Culture

Scientists discover how mother-of-pearl self-assembles into a perfect structure

image: A cross-section through a shell showing the periodically layered nacre on top of a prismatic shell structure.

Image: 
© Igor Zlotnikov

Mollusks build shells to protect their soft tissues from predators. Nacre, also known as the mother of pearl, has an intricate, highly regular structure that makes it an incredibly strong material. Depending on the species, nacres can reach tens of centimeters in length. No matter the size, each nacre is built from materials deposited by a multitude of single cells at multiple different locations at the same time. How exactly this highly periodic and uniform structure emerges from the initial disorder was unknown until now.

Nacre formation starts uncoordinated with the cells depositing the material simultaneously at different locations. Not surprisingly, the early nacre structure is not very regular. At this point, it is full of defects. "In the very beginning, the layered mineral-organic tissue is full of structural faults that propagate through a number of layers like a helix. In fact, they look like a spiral staircase, having either right-handed or left-handed orientation," says Dr. Igor Zlotnikov, research group leader at the B CUBE - Center for Molecular Bioengineering at TU Dresden. "The role of these defects in forming such a periodic tissue has never been established. On the other hand, the mature nacre is defect-free, with a regular, uniform structure. How could perfection emerge from such disorder?"

The researchers from the Zlotnikov group collaborated with the European Synchrotron Radiation Facility (ESRF) in Grenoble to take a very detailed look at the internal structure of the early and mature nacre. Using synchrotron-based holographic X-ray nano-tomography the researchers could capture the growth of nacre over time. "Nacre is an extremely fine structure, having organic features below 50 nm in size. Beamline ID16A at the ESRF provided us with an unprecedented capability to visualize nacre in three-dimensions," explains Dr. Zlotnikov. "The combination of electron dense and highly periodical inorganic platelets with delicate and slender organic interfaces makes nacre a challenging structure to image. Cryogenic imaging helped us to obtain the resolving power we needed," explains Dr. Pacureanu from the X-ray Nanoprobe group at the ESRF.

The analysis of data was quite a challenge. The researchers developed a segmentation algorithm using neural networks and trained it to separate different layers of nacre. In this way, they were able to follow what happens to the structural defects as nacre grows.

The behavior of structural defects in a growing nacre was surprising. Defects of opposite screw direction were attracted to each other from vast distances. The right-handed and left-handed defects moved through the structure, until they met, and cancelled each other out. These events led to a tissue-wide synchronization. Over time, it allowed the structure to develop into a perfectly regular and defect-free.

Periodic structures similar to nacre are produced by many different animal species. The researchers think that the newly discovered mechanism could drive not only the formation of nacre but also other biogenic structures.

Credit: 
Technische Universität Dresden

A robotic revolution for urban nature

Drones, robots and autonomous systems can transform the natural world in and around cities for people and wildlife.

International research, involving over 170 experts and led by the University of Leeds, assessed the opportunities and challenges that this cutting-edge technology could have for urban nature and green spaces.

The researchers highlighted opportunities to improve how we monitor nature, such as identifying emerging pests and ensuring plants are cared for, and helping people engage with and appreciate the natural world around them.

As robotics, autonomous vehicles and drones become more widely used across cities, pollution and traffic congestion may reduce, making towns and cities more pleasant places to spend time outside.

But the researchers also warned that advances in robotics and automation could be damaging to the environment.

For instance, robots and drones might generate new sources of waste and pollution themselves, with potentially substantial negative implications for urban nature. Cities might have to be re-planned to provide enough room for robots and drones to operate, potentially leading to a loss of green space. And they could also increase existing social inequalities, such as unequal access to green space.

Lead author Dr Martin Dallimer, from the School of Earth and Environment at the University of Leeds, said: "Technology, such as robotics, has the potential to change almost every aspect of our lives. As a society, it is vital that we proactively try to understand any possible side effects and risks of our growing use of robots and automated systems.

"Although the future impacts on urban green spaces and nature are hard to predict, we need to make sure that the public, policy makers and robotics developers are aware of the potential pros and cons, so we can avoid detrimental consequences and fully realise the benefits."

The research, published today in Nature Ecology & Evolution, is authored by a team of 77 academics and practitioners.

The researchers conducted an online survey of 170 experts from 35 countries, which they say provides a current best guess of what the future could hold.

Participants gave their views on the potential opportunities and challenges for urban biodiversity and ecosystems, from the growing use of robotics and autonomous systems. These are defined as technologies that can sense, analyse, interact with and manipulate their physical environment. This includes unmanned aerial vehicles (drones), self-driving cars, robots able to repair infrastructure, and wireless sensor networks used for monitoring.

These technologies have a large range of potential applications, such as autonomous transport, waste collection, infrastructure maintenance and repair, policing and precision agriculture.

The research was conducted as part of Leeds' Self Repairing Cities project, which aims to enable robots and autonomous systems to maintain urban infrastructure without causing disruption to citizens.

First author Dr Mark Goddard conducted the work whilst at the University of Leeds and is now based at the Northumbria University. He said: "Spending time in urban green spaces and interacting with nature brings a range of human health and well-being benefits, and robots are likely to transform many of the ways in which we experience and gain benefits from urban nature.

"Understanding how robotics and autonomous systems will affect our interaction with nature is vital for ensuring that our future cities support wildlife that is accessible to all."

Credit: 
University of Leeds

Chemists succeed in synthesis of aminoalcohols by utilizing light

image: Photosensitized synthesis of protected aminoalcohols

Image: 
WWU - Glorius Group

Whether in beta-blockers to treat high blood pressure or in natural products: So-called vicinal aminoalcohols are high-quality organic compounds that are found in many everyday products. However, their production is difficult. For a long time, chemists are trying to develop efficient methods of synthesizing them. In their recent study published in the journal Nature Catalysis, scientists led by Prof. Dr. Frank Glorius of Münster University have found a solution for the production of a special variant of aminoalcohols. "The new method helps to study the properties of the substance and to find applications for these new compounds in the future", emphasizes Frank Glorius from the Organic Chemistry Institute at Münster University.

Vicinal aminoalcohols can occur in two different variants - called regioisomers - in which the amine and alcohol functional groups exchange positions. Although they are thus very similar, they often have different biochemical properties. Installation of both amine and alcohol groups in one step poses a major challenge. The discovery of the "Asymmetric Amino Hydroxylation Reaction" with which one of the regioisomers can be produced, even rewarded the chemist Barry Sharpless with a Nobel Prize in 2001. However, the other regioisomer cannot be synthesized by similar method and remained a long-standing problem - until now. With the help of the chemists' new photo-initiated reaction method, the synthesis of the other regioisomer has now also become efficiently possible.

Background and method:

Unactivated alkenes containing a carbon-carbon double bond are known as feedstock chemicals for reaction processes due to their good availability. In general, the installation of both amine and alcohol groups in one step via this carbon-carbon double bond of unactivated alkene is at all times initiated by the amine group, followed by the addition of the alcohol group. As a result, always a particular regioisomer of the vicinal aminoalcohol is formed. Now the scientists have identified a particular class of amine-like compounds that are reactive yet stable enough to allow first the addition of the alcohol group to the carbon-carbon double bond, followed by the addition of the amine group to generate the previously inaccessible opposite regioisomer of the vicinal aminoalcohols.

"Like plants use chlorophyll to convert light into energy, we use what is called a photocatalyst", explains Dr. Tuhin Patra, first author of this study. "This species can absorb the light from blue LEDs and transfer its energy into a molecule directly involved in the reaction. This simultaneously releases the amine and alcohol groups." This process, in which the molecules transfer electrons to each other, is called energy transfer, the scientist explains.

Fascinatingly, the new method generates the least accessible regioisomer of the vicinal aminoalcohols in such a manner that both the alcohol and amine groups are protected from further reactions. Depending on the user's needs, one of the two alcohol or amine groups can now be reactivated without affecting the other. However, even both groups can be enabled to react further at the same time, if that is necessary for the synthesis of further requirements. "Previous designs usually install only one group at a time in a complex multistep overall process. Our design not only allows the installation of two different groups in one step with desired protection, but also reliably generates the least accessible regioisomer, offering the chance to investigate future applications of this compound," concludes Frank Glorius.

Credit: 
University of Münster

Public health messaging in era of social media

What The Viewpoint Says: The rapid spread of scientific misinformation on social media platforms throughout the COVID-19 pandemic is discussed in this Viewpoint, which also proposes strategies to counteract its adverse effects including surveillance of digital data and partnering with trusted messengers to engage the public and advance scientifically sound public health measures.

Authors: Raina M. Merchant, M.D., M.S.H.P., of the University of Pennsylvania in Philadelphia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.24514)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Astronomers agree: Universe is nearly 14 billion years old

ITHACA, N.Y. - From an observatory high above Chile's Atacama Desert, astronomers have taken a new look at the oldest light in the universe.

Their observations, plus a bit of cosmic geometry, suggest that the universe is 13.77 billion years old - give or take 40 million years. A Cornell University researcher co-authored one of two papers about the findings, which add a fresh twist to an ongoing debate in the astrophysics community.

The new estimate, using data gathered at the National Science Foundation's Atacama Cosmology Telescope (ACT), matches the one provided by the standard model of the universe, as well as measurements of the same light made by the European Space Agency's Planck satellite, which measured remnants of the Big Bang from 2009 to '13.

The research was published in the Journal of Cosmology and Astroparticle Physics.

The lead author of "The Atacama Cosmology Telescope: A Measurement of the Cosmic Microwave Background Power Spectra at 98 and 150 GHz" is Steve Choi, NSF Astronomy and Astrophysics Postdoctoral Fellow at the Cornell Center for Astrophysics and Planetary Science, in the College of Arts and Sciences.

In 2019, a research team measuring the movements of galaxies calculated that the universe is hundreds of millions of years younger than the Planck team predicted. That discrepancy suggested a new model for the universe might be needed and sparked concerns that one of the sets of measurements might be incorrect.

"Now we've come up with an answer where Planck and ACT agree," said Simone Aiola, a researcher at the Flatiron Institute's Center for Computational Astrophysics and first author of one of two papers. "It speaks to the fact that these difficult measurements are reliable."

Credit: 
Cornell University

Prediabetes subtypes identified

image: In people with prediabetes, there are six clearly distinguishable subtypes (clusters), which differ in development of the diseases, risk for diabetes, and development of complications.

Image: 
IDM

All prediabetes is not the same: in people in the preliminary stages of type 2 diabetes, there are six clearly distinguishable subtypes, which differ in the development of the disease, diabetes risk, and the development of secondary diseases. This is shown in a study by the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, Tübingen University Hospital and the German Center for Diabetes Research (DZD). The results have now been published in Nature Medicine. The new classification can help in the future to prevent the manifestation of diabetes or the development of diabetes complications through targeted prevention.

Diabetes is a worldwide pandemic. Since 1980, the number of people with diabetes has quadrupled worldwide. In Germany alone, 7 million people suffer from it. And the trend is still rising. By 2040, the number of people with type 2 diabetes could increase to as many as 12 million. But type 2 diabetes does not develop from one day to the next. People often go through a longer preliminary stage of diabetes, in which blood glucose levels are already elevated but people are not yet ill. "For people with prediabetes it has not been possible until now to predict whether they would develop diabetes and be at risk for serious complications such as kidney failure, or whether they would only have a harmless form with slightly higher blood glucose levels but without significant risk," said Professor Hans-Ulrich Häring, who initiated the study 25 years ago. However, such a distinction is important for the targeted prevention of the metabolic disease and thus for counteracting the diabetes pandemic. Researchers from Tübingen have now achieved an important breakthrough. Using cluster analysis* in people with prediabetes, they have discovered six distinct subtypes with different diabetes risk. A differentiated classification of prediabetes and diabetes makes it possible to carry out individual and early prevention and therapy of diabetes and its secondary diseases in a way that is adapted to the development of the disease.

Prediabetes: Six different clusters identified

The research group led by Professor Häring and Professor Fritsche at the University Hospital in Tübingen has conducted detailed studies of the metabolism of people with prediabetes who are still considered healthy. The test persons (n=899) are from the Tübingen Family Study and the study of the Tübingen Lifestyle Program. They have repeatedly undergone intensive clinical, laboratory chemical, magnetic resonance imaging and genetic examinations in Tübingen over the past 25 years. Based on key metabolic parameters such as blood glucose levels, liver fat, body fat distribution, blood lipid levels and genetic risk, the researchers were able to identify six subtypes of prediabetes. "As in manifest diabetes, there are also different disease types in the preliminary stage of diabetes, which differ in blood glucose levels, insulin action and insulin secretion, body fat distribution, liver fat and genetic risk," said first author Professor Robert Wagner from the DZD Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, summarizing the results of the study.

Three of these groups (clusters 1, 2 and 4) are characterized by a low diabetes risk. The study participants in clusters 1 and 2 were healthy. Slim people are the main members of cluster 2. They have a particularly low risk of developing complications. Cluster 4 consists of overweight people, whose metabolism is still relatively healthy. The three remaining subtypes (clusters 3, 5 and 6) are associated with an increased risk of diabetes and/or secondary diseases. People who belong to subtype 3 produce too little insulin and have a high risk of developing diabetes. People in cluster 5 have a pronounced fatty liver and a very high risk of diabetes because their bodies are resistant to the blood glucose lowering effect of insulin. In subtype 6, damage to the kidneys occurs even before diabetes is diagnosed. Here, mortality is also particularly high.

But can the classification into six prediabetes subtypes also be confirmed in other cohorts? To investigate this, the researchers extended the analysis to include almost 7000 subjects in the Whitehall II Cohort in London and there, too, identified the six prediabetes subtypes.

More targeted prevention measures

The researchers are already making further plans. "Next, in prospective studies, we will first seek to determine to what extent the new findings are applicable for the classification of individual persons into risk groups," said Professor Andreas Fritsche of Tübingen University Hospital. If this is the case, people with a high risk profile could be identified early on and receive specific treatment.

About the study

These results are based on research conducted by the Diabetes Research Department at Tübingen University Hospital over the past 25 years to characterize people with an increased risk of diabetes. The study was funded by the German Research Foundation, the Federal Ministry of Education and Research and the State of Baden-Württemberg.

"One of the DZD's goals is to develop precise prevention and therapy measures, i.e. the appropriate prevention or treatment for the right group of people at the right time. The combination of in-depth clinical and molecular research with state-of-the-art bioinformatics has made this internationally important result possible. The identification of subtypes in the preliminary stages of type 2 diabetes is an important step towards precision medicine in the prevention of diabetes and its complications," says DZD Executive Director Prof. Martin Hrab? de Angelis.

Credit: 
Deutsches Zentrum fuer Diabetesforschung DZD

Psychological distress during first months of pandemic equal to that during prior year

The coronavirus pandemic is creating a large spike in significant psychological distress among Americans, with the first month of the pandemic causing as much distress in the same number of individuals that experienced it during the whole previous year, according to a new RAND Corporation study.

Findings from the first longitudinal study of psychological distress during the pandemic show that among a representative sample of Americans, more than 10% reported experiencing symptoms of significant psychological distress during April and May of 2020 -- the same amount they reported experiencing over an entire year during a survey conducted a year earlier.

The study also found that people with distress prior to the pandemic were more likely to report distress during the pandemic. Among people with severe distress prior to the pandemic, 48% reported distress during the pandemic while among people with low or no distress prior to the pandemic, just 3% reported distress during the pandemic.

The findings are published online by the journal Preventive Medicine.

"We found equal numbers of people experienced serious psychological distress over 30 days during the pandemic as did over an entire year prior to the pandemic," said Joshua Breslau, the study's lead author and a senior behavioral scientist at RAND, a nonprofit research organization.

The study found there was a higher risk of an increase in psychological distress among people younger than age 60, suggesting that the distress may be driven more by economic stressors than fears specific to the disease, since older individuals are at higher risk of serious illness and death from the virus.

The survey was fielded using the RAND American Life Panel, a nationally representative internet panel. Participants were surveyed in February 2019 and again in May 2020, about 8 weeks after the declaration of a national emergency. There were 2,555 respondents to the first wave of the survey and 1,870 respondents to the second wave.

During each survey, participants were asked about their level of psychological distress at various points over the prior year using standard research assessment tools.

Researchers found that the past-month prevalence of serious psychological distress reported by participants of the second survey was as high (10.9%) as the past-year prevalence reported by individuals in the first survey (10.2%). Previous research has found that the 30-day prevalence of significant distress typically is about half the 12-month prevalence when both are assessed at the same time.

More than 12% of the participants reported higher levels of psychological distress during the second survey as compared to the first. Increases in distress were more common among women compared with men, those under 60 compared with those over 60, and Hispanic people compared with people of other racial/ethnic groups.

"Elevated psychological distress has been observed during prior disasters, but it has never before been seen as a persistent and complex stressor affecting the entire U.S. population," Breslau said. "Policymakers should consider targeting services to population groups at high risk for elevated psychological distress during the pandemic, including people vulnerable to the economic consequences of social distancing."

Credit: 
RAND Corporation

Using solar energy and agriculture to limit climate change, assist rural communities

image: Chad Higgins, an associate professor in the College of Agricultural Sciences at Oregon State University.

Image: 
Oregon State University

CORVALLIS, Ore. - Co-developing land for both solar photovoltaic power and agriculture could provide 20% of total electricity generation in the United States with an investment of less than 1% of the annual U.S. budget, a new paper by Oregon State University researchers found.

Wide-scale installation of agrivoltaic systems could lead to an annual reduction of 330,000 tons of carbon dioxide emissions in the U.S - the equivalent of 75,000 cars off the road per year - and the creation of more than 100,000 jobs in rural communities, while minimally impacting crop yield, the researchers say.

"Agrivoltaics provide a rare chance for true synergy: more food, more energy, lower water demand, lower carbon emissions, and more prosperous rural communities," said Chad Higgins, an associate professor in Oregon State's College of Agricultural Sciences and the senior author of the paper published in the journal Sustainability.

Agrivoltaics also align with the goals of the Green New Deal, a package of federal legislation that seeks to address climate change and economic inequalities, Higgins said.

"Rural America, agriculture in particular, can be the solution to many of our concerns, whether it be renewable energy, mitigating climate change impacts, sustainable food or good water resource management," Higgins said. "That connection is untapped mostly because there hasn't been sufficient investment in those communities.

"What we propose in this paper is all possible. It's technically possible. It's politically possible. And it would make money after the initial investment. That's the takeaway - that we should take a hard look at agriculture as a solution to problems rather than a cause of problems."

The analysis outlined in the paper prepares Higgins for the next phase of his agrivoltaics research, which includes the installation of a fully functional solar farm designed to prioritize agricultural activities on five acres of Oregon State's North Willamette Research and Extension Station in Aurora, Oregon, 20 miles south of Portland.

The next phase aims to demonstrate to the agricultural community and potential future funders how Higgins's findings can be applied in real world agricultural systems to encourage early adoption. Ground is expected to be broken in May 2021 with production expected to start in 2022.

In the Sustainability paper, Higgins and his co-author, Kyle Proctor, a doctoral student in his lab, find that an area about the size of Maryland would be needed for agrivoltaics to meet 20% of U.S. electricity generation. That's about 13,000 square miles, or 1% of current U.S. farmland.

The cost of the agrivoltaic arrays would be $1.12 trillion over a 35-year project life. The researchers believe that the private sector would invest in the bulk of the construction costs with the federal government contributing with rebates and other incentives.

Using money generated from the electricity the arrays produce, the researchers estimate it would take about 17 years to payback the $1.12 trillion. After the projected 35-year lifespan of the project, the researchers estimate the arrays would produce $35.7 billion in revenue.

Installation of the arrays would create the equivalent of 117,000 jobs lasting 20 years, with 40% being sustainable positions for operating and maintaining the arrays, the researchers say.

Higgins comes at this project with an eclectic background. He went through a self-described engineering degree collection phase and has published papers on everything from enzyme reaction kinetics to snow physics to turbulence theory.

The broad background came in handy one day in 2013 while he was strolling his "thinking walk path" on the Oregon State campus. He noticed greener pasture under recently installed solar arrays. Drawing on his background studying water, agriculture, renewable energy, mechanical and civil engineering, he started thinking about agrivoltaics research.

His initial research focused on the impact solar arrays had on the crops planted around them. That research, along with work by other scientists, has shown that crop yield is dependent on the type of crop, but in the end, when the value of the electricity generated by the solar panels is included, there is an economic net benefit from the agrivoltaic systems.

Looking to the future, Higgins believes the wide-scale installation of agrivoltaic systems opens the door for other technologies. The surplus energy generated by the solar arrays could be used to power electric tractors or to generate fertilizer on a farm. Inexpensive sensors could be installed on the solar panel platforms to support artificial intelligence-based decisions to improve agricultural productivity.

"Once we have infrastructure, once we have energy, we are ready to tackle so many more big problems," Higgins said.

Credit: 
Oregon State University

Study resolves long-running controversy over critical step in gene silencing

BOSTON - A long-running debate over how an important gene-silencing protein identifies its targets has been resolved by researchers at Massachusetts General Hospital (MGH). Their findings, reported in Nature Structural and Molecular Biology, also explain certain mysteries about the behavior of this protein, known as Polycomb repressive complex 2 (PRC2).

PRC2 helps regulate whether genes are active ("on) or silent ("off"). PRC2's role in gene silencing is critical throughout the lifespan, from embryo formation to old age. For example, PRC2 determines whether genes that suppress the growth of malignant tumors are turned on or off, which has made it the focus of pharmaceutical companies developing anti-cancer drugs.

But a mystery about PRC2 remained unsolved for years: How was the protein able to target specific genes? A major breakthrough occurred in 2008, when a team led by Jeannie Lee, MD, PhD, an investigator in the Department of Molecular Biology at MGH, proposed that RNA acts a recruiter for PRC2. RNA (or ribonucleic acid) is a molecule similar to DNA that's found in cells. RNA is usually a messenger that does DNA's bidding by spelling out the code to make proteins, but that is not the case here. Rather, Lee and her colleagues demonstrated that RNA acts as a "free agent" that binds to PRC2. RNA then targets PRC2 to a specific gene in order to silence it.

After Lee and her colleagues reported their discovery, dozens of other papers were subsequently published that supported the theory that RNA recruits PRC2 as a necessary step in gene silencing. However, studies from several prominent labs have challenged these findings, leading to an ongoing and often-heated debate about the relationship between PRC2 and RNA. These critics questioned Lee's discovery on two grounds:

PRC2 isn't specific and can bind with any RNA (some scientists noted that the protein is "promiscuous"), suggesting that RNA can't be a factor in targeting PRC2 for gene silencing.

The interaction between PRC2 and RNA often occur at genes that are active, an indication that this relationship isn't important for silencing specific genes.

The new study resolves both critiques. In the first case, explains Lee, think of PRC2 as a letter that needs to be delivered by a mail carrier, but lacks an address. How does the mail carrier know where to deliver it - that is, what is the "address" of the gene to be targeted for silencing? "The address is written on the RNA," says Lee. "RNA is an exact copy of DNA, where our genes are encoded." Lee and her colleagues identified "motifs," or unique sequences in RNA, which allow it to be recognized by PRC2. The RNA "address" then guides PRC2 to a specific gene location. This possibility had been proposed in the past, but Lee and her team now shed new light on how motifs make possible specific interactions between PRC2 and RNA that enable targeting.

Lee uses another analogy to explain why PRC2 and RNA often interact at genes that are not silenced. In the past, light bulbs could only be turned on or off, but the invention of the dimmer switch allowed for them to cast soft or bright light. Likewise, genes are not always turned completely on or off, and PRC2 acts like a dimmer switch. "We are saying that the genes are 'on,' but only yielding dim light," says Lee. "If you took away the Polycomb-RNA interaction, the genes would turn up and shine brightly."

By reconciling past disputes over how PCR2 interacts with RNA, says Lee, this new unified model advances basic science and provides invaluable insights for developers of new therapeutics.

Credit: 
Massachusetts General Hospital

New USC study on circadian clock shows "junk DNA" plays a key role in regulating rhythms

If you've ever had a bad case of jet lag, you know how a disruption to your body's circadian rhythm makes it difficult to function. Molecular circadian "clocks" exist in cells throughout the body, governing more than just sleep and wake cycles - they are crucial to many aspects of human health. For more than a decade researchers have been trying to figure out what makes them tick, in search of new insights into diseases like Alzheimer's, cancer and diabetes.

Until now, that research has focused on what is known as clock genes, which encode proteins that drive oscillating cycles of gene expression affecting physiology and behavior. But research just published in the Proceedings of the National Academy of Sciences reveals the discovery of a new cog in the circadian clock - a genome-wide regulatory layer made up of small chains of non-coding nucleotides known as micro RNAS (miRNAs).

"We've seen how the function of these clock genes are really important in many different diseases," said Steve Kay, Provost Professor of neurology, biomedical engineering and quantitative computational biology at the Keck School of Medicine of USC. "But what we were blind to was a whole different funky kind of genes network that also is important for circadian regulation and this is the whole crazy world of what we call non-coding microRNA."

"Junk DNA" proves to be a valuable tool in circadian rhythms

Formerly thought to be "junk DNA," miRNAs are now known to affect gene expression by preventing messenger RNA from making proteins. Past research has indicated miRNAs may have a role in the function of circadian clocks but determining which of the hundreds of miRNAs in the genome might be involved remained a problem.

Kay and his team, led by Lili Zhou, a research associate in the Keck School's Department of Neurology, turned to the Genomics Institute of the Novartis Research Foundation (GNF) in San Diego which has created robots capable of high throughput experiments. Working with scientists at the institute, Zhou developed a high throughput screen for a robot to test the close to 1000 miRNAs by individually transferring them into cells the team had engineered to glow on and off, based on the cell's 24-hour circadian clock cycle.

"The collaboration with GNF made it possible for us to conduct the first cell-based, genome-wide screening approach to systematically identify which of the hundreds of miRNAs might be the ones modulating circadian rhythms," said Zhou.

"Much to our surprise," said Kay, "we discovered about 110 to 120 miRNAs that do this."

With the help of Caitlyn Miller, a biochemistry undergraduate from USC Dornsife, researchers then verified the impact on circadian rhythms by inactivating certain miRNAs identified by the screen in their line of glowing cells. Knocking out the miRNAs had the opposite effect on the cells' circadian rhythm as adding them to the cells.

Physiologic and behavioral impacts of miRNAs

Researchers also focused on the physiologic and behavioral impacts of miRNAs. They analyzed the behavior of mice with a particular cluster of miRNAs inactivated - miR 183/96/182 - and saw that inactivating the cluster interfered with their wheel-running behavior in the dark compared with control mice. They then examined the impact of the miRNA cluster on brain, retina and lung tissue, and found that inactivating the cluster affected circadian rhythms in a different way in each tissue type - suggesting that the way the miRNAs regulate the circadian clock is tissue specific.

Understanding the impact of miRNAs on the circadian clock in individual tissue could reveal new ways of treating or preventing specific diseases.

"In the brain we're interested in connecting the clock to diseases like Alzheimer's, in the lung we're interested in connecting the clock to diseases like asthma," said Kay. "The next step I think for us to model disease states in animals and in cells and look at how these microRNAs are functioning in those disease states."

Credit: 
Keck School of Medicine of USC

Bacteriophage has important role in agriculture and aquaculture

image: Dedicated to fundamental bacteriophage research and its applications in medicine, agriculture, aquaculture, veterinary applications, animal production, food safety, and food production.

Image: 
Mary Ann Liebert, Inc., publications

New Rochelle, NY, January 4, 2021--Crop plants and animals can be infected by bacterial pathogens that reduce yield, cause food wastage, and carry human pathogens that spread disease on consumption. Bacteriophage can play an important role in microbial control, according to a new Special Issue on Agriculture and Aquaculture published in the peer-reviewed journal PHAGE: Therapy, Applications, and Research. Click here to read the issue.

"Although the number of problems associated with bacterial diseases in agriculture and aquiculture has increased, food producers are under pressure to reduce their reliance on antibiotics. There is therefore a clear need for effective antimicrobials to prevent and treat infections in food animals, to both reduce food waste, and prevent human infection. Clearly if developed properly, phages can at least in part, help to solve this need," says Martha Clokie, PhD, Editor-in-Chief of PHAGE and Professor of Microbiology, University of Leicester.

The Special Issue features valuable articles on a broad range of topics. These include the following:

inPhocus: A Local Perspective on Phage-Based
Biocontrol in Agriculture and Aquaculture in India

The Application of Bacteriophage Diagnostics for
Bacterial Pathogens in the Agricultural Supply Chain:
From Farm-to-Fork

Bacteriophages as Biocontrol Agents for
Flavobacterium psychrophilum Biofilms and Rainbow
Trout Infections

Effectiveness of Bacteriophages Against Biofilm-
Forming Shiga-Toxigenic Escherichia coli on Leafy
Greens and Cucumbers

Effect of Phage Targeting Therapy of Brucellosis on
Host Antibody Response in Cattle

A Rare, Virulent Clostridium perfringens
Bacteriophage Susfortuna Is the First Isolated
Bacteriophage in a New Viral Genus

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Charging ahead for electric vehicles

By applying statistical geometry to analyzing urban road networks, KAUST researchers have advanced understanding of how wireless charging roads might influence driver behavior and city planning in a future where electric vehicles (EVs) dominate the car market.

"Our work is motivated by the global trend of moving towards green transportation and EVs," says postdoc Mustafa Kishk. "Efficient dynamic charging systems, such as wireless power transfer systems installed under roads, are being developed by researchers and technology companies around the world as a way to charge EVs while driving without the need to stop. In this context, there is a need to mathematically analyze the large-scale deployment of charging roads in metropolitan cities."

Many factors come into play when charging roads are added to the urban road network. Drivers may seek out charging roads on their commute, which has implications for urban planning and traffic control. Meanwhile, the density of charging road installations in a city, and the likely time spent on and between the charging roads by commuters, could influence the size of batteries installed in EVs by car manufacturers.

Calculating the metrics that could be used to analyze a charging road network is very significant, as Kishk's lab colleague, Duc Minh Nguyen, explains.

"Our main challenge is that the metrics used to evaluate the performance of dynamic charging deployment, such as the distance to the nearest charging road on a random trip, depend on the starting and ending points of each trip," says Nguyen. "To correctly capture those metrics, we had to explicitly list all possible situations, compute the metrics in each case and evaluate how likely it is for each situation to happen in reality. For this, we used an approach called stochastic geometry to model and analyze how these metrics are affected by factors such as the density of roads and the frequency of dynamic charging deployment."

Applying this analysis to the Manhattan area of New York, which has a road density of one road every 63 meters, Kishk and Nguyen with research leader Mohamed-Slim Alouini determined that a driver would have an 80 percent chance of encountering a charging road after driving for 500 meters when wireless charging is installed on 20 percent of roads.

"This is the first study to incorporate stochastic geometry into the performance analysis of charging road deployment in metropolitan cities," Kishk says. "It is an important step towards a better understanding of charging road deployment in metropolitan cities."

Credit: 
King Abdullah University of Science & Technology (KAUST)

Comb of a lifetime: a new method for fluorescence microscopy

image: 2D arrangement of 44,400 light stopwatches enables scan-less fluorescence lifetime imaging

Image: 
Tokushima University

Fluorescence microscopy is widely used in biochemistry and life sciences because it allows scientists to directly observe cells and certain compounds in and around them. Fluorescent molecules absorb light within a specific wavelength range and then re-emit it at the longer wavelength range. However, the major limitation of conventional fluorescence microscopy techniques is that the results are very difficult to evaluate quantitatively; fluorescence intensity is significantly affected by both experimental conditions and the concentration of the fluorescent substance. Now, a new study by scientists from Japan is set to revolutionize the field of fluorescence lifetime microscopy. Read on to understand how!

A way around the conventional problem is to focus on fluorescence lifetime instead of intensity. When a fluorescent substance is irradiated with a short burst of light, the resulting fluorescence does not disappear immediately but actually "decays" over time in a way that is specific to that substance. The "fluorescence lifetime microscopy" technique leverages this phenomenon--which is independent of experimental conditions--to accurately quantify fluorescent molecules and changes in their environment. However, fluorescence decay is extremely fast, and ordinary cameras cannot capture it. While a single-point photodetector can be used instead, it has to be scanned throughout the sample's area to be able to reconstruct a complete 2D picture from each measured point. This process involves movement of mechanical pieces, which greatly limits the speed of image capture.

Fortunately, in this recent study published in Science Advances, the aforementioned team of scientists developed a novel approach to acquire fluorescence lifetime images without necessitating mechanical scanning. Professor Takeshi Yasui, from Institute of Post-LED Photonics (pLED), Tokushima University, Japan, who led the study, explains, "Our method can be interpreted as simultaneously mapping 44,400 'light stopwatches' over a 2D space to measure fluorescence lifetimes--all in a single shot and without scanning." So, how was this achieved?

One of the main pillars of their method is the use of an optical frequency comb as the excitation light for the sample. An optical frequency comb is essentially a light signal composed of the sum of many discrete optical frequencies with a constant spacing in between them. The word "comb" in this context refers to how the signal looks when plotted against optical frequency: a dense cluster of equidistant "spikes" rising from the optical frequency axis and resembling a hair comb. Using special optical equipment, a pair of excitation frequency comb signals is decomposed into individual optical beat signals (dual-comb optical beats) with different intensity-modulation frequencies, each carrying a single modulation frequency, and irradiated on the target sample. The key here is that each light beam hits the sample on a spatially distinct location, creating a one-to-one correspondence between each point on the 2D surface of the sample (pixel) and each modulation frequency of the dual-comb optical beats.

Because of its fluorescence properties, the sample re-emits part of the captured radiation while still preserving the aforementioned frequency-position correspondence. The fluorescence emitted from the sample is then simply focused using a lens onto a high-speed single-point photodetector. Finally, the measured signal is mathematically transformed into the frequency domain, and the fluorescence lifetime at each "pixel" is easily calculated from the relative phase delay that exists between the excitation signal at that modulation frequency versus the one measured.

Thanks to its superior speed and high spatial resolution, the microscopy method developed in this study will make it easier to exploit the advantages of fluorescence lifetime measurements. "Because our technique does not require scanning, a simultaneous measurement over the entire sample is guaranteed in each shot," remarks Prof. Yasui, "This will be helpful in life sciences where dynamic observations of living cells are needed." In addition to providing deeper insight into biological processes, this new approach could be used for simultaneous imaging of multiple samples for antigen testing, which is already being used for the diagnosis of COVID-19.

Perhaps most importantly, this study showcases how optical frequency combs, which were only being used as "frequency rulers," can find a place in microscopy techniques to push the envelope in life sciences. It holds promise for the development of novel therapeutic options to treat intractable diseases and enhance life expectancy, thereby benefitting the whole of humanity.

Credit: 
Institute of Post-LED Photonics, Tokushima University

Tracking COVID-19 in transmission in Chicago schools: Public health officials take data-driven approach to reopening city public schools

December 31, 2020 - Data on COVID-19 transmission among Chicago youth - particularly in the city's extensive network of Catholic schools - supports a strategy for gradual reopening of the city's public school system, according to a report in the Journal of Public Health Management and Practice. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Data from the nation's largest Catholic school system reveals that implementation of layered mitigation efforts can support the goal of reopening in-person education in a safe but not zero-risk environment," write Marielle Fricchione, MD, and colleagues of the Chicago Department of Public Health (CDPH). Based on this and other sources of data on in-person learning during COVID-19 surges, "Chicago believes it can safely move forward with in-person public education when the operational burden imposed by the second wave has subsided."

With good mitigation, in-school transmission risk appears lower than outside school

From the start of the pandemic, CDPH prioritized complete reporting, testing, and contact tracing of COVID-19 spread in schools and other youth settings. Chicago Public Schools, the third-largest school district in the United States, elected to start the 2020-21 school year with all-remote learning.

The city placed no limitations on reopening of private schools, as long as strict mitigation measures were followed. Schools that reopened were required to promptly report all suspected or confirmed school-related COVID-19 cases. That included the Archdiocese of Chicago schools, the largest private school system in the United States. For CDPH, the Archdiocese schools provided a valuable source of information on the risks of COVID-19 associated with in-school education.

The researchers analyzed data for the first seven weeks of the 2020-21 school year: a time of moderate to high COVID-19 incidence, representing a plateau between Chicago's first and second waves. During that time, the Archdiocese reported a total of 59 COVID-19 cases at 31 Archdiocese schools. Forty-nine cases were classified as "school-associated" by CDPH: 35 in students and 14 in staff.

Of three school-related COVID-19 clusters identified by CDPH, two were related to not following physical distancing guidelines outside of class time. "There was one cluster in which we could not rule out transmission in the classroom setting," Dr. Fricchione and coauthors write. When multiple cases occurred at a single Archdiocese school, siblings were usually involved. Transmission most often occurred at social events outside of school, such as family parties or sports events.

The estimated COVID attack rate among students at Archdiocese schools was 0.2 percent - significantly lower than the 0.4 percent rate for all Chicago children. For school staff, the estimated attack rate was 0.5 percent, compared to 0.7 percent for working-age adults in Chicago.

Based on the findings, along with the experience of other large urban school districts, Chicago Public Schools has planned a phased return to the classroom. Dr. Fricchione and coauthors write, "CDPH supports this plan as long as the [COVID-19] case doubling-time has improved, reflecting a stabilization of the local outbreaks."

Consistent with CDPH's Healthy Chicago 2025 initiative, the reopening plan acknowledges the negative impact on school closures on children - "especially of the city's most vulnerable students, not only as an essential service but as a way to improve health equity for students during a pandemic that has disproportionately impacted Latinx and Black residents," according to the authors. Also reflecting equity concerns, the plan calls for pre-K and special education students to be the first to return to the classroom.

The researchers emphasize the importance of consistent mitigation strategies in achieving low COVID-19 transmission rates in Archdiocese schools. Dr. Fricchione and coauthors write, "Frequent and clear communication at multiple levels--between the school system leadership and its schools, between the schools and their staff and families, and between the school system and the local public health department--was likely a key factor in ensuring mitigation measures were properly implemented."

Credit: 
Wolters Kluwer Health

OSU studies find Oregon's Medicaid expansion improved prenatal care access, birth outcomes

CORVALLIS, Ore. -- A pair of recent studies from Oregon State University found that Oregon's Medicaid expansion in 2014 has led to increased prenatal care among low-income women, as well as improved health outcomes for newborn babies.

In the three years after the expansion, one study found that Oregon saw an almost 2 percentage point increase in first trimester prenatal care utilization, relative to 18% of the pre-expansion population who lacked any access to prenatal care in the earlier stages of pregnancy.

In the same period, the second study found, Medicaid expansion was associated with a 29% reduction in low birthweight among babies born to women on Medicaid, as well as a 23% reduction in preterm births.

Prior to the state's Medicaid expansion as part of the Affordable Care Act, low-income women who were not otherwise eligible for Medicaid became eligible when they became pregnant. It was estimated that expanding Medicaid to include everyone earning up to 138% of the federal poverty level would extend coverage to an additional 77,000 women of childbearing age.

"This means that women are getting preconception care before they're pregnant," said lead author Marie Harvey, associate dean for research in OSU's College of Public Health and Human Sciences. "Then when they become pregnant, they're more easily able to get prenatal care."

Prior to pregnancy, establishing that connection with a primary care provider means women are able to receive holistic medical and public health care to improve their overall well-being.

"It's much broader than just one specific intervention or health condition," said co-author Susannah Gibbs, a researcher in the College of Public Health and Human Sciences. "You might think about smoking cessation or nutrition -- all these things that are kind of an ongoing conversation between a health care provider and someone who might in the future become pregnant.

"They might receive those interventions that improve their overall health, and lead them to be in a healthier state when they do become pregnant."

Because the state's Medicaid expansion did not change women's eligibility for Medicaid during pregnancy and utilization of prenatal services was already high, the researchers were focused on the impact of greater continuity of care, where people's access to services was not split into different health states: pregnant versus not-pregnant.

"The almost 2 percentage point increase in prenatal care utilization is encouraging," Harvey said.

The study found almost twice the magnitude of gains in pre-pregnancy enrollment in Medicaid among Hispanic women compared with non-Hispanic white women, Gibbs said.

In turn, increased pre-pregnancy enrollment in Medicaid likely contributed to the positive impacts on low birthweight and preterm births, researchers said, as women with health coverage had greater access to preventive care and preconception care.

This aligns with the "life course perspective" on health care, Harvey said, where providing women access to health care early in their lives leads to better overall health status and thus healthier pregnancies if they do become pregnant. Babies are then more likely to be born healthy, and to be connected with health services and primary health care from an early age as well.

"Once you have people in that medical care system, it is an opportunity to be connected with those individuals who are in great need of other interventions beyond medical care that reach into the broader public health space," Gibbs said.

Other OSU co-authors on one or both of the studies were Lisa Oakley, Shyama Mahakalanda, Jeff Luck and Jangho Yoon.

Credit: 
Oregon State University