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Up to 80% of metastatic colorectal cancers are likely to have spread to distant locations in the body before the original tumor has exceeded the size of a poppy seed, according to a study of nearly 3,000 patients by researchers at the Stanford University School of Medicine.

Identifying patients with early-stage colorectal tumors that are born to be bad may help doctors determine who should receive early treatments, such as systemic chemotherapy, to kill cancer cells lurking far from the tumor's original location.

"This finding was quite surprising," said Christina Curtis, PhD, assistant professor of medicine and of genetics at Stanford. "In the majority of metastatic colorectal cancer patients analyzed in this study, the cancer cells had already spread and begun to grow long before the primary tumor was clinically detectable. This indicates that metastatic competence was attained very early after the birth of the cancer. This runs counter to the prevailing assumption that metastasis occurs late in advanced primary tumors and has implications for patient stratification, therapeutic targeting and earlier detection."

Researchers and clinicians have assumed that cancers acquire the ability to metastasize through the gradual accumulation of molecular changes over time. These changes, the thinking goes, confer specific traits that eventually allow cancer cells to escape the surrounding tissue, enter the bloodstream and take up residence in new locations. In this scenario, metastasis, if it occurs, would be a relatively late event in the evolution of the primary cancer.

Curtis, who co-directs the molecular tumor board at the Stanford Cancer Institute, is the senior author of the study, which will be published online June 17 in Nature Genetics. Postdoctoral scholar Zheng Hu, PhD, is the lead author.

Second-leading cause of cancer death

Colorectal cancer is the second-leading cause of cancer death in men and women combined in the United States. It metastasizes most often to the liver. Rarely, it metastasizes to the brain, where it is almost always fatal.

The initial changes to the genome that cause cancer are called driver mutations. The driver changes that jumpstart colorectal cancer are well-known, making it a good model to learn more about how and when the disease progresses. Curtis and her colleagues sought to reconstruct when metastasis occurred on a patient-by-patient basis and to identify its drivers by analyzing tumor-genome data.

Studying tumor biopsies, the researchers compared patterns of genetic mutations in the primary tumors of 23 patients with the patterns in their liver or brain metastases. They looked for similarities or differences between primary and metastatic cancers obtained from the same person. They then used those patterns to create a kind of evolutionary tree of each patient's cancer -- similar to one a biologist might make to trace the evolution of an animal species from a single ancestor.

The trees the researchers pieced together indicated that in 17 of 21 patients (two of the original patients were excluded from the analysis), the metastatic tumors were started by just one cell, or a small group of genetically similar cells, that broke off from the primary tumor early in its development.

"The cells that formed the metastasis were more closely related to the ancestors of the primary tumor than its present-day relatives," Curtis said. "Moreover, the metastasis shared early drivers present in the 'trunk' of the evolutionary tree, but harbored few additional drivers. This suggested that these cancers acquired metastatic competence very early on during their growth."

To further pinpoint when metastasis occurred, Curtis and her team developed a computer program and statistical method to measure the time of metastatic spread relative to the size of the primary tumor in an individual patient. Their analysis provides the first quantitative evidence for early metastatic spread in human colon cancer -- a pattern observed in virtually all cases they examined. However, Curtis noted that not all colorectal tumors will metastasize and that it will be important to also understand cellular processes that keep the cancer from spreading to other organs.

A culprit: Mutated PTPRT

Curtis and her colleagues then took what they had learned and applied it to 938 people with metastatic and 1,813 people with non-metastatic colorectal cancer whose medical histories were known and whose primary tumors had been profiled to identify genetic changes in known cancer-associated genes.

"We found that specific combinations of mutations were highly predictive of metastasis," Curtis said. For example, mutations in a gene called PTPRT, in combination with mutations in classic colorectal cancer driver genes, were almost exclusively found in patients with metastatic cancers.

Previous studies have shown that the loss of PTPRT function increases the activity of a protein called STAT3, which enhances cellular survival. The researchers speculate that inhibiting STAT3 might thwart tumor growth and metastasis.

Curtis and her colleagues are now working to learn whether specific molecular changes tilt the balance of metastasis in colorectal cancers toward the liver or the brain. They are also applying similar analyses to other types of cancers.

"The concept of early systemic spread has been controversial, due in part to the challenge of quantifying this process in the human system and the reliance on animal models," Curtis said. "These data indicate that metastasis can occur early in human colorectal cancer and highlights the critical need for the earlier detection of aggressive disease. New biomarkers based on specific combinations of alterations might enable the identification of potentially lethal colorectal tumors at an earlier stage so that they may be intercepted and appropriately treated, potentially with therapies directed against their specific aberrations."

For the first time, researchers have mapped the building blocks of the human lungs and airways, in both asthma patients and normal people. The research from the Wellcome Sanger Institute, University Medical Center Groningen, Open Targets, GSK and collaborators revealed the identity of each cell type, creating the first draft Human Cell Atlas of the lung. They also discovered an entirely new cell state that produces mucus in asthma patients.

Reported today (17 June) in Nature Medicine, the maps reveal the differences between asthmatic and normal airways and identify how cells in the lung communicate with each other. Understanding the cells and their signals could lead to finding new drug targets for treating asthma.

Asthma is a common lung condition that makes breathing difficult and triggers coughing, wheezing and shortness of breath. It is caused by swelling of the tubes that carry air in and out of the lungs making it difficult to get enough oxygen. Asthma affected over 350 million people worldwide in 2015, and over 5 million people* in the UK are currently receiving treatment for asthma.

While it is often manageable with medication, asthma can cause ongoing problems and there is the risk of severe, life-threatening asthma attacks. A better understanding of healthy lung cells and the differences with asthmatic lungs is required to develop new effective medications.

To explore cell types within normal lungs and upper airways, researchers used single cell technology to study samples from 17 people. They analysed more than 36,000 individual cells from the nasal area and from three different areas of the lung. This allowed researchers to see exactly which genes were active in each cell and identify the specific cell type.

The researchers then detected the different cell types and activities in lung samples from six asthma patients, comparing them to normal lungs. They discovered there were clear differences between the cells in normal and asthmatic lungs. One symptom of asthma is an overproduction of mucus. However, not all the cells responsible for this were known. The researchers discovered a new mucus-creating cell state - the muco-cilliated state - in asthmatic lungs, that had not been seen before.

Dr Felipe Vieira Braga, a first author on the paper from the Wellcome Sanger Institute and Open Targets, said: "We have generated a detailed anatomical map of the respiratory airways, producing the first draft human lung cell atlas from both normal and asthmatic people. This has given us a better definition of the cell types in asthmatic lungs, and allowed us to discover an entirely new cell state in asthmatic patients that produces mucus."

The study revealed large differences between normal and asthmatic lungs, in the cells and how they communicated with each other. The asthmatic lungs had many more inflammatory Th2 cells, which sent the vast majority of cellular signals in asthma, compared with a broad range of cell communications in normal lungs.

Dr Martijn Nawijn, a senior author from University Medical Center Groningen, said: "We already knew that inflammatory Th2 cells played a role in asthma, but only now do we see how great that influence is. In normal people, all kinds of cells communicate with each other in order to keep the airways functioning well. But in asthma patients, almost all of those interactions are lost. Instead of a network of interactions, in asthma the inflammatory cells seem to completely dominate the communication in the airways."

Knowing the types of cells in asthmatic lungs and how they communicate, could help researchers seek new drug targets that could prevent the cells from responding to the inflammatory signals and help restore normal lung function.

The atlases also revealed that location was important for the lung cells. The study showed that cells in different areas of the lung had very different cellular activities. This has further implications for studying drug targets and designing drug trials.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute, University of Cambridge and Open Targets, and co-chair of the Human Cell Atlas Organising Committee, said: "As part of the Human Cell Atlas initiative, we have created the first comprehensive cellular map of the lungs. Our large-scale, open access data reveals the activity of different cells, their communication pathways and locations. The lung cell atlas will provide a great resource for further lung research and we hope that it will enable the identification of potential new therapeutic targets for asthma relief."

PITTSBURGH, June 17, 2019 - A new study from the University of Pittsburgh and UPMC Children's Hospital of Pittsburgh finds that an antibody in breastmilk is necessary to prevent necrotizing enterocolitis (NEC)--an often deadly bacterial disease of the intestine--in preterm infants.

Immunoglobulin A (IgA) antibodies bind to bacteria in the gut, and, according to the study, the more bacteria that's tied up with IgA, the less likely babies are to develop NEC. Since preterm infants get IgA only from mothers' milk in their fragile first weeks of life, the authors emphasize the importance of breastmilk for these babies. The study appears today in Nature Medicine.

"It's been well known for a decade that babies who get NEC have particular bacteria--Enterobacteriaceae--in their guts, but what we found is that it's not how much Enterobacteriaceae there is, but whether it's bound to IgA that matters. And that's potentially actionable," said senior author Timothy Hand, Ph.D., assistant professor of pediatric infectious diseases at the R.K. Mellon Institute for Pediatric Research and Pitt's School of Medicine.

The researchers looked at fecal samples from 30 preterm infants with NEC and 39 age-matched controls. Overall, breastmilk-fed babies had more IgA-bound gut bacteria than their formula-fed peers, and those who developed NEC were more likely to have been formula-fed.

Tracking these infants' gut microbiomes over time, Hand's team found that for the healthy babies, Enterobacteriaceae was largely tied up by IgA, allowing diverse bacterial flora to flourish. But for the NEC infants in the days leading up to diagnosis, IgA-unbound Enterobacteriaceae was free to take over.

To demonstrate causation between IgA and NEC, Hand and his team used a mouse model.

"Mice, when they're born, are equivalent in their intestinal development to a human baby born at 24 weeks," said lead author Kathyayini Gopalakrishna, M.D., a Ph.D. student in the Pitt Graduate School of Public Health's Department of Human Genetics, "so they're a perfect model to study NEC in preterm infants."

The researchers bred mice that couldn't produce IgA in their breastmilk. Pups reared on IgA-free milk were just as susceptible to NEC as their formula-fed littermates. So, breastfeeding in and of itself is not sufficient for NEC prevention. The milk must contain IgA to confer this specific benefit.

But the solution for NEC may not be as simple as putting IgA into formula, Hand said. Because breastmilk has other benefits beyond IgA, donor milk is still the best option to fill the gap when breastfeeding or providing pumped maternal milk isn't an option.

"What we showed is that IgA is necessary but may not be sufficient to prevent NEC," Hand said. "What we're arguing is that you might want to test the antibody content of donor milk and then target the most protective milk to the most at-risk infants."

Physicists from the Immanuel Kant Baltic Federal University conduct a study on nanomaterials that have been synthesized by the method of the electric explosion. Research group of the Laboratory of Novel Magnetic Materials has studied the magnetic and structural properties of metallic α-Fe magnetic nanoparticles, which were covered with non-magnetic iron oxide.

According to Alexander Omelyanchik, the researcher of the Laboratory of Novel Magnetic Materials of IKBFU, the physicists used an alternative method of the explosion of an electric conductor. The obtained nanoparticles have a high value of magnetization saturation. The chemical stability and biocompatibility of the particles are increased, which makes them useful for a number of applications, including sensing and biomedicine.

The co-authors of the research are Valeria Rodionova and Alexander Omelyanchik, the physicists from IKBFU, and their colleagues from Russian Academy of Science Ural Divisions (Institute of Electrophysics), National University of Science and Technology MISIS and Instituto di Struttura della Materia (CNR-ISM). Recently, the Journal of Magnetism and Magnetic Materials has published the scientific article High-quality α-Fe nanoparticles synthesized by the electric explosion of wires.

AMES, Iowa - New research may explain why an antioxidant that protects the brain is also associated with deterioration in areas susceptible to Alzheimer's disease.

The antioxidant, superoxide dismutase or SOD1, improves cognition by fighting off free radicals that cause oxidative damage in the brain. However, an Iowa State University research team found SOD1's protective benefits dramatically weaken when levels of tau proteins - a hallmark of Alzheimer's disease - increase. Based on the results, researchers suspect SOD1 is fighting to counteract the damaging effects of tau proteins, but eventually loses the battle.

"In individuals with Alzheimer's or mild cognitive impairment, SOD1 was related to more gray matter, which is significant for memory," said Kelsey McLimans, a recent Ph.D. graduate and research assistant in food science and human nutrition. "However, our results show 90 percent of this positive association is negated by tau. This bolsters our hypothesis that SOD1 itself isn't detrimental; it's just trying to limit the oxidative damage caused by tau."

McLimans and Bridget Clark, a former Cyclone Summer Scholar research intern, led the study published online by the journal Antioxidants & Redox Signaling. Their interest in antioxidants that occur naturally in the body and in the foods we eat led them to look at how SOD1 affects aging. Clark says the results put researchers another step closer to understanding the importance of antioxidants.

"This study could further the exploration of how nutrition might reduce and prevent neurodegeneration and aging in the brain," Clark said.

Auriel Willette, assistant professor of food science and human nutrition, who oversaw the research; Anumantha Kanthasamy, Distinguished Professor and chair of biomedical sciences; Vellareddy Anantharam, research associate professor of biomedical sciences; Alexandra Plagman, graduate research assistant; and Colleen Pappas, postdoctoral research associate, were part of the team working with McLimans and Clark. The group is the first to identify the correlation between SOD1 and tau proteins in people with varying degrees of Alzheimer's disease.

Tau spreads like fire

The researchers analyzed data from adults, ranging in age from 65 to 90, participating in the Alzheimer's Disease Neuroimaging Initiative. Of the 287 people in the study, 86 had no cognitive impairment, 135 had mild impairment and 66 had Alzheimer's disease.

Much of what researchers know about SOD1 and the brain is based on post-mortem brain analysis of patients with Alzheimer's, McLimans said. Until now, it was unknown how SOD1 related to cognition and biomarkers in the brain and cerebrospinal fluid for adults living with the disease. Willette says their results provide further evidence of tau's role in the development of Alzheimer's.

"The disease might begin or progress partly because antioxidants in our brain stop working effectively when tau levels increase," Willette said. "It's similar to a burning building. You can pump as much water as possible onto the fire, but once it's spreading out of control, no amount of water is going to stop it."

Iowa State researchers say additional studies are needed to determine if increasing production of SOD1 - possibly through diet or medication - might delay the progression of Alzheimer's disease.

NEW YORK, June 17, 2019 -- The maturation of visual acuity in both amblyopia and myopia may be closely associated with the development of pathways signaling bright features in the brain, according to research published in the Journal of Neuroscience by SUNY College of Optometry doctoral candidate Carmen Pons Torres and colleagues in the laboratory of distinguished professor Dr. Jose-Manuel Alonso.

While past research indicated that amblyopia, also known as lazy eye, equally affects the brain pathways signaling bright and dark features in an image, Ms. Pons Torres found that amblyopia affects the perception of bright features more than dark features. Her research also shows that, as amblyopia becomes more severe and the images projected in the eye lose detail, bright targets become increasingly difficult to discern. This recent work opens the possibility to treat amblyopia by strengthening weakened brain pathways that signal bright stimuli.

Amblyopia is a developmental problem of the brain that compromises visual acuity in two to five percent of children around the world. Children typically develop amblyopia in one eye and the current treatment is to patch the healthy eye to force the lazy eye to work harder.

Despite being in use for centuries, such patching treatments are problematic. Amblyopia may go undiagnosed for years and patching is less effective in mature brains, there is a high risk of amblyopia recurrence after patching interruption, and low compliance remains prominent as children often do not like to wear the eye patch and tend to remove the treatment when unsupervised.

Previous work from the Alonso lab published in the Journal of Vision by Pons, et al. has shown that low light and optical blur (e.g. reading indoors under dim light) affect the perception of bright targets more than dark targets. Both low light and optical blur are risk factors in myopia, or nearsightedness, which is another developmental problem affecting visual acuity. Another recent study from the Alonso team published in Cell Reports by SUNY Optometry postdoctoral researcher Dr. Reece Mazade, et al. found that these pathways are best stimulated with large bright long-lasting targets, particularly sky patches, which are bright, large and slow-moving.

Both new findings open the door for further exploration of new treatments that use natural visual stimuli more effectively to promote healthier visual behaviors, including wearable devices that monitor vision outdoors.

How did the Red Planet get all of its clouds? CU Boulder researchers may have discovered the secret: just add meteors.

Astronomers have long observed clouds in Mars' middle atmosphere, which begins about 18 miles (30 kilometers) above the surface, but have struggled to explain how they formed.

Now, a new study, which will be published on June 17 in the journal Nature Geoscience, examines those wispy accumulations and suggests that they owe their existence to a phenomenon called "meteoric smoke"--essentially, the icy dust created by space debris slamming into the planet's atmosphere.

The findings are a good reminder that planets and their weather patterns aren't isolated from the solar systems around them.

"We're used to thinking of Earth, Mars and other bodies as these really self-contained planets that determine their own climates," said Victoria Hartwick, a graduate student in the Department of Atmospheric and Ocean Sciences (ATOC) and lead author of the new study. "But climate isn't independent of the surrounding solar system."

The research, which included co-authors Brian Toon at CU Boulder and Nicholas Heavens at Hampton University in Virginia, hangs on a basic fact about clouds: They don't come out of nowhere.

"Clouds don't just form on their own," said Hartwick, also of the Laboratory for Atmospheric and Space Physics at CU Boulder. "They need something that they can condense onto."

On Earth, for example, low-lying clouds begin life as tiny grains of sea salt or dust blown high into the air. Water molecules clump around these particles, becoming bigger and bigger until they form the large puffs that you can see from the ground.

But, as far as scientists can tell, those sorts of cloud seeds don't exist in Mars' middle atmosphere, Hartwick said. And that's what led her and her colleagues to meteors.

Hartwick explained that about two to three tons of space debris crash into Mars every day on average. And as those meteors rip apart in the planet's atmosphere, they inject a huge volume of dust into the air.

To find out if such smoke would be enough to give rise to Mars' mysterious clouds, Hartwick's team turned to massive computer simulations that attempt to mimic the flows and turbulence of the planet's atmosphere.

And sure enough, when they included meteors in their calculations, clouds appeared.

"Our model couldn't form clouds at these altitudes before," Hartwick said. "But now, they're all there, and they seem to be in all the right places."

The idea might not be as outlandish as it sounds, she added. Research has shown that similar interplanetary schmutz may help to seed clouds near Earth's poles.

But she also says that you shouldn't expect to see gigantic thunderheads forming above the surface of Mars anytime soon. The clouds her team studied were much more like bits of cotton candy than the clouds Earthlings are used to.

"But just because they're thin and you can't really see them doesn't mean they can't have an effect on the dynamics of the climate," Hartwick said.

The researchers' simulations, for example, showed that middle atmosphere clouds could have a large impact on the Martian climate. Depending on where the team looked, those clouds could cause temperatures at high altitudes to swing up or down by as much as 18 degrees Fahrenheit (10 degrees Celsius).

And that climactic impact is what gets Brian Toon, a professor in ATOC, excited. He said that the team's findings on modern-day Martian clouds may also help to reveal the planet's past evolution and how it once managed to support liquid water at its surface.

"More and more climate models are finding that the ancient climate of Mars, when rivers were flowing across its surface and life might have originated, was warmed by high altitude clouds," Toon said. "It is likely that this discovery will become a major part of that idea for warming Mars."

PELLSTON--In an aspen-dominated hardwood forest at the northern tip of the state's Lower Peninsula, University of Michigan scientists are testing ways to make the region's forests more resilient to climate change.

About 12,000 mature trees--mostly aspen--are being cut on 77 acres at the U-M Biological Station, a 10,000-acre research and teaching facility just south of the Mackinac Bridge, near the town of Pellston.

The idea of the UMBS Adaptive Aspen Management Experiment is to replace some of the century-old aspen with a mix of tree species and age groups that may be better equipped to handle a warming climate, extreme weather events, and stresses such as insect pests.

The harvesting started in March, paused in May for bird-nesting season and student summer research, and will be completed in September. By the time it's done, about 200 truckloads of logs will have been hauled to a nearby mill for processing into wood siding and trim for homes.

Cutting some of the mature aspen, which are nearing the end of their lifetime, will stimulate the regrowth of new aspen trees and should boost understory species, as well, said U-M ecologist and biogeochemist Luke Nave, who leads the project.

"We're reaching a point with our climate where we can't pretend that it's not changing. To sit by and do nothing, when we have a forest that is vulnerable to climate change, would be irresponsible," he said.

Nave is standing in front of a tall stack of bigtooth aspen logs ready for transport to the Upper Peninsula mill. Nearby, two large, noisy machines move methodically through the forest, cutting aspen trees into 8-foot, 4-inch logs, then stacking them. Some of the trees are 100 feet tall, with trunks nearly 2 feet in diameter.

Aspen in the Great Lakes region are considered "climate change losers," according to Nave, and are not expected to fare well as the region's climate continues to warm in the coming decades. Stands dominated by a single species and containing trees of a uniform age and canopy height may be especially vulnerable.

"I'm not a finance guy, but you can think of forest management in terms of investment strategies. You don't put all your investments in one place. You try to diversify, because it protects you against risk," said Nave, an associate research scientist at the Biological Station and in the U-M Department of Ecology and Evolutionary Biology.

"So, if you have different tree species arrayed in different age classes across the forest, that's a diversified investment strategy that increases your capacity to respond to climate warming, drought and severe weather events."

The U-M aspen management project is a formal demonstration site of the Northwoods Climate Change Response Framework, a regional collaboration among scientists, land managers and private landowners to advance climate change adaptation efforts.

A 2014 forest vulnerability assessment by the Framework concluded that suitable habitat for aspen in northern Michigan will sharply decline by the end of this century if little is done to rein in global emissions of heat-trapping greenhouse gases.

The U-M aspen management project involves a $178,000 timber sale to Louisiana-Pacific Corporation, which operates a mill in the eastern Upper Peninsula town of Newberry that employs 127 people. The mill makes LP® SmartSide® siding and trim, one of Louisiana-Pacific's best-selling products.

The timber sale is expected to yield 8,600 tons of wood--7,700 tons of aspen plus other hardwoods and some pine, according to Travis Kangas, a Louisiana-Pacific resource manager.

The cutting is being done at a Biological Station site known locally as the Pellston Hill. Three aspen management strategies--resistance, resilience and transition--are being tested by harvesting trees on four units totaling 77 acres:

The transition treatment aims to rapidly move the forest away from mature-aspen dominance, toward more diverse cover types, including longer-lived species. All mature aspen will be removed from this plot while all other tree species--red oak, sugar maple, red maple, striped maple, yellow birch, paper birch, ironwood, basswood, hemlock, red pine, jack pine, white pine and balsam fir--will be retained.

American beech, which is in a severe, disease-driven decline across much of Michigan, is also present at this site. Non-diseased individuals will be retained to study whether they are naturally resistant to their insect and fungal pathogens.

The resistance treatment will attempt to retain aspen and birch in a location that's cool, shady and moist with north-facing slopes and a high groundwater table. Those factors could enable trees on this 25-acre unit to resist climate change-driven drought and heat. Nearly all the saleable trees will be cut and removed, with the intent of regenerating a mix of aspen and birch.

Two resilience treatments seek to maintain aspen stands in the future but to increase diversity of species, age classes and stand structure. Most of the mature aspen will be removed, while most of the understory trees will be retained, including red oak, red maple, non-diseased beeches, and some red and white pines.

The 77-acre harvesting zone is within a 452-acre management area that includes untreated reference areas and several young stands that regenerated after being clear-cut in the early 1970s or early 1980s.

"The forestry community is still very early in the process of learning what it means to adapt to climate change. So, demonstration projects like this will provide really useful information that will help the whole community learn about climate adaptation," said Stephen Handler, a climate change specialist with the U.S. Forest Service in Houghton, Michigan, and who also works for the Northern Institute of Applied Climate Science.

Revenues from the Biological Station timber sale will fund a study of tree-harvesting impacts on groundwater and soil carbon throughout the 452-acre management area. Proceeds from the sale will pay for the installation of dozens of groundwater monitoring wells, as well as analysis of thousands of soil and groundwater samples collected from the wells, Nave said.

The aspen management experiment will also create future research opportunities for students and faculty researchers who spend time at the U-M Biological Station each summer.

Louisiana-Pacific's Kangas said he inspected the Biological Station's timber-sale site last year to estimate the amount of usable timber and its market value, a process called cruising. He said he was impressed by the size and health of the aspen trees--mostly bigtooth aspen with some trembling (also known as quaking) aspen.

"This is a high-quality site for aspen," Kangas said. "I couldn't believe the size and volume of the trees when I first cruised it. You see aspen like this in Canada, but you just don't see it in Michigan."

A few hundred yards away, down a muddy dirt road, a two-man crew--one operating a machine called a processor (also known as a harvester) and the other at the controls of a forwarder--cuts the trees and stacks the logs.

The jaws at the end of the processor's long arm grasp the base of each tree, cut it, then flip the tree onto the ground horizontally. Limbs are sheared away as the processor pulls the tree trunk past a large chainsaw blade that quickly slices it into logs. Then the forwarder, with giant claws like some oversized arcade game, scoops logs from the ground, stacks them neatly into its bed, and transports the load to the roadside pile where a logging truck will take them to the mill.

Aspen exploit disturbances like this to regenerate a new generation of trees. Where these mature aspen trees are cut, the roots will send up countless new "suckers" to replace them, said Dean Reid, a consulting forester who set up the timber sale for the university and who acted as the liaison with Louisiana-Pacific.

"You can get 15,000 to 20,000 aspen stems of regeneration per acre," Reid said. "But aspen need direct sunlight, so most of those stems will die if shaded, and the others will compete and crowd each other out."

The aspen now nearing the end of their lifetime at the Biological Station were established following the epic logging and wildfire disturbances that transformed the forests of the Upper Great Lakes region more than a century ago.

After northern Michigan's forests were cleared in the late 1800s, a series of wildfires swept through the region and devoured the slash, the woody debris left behind after logging. Most of the Biological Station's mature aspen date to the period between 1908 and 1919, which is the last time the property was severely burned by post-logging wildfires, Nave said. The U-M Biological Station was established in 1909.

A big part of the research mission for generations of Biological Station researchers and students was to document the forest's recovery from that cataclysm. Today, through projects like the Adaptive Aspen Management Experiment, researchers there are studying how the forest will cope with a different threat, one whose effects are already being felt: climate change.

The aspen management strategies being tested at the U-M Biological Station were developed through the Northwoods Climate Change Response Framework, a project of the Northern Institute of Applied Climate Science.

In 2014, the Framework issued a report, which was published by the U.S. Forest Service, titled "Michigan forest ecosystem vulnerability assessment and synthesis." The report examined the climate-change vulnerability of forests in Michigan's northern Lower Peninsula and eastern Upper Peninsula over the next century.

The study's authors, which included U-M ecologists Inés Ibáñez and Knute Nadelhoffer, focused on two plausible climate scenarios tied to global emissions of heat-trapping greenhouse gases. They examined a high-emissions scenario--which the authors said "may be more realistic based on our current global greenhouse gas emissions trajectory"--and a lower-emissions scenario.

The high-emissions scenario projects an 11.2-degree Fahrenheit summer temperature increase in the assessment area by the end of the 21st century. At the same time, summer precipitation is projected to decline by 3.8 inches under that scenario.

This potential double whammy may result in "a much higher degree of summertime moisture stress" in the forests than indicated by precipitation values alone, according to the report.

Under both the high- and low-emissions scenarios, winters are expected to continue warming faster than other seasons and snowfall totals are projected to decline, with more winter precipitation falling as rain. Intense precipitation events may continue to become more frequent than in the past, according to the report.

"Two of the principal climate vulnerabilities that we're looking at here at the Biostation are water stress during the summer growing season and the possibility of increased windthrow--entire trees being blown over, roots and all--from ice storms and other intense precipitation events," Nave said.

"I can tell you anecdotally--from a dozen years of living and working at the Biostation--that there's been more rain and freezing rain in the winter. And these very tall, mature aspen, which grow to a uniform height and are unable to root deep because of a dense subsoil, are prone to being blown over in strong winds and during ice storms."

Additional aspen cutting in the 452-acre management area could be considered in the future, pending the results of the current study, Nave said. Future work could also include the planting of seedlings from tree species already present at the Biological Station (red oak, white pine, bigtooth aspen, sugar maple), as well as the introduction of tree species that currently reach their range limits nearby to the south (white oak, northern pin oak, shagbark hickory).

It will take a decade or more to know which of the aspen-management treatments was most effective, Nave said. It is expected that future generations of Biological Station researchers and students will carry on with the work, he said.

Earlier research has shown that growing up on a farm with animals may as much as half the risk of asthma and allergies. The protective effect is thought to be attributable to the diverse microbial exposures encountered on farms.

"We now discovered that the presence of farm-like microbiota in an early-life home seemed to protect from asthma also in urban homes. The effect was not based on the presence of large number of different microbial species but rather differences in the relative abundance of certain bacterial groups," says Pirkka Kirjavainen, Senior Researcher at the Finnish National Institute for Health and Welfare.

Wearing outdoor shoes indoors, the number of siblings and the age of the house played a role

The study found that the microbiota in homes protecting from asthma contained a wealth of bacteria typical of the outdoor environment, including bacteria in soil. On the other hand, the proportion of microbes normally occurring in the human respiratory tract and associated with respiratory tract infections was small.

"The key characteristic of microbiota in homes protecting from asthma appears to be large abundance of bacteria which originate from the outdoor environment and are beneficial or harmless to health, relative to bacteria that are a potential threat to health," Kirjavainen comments.

In urban homes, factors that increased the farm-like features in the microbiota included wearing outdoor shoes indoors, the number of siblings and the age of the house; all factors that may increase transport of outdoor microbes into the home.

Asthma is the most common chronic disease in children in Finland - can new cases be prevented in the future?

"It is interesting to see how clear of a protective effect indoor microbiota can have against the development of asthma. In contrast, it has been considerably more difficult to identify microbiota that would explain the detrimental effect of moisture damage on asthma," says Professor Juha Pekkanen.

Asthma is the most common chronic disease in children in Finland as well as in many other countries, and its prevalence is increasing with urbanisation. The new study supports the view that children's early exposure to 'right cocktail' of microbes may help their bodies to develop mechanisms protecting from asthma.

"The results suggest that asthma could be prevented in the future by modifying children's early microbial exposures," says Pekkanen.

A nationwide phase II clinical trial, coordinated out of Tufts Medical Center in Boston, has found that a topical cream was extremely effective in reversing the effects of vitiligo, a relatively common autoimmune disease that causes loss of skin pigmentation. Topical application of the medicated cream, ruxolitinib, which is currently used as an oral treatment for certain blood disorders, resulted in substantial improvement of facial vitiligo symptoms in nearly half of the trial's participants. Results of the clinical trial were presented by David Rosmarin, MD, Dermatologist at Tufts Medical Center and Primary Investigator for the study, on Saturday, June 15, at the World Congress of Dermatology in Milan, Italy.

There is no known cause of vitiligo, a disease in which the immune system attacks pigment cells in the body. Vitiligo may range from mild to severe and can be found anywhere on the body, although it typically affects exposed areas, such as the face and hands. While vitiligo is not evident at birth, about half of vitiligo patients contract the disease before age 20. Approximately 50 million people - one percent of the worldwide population - are affected by vitiligo, including musical artist Michael Jackson, actor John Hamm, model Winnie Harlow and comedian Steve Martin. Vitiligo affects all ethnic groups equally, but is more evident in ethnic minorities with darker skin. No FDA-approved re-pigmenting treatments for vitiligo currently exist.

"Unfortunately, there is often a social stigma associated with vitiligo, and it can take a significant psychosocial toll on patients," said Dr. Rosmarin. "Current treatments such as phototherapy, topical corticosteroids, and calcineurin inhibitors have limited efficacy, and phototherapy treatment can be a burden for patients to have to use a light box two or three times per week."

The two-year study, the largest randomized controlled vitiligo study ever conducted, enrolled 157 patients at 30 sites across the United States. Participants received daily or twice daily topical application of either ruxolitinib or placebo to the area of skin affected by vitiligo. About half of the highest dose of ruxolitinib patients saw a statistically significant improvement of near 50 percent in their facial vitiligo, compared to three percent who saw this level of improvement in the placebo group. Side effects of topical application of ruxolitinib were mild and included redness and irritation at the application site and mild acne.

"Topical ruxolitinib has the potential to change the way vitiligo is treated. Not only is it effective at repigmenting the skin, but it has an excellent safety profile," said Dr. Rosmarin. "We also are optimistic that many vitiligo patients may see an even better response with continuous ruxolitinib usage over an extended period of time, combined with phototherapy and sunlight exposure. Our hope is that this treatment ultimately will be a game-changer for the millions of people worldwide affected by vitiligo."

We are all familiar with the image of electrons zipping around an atom's nucleus and forming chemical bonds in molecules and materials. But what is less known is that electrons have an additional unique property: spin. It is difficult to make an analogy, but one could crudely describe electron spin as a spinning-top rotating around its axis. But what is even more interesting is that, when spins of electrons align together in a material, this leads to the well-known phenomenon of magnetism.

One of the most cutting-edge fields in technology is spintronics, a still-experimental effort to design and build devices - such as computers and memories - that run on electron spin rather than just the movement of charges (which we know as electrical current). But such applications demand new magnetic materials with new properties. For example, it would be a huge advantage if magnetism occurs in an extremely thin layer of the material - the so-called two-dimensional (2D) materials that include graphene, which is basically an atom-thick layer of graphite.

However, finding 2D magnetic materials is challenging. Chromium iodide (CrI3) recently revealed many interesting properties, but it degrades rapidly in ambient conditions and its insulating nature doesn't promise much in the way of spintronics applications, most of which require metallic and air-stable magnetic materials.

Now, the groups of Andras Kis and Oleg Yazyev at EPFL have found a new metallic and air-stable 2D magnet: platinum diselenide (PtSe2). The discovery was made by Ahmet Avsar, a postdoc in Kis's lab, who was actually looking into something else entirely.

To explain the discovery of magnetism in PtSe2, the researchers first used calculations based on density functional theory, a method that models and studies the structure of complex systems with many electrons, such as materials and nanostructures. The theoretical analysis showed that the magnetism of PtSe2 is caused by the so-called "defects" on its surface, which are irregularities in the arrangement of atoms. "More than a decade ago, we found a somewhat similar scenario for defects in graphene, but PtSe2 was a total surprise for us," says Oleg Yazyev.

The researchers confirmed the presence of magnetism in the material with a powerful magneto-resistance measurement technique. The magnetism was surprising, since perfectly crystalline PtSe2 is supposed to be non-magnetic. "This is the first time that defect-induced magnetism in this type of 2D materials is observed," says Andras Kis. "It expands the range of 2D ferromagnets into materials that would otherwise be overlooked by massive database-mining techniques."

Removing or adding one layer of PtSe2 is enough to change the way spins talk to each other across layers. And what makes it even more promising, is the fact that its magnetism, even within the same layer, can be further manipulated by strategically placing defects across its surface - a process known as "defect engineering" that can be accomplished by irradiating the material's surface with electron or proton beams.

"Such ultra-thin metallic magnets could be integrated into the next generation spin-transfer torque magnetic random-access memory [STT MRAM] devices", says Ahmet Avsar. "2D magnets could reduce the critical current required to change magnetic polarity, and help us with further miniaturization. These are the major challenges that companies are hoping to solve."

A recent study revealed that by decorating iron nanocubes with gold the functionality of nanoparticles can be increased.

One of the major challenges in nanotechnology is the precise control of shape, size and elemental composition of every single nanoparticle. Physical methods are able to produce homogeneous nanoparticles free of surface contamination. However, they offer limited opportunity to control the shape and specific composition of the nanoobjects when they are being built up.

A recent collaboration between the University of Helsinki and the Okinawa Institute of Science and Technology (OIST) Graduate University revealed that hybrid Au/Fe nanoparticles can grow in an unprecedentedly complex structure with a single-step fabrication method. Using a computational modelling framework, the groups of Professor Flyura Djurabekova at the University of Helsinki and Prof. Sowwan at OIST succeeded in deciphering the growth mechanism by a detailed multistage model.

Elegantly combined considerations of kinetic and thermodynamic effects explained the formation of embedded gold layers and the site-specific surface gold decoration. These results open up a possibility for engineering a multitude of hybrid nanoparticles for a wide range of emerging applications. Their research was recently published in the highly ranked open access journal Advanced Science.

"When nature surprises us with an unexpectedly beautiful pattern, we must recognize it and explain. This is the way to cooperate with nature that is always ready to teach and expecting us to learn," says Dr. Junlei Zhao, a postdoctoral researcher in the group of Prof. Djurabekova.

Nowadays, scientists are able to study nano-scale phenomena with great accuracy by using high-performance computational software and modern supercomputing infrastructures. These are of great support, not only for advancing fundamental science but also for finding promising solutions for many challenges of humanity.

DGIST research team succeeded in developing stem cell delivery of scaffold1 microrobot that can precisely deliver cells to a target body tissue. This research achievement is expected to enhance the treatment safety and efficiency of degenerative neural disorders as it can precisely transplant the exact amount of stem cell-based treatment cells to human body tissues and organs.

DGIST recently announced that Professor Hongsoo Choi's team in the Department of Robotics Engineering developed a 'scaffold microrobot for stem cell delivery and transplantation,' which can further enhance the existing treatment efficiency of stem cell. A joint international research was conducted with Senior Researcher Jin-young Kim at DGIST-ETH Microrobot Research Center, Professor Seong-Woon Yu and Professor Cheil Moon's team in the Department of Brain and Cognitive Sciences, Professor Sung Won Kim's team in Seoul St. Mary's Hospital, and Professor Bradley J. Nelson's team in the Institute of Robotic and Intelligent Systems at ETH, Zurich, Switzerland.

Stem cell treatment has been taking limelight as a regenerative medical technique for intractable disorder treatment, but it cannot transplant the exact amount of stem cells to the target areas in need of treatment deeply inside body or may carry injection risk. It has especially been pointed out that treatment efficiency and safety are low due to huge loss during the in vivo delivery of stem cells and a high cost of treatment.

To overcome such limitation, the DGIST research team devised scaffold microrobot in a spherical and helical type through the 3D laser lithography2. The biggest achievement of this study is that it minimized cell loss in the body through a wireless control method using an external magnetic field while transplanting stem cells quickly and precisely at the same time.

What is noteworthy is that while the existing researches tested microrobots in a static external environment and not physiological environment, this research cultured a hippocampal neural stem cell3 on a microrobot for the first time in the world. They divided the cell into specific cells such as astrocyte4, Oligodendrocyte5, and neuron6 and succeeded in precisely delivering and transplanting them in the target.

To gain this achievement, the research team showed the cell transfer and transplantation process using the microrobot inside Body-on-a-chip (BOC), a microfluidic cell culture system that replicated a physiological in vivo environment. They also extracted a rat's brain and injected the microrobot into the internal carotid artery7, and transferred it to the anterior cerebral artery8 and middle cerebral artery9 using outer magnetic field. A highlight of this joint research is that they cultured the 'hNTSCs10' provided by Professor Sung Won Kim's team at the Catholic University St. Mary's Hospital on the microrobot in 3D for successful experiment.

Professor Hongsoo Choi at the Department of Robotics Engineering said "Through this research we hope to increase the treatment efficiency and success rate for Alzheimer and central neural diseases, which couldn't be approached through the existing method of stem cell treatment. Through continuous follow-up research with hospitals and related companies, we will do our best to develop a microrobot-based precise treatment system that can be used in actual hospital and clinical sites.

A new study shows that the complement system, part of the innate immune system, plays a protective role to slow retinal degeneration in a mouse model of retinitis pigmentosa, an inherited eye disease. This surprising discovery contradicts previous studies of other eye diseases suggesting that the complement system worsens retinal degeneration. The research was performed by scientists at the National Eye Institute (NEI), part of the National Institutes of Health, and appears in the Journal of Experimental Medicine.

Retinitis pigmentosa is an incurable and unpreventable blinding eye disease that affects 1 in 4,000 people.

"Much research is devoted to studying therapies that attempt to alter the immune system's role in inherited diseases such as retinitis pigmentosa because such treatments would have broad applicability, regardless of a patient's causative mutation," said the study's principal investigator Wai T Wong, M.D., Ph.D., chief the Neuron-Glia Interactions in Retinal Disease Section at NEI.

In previous studies, activation of the complement system, which mediates some aspects of inflammation, worsens damage in age-related macular degeneration (AMD), a leading cause of blindness in people age 65 years and older.

"The current study involving retinitis pigmentosa underscores the notion that the complement system may in fact exacerbate or curb retinal degeneration depending on the context. Appreciating this complexity is important for guiding the development of therapies that target the complement immune system to treat degenerative diseases of the retina," Dr. Wong said.

Sean Silverman, Ph.D., an NEI postdoctoral researcher in Dr. Wong's lab and the lead author on the study, and colleagues monitored the genetic expression of the complement system in a transgenic mouse model of retinitis pigmentosa. They found that upregulation of complement expression and activation coincided with the onset of photoreceptor degeneration. What's more, this upregulation occurs in the exact location of the degeneration.

"Having found complement at the scene of the crime, we then wanted to know whether it was helping or hurting the degenerative process," Dr. Wong said.

Using the retinitis pigmentosa mouse model, the researchers examined the role of C3 and CR3, the central component of complement and its receptor, by comparing mice with genetically ablated C3 or CR3 to mice with normal expression. They found that the absence of C3 or CR3 made degeneration worse. Rod photoreceptors, the light-sensing cells that die off first in retinitis pigmentosa, were precipitously lost along with a surge in the expression of neurotoxic inflammatory cytokines.

They pieced together that C3 gets secreted by microglia, trash-collecting cells that in a healthy retina clear away dead cells by phagocytosis to keep the tissue working properly. Once secreted, C3 lands on dead photoreceptors labeling them for destruction and removal. The receptor, CR3, recognizes the C3 markers and conveys the information to microglia. "Breakdown of this C3-CR3 interaction results in a decreased ability of microglia to phagocytose dead photoreceptors, which then accumulate in the retina, stimulating greater inflammation and degeneration," Dr. Wong said. "Degeneration accelerates pretty quickly."

When placed alongside each other in a dish, microglia from C3- or CR3-ablated retinas turned out to be toxic to photoreceptors.

Taken together, the results show that in the context of retinitis pigmentosa, complement activation is actually helpful for clearing away dead cells and maintaining a state of homeostasis, a physiological balance, in the retina.

However, in the context of AMD, harmful effects observed from complement activation have spurred clinical trials testing complement inhibitors. "Our findings suggest that this approach may be appropriate for some disease scenarios, but may induce complex responses in other disease scenarios by inhibiting helpful and homeostatic functions of inflammation," Dr. Wong said.

A recent study published in the peer-reviewed journal PeerJ - the Journal of Life and Environmental Sciences highlights the fact that the economic benefits of commodity export for primate habitat countries has been limited relative to the extreme environmental costs of pollution, habitat degradation, loss of biodiversity, continued food insecurity and the threat of emerging diseases.

The world's primate fauna, distributed in the Neotropics, Africa and in South and Southeast Asia, represents an important global component of the Earth´s land-based biodiversity. The presence and activities of primates support a range of tropical community-wide ecological functions and services that provide vital resources to natural ecosystems, including local human populations.

Alarmingly, around 60% of primate species are now threatened with extinction and ~75% have declining populations as a result of escalating anthropogenic pressures resulting in deforestation, habitat degradation, and increased spatial conflict between an expanding human population and the natural range of primates.

The study finds that growing market demands for food and nonfood commodities from high-income nations and the global community at large are significant drivers of rapid and widespread primate habitat loss and degradation.

The global consumption of food and natural resources, along with an increasingly globalized economy has created an expanding international market for agricultural products. Such growth is also reflected in the growth of the area of deforestation that is commodity driven. Available evidence indicates that between 2001 to 2015, 160 million hectares of forest were lost in the tropics due to human activities and that 50% or more of this loss was commodity driven. That is, forests were converted to agricultural fields, cattle pastures, mines to extract minerals and metals, fossil fuel exploration, and urbanization.

Given that global commodity resource extraction is predicted to more than double, from 85bn tonnes today to 186bn by the year 2050, reversing the current trend of primate population decline and extinction due to habitat loss and degradation will require a stronger global resolve to reduce the world's per capita demand for forest-risk food and nonfood commodities from primate-range regions, while at the same time implementing sustainable land use practices that improve the standard of living for local human communities, protect local biodiversity, and mitigate climate change.

In order to avoid the impending extinction of the world´s primates, the researchers suggest a number of measures to be implemented including changing global consumer habits (e.g., using less oil seed, eating less meat), the creation of an international environmental improvement fund to mitigate the negative effects of forest-risk commodities trade, and assigning responsibility for environmental damage to those international corporations that control production, export, and supply chains.

Authors Alejandro Estrada, Paul A. Garber and Abhishek Chaudhary write, "Growing global consumer demands for food and non-food commodities from primate range regions are placing primate populations at risk of extinction. These increasing demands have resulted in an accelerated global expansion of agriculture and of extractive industries and in the growth of infrastructure to support these activities leading to widespread primate habitat loss and degradation."

"Primates and their habitats are a vital component of the world's natural heritage and culture and as our closest living biological relatives, nonhuman primates deserve our full attention, concern, and support for their conservation and survivorship", the authors argue.