Publisher Health

Today in Nature Communications, researchers at Huntsman Cancer Institute at the University of Utah report critical new insights into how cells mount an attack against melanoma tumors.
Melanoma is an aggressive type of skin cancer that can arise from excess exposure to sun, frequent sunburns, genetics, and other environmental factors. Melanoma, like all cancers, begins within cells. Specially designed and refined over billions of years, cells are experts at working to root out and fix routine errors that arise. A tumor begins when a cell makes faulty copies of itself over and over again. If left unchecked, these faulty cell copies continue to grow into complex ecosystems that become tumors. Some tumors, like melanomas, can go on to develop mechanisms to sustain themselves with blood flow and oxygen. They can also send the cancerous cells through the body to proliferate in other organs, which ultimately causes death.
Immunotherapy, which trains the immune system to fight cancer cells, can sometimes be effective in treating melanomas. Some patients experience a long-lasting and durable response to immunotherapies. Yet many patients’ tumors soon learn how to outsmart the drugs.
Understanding how cells mount a defense against an aggressive tumor like melanoma piqued the curiosity of Ryan O’Connell, PhD, a cancer researcher at HCI and professor of pathology at the University of Utah Health. His lab works to understand how immune cells and cancer cells interface. He wants to better understand the sophisticated metabolic processes within and around cells and to use those insights to develop more effective cancer therapies.
In this study, O’Connell and his team uncovered a key metabolic “switch” driven by an enzyme, nicotinamide phosphoribosyltransferase, or NAMPT. They learned how NAMPT plays an important role in how certain immune cells fight melanoma tumors.
“We were interested in better understanding NAMPT because it is increased in specific immune cells within tumors, called macrophages, in response to a substance secreted by other immune cells, called interferon, which is known to be important for effective antitumor responses,” says O’Connell. O’Connell and his team used next-generation RNA sequencing to determine which metabolic genes increase within immune cells in response to different tumor processes.
“NAMPT was a top hit,” says O’Connell. The research team found that a specific inflammatory signaling pathway triggers NAMPT. They discovered that when this inducible NAMPT pathway is disrupted, the antitumor function of cells was also impaired.
The study was co-led by Warren Voth, PhD, a research assistant professor and member of the O’Connell Lab. Voth helped design and conduct the experiments to study the role of Nampt and also mentored lab trainees who worked on the project. Using studies of cells in a laboratory setting, Voth helped to understand how NAMPT is induced in immune cells and what happens if the immune cells block NAMPT induction. The research team then created an experiment using a mouse model system and found the same NAMPT pathway was required for the mouse cells to initiate antitumor activity. Next, the team studied data from human tumors using The Cancer Genome Atlas, a federal cancer genomics program that molecularly characterized more than 20,000 primary cancer and matched normal samples across 33 cancer types. The critical role of the NAMPT pathway was also a factor in the genomic data they analyzed.
“Based on this work, we want to understand whether novel therapies that enhance the NAMPT pathway in immune cells in patient tumors could result in improved outcomes,” says O’Connell. He hopes the next step will be to understand whether therapies that strengthen this pathway in certain immune cells could be the foundation for more effective treatments. He also wants to understand whether high levels of NAMPT in tumors may predict whether a patient will respond well to some immunotherapies that have inconsistent outcomes.
This work adds to the body of evidence that the metabolic state of tumors, immune cells, and the tumor microenvironment as a whole can have profound impacts on the course of disease by controlling the identity and functionality of immune cells that either fight to destroy the tumor or act to promote cancer growth. O’Connell’s team also found strong evidence that this study has applications to other cancer types.
Story Source:
Materials provided by Huntsman Cancer Institute. Note: Content may be edited for style and length.

A new Dartmouth Engineering study shows that integrating renewable energy into the American Electric Power System (AEPS) would enhance the grid’s resilience, meaning a highly resilient and decarbonized energy system is possible. The researchers’ analysis is based upon the incremental incorporation of architectural changes that would be required to integrate renewable energy into AEPS.
The paper, “A Hetero-functional Graph Resilience Analysis of the Future American Electric Power System,” was recently published by IEEE Access.
“We concluded that there are no structural trade-offs between grid sustainability and resilience enhancements, meaning these strategic goals can be pursued simultaneously,” said Principal Investigator Amro Farid, a professor at Thayer School of Engineering at Dartmouth and research affiliate at the Massachusetts Institute of Technology (MIT).
“Whether you are of one political inclination or another, value resilience or sustainability, the efforts are entirely aligned and should serve as the basis for a bipartisan consensus on the transformation of the electric power grid,” said Farid.
The results of the structural analysis are the first to take into account the hetero-functionality of the grid’s resources, including renewable energy, using a new method that uniquely captures the true connectedness and capabilities of the grid. Using the novel hetero-functional graph theory, which Farid has been developing for over a decade, the researchers analyzed more than 175,000 energy resources throughout the United States such as power plants, substations, and transmission lines.
“Through the hetero-functional graph theory analysis of the American Electric Power Systems, we were better able to track the systems capabilities and structural resilience as the AEPS underwent both attacks and developments,” said first author Dakota Thompson, a Dartmouth Engineering PhD candidate. Dartmouth Engineering alumnus Wester Schoonenberg also contributed to the study.
The authors received funding from the National Science Foundation (NSF) as part of the American Multi-Modal Energy System (AMES) project, which supported this work.
The researchers are already working on their next project: developing a synthetic model of the AMES, including electric power, oil, natural gas, and coal infrastructure, so that the research community can study how the model can evolve to meet current and future needs.
Story Source:
Materials provided by Thayer School of Engineering at Dartmouth. Original written by Julie Bonette. Note: Content may be edited for style and length.

A biochemical reaction between an enzyme called luciferase and oxygen causes fireflies to glow and is considered one of the most well-known examples of bioluminescence in nature. Now, an international team of researchers led by Elena Goun at the University of Missouri is working to harness the power of bioluminescence in a low-cost, noninvasive portable medical imaging device that could one day be applied to many uses in biomedical research, translational medicine and clinical diagnoses.
Potential uses include developing better treatments for cancer, diabetes and infectious diseases, along with monitoring various metabolic functions, such as gut health, in both animals and humans, said Goun, an associate professor of chemistry in the College of Arts and Science and corresponding author on the study published in Nature Communications.
“This is the first example of a low-cost, portable bioluminescence imaging tool that can be used in large non-transgenic animals such as dogs,” Goun said. “The mobility and cost-effectiveness of this technology also makes it a powerful tool for use in many areas of preclinical research, clinical research and diagnostics.”
Once the imaging probe is inserted into the body and reaches a targeted internal organ, such as the liver, the level of biological activity, such as liver toxicity, determines the amount of luciferin that is released into the bloodstream. Eventually, it reaches the area of the device, setting off a biochemical reaction that creates light. A portable light detector — about 10 millimeters, smaller than the diameter of a penny — is then placed on the surface of the body near the inserted device and measures the intensity of the light. The level of detected light correlates with the amount of luciferin present, which scientists can then use when determining the health of the targeted organ.
Jeffrey Bryan, a professor of veterinary oncology in the College of Veterinary Medicine and a co-author on the study, said this technology will be helpful in a clinical setting — both in animal and human medicine — where medical professionals can determine if a treatment is working inside a patient.
“This is a way we can monitor, in a minimally invasive way, a patient’s physiological response to whatever treatment is administered to him or her,” said Bryan, who is also an associate director of comparative oncology at MU’s Ellis Fischel Cancer Center. “Right now, most of the time we are looking for responses to treatment by asking the patient how they feel and then doing big, invasive, expensive tests to see if the treatment is working. Sometimes, that requires multiple procedures. But, if we can monitor for the desired effect in a minimally invasive manner and continue monitoring the progress over a long time period with this technology, that would probably reduce the need for more invasive testing.”
In addition to the diagnostic testing benefits of this technology, Goun said their approach could have the potential to significantly reduce the number of dogs, cats and non-human primates being used for experimental testing purposes by commercial drug development companies.
“Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals,” was published in Nature Communications.
Story Source:
Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

Most of us have imagined how free it would feel to float around, like an astronaut, in conditions of reduced gravity. But have you ever considered what the effects of reduced gravity might have on muscles? Gravity is a constant force on Earth which all living creatures have evolved to rely on and adapt to. Space exploration has brought about many scientific and technological advances, yet manned spaceflights come at a cost to astronauts, including reduced skeletal muscle mass and strength.
Conventional studies investigating the effects of reduced gravity on muscle mass and function have used a ground control group that is not directly comparable to the space experimental group. Researchers from the University of Tsukuba set out to explore the effects of gravity in mice subjected to the same housing conditions, including those experienced during launch and landing. “In humans, spaceflight causes muscle atrophy and can lead to serious medical problems after return to Earth” says senior author Professor Satoru Takahashi. “This study was designed based on the critical need to understand the molecular mechanisms through which muscle atrophy occurs in conditions of microgravity and artificial gravity.”
Two groups of mice (six per group) were housed onboard the International Space Station for 35 days. One group was subjected to artificial gravity (1 g) and the other to microgravity. All mice were alive upon return to Earth and the team compared the effects of the different onboard environments on skeletal muscles. “To understand what was happening inside the muscles and cells, at the molecular level, we examined the muscle fibers. Our results show that artificial gravity prevents the changes observed in mice subjected to microgravity, including muscle atrophy and changes in gene expression,” explained Prof. Takahashi. Transcriptional analysis of gene expression revealed that artificial gravity prevented altered expression of atrophy related genes and identified novel candidate genes associated with atrophy. Specifically, a gene called Cacng1 was identified as possibly having a functional role in myotube atrophy.
This work supports the use of spaceflight datasets using 1 g artificial gravity for examining the effects of spaceflight in muscles. These studies will likely aid our understanding of the mechanisms of muscle atrophy and may ultimately influence the treatment of related diseases.
Story Source:
Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

Improved ventilation can lower the risk of transmission of the COVID-19 virus, but large numbers of decades-old public school classrooms lack adequate ventilation systems. A systematic modeling study of simple air cleaners using a box fan reported in Physics of Fluids, by AIP Publishing, shows these inexpensive units can greatly decrease the amount of airborne virus in these spaces, if used appropriately.
A low-cost air cleaner can be easily constructed from a cardboard frame topped by an air filter and a box fan. The air filter is placed between the fan and the cardboard base. The fan is oriented so that air is drawn in from the top and forced through the filter, discharging cleaned air downward.
The investigators measured the clean air delivery rate of the air cleaning system in experiments conducted at two independent laboratories. Tobacco smoke was used to simulate the airborne virus, since the virus is known to travel through the air after exhalation in droplets about the same size as smoke particulates.
The experimental measurements were incorporated into a detailed computational model of a classroom. In addition to the box fan air cleaner, a ventilation unit known as an HUV, or a horizontal unit ventilator, was included in the simulation. This type of ventilation system is very common in public schools and is usually placed along an outside wall, drawing in air near the floor and exhausting it at the top to circulate fresh air around a classroom.
A cloud of virus particles was assumed to enter the simulation from an infected individual. The investigators assumed this individual was the instructor and experimented with different placements of the box fan air cleaner.
“Placing the air cleaner near the potential infector is the most effective way to reduce the aerosol spread,” said author Jiarong Hong.
The simulations showed the best results were obtained by shifting both the box fan air cleaner and the infected instructor to a location near the HUV.
“At this location, owing to its proximity to both the infector and the HUV, the air cleaner extracts the majority of aerosols, leaving only a small percentage suspended in the air,” Hong said.
Although placing the air cleaner near an infected individual is best, it is not always possible to know who is infected. In this situation, the investigators recommend placing the air cleaner near the HUV, with the air cleaner outflow pointing toward the inlet of the HUV.
“In addition, we find that in large classrooms, distributing multiple air cleaners in the space is more effective in controlling aerosol spread than simply enhancing the flow rate of the HUV or air cleaners alone,” Hong said.
Story Source:
Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Almost half (47.5%) of women with babies aged six months or younger met the threshold for postnatal depression during the first COVID-19 lockdown, more than double average rates for Europe before the pandemic (23%), finds a new study led by UCL researchers.
Women described feelings of isolation, exhaustion, worry, inadequacy, guilt, and increased stress. Many grieved for what they felt were lost opportunities for them and their baby, and worried about the developmental impact of social isolation on their new little one.
Those whose partners were unable or unavailable to help with parenting and domestic tasks, particularly where they were also dealing with the demands of home schooling, felt the negative impacts of lockdown most acutely.
Researchers surveyed 162 mums in London between May and June 2020 using a unique social network survey designed in response to lockdown. Participants listed up to 25 people who were important to them and shared who they had interacted with and how, whether in person, by phone, video call or messaging on social media.
The women also reported on their well-being with researchers basing depression ratings on the Edinburgh Postnatal Depression Scale, the most commonly used tool. This allowed them to capture the full range of mothers’ social interactions, as well as their mental health.
The findings are published today (11 May 2021) in the journal Frontiers in Psychology.

Patients with clinically diagnosed neurological symptoms associated with COVID-19 are six times more likely to die in the hospital than those without the neurological complications, according to an interim analysis from the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID).
A paper published today in JAMA Network Open presents early results of the global effort to gather information about the incidence, severity and outcomes of neurological manifestations of COVID-19 disease.
“Very early on in the pandemic, it became apparent that a good number of people who were sick enough to be hospitalized also develop neurological problems,” said lead author Sherry Chou, M.D., M.Sc., principal investigator of the consortium and associate professor of critical care medicine, neurology, and neurosurgery at the University of Pittsburgh School of Medicine and UPMC. “A year later, we are still fighting an unknown invisible enemy and, like in any battle, we need intel — we have to learn as much as we can about neurological impacts of COVID-19 in patients who are actively sick and in survivors.”
The GCS-NeuroCOVID is the largest cohort study of neurological manifestations of COVID-19 to date, spanning 133 adult patient sites in all continents except Antarctica.
Among one group of 3,744 hospitalized adult patients with COVID-19, 82% had self-reported or clinically captured neurological symptoms. Nearly 4 out of 10 patients reported having headaches, and approximately 3 out of 10 said they lost their sense of smell or taste. Of the clinically diagnosed syndromes — abnormalities that a bedside clinician can observe, regardless of whether the patient is aware of the problem — acute encephalopathy was most common, affecting nearly half of the patients, followed by coma (17%) and strokes (6%).
Despite early concerns about the coronavirus’s ability to directly attack the brain and cause brain swelling and inflammation — meningitis and encephalitis — those events were very rare, occurring in less than 1% of hospitalized COVID-19 patients.

Published today in Nature Communications, the team from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), Alfred Health and Monash University sought to understand which patients would recover quickly from influenza and which would become severely ill.
The four-year project took samples from patients hospitalised with influenza at up to five time points during their hospital stay, and 30 days after discharge. They analysed the breadth of the immune response, enabling them to describe the specific roles of several different types of immune cells, including killer and helper T cells, B cells and innate cells.
University of Melbourne Dr Oanh Nguyen, Research Fellow at the Doherty Institute, said two significant findings of the research include understanding the biomarkers that drive recovery and identifying four specific cytokines that cause serious inflammation during influenza virus infection.
“Cytokines are key molecules needed for a robust immune response. However, too much of these cytokines can result in inflammation and in the case of influenza, much more serious infection,” Dr Nguyen said.
“We found four specific types of cytokines that would cause severe inflammation, and this provides clinicians the ability to predict whether a patient will become really sick with influenza.”
The team also consistently saw large populations of immune cells called T-follicular helper cells, working in parallel with antibody-secreting cells, in patients at around three days prior to their recovery.
“These findings are the first to report the importance of T-follicular helper cells during acute influenza virus infection, following previous discoveries from our work and others on the key role of these immune cells after influenza vaccination. Signs of these cells could be used as a biomarker for recovery from influenza,” Dr Nguyen said.
Professor Allen Cheng, Director of Infection Prevention and Healthcare Epidemiology at Alfred Health and Professor of Infectious Diseases Epidemiology at Monash University, said this had been a great collaboration between clinicians and immunologists, and a good example of ‘bedside to bench’ science.
“The COVID-19 pandemic, and before this, the swine flu pandemic, has highlighted the importance of improving our understanding of respiratory viral infections to improve the identification of patients at risk of severe outcomes and potentially future treatments,” Professor Cheng said.
University of Melbourne Professor Katherine Kedzierska, Laboratory Head at the Doherty Institute and world-leading influenza immunologist, said this research laid the groundwork for her team’s understanding of how the immune system responds to COVID-19.
“Because of our years of experience, experimental set up, knowledge and collaborations with Alfred Health for this and other influenza studies, we had the speed and agility to apply our work to immune studies of COVID-19,” Professor Kedzierska said.
“This influenza study was the blueprint for our COVID-19 research.”
Story Source:
Materials provided by University of Melbourne. Note: Content may be edited for style and length.

Researchers at Chalmers University of Technology, Sweden, have developed a new material that prevents infections in wounds — a specially designed hydrogel, that works against all types of bacteria, including antibiotic-resistant ones. The new material offers great hope for combating a growing global problem.
The World Health Organization describes antibiotic-resistant bacteria as one of the greatest threats to global health. To deal with the problem, there needs to be a shift in the way we use antibiotics, and new, sustainable medical technologies must be developed.
“After testing our new hydrogel on different types of bacteria, we observed a high level of effectiveness, including against those which have become resistant to antibiotics,” says Martin Andersson, research leader for the study and Professor at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology.
Research and development of the material has been ongoing for many years at Martin Andersson’s group at Chalmers, growing in scope along the way, with a particular focus on the possibilities for wound care. Now, the important results are published as a scientific article in the journal ACS Biomaterials Science & Engineering.
The main purpose of the studies so far has been to explore new medical technology solutions to help reduce the use of systemic antibiotics. Resistant bacteria cause what is referred to as hospital-acquired infection — a life-threatening condition and is increasing in incidence worldwide.
Mimicking the natural immune system
The active substance in the new bactericidal material consists of antimicrobial peptides, small proteins which are found naturally in our immune system.