Culture

Reproductive genome from the laboratory

image: The translation factors of the artificial genome come from the bacterium Escherischia coli. These proteins are important for the translation of DNA building instructions into proteins and are therefore essential for self-replicating systems.

Image: 
MPI f. Developmental Biology/ Jürgen Berger

The field of synthetic biology does not only observe and describe processes of life but also mimics them. A key characteristic of life is the ability to ability for replication, which means the maintenance of a chemical system. Scientists at the Max Planck Institute of Biochemistry in Martinsried generated a system, which is able to regenerate parts of its own DNA and protein building blocks.

In the field of synthetic biology, researchers investigate so-called "bottom-up" processes, which means the generation of life mimicking systems from inanimate building blocks. One of the most fundamental characteristics of all living organism is the ability to conserve and reproduce itself as distinct entities. However, the artificial "bottom-up" approach to create a system, which is able to replicate itself, is a great experimental challenge. For the first time, scientists have succeeded in overcoming this hurdle and synthesizing such a system.

Hannes Mutschler, head of the research group "Biomimetic Systems" at the Max Planck Institute for Biochemistry, and his team are dedicated to imitate the replication of genomes and protein synthesis with a "bottom-up" approach. Both processes are fundamental for the self-preservation and reproduction of biological systems. The researchers now succeeded in producing an in vitro system, in which both processes could take place simultaneously. "Our system is able to regenerate a significant proportion of its molecular components itself," explains Mutschler.

In order to start this process, the researchers needed a construction manual as well as various molecular "machines" and nutrients. Translated into biological terms, this means the construction manual is DNA, which contains the information to produce proteins. Proteins are often referred to as "molecular machines" because they often act as catalysts, which accelerate biochemical reactions in organisms. The basic building blocks of DNA are the so-called nucleotides. Proteins are made of amino acids.

Modular structure of the construction manual

Specifically, the researchers have optimized an in vitro expression system that synthesizes proteins based on a DNA blueprint. Due to several improvements, the in vitro expression system is now able to synthesize proteins, known as DNA polymerases, very efficiently. These DNA polymerases then replicate the DNA using nucleotides. Kai Libicher, first author of the study, explains: "Unlike previous studies, our system is able to read and copy comparatively long DNA genomes.

The scientists assembled the artificial genomes from up to eleven ring-shaped pieces of DNA. This modular structure enables them to insert or remove certain DNA segments easily. The largest modular genome reproduced by the researchers in the study consists of more than 116,000 base pairs, reaching the genome length of very simply cells.

Regeneration of proteins

Apart from encoding polymerases that are important for DNA replication, the artificial genome contains blueprints for further proteins, such as 30 translation factors originating from the bacterium Escherischia coli. Translation factors are important for the translation of the DNA blueprint into the respective proteins. Thus, they are essential for self-replicating systems, which imitate biochemical processes. In order to show that the new in vitro expression system is not only able to reproduce DNA, but is also able to produce its own translation factors, the researchers used mass spectrometry. With this analytic method, they determined the amount of proteins produced by the system.

Surprisingly, some of the translation factors were even present in larger quantities after the reaction than added before. According to the researchers, this is an important step towards a continuously self-replicating system that mimics biological processes.

In the future, the scientists want to extend the artificial genome with additional DNA segments. In cooperation with colleagues from the research network MaxSynBio, they want to produce an enveloped system that is able to remain viable by adding nutrients and disposing of waste products. Such a minimal cell could then be used, for example, in biotechnology as a tailor-made production machine for natural substances or as a platform for building even more complex life-like systems.

Credit: 
Max-Planck-Gesellschaft

Hubble turns lens towards gender bias, yielding lessons for Earthlings

The Hubble Space Telescope (HST) is helping find new ways to combat gender bias, according to new research from the University of Colorado Boulder's Leeds School of Business.

Stefanie K. Johnson, associate professor at the Leeds School of Business, worked with co-author Jessica F. Kirk, assistant professor at the University of Memphis, to analyze 16 application cycles for time on HST. Johnson and Kirk found that stripping out nearly all personal information can nearly eliminate gender bias from application processes, likely across industries beyond science.

The group's findings will appear shortly in the Publications of the Astronomical Society of the Pacific.

The committee in charge of granting time on the telescope approached Johnson back in 2016. The Hubble Space Telescope Time Allocation Committee (HST TAC) was looking for ways to level out the acceptance rate between male lead scientists and female lead scientists who proposed projects using the telescope.

The cycles Johnson and Kirk analyzed had 15,545 applications. Among those, only 3,533 proposals had a female lead scientist. Male lead scientists had an acceptance rate of 23%. Female lead scientists had an acceptance rate of 19%.

"The director of the Space Telescope Science Institute was looking for a solution to that gender gap," Johnson said. "Our business research background was a perfect fit for finding insights."

Johnson and Kirk found male reviewers in HST TAC were rating female scientists' proposals significantly worse than male-led proposals.

From the 2013 to 2018, the committee tested several methods of masking the gender of lead scientists, including taking scientists' names off of the front page of the proposal, using a first initial instead of a full name and listing all scientists on a proposal in alphabetical order to hide the lead scientist.

Finally, all scientists' information was removed, and applicants were instructed to write their proposals in a way that would make it difficult for the committee to know who wrote it. This is known as "dual-anonymization."

Female lead scientists performed slightly better than men when the proposals were completely anonymized. Johnson and Kirk found reviewers rated male and female lead scientist's projects equally well--meaning dual-anonymization eliminated the gender bias.

"You're making the fairest decision based on the science," Johnson said. "It's not proof that women will always do better, but hopefully the gender balance will be closer than in years past."

Johnson said companies and organizations have been using dual-anonymization for decades, but the idea has gained visibility since the launch of the women's movement in 2016. Johnson believes the data from her new study shows dual-anonymization could work for nearly any group looking to combat gender bias, not just telescope projects.

"Until now, there hasn't been a lot of data on whether it works or not," said Johnson. "What this shows is that taking gender out of the equation does allow women to perform better."

Credit: 
University of Colorado at Boulder

Global climate frameworks miss the 'big picture' on food, say scientists

image: A man pours 'Aditya' improved variety wheat into the floor duct of a seed cleaning machine in Dhangadhi, Kailali, Nepal.

Image: 
P. Lowe/CIMMYT

Global schemes to fight climate change may miss their mark by ignoring the "fundamental connections" in how food is produced, supplied and consumed, say scientists in a new paper published in the journal Nature Food. Global bodies such as the Intergovernmental Panel on Climate Change (IPCC) and the UN Framework Convention on Climate Change (UNFCCC), handle the different components of the food system separately. This includes crop and livestock production; food processing, storage and transport; and food consumption. Scientists argue this disjointed approach may harm strategies to reduce food emissions and safeguard food from climate impacts, and that a "comprehensive" and "unified" approach is needed.

Food and climate change are deeply interlinked, but food emissions need to be tracked beyond the "farm gate," that is, beyond the emissions arising from growing crops or raising livestock. Researchers are uncovering new insights on how the different subcomponents of the food system contribute to climate change mitigation and adaptation. They argue that we must understand how these components work together -- or clash in some cases -- in order to effectively address agriculture in a changing climate.

A systems approach is crucial for achieving lasting change at a large scale, and for bringing a much broader set of players into the discussion, say the authors. "Actions aimed at changing only some of the component parts of the food system are not going to solve the climate crisis," said Cynthia Rosenzweig, the lead author of the paper. "We need all actors and institutions involved in the many different parts of the food system to understand their roles and impacts, and to make the informed choices needed for widespread transformation," she explained.

Towards a unified food systems approach

The authors recommend that global reporting systems take a unified food systems approach in measuring their emissions. They argue this could improve international and national-level responses to climate change in agriculture in three important ways.

First, a systems approach would allow for much better estimates of the whole food system's contribution to total human-induced greenhouse gases. "Current best estimates of emissions from food production, related land-use changes, processing, consumption and management of food waste, range from 21 to 37 percent of all human-induced emissions," said paper co-author Tek Sapkota, a scientist with the International Maize and Wheat Improvement Centre (CIMMYT). "While this overall figure helps us recognize that the food system is an important source of greenhouse gas emissions, we need a complete accounting of emissions from all components of food systems in order to inform appropriate responses," he explained.

Secondly, a big-picture view could help us understand how growing demand for climate-friendly foods might interact with climate-efficient food production. "There is increasing awareness of the link between diets, nutrition, and climate change, informed by recent studies such as the EAT-Lancet Commission report," said co-author Prajal Pradhan from the Postdam Institute for Climate Impact Research. "Dietary changes are important, but measures need to be taken across the whole system, and must deal with production, consumption and also food loss and waste at all stages of the supply chain."

Finally, the interconnectivity of all parts of the food system means that measures in one area will have positive or negative consequences elsewhere. "We want to avoid situations where strategies to fight climate change, such as growing bioenergy crops or protecting forests, have a detrimental effect on food supply," said Luis G. Barioni, another co-author of the paper based at the Brazilian Agricultural Research Corporation (EMBRAPA). "The goal is to develop actions that strike a balance between food security, adaptation and mitigation. A food system gives us the unique vantage point to assess this," he said.

Many agricultural practices can increase yields and resilience to climate change, while also reducing greenhouse gas emissions, say the authors. Farming techniques that increase the amount of organic matter in soils -- such as leaving behind stems from harvested crops, or using livestock manure for fertilizer -- can boost the resilience of some crops to rising temperatures, without harming yields or increasing emissions. "These interactions are only clear when we look through the lens of the whole food system," emphasized Sapkota. "This kind of understanding is crucial to the success of any climate change response in agriculture."

Credit: 
International Maize and Wheat Improvement Center (CIMMYT)

NIH study supports new approach for treating cerebral malaria

image: Researchers at NIH discovered that specific immune cells accumulate within brain blood vessels of people affected by cerebral malaria. This finding suggests a new treatment strategy for the disease.

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Image courtesy of McGavern Lab/National Institute of Neurological Disorders and Stroke

Researchers at the National Institutes of Health found evidence that specific immune cells may play a key role in the devastating effects of cerebral malaria, a severe form of malaria that mainly affects young children. The results, published in the Journal of Clinical Investigation, suggest that drugs targeting T cells may be effective in treating the disease. The study was supported by the NIH Intramural Research Program.

"This is the first study showing that T cells target blood vessels in brains of children with cerebral malaria," said Dorian McGavern, Ph.D., chief of the Viral Immunology and Intravital Imaging Section at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) who co-directed the study with Susan Pierce, Ph.D., chief of the Laboratory of Immunogenetics at the National Institute of Allergy and Infectious Diseases (NIAID). "These findings build a bridge between mouse and human cerebral malaria studies by implicating T cells in the development of disease pathology in children. It is well established that T cells cause the brain vasculature injury associated with cerebral malaria in mice, but this was not known in humans."

More than 200 million people worldwide are infected annually with mosquito-borne parasites that cause malaria. In a subset of those patients, mainly young children, the parasites accumulate in brain blood vessels causing cerebral malaria, which leads to increased brain pressure from swelling. Even with available treatment, cerebral malaria still kills up to 25% of those affected resulting in nearly 400,000 deaths annually. Children who survive the infection will often have long-lasting neurological problems such as cognitive impairment.

The researchers, led by Drs. Pierce and McGavern, examined brain tissue from 23 children who died of cerebral malaria and 11 children who died from other causes. The scientists used state-of-the-art microscopy to explore the presence of cytotoxic lymphocytes (CTLs) in the brain tissue samples. CTLs are a type of T cell in our immune system that is responsible for controlling infections throughout the body.

Current treatment strategies for cerebral malaria focus on red blood cells, which are thought to clog blood vessels and create potentially fatal blockages leading to extreme pressure in the brain. However, findings in the mouse model demonstrated that CTLs damage blood vessels, leading to brain swelling and death. The role of CTLs in cerebral malaria in children hasn't been thoroughly investigated prior to this study.

The results of the current study demonstrate an increased accumulation of CTLs along the walls of brain blood vessel in the cerebral malaria tissue samples compared to non-cerebral malaria cases. In addition, the CTLs were shown to contain and release effector molecules, which damage cells, suggesting that CTLs play a critical role in cerebral malaria by damaging the walls of brain blood vessels.

"The disease appears to be an immunological accident in which the CTLs are trying to control a parasitic infection but end up injuring brain blood vessels in the process," said Dr. McGavern.

"In separate studies we discovered that treatment of mice with a drug that targets T cells rescued over 60% of otherwise fatal cases of experimental cerebral malaria," said Dr. Pierce. "Given our findings of T cells in the brain vasculature of children who died of the disease, we are excited by the possibility that this drug may be the first therapy for cerebral malaria."

The impact of HIV coinfection on the risk of developing cerebral malaria is not known. The NIH researchers compared CTL patterns in the cerebral malaria cases that were co-infected with HIV and those that were HIV negative. In the HIV-negative cases, the CTLs were seen lining up against the inside wall of brain blood vessels. In the HIV-positive cases, the CTLs had migrated across the surface to the outside of the vessels. There were also significantly more CTLs present in the HIV-positive cases.

Together these findings suggest that CTLs may play an important role in cerebral malaria and that HIV infection may worsen the disease.

Additional research is needed to uncover the role of T cells in human cerebral malaria. Future studies will also investigate how targeting T cells may help treat the disease. Plans for a clinical trial are underway to test the effects of a specific T cell blocker in cerebral malaria patients in Malawi.

Credit: 
NIH/National Institute of Neurological Disorders and Stroke

APS tip sheet: The new fate of the kaon

image: Preliminary reports of an extremely rare decay of a subatomic particle called the kaon could challenge the standard model of particle physics

Image: 
Kitahara et al., Physical Review Letters (2020)

This past September, researchers at KOTO reported four incidents of rare decays from a type of subatomic particle called a kaon. However, the decays should be too rare to detect yet, according to the standard model of particle physics--a theory that describes how matter interacts through fundamental forces like electromagnetism. The decays' presence also violates a well-known theoretical connection between charged and neutral kaon decays, so particle theorists will not accept the findings until this discrepancy is resolved. Recently, scientists Kitahara et al. have found a potential explanation as to why KOTO recognized those rare decays while larger experiments have missed them. They suggest that because KOTO is smaller than other detectors, it may not fully capture the subsequent decay of a new particle from a neutral kaon decay if the new particle flies a long distance before it decays. The presence of such rare decays of the kaon, if confirmed by further experiments, could force physicists to modify the standard model.

Credit: 
American Physical Society

Time of day affects global brain fluctuations

image: The negative association between time of day and brain signal fluctuations was strongest in visual and somatosensory regions.

Image: 
Csaba Orban

As the day progresses, the strength of the brain's global signal fluctuation shows an unexpected decrease, according to a study published on February 18 in the open-access journal PLOS Biology by Csaba Orban and a multi-disciplinary team of scientists from the Faculty of Engineering, Yong Loo Lin School of Medicine and N.1 Institute of Health at the National University of Singapore.

Circadian rhythms govern diverse aspects of physiology including sleep/wake cycles, cognition, gene expression, temperature regulation, and endocrine signaling. But despite the clear influence of circadian rhythms on physiology, most studies of brain function do not report or consider the impact of time of day on their findings.

To address this gap in knowledge, the team analysed functional magnetic resonance imaging (fMRI) data of approximately 900 subjects who were scanned between 8 am and 10 pm on two different days as part of the Human Connectome Project (HCP; http://www.humanconnectomeproject.org/). Multiple studies have shown that the brain's global signal fluctuates more strongly when one is drowsy (e.g. after insufficient sleep), and fluctuates less when one is more alert (e.g. after coffee). Based on known circadian variation in sleepiness, the authors hypothesized that global signal fluctuation would be lowest in the morning, increase in the mid-afternoon and dip in the early evening.

Instead, they observed a cumulative decrease in global signal fluctuation as the day progressed. This global decrease was most prominent in visual and somatosensory brain regions, which are known for expressing dynamic fluctuations within individuals over time. Across the whole brain, time of day was also associated with marked decreases in resting-state functional connectivity - the correlated activity between different brain regions when no explicit task is being performed.

"We were surprised by the size of the overall time-of-day effects, since the global fMRI signal is affected by many factors and there is substantial variation across individuals. At the present moment we don't have a good explanation of the directionality of our findings. However, the fact that we also observed slight time-of-day-associated variation in the breathing patterns of participants suggests that we may also need to consider clues outside of the brain to fully understand these effects," said Csaba Orban, first author of the study.

Based on the findings, the authors recommend that researchers explicitly report the time of day of fMRI scans and other experimental protocols and measurements, as this could help account for between-study variation in results and potentially even failure to replicate findings.

"We hope these findings will motivate fellow neuroscientists to give more consideration to potential effects of time of day on measures of brain activity, especially in other large-scale studies where subjects are often scanned throughout the day for logistical reasons," said Thomas Yeo, the study's senior author.

Credit: 
PLOS

New tool to study how neuronal networks recover their function after neuron loss

image: The infographic shows the great ability of neuronal networks to self-regulate and self-modulate to respond to sudden changes or severe alterations.

Image: 
J. Soriano/UB

A multidisciplinary study led by UB researchers has developed a new experimental tool that enables the application of focalized damage on an in vitro neuronal network of only a few millimetres and record the evolution of the whole network. The objective is to understand the response mechanisms that take place in the brain neuronal circuits, and which prevent a total propagation of the damage while they recover the functionality of the affected circuits. One of the main conclusions is that the network quickly activates self-regulation mechanisms that reinforce the existing connections and restore the functionality of the circuit.

The study, led by Jordi Soriano, researcher at the Institute of Complex Systems of the UB (UBICS), is framed within a multidisciplinary collaboration between UBICS, the Institute of Neurosciences of the UB (UBNeuro), the Institute of Photonic Sciences (ICFO) and Rovira i Virgili University.

The study, published in the journal eNEURO, "shows the great ability of neuronal networks to self-regulate and self-modulate to respond to sudden changes or severe alterations; it is also a good example of the importance of modelling neuronal networks as a complex system, where the whole is richer than the sum of its parts", notes Soriano.

The brain, and in general biological neuronal networks, has response mechanisms towards neuronal loss caused by damage or by a disease. In stroke, for instance, loss of blood supply causes the death of a focalized group of neurons and the alteration of the function of damaged neuronal circuits which, at the same time, alters the function of the neighbouring circuits, potentially starting an avalanche of deterioration. Understanding how these mechanisms work at a network level is intricate due to the sheer size of the brain and the intrinsic difficulty of monitoring in detail the evolution of a great number of neurons before and after the damage. This difficulty can be addressed through the design of in vitro models such as the one proposed by the researchers.

In the experiments, researchers recorded the activity of the whole neuronal network to set their characteristic functionality. They next used a high-power laser to remove a group of neurons and, then, they recorded the network again, to monitor its development over time.

Researchers saw that the closest group of neurons to the affected area loses activity immediately, but it regains activity gradually thanks to the action of the whole network. "Surprisingly, in only fifteen minutes this group reaches activity levels that are similar to the ones from before the damage took place, despite having lost a significant number of impulses from the affected area", says Soriano. "Since fifteen minutes are not enough -continues the researcher- to set new connections, we conclude that the network acts by reinforcing the existing connections, re-driving the flow of neuronal stimuli to the neighbours of the affected area, preventing their deterioration from happening, and therefore, a progressive collapse of the network".

The study, moreover, strengthens the importance of in vitro models as a complementary tool to understand the complexity of the brain and its alterations. In this context, the study is part of the European project MESO-BRAIN, which counts on the participation of the UB researcher Jordi Soriano, to design model neuronal cultures to copy the structure and dynamics of brain regions, allowing researches to study in a controlled way the action of drugs and genetic therapies to treat neurodegenerative diseases.

Credit: 
University of Barcelona

BU study: Late fall may be best time of year to try to conceive

First-of-its-kind study accounts for when couples are most likely to start trying to conceive, finding couples conceive quicker in late fall and early winter, especially in southern states.

In the US, birthdays peak in early September, but in Northern states--and Scandinavia--the peak comes earlier, in the summer or even spring. Although many factors likely go into the popularity of birthday months (a spike in November is popularly attributed to Valentine's Day), seasons themselves may play a role in how easy it is to conceive, according to a new Boston University School of Public Health (BUSPH) study.

The first-of-its-kind study, published in the journal Human Reproduction, finds that, although couples in North America and Denmark are most likely to start trying in September, it's in late November and early December that they have the best chances of conceiving, especially at lower latitudes.

"There are a lot of studies out there that look at seasonal patterns in births, but these studies don't take into account when couples start trying, how long they take to conceive, or how long their pregnancies last," says study lead author Dr. Amelia Wesselink, postdoctoral associate in epidemiology at BUSPH. "After accounting for seasonal patterns in when couples start trying to conceive, we found a decline in fecundability in the late spring and a peak in the late fall," she says. ("Fecundability" refers to the odds of conceiving within one menstrual cycle.) "Interestingly, the association was stronger among couples living at lower latitudes."

The North Americans were more likely than Danes to begin trying to conceive in the fall (possibly in the hopes of giving birth when work is less busy in the summer, Wesselink says, which may be more important in the U.S. than Scandinavia).

But, after taking those patterns into account, season affected fecundability for North Americans by 16 percent, while Danes got only an 8% seasonal boost in the fall and dip in the spring. In southern U.S. states, the seasonal variation was even stronger, at 45%, with a peak in quick conceptions in late November. Meanwhile, the relationship between season and fecundability turned out to be about the same in Denmark and in northern states and Canada.

The study used data on 14,331 pregnancy-planning women who had been trying to conceive for no more than six months, including 5,827 U.S. and Canadian participants in the BUSPH-based Pregnancy Study Online (PRESTO) and 8,504 Danish participants in the Snart Gravid and Snart Foraeldre studies based at Aarhus University in Denmark. These studies follow women with detailed surveys every two months until they either conceive or have tried to conceive for 12 menstrual cycles, gathering data on everything from intercourse frequency and menstruation, to smoking and diet, to education and income.

The findings did not significantly change after controlling for seasonally-varying factors, including intercourse frequency, sugar-sweetened beverage intake, smoking, and medication use.

"Although this study cannot identify the reasons for seasonal variation in fertility, we are interested in exploring several hypotheses on seasonally-varying factors and how they affect fertility, including meteorological variables such as temperature and humidity, vitamin D exposure, and environmental exposures such as air pollution," Wesselink says.

Credit: 
Boston University School of Medicine

Researchers show advance in next-generation lithium metal batteries

image: Professor Min-Kyu Song and graduate student Panpan Dong test a prototype of a lithium metal battery.

Image: 
WSU

PULLMAN, Wash. -- A Washington State University research team has developed a way to address a major safety issue with lithium metal batteries - an innovation that could make high-energy batteries more viable for next-generation energy storage.

The researchers used a formulation for their batteries that led to the formation of a unique, protective layer around their lithium anode, protecting the batteries from degradation and allowing them to work longer under typical conditions. Led by Min-Kyu Song, assistant professor in the WSU School of Mechanical and Materials Engineering, the researchers report on the work in the journal, Nano Energy

Lithium metal is considered the "dream material" for batteries, Song said. That's because among known solid materials, it has the highest energy density, meaning that batteries could run twice as long and hold more energy than the ubiquitous lithium-ion batteries that power most modern-day electronics. While lithium-ion batteries work by passing lithium ions between a graphite anode and a lithium cobalt oxide cathode, the anode in a lithium-metal battery is made of the high-energy lithium metal.

"If we can directly use lithium metal, we can improve the energy density of batteries dramatically," Song said.

While the advantages of lithium metal have been known for decades, researchers have never been able to make them work safely. As electrons travel between the anode and cathode through the external circuit to power a device, Christmas-tree like dendrites begin to form on the lithium metal. The dendrites grow until they cause electric shorts, fires, or explosions. Even if they don't catch on fire, the lithium metal batteries also very rapidly lose their ability to charge.

The WSU research team developed a battery in which they packed selenium disulfide, a non-toxic chemical used in dandruff shampoo, into a porous carbon structure for their cathode. They added two additives to the liquid electrolytes that are typically explored in next-generation lithium batteries.

The two additives worked synergistically and formed a protective layer on the lithium metal surface that was dense, conductive, and robust enough to suppress the growth of dendrites while allowing good cycling stability, Song said. When tested at typical current densities people would use for electronics, the protected lithium metal anode was able to re-charge 500 times and retained high efficiency.

"Such a unique protective layer led to little morphological changes of the lithium anode over cycling and effectively mitigated the growth of lithium dendrites and unwanted side reactions," he said.

The researchers believe their technology can be scalable and cost-effective.

"If commercialized, this novel formulation has real potential," Song said. "Compared to solid-state batteries which are still years away, you don't have to change the manufacturing procedures, and this would be applicable to real industry much sooner, opening up a promising route toward the development of high-energy lithium metal batteries with a long cycle life."

The researchers are continuing to work on the battery, developing a separator that will further protect the battery materials from deterioration and enhance safety without compromising performance.

Credit: 
Washington State University

Rules of life: From a pond to the beyond

image: Researcher Jim Elser and research technician Laura Steger taking samples of water for chemical analysis.

Image: 
Elser Lab/ASU

The Cuatro Cienegas Basin, located in Chihuahuan Desert in Mexico, was once a shallow sea that became isolated from the Gulf of Mexico around 43 million years ago.

This basin has an unusual characteristic of being particularly nutrient-poor and harboring a 'lost world' of many below-ground and above-ground aquatic microbes of ancient marine ancestry.

Because of these characteristics, it is an invaluable place for researchers to study and understand how life may have existed on other planets in our solar system.

In a recent study published in the journal eLIFE a team of researchers, including lead author Jordan Okie of Arizona State University's School of Earth and Space Exploration and senior author Jim Elser of the School of Life Sciences, conducted experiments in the Cuatro Cienegas Basin.

Their goal was to shed light on how fundamental features of an organism's genome - its size, the way it encodes information, and the density of information--affect its ability to thrive in an extreme environment.

"This area is so poor in nutrients that many of its ecosystems are dominated by microbes and may have similarities to ecosystems from early Earth, as well as to past wetter environments on Mars that may have supported life," says lead author Okie.

For their experiment, researchers conducted field monitoring, sampling, and routine water chemistry for 32 days in a shallow, nutrient-poor pond called Lagunita in the Cuatro Cienegas Basin.

First, they installed mescocosms (miniature ecosystems) that served as a control group and remained separate from the rest of the pond. They then added a fertilizer solution that was rich in nitrogen and phosphorus to increase microbial growth in the pond.

At the end of the experiment, they examined how the community in the pond changed in response to the additional nutrients, focusing on their ability to process biochemical information within their cells.

J. Craig Venter Institute associate professor Christopher Dupont, who is a senior author on the study, stated, "We hypothesized that microorganisms found in oligotrophic (low nutrient) environments would, out of necessity, rely on low-resource strategies for replication of DNA, transcription of RNA, and translation of protein. Conversely, a copiotrophic (high nutrient) environment favors resource-intensive strategies."

Ultimately, they found that indeed a nutrient-enriched community became dominated by species that could process biochemical information at a faster rate whereas the original low-nutrient community harbored species with reduced costs of biochemical information processing.

"This study is unique and powerful because it takes ideas from the ecological study of large organisms and applies them to microbial communities in a whole-ecosystem experiment," says Elser. "By doing so, we were able, perhaps for the first time, to identify and confirm that there are fundamental genome-wide traits associated with systematic microbial responses to ecosystem nutrient status, without regard to the species identity of those microbes."

What this may suggest for life on other planets is that organisms, no matter where they are, have to have information-processing machinery fine-tuned to the key resources around them. In turn, the supply of these resources will depend on the planetary environment.

"This is very exciting, as it suggests there are rules of life that should be generally applicable to life on Earth and beyond," says Okie.

Credit: 
Arizona State University

Notre Dame physicists see nuclear wobbling in one isotope of gold

Nuclei can be round, like a soccer ball, or oblong, like a football. Others are slightly oblong but misshapen, like a potato. One of the only two ways to observe the third shape, rarely encountered, is when the nucleus wobbles like a lopsided top.

Researchers had previously seen these rare triaxial nuclei wobble on their shorter, transverse axes. But University of Notre Dame researchers and collaborators recently discovered that the nuclei also wobble on their intermediate axes. Their research, "Longitudinal Wobbling Motion in 187Au," was published recently in the premier physics journal, Physical Review Letters.

The work took four to five days to complete once the team assembled at Argonne National Laboratory, in Illinois. Notre Dame physics graduate student, Nirupama Sensharma, who was the first author on the paper, spent about a year analyzing the data. Her work was highlighted recently in Nature.

Sensharma worked with Umesh Garg, professor in the Department of Physics, to develop an experiment using an isotope of gold to find out if the nucleus wobbled as predicted in a theoretical model developed by Stefan Frauendorf, also a professor in the Department of Physics. Frauendorf had hypothesized that triaxial nuclei would have two different types of wobbling motion.

The fundamental research, which Garg said does not have an immediate application for technology, was chosen as an editor's selection in the journal. It was also highlighted as a synopsis in Physics, the online magazine of the American Physical Society. Papers selected for coverage must include an experimental breakthrough, or provide a theory with a new perspective, among other criteria.

"Where its importance lies is in confirming the predictive power of the underlying theoretical framework, generating more confidence in other predictions about nuclear physics," Garg said. "This, among other things, can help us understand how various processes happen in stellar environments, and how heavy elements, like gold, are formed in the universe."

In 2016 Frauendorf suggested an experiment on a gold nucleus after predicting the wobbling should exist.

"Professor Garg's group created an outstanding experiment to measure the distribution of radiation," Frauendorf said, noting that the experiment validated his prediction.

The work, funded by the U.S. Department of Energy, was completed at the Argonne National Laboratory inside an instrument called Gammasphere. Gammasphere is the world's most powerful gamma ray spectrometer, and collects gamma ray data following the fusion of heavy ions. Inside Gammasphere, a beam of ions and the target nucleus combine to create a much heavier, highly excited nucleus that gives off gamma rays. By observing the pattern and properties of the gamma rays, researchers can discover the structure of the nucleus - and a wobbling nucleus has a very specific structure.

Initially, Garg and his collaborators planned to look for wobbling in 189Au, but ended up accidentally populating another isotope of gold, 187Au, more strongly. The mistake was a serendipitous one.

"That one was right, it turns out," Garg said. "But that's how science goes; if we had done the experiment exactly as planned, I probably would have come back and said, this doesn't very much seem like what we're looking for."

Credit: 
University of Notre Dame

Think all BPA-free products are safe? Not so fast, scientists warn

image: As adverse health effects of BPA have become more widely known, companies have turned to using alternative chemicals to develop plastic products -- namely water bottles and food containers -- and often labeling them "BPA-free."

Image: 
Pexels

Using "BPA-free" plastic products could be as harmful to human health -- including a developing brain -- as those products that contain the controversial chemical, suggest scientists in a new study led by the University of Missouri and published in the Proceedings of the National Academy of Sciences.

For decades, scientists have studied BPA extensively in animal models with results indicating the chemical plays a role in early pregnancy loss, placental diseases and various negative health outcomes after birth. As these adverse health effects have become more widely known, companies have turned to using alternative chemicals to develop plastic products -- namely water bottles and food containers -- and often labeling them "BPA-free." However, MU scientist Cheryl Rosenfeld warns these chemical alternatives, such as bisphenol S (BPS), still aren't safe for people to use.

In the study, Rosenfeld and her colleagues focused on examining the effects of BPS on a mouse's placenta. She said the placenta serves as a historical record of what an unborn child faces while in the womb; the placenta also can transfer whatever the mother might be exposed to in her blood, such as harmful chemicals, into the developing child.

"Synthetic chemicals like BPS can penetrate through the maternal placenta, so whatever is circulating in the mother's blood can easily be transferred to the developing child," said Rosenfeld, a professor of biomedical sciences in the College of Veterinary Medicine, investigator in the Bond Life Sciences Center, and research faculty member for the Thompson Center for Autism and Neurobehavioral Disorders at MU. "This mouse model is the best model we have now to simulate the possible effects of BPS during human pregnancy, because the placenta has a similar structure in both mice and humans."

Rosenfeld adds that the placenta serves as a primary source of serotonin for fetal brain development in both mice and humans. Serotonin, while commonly associated with the feeling of happiness, is a natural chemical that can impact a person's functions, including their emotions and physical activities such as sleeping, eating and digesting food.

"The placenta responds to both natural chemicals as well as synthetic chemicals that the body misinterprets as natural chemicals, but the body doesn't have the ability to mitigate the detrimental effects of such industrial-made chemicals," Rosenfeld said. "More importantly, these chemicals have the ability to lower the placenta's serotonin production. Lower levels of serotonin can compromise fetal brain development because during this critical time in development the brain relies on the placenta to produce serotonin. Thus, developmental exposure to BPA or even its substitute, BPS, can lead to longstanding health consequences."

Rosenfeld's research is an example of an early step in translational medicine, or research that aims to improve human health by determining the relevance of animal science discoveries to people. This research can provide the foundation for precision medicine, or personalized human health care. Precision medicine will be a key component of the NextGen Precision Health Initiative -- the University of Missouri System's top priority -- by helping to accelerate medical breakthroughs for both patients in Missouri and beyond.

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University of Missouri-Columbia

Cognitive behavior therapy for diabetes self-management leads to improved outcomes

A peer-delivered program for managing diabetes and chronic pain was shown to be beneficial for rural adults in communities that might otherwise lack access to physician-led services. Trained community members in rural Alabama delivered a diabetes self-management program that incorporated cognitive behavioral approaches to overcoming pain as a barrier to physical activity. Peer trainers were African American women who had personal experiences with diabetes and were lifelong community members. Similarly, participants were mostly low-income African American women recruited through community connections and assigned to the intervention by town block randomization. Adults who completed the 10-week program showed significant improvements in functional status, pain, and quality of life, when compared to a peer-led general health advice control group. At the end of the program, adults in the cognitive behavioral therapy-based program were more likely to report having no pain or finding alternative exercises when pain prevented them from walking. These results demonstrate that peers trained to deliver CBT-based interventions can improve health outcomes in areas where access is limited.

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American Academy of Family Physicians

Primary care patients assess econsult model for provider-to-specialist consultations

A study across five academic medical centers examined the reaction of patients to the use of an electronic consultation (eConsult) service for primary care provider-to-specialist consultation. This focus group study of adult primary care patients was conducted to better understand patients' opinions, as most previous eConsult studies focused on clinical and financial impacts and clinician responsibility. Fifty-two participants across five focus groups were introduced to the eConsult model and were asked to discuss potential benefits and drawbacks, as well as acceptability of a hypothetical copay and preferences for involvement in future eConsult decision making and communication. Participants in all five focus groups reacted favorably to the eConsult concept; quicker access to specialty care and convenience were cited as key benefits, with approval rates particularly high among those having a trusted primary care provider. Some patients wanted to be involved in eConsult decision making and communication. They also expressed a decreased enthusiasm about eConsults if a copay were to be introduced. A small number of participants were also concerned about potential misuse of the system and about the exclusion of the patient's illness narrative in the eConsult exchange.

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American Academy of Family Physicians

Researchers discover how cells clear misfolded proteins from tissues

image: Diagram of how Clusterin brings misfolded proteins and amyloid β into cells where they can be degraded by lysosomes.

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Itakura et al., 2020

Researchers in Japan have identified a new quality control system that allows cells to remove damaged and potentially toxic proteins from their surroundings. The study, which will be published February 18 in the Journal of Cell Biology, finds that the Clusterin protein and heparan sulfate proteoglycans combine to bring misfolded proteins into cells for degradation. The findings may lead to new therapeutic targets for neurodegenerative disorders, including Alzheimer’s disease.

A number of diseases are believed to be caused by the gradual buildup of misfolded proteins that can aggregate together and damage neurons and other cells in the body. To help prevent this damage, cells have developed numerous quality control systems that recognize misfolded proteins within the cell and either fold them back into their correct shape or else degrade them before they start to aggregate.

“However, approximately 11% of human proteins exist outside of the cell, where they are subjected to even more stresses that may cause them to misfold,” says Eisuke Itakura, an assistant professor in the Department of Biology at Chiba University in Japan. “In addition, Alzheimer’s disease, the most prevalent cause of dementia affecting 47.5 million people worldwide, is characterized by aggregates of amyloid β protein in the extracellular space. Despite this, how aberrant extracellular proteins are degraded remains poorly understood.”

A protein called Clusterin can bind to misfolded extracellular proteins and prevent them from aggregating. In the new study, Itakura and colleagues discovered that Clusterin can escort misfolded proteins into the cell and deliver them to the cell’s garbage-disposal units—the lysosomes—where they can be degraded. The researchers also discovered that, after binding to misfolded proteins, Clusterin enters cells by binding to proteins known as heparan sulfate proteoglycans, which are present on the surface of almost all human cells.

Itakura and colleagues found that, together, Clusterin and heparan sulfate proteoglycans allow many different cell types to internalize and degrade a wide variety of misfolded extracellular proteins. “We therefore think that this pathway is a general extracellular protein quality control system responsible for the clearance of misfolded proteins from diverse tissues and body fluids,” Itakura says.

Intriguingly, the researchers also found that Clusterin and heparan sulfate proteoglycans can import amyloid β into cells for degradation. Mutations in the gene encoding Clusterin have been linked to an increased risk of developing Alzheimer’s disease, and experiments in rats have shown that injecting Clusterin into the brain can prevent amyloid β–induced neurodegeneration. “Our results therefore suggest new avenues for the possible treatment or prevention of disorders such as Alzheimer’s disease that are associated with aberrant extracellular proteins,” Itakura says.

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Rockefeller University Press