Locking Leukemia’s Cellular Escape Hatch

Kris Wood, PhD, associate professor of
Pharmacology and Cancer Biology

Leukemia starts in cells that would normally develop into different types of blood cells. About 61,000 people in the U.S. are diagnosed each year, and depending on the type of leukemia and the age of the patient, five-year survival rates vary between about 20-80%.

After losing a close friend to an aggressive form of leukemia, acute myeloid leukemia (AML), Kris Wood, PhD, associate professor of pharmacology and cancer biology, devoted his research to helping find better treatment options for people with leukemias and lymphomas. He and his colleagues have discovered a potential new drug therapy that is preparing to enter clinical trials.

A new class of drugs called nuclear exportin inhibitors has recently been approved for use to treat cancers. Nuclear exportins are proteins that shuttle other proteins out of the nucleus of a cell. These new drugs stop the shuttle from leaving the station.

“The idea is that if you treat cells with a drug that blocks a nuclear exportin,” Wood said, “its client proteins become trapped in the nucleus.” And while researchers don’t fully understand why this is therapeutic, it works. Wood and his team investigated the mechanisms behind it. Their results were published in Nature Cancer.

First, they treated AML cells with Selinexor, a nuclear exportin inhibitor. At the same time, they used CRISPR screens to knock out thousands of genes across the genome one at a time to identify genes that made the drug work either much better or much worse when knocked out.

Equine eye docs help horse regain sight

Willy was diagnosed with equine recurrent uveitis, a common but harmful complex autoimmune disease among horses. After treatment, Willy regained most of his vision and has a high quality of life.
Source: Provided to Cornell University

Willy, a 3-year-old quarter horse, has a goofy personality and loves to spend time with his many chicken friends at owner Mariah Kauffman’s home in Snyder County, Pennsylvania.

Soon after Willy joined their family, however, Kauffman noticed that every once in a while, his eyes would cloud over, then appear clear the next day. “He started bumping into things and getting cuts on his face,” Kauffman said. “He would run into the fence and spooked easily.”

That’s when she decided to call Willy’s veterinarian, Dr. Jacqueline Rapp of Susquehanna Valley Veterinary.

Rapp quickly referred Willy to the Cornell Equine Hospital for specialty care from Dr. Kelly Knickelbein, assistant clinical professor, alongside ophthalmology residents Dr. Irini Lamkin and Dr. Brittany Schlesener.

The Cornell team diagnosed him with equine recurrent uveitis (ERU), a common but harmful complex autoimmune disease among horses, with both genetic and environmental factors.

study finds living near trails reduces risk for heart disease

The Northeast Pioneers Greenway Is One of the Four Multi-Use Trails in Winnipeg That Was Studied in the Research Project. 
Photo Courtesy of Winnipeg Trails Association

A University of Manitoba-led study found that living close to a trail used for walking, running and cycling leads to an eight per cent reduction in the risk factors for heart disease.

“If you build it, they will come, and maybe even live longer,” said Dr. Jon McGavock, professor of pediatrics and child health at the Max Rady College of Medicine, Rady Faculty of Health Sciences.

The study looked at four multi-use trails in Winnipeg – the Yellow Ribbon Greenway, Northeast Pioneers Greenway, Transcona Trail and Southside Greenway. The trails ranged from four to seven kilometers and are in largely suburban areas.

The study, published in the International Journal of Behavioral Nutrition and Physical Activity, found that the 20 kilometers of trails attracted 5,000 cyclists every week. This added up to 1.6 million cycling trips over a five-year period.

“Since the trails were built in 2012, that adds up to 4,000 to 7,000 fewer Winnipeggers living with a risk factor for heart disease,” said McGavock, who is also an investigator with the Children’s Hospital Research Institute of Manitoba. “Importantly, this health benefit was greatest for people living along the Southside Greenway, the busiest trail.”

Common drug-resistant superbug develops fast resistance to 'last resort' antibiotic

Pseudomonas under a microscope
Credit: Sean Booth

New research has found that Pseudomonas bacterium develops resistance much faster than usual to a common ‘last-resort’ antibiotic.

A study published today in Cell Reports reveals how populations of a bacterium called Pseudomonas respond to being treated with Colistin, a 'last resort' antibiotic for patients who have developed multi-drug resistant infections.

Antibiotics play a key role in human health by helping to combat bacterial infection, but bacteria can evolve resistance to antibiotics patients rely on. Antibiotic-resistant infections now cause >1 million deaths worldwide per year.

With a small number of ‘last-resort’ antibiotics available, researchers from the University of Oxford are investigating the processes that drive the rise, and fall, of resistance in common bacterial pathogen populations, which is key to tackling the increase in antimicrobial resistance (AMR).

Integration leads to leap in tech for forest inventory and management

Credit: Purdue University

Through integration of aerial and ground-based mobile mapping sensors and systems, a team of Purdue digital forestry researchers has used advanced technology to locate, count and measure over a thousand trees in a matter of hours.

“The machines are counting and measuring each tree – it is not an estimation using modeling, it is a true forest inventory,” said Songlin Fei, the Dean's Remote Sensing Chair and professor of forestry and natural resources and leader of Purdue University’s Digital Forestry initiative. “This is a groundbreaking development on our path to using technology for a quick, accurate inventory of the global forest ecosystem, which will improve our ability to prevent forest fires, detect disease, perform accurate carbon counting and make informed forest management decisions.”

The technology uses manned aircraft, unmanned drones and backpack-mounted systems. The systems integrate cameras with light detection and ranging units, or LiDAR, together with navigation sensors, including integrated global navigation satellite systems (GNSS) and inertial navigation systems (INS). A Purdue team led by Ayman Habib, Thomas A. Page Professor of Civil Engineering and head of Purdue's Digital Photogrammetry Research Group, who co-led the project with Fei, designed and created the systems.

Exotic tree plantations can disturb local wildlife, researchers find

Canthon fulgidus, a roller-dung beetle species in the study region
Credit: Dr Filipe França

Initiatives using non-native tree species can impact tropical insects in neighboring forests, according to an international study.

Scientists at the University of Bristol and Federal University of Western Pará, in Brazil have found that Eucalyptus plantation edge effects radiates up to 800 meters into the interior of nearby Amazonian forests, when applied to ecologically important dung beetles.

As the world seeks to mitigate human-induced climate change, planted forests have become widespread restoration strategies across the globe. However, the findings, published today in Forest Ecology and Management, suggest that while well-intentioned, exotic tree plantations can have a wider influence on the native biodiversity of hyperdiverse tropical forests.

In ecology, edge effect research investigates how biological populations or communities change at the boundary of two or more habitats.

Yolk-Shell Nanocrystals with Movable Gold Yolk: Next Generation of Photocatalysts

The synthesis of yolk-shell nanostructures involves sulfidation on an Au@Cu2O core-shell nanocrystal template to convert the shell composition to various metal sulphides.
Credit: Tokyo Institute of Technology

Owing to their unique permeable, hollow shell structures with inner, movable cores, yolk-shell nanocrystals are suitable for a wide variety of applications. Yolk-shell nanocrystals consisting of a gold core with various semiconductor shells have been developed by Tokyo Tech researchers, using a novel sequential ion-exchange process. These metal-semiconductor yolk-shell nanocrystals can serve as highly effective photocatalysts for many applications.

Yolk-shell nanocrystals are unique materials with fascinating structural properties, such as a permeable shell, interior void space, and movable yolk. These nanocrystals are suitable for a variety of applications, depending on the choice of materials used for their fabrication.

For example, if the inner surface of their shells are reflective, yolk-shell nanocrystals can make for a reliable photovoltaic device. A mobile core can can act as a stirrer, capable of mixing solutions held within the shell. The inner and outer surfaces of the shell provide plenty of active sites for reactions, and the yolk-shell structure's fascinating properties (a result of electronic interactions and charge-transfer between the surfaces of the structure) make these nanocrystals ideal for photocatalysis applications. Understandably, yolk-shell nanocrystals have earned the attention of researchers worldwide.

New Study Deepens Understanding of How Animals See, and What Colors

 Researchers determined that animals adapted to land see more colors than animals adapted to water. Animals adapted to open terrestrial habitats see a wider range of colors than animals adapted to forests.
 Credit: Artwork by Matt Murphy

Gathering vision data for hundreds of vertebrates and invertebrates, U of A biologists have deepened scientists’ understanding of animal vision, including the colors they see.

Researchers have determined that animals adapted to land are able to see more colors than animals adapted to water. Animals adapted to open terrestrial habitats see a wider range of colors than animals adapted to forests.

However, evolutionary history — primarily the difference between vertebrates and invertebrates — significantly influences which colors a species sees. Invertebrates see shorter wavelengths of light, compared to vertebrates.

Biological sciences doctoral student Matt Murphy and assistant professor Erica Westerman recently published these findings in Proceedings of the Royal Society B, a top British scientific journal. Their article, “Evolutionary history limits species’ ability to match color sensitivity to available habitat light,” explains how environment, evolution and, to some extent, genetic composition influence how and what colors animals see.

Copper makes seed pods explode

A stiff polymer called lignin (stained red) is deposited in a precise pattern in the cell walls of exploding seed pods. Researchers identified three laccase enzymes required to form this lignin. No lignin forms in the cell wall (stained blue) when all three genes are knocked out by CRISPR/Cas9 gene editing. 
Credit: Miguel Pérez Antón

Plants have evolved numerous strategies to spread their seeds widely. Some scatter their seeds to the wind, while others tempt animals and birds to eat their seed-filled fruits. And a few rare plants – such as the popping cress Cardamine hirsuta – have evolved exploding seed pods that propel their seeds in all directions. In their new study published in PNAS, Angela Hay and colleagues – from the Max Planck Institute for Plant Breeding Research in Cologne, Germany – investigate what genes control the mechanical structure of these exploding seed pods. Their findings show that a key micronutrient – copper – is essential for laying down a precise pattern of lignin in the seed pods. Lignin is an abundant plant polymer found in lignocellulose, the main structural material in plants. It is present in plant cells walls and is responsible for making wood stiff.

C. hirsuta seed pods consist of two, long valves. When the seeds are ready for dispersal, these valves rapidly separate and coil back, firing seeds out across a large area. The secret to these pods explosive nature is their unique mechanical design, which features three stiff rods of lignin connected by hinges. These hinges are crucial for the explosive release of potential energy stored in the pod. To create these hinged structures, lignin is deposited in a precise pattern in a single layer of seed pod cells, called endocarpb.

How animals reach their correct size

The development of hundreds of C. elegans individuals growing in micro-chambers was recorded with time-lapse microscopy.
Credit: Towbin Lab

Adults of the same species usually differ very little in their size. A team from the University of Bern and the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel has now discovered a mechanism that ensures such size uniformity. The research using nematodes showed that the speed of growth determines the speed of a genetic clock that times development. Thereby, individuals that grow slowly are given more time to grow and can reach the same adult body size.

By and large, individuals of the same species grow to the same size. This uniformity in size is astounding, since intrinsic randomness in developmental processes and in environmental conditions produce substantial differences in how fast individuals grow. Moreover, because animal growth is often exponential, even small differences in growth can amplify to large differences in size. How do animals nevertheless make sure to reach the correct size?

Lab Earthquakes Show How Grains at Fault Boundaries Lead to Major Quakes

A three-dimensional visualization shows how rock gouge can arrest a rupture (in red) but, with a combination of dynamic stressing and dynamic weakening, will ultimately re-nucleate the rupture shortly thereafter (in blue).
Credit: Vito Rubino / California Institute of Technology

By simulating earthquakes in a lab, Caltech engineers have provided strong experimental support for a form of earthquake propagation now thought responsible for the magnitude-9.0 earthquake that devastated the coast of Japan in 2011.

Along some fault lines, which are the boundaries of tectonic plates, a fine-grained gravel is formed as the plates grind against one another. The influence of this gravel on earthquakes has long been the subject of scientific speculation. In a new paper appearing in the journal Nature the Caltech researchers show that the fine gravel, known as rock gouge, first halts earthquake propagation, but then triggers the rebirth of earthquakes to generate powerful ruptures.

"Our novel experimental approach has enabled us to look into the earthquake process up close, and to uncover key features of rupture propagation and friction evolution in rock gouge," says Vito Rubino, research scientist and lead author of the Nature paper. "One of the main findings of our study is that fault sections previously thought to act as barriers against dynamic rupture may in fact host earthquakes, as a result of the activation of co-seismic friction weakening mechanisms."

Hallucinating to better text translation

Source/Credit: MIT

As babies, we babble and imitate our way to learning languages. We don’t start off reading raw text, which requires fundamental knowledge and understanding about the world, as well as the advanced ability to interpret and infer descriptions and relationships. Rather, humans begin our language journey slowly, by pointing and interacting with our environment, basing our words and perceiving their meaning through the context of the physical and social world. Eventually, we can craft full sentences to communicate complex ideas.

Similarly, when humans begin learning and translating into another language, the incorporation of other sensory information, like multimedia, paired with the new and unfamiliar words, like flashcards with images, improves language acquisition and retention. Then, with enough practice, humans can accurately translate new, unseen sentences in context without the accompanying media; however, imagining a picture based on the original text helps.

This is the basis of a new machine learning model, called VALHALLA, by researchers from MIT, IBM, and the University of California at San Diego, in which a trained neural network sees a source sentence in one language, hallucinates an image of what it looks like, and then uses both to translate into a target language. The team found that their method demonstrates improved accuracy of machine translation over text-only translation. Further, it provided an additional boost for cases with long sentences, under-resourced languages, and instances where part of the source sentence is inaccessible to the machine translator.

Bumps could smooth quantum investigations

Stamping or growing 2D materials onto a patterned surface could create models for 1D systems suitable for the exploration of quantum effects, according to a new theory by Rice University engineers. The “bumps” would manipulate the flow of electrons into bands that mimic 1D semiconductors.
Credit: Yakobson Research Group/Rice University

Atoms do weird things when forced out of their comfort zones. Rice University engineers have thought up a new way to give them a nudge.

Materials theorist Boris Yakobson and his team at Rice’s George R. Brown School of Engineering have a theory that changing the contour of a layer of 2D material, thus changing the relationships between its atoms, might be simpler to do than previously thought.

While others twist 2D bilayers -- two layers stacked together -- of graphene and the like to change their topology, the Rice researchers suggest through computational models that growing or stamping single-layer 2D materials on a carefully designed undulating surface would achieve “an unprecedented level of control” over their magnetic and electronic properties.

They say the discovery opens a path to explore many-body effects, the interactions between multiple microscopic particles, including quantum systems.

The paper by Yakobson and two alumni, co-lead author Sunny Gupta and Henry Yu, of his lab appears in Nature Communications.

Breakthrough paves way for photonic sensing at the ultimate quantum limit

Photonic chip with a microring resonator nanofabricated in a commercial foundry.
Photo credit: Joel Tasker, QET Labs

A Bristol-led team of physicists has found a way to operate mass manufacturable photonic sensors at the quantum limit. This breakthrough paves the way for practical applications such as monitoring greenhouse gases and cancer detection.

Sensors are a constant feature of our everyday lives. Although they often go unperceived, sensors provide critical information essential to modern healthcare, security, and environmental monitoring. Modern cars alone contain over 100 sensors and this number will only increase.

Quantum sensing is poised to revolutionize today's sensors, significantly boosting the performance they can achieve. More precise, faster, and reliable measurements of physical quantities can have a transformative effect on every area of science and technology, including our daily lives.

However, the majority of quantum sensing schemes rely on special entangled or squeezed states of light or matter that are hard to generate and detect. This is a major obstacle to harnessing the full power of quantum-limited sensors and deploying them in real-world scenarios.

New nanoparticles aid sepsis treatment in mice

Shaoqin “Sarah” Gong
Source: University of Wisconsin–Madison

Sepsis, the body’s overreaction to an infection, affects more than 1.5 million people and kills at least 270,000 every year in the U.S. alone. The standard treatment of antibiotics and fluids is not effective for many patients, and those who survive face a higher risk of death.

In new research published in the journal Nature Nanotechnology today, the lab of Shaoqin “Sarah” Gong, a professor with the Wisconsin Institute for Discovery at the University of Wisconsin–Madison, reported a new nanoparticle-based treatment that delivers anti-inflammatory molecules and antibiotics.

The new system saved the lives of mice with an induced version of sepsis meant to serve as a model for human infections, and is a promising proof-of-concept for a potential new therapy, pending additional research.

The new nanoparticles delivered the chemical NAD+ or its reduced form NAD(H), a molecule that has an essential role in the biological processes that generate energy, preserve genetic material and help cells adapt to and overcome stress. While NAD(H) is well known for its anti-inflammatory function, clinical application has been hindered because NAD(H) cannot be taken up by cells directly.

“To enable clinical translation, we need to find a way to efficiently deliver NAD(H) to the targeted organs or cells. To achieve this goal, we designed a couple of nanoparticles that can directly transport and release NAD(H) into the cell, while preventing premature drug release and degradation in the bloodstream,” says Gong, who also holds appointments in the Department of Biomedical Engineering and the UW School of Medicine and Public Health’s Department of Ophthalmology and Visual Sciences.

The interdisciplinary work was led by Gong along with Mingzhou Ye and Yi Zhao, two postdoctoral fellows in the Gong lab. John-Demian Sauer, a professor in the Department of Medical Microbiology and Immunology, also collaborated on the project.