Scientists have long been able to analyze the gut microbiome at the level of the 500 to 1,000 different bacterial species that mainly have a beneficial influence; only more recently have they been able to identify individual strains within a single species using powerful genomic tools and supercomputers that analyze massive amounts of genetic data.

Researchers at the University of Alabama at Birmingham now have used their microbiome “fingerprint” method to report that an individualized mosaic of microbial strains is transmitted to the infant gut microbiome from a mother giving birth through vaginal delivery. They detailed this transmission by analyzing existing metagenomic databases of fecal samples from mother-infant pairs, as well as analyzing mouse dam and pup transmission in a germ-free, or gnotobiotic, mouse model at UAB, where the dams were inoculated with human fecal microbes.

“The results of our analysis demonstrate that multiple strains of maternal microbes — some that are not abundant in the maternal fecal community — can be transmitted during birth to establish a diverse infant gut microbial community,” said Casey Morrow, Ph.D., professor emeritus in UAB’s Department of Cell, Developmental and Integrative Biology. “Our analysis provides new insights into the origin of microbial strains in the complex infant microbial community.”

The study used a strain-tracking bioinformatics tool previously developed at UAB, called Window-based Single-nucleotide-variant Similarity, or WSS. Hyunmin Koo, Ph.D., UAB Department of Genetics and Genomics Core, led the informatics analysis. The gnotobiotic mouse model studies were led by Braden McFarland, Ph.D., assistant professor in the UAB Department of Cell, Developmental and Integrative Biology.

Morrow and colleagues have used this microbe fingerprint tool in several previous strain-tracking studies. In 2017, they found that fecal donor microbes — used to treat patients with recurrent Clostridium difficile infections — remained in recipients for months or years after fecal transplants. In 2018, they showed that changes in the upper gastrointestinal tract through obesity surgery led to the emergence of new strains of microbes. In 2019, they analyzed the stability of new strains in individuals after antibiotic treatments, and earlier this year, they found that adult twins, ages 36 to 80 years old, shared a certain strain or strains between each pair for periods of years, and even decades, after they began living apart from each other.

In the current study, several individual-specific patterns of microbial strain-sharing were found between mothers and infants. Three mother-infant pairs showed only related strains, while a dozen other infants of mother-infant pairs contained a mosaic of maternal-related and unrelated microbes. It could be that the unrelated strains came from the mother, but they had not been the dominant strain of that species in the mother, and so had not been detected.

Indeed, in a second study using a dataset from nine women taken at different times in their pregnancies showed that strain variations in individual species occurred in seven of the women.

To further define the source of the unrelated strains, a mouse model was used to look at transmission from dam to pup in the absence of environmental microbes. Five different females were given transplants of different human fecal matter to create five unique humanized-microbiome mice, which were bred with gnotobiotic males. The researchers then analyzed the strains found in the human donors, the mouse dams and their mouse pups. They found four different patterns: 1) The pup’s strain of a particular species was related to the dam’s strain; 2) The pup’s strain was related to both the dam’s strain and the human donor’s strain; 3) The pup’s strain was related to the human donor’s strain, but not to the dam’s strain; and, importantly, 4) No related strains for a particular species were found between the pup, the dam and the human donor. Since these animals were bred and raised in germ-free conditions, the unrelated strains in the pups came from minor, undetected strains in the dams.

“The results of our studies support a reconsideration of the contribution of different maternal microbes to the infant enteric microbial community,” Morrow said. “The constellation of microbial strains that we detected in the infants inherited from the mother was different in each mother-infant pair. Given the recognized role of the microbiome in metabolic diseases such as obesity and type 2 diabetes, the results of our study could help to further explain the susceptibility of the infant to metabolic disease found in the mother.”

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Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

In “The European Union Emissions Trading Scheme and Fuel Efficiency of Fossil Fuel Power Plants in Germany” author Robert Germeshausen studies German power plants and finds that a reduction in fuel use by fossil fuel power plants due to the introduction of the EU ETS translates into reductions in total annual carbon emissions of about 1.5 to 2 percent within the German power sector.

To put this improvement into context, this decrease in fuel input on average is equivalent to a reduction of around four to six million tons in annual carbon emissions. The results point to the role of actual investment in generation technology to improve fuel efficiency as Germeshausen finds positive effects on large investments in machinery.

The power sector is central to climate protection strategies, including those in Germany, where it accounts for around 40 percent of total annual carbon emissions. The Intergovernmental Panel on Climate Change states that reducing the carbon intensity of electricity generation (also known as decarbonizing) is a key component of cost-effective mitigation strategies. “Hence, understanding the effects of existing climate policies on the power sector is crucial for the further development of policies to achieve mitigation targets efficiently,” writes Germeshausen.

The EU ETS puts a price on greenhouse gas emissions from regulated installations to achieve emission reductions and to provide incentives for investments in low-carbon technologies. Germeshausen utilizes administrative annual plant-level data covering around 85 percent of fossil fuel electricity generation in Germany from 2003 to 2012. Germany’s electricity generation fleet consists of a variety of hard coal, lignite, nuclear, and natural gas power plants as well as renewable energy installations.

Germeshausen draws conclusions on the effect of carbon pricing on the optimal input combination in electricity generation and also on fuel efficiency improvements as a measure to reduce carbon emissions in the power sector. He additionally analyzes potential effects on labor efficiency, investments in machinery, and utilization of power plants.

Unlike previous studies on productivity and efficiency effects from policies and regulation in the electricity generation sector, which focus mainly on the effects of deregulation on productivity and efficiency, this study differs with respect to the nature of the influence. “Understanding the impacts on regulated entities is crucial for the assessment and the further development of mitigation policies such as emission trading schemes,” Germeshausen writes. Given the high variable cost share of fuel in power generation, the introduction of a carbon price may provide carbon intensive power plants with an incentive to improve fuel efficiency.

Germeshausen finds that the ETS negatively impacts the capacity factor, i.e., carbon intensive plants produce less output in relation to their potential output compared to less carbon intensive plants. “Thus, the effect should be interpreted as a positive net effect on fuel efficiency, exceeding a potential negative fuel efficiency effect from decreased utilization of carbon intensive power plants.”

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Materials provided by University of Chicago Press Journals. Note: Content may be edited for style and length.

Published in the British-based journal Proceedings of the Royal Society B, the paper by City College scientists led by Michael Hickerson and Laura Bertola is entitled: “Asymmetrical gene flow in five co-distributed syngnathids explained by ocean currents and rafting propensity.”

It reveals that ocean circulation driving macro-algal rafting is believed to serve as an important mode of dispersal for many marine organisms. This leads to predictions on population-level genetic connectivity and the directionality of effective dispersal.

The CCNY Division of Sciences researchers used genome-wide single nucleotide polymorphism data to investigate whether gene flow directionality in two seahorses (Hippocampus) and three pipefishes (Syngnathus) follows the predominant ocean circulation patterns in the Gulf of Mexico and northwestern Atlantic. They also explored whether gene flow magnitudes are predicted by traits related to active dispersal ability and habitat preference.

“We inferred demographic histories of these co-distributed syngnathid species, and coalescent model-based estimates indicate that gene flow directionality is in agreement with ocean circulation data that predicts eastward and northward macro-algal transport,” said Hickerson. “However, the magnitude to which ocean currents influence this pattern appears strongly dependent on the species-specific traits related to rafting propensity and habitat preferences.”

The study, he said, highlights how the combination of population genomic inference together with ocean circulation data can help explain patterns of population structure and diversity in marine ecosystems.

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Materials provided by City College of New York. Note: Content may be edited for style and length.

Inflammation and immunity

When our body faces an infection, it responds with inflammation and fever. This is a sign that the immune system does its work, and leads to the activation of many cells, like soldiers in an army. Dendritic cells (DCs) are the generals of that army. They can precisely activate and instruct the soldiers to kill infected cells by presenting antigens derived from the ‘invaders’ to cells of the immune system.

Mistaken identity

There are several types of DCs that perform antigen-presenting functions in the body. A first type of conventional DCs continuously scan the body for dangerous invaders, even when there is no infection. When there is inflammation triggered by infection, another subset of DCs emerges from inflammatory monocytes. Because monocyte-derived DCs are easily prepared in vitro from monocytes isolated form human blood, it was always assumed these cells were very important antigen-presenting cells. Clinical trials using monocyte-derived DCs in cancer therapy have however been disappointing.

A study by the teams of Bart Lambrecht, Martin Guilliams, Hamida Hammad, and Charlotte Scott (all from the VIB-UGent Center for Inflammation Research) and international colleagues, shows that monocyte-derived DCs are poor antigen-presenting cells, but have wrongly been assumed to have these functions because of a case of mistaken identity.

The scientists studied mice with a viral respiratory infection (pneumonia virus of mice and influenza virus) with single-cell technologies. This single-cell resolution allowed them to finely separate the monocyte-derived cells from other DCs during their response to the infection. They found that monocyte-derived DCs do exist, but actually do not present antigens. The reason for all the confusion in the past is that a look-alike new DC emerges — called inflammatory type 2 conventional DC, or inf-cDC2 — that combines some of the best characteristics of monocytes, macrophages, and conventional DCs, to induce the best form of immunity.

Bart Lambrecht: “This was a big surprise for us. We’ve all been taught that monocyte-derived cells are excellent antigen presenting cells, certainly when there’s inflammation. Now, we show that it’s actually a new hybrid DC type that’s doing all the work. This really changes what we know about the immune system and is very important knowledge for understanding respiratory viral infections and other inflammatory diseases.”

Martin Guilliams: “It took a massive team effort but the strength of single-cell sequencing has finally cracked the complex DC code. Many contradicting findings from the last two decades now make much more sense. This also opens tremendous therapeutic opportunities, since vaccination strategies can now be designed to trigger formation of inf-cDC2s and thus generate a stronger antiviral immune response.”

Charlotte Scott: “Through the use of single cell technologies we have been able to align all the findings from the past few years and identify the distinct cell types involved. Moving forward it will be very interesting to see under what other inflammatory conditions these inf-cDC2s are generated and how they can potentially be targeted therapeutically.”

Convalescent plasma and COVID-19

The findings of the researchers also have a direct relevance for the current COVID-19 pandemic, caused by another respiratory virus. An emergency treatment that is currently being explored is the use of convalescent plasma, or the blood plasma of recovered patients.

Cedric Bosteels, lead author of the new paper: “One of the unique features of the new DCs is that they express functional Fc receptors for antibodies that are found in the plasma of patients who have recovered from COVID-19”

This study is the first to show that one of the mechanisms through which convalescent plasma and the virus-specific antibodies in it work, is via boosting of inf-cDC2. Since boosted DCs induce a much stronger immune response, this study reveals a new target for therapeutic intervention for viral infections and other inflammatory diseases.

Funding

This study was funded by the European Research Council, University Ghent, Research Foundation Flanders (FWO), and the Health Research Council New Zealand.

“We know that sleep is involved in creativity and insight,” said senior author Paul Shaw, PhD, a professor of neuroscience. “Have you ever slept on a problem, and when you wake up you’ve found the answer? Anxiety keeps people up at night, but if you find yourself in a dangerous environment, or in a situation that you don’t know how to deal with, sleep may be exactly what you need to respond to it effectively.”

Fruit flies’ sleep looks a lot like people’s. Baby flies need a lot of sleep, but as they get older, their need for sleep diminishes. Flies become more alert with caffeine and drowsier with antihistamines. And if you keep a fly awake one day, it will sleep more the next.

These similarities suggest that the sleep habits of flies might shed light on the sleep habits of people. To explore the relationship between challenging circumstances and sleep, Shaw and staff scientist and first author Krishna Melnattur, PhD, took away flies’ ability to fly.

Baby flies must expand their wings in the first half hour or so after emerging from pupal cases, or their wings will not develop properly. The researchers placed some newly emerged flies in tiny containers so they could not expand their wings, and they genetically modified other flies so that the insects’ wings failed to expand. Both scenarios rendered the young flies permanently flightless. The researchers also grounded older flies by disabling their wings. In all cases, faced with the inability to fly, the animals slept more than usual.

In subsequent experiments, the researchers traced the neurological circuit that signals to the brain that the wings aren’t functioning and triggers the impulse to sleep more.

“When we identified the neurons that were activated when we cut or glued the wings of adult flies, they turned out to be the same neurons involved in the normal developmental process of wing expansion after emergence,” Melnattur said.

The fact that wing injury and normal wing development are linked to sleep through the same neurological circuitry makes sense from an evolutionary standpoint, the researchers said. The circuit is active in young flies because their developing brains need sleep as the animals expand their wings, learn to fly and begin to navigate the world around them.

“And then the whole circuit can get reactivated later in life when something happens that forces a fly to adapt to a new normal,” Shaw said. “Suddenly, its brain needs to be as flexible as when it was young. It can no longer fly, but it still needs to get food, it needs to compete for mates, it needs to avoid dying. We think that sleep amplifies the brain plasticity the fly needs to survive.”

Shaw and Melnattur are planning experiments to determine whether increased sleep helps flightless flies survive. Their findings also may provide clues to why some people sleep more than others and why some sleep disorders arise.

“There’s huge variation in sleep time among people,” Shaw said. “Some people need five hours a night; some need nine. Sleep is an ancient process, and we’ve evolved mechanisms to change our sleep-wake balance to help us meet our needs. If these mechanisms get inappropriately activated, say by a traumatic event that triggers post-traumatic stress disorder, it can create a situation in which you’re sleeping too much or too little and it’s no longer matching up with your needs, and then you have a sleep disorder.”

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Materials provided by Washington University School of Medicine. Original written by Tamara Bhandari. Note: Content may be edited for style and length.

“Cheetahs are the fastest creatures on land, and they derive their speed and power from the flexing of their spines,” says Jie Yin, an assistant professor of mechanical and aerospace engineering at North Carolina State University and corresponding author of a paper on the new soft robots.

“We were inspired by the cheetah to create a type of soft robot that has a spring-powered, ‘bistable’ spine, meaning that the robot has two stable states,” Yin says. “We can switch between these stable states rapidly by pumping air into channels that line the soft, silicone robot. Switching between the two states releases a significant amount of energy, allowing the robot to quickly exert force against the ground. This enables the robot to gallop across the surface, meaning that its feet leave the ground.

“Previous soft robots were crawlers, remaining in contact with the ground at all times. This limits their speed.”

The fastest soft robots until now could move at speeds of up to 0.8 body lengths per second on flat, solid surfaces. The new class of soft robots, which are called “Leveraging Elastic instabilities for Amplified Performance” (LEAP), are able to reach speeds of up to 2.7 body lengths per second — more than three times faster — at a low actuation frequency of about 3Hz. These new robots are also capable of running up steep inclines, which can be challenging or impossible for soft robots that exert less force against the ground.

These “galloping” LEAP robots are approximately 7 centimeters long and weigh about 45 grams.

The researchers also demonstrated that the LEAP design could improve swimming speeds for soft robots. Attaching a fin, rather than feet, a LEAP robot was able to swim at a speed of 0.78 body lengths per second, as compared to 0.7 body lengths per second for the previous fastest swimming soft robot.

“We also demonstrated the use of several soft robots working together, like pincers, to grab objects,” Yin says. “By tuning the force exerted by the robots, we were able to lift objects as delicate as an egg, as well as objects weighing 10 kilograms or more.”

The researchers note that this work serves as a proof of concept, and are optimistic that they can modify the design to make LEAP robots that are even faster and more powerful.

“Potential applications include search and rescue technologies, where speed is essential, and industrial manufacturing robotics,” Yin says. “For example, imagine production line robotics that are faster, but still capable of handling fragile objects.

“We’re open to collaborating with the private sector to fine-tune ways they can incorporate this technology into their operations.”

The work was done with support from the National Science Foundation under grants 2010717 and 2005374.

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

Researchers from Penn State’s College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures. The researchers also say they have devised a unique way to create plasma directly in liquids.

The team, comprised of engineers, physicists, veterinary and biomedical scientists and medical professionals, is using an atmospheric-pressure plasma jet to use room temperature — “cold” — plasma to treat bacteria.

Plasma, the fourth state of matter, is typically very hot — thousands to millions of degrees. By using plasma generated at atmospheric pressure or in liquids, the researchers can create molecules and atoms with antibacterial effects without burning anything. Sean Knecht, assistant teaching professor of engineering design at Penn State and leader of the Cross-disciplinary Laboratory for Integrated Plasma Science and Engineering, said this process creates many different types of reactive particles, making the likelihood of bacterial mutations to simultaneously combat all the particles almost nonexistent.

Knecht explained that the team’s research results, published in Scientific Reports, show that plasma technology generates large amounts of reactive oxygen species or reactive particles created from molecules that contain oxygen atoms, including oxygen molecules in the air and water vapor. The plasma’s effect on different bacteria such as E. coli and Staph. aureus is significant, resulting in many bacterial deaths through multiple generations.

“Over the course of four generations of bacteria, these bacteria do not acquire any form of resistance to the plasma treatment,” he said.

Girish Kirimanjeswara, associate professor of veterinary and biomedical sciences at Penn State, said this is extremely important due to the typical way bacteria mutate, making them resistant to antibiotics.

Antibiotics target a specific metabolic pathway, essential protein or nucleic acids in bacteria. Because of this, antibiotics have to enter a bacterial cell to find and bind to that specific target. Any bacterial mutation that decreases an antibiotic’s entry capabilities or increases its rate of exit makes the antibiotic less effective. Mutations happen naturally at a low rate but can rapidly accumulate by selection pressure when introduced to antibiotics aimed at fighting the bacteria.

According to Kirimanjeswara, the team’s research results show that plasma treatment produces various reactive oxygen species at a concentration high enough to kill bacteria, but low enough to not have negative impacts on human cells. He explained that the oxygen species quickly target virtually every part of the bacteria including proteins, lipids and nucleic acids.

“One can call it a sledgehammer approach,” Kirimanjeswara said. “It is difficult to develop resistance by any single mutation or even by a bunch of mutations.”

The team also applied these findings to design a system that can create plasma directly in liquids. The researchers intend to create plasma in blood to address cardiovascular infections directly at the source. To do so, high electric voltage and large electric currents are typically used. In the plasma system created by the researchers, the electrical current and energy that might reach the patient are minimized by using dielectric, or electrically-insulating, materials. Materials that the team would typically use to create the plasma include glass and ceramic due to their capability to withstand high local temperatures. These materials tend to make blood clot and may not be very flexible, a necessity if they are to be used in the cardiovascular system. The team is investigating insulating coatings that are biocompatible, or acceptable by the human body, and flexible. Knecht said the team has identified a polymer called Parylene-C and reported the initial results in the journal IEEE Transactions on Radiation and Plasma Medical Sciences. The team is further pursuing this avenue, as polymers have low melting points and may not withstand repeated exposure to plasma.

“Biocompatible polymers can be used for plasma generation in biological liquids, but their lifetime is limited,” Knecht said. “New unique plasma generation designs must be developed to produce lower intensity plasma discharges that can extend their lifetime. That is what we are continuing to work on.”

Kirimanjeswara said scientists typically work to understand how different bacteria cause disease or how host immune responses eliminate bacteria to create new antibiotics and vaccines. Though these more traditional approaches are essential, they are often gradual and time-consuming. The team’s innovative research highlights the importance of continuing to investigate new ways to combat bacteria.

“Transformative and cross-disciplinary approaches have the potential to speed up finding solutions to urgent global problems,” he said. “It is important for the general public to be aware of and appreciate the fact that the scientific community is engaged in several approaches, some traditional and others nontraditional, to combat the growing problem of antibiotic resistance. We hope our research reinforces the idea of embracing nonantibiotic approaches to treat bacterial infections in the future.”

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Materials provided by Penn State. Original written by Samantha Chavanic. Note: Content may be edited for style and length.

A team led by James Sacchettini, Ph.D. professor and Welch Chair of Science, and Vishal Gohil, Ph.D., associate professor, both from the Department of Biochemistry and Biophysics at Texas A&M University, published a paper in Science outlining their latest discoveries of how using the cancer drug elesclomol holds promise for treating copper deficiencies in Menkes disease.

The research funding was provided by the Chancellor’s Research Initiative of The Texas A&M University System, the Welch Foundation and the National Institutes of Health.

“With all biology connected, it’s great to see this innovative research from the agriculture and life sciences departments making a significant connection to an area of human health,” said Patrick J. Stover, Ph.D., vice chancellor of Texas A&M AgriLife, dean of the College of Agriculture and Life Sciences and director of AgriLife Research.

Menkes disease

Menkes is a rare genetic disorder occurring in about 1 in every 50,000-300,000 births. Young children with the disorder typically die within three years of life due to a genetic mutation that limits their body’s ability to absorb and utilize copper from their diet. The copper deficiency leads to severe brain damage and neuromuscular deficits.

“Experimental treatments have not been effective at overcoming the most severe symptoms of the disease or early mortality,” Sacchettini said.

“Our current work documenting the efficacy of elesclomol in a mouse model of Menkes disease takes us one step closer to the clinical trials,” Gohil said.

Copper deficiency

Normally, copper is acquired through diet from foods such as fish, organ meats, nuts and beans, said Liam Guthrie, a doctoral candidate in Sacchettini’s lab and lead author of the paper. He explained that dietary copper is normally absorbed in the intestines, then exported to the liver for distribution throughout the body.

In Menkes disease, that process is disrupted. The copper absorbed by intestinal cells must be exported into the blood by a copper transport protein. If that protein is not functioning well, due to genetic mutations, the copper can’t be distributed to various parts of the body. The brain, heart and other tissues thus become copper deficient.

And, when copper is deficient in these tissues, certain enzymes fail to activate, Gohil explained. One such enzyme is mitochondrial cytochrome oxidase complex, which is required for energy production.

“Mitochondrial cytochrome oxidase is an enzyme present in almost all cells in our body and uses a majority of the oxygen that we breathe,” Gohil said.

This enzyme only works if it has copper in it, he explained. Without copper, the enzyme won’t function, and the body stops working due to lack of energy production.

Finding the drug

Gohil began working on this project in 2012, and in 2014 his team began focusing on elesclomol and showed that it can deliver copper to mitochondria and restore the production of cytochrome oxidase protein complex in copper-deficient yeast and human cells, as well as in zebrafish.

In 2017, Gohil’s graduate student Shivatheja Soma and postdoctoral fellow Mohammad Zulkifli, Ph.D., began collaborating with Guthrie, Andres Silva and others from the Sacchettini group. They began to translate the laboratory results into a preclinical mouse model of Menkes disease.

The team focused on developing procedures for using elesclomol to treat Menkes and optimizing treatment strategies to find the right doses.

“These were difficult and time-consuming experiments that required special precautions because we were working with very sick mice, ones that carried the same type of mutation as humans with severe Menkes disease,” Guthrie said. “These mice showed very similar symptoms to babies with the disease. We had hope that if we could successfully treat these mice, we would be able to translate the discoveries to infants.”

Sacchettini said the first step was to overcome the side effects of using a cancer drug to treat the disease. The major breakthrough came when their group came up with a new way to prepare the drug.

“We found that by mixing elesclomol with copper in a special formulation, we could keep the new form of the drug soluble prior to administration,” he said. “With this approach we were able to dramatically increase survival of the mice and, importantly, to normalize their brain development.”

The collaborators from the University of Maryland, led by Byung-Eun Kim, Ph.D., showed that elesclomol could overcome more than just defects in the transporter that causes Menkes disease. The medication also targeted a second copper transporter, one implicated in the development of hypertrophic heart and liver disorders in mice and humans — indicating the therapeutic applications of elesclomol may not be limited to Menkes disease.

Gohil’s group and Michael Petris, Ph.D., from the University of Missouri, showed that elesclomol escorted copper to different tissues and delivered it to copper-utilizing enzymes like cytochrome c oxidase in mitochondria.

Promising results

Through this mechanism, elesclomol prevented brain damage and improved the survival of Menkes mice from a mere 14 days to over 200 days.

While there is still more work to do in preparation for treating infants with Menkes disease, Sacchettini and Gohil say they are confident they will soon be able to extend the survival and quality of life for those born with this devastating disease.