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Rockville, Md. (April 27, 2021)--New research to be presented this week virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021 explores the positive and negative effects of lifespan-extending drugs on mitochondrial function and age-related osteoarthritis (OA).

Decreased function of mitochondria--the energy centers of the cells--is a hallmark characteristic of aging. Maintaining mitochondrial function during the aging process while delaying age-related diseases, such as OA, could be a key to extending lifespan. Previous research has found that metformin, primarily used to treat type 2 diabetes, and rapamycin, a drug used to prevent organ transplant rejection, can extend lifespan and maintain physiological function in many animal models.

In a new study, researchers from the University of Wisconsin-Madison explored the effects of rapamycin, metformin or a regimen of both medications on a guinea pig model of OA. These drugs were chosen because they have been shown to expand lifespan and healthspan through positive change in the mitochondria. The research team found that the animals treated with rapamycin and the two-drug combination had lower mitochondrial content in their muscles and the function of the mitochondria was impaired. In addition to changes in mitochondrial function, rapamycin treatment also led to a rise in blood glucose levels and worsened OA scores, a measure of disease severity.

These results suggest "there may be an indirect connection between impaired skeletal muscle mitochondrial function to exacerbated OA after rapamycin treatment," said Christian Elliehausen, first author of the study. More research is needed to examine if it is possible to "harness the positive effects of rapamycin while minimizing the negative effects," Elliehausen explained.

Rockville, Md. (April 27, 2021)--People who self-report daytime sleepiness were found to have shorter telomeres regardless of whether they had obstructive sleep apnea, according to a new study from researchers at the Mayo Clinic in Rochester, Minnesota. The findings will be presented virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Telomeres protect DNA from biological stressors, and shortened telomeres are associated with multiple cardiovascular diseases, according to the research team. This study found people reporting daytime sleepiness had similar telomere length compared to those without sleepiness; however, obstructive sleep apnea influences telomere length and was more prevalent in the sleepy group. When the researchers matched individuals between groups for the presence of sleep apnea, among other variables (e.g., age, weight), they found sleepy people without sleep apnea had shorter telomeres compared to those without sleepiness. In addition, there were no differences in telomere length between sleepy and non-sleepy individuals with sleep apnea. In essence, the study concluded daytime sleepiness was found to be linked to telomere shortening in the absence of sleep apnea.

Researchers are hopeful additional study will lead to reducing the rate of telomere shortening or reversing it altogether, which will could lower cardiovascular risk in people who report daytime sleepiness.

Rockville, Md. (April 27, 2021)--Urine analysis of COVID-19 patients revealed elevated levels of specific biomarkers of the immune system compared to those who were not infected with the coronavirus. In addition, levels of these inflammatory markers were higher in patients with comorbidities such as high blood pressure and diabetes, according to researchers from Wayne State University in Detroit. The findings will be presented virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Researchers said they undertook this study in hopes of determining whether biomarkers of COVID-19 could predict which individuals will develop "overly exuberant immune responses," also called a cytokine storm. They chose to screen the urine of COVID-19 patients because of its non-invasive nature that doesn't require the use of needles or blood samples.

Scientists said they hope the results of this study will translate to a regular screening process for COVID-19 patients to predict who is more likely to develop severe disease and to aid in a successful treatment strategy.

Rockville, Md. (April 27, 2021)--Although bronchopulmonary dysplasia (BPD)--a chronic lung disease affecting newborns--is the most common complication of preterm birth, it remains difficult to diagnose and treat. Researchers from Fundación INFANT in Buenos Aires, Argentina, and The University of Oklahoma Health Sciences Center, hope to address these difficulties using machine learning to inform the clinical care of preemies with BPD. The team will present their work virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

BPD affects between 20% and 40% of all infants with birthweight below 3 pounds, 4 ounces (1,500 grams). It usually subsides by age five but can extend into adulthood. Infants with BPD face prolonged hospitalization and are at risk of developmental delays and heart failure.

The research team presented an algorithm with a large data set of longitudinal clinical information for preterm infants, which the computer divided into three clusters. They then presented the trained algorithm with a second data set with comparable demographic characteristics. In this set, the computer was able to anticipate comorbidities and rehospitalizations better than the application of standard BPD diagnostic categories.

By more accurately aligning which biometrics correspond to different degrees of disease severity, these findings could enable better understanding of the underlying causes of BPD. They could also help clinicians diagnose BPD earlier and more precisely, allowing for personalized treatments.

Corresponding author Gaston Ofman, MD, says the next step is "to implement our analysis in real time and guide health care workers in their day-to-day care of preterm babies."

A new study found that non-pungent synthetic analog of capsaicin -- the compound that makes chili peppers hot -- made small cell lung cancer cells more responsive to treatment. Small cell lung cancer is a very aggressive form of cancer with a low survival rate.

Cisplatin-based combination chemotherapy is typically the first-line treatment for small cell lung cancer patients. Although patients initially respond very well to this chemotherapy, the tumor usually comes back within a year in a form that doesn't respond to treatments. Patients with relapsed small cell lung cancer have very few treatment options.

"Irinotecan is the only FDA approved second-line drug for small cell lung cancer, but less than 3% of patients respond to it," said research team leader Piyali Dasgupta, PhD, from Marshall University. "Therefore, agents that improve the anti-cancer activity of irinotecan would be of great value to these patients."

Jamie Friedman, a former doctoral student in Dasgupta's lab will present the new findings at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

The natural compound capsaicin has been shown to have anti-cancer effects, but its heat can also cause a burning sensation, stomach cramps, gut pain and nausea. In the new work, the researchers studied arvanil, a synthetic capsaicin analog without capsaicin's undesirable side effects.

When the researchers exposed two cisplatin-resistant lung cancer cell lines to a low concentration of arvanil, they saw no growth-inhibitory activity. However, when they treated the cells with varying concentrations of SN38 -- the active ingredient irinotecan -- they observed that the presence of arvanil greatly enhanced the ability of SN38 to slow cancer cell growth. Statistical analysis showed that the interaction between arvanil and SN38 was synergistic in nature.

"Because arvanil enhanced the anti-cancer activity of SN38 in human small cell lung cancer cells, arvanil-based combination therapies may be useful for patients with relapsed small cell lung cancer cells," said Friedman. "We hope that this work will pave the way for novel therapies for relapsed and cisplatin-resistant small cell lung cancer."

Jamie Friedman will present the findings in poster R361 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

Scientists from around the world are gathering to share the latest research at the forefront of biology during the Experimental Biology (EB) 2021 meeting. Many sessions focus on the year's most pressing priorities in bioscience: COVID-19 and the virus that causes it, SARS-CoV-2. Here are five highlights:

Legacy of COVID-19 in blood vessels may raise risk of heart disease

A study from the Medical College of Wisconsin suggests COVID-19 could cause long-term problems with the functioning of blood vessels, potentially increasing the risk of heart disease. Scientists examined arterioles, small branches of the cardiovascular system, in tissue samples from 14 people who had recovered from COVID-19 and 19 who had never had COVID-19. Arterioles regulate the flow of oxygen-rich blood to tissues by widening (dilating) and narrowing according to the body's needs at each moment. When exposed to stimuli (like chemicals or flow) that cause blood vessels to dilate, the arterioles from COVID-19 patients did not widen nearly as much as those from people without COVID-19. This effect was attributed to impaired functioning of the endothelium, the lining of the blood vessels. The effect was most pronounced in samples from people who had COVID-19 less than three months earlier; endothelium functioning was still impaired but closer to normal by eight months after infection. Over time, endothelial dysfunction in the blood vessels can lead to several forms of heart disease.

Yoshinori Nishijima will present this research online from 11:15-11:30 a.m. Thursday, April 29 (abstract). Images available.

Promising leads in the search for COVID-19 treatments

While vaccines are critical to curbing the COVID-19 pandemic, there is still a need for better treatments to improve the outlook for those who become infected. Research from the University of Oklahoma Health Sciences Center suggests drugs that inhibit a key enzyme in the SARS-CoV-2 virus could offer promising leads for an antiviral treatment. In experiments using cell cultures, the researchers found that three naturally occurring compounds significantly reduced the activity of the SARS-CoV-2 main protease, an enzyme the virus uses to replicate. The research team was able to trace how two of the compounds, phebestin and probestin, inhibit the main protease at the molecular level. They also found that these compounds did not harm mouse cells from the lining of the lungs, a test used to screen for safety concerns associated with delivering medicines through the nose. Based on these findings, the researchers say the compounds, which are members of a class of molecules called peptidic ?-hydroxy amides, warrant further study as potential antiviral drugs for COVID-19.

Nagendra Yarla will present this research online on-demand from April 27-30 (abstract). Images available.

Molecules found in stem cells could calm COVID-19 cytokine storm

Treatment options are currently limited for patients with COVID-19 who suffer an excessive immune response known as a cytokine storm, which causes life-threatening damage to organs and tissues. Research led by the Houston Methodist Research Institute demonstrates that stem cells isolated from amniotic fluid contain several molecules that might be able to help counter a cytokine storm. Unlike embryonic stem cells, these cells are routinely collected to test amniotic fluid during prenatal diagnosis, without harm to the mother or fetus. Researchers found that the amniotic stem cells contained molecules involved in communicating with immune cells, regulating immunity and inflammation, protecting and repairing the lining of the lungs and maintaining a healthy heart. The study suggests mesenchymal stem cells from amniotic fluid, which have previously been explored as a therapy for other conditions, could offer a new option for treating the severe and chronic inflammation resulting from COVID-19 infection.

Salvatore Vaiasicca will present this research online from 2:45-3 p.m. Wednesday, April 28 (abstract).

Expert roundtable: Toward understanding and containing the COVID-19 pandemic

Researchers will present a series of lightning talks on the mechanisms underlying COVID-19 infections along with updates on current and emerging treatments and vaccines. Topics include SARS-CoV-2 variants and genomic analysis; autopsy-derived insights into the pathobiology of COVID-19; the race for a vaccine; and mitigating COVID-19 in meat and poultry processing plants.

The session will be held online from 2-5 p.m. on Friday, April 30, and include a live Q&A with experts (more information).

How COVID-19 changed practices for science education

How did science educators and students adjust to constraints on in-person learning during the COVID-19 pandemic? A survey of educators in anatomy -- a field with a strong emphasis on in-person, hands-on learning -- sheds light on changing practices. Researchers from 10 universities across the U.S. and Canada conducted two surveys of anatomy educators in 2020. The first survey collected 67 responses from May through August, and the second collected 191 responses from August to December, reflecting the summer and fall terms, respectively. Respondents reported a drastic reduction of in-person lectures while remote instruction increased; they also reduced the use of cadavers and increased the use of other laboratory teaching materials, such as digital and virtual anatomical technology. These changes were most pronounced early in the pandemic. During the final months of 2020, respondents reported greater use of in-person teaching and use of cadavers, though these practices were still diminished and varied by institution compared with prepandemic levels. The researchers suggest further study can help elucidate whether these trends may represent long-term changes for anatomy education.

Derek Harmon will present this research online in poster R2047 (abstract). Images available.

EB 2021 is the premiere annual meeting of five scientific societies to be held online April 27-30, 2021. Contact the media team for more information or to obtain a free press pass to attend the virtual meeting.

Recent years have brought increased attention to the lasting effects of chemicals we unwittingly inhale, touch and ingest while going about our daily lives. The Experimental Biology (EB) 2021 meeting features the latest research on how environmental exposures affect health. Here are five highlights:

Study sheds light on health hazards of hog farms

People who work at or live near concentrated animal feeding operations, especially hog farms, commonly face an increased risk of respiratory problems and gastrointestinal diseases. New research from the University of California, Riverside, investigates the mechanisms through which exposure to hog farms may harm health. In studies using mice and cell cultures, scientists found evidence that breathing dust from hog farms leads to inflammation in the airways. The research also suggests that compounds from hog dust increase the permeability of the intestine, possibly by damaging the intestinal lining, which may help explain why farm workers are more susceptible to gastrointestinal disease. The research could help inform interventions to better protect the health of farm workers and people living near large farming operations.

Meli'sa Crawford will present this research online from 2-2:15 p.m. Friday, April 30 (abstract).

Common ingredient in antimicrobial soap and toothpaste linked with inflammation

Inflammation is a natural process our bodies use to heal and fight infections, but chronic or unwarranted inflammation can lead to diseases including arthritis and cancer. Researchers at Tennessee State University report new evidence that triclosan, an antimicrobial compound used in personal hygiene products such as soap, toothpaste and mouthwash, may cause inflammation and potentially increase the risk of associated health problems. The researchers exposed cell cultures to triclosan and measured interleukin-6 (IL-6), a biomarker used to assess inflammation. They found that triclosan exposure caused a substantial increase in IL-6 production over a 24-hour period, with levels peaking at six hours after exposure. The study adds to a growing body of evidence suggesting potential detrimental effects of triclosan, which can be ingested or absorbed through the skin when using products that contain it, according to researchers.

Wendy Wilburn will present this research online in poster R318 (abstract).

Cigarettes may pose risk even after they're extinguished

Health problems associated with smoking and being near someone who is smoking (secondhand smoke) are well established. A new study from Texas A&M University suggests the residual smoke that remains even after a cigarette is put out -- called thirdhand smoke -- could affect the health of fetuses. The researchers exposed pregnant mice to smoke contaminants from extinguished cigarettes and traced health markers in their offspring. They found that mice exposed to thirdhand smoke in utero showed a significant increase in aggregation of platelets, a component of blood involved in clotting. In other tests, these mice showed markers indicating a predisposition toward cardiovascular problems related to blood clots. Researchers say the study draws attention to the need to further investigate the potential consequences of thirdhand smoke exposure.

Ahmed Alarabi will present this research online in poster R4465 (abstract). Images available.

Gulf War veterans may be more susceptible to alcohol-induced liver damage

Some veterans of the 1990-1991 Persian Gulf War suffer Gulf War illness, a syndrome with a wide range of symptoms thought to be caused by chemical exposures encountered during combat. A new study from Central Texas Veterans Health Care System suggests these veterans may be more prone to liver damage from heavy alcohol consumption. Researchers exposed mice to chemicals similar to those thought to cause Gulf War illness and assessed the effects of ethanol on liver health in these mice, comparing them with mice that had not been exposed to the chemicals. They found that exposure to chemicals caused long-term changes to the liver, including low-level inflammation, suggesting a greater susceptibility to alcohol-induced liver disease. This type of liver disease is associated with heavy alcohol use, but researchers have struggled to understand why some people who drink heavily develop liver problems while others do not. The study bolsters the evidence that environmental exposures may play a role.

Suyeon An will present this research online in poster R4162 (abstract).

New evidence suggests role of epigenetic factors in determining anatomy

With the same genetic makeup, identical twins share many similarities. But new research suggests twins show subtle differences beneath the surface, possibly as a result of epigenetics (changes in gene expression) or environmental factors such as nutrition and chemical exposures. Scientists at the University of Colorado Anschutz Medical Campus examined cadavers donated by a pair of identical twins. Comparing the structures of nerves, veins and arteries in the neck, trunk, pelvis and limbs, they found significant differences in these structures between twins. In addition, some paired structures showed asymmetric differences within a single individual. While the researchers were not able to attribute the differences to specific causes, the study, which is the first to demonstrate unique anatomic variations in identical twins, suggests further research could help elucidate how epigenetic factors may alter our bodies over the course of a lifetime.

Chelsea Lohman Bonfiglio will present this research online in poster R2536 (abstract).

EB 2021 is the premiere annual meeting of five scientific societies to be held online April 27-30, 2021. Contact the media team for more information or to obtain a free press pass to attend the virtual meeting.

Results from a new cell study suggest that the SARS-CoV-2 spike protein can bring about long-term gene expression changes. The findings could help explain why some COVID-19 patients -- referred to as COVID long-haulers -- experience symptoms such as shortness of breath and dizziness long after clearing the infection.

SARS-CoV-2, the virus that causes COVID-19, is covered in tiny spike proteins. During infection, the spike proteins bind with receptors on cells in our body, starting a process that allows the virus to release its genetic material into the inside of the healthy cell.

"We found that exposure to the SARS-CoV-2 spike protein alone was enough to change baseline gene expression in airway cells," said Nicholas Evans, a master's student in the laboratory of Sharilyn Almodovar, PhD, at the Texas Tech University Health Sciences Center. "This suggests that symptoms seen in patients may initially result from the spike protein interacting with the cells directly."

Evans will present the research at the American Society for Biochemistry and Molecular Biology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

Culturing human airway cells requires specific conditions that allow cells to mature into the differentiated cells that would be found in the airway. The researchers optimized a previously developed culturing approach known as the air-liquid interface technique so that it would more closely simulate the physiological conditions found in the lung airway. This involved exposing cells to air and then giving them time to mature into airway cells.

The researchers found that cultured human airway cells exposed to both low and high concentrations of purified spike protein showed differences in gene expression that remained even after the cells recovered from the exposure. The top genes included ones related to inflammatory response.

"Our work helps to elucidate changes occurring in patients on the genetic level, which could eventually provide insight into which treatments would work best for specific patients," said Evans.

The researchers also compared their cultured human airway cells to studies from others where cells were collected from patients with COVID-19 infection. They were able to confirm that the optimized cell culture approach reflected what occurs in patients, making it useful for future translational studies. They plan to use the new approach to better understand how long the genetic changes last and the potential long-term consequences of these changes in relation to long-haul COVID-19 cases.

Nicholas Evans will present the findings from 12:00-12:15 p.m. Friday, April 30 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

Images available.

The two major types of cetaceans appear to have evolved their characteristic blowholes through different anatomical transformations, according to a study being presented at the American Association for Anatomy annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30.

Cetaceans, a group of marine mammals that includes whales and dolphins, evolved from ancestors that walked on land around 50 million years ago. Somewhere along the way, the forward-pointing nose shifted to an upward-pointing blowhole, making it easier for the animals to breathe air while swimming.

For the new study, researchers observed shifts in nasal passage orientation in spotted dolphin and fin whale embryos and fetuses. Both species initially develop a forward-pointing nose, like any other mammal, which gradually transforms into a blowhole by birth. Anatomical changes during prenatal development can provide clues about how certain traits evolved over time.

"The main difference we observed is in how the nostrils reach this position during prenatal development -- there does not seem to be one way to do it," said Rachel Roston, PhD, a postdoctoral fellow at the University of Washington and the study's lead author. "The dolphin species and other toothed whales showed backwards bending of the skull, whereas the fin whale and other baleen whales showed changes in the occipital bone at the back of the skull."

Researchers have previously studied other differences in the nasal passages of the two types of cetaceans; for instance, toothed whales have a single nostril whereas baleen whales have two. By focusing on the part of the skull that connects the nasal passage and the rest of the body, the new study examines previously unexplored territory at the intersection of nasal passage orientation and head-body alignment.

Roston says the work suggests that the two cetacean types may have evolved their blowholes through different developmental processes, though additional research, such as studies of the fossil record, would be needed to more rigorously test this hypothesis.

"Few, if any, other mammals have evolved such an extreme shift in nasal passage orientation and nostril position," said Roston. "Understanding how developmental transformations lead to nasal passage reorientation during prenatal development helps us understand how changes to development can lead to the evolution of extreme and unique anatomical features."

Roston will present this research in poster R4523 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

Images available.

Using a newly developed mouse model of acute lung injury, researchers found that exposure to the SARS-CoV-2 spike protein alone was enough to induce COVID-19-like symptoms including severe inflammation of the lungs.

SARS-CoV-2, the virus that causes COVID-19, is covered in tiny spike proteins. These proteins bind with receptors on our cells, starting a process that allows the virus to release its genetic material into a healthy cell.

"Our findings show that the SARS-CoV2 spike protein causes lung injury even without the presence of intact virus," said Pavel Solopov, PhD, DVM, research assistant professor at the Frank Reidy Research Center for Bioelectrics at Old Dominion University. "This previously unknown mechanism could cause symptoms before substantial viral replication occurs."

Solopov will present the new research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

Studying SARS-CoV-2 can be challenging because experiments involving the intact virus requires a Biosafety Level 3 laboratory. To overcome this hurdle, the researchers created a new model of acute lung injury that utilizes transgenic mice that express the human receptor for SARS-CoV-2 in their lungs.

"Our mouse model dramatically reduces the danger of doing this type of research by allowing COVID-19 lung injury to be studied without using the intact, live virus," said Solopov. "This will greatly increase and diversify the ability to do COVID-19 research. Our model will also likely be useful for studying other coronaviruses."

The researchers injected the genetically modified mice with a segment of the spike protein and analyzed their response 72 hours later. Another group of mice received only saline to serve as a control.

The researchers found that the genetically modified mice injected with the spike protein exhibited COVID-19-like symptoms that included severe inflammation, an influx of white blood cells into their lungs and evidence of a cytokine storm - an immune response in which the body starts to attack its own cells and tissues rather than just fighting off the virus. The mice that only received saline remained normal.

"These findings show that the genetically modified mouse together with just a segment of the spike protein can be used to study SARS-CoV-2 lung injury," said Solopov. "We can use this tool to develop a better understanding of how the spike protein causes lung symptoms -- even without the intact virus -- in order to develop new targets and therapeutics for COVID-19."

The researchers plan to continue this line of investigation by using the new mouse model to study the effectiveness of several drugs in reducing the severity of acute lung injury and COVID-19.

Pavel Solopov will present during an on-demand presentation (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

Image available.

A technology-packed tank top offers a simple, effective way to track astronauts' vital signs and physiological changes during spaceflight, according to research being presented at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30.

By monitoring key health markers over long periods of time with one non-intrusive device, researchers say the garment can help improve understanding of how spaceflight affects the body.

"Until now, the heart rate and activity levels of astronauts were monitored by separate devices," said Carmelo Mastrandrea, PhD, a postdoctoral fellow at the Schlegel-University of Waterloo Research Institute for Aging in Canada, and the study's first author. "The Bio-Monitor shirt allows simultaneous and continuous direct measurements of heart rate, breathing rate, oxygen saturation in the blood, physical activity and skin temperature, and provides a continuous estimate of arterial systolic blood pressure."

The Bio-Monitor shirt was developed for the Canadian Space Agency by Carré Technologies based on its commercially available Hexoskin garment. In a study funded by the Canadian Space Agency, a team of researchers from the Schlegel-University of Waterloo Research Institute for Aging oversaw the first test of the shirt in space for a scientific purpose. Astronauts wore the shirt continually for 72 hours before their spaceflight and 72 hours during spaceflight, except for periods of water immersion or when the device conflicted with another activity.

The shirt's sensors and accelerometer performed well, providing consistent results and a large amount of usable data. Based on these initial results, researchers say the shirt represents an improvement over conventional methods for monitoring astronauts' health, which require more hands-on attention.

"By monitoring continuously and non-intrusively, we remove the psychological impacts of defined testing periods from astronaut measurements," said Mastrandrea. "Additionally, we are able to gather information during normal activities over several days, including during daily activities and sleep, something that traditional testing cannot achieve."

In flight, the astronauts recorded far less physical activity than the two and a half hours per day recorded in the monitoring period before takeoff, a finding that aligns with previous studies showing large reductions in physical activity during spaceflight. In addition to monitoring astronauts' health and physical activity in space, Mastrandrea noted that the shirt could provide early warning of any health problems that occur as their bodies re-adapt to gravity back on Earth.

The commercial version of the Bio-Monitor shirt is available to the public, where it can be used for various applications including assessing athletic performance and monitoring the health of people with limited mobility. In addition to spaceflight, researchers are examining its potential use in other occupational settings that involve extreme environments, such as firefighting.

Mastrandrea will present this research in poster R2888 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

Images available.

New research offers an up-close view of how SARS-CoV-2, the virus that causes COVID-19, can spread to the brain. The study helps explain the alarming array of neurological symptoms reported in some patients with COVID-19, as well as why some patients suffer severe neurological effects while others experience none at all.

The researchers report evidence that SARS-CoV-2 can infect both the nerve cells that power our brains (neurons), and the cells in the brain and spinal cord that support and protect neurons (astrocytes).

"Our findings suggest that astrocytes are a pathway through which COVID-19 causes neurological damage," said Ricardo Costa, PhD, a postdoctoral fellow at the Louisiana State University (LSU) Health Shreveport and the study's first author. "This could explain many of the neurologic symptoms we see in COVID-19 patients, which include loss of sense of smell and taste, disorientation, psychosis and stroke."

Costa will present the research at the American Physiological Society annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30. The study is led by Diana Cruz-Topete, assistant professor of molecular and cellular biology at LSU Health Shreveport, and includes collaborators Oscar Gomez-Torres, PhD, and Emma Burgos-Ramos, PhD, from Universidad de Castilla-La Mancha in Spain.

In the respiratory system, SARS-CoV-2 is known to infect a person's cells by grabbing hold of proteins on the cell surface called angiotensin-converting enzyme-2 (ACE2) receptors. It has been unclear whether brain cells have this receptor.

For the study, Costa and colleagues examined RNA and proteins to determine whether cell cultures of human astrocytes and neurons expressed ACE2. They then exposed the cells to a version of the SARS-CoV-2 virus that had been modified to be safe for researchers to handle. The studies confirmed that both astrocytes and neurons express the ACE2 receptor and that both cell types can become infected with SARS-CoV-2, though astrocytes were less likely to become infected.

Astrocytes are the main gateway to the brain, responsible for shuttling nutrients from the bloodstream to the neurons while keeping harmful particles out. By resisting infection, astrocytes could help keep SARS-CoV-2 out of the brain, but once infected, they could easily pass the virus along to many neurons, according to researchers.

"While astrocytes display a higher resistance to infection, neurons seem to be more susceptible," said Costa. "This suggests that only few astrocytes getting infected could be sufficient for the infection to quickly spread to neurons and multiply quickly. These observations could explain why while some patients do not have any neurological symptoms, others seem to have severe ones."

Costa will present this research from 3:15-3:30 p.m. Tuesday, April 27 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

Images available.

New insights into how fetal and adult liver cells differ could be used to help make liver cell transplants successful long term. Transplanting functioning liver cells into a patient's liver can help replace liver function that is impaired due to disease.

Today there are many more patients waiting for liver transplants than there are donor organs available. Because liver cell transplantation only requires a portion of cells isolated from a liver, it could allow multiple patients to be treated from one donated organ.

Although liver cell transplants offer a promising life-saving alternative to transplanting the whole organ, the effects aren't long-lasting when adult liver cells are used. Clinical trials and animal studies have shown that when fetal liver cells are used for liver cell transplants, they multiply and maintain function for long periods of time. However, fetal liver cells cannot be readily obtained for clinical use.

"Our work aims to characterize the mechanisms by which fetal liver cells -- or hepatocytes -- repopulate an injured adult liver," said Anders Ohman, a doctoral candidate in the laboratory of Jennifer Sanders, PhD, at Brown University. "We can then use this information to develop novel culture conditions and therapeutic strategies that can make liver cell transplantation feasible."

Ohman will present the research at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

To better understand why fetal hepatocytes maintain their function, the researchers transplanted fetal rat hepatocytes into the spleen of mice that had part of their liver removed. Over 10 months, the fetal cells regenerated the liver and made up an increasing percentage of the organ. The researchers then used a technique called laser capture microdissection to collect normal adult liver tissue as well as tissue derived from the transplanted fetal cells.

"Our analysis of these samples identified a number of fetal characteristics that are durably retained months after transplantation into the adult liver microenvironment," said Ohman. "We also found gene expression and cellular processes that are distinct to the fetal-cell-derived tissue."

Next, the researchers aim to identify specific biological drivers of cell growth and proliferation that are responsible for the competitive advantage that the fetal cells have in repopulating the liver.

Anders Ohman will present the findings in poster R3514 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

Image available.

The placenta forms the interface between the maternal and foetal circulatory systems. As well as ensuring essential nutrients, endocrine and immunological signals get through to the foetus to support its development and growth, the placenta must also protect it from the accumulation of potentially toxic compounds. A study from Cécile Demarez, Mariana Astiz and colleagues at the University of Lübeck in Germany now reveals that the activity of a crucial placental gatekeeper in mice is regulated by the circadian clock, changing during the day-night cycle. The study, which has implications for the timing of maternal drug regimens, is published in the journal Development.

The circadian clock translates time-of-day information into physiological signals through rhythmic regulation of downstream genes. In this study, the researchers discover that in the labyrinth zone of the mouse placenta, a tissue functionally equivalent to the human chorionic villi, clock genes are expressed in a 24h rhythm. Importantly, they show that this placental clock is responsible for regulating the expression and activity of ABCB1, a drug efflux transporter with hundreds of known substrates.

An important prediction of this work is that the time-of-day of maternal treatment could be an important factor to consider to avoid non-desirable effects for the foetus during pregnancy.

"Pharmacological treatments are mostly avoided by pregnant women but in certain circumstances there is no other option," says Dr. Mariana Astiz. "An example would be maternal treatment with antiretrovirals (many of which are in fact substrates of ABCB1). So, choosing the correct time of day to take drugs like these might reduce the ammount of drug reaching the baby and hence the possible negative effects in the short and long-term."

Dr. Astiz hopes this study will provide a stimulus to design studies that specifically test hypotheses about the placental circadian clock in humans. "This is definitely a very exciting and rapidly advancing field of research."

OAK BROOK, Ill. - Exercise appears to reduce the long-term risk of bronchiectasis, a potentially serious disease of the airways, according to a study published in the journal Radiology.

Bronchiectasis is characterized by repeated cycles of inflammation and exacerbations that damage the airways, leaving them enlarged, scarred and less effective at clearing mucus. This creates an environment ripe for infections. Risk increases with age and the presence of underlying conditions like cystic fibrosis. There is no cure.

Computed tomography (CT) is used to confirm or rule out the disease in patients with symptoms like shortness of breath and coughing up mucus. Bronchiectasis has also been found on CT in asymptomatic and mildly symptomatic individuals.

Little is known about factors that can reduce the risk of bronchiectasis. While some studies have tied higher levels of cardiorespiratory fitness to a reduced risk of declining lung function and airway diseases, such as chronic obstructive pulmonary disease, its benefits in reducing the risk of bronchiectasis are unknown.

To examine the association between cardiorespiratory fitness and bronchiectasis, researchers analyzed data from the long-running Coronary Artery Disease in Young Adults (CARDIA) study. CARDIA was launched in 1984 across the U.S. to examine the risk factors for coronary artery disease in young adults.

The researchers looked at 2,177 healthy adults who were ages 18 to 30 years at the beginning of the study period. The study participants were followed up over a 30-year period with fitness tests and CT.

"We used year zero and year 20 cardiorespiratory fitness measured as exercise duration on a treadmill and ascertained bronchiectasis on chest CT at year 25," said study lead author Alejandro A. Diaz, M.D., M.P.H., assistant professor of medicine at Harvard Medical School and associate scientist at Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital in Boston. "We assessed whether differences in treadmill duration between year zero and 20 were associated with bronchiectasis on CT at year 25."

Of the 2,177 participants, 209, or 9.6%, had bronchiectasis at year 25. Preservation of cardiorespiratory fitness reduced the odds of bronchiectasis on CT at year 25.

"In an adjusted model, one minute longer treadmill duration between year zero and year 20 was associated with 12% lower odds of bronchiectasis on CT at year 25," Dr. Diaz said. "Having preserved fitness at middle age is associated with lower chances of bronchiectasis."

The researchers pointed to several possible explanations for the relationship between cardiorespiratory fitness and bronchiectasis. For one, a high level of cardiorespiratory fitness is linked with lower levels of systemic inflammation, which might help preserve the health of the airway. Good cardiorespiratory fitness also reduces the risk of certain diseases associated with bronchiectasis, such as asthma and pneumonia. Finally, high fitness levels may improve the ability of the airway to clear mucus.

The researchers observed a higher prevalence of bronchiectasis than found in previous studies. The difference may be explained by the use of CT for detecting bronchiectasis in the new study rather than the physician-based diagnosis used in previous studies.

"This study suggests that bronchiectasis on CT scans might be more frequent than previously thought," Dr. Diaz said. "However, the clinical implications of finding bronchiectasis on CT scans in people with no or mild symptoms remain to be determined."

The researchers are studying bronchiectasis in other populations like smokers to look for features of the airways and lung tissue associated with bronchiectasis flare-ups.

"These results amplify the benefits of fitness to human health when a sedentary lifestyle is a concerning world epidemic," Dr. Diaz said. "It also highlights that fitness might be a tool to preserve lung health. The airways are challenged by what we breathe in every minute, and fitness may help to preserve lung health from injuries."