Culture

Porphyromonas gingivalis is a major bacterial pathogen which leads to periodontitis also known as gum disease. In Japan, 80% of adults aged 35 and over suffer from this disease. What's more, P. gingivalis has also been linked to rheumatoid arthritis, cardiovascular disease, pancreatic cancer, and even Alzheimer's disease.

Periodontitis is an oral inflammatory disease in response to biofilms - a bacterial plaque that accumulates on surfaces like our teeth. Biofilms are primarily created by bacterial cells attaching themselves to the host, and to each other, by sticky hair-like filaments called pili. In serious cases, periodontitis can result in gum erosion and tooth loss.

A team of researchers from the Molecular Cryo-Electron Microscopy Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), alongside the groups of Professor Koji Nakayama at Nagasaki University and Professor Katsumi Imada at Osaka University, have revealed the structure of these adhesive pili and shed light on how they assemble. Their research, published in Nature Microbiology, has provided new insights into bacteriology and is a crucial step towards combatting the diseases this bacterium is associated with.

"Pili are vital for both the survival of the bacteria, and the creation of the biofilms," said Dr. Satoshi Shibata, first author and staff scientist in OIST's Unit, which is led by Associate Professor Matthias Wolf. "By taking a close look at these pili, our research has provided insights into how we can prevent biofilms from forming."

P. gingivalis is a member of the class Bacteroidia. Previous research, led by Professor Nakayama and colleagues at Nagasaki University, found that most bacteria within this class have unique Type V pili. However, until now, the structure and assembly process of these pili were unknown. "Besides periodontal pathogens, Type V pili are seen in major colon bacteria such as Bacteroides and Prevotella species and their Type V pili may contribute to formation of colon microbiota," said Professor Nakayama.

Pili themselves are made up of smaller protein units, called pilins. In the case of P. gingivalis pili, most of these are FimA pilins. Although pilins are only linked by weak interactions, they can assemble into very stable pili.

The first step to determining how this assembly occurred was to take a close look at the structure of individual pilins. "Detailed structural information of FimA is very important because pathogenicity of P. gingivalis strains is closely related with the FimA sub-types," said Professor Imada.

Professor Imada and students from Osaka University crystalized FimA pilins, revealing their unassembled state at atomic resolution.

"Based on findings from earlier experiments by the Nakayama group, we theorized that these pilins assembled themselves via a mechanism of protease-mediated strand-exchange," said Dr. Shibata. "So, our next experiment took a close look at fully assembled pili using cryo-electron microscopy."

Associate Prof. Mikio Shoji from the Nakayama group, and Dr. Shibata prepared a genetically engineered version of the FimA pilins, which successfully assembled into pili, after a protease - a protein that cuts other proteins - was added. Dr. Shibata then collected thousands of images on the high-end cryo-electron microscope at OIST and processed the data on the University's "Sango" supercomputer, resulting in a complete three-dimensional atomic model of the assembled pilus structure.

"When we added the protease, the pilins started to assemble into elongated pili like train cars connecting to form a train. This happened because the protease cut a retaining loop and released a protein strand, known as the donor strand, which triggered the assembly to begin," said Professor Wolf. Once released, the donor strand flipped out of the pilin and inserted itself into a neighboring pilins groove, thus connecting the two pilins.

Finally, in a combined team effort, the three groups took a closer look at the amino acid composition at the end of the donor strand and found that it played a critical role in the assembly mechanism. Using biochemistry, crystallography and cryo-EM, they mutated the protein, which prevented the pili from forming and thus proved how these key amino acids contribute to pilin polymerization.

Ultimately, this research is a step towards new anti-bacterial drugs, not just for the diseases caused by P. gingivalis, but for those caused by any bacteria containing Type V pili. "We're now trying to create an inhibitor that prevents pili from assembling," said Dr. Shibata. "This structure serves as a target to create new drugs, which are desperately needed to counter increasing antibiotic resistance. Finding novel antimicrobial compounds is a critical advantage in fighting these pathogens."

In the largest study to date of proteins related to Alzheimer's disease, a team of researchers has identified disease-specific proteins and biological processes that could be developed into both new treatment targets and fluid biomarkers. The findings suggest that sets of proteins that regulate glucose metabolism, together with proteins related to a protective role of astrocytes and microglia -- the brain's support cells -- are strongly associated with Alzheimer's pathology and cognitive impairment.

The study, part of the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD), involved measuring the levels and analyzing the expression patterns of more than 3,000 proteins in a large number of brain and cerebrospinal fluid samples collected at multiple research centers across the United States. This research was funded by the National Institutes of Health's National Institute on Aging (NIA) and published April 13 in Nature Medicine.

"This is an example of how the collaborative, open science platform of AMP-AD is creating a pipeline of discovery for new approaches to diagnosis, treatment and prevention of Alzheimer's disease," said NIA Director Richard J. Hodes, M.D. "This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources."

The research team, led by Erik C.B. Johnson, M.D., Ph.D, Nicholas T. Seyfried, Ph.D., and Allan Levey, M.D., Ph.D., all at the Emory School of Medicine, Atlanta, analyzed patterns of protein expression in more than 2,000 human brain and nearly 400 cerebrospinal fluid samples from both healthy people and those with Alzheimer's disease. The paper's authors, which included Madhav Thambisetty, M.D., Ph.D., investigator and chief of the Clinical and Translational Neuroscience Section in the NIA's Laboratory of Behavioral Neuroscience, identified groups (or modules) of proteins that reflect biological processes in the brain.

The researchers then analyzed how the protein modules relate to various pathologic and clinical features of Alzheimer's and other neurodegenerative disorders. They saw changes in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain samples from both people with Alzheimer's as well as in samples from individuals with documented brain pathology who were cognitively normal. This suggests, the researchers noted, that the anti-inflammatory processes designed to protect nerve cells may have been activated in response to the disease.

The researchers also set out to reproduce the findings in cerebrospinal fluid. The team found that, just like with brain tissue, the proteins involved in the way cells extract energy from glucose are increased in the spinal fluid from people with Alzheimer's. Many of these proteins were also elevated in people with preclinical Alzheimer's, i.e., individuals with brain pathology but without symptoms of cognitive decline. Importantly, the glucose metabolism/glial protein module was populated with proteins known to be genetic risk factors for Alzheimer's, suggesting that the biological processes reflected by these protein families are involved in the actual disease process.

"We've been studying the possible links between abnormalities in the way the brain metabolizes glucose and Alzheimer's-related changes for a while now," Thambisetty said. "The latest analysis suggests that these proteins may also have potential as fluid biomarkers to detect the presence of early disease."

In a previous study, Thambisetty and colleagues, in collaboration with the Emory researchers, found a connection between abnormalities in how the brain breaks down glucose and the amount of the signature amyloid plaques and tangles in the brain, as well as the onset of symptoms such as problems with memory.

"This large, comparative proteomic study points to massive changes across many biological processes in Alzheimer's and offers new insights into the role of brain energy metabolism and neuroinflammation in the disease process," said Suzana Petanceska, Ph.D., program director at NIA overseeing the AMP-AD Target Discovery Program. "The data and analyses from this study has already been made available to the research community and can be used as a rich source of new targets for the treatment and prevention of Alzheimer's or serve as the foundation for developing fluid biomarkers."

Brain tissue samples came from autopsy of participants in Alzheimer's disease research centers and several epidemiologic studies across the country, including the Baltimore Longitudinal Study of Aging (BLSA), Religious Orders Study (ROS) and Memory and Aging Project (MAP), and Adult Changes in Thought (ACT) initiatives. The brain collections also contained samples from individuals with six other neurodegenerative disorders as well as samples representing normal aging, which enabled the discovery of molecular signatures specific for Alzheimer's. Cerebrospinal fluid samples were collected from study participants at the Emory Goizueta Alzheimer's Disease Research Center. These and other datasets are available to the research community through the AD Knowledge Portal, the data repository for the AMP-AD Target Discovery Program, and other NIA supported team-science projects operating under open science principles.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process-- each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

After four Louisville, Kentucky, coal-fired power plants either retired coal as their energy source or installed stricter emissions controls, local residents' asthma symptoms and asthma-related hospitalizations and emergency department (ED) visits dropped dramatically, according to research published in Nature Energy this week by Columbia University Mailman School of Public Health, Propeller Health, University of California Berkeley, Harvard TH Chan School of Public Health, University of Texas Austin, Colorado State University, Louisville Metro Department of Public Health and Wellness, Louisville Metro Office of Civic Innovation and Technology, the Christina Lee Brown Envirome Institute and Family Allergy & Asthma.

Coal-fired power plants are known to emit pollutants associated with adverse health effects, including increased asthma attacks, asthma-related ED visits and hospitalizations.1-5 In 2014, coal-fired power plants accounted for 63% of economy-wide emissions of sulfur dioxide (SO2) in the U.S.6 Historically, Kentucky has ranked among the top five states in the U.S. for emissions from power generation.7

Starting with a pilot in 2012, the city of Louisville embarked on a project called AIR Louisville, which aimed to use data from Propeller Health's digital inhaler sensors to gain insights into the impact of local air quality on the burden of respiratory disease in the community. The public-private collaboration equipped more than 1,200 Louisville residents with asthma and COPD with Propeller sensors, which attach to patients' existing inhalers and deliver insights on medication use, symptoms and environmental factors to the Propeller app on their smartphone.

"AIR Louisville brought together local government, public and private partners and residents for a common mission: to leverage local data to make our city better and more breathable," said Louisville Mayor Greg Fischer. "We are still seeing the results of AIR Louisville in this research, which demonstrates the public health impact of retiring coal as an energy source or further controlling coal-fired emissions."

Between 2013 and 2016, one coal-fired power plant in the Louisville area retired coal as an energy source, and three others installed stricter emission controls to comply with regulations from the U.S. Environmental Protection Agency. Researchers took advantage of these circumstances to analyze the impact of the coal-fired power plant energy transitions on residents' respiratory health, using data from Propeller and local hospitals to assess how asthma-related symptoms, ED visits and hospitalizations changed over time.

The study looked at the frequency of the total number of asthma-related ED visits and hospitalizations per ZIP code in Jefferson County, as well as the frequency of asthma rescue medication use among 207 people. Data on rescue medication use for asthma was used as a proxy for patients' symptoms, as patients use their rescue medication for acute relief from symptoms such as coughing and shortness of breath.

"This study was unique in its ability to measure asthma morbidity based on both hospitalizations and daily symptoms, and to leverage an abrupt change in environmental exposure to more directly attribute changes in asthma exacerbation to changes in coal-fired power plant emissions," said Joan Casey, PhD, lead author of the paper and assistant professor of environmental health sciences at Columbia University Mailman School of Public Health.

The researchers found that energy transitions in the spring of 2015 resulted in three fewer hospitalizations and ED visits per ZIP code per quarter in the following year, when comparing areas that had high coal-fired power plant emission exposure prior to the transition to those with lower levels. This translates into nearly 400 avoided hospitalizations and ED visits each year across Jefferson County.

At the individual level, the Mill Creek SO2 scrubber installed in June 2016 was associated with a 17% immediate reduction in rescue medication use, which was maintained thereafter. The study also found the odds of having high rescue use throughout a month (on average more than four puffs per day) was reduced by 32% following the June 2016 energy transition.

"This is the first study to use digital inhaler sensors to understand the health effects of reducing emissions from coal-fired power plants," said study author Meredith Barrett, PhD, head of population health research for Propeller Health. "We hope this evidence will encourage government officials to support stricter standards when regulating coal-fired power plants and encourage us towards cleaner power options, thereby protecting the health of the people who live near these facilities."

People with a gene variant that puts them at high risk for Alzheimer's disease are protected from its debilitating effects if they also carry a variant of a completely different gene, Stanford University School of Medicine investigators report in a large new study.

Their findings, to be published Apr. 13 in JAMA Neurology, suggest that a substantial fraction of the estimated 15% of Americans carrying the high-risk gene variant are protected to some degree from Alzheimer's disease by a variant of the other gene. (A gene will often come in a variety of versions, or variants, that can produce different traits.)

The findings also may help drug developers better identify clinical trial participants and treatments for what, despite billions of dollars spent in pursuit of effective therapies, remains a disease without a cure.

About 5 million Americans -- including roughly 1 in 10 people age 65 or older and one-third of those age 85 or older -- have symptomatic Alzheimer's disease. Even larger numbers have a subtler precursor called mild cognitive impairment. About half with this condition move on to full-blown Alzheimer's. There are medications that can slow development of cognitive symptoms somewhat, but no available drugs prevent the disease's progression or extend patients' lives.

What causes Alzheimer's isn't well understood. There are probably numerous factors. But scientists have known for three decades about one main contributor to the disorder: a gene variant, ApoE4, that's more than three times as frequent in Alzheimer's patients than among people without the disease.

"While 15% of healthy people have the ApoE4 gene variant, it's present in more than 50% of Alzheimer's patients," said Michael Greicius, MD, MPH, associate professor of neurology and director of the Stanford Center for Memory Disorders. "One copy of ApoE4 triples or quadruples your risk, compared with no copies. If you're carrying two copies, your risk goes up tenfold."

Greicius is the senior author of the study. Postdoctoral scholar Michael Belloy, PhD, is the lead author.

Not all ApoE4 carriers develop Alzheimer's disease

"Having one or two copies of ApoE moves the age at which you get sick earlier by five to ten years," Greicius said. "But, it turns out, not all ApoE4 carriers are destined to develop the disease. The gene variant we studied protects you from getting Alzheimer's."

A hallmark of Alzheimer's is the aggregation in the brain of gummy deposits, or plaques, composed of a protein called beta-amyloid. Amyloid aggregation starts more than 10 years before symptoms appear.

"By the time someone is symptomatic, the amyloid horse is out of the barn," Greicius said.

Recent technological advances have enabled the early prediction of Alzheimer's onset by analyzing beta-amyloid levels and other protein levels in cerebrospinal fluid, and by detecting the buildup of Alzheimer's plaques in the brain via imaging. These biomarkers make it possible to predict the disorder's onset before outward symptoms become apparent, or to confirm diagnoses already reached on the basis of behavioral observations.

Yet even having two copies of ApoE4 by no means ensures that a person will develop Alzheimer's. Some such people live to age 85 or 90 without symptoms; they're protected, somehow, from the debilitating effects of this gene variant.

Greicius wondered why. Did some of these people share genetic variants that protect them?

The role of klotho

He and his collaborators focused on a variant of a gene for a protein called klotho. High blood levels of klotho predict longevity in animal studies. There's also evidence for this in humans. For complicated reasons, carrying a single copy of the klotho variant -- a genetic status referred to as heterozygous -- but not two copies increases circulating levels of the klotho protein.

To assess the relationship between klotho-variant status and ApoE4-asociated Alzheimer's risk, the researchers combed through publicly available databases for data on 22,748 ApoE4 carriers with and without symptoms of Alzheimer's disease. All subjects were age 60 or older and of Northwestern European ancestry.

The researchers tallied the likelihood of those subjects with or without a single copy of the klotho variant winding up with Alzheimer's symptoms versus remaining asymptomatic. They tracked asymptomatic ApoE4 carriers over time to determine whether those with a single copy of klotho were less likely to have developed Alzheimer's symptoms. They also analyzed about 650 subjects to see if those with a single copy were less likely to develop cerebrospinal beta-amyloid levels or beta-amyloid brain deposits predicting the disease's onset.

The results were unambiguous.

"In this ApoE4 carrier group, carrying one copy -- but not two -- of the klotho variant reduced Alzheimer's risk by 30%," Belloy, the study's lead author, said. It substantially slowed the progression from symptom-free status to signs of mild cognitive impairment or outright Alzheimer's disease. And it lowered the beta-amyloid burden in the brains of ApoE4 carriers who had not yet progressed to dementia.

Some 25% of Americans are heterozygous for the protective klotho variant. (A much smaller share have two copies, and the rest have none.) Genetic testing for klotho status among ApoE4 carriers could provide a better predictor of Alzheimer's risk in people with the ApoE4 variant, Greicius said.

In addition, drug companies will want to consider excluding patients with a single klotho copy in their clinical trials to maximize the contrast in outcomes among ApoE4-positive participants receiving or not receiving an experimental treatment, Greicius said.

These trials often preferentially recruit ApoE4 carriers, who are predisposed to Alzheimer's, in order to make it easier to detect within a reasonable time frame whether an experimental drug works. By eliminating prospective participants who carry ApoE4 but are potentially protected from Alzheimer's by the klotho variant pinpointed in the new study, researchers can hope to get a clearer picture of a test drug's value.

Learning more about how the protective gene variant works may also lead to a more sophisticated understanding of ApoE4's debilitating effect on cognition -- and, importantly, help researchers to zero in on therapeutic targets for the prevention or mitigation of those effects, Greicius said.

What is the origin of the famous interstellar object 'Oumuamua? How was it formed and where did it come from? An article published on April 13 in Nature Astronomy by ZHANG Yun from National Astronomical Observatories of Chinese Academy of Sciences (NAOC) and Douglas N. C. Lin from University of California, Santa Cruz, offers a first comprehensive answer to this mystery, which involves tidal forces like those felt by Earth's oceans and explains all of the unusual characteristics of this interstellar object.

'Oumuamua was discovered on October 19, 2017, by the Panoramic Survey Telescope and Rapid Response System 1 (Pan-STARRS1) located at Hawaii. As the first known interstellar object to visit our Solar System, 'Oumuamua is absolutely nothing like anything else in the Solar System.Its dry surface, unusually elongated shape and puzzling motion even drove some scientists to wonder if it was an alien probe.

"It is really a mystery," said ZHANG Yun, first author of the study, "but some signs, like its colors and the absence of radio emission, point to 'Oumuamua being a natural object."

"Our objective is to come up with a comprehensive scenario, based on well understood physical principle to piece together all the tantalizing clues," said Douglas Lin, coauthor of the study.

It was generally assumed that the first discovered interstellar object would be an icy body, like comets. In effect, icy objects are constantly tossed out of their host systems. They are also much more visible due to their apparent coma. However, 'Oumuamua's dry appearance, similar to rocky bodies, like asteroids in the Solar System, indicates a different ejection scenario.

"The discovery of 'Oumuamua implies that the population of rocky interstellar objects is much larger than we previously thought. On average, each planetary system should eject in total about a hundred trillion objects like 'Oumuamua. We need to construct a very efficient scenario." said ZHANG. "In space, some objects occasionally come very close to a bigger one. Tidal forces of the bigger one can disrupt these small ones, like the things happened to comet Shoemaker-Levy 9 when it closely passed by Jupiter."

ZHANG and Lin ran high-resolution computer simulations to model the dynamics of an object closely flying by a star. They found that the star can dramatically split the object, if it comes enough close to the star, into extremely elongated fragments,and then eject them into the interstellar space.

"The elongated shape is more compelling when we considered the phase transition of material during the stellar encounter. The long-to-short axis ratio can be even larger than ten." ZHANG said. Due to the intense stellar radiation, the surfaces of fragments melt at very short distance to the star and re-condense at further distances. Like melting chocolate beans, the surface materials stick together to maintain the elongated shape.

"Heat diffusion also consumes large amounts of volatiles.These fragments become dry and have 'Oumuamua-likesurface." ZHANG added. "However, some water ice buried under the surface can be preserved. These residual water ice could be activated during its Solar System passage to causeits non-gravitational motion."

"The tidal fragmentation scenario not only provides a way to form one single 'Oumuamua, but also accounts for the vast population of rocky interstellar objects." ZHANG said. Their calculations demonstrate the efficiency of stellar tides in producing this kind of objects. Possible progenitors, including long-period comets, debris disks, and even planets, can be transformed into 'Oumuamua-size pieces during stellar encounters. The inferred number density of interstellar objects is consistent with 'Oumuamua's occurrence rate.

This work highlights the prolificacy of 'Oumuamua-like interstellar object population between stars. Since these objects pass through the domains of habitable zones, the prospect of transport of matter capable of generating life by these objects cannot be ruled out.

"This work provides a plausible narrative that links its strange properties to the process of planet formation that is ubiquitous in the Milky Way Galaxy," said Gregory Laughlin, a professor of astronomy at Yale University.

" 'Oumuamua is just the tip of the iceberg. We anticipate many more interstellar visitors with similar traits will be discovered by future observation with the forthcoming Vera C. Rubin Observatory," Lin said.

"This is a very new field. These interstellar objects could provide critical clues about how planetary systems form and evolve, and how life started on the Earth." ZHANG said.

"This work does a remarkable job of explaining a variety of unusual properties of 'Oumuamua with a single, coherent model." said US Naval Academy astronomer Matthew Knight, co-leader of the 'Oumuamua International Space Science Institute team, "As future interstellar objects are discovered in coming years, it will be very interesting to see if any exhibit 'Oumuamua-like properties. If so, it may indicate that the processes described in this study are widespread."

A group of animal biologists and chemists at the Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, has used a chemical genomics approach to explore the underlying mechanism of winter depression-like behavior and identified a drug that rescues winter depression-like behavior in medaka fish.

Seasonal changes in the environment can lead to depression- and anxiety-like behavior in humans as well as animals. At high latitudes, including northern regions of the United States and Nordic countries, about 10% of the population suffers from winter depression (Seasonal Affective Disorder: SAD), with typical symptoms including low mood, sleep problems, disrupted circadian rhythms, social withdrawal, decreased libido, and changes in appetite and body weight, and related suicide and social withdrawal becoming a serious public health issue.

Animal models play an essential role in understanding the mechanistic nature of biological and behavioral processes, as well as in the discovery of new drugs. Small fish such as medaka have emerged as powerful models for the study of complex brain disorders and have become valuable pharmacogenetic tools. Medaka were found to be an excellent animal model for winter depression, with decreased sociability and increased anxiety-like behavior in medaka exposed to winter conditions.

To understand the underlying mechanisms of winter depression, the research group employed a chemical genomics approach. An in vivo broad-spectrum chemical screen identified the traditional Chinese medicine, celastrol, as rescuing winter behavior. NRF2 is a celastrol target expressed in the habenula, known to play a critical role in the pathophysiology of depression. Although fish do not have a defined prefrontal cortex (PFC), the habenula is evolutionarily highly conserved and connects the limbic forebrain and monoaminergic system. Depression is considered an adaptation to a harsh environment. Given the striking parallels between patients with SAD and medaka kept under winter-like conditions, the present findings provide important insights into the mechanism of winter depression and offer new potential therapeutic targets for its treatment involving NRF2.

Irvine, Calif., April 13, 2020 - Researchers at the University of California, Irvine and other institutions have architecturally designed plate-nanolattices - nanometer-sized carbon structures - that are stronger than diamonds as a ratio of strength to density.

In a recent study in Nature Communications, the scientists report success in conceptualizing and fabricating the material, which consists of closely connected, closed-cell plates instead of the cylindrical trusses common in such structures over the past few decades.

"Previous beam-based designs, while of great interest, had not been so efficient in terms of mechanical properties," said corresponding author Jens Bauer, a UCI researcher in mechanical & aerospace engineering. "This new class of plate-nanolattices that we've created is dramatically stronger and stiffer than the best beam-nanolattices."

According to the paper, the team's design has been shown to improve on the average performance of cylindrical beam-based architectures by up to 639 percent in strength and 522 percent in rigidity.

Members of the architected materials laboratory of Lorenzo Valdevit, UCI professor of materials science & engineering as well as mechanical & aerospace engineering, verified their findings using a scanning electron microscope and other technologies provided by the Irvine Materials Research Institute.

"Scientists have predicted that nanolattices arranged in a plate-based design would be incredibly strong," said lead author Cameron Crook, a UCI graduate student in materials science & engineering. "But the difficulty in manufacturing structures this way meant that the theory was never proven, until we succeeded in doing it."

Bauer said the team's achievement rests on a complex 3D laser printing process called two-photon lithography direct laser writing. As an ultraviolet-light-sensitive resin is added layer by layer, the material becomes a solid polymer at points where two photons meet. The technique is able to render repeating cells that become plates with faces as thin as 160 nanometers.

Bauer said the team's achievement rests on a complex 3D laser printing process called two-photon polymerization direct laser writing. As a laser is focused inside a droplet of an ultraviolet-light-sensitive liquid resin, the material becomes a solid polymer where molecules are simultaneously hit by two photons. By scanning the laser or moving the stage in three dimensions, the technique is able to render periodic arrangements of cells, each consisting of assemblies of plates as thin as 160 nanometers.

One of the group's innovations was to include tiny holes in the plates that could be used to remove excess resin from the finished material. As a final step, the lattices go through pyrolysis, in which they're heated to 900 degrees Celsius in a vacuum for one hour. According to Bauer, the end result is a cube-shaped lattice of glassy carbon that has the highest strength scientists ever thought possible for such a porous material.

Bauer said that another goal and accomplishment of the study was to exploit the innate mechanical effects of the base substances. "As you take any piece of material and dramatically decrease its size down to 100 nanometers, it approaches a theoretical crystal with no pores or cracks. Reducing these flaws increases the system's overall strength," he said.

"Nobody has ever made these structures independent from scale before," added Valdevit, who directs UCI's Institute for Design and Manufacturing Innovation. "We were the first group to experimentally validate that they could perform as well as predicted while also demonstrating an architected material of unprecedented mechanical strength."

Nanolattices hold great promise for structural engineers, particularly in aerospace, because it's hoped that their combination of strength and low mass density will greatly enhance aircraft and spacecraft performance.

BUFFALO, N.Y. -- Foxglove plants, found in many gardens, are known for the showers of bell-shaped flowers they produce.

But plants belonging to this genus, Digitalis, also harbor a less visible asset: Chemicals called cardiac glycosides, which have been recorded to treat heart failure since the 1780s, says University at Buffalo biologist Zhen Wang.

Wang's research investigates how foxgloves create these medicinal compounds, with an eye toward improving the process. Farming foxgloves is time-consuming and labor-intensive, and Wang hopes to change that.

Specifically, her lab is investigating the chemical processes the plants use to create cardiac glycosides: what steps are taken, what genes are turned on, and what enzymes are deployed.

"The reason why plants make so many natural products with medicinal properties is because they are also fighting diseases," says Wang, PhD, assistant professor of biological sciences in the UB College of Arts and Sciences. "Plants aren't like animals. They can't run away when stresses come, so they cope with this by becoming the most extraordinary chemists on the planet."

And yet, "How plants synthesize many natural products is largely unknown," Wang says. "I want to understand how we can harness the power of nature to make the process of producing medicinal compounds more efficient and sustainable. Foxgloves make these powerful compounds, but it takes two years to do so, and they don't make them in a very large quantity. How can we improve this process?"

Two new studies illuminate chemical compounds in foxgloves

Wang's team recently published a pair of papers detailing the characteristics of cardiac glycosides in two foxglove species: Digitalis purpurea, a showy purple flower found in many gardens; and Digitalis lanata, which is grown for medicinal purposes.

"This kind of study is important because we first have to know the accurate structure of natural compounds before we can explore their medicinal effects," Wang says.

The first paper, published online in January in the Journal of Chromatography A, describes methods for assessing the exact mass and structure of cardiac glycosides, and compares compounds found in Digitalis purpurea and Digitalis lanata. The second study, published online in March in the journal Data in Brief, expands on the first, providing additional data on characteristics of cardiac glycosides in both species.

"When we looked at the cardiac glycosides in each of them, we found drastic differences," Wang says. "In the industrial strain that's grown for medicine, you see much higher amounts of cardiac glycosides, with much more diversity. I think this just highlights the adaptation of plants and how versatile they are as chemists."

Both studies included contributions from researchers in the UB Department of Chemistry.

Improving on the foxglove's natural skills

Digitalis lanata is cultivated for medicine because it makes a cardiac glycoside called digoxin. This compound is toxic in large quantities, but it's prescribed sparingly, in small doses, to treat heart failure and certain heart rhythm abnormalities.

Current methods for producing digoxin are cumbersome: Because each foxglove plant makes only a little bit of the chemical, farmers must grow the crop in huge quantities, Wang says. That uses up a lot of agricultural land. The wait time is also long.

"It takes two years, from the time you plant the seed to the time the leaves are ready to harvest, and then you have to dry it in the silo," Wang says. "Then, the plant is crushed into powder, and the compound is extracted and purified using chemical processes."

If Wang's team can figure out, step-by-step, how foxgloves make cardiac glycosides, scientists could leverage that information to explore a variety of improvements.

Biologists could engineer fast-growing microbes, such as yeast or harmless strains of bacteria, to produce cardiac glycosides more quickly. Plant scientists could genetically engineer foxgloves to make larger amounts of digoxin, which would increase the efficiency of farms and free up land for other useful crops.

Medicinal chemists could also work to develop new drugs that are similar to digoxin but safer.

"We can learn from nature," Wang says. "We can study all of the available compounds that are found in the plants and then come up with our own design of compounds that are safer and more effective. That's why I think it's important to not just focus on the current drug digoxin, but to expand our focus to all the compounds in the same class, the cardiac glycosides."

Unprecedented observations of a nova outburst in 2018 by a trio of satellites, including two NASA missions, have captured the first direct evidence that most of the explosion's visible light arose from shock waves -- abrupt changes of pressure and temperature formed in the explosion debris.

A nova is a sudden, short-lived brightening of an otherwise inconspicuous star. It occurs when a stream of hydrogen from a companion star flows onto the surface of a white dwarf, a compact stellar cinder not much larger than Earth. NASA's Fermi and NuSTAR space telescopes, together with the Canadian BRITE-Toronto satellite and several ground-based facilities, studied the nova.

"Thanks to an especially bright nova and a lucky break, we were able to gather the best-ever visible and gamma-ray observations of a nova to date," said Elias Aydi, an astronomer at Michigan State University in East Lansing who led an international team from 40 institutions. "The exceptional quality of our data allowed us to distinguish simultaneous flares in both optical and gamma-ray light, which provides smoking-gun evidence that shock waves play a major role in powering some stellar explosions."

The 2018 outburst originated from a star system later dubbed V906 Carinae, which lies about 13,000 light-years away in the constellation Carina. Over time -- perhaps tens of thousands of years for a so-called classical nova like V906 Carinae -- the white dwarf's deepening hydrogen layer reaches critical temperatures and pressures. It then erupts in a runaway reaction that blows off all of the accumulated material.

Each nova explosion releases a total of 10,000 to 100,000 times the annual energy output of our Sun. Astronomers discover about 10 novae each year in our galaxy.

Fermi detected its first nova in 2010 and has observed 14 to date. Although X-ray and radio studies had shown the presence of shock waves in nova debris in the weeks after the explosions reached peak brightness, the Fermi discovery came as a surprise.

Gamma rays -- the highest-energy form of light -- require processes that accelerate subatomic particles to extreme energies. When these particles interact with each other and with other matter, they produce gamma rays. But astronomers hadn't expected novae to be powerful enough to produce the required degree of acceleration.

Because the gamma rays appear at about the same time as the peak in visible light, astronomers concluded that shock waves play a more fundamental role in the explosion and its aftermath.

In 2015, a paper led by Brian Metzger at Columbia University in New York showed how comparing Fermi gamma-ray data with optical observations would allow scientists to learn more about nova shock waves. In 2017, a study led by Kwon-Lok Li at Michigan State found that the overall gamma-ray and visible emissions rose and fell in step in a nova known as V5856 Sagittarii. This implied shock waves produced more of the eruption's light than the white dwarf itself.

The new observations from V906 Carinae, presented in a paper led by Aydi and published on Monday, April 13, in Nature Astronomy, spectacularly confirm this conclusion.

On March 20, 2018, the All-Sky Automated Survey for Supernovae, a set of two dozen robotic telescopes distributed around the globe and operated by Ohio State University, discovered the nova. By month's end, V906 Carinae was dimly visible to the naked eye.

Fortuitously, a satellite called BRITE-Toronto was already studying the nova's patch of sky. This miniature spacecraft is one of five 7.9-inch (20 centimeter) cubic nanosatellites comprising the Bright Target Explorer (BRITE) Constellation. Operated by a consortium of universities from Canada, Austria and Poland, the BRITE satellites study the structure and evolution of bright stars and observe how they interact with their environments.

BRITE-Toronto was monitoring a red giant star called HD 92063, whose image overlapped the nova's location. The satellite observed the star for 16 minutes out of every 98-minute orbit, returning about 600 measurements each day and capturing the nova's changing brightness in unparalleled detail.

"BRITE-Toronto revealed eight brief flares that fired up around the time the nova reached its peak, each one nearly doubling the nova's brightness," said Kirill Sokolovsky at Michigan State. "We've seen hints of this behavior in ground-based measurements, but never so clearly. Usually we monitor novae from the ground with many fewer observations and often with large gaps, which has the effect of hiding short-term changes."

Fermi, on the other hand, almost missed the show. Normally its Large Area Telescope maps gamma rays across the entire sky every three hours. But when the nova appeared, the Fermi team was busy troubleshooting the spacecraft's first hardware problem in nearly 10 years of orbital operations -- a drive on one of its solar panels stopped moving in one direction. Fermi returned to work just in time to catch the nova's last three flares.

In fact, V906 Carinae was at least twice as bright at billion-electron-volt, or GeV, energies as any other nova Fermi has observed. For comparison, the energy of visible light ranges from about 2 to 3 electron volts.

"When we compare the Fermi and BRITE data, we see flares in both at about the same time, so they must share the same source -- shock waves in the fast-moving debris," said Koji Mukai, an astrophysicist at the University of Maryland Baltimore County and NASA's Goddard Space Flight Center in Greenbelt, Maryland. "When we look more closely, there is an indication that the flares in gamma rays may lead the flares in the visible. The natural interpretation is that the gamma-ray flares drove the optical changes."

The team also observed the eruption's final flare using NASA's NuSTAR space telescope, which is only the second time the spacecraft has detected X-rays during a nova's optical and gamma-ray emission. The nova's GeV gamma-ray output far exceeded the NuSTAR X-ray emission, likely because the nova ejecta absorbed most of the X-rays. High-energy light from the shock waves was repeatedly absorbed and reradiated at lower energies within the nova debris, ultimately only escaping at visible wavelengths.

Putting all of the observations together, Aydi and his colleagues describe what they think happened when V906 Carinae erupted. During the outburst's first few days, the orbital motion of the stars swept a thick debris cloud made of multiple shells of gas into a doughnut shape that appeared roughly edge-on from our perspective. The cloud expanded outward at less than about 1.3 million mph (2.2 million kph), comparable to the average speed of the solar wind flowing out from the Sun.

Next, an outflow moving about twice as fast slammed into denser structures within the doughnut, creating shock waves that emitted gamma rays and visible light, including the first four optical flares.

Finally, about 20 days after the explosion, an even faster outflow crashed into all of the slower debris at around 5.6 million mph (9 million kph). This collision created new shock waves and another round of gamma-ray and optical flares. The nova outflows likely arose from residual nuclear fusion reactions on the white dwarf's surface.

Astronomers have proposed shock waves as a way to explain the power radiated by various kinds of short-lived events, such as stellar mergers, supernovae -- the much bigger blasts associated with the destruction of stars -- and tidal disruption events, where black holes shred passing stars. The BRITE, Fermi and NuSTAR observations of V906 Carinae provide a dramatic record of such a process. Further studies of nearby novae will serve as laboratories for better understanding the roles shock waves play in other more powerful and more distant events.

Loss of smell and taste has been anecdotally linked to COVID-19 infections. In a study published April 12, 2020 in the journal International Forum of Allergy & Rhinology, researchers at UC San Diego Health report the first empirical findings that strongly associate sensory loss with COVID-19, the respiratory disease caused by the novel coronavirus.

"Based on our study, if you have smell and taste loss, you are more than 10 times more likely to have COVID-19 infection than other causes of infection. The most common first sign of a COVID-19 infection remains fever, but fatigue and loss of smell and taste follow as other very common initial symptoms," said Carol Yan, MD, an otolaryngologist and head and neck surgeon at UC San Diego Health. "We know COVID-19 is an extremely contagious virus. This study supports the need to be aware of smell and taste loss as early signs of COVID-19."

Yan and colleagues surveyed 1,480 patients with flu-like symptoms and concerns regarding potential COVID-19 infection who underwent testing at UC San Diego Health from March 3 through March 29, 2020. Within that total, 102 patients tested positive for the virus and 1,378 tested negative. The study included responses from 59 COVID-19-positive patients and 203 COVID-19-negative patients.

Yan said the study demonstrated the high prevalence and unique presentation of certain sensory impairments in patients positive with COVID-19. Of those who reported loss of smell and taste, the loss was typically profound, not mild. But encouragingly, the rate of recovery of smell and taste was high and occurred usually within two to four weeks of infection.

"Our study not only showed that the high incidence of smell and taste is specific to COVID-19 infection, but we fortunately also found that for the majority of people sensory recovery was generally rapid," said Yan. "Among the Covid-19 patients with smell loss, more than 70 percent had reported improvement of smell at the time of survey and of those who hadn't reported improvement, many had only been diagnosed recently."

Sensory return typically matched the timing of disease recovery. Interestingly, the researchers found that persons who reported experiencing a sore throat more often tested negative for COVID-19.

In an effort to decrease risk of virus transmission, UC San Diego Health now includes loss of smell and taste as a screening requirement for visitors and staff, as well as a marker for testing patients who may be positive for the virus.

Other known symptoms of COVID-19 include fever, fatigue, cough and difficulty breathing. Respondents in Yan's study were most often persons with milder forms of COVID-19 infection who did not require hospitalization or intubation. The findings, she said, underline the importance of identifying early or subtle symptoms of COVID-19 infection in people who may be at risk of transmitting the disease as they recuperate within the community.

"It is our hope that with these findings other institutions will follow suit and not only list smell and taste loss as a symptom of COVID-19, but use it as a screening measure for the virus across the world," Yan said.

DALLAS, April 13, 2020 -- Type 2 diabetes (T2D) affects treatment options for patients who have both coronary artery disease (CAD) and T2D, according to a new American Heart Association Scientific Statement, published today in the Association's flagship journal Circulation. The scientific statement provides an overview of the latest advances for treating people who have both CAD and T2D and details the complexities of care for these conditions together.

"Recent scientific studies have shown that people with T2D may need more aggressive or different medical and surgical treatments compared to people with CAD who do not have T2D," said Suzanne V. Arnold, M.D., M.H.A., chair of the writing group for the scientific statement, associate professor of medicine at the University of Missouri Kansas City, and a cardiologist at Saint Luke's Mid America Heart Institute, also in Kansas City, Missouri.

When a person has T2D, their body is not able to efficiently use the insulin it makes to keep glucose (blood sugar) at a healthy level, and people with T2D often have overweight or obesity, high blood pressure and high cholesterol, which further increases the risk of cardiovascular disease. For many years, reducing glucose to healthy levels was considered the most important goal of therapy for T2D.

"What we've learned in the past decade is how you control glucose levels has a huge influence on cardiovascular risk. Lowering blood sugars to a certain level is not sufficient. There are now more options for controlling glucose in people with T2D, and each patient should be evaluated for their personal risk of cardiovascular disease, stroke and kidney disease. This combined health information as well as the patient's age should be used to determine the appropriate therapies to lower glucose," said Arnold.

Metformin is the most frequently recommended medication for initial treatment to lower glucose in people diagnosed with T2D. Metformin sometimes leads to mild weight loss, is at least neutral in terms of cardiovascular effects, is inexpensive and has a long use and safety history. However, the statement notes that the latest research indicates several newer classes of medications may both lower glucose and reduce the risk of cardiovascular diseases.

Sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), which are oral medications, were the first class to show clear benefits on cardiovascular outcomes. In a recent study of people with T2D and a diagnosis of heart disease, researchers found that patients taking SGLT2 inhibitors were significantly less likely to die of cardiovascular disease. They had a reduced risk of heart failure, less progression of chronic kidney disease and also lost weight.

Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) are a class of injectable medications that lower blood glucose and can also cause a reduction in weight. Recent study results about their efficacy in reducing cardiovascular diseases have been mixed. However, a few GLP-1 receptor agonists have been shown to reduce the risk of major cardiovascular events caused by cholesterol build-up in the arteries, such as heart attacks and strokes.

For older adults, relaxing glycemic control slightly might be beneficial because it may reduce the risk of hypoglycemia - when glucose levels become too low. "Hypoglycemia is incredibly hard on the heart and should be avoided particularly in older patients. We must ensure that we are weighing all of the options in consideration of the whole patient, keeping in mind that what may be appropriate for a 60-70 year old patient is likely not the same as for an 85-year old," said Arnold. With some medications, such as metformin, SGLT2 inhibitors and GLP-1 receptor agonists, the risk of hypoglycemia may be reduced.

Preventing blood from forming clots is also an important goal of CAD treatment. "Aspirin, which is a blood thinner, may be appropriate for many people with CAD, but may not work as effectively in people with T2D and CAD. Therefore, newer, stronger antiplatelet medications (a form of blood thinner) should be considered. Since all antiplatelet medications increase the risk of bleeding, it is important to balance the risk for each patient of increased bleeding versus the benefit of reducing the tendency of the blood to clot," said Arnold.

Type 2 diabetes may also influence what type of interventional procedure is best to use to re-open an artery to increase blood flow in indicated patients. Studies have found a greater reduction in the 5-year risk of death, heart attack or recurrent angina/chest pain when patients with T2D and CAD undergo coronary artery bypass graft (CABG) surgery to widen a narrowed blood vessel instead of treating the narrowing with angioplasty and stenting. In contrast, the advantage of bypass over stenting is not as dramatic in people without T2D.

Additionally, unhealthy cholesterol levels, such as high LDL (bad cholesterol), low HDL (good cholesterol) and high triglycerides (blood fat), which are major risk factors for CAD, are common among people with T2D. In many patients, even if LDL levels are not exceptionally high, people with T2D often have a type of LDL particle that is more likely to increase the risk of atherosclerosis, the slow narrowing of the arteries that underlies heart disease.

The vast majority of patients with T2D have hypertension. Blood pressure control is critically important in the management of CAD in patients with T2D.

"More aggressive steps may be needed to improve the cholesterol levels in people with T2D. Statins, the cornerstone of cholesterol-lowering therapy, may slightly increase blood sugar levels, however, the overall cardiovascular risk reduction they provide is far more beneficial. Blood sugar changes are not a reason to avoid prescribing statins for people with type 2 diabetes," said Arnold.

Some patients with CAD and T2D may also benefit from lowering cholesterol with additional classes of medications, such as oral cholesterol absorption inhibitors or newer injectable medications, which have been shown to be beneficial in people with diabetes.

"While treatment with medication is very important in the treatment of people who have both T2D and CAD, no pill is a substitute for a healthy lifestyle. No matter what new medicines there are, a heart-healthy diet, achieving and maintaining a healthy weight, regular physical activity and treating sleep disorders remain the major cornerstones of treatment for T2D and cardiovascular disease," said Arnold.

Mathematical modeling can take what information is reported about the coronavirus, including the clearly underreported numbers of cases, factor in knowns like the density and age distribution of the population in an area, and compute a more realistic picture of the virus' infection rate, numbers that will enable better prevention and preparation, modelers say.

"Actual pandemic preparedness depends on true cases in the population whether or not they have been identified," says Dr. Arni S.R. Srinivasa Rao, director of the Laboratory for Theory and Mathematical Modeling in the Division of Infectious Diseases at the Medical College of Georgia at Augusta University. "With better numbers we can better assess how long the virus will persist and how bad it will get. Without these numbers, how can health care systems and workers prepare for what is needed?"

Better numbers also are critical to better protecting the population and overall pandemic preparedness, Rao and his colleague Dr. Steven G. Krantz, professor of mathematics at Washington University in St. Louis, Missouri write in the journal Infection Control and Hospital Epidemiology.

"We wanted to provide info on the real magnitude of the problem, not just the tip of the iceberg," corresponding author Rao says.

They used their mathematical model, which takes COVID-19 numbers from sources like the World Health Organization, then used factors like an area's population density, proportion of population living in urban areas where people tend to live in closer proximity, and populations in three age groups -- ages zero to 14, 15 to 64 and 65+ -- to grow more accurate numbers. Because this virus is so infectious, they also considered "transmission probability," Rao says.

They also looked at the number of new cases daily above 10 and up to the first reported peak, and the date ranges for those peaks as an indicator of the trend in reported case numbers. Emerging information about how long the virus survives on a variety of surfaces and in the air will further refine their model, Rao says. The cutoff date for this study was March 9.

They found, for example, that Italy -- where images of jammed intensive care units were one of the clearest indicators of the virus' impact in this geographically small but fifth mostly densely populated European country with a high urbanization score -- did a comparatively good job of reporting early on, with 1 case reported for every four cases that Rao and Krantz projected. That means about 30,223 cases were not reported, according to their model, and Rao noted that Italy had not reached its peak by their March 9 study deadline.

With such a small percentage of people actually being tested in all countries, particularly at that time, South Korea also was reporting 1 case for about every four likely cases. In Spain -- where drive-thru funerals have been reported as occurring every 15 minutes, with nearly 20,000 deaths and a peak in cases March 19, when they reported a 27% increase in active cases -- the country was reporting 1 case for about every 53 likely actual cases, based on the mathematical model. That translates to about 87,405 cases and people not reported. The two modelers saw some of the higher numbers they projected actually playing out within a week of their study's conclusion in several of these European countries, Rao says.

In China, with its huge population numbers at more than 1.4 billion and widely perceived inconsistencies in data reporting, they projected two ranges for the number reported compared to the actual number of cases: 1 in 149 and 1 in 1,104, which translates to anywhere from 12 million to 89 million cases not reported.

A rate could not be calculated March 9 for the United States, where the virus appears to have shown up later, and reported case numbers were just reaching 500, a baseline for projections by mathematical modelers. Rao suspects that the actual number at that date in the U.S. was probably more like 90,000 cases.

A quick follow-up assessment of U.S. numbers by Rao on April 6 using their model indicated more than 561,000 cases with 367,000 actually reported and 8,910 deaths at that date. That calculates to a reporting rate of 2 out of every 3 actual cases in the U.S., reflecting the improvement in tracing positive cases, he says.

Among those 194,000 not yet reported, he projects that includes 3,298 children age 14 and younger, 147,441 ages 15-64 and 43,262 age 65+. That also means that in the U.S., at least 194,000 people at that April 6th moment likely don't know they were positive, more clear evidence of the need for social distancing and other preventive measures currently underway, Rao says.

The modelers visualized the disparities between reported cases and what they projected with a Meyer wavelet, which as the name implies goes up, peaks, and then recedes like a wave. In this case the higher the wave, the higher the underreporting, and lowering the wave means improved reporting, Rao says, of the consistent oscillations generated.

If reported numbers were more precise, mathematical models wouldn't be needed, Rao says, noting that underreporting is a problem for many conditions, not just COVID-19, including common, noninfectious problems like heart disease. "A model tells us something which has not been directly observed," he says. "It's a biological experiment done on computers rather than in a lab."

Rao notes the accuracy of reported cases likely has improved since March 9 with the slowly increased availability of testing, and that the earlier the testing, the earlier the actual peaking of infections.

In the meantime, he encourages everyone to continue to use steps like social isolation and self-quarantine to protect themselves and others by helping fight continued spread of the virulent virus.

"Social distancing is a must, must, must," Rao says.

As of March 9, there were 109,000 cases and 3,800 deaths reported worldwide, the majority from China as well as Italy, South Korea, Iran, France, Germany and Spain. As of the first full week in April -- about a month after their study deadline --nearly 1.4 million cases with more than 81,000 deaths were reported worldwide. More recent figures include the U.S. having more than 362,000 cases and about 11,000 deaths, Spain with more than 135,000 cases and more than 13,000 deaths, and Italy, Germany, France, China, Iran, the United Kingdom, Turkey and Switzerland falling next in line.

In a related research letter in the journal Current Science, they reported about 1 in 4 COVID-19 cases were detected in the month of March in India, that social distancing and other prevention/treatment policies should continue until new cases are not seen there and that spread from urban to more rural populations should be controlled.

WATERLOO, Ontario, April 13, 2020--A new peer-reviewed paper from five prominent ocular scientists will help eye care practitioners (ECPs) instruct and reassure contact lens wearers during the global COVID-19 / coronavirus pandemic. Published in Contact Lens & Anterior Eye, "The COVID-19 Pandemic: Important Considerations for Contact Lens Practitioners" delves into multiple aspects of eye health amidst the global health crisis, with a specific emphasis on the safe use of contact lenses.

The paper and related ECP and patient resources can be accessed from COVIDEyeFacts.org.

"Our findings indicate that contact lenses remain a perfectly acceptable form of vision correction during the coronavirus pandemic, as long as people observe good hand hygiene and follow appropriate wear-and-care directions," said Dr. Lyndon Jones, director of the Centre for Ocular Research & Education (CORE) at the University of Waterloo and the paper's lead author. "Unfortunately, we have seen a number of erroneous reports regarding contact lenses and spectacles in recent days. Our goal is to make sure that science-backed truths are understood and shared, helping eye care practitioners provide accurate, timely counsel to patients."

Based on the paper, CORE has developed five facts (also available as a downloadable infographic) for ECPs to share with anyone who relies on contact lenses or glasses / spectacles:

1. People Can Keep Wearing Contact Lenses. There is currently no scientific evidence that contact lens wearers have an increased risk of contracting COVID-19 compared with glasses / spectacles wearers. Patients should consult their eye care practitioners with questions.

2. Good Hygiene Habits are Critical. Thorough handwashing and drying are essential, as well as properly wearing and caring for contact lenses, ensuring good contact lens case hygiene, and regularly cleaning glasses / spectacles with soap and water. These habits will help wearers stay healthy and out of their doctor's office or hospital, thereby minimizing impacts on the wider healthcare system.

3. Regular Eyeglasses / Spectacles Do Not Provide Protection. No scientific evidence supports rumors that everyday eyeglasses / spectacles offer protection against COVID-19.

4. Keep Unwashed Hands Away from the Face. Whether people wear contact lenses, glasses / spectacles or require no vision correction at all, individuals should avoid touching their nose, mouth and eyes with unwashed hands, consistent with World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (CDC) recommendations.

5. If You Are Sick, Temporarily Stop Wearing Contact Lenses. Contact lens wearers who are ill should temporarily revert to wearing eyeglasses / spectacles. They can resume use with fresh, new contact lenses and lens cases once they return to full health and have spoken with their eye care practitioner.

On April 8, the CDC issued updated guidance on contact lens wear during the COVID-19 pandemic, further supporting key findings from the Contact Lens & Anterior Eye paper. The CDC additionally points out that personal eyeglasses and contact lenses do not qualify as personal protective equipment (PPE).

The Contact Lens & Anterior Eye paper also reviews why management of adverse events should be retained within optometric systems, offers guidance on sleeping in contact lenses, considers wearing modalities and lens materials, and offers areas for further study.

Unraveling interactions between metal ions and peptides in the body may eventually lead to improved treatments for diabetes, Alzheimer's and other diseases. Understanding these interactions is the focus of research, co-led by KAUST, that is revealing how metals, such as copper, can affect the formation of harmful clumps of misfolded peptide clusters called fibrils, which underpin many diseases.

Errant peptides are linked to neurological conditions such as Alzheimer's, as well as to blood sugar control disease diabetes. Blood sugar levels are normally controlled via peptide hormones released by specialist cells called β-cells. As well as insulin, healthy β-cells also release amylin, a peptide hormone that helps to reduce spikes in blood sugar level after eating by slowing stomach emptying. But amylin is prone to forming misfolded clumps, especially in the presence of copper ions, that damage β-cells and contribute to type II diabetes.

However, metal ions can also counteract peptide aggregation in some circumstances, says KAUST researcher, Mariusz Jaremko, who led the work in collaboration with researchers from the University of Wroclaw in Poland. To study the process in more detail, the team is examining the interaction between copper(II) ions and amylin and its molecular analogs. "Such knowledge would give us insights into the molecular mechanisms of type II diabetes, enabling us to design new strategies and therapies against this disease," Jaremko says.

In their latest work, the team studied the influence of copper ions on the aggregation of two analogs of human amylin: an amylin-mimicking drug called pramlintide and amylin from rats. "We found that differences in the structures of pramlintide and rat amylin mean that copper ions impede the aggregation of pramlintide, but not rat amylin," says Mawadda Alghrably, a Ph.D. student in Jaremko's team.

The researchers investigated the process using multiple techniques, including nuclear magnetic resonance (in collaboration with Abdul-Hamid Emwas from KAUST CoreLabs), and a "thioflavin T" fluorescence assay of protein aggregation. They found that although both amylin analogs bind copper, pramlintide could bind it in two different ways due to an extra copper-binding histidine amino acid that is present in pramlintide but not rat amylin. Copper-ion binding to this histidine probably explained why copper reduced pramlintide aggregation but not rat amylin aggregation, the researchers concluded.

The team is continuing to decipher the molecular basis of amylin aggregation, Alghrably says. "Understanding how these molecules behave, could ultimately help to facilitate the design of new efficient drugs and therapies for type II diabetes," she says.

In a new study, published in the journal Nature, Michigan State University scientists show how plant genes select which microbes get to live inside their leaves in order to stay healthy.

This is the first study to show a causal relationship between plant health and assembly of the microbial community in the phyllosphere -- the total above-ground portions of plants. The work suggests that organisms, from plants to animals, may share a similar strategy to control their microbiomes.

Microbiome studies are a hot topic in human health science. When scientists mention that human 'gut bacteria' should be well balanced, they refer to the gut microbiome, the genetic material of all the microbes living in human digestive systems.

"The field of large-scale plant microbiome study is only about a decade old," said Sheng Yang He, lead co-author of the study, a member of the MSU-DOE Plant Research Laboratory and a Howard Hughes Medical Institute Investigator. "We want to know if plants need a properly assembled phyllosphere microbiome.

Plant genes: Gatekeepers of microbes:

"In nature, plants are bombarded by zillions of microbes," said He, a University Distinguished Professor who holds joint appointments in the Department of Plant Biology and the Department of Microbiology and Molecular Genetics in the MSU College of Natural Science. "If everything is allowed to grow in the plants, it would probably be a mess. We want to know if the numbers and types of microbes matter, if there is a perfect composition of microbes. If so, do plants have a genetic system to host and nurture the right microbiome?"

It seems plants do. The newly discovered mechanism involves two genetic networks. One involves the plant immune system and the other controls hydration levels inside leaves. Both networks work together to select which microbes survive inside of plant leaves.

"When we remove both networks from a plant, the microbiome composition inside the leaves changes," He said. "The numbers and mix of bacteria types are abnormal, and our team sees symptoms of tissue damage in plants."

"The symptoms are conceptually like those associated with inflammatory bowel disease in humans," he said. "This is probably because the genes involved are ancient, in evolutionary terms. These genes are found in most plants, while some even have similarities to those involved in animal immunity. "

According to the scientists in the He lab, this may be the first time dysbiosis-associated sickness is formally described in the plant kingdom. The fact it seems conceptually similar to human health suggests a fundamental process in life.

Developing new tech to determine causality:

The reason it is difficult to find causality in microbiome studies is because it is practically impossible to cut through the noise of zillions of microbes.

The He lab has worked around this problem by developing a germ-free growth chamber they call the gnotobiotic system - an environment for rearing organisms in which all the microorganisms are either known or excluded.

"Very few people have grown a sterile plant in sterile, organic-rich material," He said. "Our system uses a peat-based soil-like substrate, basically greenhouse potting soil. We use heat and pressure to kill all the germs in the soil, and the plants can grow under this germ-free condition."

Researchers can then introduce microbes in a controlled fashion, into this environment.

"You can add one, two, or even a community of bacteria," He said. "In our study, we extracted a community of bacteria from dysbiotic, or sick, plants and introduced them to our healthy plants, and vice-versa. We found that both the microbiome composition and the plant genetic systems are required for plant health."

For example, a plant with defective genetics could not take advantage of a microbiome transplanted from a healthy plant. The microbiome slowly reverted to the state that caused sickness.

On the other end, a healthy plant exposed to a sick plant's microbiome also suffered. Although it had the genetic tools to select the right microbes, microbe availability was limited and abnormal. The plant couldn't fix the situation.

Microbe levels and composition matter:

It turns out that increased microbiome diversity correlates with plant health. Somehow, plant genes are gatekeepers that encourage this diversity.

The sick plants in the study had 100 times more microbes in a leaf, compared to a healthy plant. But the population was less diverse. To figure out why, the scientists did thousands of one-on-one bacteria face-offs to tease out which strains were aggressive.

In the sick plants, proteobacteria strains - many of which are harmful to plants - jumped from two-thirds the composition of a healthy microbiome to 96% in the abnormal population. Fermicutes strains, many which may be helpful to plants, went down in numbers.

"Perhaps, when the population of microbiome is abnormally higher in that sick plant, the microbes are physically too close to each other," He said. "Suddenly, they fight over resources, and the aggressive - in this case harmful - ones unfortunately win. Healthy plants seem to prevent this takeover from happening."

The big picture: Supporting plant health

The study is yet another example of how diversity is important to support healthy living systems. Each type of microbe might impart different benefits to plants, such as increased immunity, stress tolerance or nutrient absorption.

Scientists such as He want to be able to manipulate the plant genetic system to reconfigure the plant microbiome. Plants could become more efficient at selecting their microbial partners and experience improved plant health, resilience, and productivity.

"Our field is still young," He said. "Microbiome research tends to focus on human gut bacteria. But many more bacteria live on plant leaves, the lungs of our planet. It would be wonderful to understand how microbes impact the health of the phyllosphere in natural ecosystems and crop fields."