Could there be life below Saturn’s moon Enceladus and Jupiter’s moon Europa?

Illustration (not to scale) of the plume (white ejections) of Saturnian moon Enceladus, based on analysis of data from NASA’s Cassini spacecraft, which dived through the Enceladus plume in 2015. Scientists have now discovered hydrogen gas in the erupting material in the plume — providing further evidence for hydrothermal activity and making it more likely that the underground ocean of Enceladus could have conditions suitable for microbial life. (credit: NASA/JPL-Caltech)

Two NASA missions — Cassini and Hubble — have provided new evidence for life on icy, ocean-bearing moons of Saturn and Jupiter, NASA announced Friday, April 14, 2017.

Scientists from Southwest Research Institute (SwRI) have discovered hydrogen gas in the plume of material erupting from Saturn’s moon Enceladus — suggesting conditions suitable for microbial life in an underground ocean. The finding, published April 14, 2017 in the journal Science, was based on analysis of data from NASA’s Cassini spacecraft.

The researchers suggest that the hydrogen was most likely formed in chemical reactions between the moon’s rocky core and warm water from vents in the moon’s subsurface ocean floor. These vents could have features similar to hydrothermal vents on Earth, which emit hot, mineral-laden fluid containing hydrogen (in the form of hydrogen sulfide) and are thought to power microbe life on the seafloor.*

This infographic illustrates how scientists on NASA’s Cassini mission think water interacts with rock at the bottom of the ocean of Saturn’s icy moon Enceladus, producing hydrogen gas (H2). The graphic shows water from the ocean circulating through the seafloor, where it is heated and interacts chemically with the rock. This warm water, laden with minerals and dissolved gases (including hydrogen and possibly methane) then pours into the ocean, creating chimney-like vents through the ice. The scientists have determined that nearly 98 percent of the gas in the plume is water vapor, about 1 percent is hydrogen, and the rest is a mixture of other molecules including carbon dioxide, methane (CH4), and ammonia (NH3). (credit: NASA/JPL-Caltech/Southwest Research Institute)

“The amount of molecular hydrogen we detected is high enough to support microbes similar to those that live near hydrothermal vents on Earth,” said SwRI’s Christopher Glein, PhD, a co-author on the paper and a pioneer of extraterrestrial chemical oceanography. “If similar organisms are present in Enceladus, they could ‘burn’ the hydrogen to obtain energy for chemosynthesis, which could conceivably serve as a foundation for a larger ecosystem.”

New Hubble observations suggest where to look for signs of life on Europa

Best evidence yet for reoccurring water vapor plumes erupting from Jupiter’s Europa moon (credit: NASA, ESA W. Sparks (STScI), USGS Astrogeology Science Center)

NASA also announced new Hubble Space Telescope observations of Jupiter’s moon Europa, reported in a paper published in The Astrophysical Journal Letters. A newly discovered plume seen towering 62 miles above the surface in 2016 is at precisely the same location as a similar plume seen on the moon two years earlier by Hubble. The scientists suggest this offers a promising location for study of Europa’s internal water and ice — and for seeking evidence of Europa’s habitability.

Scientists hope to learn more with NASA’s Europa Clipper mission, planned for launch in the 2020s. It will feature a powerful ultraviolet camera that will make similar measurements to Hubble’s (but from thousands of times closer) and a next-generation version of the Cassini instrument.

* NASA astrobiologists suggest that bacteria living in and around the dark hydrothermal vents extract their energy from hydrogen sulfide (HS) and other molecules that billow out of the seafloor. Just like plants, the bacteria use their energy to build sugars out of carbon dioxide and water; sugars then provide fuel and raw material for the rest of the microbe’s activities. But  instead of photosynthesis, the microbes derive their energy from chemicals in a process called “chemosynthesis”: Hydrothermal vents extract their energy from hydrogen sulfide (HS) and other molecules that billow out of the seafloor. Recently, researchers have determined that fossilized evidence of bacteria from ancient seafloor hydrothermal vent-precipitates (found in the Nuvvuagittuq belt in Quebec, Canada) is at least 3.77 billion years old (or possibly as much as 4.28 billion years old). The minimum age of the fossils would make them the oldest indication of life on Earth so far.


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Abstract of Cassini finds molecular hydrogen in the Enceladus plume: Evidence for hydrothermal processes

Saturn’s moon Enceladus has an ice-covered ocean; a plume of material erupts from cracks in the ice. The plume contains chemical signatures of water-rock interaction between the ocean and a rocky core. We used the Ion Neutral Mass Spectrometer onboard the Cassini spacecraft to detect molecular hydrogen in the plume. By using the instrument’s open-source mode, background processes of hydrogen production in the instrument were minimized and quantified, enabling the identification of a statistically significant signal of hydrogen native to Enceladus. We find that the most plausible source of this hydrogen is ongoing hydrothermal reactions of rock containing reduced minerals and organic materials. The relatively high hydrogen abundance in the plume signals thermodynamic disequilibrium that favors the formation of methane from CO2 in Enceladus’ ocean.

Abstract of Active Cryovolcanism on Europa?

Evidence for plumes of water on Europa has previously been found using the Hubble Space Telescope using two different observing techniques. Roth et al. found line emission from the dissociation products of water. Sparks et al. found evidence for off-limb continuum absorption as Europa transited Jupiter. Here, we present a new transit observation of Europa that shows a second event at the same location as a previous plume candidate from Sparks et al., raising the possibility of a consistently active source of erupting material on Europa. This conclusion is bolstered by comparison with a nighttime thermal image from the Galileo Photopolarimeter-Radiometer that shows a thermal anomaly at the same location, within the uncertainties. The anomaly has the highest observed brightness temperature on the Europa nightside. If heat flow from a subsurface liquid water reservoir causes the thermal anomaly, its depth is ≈1.8–2 km, under simple modeling assumptions, consistent with scenarios in which a liquid water reservoir has formed within a thick ice shell. Models that favor thin regions within the ice shell that connect directly to the ocean, however, cannot be excluded, nor modifications to surface thermal inertia by subsurface activity. Alternatively, vapor deposition surrounding an active vent could increase the thermal inertia of the surface and cause the thermal anomaly. This candidate plume region may offer a promising location for an initial characterization of Europa’s internal water and ice and for seeking evidence of Europa’s habitability.

Nanopores map small changes in DNA for early cancer detection

To detect DNA methylation changes (for cancer early warning), researchers punched a tiny hole (pore) in a flat sheet of graphene (or other  2D material). They then submerged the material in a salt solution and applied an electrical voltage to force the DNA molecule through the pore. A dip in the ionic current (black A) identified a methyl group (green) is passing through, but a dip in the electrical current (blue A) could detect smaller DNA changes. (credit: Beckman Institute Nanoelectronics and Nanomaterials Group)

University of Illinois researchers have designed a high-resolution method to detect, count, and map tiny additions to DNA called methylations*, which can be a early-warning sign of cancer.

The method threads DNA strands through a tiny hole, called a nanopore, in an atomically thin sheet of graphene or other 2D material** with an electrical current running through it.

Many methylations packed close together suggest an early stage of cancer, explained study leader Jean-Pierre Leburton, a professor of electrical and computer engineering at Illinois.

There have been previous attempts to use nanopores to detect methylation (by measuring ionic changes), which have been limited in resolution (how precise the measurement is). The Illinois group instead applied a current directly to the conductive sheet surrounding the pore. Working with Klaus Schulten, a professor of physics at Illinois, Leburton’s group at Illinois’ Beckman Institute for Advanced Science and Technology, they used advanced computer simulations to test applying current to different flat materials, such as graphene and molybdenum disulfide, while methylated DNA was threaded through.

“Our simulations indicate that measuring the current through the membrane instead of just the solution around it is much more precise,” Leburton said. “If you have two methylations close together, even only 10 base pairs away, you continue to see two dips and no overlapping. We also can map where they are on the strand, so we can see how many there are and where they are.”

Leburton’s group is now working with collaborators to improve DNA threading, to cut down on noise in the electrical signal, and to perform experiments to verify their simulations.

The study was published in 2D Materials and Applications, a new open-access journal from Nature Press. Grants from Oxford Nanopore Technology, the Beckman Institute, the National Institutes of Health, and the National Science Foundation supported this work.

* Methylation refers to the addition of a methyl group, which contains one carbon atom bonded to three hydrogen atoms, with the formula CH3.

** Such as graphene and molybdenum disulfide (MoS2).


NewsIllinois | Nanopore detection of DNA methylation

This contact lens could someday measure blood glucose and other signs of disease

Transparent biosensors in contact lenses (made visible in this artist’s rendition) could soon help track our health. (credit: Jack Forkey/Oregon State University)

Transparent biosensors embedded into contact lenses could soon allow doctors and patients to monitor blood glucose levels and many other telltale signs of disease from teardops without invasive tests, according to Oregon State University chemical engineering professor Gregory S. Herman, Ph.D. who presented his work Tuesday April 4, 2017 at the American Chemical Society (ACS) National Meeting & Exposition.

Herman and two colleagues previously invented a compound composed of indium gallium zinc oxide (IGZO). This semiconductor is the same one that has revolutionized electronics, providing higher resolution displays on televisions, smartphones and tablets while saving power and improving touch-screen sensitivity.

In his research, Herman’s goal was to find a way to help people with diabetes continuously monitor their blood glucose levels more efficiently using bio-sensing contact lenses. Continuous glucose monitoring — instead of the prick-and-test approach — helps reduce the risk of diabetes-related health problems. But most continuous glucose monitoring systems require inserting electrodes in various locations under the skin. This can be painful, and the electrodes can cause skin irritation or infections.

Herman says bio-sensing contact lenses could eliminate many of these problems and improve compliance since users can easily replace them on a daily basis. And, unlike electrodes on the skin, they are invisible, which could help users feel less self-conscious about using them.

A schematic illustration of an experimental device (credit: Du X et al./ ACS Applied Materials & Interfaces)

To test this idea, Herman and his colleagues first developed an inexpensive method to make IGZO electronics. Then, they used the approach to fabricate a biosensor containing a transparent sheet of IGZO field-effect transistors and glucose oxidase, an enzyme that breaks down glucose. When they added glucose to the mixture, the enzyme oxidized the blood sugar. As a result, the pH level in the mixture shifted and, in turn, triggered changes in the electrical current flowing through the IGZO transistor.

In conventional biosensors, these electrical changes would be used to measure the glucose concentrations in the interstitial fluid under a patient’s skin. But glucose concentrations are much lower in the eye. So any biosensors embedded into contact lenses will need to be far more sensitive. To address this problem, the researchers created nanostructures within the IGZO biosensor that were able to detect glucose concentrations much lower than found in tears.*

In theory, Herman says, more than 2,000 transparent biosensors — each measuring a different bodily function — could be embedded in a 1-millimeter square patch of an IGZO contact lens. Once developed, the biosensors could transmit vital health information to smartphones and other Wi-Fi or Bluetooth-enabled devices.

Herman’s team has already used the IGZO system in catheters to measure uric acid, a key indicator of kidney function, and is exploring the possibility of using it for early detection of cancer and other serious conditions. However, Herman says it could be a year or more before a prototype bio-sensing contact lens is ready for animal testing.

(credit: Google)

The concept appears similar to Goggle’s smart contact lens project, using a tiny wireless chip and miniaturized glucose sensor that are embedded between two layers of soft contact lens material, announced in 2014, but Herman says the Google design is more limited and that the research has stalled.

Herman acknowledges funding from the Juvenile Diabetes Research Foundation and the Northwest Nanotechnology Infrastructure, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation.

* “We have functionalized the back-channel of IGZO-FETs with aminosilane groups that are cross-linked to glucose oxidase and have demonstrated that these devices have high sensitivity to changes in glucose concentrations. Glucose sensing occurs through the decrease in pH during glucose oxidation, which modulates the positive charge of the aminosilane groups attached to the IGZO surface. The change in charge affects the number of acceptor-like surface states which can deplete electron density in the n-type IGZO semiconductor. Increasing glucose concentrations leads to an increase in acceptor states and a decrease in drain-source conductance due to a positive shift in the turn-on voltage. The functionalized IGZO-FET devices are effective in minimizing detection of interfering compounds including acetaminophen and ascorbic acid.” — Du XLi YMotley JRStickle WFHerman GS, Glucose Sensing Using Functionalized Amorphous In-Ga-Zn-O Field-Effect Transistors. ACS Applied Materials & Interfaces. 2016 03 30.


Abstract of Implantable indium gallium zinc oxide field effect biosensors

Amorphous indium gallium zinc oxide (IGZO) field effect transistors (FETs) are a promising technology for a wide range of electronic applications including implantable and wearable biosensors. We have recently developed novel, low-cost methods to fabricate IGZO-FETs, with a wide range of form factors. Attaching self-assembled monolayers (SAM) to the IGZO backchannel allows us to precisely control surface chemistry and improve stability of the sensors. Functionalizing the SAMs with enzymes provides excellent selectivity for the sensors, and effectively minimizes interference from acetaminophen/ascorbic acid. We have recently demonstrated that a nanostructured IGZO network can significantly improve sensitivity as a sensing transducer, compared to blanket IGZO films. In Figure (a) we show a scanning electron microscopy image of a nanostructured IGZO transducer located between two indium tin oxide source/drain electrodes. In Figure (b) we show an atomic force microscope image of the close packed hexagonal IGZO nanostructured network (3×3 mm2), and Figure (c) shows the corresponding height profile along the arrow shown in (b). We will discuss reasons for improved sensitivity for the nanostructured IGZO, and demonstrate high sensitivity for glucose sensing. Finally, fully transparent glucose sensors have been fabricated directly on catheters, and have been characterized by a range of techniques. These results suggest that IGZO-FETs may provide a means to integrate fully transparent, highly-sensitive sensors into contact lenses.

The next agricultural revolution: a ‘bionic leaf’ that could help feed the world

The radishes on the right were grown with the help of a bionic leaf that produces fertilizer with bacteria, sunlight, water, and air. (credit: Nocera lab, Harvard University)

Harvard University chemists have invented a new kind of “bionic” leaf that uses bacteria, sunlight, water, and air to make fertilizer right in the soil where crops are grown. It could make possible a future low-cost commercial fertilizer for poorer countries in the emerging world.

The invention deals with the renewed challenge of feeding the world as the population continues to balloon.* “When you have a large centralized process and a massive infrastructure, you can easily make and deliver fertilizer,” Daniel Nocera, Ph.D., says. “But if I said that now you’ve got to do it in a village in India onsite with dirty water — forget it. Poorer countries in the emerging world don’t always have the resources to do this. We should be thinking of a distributed system because that’s where it’s really needed.”

The research was presented at the national meeting of the American Chemical Society (ACS) today (April 3, 2017). The new bionic leaf builds on a previous Nocera-team invention: the “artificial leaf” — a device that mimics photosynthesis: When exposed to sunlight, it mimics a natural leaf by splitting water into hydrogen and oxygen. These two gases would be stored in a fuel cell, which can use those two materials to produce electricity from inexpensive materials.

That was followed by “bionic leaf 2.0,” a water-splitting system that carbon dioxide out of the air and uses solar energy plus hydrogen-eating Ralstonia eutropha bacteria to produce liquid fuel with 10 percent efficiency, compared to the 1 percent seen in the fastest-growing plants. It provided biomass and liquid fuel yields that greatly exceeded those from natural photosynthesis.

Fertilizer created from sunlight + water + carbon dioxide and nitrogen from the air

For the new “bionic leaf,” Nocera’s team has designed a system in which bacteria use hydrogen from the water split by the artificial leaf plus carbon dioxide from the atmosphere to make a bioplastic that the bacteria store inside themselves as fuel. “I can then put the bug [bacteria] in the soil because it has already used the sunlight to make the bioplastic,” Nocera says. “Then the bug pulls nitrogen from the air and uses the bioplastic, which is basically stored hydrogen, to drive the fixation cycle to make ammonia for fertilizing crops.”

The researchers have used their approach to grow five crop cycles of radishes. The vegetables receiving the bionic-leaf-derived fertilizer weigh 150 percent more than the control crops. The next step, Nocera says, is to boost throughput so that one day, farmers in India or sub-Saharan Africa can produce their own fertilizer with this method.

Nocera said a paper describing the new system will be submitted for publication in about six weeks.

* The first “green revolution” in the 1960s saw the increased use of fertilizer on new varieties of rice and wheat, which helped double agricultural production. Although the transformation resulted in some serious environmental damage, it potentially saved millions of lives, particularly in Asia, according to the United Nations (U.N.) Food and Agriculture Organization. But the world’s population continues to grow and is expected to swell by more than 2 billion people by 2050, with much of this growth occurring in some of the poorest countries, according to the U.N. Providing food for everyone will require a multi-pronged approach, but experts generally agree that one of the tactics will have to involve boosting crop yields to avoid clearing even more land for farming.


American Chemical Society | A ‘bionic leaf’ could help feed the world

Scientists grow beating heart tissue on spinach leaves

(credit: Worcester Polytechnic Institute)

A research team headed by Worcester Polytechnic Institute (WPI) scientists* has solved a major tissue engineering problem holding back the regeneration of damaged human tissues and organs: how to grow small, delicate blood vessels, which are beyond the capabilities of 3D printing.**

The researchers used plant leaves as scaffolds (structures) in an attempt to create the branching network of blood vessels — down to the capillary scale — required to deliver the oxygen, nutrients, and essential molecules required for proper tissue growth.

In a series of unconventional experiments, the team cultured beating human heart cells on spinach leaves that were stripped of plant cells.*** The researchers first decellularized spinach leaves (removed cells, leaving only the veins) by perfusing (flowing) a detergent solution through the leaves’ veins. What remained was a framework made up primarily of biocompatible cellulose, which is already used in a wide variety of regenerative medicine applications, such as cartilage tissue engineering, bone tissue engineering, and wound healing.

A spinach leaf (left) was decellularized in 7 days, leaving only the scaffold (right), which served as an intact vascular network. As a test, red dye was pumped through its veins, simulating blood, oxygen, and nutrients. Cardiomyocytes (cardiac muscle cells) derived from human pluripotent stem cells were then seeded onto the surface of the leaf scaffold, forming cell clusters that demonstrated cardiac contractile function and calcium-handling capabilities for 21 days. (credit: Worcester Polytechnic Institute)

After testing the spinach vascular (leaf vessel structure) system mechanically by flowing fluids and microbeads similar in size to human blood cells through it, the researchers seeded the vasculature with human umbilical vein endothelial cells (HUVECs) to grow endothelial cells (which line blood vessels).

Human mesenchymal stem cells (hMSC) and human pluripotent stem-cell-derived cardiomyocytes (cardiac muscle cells) (hPS-CM) were then seeded to the outer surfaces of  the plant scaffolds. The cardiomyocytes spontaneously demonstrated cardiac contractile function (beating) and calcium-handling capabilities over the course of 21 days.

The decellurize-recellurize process (credit: Joshua R. Gershlak et al./Biomaterials)

The future of ”crossing kingdoms”

These proof-of-concept studies may open the door to using multiple spinach leaves to grow layers of healthy heart muscle, and a potential tissue engineered graft based upon the plant scaffolds could use multiple leaves, where some act as arterial support and some act as venous return of blood and fluids from human tissue, say the researchers.

“Our goal is always to develop new therapies that can treat myocardial infarction, or heart attacks,” said Glenn Gaudette, PhD, professor of biomedical engineering at WPI and corresponding author of an open-access paper in the journal Biomaterials, published online in advance of the May 2017 issue.

“Unfortunately, we are not doing a very good job of treating them today. We need to improve that. We have a lot more work to do, but so far this is very promising.”

Currently, it’s not clear how the plant vasculature would be integrated into the native human vasculature and whether there would be an immune response, the authors advise.

The researchers are also now optimizing the decellularization process and seeing how well various human cell types grow while they are attached to (and potentially nourished by) various plant-based scaffolds that could be adapted for specialized tissue regeneration studies. “The cylindrical hollow structure of the stem of Impatiens capensis might better suit an arterial graft,” the authors note. “Conversely, the vascular columns of wood might be useful in bone engineering due to their relative strength and geometries.”

Other types of plants could also provide the framework for a wide range of other tissue engineering technologies, the authors suggest.****

The authors conclude that “development of decellularized plants for scaffolding opens up the potential for a new branch of science that investigates the mimicry between kingdoms, e.g., between plant and animal. Although further investigation is needed to understand future applications of this new technology, we believe it has the potential to develop into a ‘green’ solution pertinent to a myriad of regenerative medicine applications.”

* The research team also includes human stem cell and plant biology researchers at the University of Wisconsin-Madison, and Arkansas State University-Jonesboro.

** The research is driven by the pressing need for organs and tissues available for transplantation, which far exceeds their availability. More than 100,000 patients are on the donor waiting list at any given time and an average of 22 people die each day while waiting for a donor organ or tissue to become available, according to a 2016 paper in the American Journal of Transplantation

*** In addition to spinach leaves, the team successfully removed cells from parsley, Artemesia annua (sweet wormwood), and peanut hairy roots.

**** “Tissue engineered scaffolds are typically produced either from animal-derived or synthetic biomaterials, both of which have a large cost and large environmental impact. Animal-derived biomaterials used extensively as scaffold materials for tissue engineering include native [extracellular matrix]  proteins such as collagen I or fibronectin and whole animal tissues and organs. Annually, 115 million animals are estimated to be used in research. Due to this large number, a lot of energy is necessary for the upkeep and feeding of such animals as well as to dispose of the large amount of waste that is generated. Along with this environmental impact, animal research also has a plethora of ethical considerations, which could be alleviated by forgoing animal models in favor of more biologically relevant in vitro human tissue models,” the authors advise.

Worcester Polytechnic Institute | Spinach leaves can carry blood to grow human tissues

 

Travelers to Mars risk leukemia cancer, weakened immune function from radiation, NASA-funded study finds

The spleen from a mouse exposed to a mission-relevant dose (20 cGy, 1 GeV/n) of iron ions (bottom) was ~ 30 times the normal volume compared with the spleen from a control mouse (top). (credit: C Rodman et al./Leukemia)

Radiation encountered in deep space travel may increase the risk of leukemia cancer in humans traveling to Mars, NASA-funded researchers at the Wake Forest Institute for Regenerative Medicine and colleagues have found, using mice transplanted with human stem cells.

“Our results are troubling because they show radiation exposure could potentially increase the risk of leukemia,” said Christopher Porada, Ph.D., associate professor of regenerative medicine and senior researcher on the project.

Radiation exposure is believed to be one of the most dangerous aspects of traveling to Mars, according to NASA. The average distance to Mars is 140 million miles, and a round trip could take three years.

The goal of the study, published in the journal Leukemia, was to assess the direct effects of simulated solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation on human hematopoietic stem cells (HSCs). These stem cells comprise less than 0.1% of the bone marrow of adults, but produce the many types of blood cells that circulate through the body and work to transport oxygen, fight infection, and eliminate any malignant cells that arise.

For the study, human HSCs from healthy donors of typical astronaut age (30–55 years) were exposed to Mars mission-relevant doses of protons and iron ions — the same types of radiation that astronauts would be exposed to in deep space, followed by laboratory and animal studies to define the impact of the exposure.

“Radiation exposure at these levels was highly deleterious to HSC function, reducing their ability to produce almost all types of blood cells, often by 60–80 percent,” said Porada. “This could translate into a severely weakened immune system and anemia during prolonged missions in deep space.”

The radiation also caused mutations in genes involved in the hematopoietic process and dramatically reduced the ability of HSCs to give rise to mature blood cells.

Previous studies had already demonstrated that exposure to high doses of radiation, such as from X-rays, can have harmful (even life-threatening) effects on the body’s ability to make blood cells, and can significantly increase the likelihood of cancers, especially leukemias. However, the current study was the first to show a damaging effect of lower, mission-relevant doses of space radiation.

Mice develop T-cell acute lymphoblastic leukemia, weakened immune function

The next step was to assess how the cells would function in the human body. For that purpose, mice were transplanted with GCR-irradiated human HSCs, essentially “humanizing” the animals. The mice developed what appeared to be T-cell acute lymphoblastic leukemia — the first demonstration that exposure to space radiation may increase the risk of leukemia in humans.

“Our results show radiation exposure could potentially increase the risk of leukemia in two ways,” said Porada. “We found that genetic damage to HSCs directly led to leukemia. Secondly, radiation also altered the ability of HSCs to generate T and B cells, types of white blood cells involved in fighting foreign ‘invaders’ like infections or tumor cells. This may reduce the ability of the astronaut’s immune system to eliminate malignant cells that arise as a result of radiation-induced mutations.”

Porada said the findings are particularly troubling given previous work showing that conditions of weightlessness/microgravity present during spaceflight can also cause marked alterations in astronaut’s immune function, even after short duration missions in low-earth orbit, where they are largely protected from cosmic radiation.

Taken together, the results indicate that the combined exposure to microgravity and SEP/GCR radiation that would occur during extended deep space missions, such as to Mars, could potentially exacerbate the risk of immune-dysfunction and cancer,

NASA’s Human Research Program is also exploring conditions of microgravity, isolation and confinement, hostile and closed environments, and distance from Earth. The ultimate goal of the research is to make space missions as safe as possible.

Researchers at Wake Forest Baptist Medical Center, Brookhaven National Laboratory, and the University of California Davis Comprehensive Cancer Center were also involved in the study.


Abstract of In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Scientists reverse aging in mice by repairing damaged DNA

A research team led by Harvard Medical School professor of genetics David Sinclair, PhD, has made a discovery that could lead to a revolutionary new drug that allows cells to repair DNA damaged by aging, cancer, and radiation.

In a paper published in the journal Science on Friday (March 24), the scientists identified a critical step in the molecular process related to DNA damage.

The researchers found that a compound known as NAD (nicotinamide adenine dinucleotide), which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. In an experiment, they found that treating mice with a NAD+ precursor called NMN (nicotinamide mononucleotide) improved their cells’ ability to repair DNA damage.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said senior author Sinclair.

Disarming a rogue agent: When the NAD molecule (red) binds to the DBC1 protein (beige), it prevents DBC1 from attaching to and incapacitating a protein (PARP1) that is critical for DNA repair. (credit: David Sinclair)

Human trials of NMN therapy will begin within the next few months to “see if these results translate to people,” he said. A safe and effective anti-aging drug is “perhaps only three to five years away from being on the market if the trials go well.”

What it means for astronauts, childhood cancer survivors, and the rest of us

The researchers say that in addition to reversing aging, the DNA-repair research has attracted the attention of NASA. The treatment could help deal with radiation damage to astronauts in its Mars mission, which could cause muscle weakness, memory loss, and other symptoms (see “Mars-bound astronauts face brain damage from galactic cosmic ray exposure, says NASA-funded study“), and more seriously, leukemia cancer and weakened immune function (see “Travelers to Mars risk leukemia cancer, weakend immune function from radiation, NASA-funded study finds“).

The treatment could also help travelers aboard aircraft flying across the poles. A 2011 NASA study showed that passengers on polar flights receive about 12 percent of the annual radiation limit recommended by the International Committee on Radiological Protection.

The other group that could benefit from this work is survivors of childhood cancers, who are likely to suffer a chronic illness by age 45, leading to accelerated aging, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer, the researchers noted.

For the past four years, Sinclair’s team has been working with spinoff MetroBiotech on developing NMN as a drug. Sinclair previously made a link between the anti-aging enzyme SIRT1 and resveratrol. “While resveratrol activates SIRT1 alone, NAD boosters [like NMN] activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.

Sinclair is also a professor at the University of New South Wales School of Medicine in Sydney, Australia.


Abstract of A conserved NAD+ binding pocket that regulates protein-protein interactions during aging

DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.

Do-it-yourself robotics kit gives science, tech, engineering, math students tools to automate biology and chemistry experiments

Bioengineers combined a Lego Mindstorms system (left) with a motorized pipette (center) for dropping fluids, allowing for simple experiments like showing how liquids of different salt densities can be layered. (credit: Riedel-Kruse Lab)

Stanford bioengineers have developed liquid-handling robots to allow students to modify and create their own robotic systems that can transfer precise amounts of fluids between flasks, test tubes, and experimental dishes.

The bioengineers combined a Lego Mindstorms robotics kit with a cheap and easy-to-find plastic syringe to create robots that approach the performance of the far more costly automation systems found at universities and biotech labs.

Step-by-step DIY plans

Children 10–13 years old built and explored the functionality of these robots by performing experiments (credit: Lukas C. Gerber et al./PloS Biology)

The idea is to enable students to learn the basics of robotics and the wet sciences in an integrated way. Students learn STEM skills like mechanical engineering, computer programming, and collaboration while gaining a deeper appreciation of the value of robots in life-sciences experiments.

“We really want kids to learn by doing,” said Ingmar Riedel-Kruse, assistant professor of bioengineering and a member of Stanford Bio-X, who led the team. “We show that with a few relatively inexpensive parts, a little training and some imagination, students can create their own liquid-handling robots and then run experiments on it — so they learn about engineering, coding, and the wet sciences at the same time.”

In an open-access paper in the journal PLoS Biology and on Riedel-Kruse’s lab website, the team offers step-by-step building plans and several fundamental experiments targeted to elementary, middle and high school students. They also offer experiments that students can conduct using common household consumables like food coloring, yeast or sugar.

In one experiment, colored liquids with distinct salt concentrations are layered atop one another to teach about liquid density. Other tests measure whether liquids are acids like vinegar or bases like baking soda, or which sugar concentration is best for yeast.

Funding was provided by grants from the National Science Foundation (Cyberlearning and National Robotics Initiative).


Stanford University School of Engineering | SFENG Robots Riedel Kruse v4


Abstract of Liquid-handling Lego robots and experiments for STEM education and research

Liquid-handling robots have many applications for biotechnology and the life sciences, with increasing impact on everyday life. While playful robotics such as Lego Mindstorms significantly support education initiatives in mechatronics and programming, equivalent connections to the life sciences do not currently exist. To close this gap, we developed Lego-based pipetting robots that reliably handle liquid volumes from 1 ml down to the sub-μl range and that operate on standard laboratory plasticware, such as cuvettes and multiwell plates. These robots can support a range of science and chemistry experiments for education and even research. Using standard, low-cost household consumables, programming pipetting routines, and modifying robot designs, we enabled a rich activity space. We successfully tested these activities in afterschool settings with elementary, middle, and high school students. The simplest robot can be directly built from the widely used Lego Education EV3 core set alone, and this publication includes building and experiment instructions to set the stage for dissemination and further development in education and research.

Graphene sheets allow for very-low-cost diagnostic devices

A new, very-low-cost diagnostic method. Mild heating of graphene oxide sheets makes it possible to bond particular compounds (blue, orange, purple) to the sheets’ surface, a new study shows. These compounds in turn select and bond with specific molecules of interest, including DNA and proteins, or even whole cells. In this image, the treated graphene oxide on the right has oxygen molecules (red) clustered together, making it nearly twice as efficient at capturing cells (green) as the material on the left. (credit:  the researchers)

A new method developed at MIT and National Chiao Tung University, based on specially treated sheets of graphene oxide, could make it possible to capture and analyze individual cells from a small sample of blood. It could potentially lead to very-low-cost diagnostic devices (less than $5 a piece) that are mass-producible and could be used almost anywhere for point-of-care testing, especially in resource-constrained settings.

A single cell can contain a wealth of information about the health of an individual. The new system could ultimately lead to a variety of simple devices that could perform a variety of sensitive diagnostic tests, even in places far from typical medical facilities, for cancer screening or treatment follow-up, for example.

How to capture DNA, proteins, or even whole cells for analysis

The material (graphene oxide, or GO) used in this research is an oxidized version of the two-dimensional form of pure carbon known as graphene. The key to the new process is heating the graphene oxide at relatively mild temperatures.

This low-temperature annealing, as it is known, makes it possible to bond particular compounds to the material’s surface that can be used to capture molecules of diagnostic interest.

Schematic showing oxygen clustering, resulting in improved ability to recognize foreign molecules (credit: Neelkanth M. Bardhan et al./ACS Nano)

The heating process changes the material’s surface properties, causing oxygen atoms to cluster together, leaving spaces of bare graphene between them. This leaves room to attach other chemicals to the surface, which can be used to select and bond with specific molecules of interest, including DNA and proteins, or even whole cells. Once captured, those molecules or cells can then be subjected to a variety of tests.*

Nanobodies

The new research demonstrates how that basic process could potentially enable a suite of low-cost diagnostic systems.

For this proof-of-concept test, the team used molecules that can quickly and efficiently capture specific immune cells that are markers for certain cancers. They were able to demonstrate that their treated graphene oxide surfaces were almost twice as effective at capturing such cells from whole blood, compared to devices fabricated using ordinary, untreated graphene oxide.

They did this by enzymatically coating the treated graphene oxide surface with peptides called “nanobodies” — subunits of antibodies, which can be cheaply and easily produced in large quantities in bioreactors and are highly selective for particular biomolecules.**

The new process allows for rapid capture and assessment of cells or biomolecules within about 10 minutes and without the need for refrigeration of samples or incubators for precise temperature control. And the whole system is compatible with existing large-scale manufacturing methods.

The researchers believe many different tests could be incorporated on a single device, all of which could be placed on a small glass slide like those used for microscopy. The basic processing method could also make possible a wide variety of other applications, including solar cells and light-emitting devices.

The findings are reported in the journal ACS Nano. Authors include Angela Belcher, the James Mason Crafts Professor in biological engineering and materials science and engineering at MIT and a member of the Koch Institute for Integrative Cancer Research; Jeffrey Grossman, the Morton and Claire Goulder and Family Professor in Environmental Systems at MIT; Hidde L. Ploegh, a professor of biology and member of the Whitehead Institute for Biomedical Research; Guan-Yu Chen, an assistant professor in biomedical engineering at National Chiao Tung University in Taiwan; and Zeyang Li, a doctoral student at the Whitehead Institute.

“Efficiency is especially important if you’re trying to detect a rare event,” Belcher says. “The goal of this was to show a high efficiency of capture.” The next step after this basic proof of concept, she says, is to try to make a working detector for a specific disease model.

The work was supported by the Army Research Office Institute for Collaborative Biotechnologies and MIT’s Tata Center and Solar Frontiers Center.

* Other researchers have been trying to develop diagnostic systems using a graphene oxide substrate to capture specific cells or molecules, but these approaches used just the raw, untreated material. Despite a decade of research, other attempts to improve such devices’ efficiency have relied on external modifications, such as surface patterning through lithographic fabrication techniques, or adding microfluidic channels, which add to the cost and complexity. Those methods for treating graphene oxide for this purpose require high-temperature treatments or the use of harsh chemicals; the new system, which the group has patented, requires no chemical pretreatment and an annealing temperature of just 50 to 80 degrees Celsius (122 to 176 F).

** The researchers found that increasing the annealing time steadily increased the efficiency of cell capture: After nine days of annealing, the efficiency of capturing cells from whole blood went from 54 percent, for untreated graphene oxide, to 92 percent for the treated material. The team then performed molecular dynamics simulations to understand the fundamental changes in the reactivity of the graphene oxide base material. The simulation results, which the team also verified experimentally, suggested that upon annealing, the relative fraction of one type of oxygen (carbonyl) increases at the expense of the other types of oxygen functional groups (epoxy and hydroxyl) as a result of the oxygen clustering. This change makes the material more reactive, which explains the higher density of cell capture agents and increased efficiency of cell capture.


Abstract of Enhanced Cell Capture on Functionalized Graphene Oxide Nanosheets through Oxygen Clustering

With the global rise in incidence of cancer and infectious diseases, there is a need for the development of techniques to diagnose, treat, and monitor these conditions. The ability to efficiently capture and isolate cells and other biomolecules from peripheral whole blood for downstream analyses is a necessary requirement. Graphene oxide (GO) is an attractive template nanomaterial for such biosensing applications. Favorable properties include its two-dimensional architecture and wide range of functionalization chemistries, offering significant potential to tailor affinity toward aromatic functional groups expressed in biomolecules of interest. However, a limitation of current techniques is that as-synthesized GO nanosheets are used directly in sensing applications, and the benefits of their structural modification on the device performance have remained unexplored. Here, we report a microfluidic-free, sensitive, planar device on treated GO substrates to enable quick and efficient capture of Class-II MHC-positive cells from murine whole blood. We achieve this by using a mild thermal annealing treatment on the GO substrates, which drives a phase transformation through oxygen clustering. Using a combination of experimental observations and MD simulations, we demonstrate that this process leads to improved reactivity and density of functionalization of cell capture agents, resulting in an enhanced cell capture efficiency of 92 ± 7% at room temperature, almost double the efficiency afforded by devices made using as-synthesized GO (54 ± 3%). Our work highlights a scalable, cost-effective, general approach to improve the functionalization of GO, which creates diverse opportunities for various next-generation device applications.

Programmable shape-shifting molecular robots respond to DNA signals

Japanese researchers have developed an amoeba-like shape-changing molecular robot — assembled from biomolecules such as DNA, proteins, and lipids — that could act as a programmable and controllable robot for treating live culturing cells or monitoring environmental pollution, for example.

This the first time a molecular robotic system can recognize signals and control its shape-changing function, and their molecular robots could in the near future function in a way similar to living organisms, according to the researchers.

Developed by a research group at Tohoku University and Japan Advanced Institute of Science and Technology, the molecular robot integrates molecular machines within an artificial cell membrane and is about one micrometer in diameter — similar in size to human cells. It can start and stop its shape-changing function in response to a specific DNA signal.

Schematic diagram of the molecular robot. (A) In response to a start-stop DNA signal, molecular actuators (microtubules) inside the robot change the shape of the artificial cell membrane (liposome), controlled by a “molecular clutch” that transmits the force from the actuator (kinesin proteins, shown in green, assemble DNA to the cell membrane when activated). (B) Microscopy images of molecular robots. When the input DNA signal is “stop,” the clutch is turned “OFF,” deactivating the shape-changing behavior. The shape-changing is activated when the the clutch is turned “ON.” Scale bar: 20 μm. The white arrow indicates the molecular actuator part that transforms the shape of the membrane. (credit: Yusuke Sato)

The movement force is generated by molecular actuators (microtubules) controlled by a molecular clutch (composed of DNA and kinesin — a “walker” that carries molecules along microtubules in the body). The shape of the robot’s body (artificial cell membrane, or liposome — a vesicle made from a lipid bilayer) is changed (from static to active) by the actuator, triggered by specific DNA signals activated by UV irradiation.

Kinesin motor protein “walking” along microtubule filament (credit: Jzp706/CC)

The realization of a molecular robot whose components are designed at a molecular level and that can function in a small and complicated environment, such as the human body, is expected to significantly expand the possibilities of robotics engineering, according to the researchers.*

“With more than 20 chemicals at varying concentrations, it took us a year and a half to establish good conditions for working our molecular robots,” says Associate Professor Shin-ichiro Nomura at Tohoku University’s Graduate School of Engineering, who led the study. “It was exciting to see the robot shape-changing motion through the microscope. It meant our designed DNA clutch worked perfectly, despite the complex conditions inside the robot.”

Programmable by DNA computing devices

The research results were published in an open-access paper in Science Robotics on March 1, 2017.

The authors say that “combining other molecular devices would lead to the realization of a molecular robot with advanced functions. For example, artificial nanopores, such as an artificial channel composed of DNA, could be used to sense signal molecules in the surrounding environments through the channel.

“In addition, the behavior of a molecular robot could be programmed by DNA computing devices, such as judging the condition of environments. These implementations could allow for the development of molecular robots capable of chemotaxis [movement in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance], [similar to] white blood cells, and beyond.”

The research was supported by the JSPS KAKENHI, AMED-CREST and Tohoku University-DIARE.

* In the current design, “there are still limitations in the functions of the robot. For example, the switching of robot behavior is not reversible. The shape change is not directional and as yet not possible for complex tasks, for example, locomotion. However, to the best of our knowledge, this is the first implementation of a molecular robot that can control its shape-changing behavior in response to specific signal molecules.” — Yusuke Sato et al./Science Robotics


Abstract of Micrometer-sized molecular robot changes its shape in response to signal molecules

Rapid progress in nanoscale bioengineering has allowed for the design of biomolecular devices that act as sensors, actuators, and even logic circuits. Realization of micrometer-sized robots assembled from these components is one of the ultimate goals of bioinspired robotics. We constructed an amoeba-like molecular robot that can express continuous shape change in response to specific signal molecules. The robot is composed of a body, an actuator, and an actuator-controlling device (clutch). The body is a vesicle made from a lipid bilayer, and the actuator consists of proteins, kinesin, and microtubules. We made the clutch using designed DNA molecules. It transmits the force generated by the motor to the membrane, in response to a signal molecule composed of another sequence-designed DNA with chemical modifications. When the clutch was engaged, the robot exhibited continuous shape change. After the robot was illuminated with light to trigger the release of the signal molecule, the clutch was disengaged, and consequently, the shape-changing behavior was successfully terminated. In addition, the reverse process—that is, initiation of shape change by input of a signal—was also demonstrated. These results show that the components of the robot were consistently integrated into a functional system. We expect that this study can provide a platform to build increasingly complex and functional molecular systems with controllable motility.