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Archive - Nov 2, 2015

Pineapple Genome Sequence and Evolution of Drought-Resistant CAM Photosynthesis

By sequencing its genome, scientists are homing in on the genes and genetic pathways that allow the juicy pineapple plant to thrive in water-limited environments. The new findings, reported online on November 2, 2015 in an open-access article in Nature Genetics, also open a new window on the complicated evolutionary history of grasses like sorghum and rice, which share a distant ancestor with pineapple. The Nature Genetics article is titled “The Pineapple Genome and the Evolution of CAM Photosynthesis.” Humans have cultivated pineapple for more than 6,000 years, beginning in present-day southwest Brazil and northeast Paraguay. Today, more than 85 countries produce about 25 million metric tons of pineapple fruit each year, with a gross production value approaching $9 billion. Like many plants, the ancestors of pineapple and grasses experienced multiple doublings of their genomes. Tracking the remnants of these "whole-genome duplications" in different plant species helps researchers trace their shared - and independent - evolutionary histories. "Our analysis indicates that the pineapple genome has one fewer whole genome duplication than the grasses that share an ancestor with pineapple, making pineapple the best comparison group for the study of cereal crop genomes," said University of Illinois Plant Biology Professor Ray Ming, Ph.D., who led the multi-institutional pineapple genome sequencing effort. The work uncovered evidence of two whole-genome duplications in the pineapple's history, and validated previous findings of three such duplications in grasses. Photosynthesis converts solar energy to chemical energy, allowing plants to build the tissues that sustain life on Earth.

Potential Glioblastoma Drug Shrinks Deadly Human Brain Tumors Grown in Mice by Half; Drug Successfully Targets Transient Interface Between Partner Misfiring OLIG2 Transcription Factors to Inhibit Key Binding in the Lethal Cancer

Patients with glioblastoma, a type of malignant brain tumor, usually survive fewer than 15 months following diagnosis. Because there are no effective treatments for this deadly cancer, University of California, San Diego (UCSD) researchers developed a new computational strategy to search for molecules that could be developed into potential glioblastoma drugs. In mouse models of human glioblastoma, one molecule they found shrank the average tumor size by half. The study was published online on October 30, 2015 in an open-access article in Oncotarget. The article is titled “Multiple Spatially Related Pharmacophores Define Small Molecule Inhibitors of OLIG2 in Glioblastoma.” The newly discovered molecule works against glioblastoma by wedging itself in the temporary interface between two proteins whose binding is essential for the tumor's survival and growth. This study is the first to demonstrate successful inhibition of this type of protein, known as a transcription factor. "Most drugs target stable pockets within proteins, so when we started out, people thought it would be impossible to inhibit the transient interface between two transcription factors," said first author Igor Tsigelny, Ph.D., Research Scientist at UC San Diego Moores Cancer Center, as well as the San Diego Supercomputer Center and Department of Neurosciences at UCSD. "But we addressed this challenge and created a new strategy for drug design -- one that we expect many other researchers will immediately begin implementing in the development of drugs that target similar proteins, for the treatment of a variety of diseases." Transcription factors control which genes are turned "on" or "off" at any given time. For most people, transcription factors labor ceaselessly in a highly orchestrated system.

Using Directed Molecular Evolution System, MGH Team Develops Broad-Range Cas9 Enzyme Variant from S. aureus That Targets Many Genomic Sites Previously Inaccessible to CRISPR-Cas9 Editing Technology

A team of Massachusetts General Hospital (MGH) investigators has shown that a method they developed to improve the usefulness and precision of the most common form of the gene-editing tools CRISPR-Cas9 RNA-guided nucleases can be applied to Cas9 enzymes from other bacterial sources. In an article published online on November 2, 2015 in Nature Biotechnology, the team reports evolving a variant of SaCas9 - the Cas9 enzyme from the Streptococcus aureus bacteria - that recognizes a broader range of nucleotide sequences, allowing targeting of genomic sites previously inaccessible to CRISPR-Cas9 technology. The article is titled “Broadening the Targeting Range of Staphylococcus aureus CRISPR-Cas9 by Modifying PAM Recognition.” "The development of Cas9 variants with a broader targeting range is particularly important for applications requiring precise targeting of genomic sequences," says Benjamin Kleinstiver, Ph.D., a research fellow in the MGH Molecular Pathology Unit and lead and co-corresponding author of the new Nature Biotechnology paper. "In addition, the coding sequence of SaCas9 is 23 percent smaller than that of SpCas9 - the version derived from Streptococcus pyogenes - a size difference that makes SaCas9 advantageous for potential therapeutic applications requiring delivery by viruses." CRISPR-Cas9 nucleases are comprised of a short RNA molecule, 20 nucleotides of which match the target DNA sequence, and a Cas9 bacterial enzyme that cuts the DNA in the desired location. Along with the match between the RNA and DNA sequences, Cas9 needs to recognize an adjacent nucleotide sequence called a protospacer adjacent motif (PAM). In a previous study reported earlier this year in Nature, the MGH team described a genetic system that enabled them to rapidly evolve SpCas9 to recognize different PAM sequences.

Novel Exosome Isolation and Exosomal MicroRNA Purification Kits Launched by Canada’s Norgen Biotek

Norgen Biotek, Corp., an innovative privately-held Canadian biotechnology company that is focused on advancing powerful tools for nucleic acid (NA) and protein purification, announced on Monday, November 2, 2015, the launch of novel kits for the fast and simple isolation of exosomes from plasma/serum, urine, and cell culture media. These kits are based on the use of Norgen's proprietary resin to purify and concentrate the exosomes. The company says these new kits are simple, rapid, and scalable. Furthermore, Norgen said it has developed kits for the isolation of high-quality RNA from exosomes. Norgen's exosomal RNA kits are designed to isolate all sizes of extracellular vesicle (EV) RNA, including microRNA. The company believes that the kits provide a clear advantage over other available kits in that they do not require any special instrumentation, protein precipitation reagents, extension tubes, or phenol/chloroform or protease treatments. Moreover, the kits allow the user to elute into flexible elution volumes. Norgen states that the purified RNA is free from any protein-bound circulating RNA and is of the highest integrity. The purified RNA can be used in a number of downstream applications including real-time PCR, RT-PCR, Northern blotting, RNase protection, primer extension, expression array assays, and next-generation sequencing, the company states. Norgen also launched four kits that allow for the depletion of exosomes from fetal bovine serum. Extensive testing has shown that depleted FBS provides the same cellular growth rates as the standard FBS. "The study of exosomes is an exciting new field, and Norgen's technology is well suited for the purification of exosomes and exosomal RNA,” said Dr. Yousef Haj-Ahmad, President & CEO of Norgen.

Uniquely in Oocytes, Spindle Assembly Checkpoint (SAC) Responds to DNA Damage and Can Prevent Birth Defects and Spontaneous Miscarriages

Researchers from the University of Southampton in the UK have established that eggs have a protective “checkpoint” that helps to prevent DNA-damaged eggs from being fertilized. Damage to an egg’s DNA can result in infertility, birth defects, and miscarriages. This damage can occur as a result of the natural aging process and also as a result of women taking certain types of medication following chemotherapy, or undergoing radiotherapy. The researchers found that damage to DNA during meiosis, the process that results in the formation of sperm cells and egg cells, activates the spindle assembly checkpoint (SAC) in the maturing egg, known as an oocyte, which prevents it from fully developing and stops it from being fertilized. While the SAC is known to exist in most cells in our body, where it helps to make sure chromosomes are shared equally when a cell divides into two, this checkpoint, uniquely in oocytes, appears to respond to DNA damage in the chromosomes. Lead author of the study Professor Keith Jones, Head of Biological Sciences at the University of Southampton, said, “The discovery of such a checkpoint is an important breakthrough that allows further investigation into what could affect the strength of the checkpoint.” The new work was published online on Novmber 2, 2015 in an open-access article in Nature Communications. The article is titled “DNA Damage-Induced Metaphase I Arrest Is Mediated by the Spindle Assembly Checkpoint and Maternal Age.” “My group aims to go on to understand how the initial DNA damage trigger actually manages to switch-on this checkpoint, because the connection is far from clear.” “However, we already know that a woman’s age is an important factor affecting her fertility, and, as such, it would be important to determine if this checkpoint is reduced by the aging process.

Fastest, Most Responsive Flexible Silicon Phototransistor Ever Made

Inspired by mammals' eyes, University of Wisconsin-Madison electrical engineers have created the fastest, most responsive flexible silicon phototransistor ever made. The innovative phototransistor could improve the performance of myriad products -- ranging from digital cameras, night-vision goggles, and smoke detectors to surveillance systems and satellites -- that rely on electronic light sensors. Integrated into a digital camera lens, for example, it could reduce bulkiness and boost both the acquisition speed and quality of video or still photos. Developed by UW-Madison collaborators Zhenqiang "Jack" Ma, Ph.D., Professor of Electrical and Computer Engineering, and Research Scientist Jung-Hun Seo, Ph.D., the high-performance phototransistor far and away exceeds all previous flexible phototransistor parameters, including sensitivity and response time. The researchers published details of their advance online on October 26, 2015 in the journal Advanced Optical Materials. The article is titled “Flexible Phototransistors Based on Single-Crystalline Silicon Nanomembranes.” Like human eyes, phototransistors essentially sense and collect light, then convert that light into an electrical charge proportional to its intensity and wavelength. In the case of our eyes, the electrical impulses transmit the image to the brain. In a digital camera, that electrical charge becomes the long string of 1’s and 0’s that create the digital image. While many phototransistors are fabricated on rigid surfaces, and therefore are flat, the phototransistors created by Dr. Ma and Dr. Seo are flexible, meaning they more easily mimic the behavior of mammalian eyes. "We actually can make the curve any shape we like to fit the optical system," Dr. Ma says. "Currently, there's no easy way to do that."