The ability to proliferate and evolve is one of the defining characteristics of living organisms. However, no artificial materials with these characteristics have been created. In order to develop an artificial molecular system that can multiply and evolve, the information (genes) coded in DNA must be translated into RNA, proteins must be expressed, and the cycle of DNA replication with those proteins must continue over a long period in the system. To date, it has been impossible to create a reaction system in which the genes necessary for DNA replication are expressed while those genes simultaneously carry out their function.

The group succeeded in translating the genes into proteins and replicating the original circular DNA with the translated proteins by using a circular DNA carrying two genes necessary for DNA replication (artificial genomic DNA) and a cell-free transcription-translation system⁽¹⁾. Furthermore, they also successfully improved the DNA to evolve to a DNA with a 10-fold increase in replication efficiency by continuing this DNA replication cycle for about 60 days.

By adding the genes necessary for transcription and translation to the artificial genomic DNA developed by the group, it could be possible to develop artificial cells that can grow autonomously simply by feeding them low-molecular-weight compounds such as amino acids and nucleotides, in the future. If such artificial cells can be created, we can expect that useful substances currently produced using living organisms (such as substances for drug development and food production) will become more stable and easier to control.

This research has been led by Professor Norikazu Ichihashi, a research director of the project “Development of a self-regenerative artificial genome replication-transcription-translation system” in the research area “Large-scale genome synthesis and cell programming” under the JST’s Strategic Basic Research Programs CREST (Team type). In this research area, JST aims to elucidate basic principles in relation to the structure and function of genomes for the creation of a platform technology for the use of cells.

*(1) A cell-free transcription and translation system

A reaction solution containing all the factors necessary for the RNA transcription from genes encoded in DNA and translation into proteins outside the cell. The present study used the reconstituted PURE system (Shimizu et al. Nat Biotechnol. 2001), composed entirely of purified, known proteins and RNA. Hence, the system is free of unknown elements. This system was developed by Yoshihiro Shimizu (RIKEN Center for Frontier Biosciences) and his colleagues in the Takuya Ueda’s laboratory at the University of Tokyo.

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Materials provided by Japan Science and Technology Agency. Note: Content may be edited for style and length.

A research group under Professor Seung-Jae V. Lee from the Department of Biological Sciences identified a single amino acid change in the tumor suppressor protein phosphatase and tensin homolog (PTEN) that dramatically extends healthy periods while maintaining longevity. This study highlights the importance of the well-conserved tumor suppressor protein PTEN in health span regulation, which can be targeted to develop therapies for promoting healthy longevity in humans. The research was published in Nature Communications on September 24, 2021.

Insulin and insulin-like growth factor-1 (IGF-1) signaling (IIS) is one of the evolutionarily conserved aging-modulatory pathways present in life forms ranging from tiny roundworms to humans. The proper reduction of IIS leads to longevity in animals but often causes defects in multiple health parameters including impaired motility, reproduction, and growth.

The research team found that a specific amino acid change in the PTEN protein improves health status while retaining the longevity conferred by reduced IIS. They used the roundworm C. elegans, an excellent model animal that has been widely used for aging research, mainly because of its very short normal lifespan of about two to three weeks. The PTEN protein is a phosphatase that removes phosphate from lipids as well as proteins. Interestingly, the newly identified amino acid change delicately recalibrated the IIS by partially maintaining protein phosphatase activity while reducing lipid phosphatase activity.

As a result, the amino acid change in the PTEN protein maintained the activity of the longevity-promoting transcription factor Forkhead Box O (FOXO) protein while restricting the detrimental upregulation of another transcription factor, NRF2, leading to long and healthy life in animals with reduced IIS.

Professor Lee said, “Our study raises the exciting possibility of simultaneously promoting longevity and health in humans by slightly tweaking the activity of one protein, PTEN.” This work was supported by the MInistry of Science and ICT through the National Research Foundation of Korea.

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Materials provided by The Korea Advanced Institute of Science and Technology (KAIST). Note: Content may be edited for style and length.

Life-threatening fungal infections impact the health of millions of humans across the globe each year. With the limited efficacy of commercially available drugs, the need for novel antifungal compounds is on the rise.

The Wang research team examined the structural dynamics of fungal polysaccharides and their responses to cell wall stress. Specifically, the team examined the cell wall of Aspergillus fumigatus, a fungal pathogen that causes life-threatening disease in immunocompromised individuals.

The research team coupled its expertise in solid-state nuclear magnetic resonance spectroscopy with a functional genomics approach using multiple mutants of Aspergillus fumigatus, each of which selectively eliminates a single type of structural carbohydrate at one time.

“This research strategy allowed us to evaluate the structural role of each major carbohydrate by tracking the changes in cell wall structure after the removal of a component,” Wang said. “The spectroscopy method provided atomic resolution on the structure of polysaccharides and associated proteins using intact fungal cell walls free from any treatment that might perturb the native status of these biomolecules.”

The data led to the development of a revised model of fungal cell wall organization and the assembly of five categories of polysaccharides, including chitin, β-glucan, mannan, α-glucan, and galactosaminogalactan. The findings confirmed an overlooked but prominent role of α-glucans in the cell wall structuration. The mutants produce stiffer and more water-proof cell walls for better protection, which might be a general mechanism used by these microbes to handle stresses.

The research involved an interdisciplinary collaboration with scientists from Institut Pasteur in France, University of Crete in Greece, as well as the Guangxi Academy of Sciences and Chinese Academy of Sciences in China. Scientists involved in this study also utilized instrumentation at the National Science Foundation’s National High Magnetic Field Laboratory in Tallahassee, Fla.

“Now that we revealed the structural principles used by fungi to respond to cell wall defects, it is time to explore how fungi reconstruct this carbohydrate armor to survive through antifungal treatments and severe environments,” said Wang.

Their findings and methodology may open a new research avenue of looking at these complex biomaterials in many different pathogenic fungal species and assessing the mode of actions of novel antifungal molecules, which will assist in the combat against invasive fungal infections.

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Materials provided by Louisiana State University. Note: Content may be edited for style and length.

“We found some unexpected things when we started looking at the effect of these sensory stimuli on individual cells and connections within the worms’ brains,” says Chalasani, member of the Molecular Neurobiology Laboratory and senior author of the new work, published in the journal PLOS Computational Biology on November 9, 2021.

Chalasani is interested in how, at a cellular level, the brain processes information from the outside world. Researchers can’t simultaneously track the activity of each of the 86 billion brain cells in a living human — but they can do this in the microscopic worm Caenorhabditis elegans, which has only 302 neurons. Chalasani explains that in a simple animal like C. elegans, researchers can monitor individual neurons as the animal is carrying out actions. That level of resolution is not currently possible in humans or even mice.

Chalasani’s team set out to study how C. elegans neurons react to smelling each of five different chemicals: benzaldehyde, diacetyl, isoamyl alcohol, 2-nonanone, and sodium chloride. Previous studies have shown that C. elegans can differentiate these chemicals, which, to humans, smell roughly like almond, buttered popcorn, banana, cheese, and salt. And while researchers know the identities of the small handful of sensory neurons that directly sense these stimuli, Chalasani’s group was more interested in how the rest of the brain reacts.

The researchers engineered C. elegans so that each of their 302 neurons contained a fluorescent sensor that would light up when the neuron was active. Then, they watched under a microscope as they exposed 48 different worms to repeated bursts of the five chemicals. On average, 50 or 60 neurons activated in response to each chemical.

By looking at basic properties of the datasets — such as how many cells were active at each time point — Chalasani and his colleagues couldn’t immediately differentiate between the different chemicals. So, they turned to a mathematical approach called graph theory, which analyzes the collective interactions between pairs of cells: When one cell is activated, how does the activity of other cells change in response?

This approach revealed that whenever C. elegans was exposed to sodium chloride (salt), there was first a burst of activity in one set of neurons — likely the sensory neurons — but then about 30 second later, triplets of other neurons began to strongly coordinate their activities. These same distinct triplets weren’t seen after the other stimuli, letting the researchers accurately identify — based only on the brain patterns — when a worm had been exposed to salt.

“C. elegans seems to have attached a high value to sensing salt, using a completely different circuit configuration in the brain to respond,” says Chalasani. “This might be because salt often represents bacteria, which is food for the worm.”

The researchers next used a machine-learning algorithm to pinpoint other, more subtle, differences in how the brain responded to each of the five chemicals. The algorithm was able to learn to differentiate the neural response to salt and benzaldehyde but often confused the other three chemicals.

“Whatever analysis we’ve done, it’s a start but we’re still only getting a partial answer as to how the brain discriminates these things,” says Chalasani.

Still, he points out that the way the team approached the study — looking at the brain’s network-wide response to a stimulus, and applying graph theory, rather than just focusing on a small set of sensory neurons and whether they’re activated — paves the way toward more complex and holistic studies of how brains react to stimuli.

The researchers’ ultimate goal, of course, isn’t to read the minds of microscopic worms, but to gain a deeper understanding of how humans encode information in the brain and what happens when this goes awry in sensory processing disorders and related conditions like anxiety, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders and others.

The other authors of the new study were Saket Navlakha of Cold Spring Harbor Laboratory and Javier How of UC San Diego. The work was supported by grants from the Pew Charitable Trusts, the National Institutes of Health and the National Science Foundation.

The work stems from a discovery made over a decade ago by the late Simon Chan, associate professor of plant biology in the UC Davis College of Biological Sciences, and colleagues.

Plants, like other sexual organisms, inherit a matching set of chromosomes from each parent. In order to transmit a favorable trait, such as pest or drought resistance, to all their offspring, the plant would have to carry the same genetic variant on each chromosome. But creating plants that “breed true” in this way can take generations of cross-breeding.

In 2010, Chan and postdoctoral fellow Ravi Maruthachalam serendipitously discovered a way to eliminate the genetic contribution from one parent while breeding the lab plant Arabidopsis. They had modified a protein called CENH3, found in the centromere, a structure in the center of a chromosome. When they tried to cross wildtype Arabidopsiswith plants with modified CENH3, they got plants with half the normal number of chromosomes. The part of the genome from one parent plant had been eliminated to create a haploid plant.

That work was published in Nature in March 2010, setting off efforts to achieve the same result in crop plants such as maize, wheat and tomato.

Clearing up a mystery

But replicating Chan’s exact strategy outside Arabidopsis has so far proved fruitless, said Professor Luca Comai, UC Davis Department of Plant Biology and Genome Center, who is senior author on the new paper. Recently, other labs have created plants with one set of chromosomes by manipulating CENH3, but it’s not clear how the results are related.

“The mechanistic basis of CENH3 effects on haploid induction was mysterious,” Comai said. There appear to be different rules for each species, he said.

Much of that mystery has now been cleared up. Mohan Marimuthu, researcher at the UC Davis Genome Center and Department of Plant Biology, with Comai, Maruthachalam (now at the Indian Institute of Science Education and Research, Kerala) and colleagues found that when CENH3 protein is altered, it is removed from the DNA in the egg before fertilization, weakening the centromere.

“In the subsequent embryonic divisions, the CENH3-depleted centromeres contributed by the egg fail to compete with the CENH3-rich ones contributed by the sperm and the female genome is eliminated,” Comai said.

The finding that any selective depletion of CENH3 engenders centromere weakness explains the original results by Chan and Maruthachalam as well as new results from other labs in wheat and maize, Comai said. This new knowledge should make it easier to induce haploids in crop plants, he said.

Additional authors on the paper are: at UC Davis, Anne Britt and Sundaram Kuppu; Ramesh Bondada, Indian Institute of Science Education and Research; and Ek Han Tan, University of Maine. The work was supported by grants from CSIRO (Australia), Bill and Melinda Gates Foundation, Gordon and Betty Moore Foundation, Howard Hughes Medical Institute, and the Indian Ministry of Education.

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Materials provided by University of California – Davis. Original written by Andy Fell. Note: Content may be edited for style and length.

The study confirms the behavioral and physical effects of commuting on work quality. The study also shows how data from personal tech devices can help improve employee productivity and satisfaction.

“Your commute predicts your day,” said Andrew Campbell, the Albert Bradley 1915 Third Century Professor of computer science at Dartmouth, the lead researcher and co-author of the study. “This research demonstrates that mobile sensing is capable of identifying how travel to and from the office affects individual workers.”

Participants in the study used a Garmin vivoSmart 3 activity tracker and a smartphone-based sensing app to capture physiological and behavioral patterns during commuting, including activity levels, phone usage, heart rate, and stress. The system also captured external factors such as location, weather, commute duration, and commute variability.

Researchers analyzed data from 275 workers collected over a one-year period prior to the outbreak of the COVID-19 pandemic. The workers, close to 95% of whom drove, were monitored as they traveled. They were also monitored for 30-minute periods before and after commuting.

“We were able to build machine learning models to accurately predict job performance,” said Subigya Nepal a PhD student at Dartmouth and lead author of the paper. “The key was being able to objectively assess commuting stress along with the physiological reaction to the commuting experience.”

The study assessed workers using two recognized criteria of job performance: counterproductive work behavior and organizational citizenship behavior. Counterproductive behavior deliberately harms an organization, whereas citizenship behaviors are beneficial. Baselines for both measures were established regularly through self-reporting questionnaires.

“Compared to low performers, high performers display greater consistency in the time they arrive and leave work,” said Pino Audia, a professor of Management and Organizations at the Tuck School of Business, a senior scientist on the study team, and a co-author of the study. “This dramatically reduces the negative impacts of commuting variability and suggests that the secret to high performance may lie in sticking to better routines.”

Additional differences in the commuting patterns of high and low performers include:

• High performers tend to have physiological indicators that are consistent with physical fitness and stress resilience.
• Low performers have higher stress levels in the times before, during, and after commutes.
• Low performers use their phone more during their commutes.

Overall, the research also found that workers spend more time commuting home from work than they do traveling to work.

According to the study, previous research on commuting indicates that stress, anxiety, and frustration from commuting can lead to a less efficient workforce, increased counterproductive work behavior, and reduced organizational citizenship behavior.

This is the first study using unobtrusive wearables and smartphones to predict worker performance from commuting data alone. According to the researchers, previous studies have used more intrusive and expensive technology — such as headmounts and electrodes — to understand the commuting experience, but no study has previously connected commuting data with the impact on workplace performance.

“The insights from this proof-of-concept study demonstrate that this is an important area of research for future of work,” said Campbell, co-director of Dartmouth’s DartNets Lab.

The study also demonstrates that not all commutes can be bad. By tracking commuting traits such as walking distance and steps, the research confirms that commuters who are involved in active forms of commuting typically experience increased productivity at work.

In the future, the researchers expect that ubiquitous sensing technology will be able to detect commuter stress and offer tailored interventions such as music, podcasts, connecting them to friends and family, or offering tips for short stops.

The study was accepted for publication in Future of Work: COVID-19 and Beyond, a special issue ofIEEE Pervasive Computing.

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Materials provided by Dartmouth College. Original written by David Hirsch. Note: Content may be edited for style and length.