Leftover bacteria fragments may extend symptoms of Lyme disease

 

• For some people with Lyme disease, symptoms extend well beyond “successful” treatment with antibiotics.
• A new study finds that dead, left-behind bits of the bacteria that cause Lyme disease may be the culprit.
• The research shows that these unviable fragments cause even more neurological and musculoskeletal inflammation than the live bacteria.
• It is hoped that future treatment can neutralize or clear out these lingering fragments.

A 2-to-4-week regimen of oral antibiotics cures Lyme disease for most people. However, for some, the symptoms linger for months. Among these symptoms are cognitive dysfunction — difficulty thinking — and musculoskeletal pain.

A new study from researchers at Tulane University, in New Orleans, has discovered what may be the reason.

After antibiotics have treated the bacteria responsible for Lyme disease, dead fragments are left behind, and these cause inflammation in the central and peripheral nervous systems.

Lead study author Dr. Geetha Parthasarathy, an assistant professor of microbiology and immunology at Tulane University’s National Primate Research Center, explains:

“As neuroinflammation is the basis of many neurological disorders, lingering inflammation in the brain due to these unresolved fragments could cause long-term health consequences.”

Dr. Michal Křupka, of Palacký University Olomouc, in Czechia — who was not involved in the study — told Medical News Today, “Excessive activation of the immune system is thought to play a role in this case, rather than the infection itself.”

Traces of post-treatment Lyme disease syndrome

According to the study, 10–35% of people with Lyme disease eventually develop post-treatment Lyme disease syndrome (PTLDS).

In PET brain scans of people with PTLDS, other researchersTrusted Source have detected signs of glial activation many months after treatment, signifying persistent neuroinflammation. Glial cells are types of brain cells; they play a number of supporting roles for neurons.

The type of bacteria that cause Lyme disease is Borrelia burgdorferi.

For this study, the researchers analyzed the effect of B. burgdorferi detritus in the brains of rhesus macaques who had been exposed to sonicated fragments of the bacteria. Sonication involves using ultrasound vibration to break up cells.

In particular, the team investigated the effects of these fragments in the frontal cortex and dorsal root gangliaTrusted Source of the monkeys.

Surprisingly, glial inflammation in these areas was several times more pronounced than it was in macaques who had been exposed to live B. burgdorferi. Researchers found that it was significantly more prevalent in the frontal cortex than in the dorsal root ganglion.

The researchers demonstrated that B. burgdorferi fragments resulted in the cell death of neurons.

They speculate that bacteria broken down by antibiotics release “multiple ligands, such as lipoproteins, flagellins, DNA, RNA, and others” in higher quantities than live bacteria.

Post-infection havoc

In someone with Lyme disease, B. burgdorferi enter the body through a tick bite. It can cause a characteristic bull’s-eye rash, followed by a headache, a fever, and malaise, after which the bacteria disseminate to other organs.

“Fragments do not have to travel to the brain,” said Dr. Křupka. “It would probably be parts of bacteria that entered the brain during acute neuroinfection, and [which] may persist even after antibiotic treatment. These residues could then cause a chronic inflammatory reaction.”

Dr. Parthasarathy plans further investigation into ineffective clearing out of bacterial fragments. She also intends to explore new anti-inflammatory strategies for B. burgdorferi.

Source: Medical News Today

Changing your diet could add up to a decade to life expectancy, study finds

 A young adult in the U.S. could add more than a decade to their life expectancy by changing their diet from a typical Western diet to an optimized diet that includes more legumes, whole grains and nuts, and less red and processed meat, according to a new study publishing Feb. 8 in PLOS Medicine by Lars Fadnes of the University of Bergen, Norway, and colleagues. For older people, the anticipated gains to life expectancy from such dietary changes would be smaller but still substantial.

Food is fundamental for health and, globally, dietary risk factors are estimated to lead to 11 million deaths and 255 million disability-adjusted life-years annually. In the new study, researchers used existing meta-analyses and data from the Global Burden of Diseases study to build a model that enables the instant estimation of the effect on life expectancy (LE) of a range of dietary changes. The model is also now available as a publicly available online tool called the Food4HealthyLife calculator (https://food4healthylife.org/).

For young adults in the United States, the model estimates that a sustained change from a typical Western diet to the optimal diet beginning at age 20 would increase LE by more than a decade for women (10.7 [uncertainty interval 5.9-14.1] years) and men (13.0 [6.9-17.3] years). The largest gains in years of LE would be made by eating more legumes (females: 2.2 [1.0-3.4]; males: 2.5 [1.1-3.9]), more whole grains (females: 2.0 [0.7-3.3]; males: 2.3 [0.8-3.8]), and more nuts (females: 1.7 [0.8-2.7]; males: 2.0 [1.0-3.0]), less red meat (females: 1.6 [0.7-2.5]; males: 1.9 [0.8-3.0]) and less processed meat (females: 1.6 [0.7-2.5]; males: 1.9 [0.8-3.0]). Changing from a typical diet to the optimized diet at age 60 years could still increase LE by 8.0 (4.8-11.2) years for women and 8.8 (5.2-12.5) years for men, and 80-year-olds could gain 3.4 years (females: 2.1-4.7 and males: 2.1-4.8) from such dietary changes.

"Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains," the authors say. "The Food4HealthyLife calculator could be a useful tool for clinicians, policy makers, and lay-people to understand the health impact of dietary choices."

Fadnes adds, "Research until now have shown health benefits associated with separate food group or specific diet patterns but given limited information on the health impact of other diet changes. Our modeling methodology has bridged this gap."

Source: ScienceDaily

Global study finds the extent of pharmaceutical pollution in the world's rivers

 A new study looking at the presence of pharmaceuticals in the world's rivers found concentrations at potentially toxic levels in more than a quarter of the locations studied.

The new study looked at 258 rivers across the globe, including the Thames in London and the Amazon in Brazil, to measure the presence of 61 pharmaceuticals, such as carbamazepine, metformin and caffeine.

The researchers studied rivers in over half of the world's countries -- with rivers in 36 of these countries having never previously been monitored for pharmaceuticals.

The study forms part of the University of York-led Global Monitoring of Pharmaceuticals Project, which has expanded significantly over the last two years, with the new study becoming the first truly global-scale investigation of medicinal contamination in the environment.

With their latest study, the researchers found that:

• pharmaceutical pollution is contaminating water on every continent
• strong correlations between the socioeconomic status of a country and higher pollution of pharmaceuticals in its rivers (with lower-middle income nations the most polluted)
• high levels of pharmaceutical pollution was most positively associated with regions of high median age as well as high local unemployment and poverty rates
• the most polluted countries and regions of the world are the ones that have been researched the least (namely sub-saharan Africa, South America and parts of southern Asia).
• the activities most associated with the highest levels of pharmaceutical pollution included rubbish dumping along river banks, inadequate wastewater infrastructure and pharmaceutical manufacturing, and the dumping of the contents of residual septic tanks into rivers.

The study revealed that a quarter of the sites contained contaminants (such as sulfamethoxazole, propranolol, ciprofloxacin and loratadine) at potentially harmful concentrations.

The researchers hope that by increasing the monitoring of pharmaceuticals in the environment, they can develop strategies to limit the effects potentially caused by the presence of pollutants.

The study included noteworthy rivers such as the Amazon, Mississippi, Thames and the Mekong. Water samples were obtained from sites spanning from a Yanomami Village in Venezuela, where modern medicines are not used, to some of the most populated cities on the planet, such as Delhi, London, New York, Lagos, Las Vegas, and Guangzhou.

Areas of political instability such as Baghdad, the Palestinian West Bank and Yaoundé in Cameroon were also included. The climates where samples were obtained varied from high altitude alpine tundra in Colorado and polar regions in Antarctica, to Tunisian deserts.

While previous studies have monitored active pharmaceuticals ingredients (APIs) in rivers, these have ignored many of the countries of the world, have typically measured only a select few contaminants, and employed different analytical methods. Cumulatively, this has made it difficult to quantify the scale of the problem from a global perspective.

The water sample analysis occurred at the University of York's Centre of Excellence in Mass Spectrometry.

Co-leader of the project Dr John Wilkinson, from the Department of Environment and Geography, said: "With 127 collaborators across 86 institutions worldwide, the Global Monitoring of Pharmaceuticals Project is an excellent example of how the global scientific community can come together to tackle large-scale environmental issues.

"We've known for over two decades now that pharmaceuticals make their way into the aquatic environment where they may affect the biology of living organisms. But one of the largest problems we have faced in tackling this issue is that we have not been very representative when monitoring these contaminants, with almost all of the data focused on a select few areas in North America, Western Europe and China.

"Through our project, our knowledge of the global distribution of pharmaceuticals in the aquatic environment has now been considerably enhanced. This one study presents data from more countries around the world than the entire scientific community was previously aware of: 36 new countries to be precise where only 75 had ever been studied before."

The researchers suggest their approach could also be expanded in the future to include other environmental media such as sediments, soils and biota, and could allow for the development of global-scale datasets on pollution.

'' is published in Proceedings of the National Academy of Science (PNAS).

The data for specific rivers will be available in the supplemental information associated with the publication (via PNAS). It will also be published on the Global Monitoring of Pharmaceuticals Project website.

The study used 'predicted no adverse effect concentrations (PNECs)' to determine where there may be risk for adverse effects (such as toxicity). If the team measured a concentration in the environment above the PNEC, then there was potential for organisms living there to be adversly affected by the pharmaceutical. This can manifest in many ways largely dependent on what the pharmaceutical is, what organism is being exposed and at what concentration. Examples can include disrupted reproductive capabilities, altered behaviour or physiology and even changes in heart rate.

The contaminants found at potentially harmful concentrations include:

• propranolol (a beta-blocker for heart problems such as high blood pressure)
• sulfamethoxazole (an antibiotic for bacterial infection)
• ciprofloxacin (an antibiotic for bacterial infection)
• loratadine (an antihistamine for allergies)

Source: ScienceDaily

Time crystals that persist indefinitely at room temperature could have applications in precision timekeeping

 We have all seen crystals, whether a simple grain of salt or sugar, or an elaborate and beautiful amethyst. These crystals are made of atoms or molecules repeating in a symmetrical three-dimensional pattern called a lattice, in which atoms occupy specific points in space. By forming a periodic lattice, carbon atoms in a diamond, for example, break the symmetry of the space they sit in. Physicists call this "breaking symmetry."

Scientists have recently discovered that a similar effect can be witnessed in time. Symmetry breaking, as the name suggests, can arise only where some sort of symmetry exists. In the time domain, a cyclically changing force or energy source naturally produces a temporal pattern.

Breaking of the symmetry occurs when a system driven by such a force faces a déjà vu moment, but not with the same period as that of the force. 'Time crystals' have in the past decade been pursued as a new phase of matter, and more recently observed under elaborate experimental conditions in isolated systems. These experiments require extremely low temperatures or other rigorous conditions to minimize undesired external influences, called noise.

In order for scientists to learn more about time crystals and employ their potential in technology, they need to find ways to produce time crystalline states and keep them stable outside the laboratory.

Cutting-edge research led by UC Riverside and published this week in Nature Communications has now observed time crystals in a system that is not isolated from its ambient environment. This major achievement brings scientists one step closer to developing time crystals for use in real-world applications.

"When your experimental system has energy exchange with its surroundings, dissipation and noise work hand-in-hand to destroy the temporal order," said lead author Hossein Taheri, an assistant research professor of electrical and computer engineering in UC Riverside's Marlan and Rosemary Bourns College of Engineering. "In our photonic platform, the system strikes a balance between gain and loss to create and preserve time crystals."

The all-optical time crystal is realized using a disk-shaped magnesium fluoride glass resonator one millimeter in diameter. When bombarded by two laser beams, the researchers observed subharmonic spikes, or frequency tones between the two laser beams, that indicated breaking of temporal symmetry and creation of time crystals.

The UCR-led team utilized a technique called self-injection locking of the two lasers to the resonator to achieve robustness against environmental effects. Signatures of the temporally repeating state of this system can readily be measured in the frequency domain. The proposed platform therefore simplifies the study of this new phase of matter.

Without the need for a low temperature, the system can be moved outside a complex lab for field applications. One such application could be highly accurate measurements of time. Because frequency and time are mathematical inverses of each other, accuracy in measuring frequency enables accurate time measurement.

"We hope that this photonic system can be utilized in compact and lightweight radiofrequency sources with superior stability as well as in precision timekeeping," said Taheri.

The open-access Nature Communications paper, "All-optical dissipative discrete time crystals," is available here. Taheri was joined in the research by Andrey B. Matsko at NASA's Jet Propulsion Laboratory, Lute Maleki at OEwaves Inc. in Pasadena, Calif., and Krzysztof Sacha at Jagiellonian University in Poland.

Source: ScienceDaily

Mapping mutation ‘hotspots’ in cancer reveals new drivers and biomarkers

 Researchers led by bioengineers at the University of California San Diego have identified and characterized a previously unrecognized key player in cancer evolution: clusters of mutations occurring at certain regions of the genome. The researchers found that these mutation clusters contribute to the progression of about 10% of human cancers and can be used to predict patient survival.

The findings are reported in a paper published Feb. 9 in Nature.

The work sheds light on a class of mutations called clustered somatic mutations -- clustered meaning they group together at specific areas in a cell's genome, and somatic meaning they are not inherited, but caused by internal and external factors such as aging or exposure to UV radiation, for example.

Clustered somatic mutations have so far been an understudied area in cancer development. But researchers in the lab of Ludmil Alexandrov, a professor of bioengineering and cellular and molecular medicine at UC San Diego, saw something highly unusual about these mutations that warranted further study.

"We typically see somatic mutations occurring randomly across the genome. But when we looked closer at some of these mutations, we saw that they were occurring in these hotspots. It's like throwing balls on the floor and then suddenly seeing them cluster in a single space," said Alexandrov. "So we couldn't help but wonder: What is happening here? Why are there hotspots? Are they clinically relevant? Do they tell us something about how cancer has developed?"

"Clustered mutations have largely been ignored because they only make up a very small percentage of all mutations," said Erik Bergstrom, a bioengineering PhD student in Alexandrov's lab and the first author of the study. "But by diving deeper, we found that they play an important role in the etiology of human cancer."

The team's discoveries were enabled by creating the most comprehensive and detailed map of known clustered somatic mutations. They started by mapping all the mutations (clustered and non-clustered) across the genomes of more than 2500 cancer patients -- an effort that in total encompassed 30 different cancer types. The researchers created their map using next-generation artificial intelligence approaches developed in the Alexandrov lab. The team used these algorithms to detect clustered mutations within individual patients and elucidate the underlying mutational processes that give rise to such events. This led to their finding that clustered somatic mutations contribute to cancer evolution in approximately 10% of human cancers.

Taking it a step further, the researchers also found that some of the cancer-driving clusters -- specifically those found in known cancer driver genes -- can be used to predict the overall survival of a patient. For example, the presence of clustered mutations in the BRAF gene -- the most widely observed driver gene in melanoma -- results in better overall patient survival compared to individuals with non-clustered mutations. Meanwhile, the presence of clustered mutations in the EGFR gene -- the most widely observed driver gene in lung cancer -- results in decreased patient survival.

"What's interesting is that we see differential survival in terms of just having clustered mutations detected within these genes, and this is detectable with existing platforms that are commonly used in the clinic. So this acts as a very simple and precise biomarker for patient survival," said Bergstrom.

"This elegant work emphasizes the importance of developing AI approaches to elucidate tumor biology, and for biomarker discovery and rapid development using standard platforms with direct line of sight translation to the clinic," said Scott Lippman, director of Moores Cancer Center and associate vice chancellor for cancer research and care at UC San Diego. "This highlights UC San Diego's strength in combining engineering approaches in artificial intelligence for solving current problems in cancer medicine."

A new mode of cancer evolution

In this study, the researchers also identified various factors that cause clustered somatic mutations. These factors include UV radiation, alcohol consumption, tobacco smoking, and most notably, the activity of a set of antiviral enzymes called APOBEC3.

APOBEC3 enzymes are typically found inside cells as part of their internal immune response. Their main job is to chop up any viruses that enter the cell. But in cancer cells, the researchers think that the APOBEC3 enzymes may be doing more harm than good.

The researchers found that cancer cells -- which are often rife with circular rings of extrachromosomal DNA (ecDNA) that harbor known cancer driver genes -- have clusters of mutations occurring across individual ecDNA molecules. The researchers attribute these mutations to the activity of APOBEC3 enzymes. They hypothesize that APOBEC3 enzymes are mistaking the circular rings of ecDNA as foreign viruses and attempt to restrict and chop them up. In doing so, the APOBEC3 enzymes cause clusters of mutations to form within individual ecDNA molecules. This in turn plays a key role in accelerating cancer evolution and likely leads to drug resistance. The researchers named these rings of clustered mutations kyklonas, which is the Greek word for cyclones.

"This is a completely novel mode of oncogenesis," said Alexandrov. Along with the team's other findings, he explained, "this lays the foundation for new therapeutic approaches, where clinicians can consider restricting the activity of APOBEC3 enzymes and/or targeting extrachromosomal DNA for cancer treatment."

This work was supported by a Cancer Grand Challenge award from Cancer Research UK as well as funding from the U.S. National Institutes of Health, Alfred P. Sloan Foundation, and Packard Foundation.

Source: ScienceDaily

Calorie restriction trial reveals key factors in extending human health

 Decades of research has shown that limits on calorie intake by flies, worms, and mice can enhance life span in laboratory conditions. But whether such calorie restriction can do the same for humans remains unclear. Now a new study led by Yale researchers confirms the health benefits of moderate calorie restrictions in humans -- and identifies a key protein that could be harnessed to extend health in humans.

The findings were published Feb. 10 in Science.

The research was based on results from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) clinical trial, the first controlled study of calorie restriction in healthy humans. For the trial, researchers first established baseline calorie intake among more than 200 study participants. The researchers then asked a share of those participants to reduce their calorie intake by 14% while the rest continued to eat as usual, and analyzed the long-term health effects of calorie restriction over the next two years.

The overall aim of the clinical trial was to see if calorie restriction is as beneficial for humans as it is for lab animals, said Vishwa Deep Dixit, the Waldemar Von Zedtwitz Professor of Pathology, Immunobiology, and Comparative Medicine, and senior author of the study. And if it is, he said, researchers wanted to better understand what calorie restriction does to the body specifically that leads to improved health.

Since previous research has shown that calorie restriction in mice can increase infections, Dixit also wanted to determine how calorie restriction might be linked to inflammation and the immune response.

"Because we know that chronic low-grade inflammation in humans is a major trigger of many chronic diseases and, therefore, has a negative effect on life span," said Dixit, who is also director of the Yale Center for Research on Aging. "Here we're asking: What is calorie restriction doing to the immune and metabolic systems and if it is indeed beneficial, how can we harness the endogenous pathways that mimic its effects in humans?"

Dixit and his team started by analyzing the thymus, a gland that sits above the heart and produces T cells, a type of white blood cell and an essential part of the immune system. The thymus ages at a faster rate than other organs. By the time healthy adults reach the age of 40, said Dixit, 70% of the thymus is already fatty and nonfunctional. And as it ages, the thymus produces fewer T cells. "As we get older, we begin to feel the absence of new T cells because the ones we have left aren't great at fighting new pathogens," said Dixit. "That's one of the reasons why elderly people are at greater risk for illness."

For the study, the research team used magnetic resonance imaging (MRI) to determine if there were functional differences between the thymus glands of those who were restricting calories and those who were not. They found that the thymus glands in participants with limited calorie intake had less fat and greater functional volume after two years of calorie restriction, meaning they were producing more T cells than they were at the start of the study. But participants who weren't restricting their calories had no change in functional volume.

"The fact that this organ can be rejuvenated is, in my view, stunning because there is very little evidence of that happening in humans," said Dixit. "That this is even possible is very exciting."

With such a dramatic effect on the thymus, Dixit and his colleagues expected to also find effects on the immune cells that the thymus was producing, changes that might underlie the overall benefits of calorie restriction. But when they sequenced the genes in those cells, they found there were no changes in gene expression after two years of calorie restriction.

This observation required the researchers to take a closer look, which revealed a surprising finding: "It turns out that the action was really in the tissue microenvironment not the blood T cells," Dixit said.

Dixit and his team had studied adipose tissue, or body fat, of participants undergoing calorie restriction at three time points: at the beginning of the study, after one year, and after two. Body fat is very important, Dixit said, because it hosts a robust immune system. There are several types of immune cells in fat, and when they are aberrantly activated, they become a source of inflammation, he explained.

"We found remarkable changes in the gene expression of adipose tissue after one year that were sustained through year two," said Dixit. "This revealed some genes that were implicated in extending life in animals but also unique calorie restriction-mimicking targets that may improve metabolic and anti-inflammatory response in humans."

Recognizing this, the researchers then set out to see if any of the genes they identified in their analysis might be driving some of the beneficial effects of calorie restriction. They honed in on the gene for PLA2G7 -- or group VII A platelet activating factor acetylhydrolase -- which was one of the genes significantly inhibited following calorie restriction. PLA2G7 is a protein produced by immune cells known as macrophages.

This change in PLA2G7 gene expression observed in participants who were limiting their calorie intake suggested the protein might be linked to the effects of calorie restriction. To better understand if PLA2G7 caused some of the effects observed with calorie restriction, the researchers also tracked what happened when the protein was reduced in mice in a laboratory experiment.

"We found that reducing PLA2G7 in mice yielded benefits that were similar to what we saw with calorie restriction in humans," said Olga Spadaro, a former research scientist at the Yale School of Medicine and lead author of the study. Specifically, the thymus glands of these mice were functional for a longer time, the mice were protected from diet-induced weight gain, and they were protected from age-related inflammation.

These effects occurred because PLA2G7 targets a specific mechanism of inflammation called the NLRP3 inflammasome, researchers said. Lowering PLA2G7 protected aged mice from inflammation.

"These findings demonstrate that PLA2G7 is one of the drivers of the effects of calorie restriction," said Dixit. "Identifying these drivers helps us understand how the metabolic system and the immune system talk to each other, which can point us to potential targets that can improve immune function, reduce inflammation, and potentially even enhance healthy lifespan."

For instance, it might be possible to manipulate PLA2G7 and get the benefits of calorie restriction without having to actually restrict calories, which can be harmful for some people, he said.

"There's so much debate about what type of diet is better -- low carbohydrates or fat, increased protein, intermittent fasting, etc. -- and I think time will tell which of these are important," said Dixit. "But CALERIE is a very well-controlled study that shows a simple reduction in calories, and no specific diet, has a remarkable effect in terms of biology and shifting the immuno-metabolic state in a direction that's protective of human health. So from a public health standpoint, I think it gives hope."

Source: ScienceDaily

Biohybrid fish made from human cardiac cells swims like the heart beats

 Harvard University researchers, in collaboration with colleagues from Emory University, have developed the first fully autonomous biohybrid fish from human stem-cell derived cardiac muscle cells. The artificial fish swims by recreating the muscle contractions of a pumping heart, bringing researchers one step closer to developing a more complex artificial muscular pump and providing a platform to study heart disease like arrhythmia.

"Our ultimate goal is to build an artificial heart to replace a malformed heart in a child," said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and senior author of the paper. "Most of the work in building heart tissue or hearts, including some work we have done, is focused on replicating the anatomical features or replicating the simple beating of the heart in the engineered tissues. But here, we are drawing design inspiration from the biophysics of the heart, which is harder to do. Now, rather than using heart imaging as a blueprint, we are identifying the key biophysical principles that make the heart work, using them as design criteria, and replicating them in a system, a living, swimming fish, where it is much easier to see if we are successful."

The research is published in Science.

The biohybrid fish developed by the team builds off previous research from Parker's Disease Biophysics Group. In 2012, the lab used cardiac muscle cells from rats to build a jellyfish-like biohybrid pump and in 2016 the researchers developed a swimming, artificial stingray also from rat heart muscle cells.

In this research, the team built the first autonomous biohybrid device made from human stem-cell derived cardiomyocytes. This device was inspired by the shape and swimming motion of a zebrafish. Unlike previous devices, the biohybrid zebrafish has two layers of muscle cells, one on each side of the tail fin. When one side contracts, the other stretches. That stretch triggers the opening of a mechanosensitive protein channel, which causes a contraction, which triggers a stretch and so on and so forth, leading to a closed loop system that can propel the fish for more than 100 days.

"By leveraging cardiac mechano-electrical signaling between two layers of muscle, we recreated the cycle where each contraction results automatically as a response to the stretching on the opposite side," said Keel Yong Lee, a postdoctoral fellow at SEAS and co-first author of the study. "The results highlight the role of feedback mechanisms in muscular pumps such as the heart."

The researchers also engineered an autonomous pacing node, like a pacemaker, which controls the frequency and rhythm of these spontaneous contractions. Together, the two layers of muscle and the autonomous pacing node enabled the generation of continuous, spontaneous, and coordinated, back-and-forth fin movements.

"Because of the two internal pacing mechanisms, our fish can live longer, move faster and swim more efficiently than previous work," said Sung-Jin Park, a former postdoctoral fellow in the Disease Biophysics Group at SEAS and co-first author of the study. "This new research provides a model to investigate mechano-electrical signaling as a therapeutic target of heart rhythm management and for understanding pathophysiology in sinoatrial node dysfunctions and cardiac arrhythmia."

Park is currently an Assistant Professor at the Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University School of Medicine.

Unlike a fish in your refrigerator, this biohybrid fish improves with age. Its muscle contraction amplitude, maximum swimming speed, and muscle coordination all increased for the first month as the cardiomyocyte cells matured. Eventually, the biohybrid fish reached speeds and swimming efficacy similar to zebrafish in the wild.

Next, the team aims to build even more complex biohybrid devices from human heart cells.

"I could build a model heart out of Play-Doh, it doesn't mean I can build a heart," said Parker. "You can grow some random tumor cells in a dish until they curdle into a throbbing lump and call it a cardiac organoid. Neither of those efforts is going to, by design, recapitulate the physics of a system that beats over a billion times during your lifetime while simultaneously rebuilding its cells on the fly. That is the challenge. That is where we go to work."

The research was co-authored by David G. Matthews, Sean L. Kim, Carlos Antonio Marquez, John F. Zimmerman, Herdeline Ann M. Ardona, Andre G. Kleber and George V. Lauder.

It was supported in part by National Institutes of Health National Center for Advancing Translational Sciences grant UH3TR000522, and National Science Foundation Materials Research Science and Engineering Center grant DMR-142057.

Source: Sciencedaily