to synthesize reticuline, another morphine precursor that appears earlier in the transformation process than thebaine. In the new system, the team added genes from other bacteria and enzyme genes from opium poppies, Coptis japonica, and from the model plant Arabidopsis.

February 25th

X-Ray Crystallography of Hanta Virus Protein Reveals Targets for Drug Design

Bank voles are small rodents that are not dangerous by themselves, but their excreta can contain one of the dangerous hantaviruses. While bank voles are unaffected by the infection, hantaviruses can cause potentially fatal diseases in humans for which no treatments exist. In central and northern Europe, infection is accompanied by fever, headache, or even renal failure. The strain that occurs in East Asia -- the Hantaan virus -- is even more dangerous: up to five percent of infected patients die of hemorrhagic fever, renal failure, or severe respiratory disorders. Dr. Daniel Olal and Dr. Oliver Daumke of the Max Delbruck protein is therefore an ideal target structure for future drugs. "Our structure could be useful for Center (MDC) for Molecular Medicine in Berlin have now analyzed the nucleoprotein of the Hantaan virus by means of X-ray crystallography and identified its three-dimensional structure. Dr. Olal and Dr. Daumke have worked out how individual nucleoproteins oligomerize in the presence of RNA molecules, and they have found hexameric circular complexes. "We already know about cellular defense mechanisms that inhibit viral growth. We think that the circular structures we have identified could play a part in this," says Dr. Olal. The nucleoprotein plays an important part in replication of the viral genome. If its function is disrupted, the cell cannot produce functional virus particles. This the design of small molecules that specifically block the nucleoprotein," says Dr. Olal. The researchers have identified three binding pockets on the surface of the protein that could serve as docking sites for such compounds. The new work was reported online on February 25, 2016 in the journal Cell Reports.

Molecular Medicine Tri-Conference in San Francisco March 6-11; BioQuick News Is a Media Sponsor

The Molecular Medicine Tri-Conference 2016 is scheduled to take place in San Francisco from March 6 to March 11. If you are working in diagnostics and drug discovery, this is perhaps the must-attend event of the year. Attracting over 3,300 drug discovery and development professionals from over 40 countries in 2015, the Tri-Conference has grown into a diverse event, focusing on Molecular Medicine, specifically on Discovery, Genomics, Diagnostics, and Information Technology. With a 23-year history, this year’s expanded coverage includes additional programs on Molecular Diagnostics for Infectious Disease, Precision Medicine, and Cancer Immunotherapy, as well as new symposia on Companion Diagnostics and on the Commercialization of Molecular Diagnostics. You will have the opportunity to listen to many of the over-500 speakers from across all industries, all research fields, and from all over the world. A link to the registration page for the Molecular Medicine Tri-Conference is provided below, as are links to the current speaker list and to the Event-at-a-Glance brochure. BioQuick News is an official media sponsor of the Molecular Medicine Tri-Conference 2016. Other media sponsors of Tri-Conference 2016 include Science, Genetic Engineering & Biotechnology News, The Scientist, and BioIT World. A link to the list of media sponsors is also provided below.

[Registration] [Speaker List] [Event-at-a-Glance] [Media Sponsors]

Switch Function Discovery Could Be Used to Control Natural Killer Cell Activity; ID2 Protein Switch Tunes NK Cell Sensitivity to Growth Factor IL-15

The immune cells called natural killer cells hunt and destroy foreign cells in the body, including cancer cells that spread and form tumors. A team led by Dr. Nick Huntington (photo), from Australia’s Walter and Eliza Hall Institute’s Molecular Immunology Division, has found, for the first time, how the “switch” that turns on these natural killer cells works. The team found that the switch, a protein called ID2, functions by allowing natural killer cells to become responsive to growth factors in the blood. Dr. Huntington said a growth factor called IL-15 keeps natural killer cells active and alive -- if it is taken away these cells die. The findings were published in the January 19, 2016 issue of Immunity. The article is titled “The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15.” "This is an exciting discovery because previous research has shown that these natural killer cells are really potent in killing tumors: breast and colon cancer and melanoma cells," Dr. Huntington said. "We knew this switch -- or master regulator -- was essential for the natural killer cell development, but we had no idea how this worked." Dr. Huntington said the research allowed scientists to think of new strategies to regulate the activity of natural killer cells by targeting the switch and these strategies could lead to new treatments. "If we can give an advantage to natural killer cells by boosting their activity or numbers or survival in the body then we can try to win that fight against cancer," he said. Natural killer cells, a type of white blood cell prevalent in the body, deliver lethal toxic granules into cells that have become cancerous or infected, causing them to rupture and die. Dr.

PCSK9-Inhibitor Drug Class Proves Game-Changer for Patient with Extremely High Cholesterol

A 59-year-old heart patient with dangerously high levels of cholesterol that could not be adequately reduced by statin drugs now has near-normal cholesterol levels, thanks to a new class of drugs that grew out of work done by UT Southwestern Medical Center researchers. Two of these drugs, in a category known as PCSK9 inhibitors, were approved by the Food and Drug Administration last summer for use by some individuals with extremely high cholesterol levels. “If you take the core patients who are at highest risk, it makes you appreciate how important this drug class is,” said Dr. Amit Khera (at right in photo), Director of the Preventive Cardiology Program and Associate Professor of Internal Medicine at UT Southwestern. Frank Brown (at left in photo) of Dallas, grandfather of six and the owner of Frank’s Wrecker Service in Dallas, has familial hypercholesterolemia, an inherited condition that causes high levels of cholesterol, especially of low-density-lipoprotein (LDL) cholesterol or “bad cholesterol.” High levels of LDL cholesterol are strongly associated with heart disease. Mr. Brown, with a history of two heart attacks, had been aggressively treated with multiple drugs to reduce his cholesterol levels, but they remained stubbornly high. “When I first met Mr. Brown, he had a strong family history of heart disease, he had a cholesterol level that was ridiculously high with an LDL of 384, and he was having chest pains,” said Dr. Khera, who is Mr. Brown’s cardiologist. Dr. Khera, who holds the Dallas Heart Ball Chair in Hypertension and Heart Disease at UT Southwestern, was treating Mr.