Culture

A therapeutic intervention for amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, could be on the horizon thanks to unexpected findings by University of Arizona researchers.

ALS is the progressive degeneration of motor neurons that causes people to lose the ability to move and eventually speak, eat and breathe.

Within the neuronal cells of patients with ALS and other neurodegenerative diseases, two proteins - TDP-43 and FUS - are often found in bundles of molecular junk called aggregates, which can accumulate to deadly levels.

"It's not clear yet if TDP-43 aggregates themselves are truly toxic or a sign that things have gotten really bad in a cell, and this is its last Hail Mary trying to keep things in order," said Ross Buchan, assistant professor of molecular and cellular biology and a member of the BIO5 Institute. "These aggregates could possibly be toxic because they are trapping other useful molecules and not letting them do their job."

Buchan and his team set out to investigate how healthy cells clear harmful aggregates from the cell.

What they found was that the aggregates were being removed via endocytosis, which was surprising for two reasons. First, the textbook definition of endocytosis is a process in which proteins, nutrients and chemical signals from outside the cell are brought inside to be degraded and recycled by the lysosome. But in this case, endocytosis was working on aggregates that were already inside the cell. And second, there's already a mechanism, called autophagy, in place for recycling junk that originated from within a cell, yet endocytosis was doing what autophagy should have been doing instead.

"Autophagy - and also likely, although it's still uncertain, endocytosis - often slows as we age, and there are genes that are mutated in that pathway that are associated with some neurodegenerative diseases. So people thought the reason aggregates form when we get old, or when you have these diseases, is because that pathway isn't working very well," Buchan said.

Additionally, the accumulation of aggregates slows the endocytosis pathway further, creating a negative feedback loop within the cell.

"If we genetically or chemically impede the pathway, then the TDP-43 protein accumulates and becomes super toxic. The cool thing, as far as a therapy for ALS is concerned, is that we can also do the reverse," Buchan said. "We can make the endocytosis pathway work better by over-expressing parts of it, like putting the gas pedal down so it goes really fast. When we do that, then the TDP-43 aggregates are cleared really efficiently and it's no longer toxic."

Many of the paper's experiments were performed in yeast cells, but the general findings are likely translatable to human cells based on initial findings. Buchan called yeast "a powerful genetic tool," for understanding cellular processes, including those in human disease.

While the results from Buchan's lab are unexpected - "If I were to pull a textbook off the self, it would say endocytosis is for things that are outside the cell, not inside, so it's still pretty heretical," he said - there are other labs with data suggesting endocytosis can also clear already internalized proteins.

The next step is to determine how TPD-43 and FUS enter the endocytic pathway, and then to develop ways to make endocytosis work better in these cells.

"There are genetic ways to do that, but not chemically at the moment," Buchan said. "We think if we have a drug that inhibits the negative regulators of endocytosis, the pathway will go faster as a result. We have a couple ideas of where to start next."

Macrophages are part of the innate immune system and essential for brain development and function. Using a novel method, scientists from Jena University Hospital, the University of Bonn and the Memorial Sloan Kettering Cancer Center in New York (USA) succeeded in visualizing macrophages that were formed in the bone marrow. In studies on mice, this technology enabled the researchers to observe that shortly after a stroke, numerous macrophages that had migrated from the blood begin to attack dead and adjacent healthy brain tissue. The results have now been published in the journal Nature Neuroscience.

In ancient Greek, the term macrophage means something like "big eater". These cells are components of our innate immune system that are present in every tissue of our body. In the brain, these resident immune cells are called microglia and play an essential role in normal brain development and function. During inflammatory processes, for example after stroke, brain infections, multiple sclerosis or Alzheimer's disease, other macrophages come into play, which are recruited from the bone marrow. Does it make a difference with regard to brain diseases whether the macrophages are resident in the brain or have migrated into the brain? This question has so far remained unresolved because scientists have not been able to differentiate between the two cell types using conventional methods.

This is precisely where the research of the working group led by Prof. Dr. Ralf Stumm from Jena University Hospital and his partners Prof. Dr. Elvira Mass from the University of Bonn and Prof. Dr. Frederic Geissmann from the Memorial Sloan Kettering Cancer Center in New York (USA) comes in. The team studied mice in which the genetic information for a molecular switch was introduced into a gene called Cxcr4. If this switch is activated with a special agent, stem cells in the bone marrow, from which all blood-circulating immune cells originate, produce a colored fluorescent protein.

Microglia in the brain do not light up

"The trick with our model is that this feature is transferred to the daughter cells circulating in the blood, whereas resident microglia in the brain are not marked," explains pharmacologist Stumm. Immigrated immune cells can therefore be easily distinguished from microglia by their color. The researchers were able to show that during a healthy mouse life, virtually no macrophages generated by bone marrow stem cells settle in the brain. This complements earlier findings by professors Geissmann and Mass that macrophages located in tissues develop very early during embryonic development, colonize the entire embryo and from then on maintain themselves through cell division.

With the help of their model study on mice, the researchers have now discovered that shortly after a stroke, numerous macrophages that had migrated from the blood begin to attack dead and adjacent healthy brain tissue. Contrary to previous assumptions, the outsiders withdrew completely from the healthy brain tissue in the following days and were then only found in the dead brain tissue.

Researchers inactivated the Cxcr4 gene function

In a next step, the researchers inactivated the Cxcr4 gene function, leaving intact the molecular switch that helps them detect the immigrated immune cells. "We were interested in Cxcr4 because this protein acts like an antenna, i.e. as a receptor, for a messenger substance that is believed to be involved in inflammatory processes in the brain," says Prof. Stumm. The researchers found that a stroke initially attracted fewer macrophages into the brain when the Cxcr4 function was missing. In the following days, the macrophages that had migrated into the brain migrated only incompletely into the dead brain tissue. Some remained in healthy brain tissue for far too long and prevented the resident microglia from settling down.

"Moreover, numerous genes that are necessary for a protective immune response were not switched on in the immigrated macrophages, whereas inflammation-promoting genes were overexpressed in the resident macrophages," says Prof. Mass, who is a member of the Cluster of Excellence ImmunoSensation at the University of Bonn. Furthermore, the absence of the Cxcr4 receptor in mice with stroke resulted in increased tissue damage and a worse overall condition of the mice.

Genetic switch is a universal tool

Overall, the researchers see two milestones achieved: Their genetic switch is a universal tool that enables scientists to better investigate the function of immune cells originating from the bone marrow. Furthermore, they show that the Cxcr4 receptor is part of an immune response with which macrophages originating from the bone marrow protect the damaged brain. "The better we understand the spatial and temporal activation of the Cxcr4 molecule during a stroke, the better we will be able to treat patients with Cxcr4-inhibiting drugs in the future," says Prof. Stumm.

A new study published by The BMJ adds to evidence that rosiglitazone - a drug used to treat type 2 diabetes - is associated with increased risk of heart problems, especially heart failure.

This study led by the Yale School of Public Health is the most comprehensive evaluation of the cardiovascular risk of rosiglitazone ever done. Rosiglitazone belongs to a class of drugs known as thiazolidinediones. While it was designed to control blood sugar levels in patients with type 2 diabetes, it can also increase the risk of serious heart problems. This has led to suspension of the drug in Europe and previous restrictions on its use in the United States.

"Since 2007, studies have reported conflicting findings about whether rosiglitazone increases the risk of heart attacks," said Joshua Wallach, assistant professor at the Yale School of Public Health and the study's lead author. "However, these studies did not have access to the raw data, also known as individual patient level data (IPD), from clinical trials, which are more reliable when estimating a drug's true safety profile."

Recent efforts by GlaxoSmithKline (GSK) - rosiglitazone's manufacturer - to make IPD available to external investigators, prompted a team of U.S. researchers to analyze the raw clinical data and clarify some of the uncertainties surrounding rosiglitazone's cardiovascular risk.

Wallach and co-authors analyzed the results of more than 130 trials involving over 48,000 adult patients that compared rosiglitazone with any control for at least 24 weeks. IPD were available for 33 trials, which included 21156 patients; the remaining trials only had summary level data available.

When the researchers analyzed the IPD from trials made available by GSK, they found rosiglitazone was associated with a 33% increased risk of a composite cardiovascular event (heart attack, heart failure, cardiovascular and non-cardiovascular related death) compared with controls. This was estimated from the 274 events among 11,837 rosiglitazone patients and 219 events among 9,319 control patients.

When examining cardiovascular events independently, the analyses of the 33 GSK trials with IPD resulted in higher estimates of the risk of heart attacks than the analyses of trials with IPD and summary level data. These findings highlight the potential for different results derived from different data sources, and demonstrate the need for greater clinical trial transparency and data sharing to accurately assess the safety of drugs, the researchers said.

"Our study suggests that when evaluating drug safety and performing meta-analyses focused on safety, IPD might be necessary to accurately classify all adverse events," the researchers said.

"By including these data in research, patients, clinicians, and researchers would be able to make more informed decisions about the safety of interventions."

"Although rosiglitazone is no longer available in Europe, and now rarely prescribed in the U.S., the rosiglitazone story is an important lesson in the value of clinical trial transparency" said Wallach. "Our study demonstrates how data-sharing platforms can be used to improve our understanding of drug safety."

Citizen scientists have uncovered a bizarre pairing of two brown dwarfs, objects much smaller than the Sun that lack enough mass for nuclear fusion. The discovery, reported in The Astrophysical Journal and confirmed by a scientific team led by astrophysicist Jackie Faherty at the American Museum of Natural History, shows that brown dwarf systems--the formation of which are still poorly understood--can be very low mass and extremely far apart yet inexorably linked.

"Astronomers would conclude that brown dwarfs separated by billions of miles would dissolve as they moved through the galaxy over time," said Faherty, a senior scientist in the Museum's Department of Astrophysics and a co-founder of the citizen science project Backyard Worlds: Planet 9, which led to the new discovery. "But we've found one that is still very much together."

The Backyard Worlds project lets anyone with a computer and an internet connection flip through images taken by NASA's Wide Field Infrared Survey Explorer (WISE) spacecraft and help astronomers identify new worlds beyond our solar system. If an object is close enough to Earth, it will appear to "jump" when multiple images taken of the same spot in the sky a few years apart are compared. The goal for Backyard Worlds volunteers--of which there are more than 50,000--is to flag the moving objects they see in these digital flipbooks for further investigation by the science team. So far, volunteers have reviewed more than 4 million flipbooks.

In June 2018, citizen scientists flipping through the Backyard Worlds images noticed an unusual pairing: one object that appeared faint but moved fast--the telltale sign of a new brown dwarf--and another brighter object moving nearby and at the same rate. The Backyard Worlds science team was alerted and became immediately excited about this rare cosmic sighting.

Brown dwarfs, sometimes called "failed stars," are spread throughout the Milky Way. They lack enough mass to sustain stable nuclear fusion but they are hot enough to glow brightest in the infrared range of the light spectrum. While stars and brown dwarfs can be found in pairs or larger groupings, finding a pair with low total mass and at a very large separation from each other is not common.

In December 2018, members of the Backyard Worlds science team used the Baade Magellan telescope in Chile outfitted with the FIRE spectrograph to confirm that the fainter source is indeed a member of one of the coldest classes of brown dwarfs: a T8. The brighter object was also confirmed as a low-temperature object: an L1. In addition, they learned that the L1 was previously observed with the European Space Agency's Gaia telescope and found to be just 78 light years from the Sun.

The researchers used the distance calculated by Gaia to precisely measure the brightness of each source and extract mass estimates. They found that the T8 object has about 34 times the mass of Jupiter, and the L1 has about 72 times the mass of Jupiter. They are separated by 341 astronomical units (1 astronomical unit is roughly the distance between the Sun and the Earth, about 93 million miles). The system is estimated to be a few billion years old.

"While there are a handful of young pairings that rival this mass and separation, there is no known older system that rivals it, which raises the question: how and why did this cosmic pair survive?" said Marc Kuchner, an astrophysicist and citizen science officer for NASA's Science Mission Directorate.

"This is an excellent example of citizen scientists on the case," Faherty said. "We are still searching for clues as to how brown dwarfs form and this system is a provocative instance of what is possible at the extremes of survivability in the Milky Way."

Secular cultures which are tolerant of minority groups and respectful of individuals' rights tend to have more wealth, education and democracy, a new study by University of Bristol scientists has found.

New research, which surveyed nearly half a million people across 109 countries, shows that changes in culture generally comes before any improvements in wealth, education and?democracy, rather than the other way around.

Researchers from the University of Bristol (UK) and University of Tennessee (US) used the global survey data to show how secularism and openness towards minorities can be used to statistically predict future GDP per capita, secondary education enrollment and democratisation.

The outcome shows that pre-existing cultural values predicted future levels of economic growth and prosperity.

One of the policy implications of the study's analysis is that promotion of a country's development must take preexisting cultural values into account. For instance, promoting democracy, whether through economic exchange or regime change, will only succeed if combined with promoting openness and tolerance of minority groups.

The first places to see dramatic increases in wealth, health, education and democracy tended to be Western countries, but the causes are hard to prove. This research shows that - at least in the 20th Century - places which had the greatest improvement also tended to have pre-existing secular and tolerant cultures.

The question posed by the study's researchers was to determine if these cultural values evolved first, or if they emerged because of increased prosperity.

Dr Daniel Lawson, the study's statistician from the University of Bristol's School of Mathematics, said: "We used careful statistical methods to learn cultural values from survey data, and compared them to historical statistics.

"With access to massive digitised datasets, history is becoming a science. Our data-driven analysis supports the notion that a 'good' society - valuing diversity, tolerance and openness - may also be a 'productive' society, which is a reason to be hopeful about the future."

Damian Ruck, from the University of Tennessee, added: "This study investigates the co-evolution of cultural values with health, wealth, education and democracy around the world.

"It shows that promoting a culture of secularism, tolerance and openness, along with improved public health, may be the first step on the road to development."

Daily exposure to ground level ozone in cities worldwide is associated with an increased risk of death, finds the largest study of its kind published by The BMJ today.

The findings - based on data from over 400 cities in 20 countries across the world - show that more than 6,000 deaths each year would have been avoided in the selected cities if countries had implemented stricter air quality standards.

Ground level ozone is a highly reactive gas commonly found in urban and suburban environments, formed when pollutants react in sunlight.

Current air quality thresholds (in micrograms per cubic meter of ambient air) range from 100 μg/m3 (WHO), 120 μg/m3 (European Union directive), 140 μg/m3 (US National Ambient Air Quality Standard), and 160 μg/m3 (Chinese Ambient Air Quality Standard).

Recent reviews suggest that 80% of the world's population in urban areas are exposed to air pollution levels above the WHO threshold.

Most previous studies have found positive associations between ground level ozone and mortality, but differences in study design and quality make it difficult to draw consistent conclusions across different regions.

To try and address this, an international research team analyse deaths and environmental measures (weather and air pollutants) in 406 cities in 20 countries, with overlapping periods between 1985 and 2015.

Using data from the Multi-City Multi-Country Collaborative Research Network, they derived daily average ozone levels (above a maximum background level of 70 μg/m3), particulate matter, temperature, and relative humidity at each location to estimate the daily number of extra deaths attributable to ozone.

A total of 45,165,171 deaths were analysed in the 406 cities. On average, a 10 μg/m3 increase in ozone during the current and previous day was associated with a 0.18% increased risk of death, suggesting evidence of a potential direct (causal) association.

This equates to 6,262 extra deaths each year (or 0.2% of total mortality) in the 406 cities that could potentially have been avoided if countries had implemented stricter air quality standards in line with the WHO guideline.

What's more, smaller but still substantial mortality impacts were found even for ozone concentrations below WHO guideline levels, supporting the WHO initiative of encouraging countries to revisit current air quality guidelines and enforcing stronger emission restrictions to meet these recommendations, say the researchers.

This is an observational study, so can't establish cause, and the researchers point to some limitations. For example, areas such as South America, Africa, and the Middle East were unrepresented or not assessed, and differences in monitoring and data collection between countries may have affected the accuracy of their estimates.

Nevertheless, they say their results suggest that ozone related mortality "could be potentially reduced under stricter air quality standards."

Moreover, interventions to further reduce ozone pollution "would provide additional health benefits, even in regions that meet current regulatory standards and guidelines," they add.

"These findings have important implications for the design of future public health actions; particularly, for example, in relation to the implementation of mitigation strategies to reduce the impacts of climate change," they conclude.

New Rochelle, NY, February 10, 2020--The dramatic shift in how nasal tip surgery is being performed given changes in the intended goals and evolving techniques is highlighted in a Special Communication by and interview with Dean Toriumi, MD, published in the Official Journal of the American Academy of Facial Plastic and Reconstructive Surgery, Facial Plastic Surgery & Aesthetic Medicine, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Both the Special Communication and the Interview can be viewed free on the Facial Plastic Surgery and Aesthetic Medicine website through March 10, 2020.

In the Special Communication titled "Nasal Tip Contouring: Anatomic Basis for Management," Dr. Toriumi addresses the complexity of nasal tip contouring and helps rhinoplasty surgeons navigate the many techniques available to them. He discusses the ideal nasal tip contour, options for stabilizing the base of the nose, techniques for reorienting existing tip structures, and shield tip grafting. He also recommends learning as much as possible from each case by following previous patients.

In an interview with Dr. Toriumi, led by journal Editor-in-Chief, Dr. John Rhee and titled "Evolution of a Rhinoplasty Master," Dr. Toriumi highlights a key theme over the past 30 years: the use of structural grafting to make the nose stronger and provide a better long-term aesthetic and functional outcome. Dr. Toriumi points out that structure rhinoplasty is neither preservation rhinoplasty nor is it destructive. Instead, the existing structures are supported by adding cartilage grafts. In describing the evolution in tip grafting, he says that shield tip graft can be very useful if used properly. Dr. Toriumi also discusses complex techniques at high execution risk that should be performed by more experienced surgeons. The interview also focuses on future trends in the field.

"Dr. Toriumi has been a generational thought leader in rhinoplasty. This is yet another blockbuster article that takes us along on his personal decades-long journey and evolution in addressing the nasal tip," says Facial Plastic Surgery & Aesthetic Medicine Editor-in-Chief John S. Rhee, MD, MPH, Medical College of Wisconsin, Milwaukee.

Science now supports the saying, "happy wife, happy life." Michigan State University research found that those who are optimistic contribute to the health of their partners, staving off the risk factors leading to Alzheimer's disease, dementia and cognitive decline as they grow old together.

"We spend a lot of time with our partners," said William Chopik, assistant professor of psychology and co-author of the study. "They might encourage us to exercise, eat healthier or remind us to take our medicine. When your partner is optimistic and healthy, it can translate to similar outcomes in your own life. You actually do experience a rosier future by living longer and staving off cognitive illnesses."

An optimistic partner may encourage eating a salad or work out together to develop healthier lifestyles. For example, if you quit smoking or start exercising, your partner is close to following suit within a few weeks and months.

"We found that when you look at the risk factors for what predicts things like Alzheimer's disease or dementia, a lot of them are things like living a healthy lifestyle," Chopik said. "Maintaining a healthy weight and physical activity are large predictors. There are some physiological markers as well. It looks like people who are married to optimists tend to score better on all of those metrics."

The study, published in the Journal of Personality and co-authored by MSU graduate student Jeewon Oh and Eric Kim, a research scientist in the Department of Social and Behavioral Sciences at the Harvard T.H. Chan School of Public Health, followed nearly 4,500 heterosexual couples from the Health and Retirement Study for up to eight years. The researchers found a potential link between being married to an optimistic person and preventing the onset of cognitive decline, thanks to a healthier environment at home.

"There's a sense where optimists lead by example, and their partners follow their lead," Chopik said. "While there's some research on people being jealous of their partner's good qualities or on having bad reactions to someone trying to control you, it is balanced with other research that shows being optimistic is associated with perceiving your relationship in a positive light."

The research also indicated that when couples recall shared experiences together, richer details from the memories emerge. A recent example, Chopik explained, was Google's tearjerker Super Bowl ad, "Loretta," in which an elderly man uses his Google Assistant to help him remember details about his late wife.

"The things he was recollecting were positive things about his partner," Chopik said. "There is science behind the Google ad. Part of the types of memories being recalled were positive aspects of their relationship and personalities."

With all of its benefits, is optimism something that can be prescribed? While there is a heritable component to optimism, Chopik says there is some evidence to suggest that it's a trainable quality.

"There are studies that show people have the power to change their personalities, as long as they engage in things that make them change," Chopik said. "Part of it is wanting to change. There are also intervention programs that suggest you can build up optimism."

Across the board, everyone benefits from a healthy dose of optimism from their partner. For the glass-is-half-empty people, a partner can still quench their thirst. For the glass-is-half-full people? Their cup runneth over.

Human beings altered one of the highest peaks in the Himalayas hundreds of years before a person ever set foot there, new research has found.

The study, publishing today in the Proceedings of the National Academy of Sciences, indicates that the byproducts of burning coal in Europe in the late 18th century made their way to the Dasuopu glacier in the central Himalayas, some 6,400 miles as the crow flies from London, the birthplace of the Industrial Revolution.

"The Industrial Revolution was a revolution in the use of energy," said Paolo Gabrielli, lead author of the study and a principal investigator and research scientist at The Ohio State University Byrd Polar and Climate Research Center and the School of Earth Sciences.

"And so the use of coal combustion also started to cause emissions that we think were transported by winds up to the Himalayas."

The research team that published this study was part of a larger international team that traveled to Dasuopu in 1997 to drill ice cores from the glacier. The cores provide a record of snowfall, atmospheric circulation and other environmental changes over time; the Byrd Center has one of the largest collections of ice cores in the world.

Dasuopu -- at 7,200 meters or 23,600 feet above sea level -- is the highest-altitude site in the world where scientists have obtained a climate record from an ice core. Dasuopu is located on Shishapangma, one of the world's 14 tallest mountains, which are all located in the Himalayas.

For this study, the research team analyzed one core taken from Dasuopu in 1997 for 23 trace metals.

The ice cores operate as a sort of timeline, and show new ice forming in layers on the glacier over time. It is possible for researchers to tell almost the precise year a layer of the glacier formed because of environmental clues like snowfall or other known natural or man-made disasters. The ice the researchers evaluated formed between 1499 and 1992, the team determined. Their goal was to see whether human activity had affected the ice in any way, and, if so, when the effects had begun.

Their analysis showed it had: The team found higher-than-natural levels of a number of toxic metals, including cadmium, chromium, nickel and zinc, in the ice starting at around 1780 - the very start of the Industrial Revolution in the United Kingdom. Those metals are all byproducts of burning coal, a key part of industry at the end of the 18th century and throughout the 19th and 20th centuries.

The researchers found that those metals were likely transported by winter winds, which travel around the globe from west to east.

They also believe it is possible that some of the metals, most notably zinc, came from large-scale forest fires, including those used in the 1800s and 1900s to clear trees to make way for farms.

"What happens is at that time, in addition to the Industrial Revolution, the human population exploded and expanded," Gabrielli said. "And so there was a greater need for agricultural fields -- and, typically, the way they got new fields was to burn forests."

Burning trees adds metals, primarily zinc, to the atmosphere. Gabrielli said it is difficult to tell whether the glacial contamination comes from man-made or natural forest fires. And there are few high-altitude records of large-scale fires from around the world, making that contamination more difficult to track.

The contamination in the ice core records was most intense from about 1810 to 1880, the scientists' analysis found. Gabrielli said that is likely because winters were wetter than normal in Dasuopu during that time period, meaning more ice and snow formed. That ice and snow, he said, would have been contaminated by fly ash from the burning of coal or trees that made its way into the westerly winds -- and greater quantities of contaminated ice and snow means more contamination on the glacier.

Noteworthy to Gabrielli was that the contamination appeared long before humans scaled the mountains around Dasuopu. The first mountain climbers reached the summit of Mount Everest, at 29,029 feet the world's highest peak above sea level, in 1953. Shishapangma, at 26,335 feet the 14th-highest peak in the world, was first climbed in 1964. The Dasuopo glacier drilling site is about 2,700 feet below the summit.

Gabrielli said it is also important to note the difference between "contamination" and "pollution."

"The levels of metals we found were higher than what would exist naturally, but were not high enough to be acutely toxic or poisonous," he said. "However, in the future, bioaccumulation may concentrate metals from meltwater at dangerous toxic levels in the tissues of organisms that live in ecosystems below the glacier."

This study shows that human activity altered the atmosphere in the Himalayas starting at the end of the 18th century. But a previous study Byrd Polar Center researchers published in 2015 showed that in other parts of the world, namely Peru, human mining for silver contaminated the air in South America as many as 240 years before the Industrial Revolution.

"What is emerging from our studies, both in Peru and in the Himalayas, is that the impact of humans started at different times in different parts of the planet," Gabrielli said.

Tokyo - For a long time the liquid state of pure substances was believed to be a continuous state in which the component atoms or molecules are all equivalent. However, it has now been widely shown that there can be multiple different phases within liquids, even those containing only one component. Understanding what causes the components of liquids to switch from one state to another is currently a subject of particular interest. Researchers from The University of Tokyo Institute of Industrial Science have expanded the understanding of liquid behavior by describing the role of hydrodynamics in these transitions. Their findings are published in the Proceedings of the National Academy of Sciences of the United states of America (PNAS).

Significant advances have been made in the experimental study of liquid-liquid transitions (LLT) between different liquid phases in the same system, by focusing on particular cases where the kinetics are slow, leading to easy measurement. However, gaining a theoretical understanding of what is happening in LLT on a microscopic level remains challenging owing to the complexity of the many-body systems.

An intrinsic factor in liquid behavior is hydrodynamics--the flow of liquids in motion; however, its role in LLT is yet to be considered owing to the modeling challenges involved. Now, the researchers have devised a model based on two factors that describe the ordering of the liquid; the density, and the local organization of the liquid atoms or molecules at a particular point.

"Our Ginzburg-Landau-type model evaluates the system using two order parameters; one that is conserved--density; and one that is not-- local structural order," study lead author Kyohei Takae explains. "What we found was that the growth of the liquid domain we studied was affected by density changes that cause hydrodynamic fluctuations."

It was shown that when the density changes as a result of the phase transition, hydrodynamic flow is induced leading to changes in both the rate of domain growth and the long-range interaction between the domains. Hydrodynamic interaction was therefore found to be critical to LLT and the pattern evolution and kinetics.

"Gaining a thorough understanding of liquids on a microscopic level is critical to our fundamental knowledge, and we hope it will also help with optimizing industrial processes," study author Hajime Tanaka explains. "By revealing the role of hydrodynamics in LLT we expect to precipitate future investigations into dynamically perturbed systems, such as those under externally applied flow."

The world is waking up to the fact that human-driven carbon emissions are responsible for warming our climate, driving unprecedented changes to ecosystems, and placing us on course for the sixth mass extinction event in Earth's history.

However, new research publishing this week in leading international journal PNAS, sheds fresh light on the complicated interplay of factors affecting global climate and the carbon cycle - and on what transpired millions of years ago to spark two of the most devastating extinction events in Earth's history.

Using chemical data from ancient mudstone deposits in Wales, an international team involving scientists from Trinity College Dublin discovered that periodic changes in the shape of Earth's orbit around the Sun were partly responsible for changes in the carbon-cycle and global climate during and in between the Triassic-Jurassic Mass Extinction (around 201 million years ago, when around 80% of the species on Earth disappeared forever) and the Toarcian Oceanic Anoxic Event (around 183 million years ago).

In addition, volcanic activity released large amounts of greenhouse gases into the oceans and atmosphere at that point in time, which resulted in major global carbon cycle perturbations as well as global climate and environmental change.

Dr Micha Ruhl, Assistant Professor in Sedimentology at Trinity, said:

"Our work shows that for the 18 million years or so in between the Triassic-Jurassic mass extinction and the Toarcian Oceanic Anoxic Event, Earth's global carbon-cycle was in a constant state of change."

"Periodic changes in the shape of Earth's orbit around the sun impacted on the amount of energy received by Earth from the sun, which in turn impacted climatic and environmental processes, as well as the carbon-cycle, on local, regional and global scales."

"Although this phenomenon is well known for having caused the glacial cycles in more recent times, the present study shows that these external forcing mechanisms on Earth's systems were also operating, and controlling Earth's carbon cycle in the distant past, even during non-glacial times when Earth was marked by hot-house climate conditions."

Present-day orbital configurations and solar system processes should have resulted in a future return to glacial conditions. However, anthropogenic carbon release will likely have disrupted this natural process, causing rapid global warming, rather than a steady return to cooler climates.

The study of past global change events, such as the end-Triassic mass extinction and the Toarcian Oceanic Anoxic Event, as well as the time in between, allows scientists to disentangle the different processes that control global carbon cycle change and constrain tipping points in Earth's climate system.

A major international research team, made up of scientists from across Europe, North and South America and China, and including Dr Micha Ruhl and other researchers from Trinity, will soon commence drilling a 1 km deep borehole to retrieve rock samples.

These samples will comprise detailed climatic and environmental information and allow for further improved understanding of the processes that led to past major global change events and mass extinctions. Drilling of this borehole will occur as part of the International Continental Drilling Program.

Rutgers biomedical engineers have developed a "bio-ink" for 3D printed materials that could serve as scaffolds for growing human tissues to repair or replace damaged ones in the body.

The study was published in the journal Biointerphases.

Bioengineered tissues show promise in regenerative, precision and personalized medicine; product development; and basic research, especially with the advent of 3D printing of biomaterials that could serve as scaffolds, or temporary structures to grow tissues.

Hyaluronic acid, a natural molecule found in many tissues throughout the body, has many properties ideal for creating customized scaffolds, but lacks the durability required. The Rutgers engineers use modified versions of hyaluronic acid and polyethylene glycol to form a gel that is strengthened via chemical reactions and would serve as a scaffold.

"Instead of an ink color for an inkjet printer, we want the mixture to have properties that are right for specific cells to multiply, differentiate and remodel the scaffold into the appropriate tissue," said senior author David I. Shreiber, a professor who chairs the Department of Biomedical Engineering in the School of Engineering at Rutgers University-New Brunswick. "We focus on the stiffness of the gel and scaffold binding sites that cells can latch onto."

Groups of cells in the body generally make their own support structures, or scaffolds, but scientists can build them from proteins, plastics and other sources, according to the National Institutes of Health.

Shreiber and lead author Madison D. Godesky, who earned a doctorate at Rutgers, envisioned a system where hyaluronic acid and polyethylene glycol serve as the basic "ink cartridges" for 3D printing. The system would also have other ink cartridges featuring different cells and ligands, which serve as binding sites for cells. The system would print gel scaffolds with the right stiffness, cells and ligands, based on the type of tissue desired.

"Both the stiffness and the binding sites provide important signals to cells," Godesky said. "What especially distinguishes our work from previous studies is the potential to control the stiffness and ligands independently through combinations of inks."

RESEARCH TRIANGLE PARK, N.C. -- A material from a rare earth element, tellurium, could produce the world's smallest transistor, thanks to an Army-funded project.

Computer chips use billions of tiny switches called transistors to process information. The more transistors on a chip, the faster the computer.

A project at Purdue University in collaboration with Michigan Technological University, Washington University in St. Louis, and the University of Texas at Dallas, found that the material, shaped like a one-dimensional DNA helix, encapsulated in a nanotube made of boron nitride, could build a field-effect transistor with a diameter of two nanometers. Transistors on the market are made of bulkier silicon and range between 10 and 20 nanometers in scale.

"This research reveals more about a promising material that could achieve faster computing with very low power consumption using these tiny transistors," said Joe Qiu, program manager for the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, which funded this work. "That technology would have important applications for the Army."

The Army-funded research is published in the journal Nature Electronics. The Army is focused on integration, speed and precision to ensure the Army's capability development process is adaptable and flexible enough to keep pace with the rate of technology change.

"This tellurium material is really unique. It builds a functional transistor with the potential to be the smallest in the world," said Dr. Peide Ye, Purdue's Richard J. and Mary Jo Schwartz Professor of Electrical and Computer Engineering.

One way to shrink field-effect transistors, the kind found in most electronic devices, is to build the gates that surround thinner nanowires. These nanowires are protected within nanotubes.

Ye and his team worked to make tellurium as small as a single atomic chain and then build transistors with these atomic chains or ultrathin nanowires.

They started off growing one-dimensional chains of tellurium atoms, and were surprised to find that the atoms in these one-dimensional chains wiggle. These wiggles were made visible through transmission electron microscopy imaging performed at the University of Texas at Dallas and at Purdue.

"Silicon atoms look straight, but these tellurium atoms are like a snake. This is a very original kind of structure," Ye said.

The wiggles were the atoms strongly bonding to each other in pairs to form DNA-like helical chains, then stacking through weak forces called van der Waals interactions to form a tellurium crystal.

These van der Waals interactions set apart tellurium as a more effective material for single atomic chains or one-dimensional nanowires compared with others because it's easier to fit into a nanotube, Ye said.

Because the opening of a nanotube cannot be any smaller than the size of an atom, tellurium helices of atoms could achieve smaller nanowires and, therefore, smaller transistors.

The researchers successfully built a transistor with a tellurium nanowire encapsulated in a boron nitride nanotube. A high-quality boron nitride nanotube effectively insulates tellurium, making it possible to build a transistor.

"Next, the researchers will optimize the device to further improve its performance, and demonstrate a highly efficient functional electronic circuit using these tiny transistors, potentially through collaboration with ARL researchers," Qiu said.

Hemp is technically legal in Texas, but proving that hemp is not marijuana can be a hurdle, requiring testing in a licensed laboratory. So, when a truck carrying thousands of pounds of hemp was recently detained by law enforcement near Amarillo, the driver spent weeks in jail awaiting confirmation that the cargo was legal.

Stories like that one inspired a team of Texas A&M AgriLife researchers to create a "hemp scanner" that could easily fit in a police cruiser and distinguish hemp and marijuana instantly, without damaging any of the product. The study was published in January in the scientific journal RSC Advances.

HEMP'S HEYDAY

In 2019, Texas lawmakers made a distinction between hemp and marijuana based on the level of THC, or tetrahydrocannabinol, in a plant. THC is the major psychoactive agent in marijuana. If a plant has less than 0.3% THC, it is designated hemp.

Both federal and state restrictions on hemp have loosened in recent years. As a result, the value of hemp has skyrocketed, said Dmitry Kurouski, Ph.D., assistant professor of biochemistry and biophysics at the Texas A&M University College of Agriculture and Life Sciences, who led the study. Hemp is rich in compounds that are prized for their medicinal properties and flavor. The most well-known is CBD, or cannabidiol, which is thought to help with pain, anxiety and depression.

But farmers wanting to grow valuable hemp plants need a way to know that the plants contain little to no THC. When hemp can be legally grown in Texas later this year, producers will want to know if their plants' THC levels are approaching 0.3%, which would classify the plants as marijuana and therefore illegal to have and grow. An easy test for THC would be a boon for farmers as well as for law enforcement.

COULD AN EXISTING SCANNER WORK?

Kurouski said that the catalyst for creating the hemp scanner was his colleague David Baltensperger, Ph.D., professor of soil and crop sciences at the Texas A&M University College of Agriculture and Life Sciences. Baltensperger had worked with both farmers and police officers and knew about the demand for a better test for THC, Kurouski said.

Kurouski's lab was experienced in using a technique called Raman spectroscopy to create quick and noninvasive tests for plant diseases and foods' nutritional content. The technique uses harmless laser light to illuminate structures within materials. Each material's scan is unique, akin to a fingerprint.

Kurouski had a hunch that Raman could be used to create a quick and accurate test for THC. A portable Raman scanner had been created for previous studies by lab members Lee Sanchez, a research assistant, and Charles Farber, a graduate student.

What was then needed was a way to scan many marijuana and hemp plants in order to search for patterns in how their Raman spectra differed.

FINGERPRINTING THC

Testing dozens of samples of marijuana and hemp fell to Sanchez. The testing needed to happen near Denver, where recreational marijuana is legal.

"Lee Sanchez was the hero who was traveling to Colorado three times, staying there in hotels and driving from one location to another. Most of those locations are old fire stations. They are not fancy greenhouses but old, shaky buildings with plants inside," Kurouski said.

Back in Texas, Sanchez and Kurouski analyzed the collected spectra. A statistical analysis method found seven regions in the spectra that differed slightly among marijuana and hemp varieties, a high-tech version of the "spot the difference" brain teaser. Taken together, the readout in these seven regions distinguishes hemp and marijuana with 100% accuracy.

"We know plants from A to Z in terms of their spectroscopic signature," Kurouski said. "But when we saw such a crystal-clear picture of THC that appeared in one second of spectral acquisition, that was mind-blowing."

WHAT'S NEXT?

Now that Kurouski's team has demonstrated its quick, noninvasive test for THC, they are looking to collaborate with industry to mass-produce their hemp scanner. Mass production could feasibly begin in two or three years, Kurouski said.

The team also aims to create a similar test for CBD. Farmers looking to grow hemp may want to know the amount of CBD in their plants to better estimate their value.

The study also uncovered the scanner's ability to distinguish among different varieties of hemp and marijuana. In the changing legal landscape, there are thousands of varieties of cannabis, many of questionable quality.

"Our colleagues, the farmers, were positively surprised that we could identify the variety with 98% accuracy," Kurouski said. "That blew them away."

It's no coincidence that some of the worst viral disease outbreaks in recent years -- SARS, MERS, Ebola, Marburg and likely the newly arrived 2019-nCoV virus -- originated in bats.

A new University of California, Berkeley, study finds that bats' fierce immune response to viruses could drive viruses to replicate faster, so that when they jump to mammals with average immune systems, such as humans, the viruses wreak deadly havoc.

Some bats -- including those known to be the original source of human infections -- have been shown to host immune systems that are perpetually primed to mount defenses against viruses. Viral infection in these bats leads to a swift response that walls the virus out of cells. While this may protect the bats from getting infected with high viral loads, it encourages these viruses to reproduce more quickly within a host before a defense can be mounted.

This makes bats a unique reservoir of rapidly reproducing and highly transmissible viruses. While the bats can tolerate viruses like these, when these bat viruses then move into animals that lack a fast-response immune system, the viruses quickly overwhelm their new hosts, leading to high fatality rates.

"Some bats are able to mount this robust antiviral response, but also balance it with an anti-inflammation response," said Cara Brook, a postdoctoral Miller Fellow at UC Berkeley and the first author of the study. "Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology."

The researchers note that disrupting bat habitat appears to stress the animals and makes them shed even more virus in their saliva, urine and feces that can infect other animals.

"Heightened environmental threats to bats may add to the threat of zoonosis," said Brook, who works with a bat monitoring program funded by DARPA (the U.S. Defense Advanced Research Projects Agency) that is currently underway in Madagascar, Bangladesh, Ghana and Australia. The project, Bat One Health, explores the link between loss of bat habitat and the spillover of bat viruses into other animals and humans.

"The bottom line is that bats are potentially special when it comes to hosting viruses," said Mike Boots, a disease ecologist and UC Berkeley professor of integrative biology. "It is not random that a lot of these viruses are coming from bats. Bats are not even that closely related to us, so we would not expect them to host many human viruses. But this work demonstrates how bat immune systems could drive the virulence that overcomes this."

The new study by Brook, Boots and their colleagues was published this month in the journal eLife.

Boots and UC Berkeley colleague Wayne Getz are among 23 Chinese and American co-authors of a paper published last week in the journal EcoHealth that argues for better collaboration between U.S. and Chinese scientists who are focused on disease ecology and emerging infections.

Vigorous flight leads to longer lifespan - and perhaps viral tolerance

As the only flying mammal, bats elevate their metabolic rates in flight to a level that doubles that achieved by similarly sized rodents when running.

Generally, vigorous physical activity and high metabolic rates lead to higher tissue damage due to an accumulation of reactive molecules, primarily free radicals. But to enable flight, bats seem to have developed physiological mechanisms to efficiently mop up these destructive molecules.

This has the side benefit of efficiently mopping up damaging molecules produced by inflammation of any cause, which may explain bats' uniquely long lifespans. Smaller animals with faster heart rates and metabolism typically have shorter lifespans than larger animals with slower heartbeats and slower metabolism, presumably because high metabolism leads to more destructive free radicals. But bats are unique in having far longer lifespans than other mammals of the same size: Some bats can live 40 years, whereas a rodent of the same size may live two years.

This rapid tamping down of inflammation may also have another perk: tamping down inflammation related to antiviral immune response. One key trick of many bats' immune systems is the hair-trigger release of a signaling molecule called interferon-alpha, which tells other cells to "man the battle stations" before a virus invades.

Brook was curious how bats' rapid immune response affects the evolution of the viruses they host, so she conducted experiments on cultured cells from two bats and, as a control, one monkey. One bat, the Egyptian fruit bat (Rousettus aegyptiacus), a natural host of Marburg virus, requires a direct viral attack before transcribing its interferon-alpha gene to flood the body with interferon. This technique is slightly slower than that of the Australian black flying fox (Pteropus alecto), a reservoir of Hendra virus, which is primed to fight virus infections with interferon-alpha RNA that is transcribed and ready to turn into protein. The African green monkey (Vero) cell line does not produce interferon at all.

When challenged by viruses mimicking Ebola and Marburg, the different responses of these cell lines were striking. While the green monkey cell line was rapidly overwhelmed and killed by the viruses, a subset of the rousette bat cells successfully walled themselves off from viral infection, thanks to interferon early warning.

In the Australian black flying fox cells, the immune response was even more successful, with the viral infection slowed substantially over that in the rousette cell line. In addition, these bat interferon responses seemed to allow the infections to last longer.

"Think of viruses on a cell monolayer like a fire burning through a forest. Some of the communities -- cells -- have emergency blankets, and the fire washes through without harming them, but at the end of the day you still have smoldering coals in the system -- there are still some viral cells," Brook said. The surviving communities of cells can reproduce, providing new targets for the the virus and setting up a smoldering infection that persists across the bat's lifespan.

Brook and Boots created a simple model of the bats' immune systems to recreate their experiments in a computer.

"This suggests that having a really robust interferon system would help these viruses persist within the host," Brook said. "When you have a higher immune response, you get these cells that are protected from infection, so the virus can actually ramp up its replication rate without causing damage to its host. But when it spills over into something like a human, we don't have those same sorts of antiviral mechanism, and we could experience a lot of pathology."

The researchers noted that many of the bat viruses jump to humans through an animal intermediary. SARS got to humans through the Asian palm civet; MERS via camels; Ebola via gorillas and chimpanzees; Nipah via pigs; Hendra via horses and Marburg through African green monkeys. Nonetheless, these viruses still remain extremely virulent and deadly upon making the final jump into humans.

Brook and Boots are designing a more formal model of disease evolution within bats in order to better understand virus spillover into other animals and humans.

"It is really important to understand the trajectory of an infection in order to be able to predict emergence and spread and transmission," Brook said.