Culture

For veterans, a hidden side effect of COVID: Feelings of personal growth

The U.S. military veteran population is known to have abnormally high rates of suicide, so health officials have been concerned that the COVID-19 pandemic might elevate risk of psychiatric disorders, particularly among those suffering from post-traumatic stress and related disorders.

A recent national study of more than 3,000 veterans participating in the National Health and Resilience in Veterans Study did find that 12.8% reported post-traumatic stress disorder (PTSD) symptoms related to COVID-19 and 8% said they had contemplated suicide during the pandemic.

However, the same survey, published April 8 in JAMA Network Open, revealed another, startling finding. A full 43.3% of respondents -- more than three times the number of those reporting COVID-related PTSD symptoms and five times the number of those who had contemplated suicide -- said that they have experienced positive psychological benefits during the pandemic. These veterans reported greater appreciation of life, closer interpersonal relationships, and an increased sense of personal strength.

"Yes, there have certainly been many negative mental health consequences of the pandemic, but we are also seeing that a considerable proportion of people may experience positive psychological changes," said Robert Pietrzak, director of the Translational Psychiatric Epidemiology Laboratory of the U.S. Department of Veterans Affairs' National Center for PTSD, associate professor of psychiatry and public health at Yale, and lead author of the paper. "This suggests that the experience of stress and trauma related to the pandemic can lead to positive personal growth."

Over the past decade, Pietrzak and Steven Southwick, the Glenn H. Greenberg Professor Emeritus of Psychiatry at Yale and senior author of the new paper, have been studying veterans who experience what is known as "post-traumatic growth" following a traumatic experience. Scientists have long been fascinated with the concept of resilience -- how people who endure trauma find a way to bounce back. The concept of post-traumatic growth posits that while trauma can increase risk for mental disorders such as PTSD, it may also spur positive personal growth.

For the latest findings, Pietrzak and Southwick initially asked veterans about their psychological health between November of 2019 and March 2020. The advent of the pandemic motivated them to follow up that survey with another, of the same group, a year later. In this second survey, they asked questions about PTSD symptoms and possible positive psychological changes related to the pandemic.

Of the 3,078 veterans who responded to both surveys, 43.3% reported that the pandemic led to positive psychological changes in their lives. Among veterans who screened positive for COVID-related PTSD symptoms, more than 70% reported experiencing these changes.

"Post-traumatic growth is a process that often happens naturally and is stimulated by reflective processing about a traumatic event," Pietrzak said. "Sometimes you need to be sufficiently shaken by an experience and even experience symptoms of PTSD to begin to process it at a deeper level and ultimately be able to grow from it."

Greater post-traumatic growth -- particularly an increased appreciation of life and improved interpersonal relationships -- was also associated with a 40% lower likelihood of contemplating suicide during the pandemic. This finding suggests that psychological interventions to promote post-traumatic growth may be a helpful measure to prevent suicide among veterans.

While the scientific study of post-traumatic growth is relatively new, the concept is not. Ancient religious and spiritual traditions, philosophers, and scholars have long expressed the potentially transformative power of suffering.

"The saying 'Grow through what you go through' captures the essence of post-traumatic growth," Pietrzak said.

He and his colleagues plan to continue to follow their cohort of veterans over time to examine the longer-term course of post-traumatic growth and whether it may help promote resilience to subsequent traumatic events.

Credit: 
Yale University

Picosecond electron transfer in peptides can help energy technologies

Biological energy flows, such as in photosynthesis and respiration, depend on the transfer of electrons from one molecule to another. Despite its importance to sustaining life, factors governing the rate of electron transfer, especially over long distances, are not well understood because the systems that mediate such ultrafast processes are very complex. A better understanding of electron transfer rates would help scientists improve chemical transformations, energy conversion, electronic devices, and photonic technologies.

Now, an international team of researchers led by UC Riverside has observed picosecond charge transfer mediated by hydrogen bonds in peptides. A picosecond is one trillionth of a second. As short-chain analogs of proteins, crucially important building blocks of living organisms, peptides are chains of chemically linked amino acids. The discovery shows the role of hydrogen bonds in electron transfer. The results are published in Proceedings of the National Academy of Sciences.

Valentine Vullev, a professor of bioengineering at UC Riverside's Marlan and Rosemary Bourns College of Engineering, along with Daniel Gryko from the Polish Academy of Sciences, and Harry Gray from the California Institute of Technology, led a team that discovered unusually ultrafast electron transfer from a donor to an acceptor molecule connected with oligopeptide linkers stretching up to 20 covalent bonds. Electron transfer usually takes a microsecond, or one millionth of a second, in peptides with such long through-bond distances.

The researchers were surprised to observe picosecond electron transfer, a rate 1 million times faster than previously known for such systems.

"It shouldn't work, but it does," Vullev said. "The picosecond charge transfer we observed contradicts structural biology, assuming the expected random distribution of structures of the flexible peptide chains."

The team chose donor and receptor molecules linked by short peptides they discovered actually assume well-defined structures stabilized by hydrogen bonds. Further analysis revealed that hydrogen bonds within each molecule brought the donor and acceptor close to each other in a scorpion-shaped molecular architecture, enabling picosecond electron transfer.

"This revolutionary design demonstrates short peptides can not only assume well-defined secondary conformations when templated by organic components but also provide a hydrogen-bonding network that can mediate electron transfer with unusually high efficiencies," Vullev said. "Our work provides unprecedented paradigms for the design and development of charge-transfer pathways along flexible bridges, as well as insights into structural motifs for mediating electron transfer in proteins."

The findings could lead to advances in energy storage as well as spur development of organic electronics that use conducting polymers instead of conducting minerals.

"One of the most exciting and fulfilling aspects about working in our group is being at the forefront of such discoveries and observing these spectacular results," said co-author John Clark, a doctoral student in Vullev's lab who did photochemical measurements for the research.

Credit: 
University of California - Riverside

Lipid research may help solve COVID-19 vaccine challenges

image: University of Texas at Dallas scientists developed a method to stabilize liposomes in a crystalline exoskeleton, which allows the biomolecules to remain stable at room temperature. This illustration depicts a proteoliposome -- a spherical bilayer of fat molecules (white and blue) -- stabilized in a structure called a zeolitic-imidazole framework composed of zinc acetate and methylimidazole. Inserted into the lipid bilayer -- which mimics a cell membrane -- are modeled structures of CopA proteins, with a section (in pink) that resides inside the lipid and sections above the lipid surface (brown) and slightly inside the liposome (also brown, but inside).

Image: 
University of Texas at Dallas

New research by University of Texas at Dallas scientists could help solve a major challenge in the deployment of certain COVID-19 vaccines worldwide -- the need for the vaccines to be kept at below-freezing temperatures during transport and storage.

In a study published online April 13 in Nature Communications, the researchers demonstrate a new, inexpensive technique that generates crystalline exoskeletons around delicate liposomes and other lipid nanoparticles and stabilizes them at room temperature for an extended period -- up to two months -- in their proof-of-concept experiments.

The Moderna and Pfizer/BioNTech COVID-19 vaccines use lipid nanoparticles -- basically spheres of fat molecules -- to protect and deliver the messenger RNA that generates a vaccine recipient's immune response to the SARS-CoV-2 virus.

"The expense of keeping these vaccines very cold from the time they're made to the time they're delivered is a challenge that needs to be addressed, especially because many countries don't have sufficient infrastructure to maintain this kind of cold chain," said Dr. Jeremiah Gassensmith, associate professor of chemistry and biochemistry and of bioengineering at UT Dallas and a corresponding author of the study. "Although we did not include in this work the specific lipid nanoparticles used in current COVID-19 vaccines, our findings are a step toward stabilizing a lipid nanoparticle in a way that's never been done before, so far as we know."

The idea for the research project began during a coffee-break discussion between Gassensmith and Dr. Gabriele Meloni, a corresponding co-author of the study and assistant professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics at UT Dallas.

Gassensmith's area of expertise is biomaterials and metal-organic frameworks, while Meloni's research focus is transmembrane transporter proteins. These proteins reside within cell membranes and are crucial for moving a variety of small molecules, including ions and trace metals, in and out of cells for several purposes.

"Membrane proteins sit in a cell membrane, which is a lipid bilayer," Meloni said. "To study their structure and biophysical and biochemical properties, we must extract these proteins from the membrane using detergents and then reconstitute them back into an artificial membrane -- a proteoliposome -- that mimics the proteins' natural environment."

Shell Creation

Lipid nanoparticles and liposomes are similar in structure, and neither are thermodynamically stable at room temperature, Gassensmith said. The lipid structures can fuse or aggregate, exposing any embedded membrane proteins or cargo to degradation.

"One of the challenges in my field of research is that both membrane proteins and lipid bilayers are very delicate and intrinsically metastable, and we're trying to combine them in order to understand how these proteins function," Meloni said. "We have to handle them carefully and prepare them fresh each time. They cannot be stored for long periods and are not easily shipped to colleagues in other labs."

The researchers joined forces to develop a methodology to stabilize this kind of lipid system and demonstrated their results using transmembrane proteins from Meloni's lab as a case study.

They mixed liposomes -- some with embedded proteins, some without -- with a combination of two inexpensive chemicals, zinc acetate and methylimidazole, in a buffer solution. In about a minute, a crystal matrix began to form around individual liposomes.

"We think that the lipids interact with the zinc just strongly enough to form an initial zinc-methylimidazole structure that then grows around the lipid sphere and completely envelops it, like an exoskeleton," Gassensmith said. "It's analogous to biomineralization, which is how certain animals form shells. We sort of co-opted nature in creating this totally fake shell, where the biomacromolecules -- the lipids and proteins -- catalyze the growth of this exoskeleton."

The ability of biomimetic shells to form around biological molecules is not new, Gassensmith said, but the process hasn't worked well with lipids or liposomes because the metal salts that comprise the shell material suck water out of the liposomes by osmosis and cause them to explode.

"One of the keys to this research was identifying the buffer solution in which everything resides," Gassensmith said.

Building a Buffer

Three graduate students collaborated on the project to develop the unique buffer medium that allows the reaction to occur.

"The buffer medium maintains the ionic strength of the solution and keeps the pH stable so that when you add a huge amount of metal salts, it doesn't osmotically shock the system," said Fabián Castro BS'18, a chemistry doctoral student in Gassensmith's lab and a lead author of the study.

Castro and co-lead authors Sameera Abeyrathna and Nisansala Abeyrathna, chemistry doctoral students (and siblings) in Meloni's lab, worked together to develop the buffer formulation.

Once the biomolecules have grown a shell, they are locked in, and the lipids remain stable. While the exoskeleton is very stable, it has a fortuitous Achilles' heel.

"The shell will dissolve if it encounters something that is attracted to zinc," Gassensmith said. "So, to release and reconstitute the liposomes, we used a zinc chelating factor called EDTA (ethylenediaminetetraacetic acid), which is a common, inexpensive food additive and medicine used to treat lead poisoning."

In addition to the laboratory experiments, in another proof-of concept exercise, Gassensmith mailed through the U.S. Postal Service a sample of the stabilized lipid particles to his mother in Rhode Island. She shipped them back to Texas, but because the COVID-19 pandemic forced the shutdown of most UT Dallas research labs in 2020, the samples sat untouched for about two months until the graduate students returned to campus to examine them. Although the informal experiment lasted much longer than the researchers had expected, the samples survived and functioned "just fine," Gassensmith said.

"This project required two different types of expertise -- my group's expertise in membrane transport proteins and Dr. Gassensmith's long track record working with metal-organic frameworks," Meloni said. "Our success clearly demonstrates how such collaborative research can bring about novel and useful results."

Credit: 
University of Texas at Dallas

Study: Ag policy in India needs to account for domestic workload

ITHACA, N.Y. - Women's increased agricultural labor during harvest season, in addition to domestic house care, often comes at the cost of their health, according to new research from the Tata-Cornell Institute for Agriculture and Nutrition (TCI).

Programs aimed at improving nutritional outcomes in rural India should account for the tradeoffs that women experience when their agricultural work increases, according to the study, "Seasonal time trade-offs and nutrition outcomes for women in agriculture: Evidence from rural India," which published in the journal Food Policy on March 24.

"To earn more income during peak seasons, landless women have no choice but to spend time in agricultural work, besides engaging in domestic work," said first author Vidya Vemireddy, a TCI alumna and assistant professor at the Indian Institute of Management Ahmedabad. "In contrast, women who have larger farms or higher incomes may choose to reduce the time they spend on agriculture and household activities via hired labor or labor-saving technologies."

To see how time constraints impact women's nutritional outcomes, Vemireddy and TCI director Prabhu Pingali surveyed 960 women from rural Maharashtra, India, about their time use and diets. Their work included an index of standardized local recipes to measure nutrient intake and cooking time.

Pingali is also a professor in the Charles H. Dyson School of Applied Economics and Management, with joint appointments in the Division of Nutritional Sciences and the Department of Global Development in the College of Agriculture and Life Sciences.

Women in rural India face severe constraints on time. They spend about 32% of their time on agricultural activities such as transplanting, weeding and harvesting, while also responsible for unpaid household labor like cooking, cleaning, fetching water and caring for children, Vemireddy and Pingali say. This workload increases during peak agricultural seasons, when they must spend up to five and a half hours per day sowing and harvesting.

Men, by comparison, face fewer time constraints since they spend very little time doing housework.

During peak agricultural seasons, the increased labor leaves women with less time for other personal activities. Vemireddy and Pingali found that these time trade-offs are associated with a decrease in caloric, protein, iron and zinc intake. More specifically, each 100-rupee increase in a woman's agricultural wages per day - meaning she spent more time working on the farm - is associated with a loss of 112.3 calories, 1.5 g of protein, 0.7 mg of iron and 0.4 mg of zinc.

This decrease is likely due to the women having less time and energy to cook nutritious meals, according to Pingali. "Most of the women we surveyed cooked two meals per day," Pingali said. "When faced with a longer workday on the farm, they might have less time to cook in the morning or be too tired in the evening, choosing instead to make easier, less time-consuming, and less nutritious dishes."

These nutritional deficits are worse for landless women who work on other people's farms, grow only food crops, or grow a mix of food and cash crops. By contrast, women who own large tracts of land and specialize in cash crops like cotton see little decline in nutrition during peak seasons, possibly because they have higher incomes.

The negative relationship between women's nutrition and increased farm work has important implications for development programs and interventions that seek to use agriculture to improve nutrition outcomes, such as encouraging households to grow kitchen gardens, the researchers said.

"Agricultural policies and programs that require greater involvement of women must recognize the consequences of increased time burdens and their adverse effects on nutrition," Vemireddy said. "The programs should be designed in such a way that the benefits of women's participation in agriculture outweigh the losses, such as time for well-being enhancing activities."

Vemireddy and Pingali said labor-saving strategies and technologies can lower the burdens placed on women by agricultural and household labor.

However, they said, managing time burdens alone can only improve nutrition so much. Successfully addressing malnutrition in India will still require a reorientation of the country's food policies to make nutrient-rich foods more accessible and affordable.

Credit: 
Cornell University

TGen identifies gene that could help prevent or delay onset of Alzheimer's disease

PHOENIX, Ariz. -- April 13, 2021 -- Findings of a study by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that increasing expression of a gene known as ABCC1 could not only reduce the deposition of a hard plaque in the brain that leads to Alzheimer's disease, but might also prevent or delay this memory-robbing disease from developing.

ABCC1, also known as MRP1, has previously been shown in laboratory models to remove a plaque-forming protein known as amyloid beta (Abeta) from specialized endothelial cells that surround and protect the brain and cerebral spinal cord. Building on previous studies, TGen conducted a series of pre-clinical genomic laboratory experiments. Results suggest that ABCC1 not only could export Abeta out of the brain, but that increasing the expression of ABCC1 could reduce Abeta production, thus preventing, or delaying, the onset of Alzheimer's.

The findings were published in the scientific journal Biology Open.

"Much work remains toward developing a drug that slows the development of or prevents Alzheimer's disease, but our findings suggest that targeting ABCC1 offers a promising path that could eventually lead to effective therapeutics," said Wayne Jepsen, a Postdoctoral Fellow in TGen's Neurogenomics Division, and the study's lead author.

Alzheimer's disease is the sixth leading cause of death in the U.S., annually killing more than 120,000 people. There is no treatment that can effectively prevent or slow this disease. An estimated 5.8 million Americans age 65 or older have Alzheimer's, and that number is expected to more than double over the next 30 years.

Symptoms of Alzheimer's include: memory loss; difficulty learning new things and problems coping with new situations; difficulty with language and problems with reading, writing and working with numbers; difficulty organizing thoughts and thinking logically; and a shortened attention span.

ABCC1 is an Alzheimer's drug target

TGen's study results suggest that ABCC1 is a valid drug target for Alzheimer's because of the multiple ways the gene influences Abeta; not only potentially exporting it from the brain, but also in the way it modulates cellular processes involving amyloid precursor protein (APP), which is abundant in the brain and can be cut up into smaller pieces via the alpha- or beta-secretase pathways.

The alpha-secretase pathway is associated with the development and protection of neurons, which are the functioning cells of the brain and central nervous system. The resulting soluble APP alpha peptide is also associated with memory formation and a process called synaptic plasticity, in which the synapses that connect neurons and allow them to communicate are able to change and adapt to new information.

The beta-secretase pathway leads to the formation of Abeta, a peptide that accumulates to form amyloid plaques, which along with neurofibrillary tangles are the two pathological hallmarks that define Alzheimer's. Scientists have hypothesized that decreasing Abeta production could slow the progression of Alzheimer's.

TGen's experiments indicated that: ABCC1 modulates APP processing away from the formation of amyloid; confirms previous reports that ABCC1 exports Abeta from the inside of cells to the outside of cells; and that thiethylperazine, a drug long used to ease nausea and vomiting, increases ABCC1 transport activity.

"Compounds that can dramatically increase ABCC1 transport activity, or that can increase ABCC1 expression, may prove to be viable drugs for the treatment or prevention of Alzheimer's disease by not only increasing clearance of Abeta from the brain, but also by reducing the amount of Abeta that is produced," said Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, and the study's senior author.

"Interestingly, due to the historical focus in cancer research on finding ABCC1 inhibiting drugs, we are betting that there are already drugs out there that are known to have an opposite ABCC1-activating effect, and our data suggest that such drugs should be examined for anti-Alzheimer's disease activity," Dr. Huentelman said.

Dr. Todd Levine, a neurologist at HonorHealth and an adjunct faculty member at TGen who has reviewed the study but is not an author, said he believes the focus on ABCC1 is a potentially important new avenue of Alzheimer's research: "While it is still early days, the authors of this study present a compelling case for further investigation of ABCC1 as a potential target for new therapeutics against this devastating disease for which better treatments are urgently needed."

Credit: 
The Translational Genomics Research Institute

Tropical forest soils capture CO2 under elevated nitrogen deposition

image: An N-rich primary tropical forest at the Dinghushan Biosphere Reserve in southern China, where the first long-term simulated N deposition research site was established (in 2002) in China.

Image: 
SCBG

In a new study, Dr. LU Xiankai and his colleagues from the South China Botanical Garden (SCBG) of the Chinese Academy of Sciences (CAS) found that tropical forests can capture carbon dioxide (CO2) into soils and thus reduce emitted CO2. But how exactly do tropical forest soils capture atmospheric CO2?

Current knowledge of forest soil carbon sequestration mainly focuses on temperate and boreal forests, where most ecosystems are nitrogen-limited, and an increase in nitrogen supply can enhance net primary productivity (NPP) and subsequent soil carbon sequestration.

Traditionally, many scientists thought that nitrogen-rich tropical forests are unlikely to increase belowground soil carbon storage under greater nitrogen supply due to a lack of stimulation of NPP. However, this assumption has not been fully verified under field conditions, and belowground ecosystems have always been neglected by scientists.

Dr. LU and his colleagues initiated more than a decade of continuous nitrogen addition experiments in a nitrogen-rich tropical forest ecosystem and quantitatively demonstrated that excessive nitrogen deposition significantly increased soil carbon storage by 7-21%.

According to the researchers, soil carbon sequestration efficiency was estimated to be 9 kg of carbon per unit of added nitrogen, which is comparable to temperate forest ecosystems. Interestingly, soil nitrogen retention was significantly and positively correlated with carbon sequestration.

Combining these field experiments with other global data, they concluded that nitrogen deposition stimulates soil carbon sequestration, which is prevalent throughout nitrogen-limited and nitrogen-rich ecosystems, however the underlying mechanisms of these two ecosystems are different.

In nitrogen-limited ecosystems, nitrogen deposition stimulates soil carbon sequestration of organic carbon by increasing aboveground plant litter inputs to forest soils and reducing CO2 emissions from soils. In nitrogen-rich forests, however, the subsequent decreases in CO2 emissions and dissolved organic carbon leaching from soils are the two major drivers of carbon sequestration.

The researchers showed that organic matter interacting with soil minerals plays the dominant role in regulating the stabilization of soil carbon stocks for the two ecosystems.

"This study for the first time proves that excess nitrogen deposition can promote soil organic carbon accumulation in nitrogen-rich tropical forests," said Dr. LU, the first author of the study and principal investigator of the Nitrogen Biogeochemistry Lab at SCBG. "We have highlighted that these mechanisms can be incorporated into state-of-the-art Earth models, improving prediction of terrestrial carbon cycles under global change scenarios."

"Our findings, however, do not imply that we encourage loosening limits on nitrogen emissions into the atmosphere, in view of their adverse impacts on the environment and human health," said LU.

Credit: 
Chinese Academy of Sciences Headquarters

New method of artificially creating genetic switches for yeast

image: A genetic switch

Image: 
Masahiro Tominaga, Kenta Nozaki, Daisuke Umeno, Jun Ishii, Akihiko Kondo.

A group of researchers from Kobe University and Chiba University has successfully developed a flexible and simple method of artificially producing genetic switches for yeast, a model eukaryotic organism. The group consisted of Researcher TOMINAGA Masahiro*1, Associate Professor ISHII Jun*2 and Professor KONDO Akihiko*3 (of Kobe University's Graduate School of Science, Technology and Innovation/Engineering Biology Research Center), and Professor UMENO Daisuke et al. (of Chiba University's Graduate School of Engineering).

Genetic switches are gene regulatory networks that control gene expression. The researchers established a platform for creating genetic switches that could be applied to the development of sophisticated, artificially controlled yeast cells to produce large quantities of valuable compounds. These research results were published in 'Nature Communications' on March 23, 2021.

*1 Technology Research Association of Highly Efficient Gene Design (TRAHED) researcher.
*2 Ibid. Vice Director of the Kobe Center.
*3 Ibid. Director of the Kobe Center.

Main Points

Genetic switches are necessary in order to artificially generate new functions in an organism. These switches control the amount of proteins produced by a gene (i.e. gene expression (*1)) and the timing of this production.

There has been a lag in the development of genetic switches for eukaryotic organisms in particular, as well as a significant limitation on the number of genes that can be controlled at the same time.

The researchers developed a new selection platform in which the cutoff threshold can be set. This enabled them to succeed in creating highly functional, artificial genetic switches for yeast that can be produced easily and flexibly.

The developed platform is expected to have a wide range of applications in situations that require precise control of expression levels and timing for a large number of genes. This includes optimizing the balance of metabolic enzyme expression in the construction of cells for producing useful substances that have complex intracellular metabolisms.

Research Background

The number and type of genes that an organism possesses do not solely determine its life functions. The timing and quantity of proteins produced by a gene (i.e. gene expression) are other factors that are known to result in significant alterations. In the field of synthetic biology, recent advances have made it possible to generate many novel cell functions by artificially controlling the expression of certain genes. Genetic switches are necessary in order to control the rate and timing of gene expression. A genetic switch (Figure 1) is a regulatory system that turns the expression of a particular gene 'on' or 'off' in response to a stimulus (or inducer) from either inside or outside the cell (for example, the presence of a chemical substance). Consequently, genetic switches are an essential tool for synthetic biology, which aims to artificially design and construct cellular functions.

Many genetic switches have been developed for simple, single cell organisms (prokaryotes) such as E. coli. However, the systems of gene expression in eukaryotic organisms, such as humans, plants and yeast, are more complex. Consequently, there is a lag in the development of genetic switches for these organisms. Even though yeast is a model eukaryotic organism, attempts to engineer the functions of its cells have faced great limitations.

Research Methodology

When constructing genetic switches, it is very difficult to predict where and how to alter the switches to enable gene expression to be controlled. Evolutionary molecular engineering is a useful method for determining this (Figure 2). The method involves creating a library of genetic switch variants by randomly inducing mutation (*2) in part of or the entire genetic switch, and then selecting the variants that show intended performance. Although it is easy to produce a large number of variants, the desired variants within this number must be quickly identified. An artificial process of elimination (selection) was carried out to select the cells that remained both when gene expression was 'off' and when gene expression was turned 'on' by a specific inducer. However, if the selection is too strong or too weak, it is not possible to single out the best variants. Although it is necessary to select functional genetic switch variants that are suitably robust in both 'on' and 'off' states, it is very difficult to predict how strong the selection should be beforehand.

The team of researchers from Kobe University and Chiba University established a workflow system whereby they could generate selections of varying strengths in parallel by changing the type or concentration of the chemicals used for selection. After selecting a group of variants, the researchers exposed each one to an external stimulus (inducer) and analyzed the extent to which this turned gene expression on by observing the change in the level of light emitted from GFPs (green fluorescent proteins). This allowed them to determine the most appropriate selection, in other words to easily identify genetic switch variants that demonstrated a high level of performance. Using this method, the researchers successfully developed three new genetic switches that were as efficient as the best-performing switch developed for yeast up until now.

By integrating these three genetic switches, the researchers produced yeast that could biosynthesize orange pigment (β-carotene) under AND-gated control (i.e. where β-carotene could only be produced if two specific chemical compounds, DAPG and HSL, were present) (Figure 3).

Further Developments

The selection method developed by this research group will expedite the development of a wide range of genetic switches for yeast, with various performance levels and characteristics. This will also lead to a rapid increase in the number of genes that can be controlled in parallel. Combining these new genetic switches will make it possible to artificially design cellular functions. For example, this could contribute towards the development of sophisticated, artificially regulated yeast cells for producing large quantities of useful organic compounds.

Glossary

1. Gene expression: Genes encode proteins and are made up of 4 types of bases: A, T, G and C. Proteins are produced according to the arrangement of these bases. This process is called gene expression.
2. Mutation: A change in the type of bases that make up a gene. Mutations alter the instructions for making proteins and can result in changes in protein function.

Acknowledgements

This research received funding from the following:

The Japan Agency for Medical Research and Development (AMED)'s 'Project Focused on Developing Key Technology for Discovering and Manufacturing Drugs for Next-Generation Treatment and Diagnosis' (grant numbers JP19ae0101055 and JP19ae0101060).

The New Energy and Industrial Technology Development Organization (NEDO)'s project for the 'Development of Production Techniques for Highly Functional Biomaterials Using Smart Cells of Plants and Other Organisms' (Project Number P16009).

The Japan Science and Technology Agency's JST-Mirai Program (grant number JPMJMI17EJ).

A Grant-in-Aid for Scientific Research on Innovative Areas from the Japan Society for the Promotion of Science (JSPS) in the project area entitled 'Creation of Complex Functional Molecules by Rational Redesign of Biosynthetic Machineries' (JP16H06450)

JSPS KAKENHI grants (numbers JP18K14374, JP15H04189 and JP15K14228).

Journal Information

Title:
"Robust and flexible platform for directed evolution of yeast genetic switches"
DOI: 10.1038/s41467-021-22134-y

Authors:
Masahiro Tominaga, Kenta Nozaki, Daisuke Umeno, Jun Ishii, Akihiko Kondo.

Journal:
Nature Communications

Credit: 
Kobe University

Cascading effects of noise on plants persist over long periods and after noise is removed

image: Pinyon pine seedling counted during vegetation surveys.

Image: 
Photo by Sarah Termondt

Though noise may change moment by moment for humans, it has a more lasting effect on trees and plants.

A new Cal Poly study reveals that human noise pollution affects the diversity of plant life in an ecosystem even after the noise has been removed. This is the first study that explores the long-term effects of noise on plant communities. It was published in the Proceedings of the Royal Society B.

In a study conducted twelve years ago near natural gas wells in New Mexico, researchers found that there were 75% fewer piñon pine seedlings in noisy sites as in quiet ones. This was most likely due to the noise driving away the Woodhouse's scrub jay, which plants thousands of pine seeds while storing them to eat during the winter months.

A research team recently returned to the sites to find out whether the piñon pine had recovered over time.

Because companies change the sites where they use noisy compressors to help produce natural gas, some of the previously noisy sites had become quiet. In these areas, there were fewer seedlings and saplings compared to sites that didn't have compressors added to the wellpad to speed up gas extraction. The decrease in saplings results from the time when the site was noisy, but the decrease in seedlings shows that piñon pine seeds still weren't sprouting once the noise was removed.

"The effects of human noise pollution are growing into the structure of these woodland communities," said biology professor and senior author Clint Francis. "What we're seeing is that removal of the noise doesn't necessarily immediately result in a recovery of ecological function."

While it's possible that the piñon pine has decreased because of a lack of opportunities to produce, it's more likely that the Woodhouse's scrub jay hasn't returned to the formerly noisy area and so isn't planting seeds.

"Some animals, like scrub-jays, have episodic memory," said Jennifer Phillips, the lead author who worked on the project while a postdoc at Cal Poly and who is now a professor teaches at Texas A&M-San Antonio. "Animals like the scrub-jay that are sensitive to noise learn to avoid particular areas. It may take time for animals to rediscover these previously noisy areas, and we don't know how long that might take."

Researchers also found differences in juniper seedlings and communities of flowering plants depending on current noise levels and whether noise levels had recently changed because noisy compressors were moved. Sites with greater noise had fewer juniper seedlings and different types of plants than quiet sites. Because of the complexity of ecosystems, the cause of these changes is still unknown.

"Our results reveal that plant communities change in lots of ways with noise exposure," Francis said. "We have a decent understanding of how and why foundational trees like piñon pine are affected by noise from our previous work with jays, but we are also seeing large changes in plant communities through changes in the abundance of shrubs and annual plants. These changes likely reflect impacts of noise on animals that eat plants, such as deer, elk and various insects, plus the many pollinators that are important for plant reproduction. In essence our research indicates that the consequences of noise are far-reaching and reverberate throughout the ecosystem through lots of species."

Future studies can offer a more fine-tuned look at how noise is causing these ecosystem changes. Researchers want to know more about which herbivores, seed dispersers and pollinators avoid or are attracted to noise and how changes in insect and animal behavior combine to affect plant communities.

Based on patterns from over a decade of an ecosystem experiencing noise pollution, evidence suggests that plant communities may take a long time to recover from the effects of human noise. Still, co-author and lead botanist Sarah Termondt, a Cal Poly research affiliate, emphasizes the need to understand the full and lasting costs of noise. "Continuing to look at long-term changes in floristic inventories over time will elucidate whether communities do eventually recover after long periods of noise pollution, even once it is removed from the landscape," she said.

When changes to plant communities are viewed alongside the growing evidence for the problems that noise creates for animals, it is increasingly difficult to ignore the near absence of noise regulations across the U.S.

Credit: 
California Polytechnic State University

Joyful screams perceived more strongly than screams of fear or anger

Screaming can save lives. Non-human primates and other mammalian species frequently use scream-like calls when embroiled in social conflicts or to signal the presence of predators and other threats. While humans also scream to signal danger or communicate aggression, they scream when experiencing strong emotions such as despair or joy as well. However, past studies on this topic have largely focused on alarming fear screams.

Humans respond to positive screams more quickly and with higher sensitivity

In a new study, a team at the University of Zurich Department of Psychology led by Sascha Frühholz investigated the meaning behind the full spectrum of human scream calls. The results revealed six emotionally distinct types of scream calls indicating pain, anger, fear, pleasure, sadness and joy. "We were surprised by the fact that listeners responded more quickly and accurately, and with a higher neural sensitivity, to non-alarming and positive scream calls than to alarming screams," says Frühholz.

Cognitive processing of joyful screams is more efficient

The research team carried out four experiments for their study. Twelve participants were asked to vocalize positive and negative screams that might be elicited by various situations. A different group of individuals rated the emotional nature of the screams and classified them into different categories. While participants listened to the screams, their brain activity underwent functional magnetic resonance imaging (fMRI) to monitor how they perceived, recognized, processed and categorized the sounds. "The frontal, auditory and limbic brain regions showed much more activity and neural connectivity when hearing non-alarm screams than when processing alarm scream calls," explains Frühholz.

More complex social environments have reshuffled neurocognitive priorities

It was previously assumed that human and primate cognitive systems were specially tailored for recognizing threat and danger signals in the form of screams. In contrast to primates and other animal species, however, human scream calls seem to have become more diversified over the course of human evolution - something that Frühholz considers to be a big evolutionary leap. "It's highly possible that only humans scream to signal positive emotions like great joy or pleasure. And unlike with alarm calls, positive screams have become increasingly important over time," he says. Researchers suggest that this may be due to the communicative demands brought about by humans' increasingly complex social environments.

Credit: 
University of Zurich

US power sector is halfway to zero carbon emissions

image: Projected versus actual outcomes for the U.S. power sector.

Image: 
Berkeley Lab

Concerns about climate change are driving a growing number of states, utilities, and corporations to set the goal of zeroing out power-sector carbon emissions. To date 17 states plus Washington, D.C. and Puerto Rico have adopted laws or executive orders to achieve 100% carbon-free electricity in the next couple of decades. Additionally, 46 U.S. utilities have pledged to go carbon free no later than 2050. Altogether, these goals cover about half of the U.S. population and economy.

These are ambitious targets, but a new look at the past 15 years in the electricity sector shows that large reductions in emissions are possible.

New research from the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) analyzes historical trends to examine how much progress the power sector has already made in reducing emissions. The study, "Halfway to Zero: Progress towards a Carbon-Free Power Sector," looks back at the 2005 Annual Energy Outlook from the Energy Information Administration (EIA), the U.S. government's official agency for data collection and analysis.

"Business-as-usual projections saw annual carbon dioxide emissions rising from 2,400 to 3,000 million metric tons (MMT) from 2005 to 2020," said Berkeley Lab scientist Ryan Wiser, lead author of the study. "But actual 2020 emissions fell to only 1,450 MMT. The U.S. cut power sector emissions by 52% below projected levels - we are now 'halfway to zero.'"

According to the study, relative to projected values, total consumer electricity costs were 18% lower; costs to human health and the climate were 92% and 52% lower, respectively; and the number of jobs in electricity generation was 29% higher.

Drivers of change

From technological advances to policy, the study identified the main drivers from the last 15 years that contributed to lower carbon emissions in the U.S. power sector. Total demand for electricity was almost exactly the same in 2020 as it was in 2005, and was 24% lower than projected fifteen years earlier. "This drop in demand was due in part to sectoral and economic changes, but also to greater energy efficiency driven by policies and technology advancement," said Wiser.

The researchers found that wind and solar power dramatically outperformed expectations, delivering 13 times more generation in 2020 than projected. This is also a result of technology development and state and federal policies, as prices plummeted for new wind and solar technologies. In addition, nuclear generation has largely held steady, tracking the past projections and helping to ensure no backsliding in carbon emission.

The study found that switching from coal to natural gas for power generation played a big role in lowering carbon emissions. Natural gas generation grew rapidly, driven by the shale gas revolution and low fuel prices.

The researchers also found that changes over the last 15 years had numerous other economic and environmental benefits. For example, total electric bills for consumers were 18% lower in 2020 than previously projected by EIA, for a total savings of $86 billion per year.

According to the study, reduced sulfur and nitrogen emissions led to lower health impacts, such as respiratory disease, with premature deaths falling from 38,000 to 3,100 per year. "Compared to the business-as-usual projection, not only did the nation significantly reduce its carbon footprint, but it did so while also reducing total energy bills and health burdens," said co-author and Berkeley Lab scientist Dev Millstein.

The study also found that while employment patterns shifted along with changes in the power sector, electricity supply is supporting 200,000 more jobs than might have been the case under the earlier projection.

Looking forward

While a look back shows that dramatic changes in emissions are possible over a 15-year span, the study points out that this does not guarantee the next 15 years will see similar progress.

Given advancements in wind, solar, and battery technologies, these resources are likely to play important near-term roles in further power-sector decarbonization. According to the study, a large share of the capacity needed to approach a zero-carbon power-sector target is already in the development pipeline: about 660 gigawatts (GW) of wind and solar have requested transmission access, more than half of what might be required to approach a zero-carbon power-sector target. Not all proposed projects will be built, but the scale indicates interest in development.

Wiser points out there are significant infrastructure requirements related to scaling up renewable energy. The power sector will have to ensure electricity delivery, reliability, and resilience; build new transmission infrastructure; change planning and grid operations; revise siting processes; and focus attention on impacted workers and communities.

Another major challenge is how to meet the last portion of demand, to ensure a reliable power supply when the wind doesn't blow and the sun doesn't shine. The study concludes that further research, development, and demonstration is needed for the numerous technologies that can fill this gap, such as longer-duration energy storage, hydrogen or synthetic fuels, bioenergy, fossil or biomass generation with carbon capture, nuclear energy, geothermal energy, and solar-thermal with storage.

"As the country maps out a plan for further decarbonization, experience from the past 15 years offers two central lessons," said Wiser. "First, policy and technology advancement are imperative to achieving significant emissions reductions. Second, our ability to predict the future is limited, and so it will be crucial to adapt as we gain policy experience and as technologies advance in unexpected ways."

Credit: 
DOE/Lawrence Berkeley National Laboratory

Life expectancy lower near superfund sites

image: Hanadi S. Rifai, John and Rebecca Moores Professor of Civil and Environmental Engineering at University of Houston, reports that living near a toxic waste or Superfund site can cut your life short.

Image: 
University of Houston

Living near a hazardous waste or Superfund site could cut your life short by about a year, reports Hanadi S. Rifai, John and Rebecca Moores Professor of Civil and Environmental Engineering at the University of Houston. The study, published in Nature Communications and based on evaluation of 65,226 census tracts from the 2018 Census, is the first nationwide review of all hazardous waste sites and not just the 1,300 sites on the national priority list managed by the federal government.

The analysis shows a decrease of more than two months in life expectancy for those living near a Superfund site. When coupled with high disadvantage of sociodemographic factors like age, sex, marital status and income, the decrease could be nearly 15 months, according to the analysis. Prior studies confirmed that those living near hazardous waste sites generally have greater sociodemographic disadvantage and, as a result, poorer health. The average life expectancy in the U.S. is 78.7 years, and millions of children have been raised within less than a one-mile radius from a federally designated Superfund site.

"We have ample evidence that contaminant releases from anthropogenic sources (e.g., petrochemicals or hazardous waste sites) could increase the mortality rate in fence-line communities," reports Rifai. "Results showed a significant difference in life expectancy among census tracts with at least one Superfund site and their neighboring tracts with no sites."

Nationally there are thousands of so-called Superfund, or contaminated, sites that pose a risk to human health and the environment. These sites include manufacturing facilities, processing plants, landfills and mining sites where hazardous waste was dumped, left out in the open or poorly managed.

The study presents a nationwide geocoded statistical modeling analysis of the presence of Superfund sites, their flood potential, and the impact on life expectancy independently and in context of other sociodemographic determinants. Life expectancy is one of the most basic indicators of public health. Studies show a 1% increase in life expectancy could lead to a 1.7% to 2% increase in population.

Analysis revealed that out of 12,717 census tracts with at least one Superfund site, the adverse effect of this presence was more severe on the ones with higher sociodemographic disadvantage. For instance, the presence of a Superfund site in a census tract with smaller than median income ($52,580) could reduce life expectancy by as much as seven months.

While many studies have broken down mortality rates associated with different diseases, only a few have paid attention to hazardous waste and Superfund sites and their potential impact on mortality rates.

Other recent national studies showed a significant correlation between the residential proximity to Superfund sites and the occurrence of Non-Hodgkin's lymphoma, especially among males. In Texas, the Texas Department of State Health Services recently examined a cancer cluster in downtown Houston around a former railroad creosote treatment facility, finding the observed number of childhood acute lymphoblastic leukemia cases was greater than expected based on cancer rates in Texas.

Rifai also examined the impact of flooding, which could cause the transport of contaminants from Superfund sites and potentially affect neighborhoods farther than the nearby fence-line communities.

"When you add in flooding, there will be ancillary or secondary impacts that can potentially be exacerbated by a changing future climate," said Rifai. "The long-term effect of the flooding and repetitive exposure has an effect that can transcend generations."

Credit: 
University of Houston

Finding resiliency in local, community news gathering

image: Community newspapers often serve as the public's main source of accurate, local news. They also can be an important way to share the impact of major national events, such as a global pandemic. As the COVID-19 pandemic began spreading throughout the United States, journalism scholars at the University of Missouri and the University of Kansas found that community newspapers across the country began to reevaluate the way they had been doing business for decades.

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University of Missouri

When the Webster-Kirkwood Times, a community newspaper in the greater St. Louis, Missouri area, had to endure layoffs and stop publishing its print edition -- due to a loss in revenue as a result of the COVID-19 pandemic -- its readers felt the loss and began supporting the newspaper in earnest.

"A lot of times people don't know what they've got until it's gone," said Jaime Mowers, editor-in-chief of the Webster-Kirkwood Times. "Now, there is such a newfound appreciation for the newspaper. It's amazing to have the community's support, knowing we are loved that much and appreciated enough to be able to bring our print edition back. We are part of the fabric of our community, and we're lucky to still be a part of that."

Community newspapers, like the Webster-Kirkwood Times and those in rural America, often serve as the public's main source of accurate, local news. They also can be an important way to share the impact of major national events, such as a global pandemic. As the COVID-19 pandemic began spreading throughout the United States, journalism scholars at the University of Missouri and the University of Kansas found that community newspapers across the country began to reevaluate the way they had been doing business for decades.

In their new study, the journalism scholars analyzed six weeks of news articles and columns in community newspapers that described COVID-19's impact on the journalism profession. They found journalists in these local newsrooms were now open to the idea that "everything is on the table" for their survival. As part of that philosophy, journalists are beginning to embrace the need for self-advocating for their profession in a way that prior generations were historically uncomfortable doing, said Ryan J. Thomas, associate professor of journalism studies in the Missouri School of Journalism.

"There has been a tendency within journalism to avoid journalism itself becoming the story, and let the quality of the work speak for itself," Thomas said. "Journalists have been holding onto this view that if they put out a quality product, the public will appreciate them. But what we've found, and which is also consistent with a few other similar studies, is that journalists' internal view of their own profession is changing. Journalists are now recognizing the need to be their own advocates, not only for the importance of their role in a democracy, but also for their own survival -- by trying to encourage people to subscribe, renew their subscription and so on."

Within two months of the COVID-19 pandemic reaching the U.S., at least 30 local newspapers across the country closed or merged due to financial situations. Meanwhile, hundreds of other community newspapers responded with layoffs, furloughs and production changes, such as shifting to an exclusive online format and reducing the number of print editions. Thomas said this shift in thinking also recognizes that reliance on an advertising model, the source of revenue for much traditional journalism, is a risky venture. He said their research revealed a debate between editors and publishers about whether or not paywalls -- a newer form of revenue for many media organizations -- should be used to access news about the coronavirus.

"On one hand, journalism is a public service and information about the coronavirus is essential for making the community aware of the health threats and safety measures that should be taken," Thomas said. "On the other hand, if that information is located behind a paywall, people cannot access it. However, a paywall is also one source of revenue and can help keep the lights on. That's what makes this a complicated situation."

Teri Finneman, an associate professor in the School of Journalism and Mass Communications at the University of Kansas, and co-author on the study, was glad to see how honest journalists were when writing about their situations.

"Over the last decade or so, I think the public keeps hearing the soundbite that journalism is dying, but I don't know if the public truly understands how journalism works," said Finneman, who received her master's degree and doctorate from MU. "So, it's important that journalists have more of these honest conversations with the public, so that the public has a greater understanding of what journalists need to be able to adequately serve them. Journalism does have business model challenges, and while some areas in journalism are thriving and great work is being done, journalism still needs communities to invest into their local newsrooms similar to the effort that journalists are making who are invested in serving the needs of their local communities."

Credit: 
University of Missouri-Columbia

Stellar feedback and an airborne observatory; scientists determine a nebula younger than believed

image: An international team led by West Virginia University researchers studied RCW 120 to analyze the effects of stellar feedback, and found that RCW 120 must be less than 150,000 years old, which is very young for such a nebula.

Image: 
West Virginia University

In the southern sky, situated about 4,300 light years from Earth, lies RCW 120, an enormous glowing cloud of gas and dust. This cloud, known as an emission nebula, is formed of ionized gases and emits light at various wavelengths. An international team led by West Virginia University researchers studied RCW 120 to analyze the effects of stellar feedback, the process by which stars inject energy back into their environment. Their observations showed that stellar winds cause the region to expand rapidly, which enabled them to constrain the age of the region. These findings indicate that RCW 120 must be less than 150,000 years old, which is very young for such a nebula.

About seven light years from the center of RCW 120 lies the boundary of the cloud, where a plethora of stars are forming. How are all of these stars being formed? To answer that question, we need to dig deep into the origin of the nebula. RCW 120 has one young, massive star in its center, which generates powerful stellar winds. The stellar winds from this star are much like those from our own Sun, in that they throw material out from their surface into space. This stellar wind shocks and compresses the surrounding gas clouds. The energy that is being input into the nebula triggers the formation of new stars in the clouds, a process known as "positive feedback" because the presence of the massive central star has a positive effect on future star formation. The team, featuring WVU postdoctoral researcher Matteo Luisi, used SOFIA (the Stratospheric Observatory for Infrared Astronomy) to study the interactions of massive stars with their environment.

SOFIA is an airborne observatory consisting of an 8.8-foot (2.7-meter) telescope carried by a modified Boeing 747SP aircraft. SOFIA observes in the infrared regime of the electromagnetic spectrum, which is just beyond what humans can see. For observers on the ground, water vapor in the atmosphere blocks much of the light from space that infrared astronomers are interested in measuring. However, its cruising altitude of seven miles (13 km), puts SOFIA above most of the water vapor, allowing researchers to study star-forming regions in a way that would not be possible from the ground. Overnight, the in-flight observatory observes celestial magnetic fields, star-forming regions (like RCW 120), comets and nebulae. Thanks to the new upGREAT receiver that was installed in 2015, the airborne telescope can make more precise maps of large areas of the sky than ever before. The observations of RCW 120 are part of the SOFIA FEEDBACK survey, an international effort led by researchers Nicola Schneider at the University of Cologne and Alexander Tielens at the University of Maryland, which makes use of upGREAT to observe a multitude of star-forming regions.

The research team opted to observe the spectroscopic [CII] line with SOFIA, which is emitted from diffuse ionized carbon in the star-forming region. "The [CII] line is probably the best tracer of feedback on small scales, and--unlike infrared images--it gives us velocity information, meaning we can measure how the gas moves. The fact that we can now observe [CII] easily across large regions in the sky with upGREAT makes SOFIA a really powerful instrument to explore stellar feedback in more detail than was possible previously," says Matteo.

Using their [CII] observations from SOFIA, the research team found that RCW 120 is expanding at 33,000 mph (15 km/s), which is incredibly fast for a nebula. From this expansion speed, the team was able to put an age limit on the cloud and found that RCW 120 is much younger than previously believed. With the age estimate, they were able to infer the time it took for the star formation at the boundary of the nebula to kick in after the central star had been formed. These findings suggest that positive feedback processes occur on very short timescales and point to the idea that these mechanisms could be responsible for the high star formation rates that occurred during the early stages of the universe.

Looking forward, the team hopes to expand this type of analysis to the study of more star forming regions. Matteo says, "The other regions we are looking at with the FEEDBACK survey are in different stages of evolution, have different morphologies, and some have many high-mass stars in them, as opposed to only one in RCW 120. We can then use this information to determine what processes primarily drive triggered star formation and how feedback processes differ between various types of star-forming regions."

Credit: 
West Virginia University

Chemical modification of RNA could play key role in polycystic kidney disease

image: Vishal Patel, M.D.

Image: 
UT Southwestern Medical Center

DALLAS - April 13, 2021 - A chemical modification of RNA that can be influenced by diet appears to play a key role in polycystic kidney disease, an inherited disorder that is the fourth leading cause of kidney failure in the U.S., UT Southwestern researchers report in a new study. The findings, published online today in Cell Metabolism, suggest new ways to treat this incurable condition.

About 600,000 Americans and 12.5 million people worldwide have autosomal dominant polycystic kidney disease (PKD), a condition caused by mutations in either of two genes, PKD1 or PKD2. These mutations cause kidney tubules - small tubes that filter blood and generate urine - to dilate, forming cysts that grossly enlarge the kidneys. In about 50 percent of patients, these cysts eventually cause kidney failure, necessitating dialysis or a kidney transplant.

Although one FDA-approved drug exists to treat PKD, it merely slows the decline in kidney function, explain study leaders Vishal Patel, M.D., associate professor of internal medicine at UTSW, and Harini Ramalingam, Ph.D., a postdoctoral fellow in Patel's lab. More treatments for this condition are urgently needed, they say, but the molecular mechanisms that cause PKD to develop and progress are still not fully known.

To better understand this condition, Patel, Ramalingam, and their colleagues investigated whether chemical modifications to the genetic molecule RNA, which translates instructions from DNA to produce proteins in the body, could play a part.

The researchers investigated whether the most common RNA chemical modification known as m6A, which occurs when a methyl group is chemically attached to an RNA component called adenosine, might be altered in PKD. Specifically, they looked at the activity of Mettl3, the enzyme that performs this methylation reaction. In three mouse models of PKD, they found that Mettl3 activity and the resulting m6A levels were significantly higher than in healthy animals without this condition. The same was true for kidney samples from PKD patients compared with healthy kidney samples.

Further investigation showed that in the mouse models, Mettl3 activity increased before the first kidney cysts made their appearance, suggesting that it might be an initiating event for the disease. When researchers genetically altered healthy mice to overproduce Mettl3, the animals developed small kidney cysts, even though they didn't carry any PKD mutations. Conversely, shutting down Mettl3 in the PKD models significantly slowed cyst growth, suggesting that the enzyme plays a key role in disease progression.

Next, the scientific team tested whether limiting methionine, the dietary nutrient that supplies the raw materials for methylation, might stem cyst formation. When researchers grew kidney tissue in petri dishes with varying concentrations of methionine, cysts increased with higher concentrations. The researchers saw an opposite phenomenon when PKD mice were fed a low-methionine diet - these animals had less severe PKD.

Ramalingam notes that the findings have two important implications. First, it may be possible to partially control PKD with a vegan or vegetarian diet, since methionine is found in meat and fish. Second, identifying chemicals that stem Mettl3 activity may lead to new drugs to treat this condition.

"Both of these possibilities represent new avenues for PKD research that didn't exist before," she says.

Credit: 
UT Southwestern Medical Center

Past Global Changes Horizons - a new paleoscience magazine for teenagers and young adults

image: Illustration from the article “From the depths of the Amundsen Sea” (p. 12) by Margot Courtillat in Past Global Changes Horizons magazine, volume 1.

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Illustration by Cirenia Arias Baldrich for Past Global Changes Horizons, vol. 1

Past Global Changes Horizons is a scientific review of why the study of Earth's history is important, and uses comics, pictures, and drawings that support short papers with strong messages about past sciences and how to prepare for a changing future. Articles cover different environments across the planet, from caves to oceans, and from Antarctica to the Rift valley in Africa.

Each of the 18 contributions addresses a scientific question and includes appealing and understandable figures or images, without sacrificing scientific rigor. Tips and suggestions for further research and discussion topics are also included, meaning Horizons is not only designed for students but also potentially for teachers.

It is currently an online magazine, but there will be the option (via the Past Global Changes website) to request free hard copies in May 2021. A second print run is planned for October 2021.

The first issue of Horizons was edited by Graciela Gil-Romera and Boris Vannière, and the editor-in-chief is PAGES' Science Officer Sarah Eggleston. The magazine is in English.

Graciela Gil-Romera said Horizons was created due to a lack of relatable outreach and science communication resources for this influential group.

"This is precisely the age group where more is needed to help shape their transition into decision-makers in adulthood," she said.

"The younger generation is being bombed with fake news, extremism, and environmental anxiety. Scientists have produced this magazine for them to show that we can all be scientists, and to create not only more environmental awareness, but also to inspire them that there is still time to build a better future, and we know this thanks to the past."

Boris Vanniere believes it is imperative for active scientists to inspire and mobilise the next generation.

"Dissemination of scientific knowledge requires more attention and direct efforts on the part of scientists to reach and address all members of society, especially the younger generation," he said.

"The objective of education is to contribute to citizen power and democratic life. Only well-informed people can judge government action. Scientific advisors are useful, but only citizens who can nurture their free will will be able to see clearly the promises and uncertainties ahead, and then be freer and stronger."

Horizons is planned as an annual publication. It is a great opportunity for more senior scientists to reach out to the next generation and get them excited about their individual research topics. All topics that echo the younger generation's questions about our relationship with the environment and the Earth system, and their history, are encouraged for future issues.

Credit: 
Past Global Changes IPO