The obscured “zone of avoidance” in space is a place of mystery, and scientists are peering at what’s inside it.
You can’t move a pharmaceutical scientist from a lab to a kitchen and expect the same research output. Enzymes behave exactly the same: They are dependent upon a specific environment. But now, in a study recently published in ACS Synthetic Biology, researchers from Osaka University have imparted an analogous level of adaptability to enzymes, a goal that has remained elusive for over 30 years.
Enzymes perform impressive functions, enabled by the unique arrangement of their constituent amino acids, but usually only within a specific cellular environment. When you change the cellular environment, the enzyme rarely functions well—if at all. Thus, a long-standing research goal has been to retain or even improve upon the function of enzymes in different environments; for example, conditions that are favorable for biofuel production. Traditionally, such work has involved extensive experimental trial-and-error that might have little assurance of achieving an optimal result.
Artificial intelligence (a computer-based tool) can minimize this trial-and-error, but still relies on experimentally obtained crystal structures of enzymes—which can be unavailable or not especially useful. Thus, “the pertinent amino acids one should mutate in the enzyme might be only best-guesses,” says Teppei Niide, co-senior author. “To solve this problem, we devised a methodology of ranking amino acids that depends only on the widely available amino acid sequence of analogous enzymes from other living species.”
Genetic engineering is a rapidly progressing scientific discipline, with tremendous current application and future potential. It’s a bit dizzying for a science communicator who is not directly involved in genetics research to keep up. I do have some graduate level training in genetics so at least I understand the language enough to try to translate the latest research for a general audience.
Many readers have by now heard of CRISPR – a powerful method of altering or silencing genes that brings down the cost and complexity so that almost any genetics lab can use this technique. CRISPR is actually just the latest of several powerful gene-altering techniques, such as TALEN. CRISPR is essentially a way to target a specific sequence of the DNA, and then deliver a package which does something, like splice the DNA. But you also need to target the correct cells. In a petri dish, this is simple. But in living organism, this is a huge challenge. We have developed several viral vectors that can be targeted to specific cell types in order to deliver the CRIPR (or TALEN), which then targets the specific DNA.
Now I would like to present a different technique I have not previously written about here – alternative splicing. A recent study presents what seems like a significant advance in this technology, so it’s a good time to review it. “Alternative splicing” refers to a natural phenomenon of genetics. Genes are composed of introns and exons. I always thought the nomenclature was counterintuitive, but the exons are actually the part of the gene that gets expressed into a protein. The introns are the part that is not expressed, so they are cut out of the gene when it is being converted into mRNA, and the exons are stitched together to form the sequence that is translated into a protein. Alternative splicing refers to the fact that the way in which the introns are removed and the exons stitched together can vary, creating alternative forms of the resulting protein.
ARI gene groups (ARI downregulated genes, those highly expressed in BA17 and BA39/40 relative to other regions in controls; ARI upregulated genes, those expressed at low level in BA17 and BA39/40 relative to other regions in controls) were created through taking the union (without duplicates) across all ten identified ASD-attenuated regional comparisons, and sorting genes into the two groups based on gene-expression profiles across regions. The details of this process are described in the Supplementary Methods, along with functional annotation procedures.
Standard workflows using WGCNA17 were followed as previously described in Parikshak et al.5 and Gandal et al.1 (with minor modifications) to identify gene and transcript co-expression modules. Details regarding network formation, module identification, and module functional characterization are described in the Supplementary Methods.
Frozen brain samples were placed on dry ice in a dehydrated dissection chamber to reduce degradation effects from sample thawing and/or humidity. Approximately 50 mg of cortex was sectioned, ensuring specific grey matter–white matter boundary. The tissue section was homogenized in RNase-free conditions with a light detergent briefly on ice using a dounce homogenizer, filtered through a 40-μM filter and centrifuged at 1,000 g for 8 min at 4 °C. The pelleted nuclei were then filtered through a two-part micro gradient (30%/50%) for 20 min at 4 °C. Clean nuclei were pelleted away from debris. The nuclei were washed two more times with PBS/1%BSA/RNase and spun down at 500 g for 5 min. Cells were inspected for quality (shape, colour and membrane integrity) and counted on a Countess II instrument. They were then loaded onto the 10X Genomics platform to isolate single nuclei and generate libraries for RNA sequencing on the NovaS4 or NovaS2 Illumina machines.
A team of researchers from Korea University, Ajou University and Hanyang University, all in the Republic of Korea, has created a tiny aquabot propelled by fins made of a porous hydrogel imbued with nanoparticles. In their paper published in the journal Science Robotics, the group describes how the hydrogel works to power a tiny boat and reveals how much voltage was required.
Scientists and engineers have been working for several years to build tiny, soft robots for use in medical applications and have found that hydrogels are quite suitable for the task. Unfortunately, such materials also have undesirable characteristics, most notably, poor electro-connectivity. In this new effort, the researchers took a new approach to making hydrogels more amenable for use with electricity as a power source —adding conductive nanoparticles.
The work involved adding a small number of nanoparticles to a part of a porous hydrogel which they then used as a wrinkled nanomembrane electrode (WNE) actuator. Adding the nanoparticles allowed the hydrogel to conduct electricity in a reliable way. Testing showed the actuator could be powered with as little as 3 volts of electricity. The researchers then fashioned two of the actuators into finlike shapes and attached them to a tiny plastic body. Electronics added to the body controlled the electricity sent to the fins. The resulting robot had a water bug appearance, floating on the surface of the water in a tank.
A Ludwig Cancer Research study has developed a novel nanotechnology that triggers potent therapeutic anti-tumor immune responses and demonstrated its efficacy in mouse models of multiple cancers. Led by Co-director Ralph Weichselbaum, investigator Wenbin Lin and postdoctoral researcher Kaiting Yang at the Ludwig Center at Chicago, the study describes the synthesis, mechanism of action and preclinical assessment of the nanoparticle, which is loaded with a drug that activates a protein central to the efficient induction of anti-cancer immunity. The study, which overcomes significant technical barriers to targeting that protein-;stimulator of interferon genes, or STING-;for cancer therapy, appears in the current issue of Nature Nanotechnology.
“The nanoparticles developed by the Lin lab release a drug that targets macrophages and can activate potent antitumor immune responses that extend the survival of mice bearing a variety of tumors,” said Chicago Center Co-director Weichselbaum. “When used in combination with radiotherapy and immunotherapy, they even help control ‘cold tumors’ that are otherwise almost completely impervious to immune attack.”
STING is part of cellular sensing system for DNA fragments, which are generated by infection or cancer treatments that damage DNA, like radiotherapy and some chemotherapies. Its activation promotes inflammation and drives immune cells like macrophages and dendritic cells to process and present cancer antigens to T cells, helping to stimulate and direct the immune assault on tumors. Though STING is a prized target for drug development, the drug-like molecules that can activate the molecular sensor-;known as cyclic dinucleotides (CDNs)-;have been plagued by issues of poor bioavailability, low stability and high toxicity in the absence of any means to target them specifically to tumors.
A team of researchers at Shanghai Jiao Tong University, working with a pair of colleagues from Harvard University, has developed a new way to synthesize single quantum nanomagnets that are based on metal-free, multi-porphyrin systems. In their paper published in the journal Nature Chemistry, the group describes their method and possible uses for it.
Molecular magnets are materials that are capable of exhibiting ferromagnetism. They are different from other magnets because their building blocks are composed of organic molecules or a combination of coordination compounds. Chemists have been studying their properties with the goal of using them to develop medical therapies such advanced magnetic resonance imaging, new kinds of chemotherapy and possibly magnetic-field-induced local hyperthermia therapy. In this new effort, the researchers have developed a way to create molecular nanomagnets with quantum properties.
The technique involved first synthesizing a monoporphyrin using what they describe as conventional “solution chemistry”—the monoporhyrins were created by using an atomic-force microscope to pull hydrogen atoms off of polyporphyrins. The researchers then applied the result to a base of gold, which they placed in an oven and heated to 80 °C. This forced the rings in the material to become chained. They then turned the oven up to 290°C and then let the material cook for another 10 minutes. This resulted in the formation of additional carbon cycles and the creation of quantum nanomagnets.
A recently released set of topography maps provides new evidence for an ancient northern ocean on Mars. The maps offer the strongest case yet that the planet once experienced sea-level rise consistent with an extended warm and wet climate, not the harsh, frozen landscape that exists today.
“What immediately comes to mind as one the most significant points here is that the existence of an ocean of this size means a higher potential for life,” said Benjamin Cardenas, assistant professor of geosciences at Penn State and lead author on the study recently published in the Journal of Geophysical Research: Planets.
“It also tells us about the ancient climate and its evolution. Based on these findings, we know there had to have been a period when it was warm enough and the atmosphere was thick enough to support this much liquid water at one time.”
Circa 1999 this can lead to genetic editing that allows people to handle even a nuclear fallout level of radiation and even allow them to handle outer space better.
Rockville, MD — No, it’s not the cockroach, but rather a strain of pink bacteria that can survive 1.5 million rads of gamma irradiation — a dose 3,000 times the amount that would kill a human. This dose of radiation shreds the bacteria’s genome into hundreds of pieces. The organism’s remarkable ability to repair this DNA damage completely in a day and go on living offers researchers tantalizing clues to better understanding the mechanism of cellular repair. Advances in this area could in turn improve our understanding of cancer which is frequently caused by unrepaired DNA damage. Genetically engineering the microbe could lead to improved ways to cleanup pollution and to new industrial processes.
U.S. Department of Energy-funded researchers at The Institute for Genomic Research (TIGR) describe the complete genetic sequence of the bacteria Deinococcus radiodurans in the November 19 issue of Science.
“This is a significant accomplishment,” Secretary of Energy Bill Richardson said. “The Department of Energy began microbial genome work to support bold science and to help meet our unique environment and energy mission needs. Besides the insights into the way cells work, this new research may help provide a new safe and inexpensive tool for some of the nation’s most difficult cleanup challenges.”
Black holes have properties characteristic of quantum particles, a new study reveals, suggesting that the puzzling cosmic objects can be at the same time small and big, heavy and light, or dead and alive, just like the legendary Schrödinger’s cat.
The new study, based on computer modeling, aimed to find the elusive connection between the mind-boggling time-warping physics of supermassive objects such as black holes and the principles guiding the behavior of the tiniest subatomic particles.