From slow-motion footage on YouTube to deep-space satellite imagery to weird washcloths on the International Space Station, this was a big year for science.
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How retroviruses like HIV spread in their hosts had been unknown — until a Yale team devised a way to watch it actually happen in a living organism. The elaborate and sometimes surprising steps the virus takes to reach and spread in the lymph nodes of a mouse have been captured on videos and described in the Oct. 2 issue of the journal Science.
“It’s all very different than what people thought,” said Walther Mothes, associate professor of microbial pathogenesis and co-senior author the paper.
Tracking fluorescently stained viruses in mice, the Yale team led by Mothes and co-senior author Priti Kumar, assistant professor of medicine and microbial pathogenesis, used sophisticated imaging technology to capture the action as the viral particles bind to macrophages via a sticky protein that is located at the capsule of the lymph node.
But that is only the first step of the journey. The captured viral particles open to a rare type of B-cell, seen in red in the accompanying movie. The virus particles then attach themselves to the tail of these B-cells and are dragged into the interior of the lymph node. In one to two days, these B-cells establish stable connections with tissue, enabling full transmission of the virus.
The insights provided by the videos identify a potential way to prevent HIV from infecting surrounding tissue. If researchers could develop a way to block the action of the sticky protein the virus uses to bind to macrophages, then the virus’ transmission could be halted, Mothes suggested.
Elon Musk believes Tesla cars will be fully autonomous by 2018, and have an all-electric range of more than 1,000km, double what it is today. He also predicts that by 2035 all new cars will not require a driver.
A renowned futurist and CEO of Tesla and SpaceX, Musk predicts that the range of the Model S can be increased by between 5% and 10% every year, as battery technology improves. He also claims the AutoPilot self-driving feature currently being beta tested by Tesla will be rolled-out to all compatible Model S vehicles by the end of October. AutoPilot provides automatic steering, accelerating and braking on motorways, but only in countries which have updated their road laws to allow it.
In an interview on Dutch television, Musk said: "My guess is that we could probably break 1,000km within a year or two. I'd say 2017 for sure...in 2020 I guess we could probably make a car go 1,200km. I think maybe 5-10% a year [improvement], something like that." A Model S was recently driven 452 miles (723km) on a single charge, but drove at an average speed of just 24mph. Musk says his predictions account for driving at a more realistic speed. Musk added that AutoPilot will be switched on in a month's time, adding: "My guess for when we'll have full autonomy is about three years, approximately three years." This is much sooner than 2020, when analysts had expected to see autonomous cars from Google - and possible Apple - go on sale.
But this is with a caveat. "Regulators will not allow full autonomy for one to two years – maybe one to three years – after that," Musk said. "It depends on the particular market; in some markets the regulators will be more forward leaning than others. But in terms of when [full autonomy] will be technologically possible, I think three years."
Looking even further ahead, Musk predicts that – providing "civilisation is still around" – by 2035 "we'll see a very large percentage of cars being electric [on the road] probably all cars being built will have full autonomy in 20 years." Again, however, a caveat exists, in that cars are not replaced as often as smartphones, so it will take a considerable amount of time for all vehicles on the world's roads (around 2.5 billion) to become electric and autonomous. Musk reckons it would take another 20 years to fully replace all cars and trucks being used in 2035 with electric vehicles.
An ultra-thin invisibility “skin” cloak that can conform to the shape of an object and conceal it from detection with visible light has been developed by scientists at Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley.
Working with blocks of gold nanoantennas, the Berkeley researchers created a “skin cloak” just 80 nanometers in thickness that was wrapped around a three-dimensional object about the size of a few biological cells and shaped with multiple bumps and dents. The surface of the skin cloak was meta-engineered to reflect light waves, making the object invisible to optical detection when the cloak is activated.
“This is the first time a 3D object of arbitrary shape has been cloaked from visible light,” said Xiang Zhang, director of Berkeley Lab’s Materials Sciences Division. “Our ultra-thin cloak now looks like a coat. It is easy to design and implement, and is potentially scalable for hiding macroscopic objects.”
Zhang, who holds the Ernest S. Kuh Endowed Chair at UC Berkeley and is a member of the Kavli Energy NanoSciences Institute at Berkeley (Kavli ENSI), is the corresponding author of a paper describing this research in the journal Science.
Earth-like planets orbiting close to small stars probably have magnetic fields that protect them from stellar radiation and help maintain surface conditions that could be conducive to life, according to research from astronomers at the University of Washington.
A planet's magnetic field emanates from its core and is thought to deflect the charged particles of the stellar wind, protecting the atmosphere from being lost to space. Magnetic fields, born from the cooling of a planet's interior, could also protect life on the surface from harmful radiation, as the Earth's magnetic field protects us.
Low-mass stars are among the most common in the universe. Planets orbiting near such stars are easier for astronomers to target for study because when they transit, or pass in front of, their host star, they block a larger fraction of the light than if they transited a more massive star. But because such a star is small and dim, its habitable zone—where an orbiting planet gets the heat necessary to maintain life-friendly liquid water on the surface—also lies relatively close in.
And a planet so close to its star is subject to the star's powerful gravitational pull, which could cause it to become tidally locked, with the same side forever facing its host star, as the moon is with the Earth. That same gravitational tug from the star also creates tidally generated heat inside the planet, or tidal heating. Tidal heating is responsible for driving the most volcanically active body in our solar system, Jupiter's moon Io.
In a paper published Sept. 22 in the journal Astrobiology, lead author Peter Driscoll sought to determine the fate of such worlds across time: "The question I wanted to ask is, around these small stars, where people are going to look for planets, are these planets going to be roasted by gravitational tides?" He was curious, too, about the effect of tidal heating on magnetic fields across long periods of time.
Their simulations ranged from one stellar mass—stars the size of our sun—down to about one-tenth of that size. By merging their models, they were able, Barnes said, "to produce a more realistic picture of what is happening inside these planets." Barnes said there has been a general feeling in the astronomical community that tidally locked planets are unlikely to have protective magnetic fields "and therefore are completely at the mercy of their star." This research suggests that assumption false.
Far from being harmful to a planet's magnetic field, tidal heating can actually help it along—and in doing so also help the chance for habitability. This is because of the somewhat counterintuitive fact that the more tidal heating a planetary mantle experiences, the better it is at dissipating its heat, thereby cooling the core, which in turn helps create the magnetic field.
Holograms have a wide variety of applications, from 3D displays to data storage, but the potential applications are currently limited by the complexity and cost of hologram fabrication. In an attempt to simplify the hologram fabrication process, scientists have developed a way to print holograms using a relatively simple and inexpensive laser-printing technique. They hope that the new method will make hologram fabrication more accessible for small-scale and personal use, opening up new types of applications such as integration with smart phones. The researchers, led by Dr. Haider Butt at the University of Birmingham, have published a paper on the printable holograms in a recent issue of Applied Physics Letters.
As the researchers explain in their paper, traditional holography fabrication requires specialized knowledge, expensive equipment, and time-consuming recording techniques. Recently, scientists have developed an alternative technique that uses a laser pulse that is split into two beams to create an interference pattern on a surface, producing the characteristic 3D holographic pattern. However, this approach has its own challenges, as it requires precise alignment of the two laser beams and suffers from low light intensity after beam splitting.
In the new paper, the researchers have overcome these challenges by developing a single-pulse laser technique that can rapidly print 2D and 3D holograms in seconds on flat or curved surfaces and on a variety of materials. The nanosecond laser can print 1 cm2 of hologram area in just 5 nanoseconds. The researchers explain that the overall speed is not limited by the laser pulse, but by the need to reposition the surface in between lasing, which could potentially be done much faster using robotics.
"The technique is slightly different from the conventional methods, which divide a single pulsed beam using beam splitters and then recombine them to produce holograms and nanopatterns," Butt told Phys.org. "Here we use only a single beam, which is reflected normally from a mirror. The incident and reflected beams interfere, and this interference pattern is used for writing/printing holograms. The technique requires far fewer optical components, it is very simple, reliable, and can be used for ablating a myriad of materials and substrates."
The scientists demonstrated the new technique by printing a holographic 2D signature and a holographic 3D coin. They expect that the method could be especially useful for printing holograms on sensors and "smart" materials that change in response to various stimuli. Printable holograms could also be integrated into smart phones, where, as the researchers explain, they can be used to interpret colorimetric data in pictures.
"The holograms printed with this method can be printed using dynamic materials, which are able to respond to any stimuli in their environments," Butt said. "And they will change their color in response to any environmental changes. Using smart phone cameras and applications, such colorimetric changes can be read, interpreted, and communicated remotely."
Additional applications may include 3D artwork, smart windows, and bio-sensing, among others. "This work can lead to further applications, such as holographic data storage, optical sensors, and printable optical devices," Butt said. "We and our collaborators are currently pursuing all these research paths and achieving good results."
More information: Qiancheng Zhao, et al. "Printable ink holograms." Applied Physics Letters. DOI: 10.1063/1.4928046
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins. Their approach provides a new platform to view and record these nanoscale interactions in real time. As they report Sept. 28 in Nature Biotechnology, this tool should provide fast and reliable characterization of the different mechanisms cellular proteins use to bind to DNA strands—information that could shed new light on the atomic-scale interactions within our cells and help design new drug therapies against pathogens by targeting enzymes that interact with DNA.
"There are other single-molecule tools around, but our new tool is far more sensitive," said senior author and UW physics professor Jens Gundlach. "We can really pick up atomic-scale movements that a protein imparts onto DNA." As can happen in the scientific process, they developed this tool—the single-molecule picometer-resolution nanopore tweezers, or SPRNT—while working on a related project.
The UW team has been exploring nanopore technology to read DNA sequences quickly. Our genes are long stretches of DNA molecules, which are made up of combinations of four chemical DNA "letters." In their approach, Gundlach and his team measure an electrical current through a biological pore called MspA, which is embedded within a modified cell membrane. As DNA passes through a tiny opening in the pore—an opening that is just 0.00000012 centimeters wide, or 1/10,000th the width of a human hair—the current shifts based on the sequence of DNA letters. They use these changes in current to infer DNA sequences.
Gundlach and his team, in the process of investigating nanopore sequencing, tried out a variety of molecular motors to move DNA through the pore. They discovered that their experimental setup was sensitive enough to observe motions much smaller than the distance between adjacent letters on the DNA. As they report in their paper, SPRNT is more than seven times more sensitive than existing techniques to measure interactions between DNA and proteins.
"Generally, most existing techniques to look at single-molecule movements—such as optical tweezers—have a resolution, at best, of about 300 picometers," said Gundlach. "With SPRNT, we can have 40 picometer resolution." For reference, 40 picometers are 0.000000004 centimeters, or about 0.0000000016 inches.
"We realized we can detect minute differences in the position of the DNA in the pore," said UW physics postdoctoral researcher Andrew Laszlo, a co-author on the paper. "We could pick up differences in how the proteins were binding to DNA and moving it through the pore."
The newest high-resolution images of Pluto from NASA's New Horizons are both dazzling and mystifying, revealing a multitude of previously unseen topographic and compositional details. The image below—showing an area near the line that separates day from night—captures a vast rippling landscape of strange, aligned linear ridges that has astonished New Horizons team members.
It's a unique and perplexing landscape stretching over hundreds of miles," said William McKinnon, New Horizons Geology, Geophysics and Imaging (GGI) team deputy lead from Washington University in St. Louis. "It looks more like tree bark or dragon scales than geology. This'll really take time to figure out; maybe it's some combination of internal tectonic forces and ice sublimation driven by Pluto's faint sunlight."
The "snakeskin" image of Pluto's surface is just one tantalizing piece of data New Horizons sent back in recent days. The spacecraft also captured the highest-resolution color view yet of Pluto, as well as detailed spectral maps and other high-resolution images.
The new "extended color" view of Pluto – taken by New Horizons' wide-angle Ralph/Multispectral Visual Imaging Camera (MVIC) on July 14 and downlinked to Earth on Sept. 19 – shows the extraordinarily rich color palette of Pluto.
New findings from NASA's Mars Reconnaissance Orbiter (MRO) provide the strongest evidence yet that liquid water flows intermittently on present-day Mars.
"We found the hydrated salts only when the seasonal features were widest, which suggests that either the dark streaks themselves or a process that forms them is the source of the hydration. In either case, the detection of hydrated salts on these slopes means that water plays a vital role in the formation of these streaks," said Lujendra Ojha of the Georgia Institute of Technology (Georgia Tech) in Atlanta, lead author of a report on these findings published Sept. 28 by Nature Geoscience.
Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.
During the most recent Republican presidential debate, frontrunner Donald Trump once again dragged out the still widespread myth that vaccines cause autism. This dangerous fiction was debunked as early as 2002 by the New England Journal of Medicine and has been consistently contradicted by research ever since. As a result, anti-vaxxers changed strategy: Instead of blaming thimerosal for causing autism, they now focus on the vaccine schedule itself, essentially claiming that too many shots in too short of a timespan overwhelms a child's immune system.
That is nonsense. The number of antigens (i.e., molecules that trigger an antibody response) contained within vaccines has decreased dramatically over the past several decades. In the Genetic Expert News Service, Emory University infectious disease professor Dr. Walter Orenstein says that the total number of antigens in all vaccines combined is about 150, which is practically nothing compared to the roughly2,000-6,000 antigens children face every single day. By crawling around on the floor and sticking their hands in their mouths, children are "vaccinating" themselves all day long.
Despite the lack of scientific logic to the anti-vaxxers' argument, a team of researchers decided to address the issue of vaccine schedules head-on. Their results are reported in the journal PNAS. The team divided 79 rhesus macaque monkeys into six experimental groups, each containing 12-16 animals. They then administered various combinations of vaccines to the animals in those groups. [Note that some vaccines contain EtHg, a metabolic derivative of thimerosal, while others do not. Also note that the vaccines used are the same as or similar to those used to vaccinate children (PDF).]
After all shots were administered, the macaques' behavior was assessed and their brains were examined for signs of autism. What did they find? Nothing. Absolutely nothing. There were neither significant differences in brain structure nor significant differences in the negative behaviors associated with autism. In other words, all the monkeys developed normally.
Critics will argue that this experiment was performed in macaques, not humans, and is therefore unreliable. Of course, it is unethical to give children placebos in place of vaccines (not to mention cutting their brains open), so this experiment cannot be performed in humans.
Pharmaceutical companies spend billions testing prospective drugs by conducting “wet lab” experiments that can take years to complete. But what if the same results could be obtained in a matter of minutes by running computer model simulations instead? A Silicon Valley startup says it has created a novel machine learning algorithm that does just that.
TwoXar (pronounced “two-czar”) was founded last year by two men both named Andrew Radin (more on that later). The Radins were interested in using advances in data science and large-scale computing to speed up the pace of drug discovery, which would give pharmaceutical companies better candidates for clinical studies.
“The traditional method of drug discovery is you examine a disease, you devise that there’s a protein of interest to you, and if you can regulate an activity with a drug, then perhaps it will help out,” TwoXar CEO Andrew A. Radin tells Datanami. “That’s a multi-year process to do all that work.”
TwoXar’s DUMA Drug Discovery platform can replace years’ worth of biological lab work with a digital equivalent that leans heavily on data science and leverages the incredible amount of medical, biological, and drug data that already exists in the public sphere.
“Our core IP [intellectual property], if you will, is this ability to take extremely diverse data sets and draw relationships between those data sets,” Radin says. “We’re combining clinical data in combination with gene expression assays, protein interaction networks, drug protein binding databases, and physical attributes about the molecules themselves.”
The hardest part is actually obtaining the relevant data. Most of the data is in the public sphere, thanks to the billions in spent by the NIH, the FDA, the European Union, and the Canadian government to back primary medical, chemical, and biological research. Once the right data is loaded into the system, it’s as simple as pressing the “go” button and waiting for the system to spit out its answer.
Findings from a pair of new studies could speed up the development of a universally accurate diagnostic test for human herpes simplex viruses (HSV), according to researchers at Johns Hopkins and Harvard universities and the National Institutes of Health (NIH). The work may also lead to the development of a vaccine that protects against the virus.
Reciprocal cooperation is assumed to require complex cognitive and social skills, skills that we thought fishes don’t have.
New research from the ARC Centre of Excellence for Coral Reef Studies at James Cook University discovered that a particular kind of fish (rabbitfish) are especially guard-like, thus while one is feeding the other will help, support and cooperate with the other.
While we already have studies confirming that mammals and highly social birds have such reciprocal skills, until now we believed these weren’t probable for fishes.
Dr. Simon Brandl from the ARC Centre of Excellence for Coral Reef Studies said: “We found that rabbitfish pairs coordinate their vigilance activity quite strictly, thereby providing safety for their foraging partner, in other words, one partner stays ‘on guard’ while the other feeds – these fishes literally watch each others’ back this behaviour is so far unique among fishes and appears to be based on reciprocal cooperation between pair members.”
Cutting-edge gene-editing techniques have produced an unexpected byproduct — tiny pigs that a leading Chinese genomics institute will soon sell as pets.
BGI in Shenzhen, the genomics institute that is famous for a series of high-profile breakthroughs in genomic sequencing, originally created the micropigs as models for human disease, by applying a gene-editing technique to a small breed of pig known as Bama. On 23 September 2015, at the Shenzhen International Biotech Leaders Summit in China, BGI revealed that it would start selling the pigs as pets. The animals weigh about 15 kilograms when mature, or about the same as a medium-sized dog.
At the summit, the institute quoted a price tag of 10,000 yuan (US$1,600) for the micropigs, but that was just to "help us better evaluate the market”, says Yong Li, technical director of BGI’s animal-science platform. In future, customers will be offered pigs with different coat colors and patterns, which BGI says it can also set through gene editing.
With gene editing taking biology by storm, the field's pioneers say that the application to pets was no big surprise. Some also caution against it. “It's questionable whether we should impact the life, health and well-being of other animal species on this planet light-heartedly,” says geneticist Jens Boch at the Martin Luther University of Halle-Wittenberg in Germany. Boch helped to develop the gene-editing technique used to create the pigs, which uses enzymes known as TALENs (transcription activator-like effector nucleases) to disable certain genes.
How to regulate the various applications of gene-editing is an open question that scientists are already discussing with agencies across the world. BGI agrees on the need to regulate gene editing in pets as well as in the medical research applications that make up the core of its micropig activities. Any profits from the sale of pets will be invested in this research. “We plan to take orders from customers now and see what the scale of the demand is,” says Li.
The decision to sell the pigs as pets surprised Lars Bolund, a medical geneticist at Aarhus University in Denmark who helped BGI to develop its pig gene-editing programme, but he admits that they stole the show at the Shenzhen summit. “We had a bigger crowd than anyone,” he says. “People were attached to them. Everyone wanted to hold them.”
They could meet a preexisting demand. In the United States, for instance, reports have surfaced of people who wanted a porcine lap pet, but were disappointed when animals touted as 'teacup' pigs weighing only 5 kilograms grew into 50-kilogram animals. Genetically-edited micropigs stay reliably small, the BGI team says.
A team of researchers with members from the University of California and Rice University has found a way to get a flat transistor to defy theoretical limitations on Field Effect Transistors (FETs). In their paper published in the journal Nature, the team describes their work and why they believe it could lead to consumer devices that have both smaller electronics and longer battery life. Katsuhiro Tomioka with Erasmus MC University Medical Center in the Netherlands offers a News & Views article discussing the work done by the team in the same journal edition.
As Tomioka notes, the materials and type of architecture currently used in creating small consumer electronic devices is rapidly reaching a threshold upon which a tradeoff will have to be made—smaller transistors or more power requirements—this is because of the unique nature of FETs, shortening the channel they use requires more power, on a logarithmic scale. Thus, to continue making FETs ever smaller and to get them to use less power means two things, the first is that a different channel material must be found, one that allow high switch-on currents at low voltages. The second is a way must be found to lower the voltage required for the FETs.
Researchers have made inroads on the first requirement, building FETs with metal-oxide-semiconductor materials, for example. The second has proved to be more challenging. In this latest effort, the researchers looked to tunneling to reduce voltage demands, the results of which are called, quite naturally, tunneling FETs or TFETs—they require less voltage because they are covered (by a gate stack) and work by transporting a charge via quantum-tunneling. The device the team built is based on a 2D bilayer of molybdenum disulfide and bulk germanium—it demonstrated a negative differential resistance, a marker of tunneling, and a very steep subthreshold slope (the switching property associated with rapid turn-on) which fell below the classical theoretical limit.
The work by the team represents substantial progress in solving the miniturization problem for future electronics devices, but as the team notes, there is still much to do. They express optimism that further improvements will lead to not just better consumer devices, but tiny sensors that could be introduced into the body to help monitor health.
Tufts University biomedical engineers are using low-energy, ultrafast laser technology to make high-resolution, 3-D structures in silk protein hydrogels. The laser-based micropatterning represents a new approach to customized engineering of tissue and biomedical implants.
Researchers at QMUL have developed a way of assembling organic molecules into complex tubular tissue-like structures without the use of moulds or techniques like 3D printing.
The study, which will appear on Monday 28 September in the journal Nature Chemistry, describes how peptides and proteins can be used to create materials that exhibit dynamic behaviors found in biological tissues like growth, morphogenesis, and healing.
The method uses solutions of peptide and protein molecules that, upon touching each other, self-assemble to form a dynamic tissue at the point at which they meet. As the material assembles itself it can be easily guided to grow into complex shapes.
This discovery could lead to the engineering of tissues like veins, arteries, or even the blood-brain barrier, which would allow scientists to study diseases such as Alzheimer’s with a high level of similarity to the real tissue, which is currently impossible. The technique could also contribute to the creation of better implants, complex tissues, or more effective drug screening methods.
Alvaro Mata, Director of the Institute of Bioengineering at QMUL and lead author of the paper, said: “What is most exciting about this discovery is the possibility for us to use peptides and proteins as building-blocks of materials with the capacity to controllably grow or change shape, solely by self-assembly.
Karla Inostroza-Brito, PhD student and first author of the paper said: “The system is dynamic so it can be triggered on demand to enable self-assembly with a high degree of control, which allows the creation of complex shapes with a structure that resembles elements of native tissue.“
NASA is developing the capabilities needed to send humans to an asteroid by 2025 and Mars in the 2030s – goals outlined in the bipartisan NASA Authorization Act of 2010 and in the U.S. National Space Policy, also issued in 2010.
Mars is a rich destination for scientific discovery and robotic and human exploration as mankind expands its presence into the solar system. Its formation and evolution are comparable to Earth, helping us to learn more about our own planet’s history and future. Mars had conditions suitable for life in its past. Future exploration could uncover evidence of life, answering one of the fundamental mysteries of the cosmos: Does life exist beyond Earth?
While robotic explorers have studied Mars for more than 40 years, NASA’s path for the human exploration of Mars begins in low-Earth orbit aboard the International Space Station. Astronauts on the orbiting laboratory are helping us prove many of the technologies and communications systems needed for human missions to deep space, including Mars. The space station also advances our understanding of how the body changes in space and how to protect astronaut health.
Our next step is deep space, where NASA will send a robotic mission to capture and redirect an asteroid to orbit the moon. Astronauts aboard the Orion spacecraft will explore the asteroid in the 2020s, returning to Earth with samples. This experience in human spaceflight beyond low-Earth orbit will help NASA test new systems and capabilities, such as Solar Electric Propulsion, which we’ll need to send cargo as part of human missions to Mars. Beginning in FY 2018, NASA’s powerful Space Launch System rocket will enable these “proving ground” missions to test new capabilities. Human missions to Mars will rely on Orion and an evolved version of SLS that will be the most powerful launch vehicle ever flown.
A fleet of robotic spacecraft and rovers already are on and around Mars, dramatically increasing our knowledge about the Red Planet and paving the way for future human explorers. The Mars Science Laboratory Curiosity rover measured radiation on the way to Mars and is sending back radiation data from the surface. This data will help us plan how to protect the astronauts who will explore Mars. Future missions like the Mars 2020 rover, seeking signs of past life, also will demonstrate new technologies that could help astronauts survive on Mars.
Engineers and scientists around the country are working hard to develop the technologies astronauts will use to one day live and work on Mars, and safely return home from the next giant leap for humanity. NASA also is a leader in a Global Exploration Roadmap, working with international partners and the U.S. commercial space industry on a coordinated expansion of human presence into the solar system, with human missions to the surface of Mars as the driving goal. Follow our progress at www.nasa.gov/exploration and www.nasa.gov/mars.
A team of Harvard researchers and other collaborators led by Professor of Chemistry and Chemical Biology Matthew Shair has demonstrated that a molecule isolated from sea sponges and later synthesized in Shair's lab, can halt the growth of cancerous cells and could open the door to a new treatment for leukemia. The study is described in a September 28th paper in Nature.
"Once we learned this molecule named cortistatin A was very potent and selective in terms of inhibiting the growth of AML cells, we tested it in mouse models of AML and found that it was as efficacious as any other molecule we had seen, without having deleterious effects," Shair said. "This suggests we have identified a promising new therapeutic approach."
It's one that could be available to test in patients relatively soon. "We synthesized cortistatin A and we are working to develop novel therapeutics based on it by optimizing its drug-like properties," Shair said. "Given the dearth of effective treatments for AML, we recognize the importance of advancing it toward clinical trials as quickly as possible."
The drug development process takes years, but Shair's lab is very close to having what is known as a development candidate that could be taken into late-stage preclinical development and then into clinical trials. An industrial partner will be needed to progress the technology along that path and toward eventual regulatory approval. Harvard's Office of Technology Development (OTD) is engaged in advanced discussions toward that end.
The molecule works, Shair explained, by inhibiting a pair of nearly identical kinases, called CDK8 and CDK19, that his work indicates play a key role in the growth of AML cells.
Shair's lab became interested in the molecule several years ago, shortly after it was first isolated and described by other researchers. The early studies suggested it appeared to inhibit just a handful of kinases. "We tested approximately 400 kinases, and found that it inhibits only CDK8 and CDK19 in cells, which makes it among the most selective kinase inhibitors identified to date," Shair said. "Having compounds that precisely hit a specific target, like cortistatin A can help reduce side-effects and increase efficacy. In a way, it shatters a dogma because we thought it wasn't possible for a molecule to be this selective and bind in a site common to all ~500 human kinases, but this molecule does it, and it does it because of its three-dimensional structure. What's interesting is that most kinase inhibitor drugs do not have this type of three-dimensional structure. Nature is telling us that one way to achieve this level of specificity, is to make molecules more like cortistatin A."
Snails small enough to fit almost 10 times into the eye of a needle have been discovered in Guangxi province, Southern China. With their shells measuring 0.86mm in height, the researchers believe they are the smallest land snails ever found.
The Angustopila dominikae snail – named after the wife of one of the authors ofthe study published in the journal ZooKeys – is just visible to the naked eye but very difficult to spot. Barna Páll-Gergely, co-author and scientist from Shinshu university in Japan said he was excited to find the “really really tiny” snails.
“These are very probably extreme endemic species. If we find them in more than one locality that is somewhat surprising,” he said. The seven species of record-breaking “microsnails” were discovered by the researchers while collecting soil samples from the base of limestone rocks in Guangxi province. They say it is likely they are indigenous to the area, with the most similar species living about 621 miles away in Thailand.
Using nanometer-scale components, researchers have demonstrated the first optical rectenna, a device that combines the functions of an antenna and a rectifier diode to convert light directly into DC current.
Based on multiwall carbon nanotubes and tiny rectifiers fabricated onto them, the optical rectennas could provide a new technology for photodetectors that would operate without the need for cooling, energy harvesters that would convert waste heat to electricity - and ultimately for a new way to efficiently capture solar energy.
In the new devices, developed by engineers at the Georgia Institute of Technology, the carbon nanotubes act as antennas to capture light from the sun or other sources. As the waves of light hit the nanotube antennas, they create an oscillating charge that moves through rectifier devices attached to them. The rectifiers switch on and off at record high petahertz speeds, creating a small direct current.
Billions of rectennas in an array can produce significant current, though the efficiency of the devices demonstrated so far remains below one percent. The researchers hope to boost that output through optimization techniques, and believe that a rectenna with commercial potential may be available within a year.
"We could ultimately make solar cells that are twice as efficient at a cost that is ten times lower, and that is to me an opportunity to change the world in a very big way" said Baratunde Cola, an associate professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech. "As a robust, high-temperature detector, these rectennas could be a completely disruptive technology if we can get to one percent efficiency. If we can get to higher efficiencies, we could apply it to energy conversion technologies and solar energy capture."
The ultra-stable properties of the proteins that allow deep-diving whales to remain active while holding their breath for up to two hours could help Rice University biochemist John Olson and his colleagues finish a 20-year quest to create lifesaving synthetic blood for human trauma patients.
In a new study featured this week in the Journal of Biological Chemistry, Olson and colleagues George Phillips, Lucian Smith and Premila Samuel compared the muscle protein myoglobin from humans, whales and other deep-diving mammals. Myoglobin holds oxygen for ready use inside muscle cells, and the study found that marine mammals have ultra-stable versions of myoglobin that tend not to unfold. The researchers found that stability was the key for cells to make large amounts of myoglobin, which is explains why deep-diving mammals can load their muscle cells with far more myoglobin than humans.
“Whales and other deep-diving marine mammals can pack 10-20 times more myoglobin into their cells than humans can, and that allows them to ‘download’ oxygen directly into their skeletal muscles and stay active even when they are holding their breath,” said Olson, Rice’s Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology. “The reason whale meat is so dark is that it’s filled with myoglobin that is capable of holding oxygen. But when the myoglobin is newly made, it does not yet contain heme. We found that the stability of heme-free myoglobin is the key factor that allows cells to produce high amounts of myoglobin.”
That’s important to Olson because he wants to create a strain of bacteria that can generate massive quantities of another protein that’s closely related to myoglobin. Olson has spent two decades studying hemoglobin, a larger, more complex oxygen-carrying protein in blood. Olson’s goal is to create synthetic blood for use in transfusions. Hospitals and trauma specialists currently rely on donated whole blood, which is often in short supply and has a limited storage life. A crucial part of Olson’s plan is maximizing the amount of hemoglobin that a bacterium can express.
A new smart research system developed at Uppsala University accelerates research on cancer treatments by finding optimal treatment drug combinations. It was developed by a research group led by Mats Gustafsson, Professor of Medical Bioinformatics.
The “lab robot” system plans and conducts experiments with many substances, and draws its own conclusions from the results. The idea is to gradually refine combinations of substances so that they kill cancer cells without harming healthy cells.
Instead of just combining a couple of substances at a time, the new lab robot can handle about a dozen drugs simultaneously. The future aim is to handle many more, preferably hundreds. The method is iterative search for anti-cancer drug combinations. The procedure starts by generating an initial generation (population) of drug combinations randomly or guided by biological prior knowledge and assumptions. In each iteration the aim is to propose a new generation of drug combinations based on the results obtained so far. The procedure iterates through a number of generations until a stop criterion for a predefined fitness function is satisfied.
There are a few such laboratories in the world with this type of lab robot, but researchers “have only used the systems to look for combinations that kill the cancer cells, not taking the side effects into account,” says Gustafsson.
The next step: Make the robot system more automated and smarter. The scientists also want to build more knowledge into the guiding algorithm of the robot, such as prior knowledge about drug targets and disease pathways.
For patients with the same cancer type returning multiple times, sometimes the cancer cells develop resistance against the pharmacotherapy used. The new robot systems may also become important in the efforts to find new drug compounds that make these resistant cells sensitive again.
The research is described in an open-access article published Tuesday (Sept. 22, 2015) in Scientific Reports.
By using powerful photon beams, researchers have shown that they can now control the chemical environment and provide nanoscale structural detail while simultaneously imaging the mineral calcite as it is pushed to its extremes.
For scientists to understand a system, they often push it to its limits. In geochemistry, that means putting minerals under extreme conditions and watching how they react. This can be done in a number of ways, but the approach is usually the same: develop tools necessary to observe reactions in better detail and look at how minerals react when their natural environment is destabilized.
The X-ray Reflection Interfacial Microscope, a new surface microscope at the U.S. Department of Energy's (DOE's) Argonne National Laboratory, has led to a major breakthrough. By using powerful photon beams generated by the Advanced Photon Source (APS), a DOE User Facility located at Argonne, researchers have shown that they can now control the chemical environment and provide nanoscale structural detail while simultaneously imaging the mineral calcite as it is pushed to its extremes.
"There are some very extreme natural environments on our planet," said Argonne's Paul Fenter, Interfacial Processes Group Leader and co-author of the study appearing today in the journal Science. "If you can understand how minerals react at the most extreme conditions, this gives you confidence in our understanding of reactions under less extreme conditions."
Our natural world rests in a delicate balance controlled by the movement of nutrients and toxins through waterways. Minerals like calcite grow and dissolve in response to changes in the water composition, which can be characterized by its level of acidity (i.e., the pH). A key feature of this experiment was the use of the X-rays to drive the calcite out of equilibrium while simultaneously observing how it dissolves.
"These reactions are well-known," said Nouamane Laanait, the paper's first author and current Eugene P. Wigner Fellow at Oak Ridge National Laboratory. "They are the same as those that control how calcite dissolves in oceans in response to increased CO2 levels. This work demonstrates that if one has precise control over the beam probe and appropriate modeling of the beam interactions [with the sample], then one can learn a great deal that would be inaccessible otherwise."
To see what happens to the calcite when it is destabilized, researchers used a technique called X-ray reflection interface microscopy (XRIM) at the APS. Piercing through water solution and reflecting off the calcite's surface like a mirror, focused X-rays changed the water's acidity level, starting a chain of reactions that lowered the pH and caused the calcite to dissolve. Tiny pits, similar to ones observed in previous experiments, began to form with simple round or rectangular shapes. The rate at which these pits formed and grew let researchers know that the X-ray beam was, in fact, controlling the local chemistry as predicted. What they didn't predict came next.
As the X-rays pushed the calcite to more extreme levels of instability, researchers were surprised to see that the dissolving pits became distorted and formed ink splatter-like irregularities, indicating that some parts were dissolving quicker than others. Known as reaction front instabilities, these irregularities had not previously been observed in real time.
"Calcite is well-studied," said Fenter, "and so we have a very good understanding of how it grows and dissolves over a wide range of conditions. That we were able to observe a new mode of dissolution was exciting since it suggests that there is still much to be learned."
The CRISPR/Cas9 technique is revolutionizing genetic research: Scientists have already used it to engineer crops, livestock andeven human embryos, and it may one day yield new ways to treat disease.
But now one of the technique's pioneers thinks that he has found a way to make CRISPR even simpler and more precise. In a paper published in Cell on 25 September, a team led by synthetic biologist Feng Zhang of the Broad Institute in Cambridge, Massachusetts, reports the discovery of a protein1 called Cpf1 that may overcome one of CRISPR-Cas9’s few limitations; although the system works well for disabling genes, it is often difficult to truly edit them by replacing one DNA sequence with another.
The CRISPR/Cas9 system evolved as a way for bacteria and archaea to defend themselves against invading viruses. It is found in a wide range of these organisms, and uses an enzyme called Cas9 to cut DNA at a site specified by 'guide' strands of RNA. Researchers have turned CRISPR/Cas9 into a molecular-biology powerhouse that can be used in other organisms. The cuts made by the enzyme are repaired by the cell’s natural DNA-repair processes.
CRISPR is much simpler than previous gene-editing methods, but Zhang thought there was still room for improvement. So he and his colleagues searched the bacterial kingdom to find an alternative to the Cas9 enzyme commonly used in laboratories. In April, they reported that they had discovered a smaller version of Cas9 in the bacterium Staphylococcus aureus2. The small size makes the enzyme easier to shuttle into mature cells — a crucial destination for some potential therapies. The team was also intrigued by Cpf1, a protein that looks very different from Cas9, but is present in some bacteria with CRISPR. The scientists evaluated Cpf1 enzymes from 16 different bacteria, eventually finding two that could cut human DNA.
They also uncovered some curious differences between how Cpf1 and Cas9 work. Cas9 requires two RNA molecules to cut DNA; Cpf1 needs only one. The proteins also cut DNA at different places, offering researchers more options when selecting a site to edit. “This opens up a lot of possibilities for all the things we could not target before,” says epigeneticist Luca Magnani of Imperial College London.
Cpf1 also cuts DNA in a different way. Cas9 cuts both strands in a DNA molecule at the same position, leaving behind what molecular biologists call ‘blunt’ ends. But Cpf1 leaves one strand longer than the other, creating a 'sticky' end. Blunt ends are not as easy to work with: a DNA sequence could be inserted in either end, for example, whereas a sticky end will only pair with a complementary sticky end. “The sticky ends carry information that can direct the insertion of the DNA,” says Zhang. “It makes the insertion much more controllable.”
Zhang’s team is now working to use these sticky ends to improve the frequency with which researchers can replace a natural DNA sequence. Cuts left by Cas9 tend to be repaired by sticking the two ends back together, in a relatively sloppy repair process that can leave errors. Although it is possible that the cell will instead insert a designated, new sequence at that site, that kind of repair occurs at a much lower frequency. Zhang hopes that the unique properties of how Cpf1 cuts may be harnessed to make such insertions more frequent.
For Bing Yang, a plant biologist at the Iowa State University in Ames, this is the most exciting aspect of Cpf1. “Boosting the efficiency would be a big step for plant science,” he says. “Right now, it is a major challenge.”
Researchers found that long-chain hydrocarbons are significantly under-reported in car manufacturer's data. These hydrocarbons are a key component of two of the worst air pollutants, ozone and particulate matter. The authors believe these "hidden" emissions are having a large impact on air quality in cities like London. The tailpipes of diesel fueled trucks and cars produce an array of emissions that have different impacts on the air that people breathe.
The nitrogen dioxide and particles that are emitted from burning diesel have a direct impact on human health in cities. But diesel also contains more complex, long-chain hydrocarbons, whose role in air pollution has been little understood until now. They can form dangerous air pollutants, especially ozone and particulate matter, which are emitted into the air as unburned fuel or diesel vapor. Researchers from the University of York have been able to detect these complicated compounds in the London air, using sophisticated measuring technology.
The researchers found that close to 50% of the ozone production potential in London in winter was due to these diesel elements. In summertime, it was around 25%. The authors believe that these hydrocarbons are having a direct effect on health.
"I think it is having a large impact on air quality in our cities, the number of deaths associated with particle pollution are much higher than those from nitrogen dioxide, this is a route to increase particle pollution so it could have a major impact on human health", one of the authors said.
The study also found that the scale of these hydrocarbons in the air was far in excess of the levels expected by government, which are based on data from car manufacturers' emissions tests.