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Scientists are one step closer to discovering the causes of immune diseases such as asthma, multiple sclerosis and arthritis. Research from the Wellcome Sanger Institute, GSK and Biogen, under the Open Targets initiative, has shown that thousands of differences in DNA between individuals, associated with immune diseases, are linked with the switching-on of a specific subtype of immune cells.

Published today (23rd September) in Nature Genetics, this study will help narrow down the search for the molecular pathways involved in immune diseases and could lead to finding drug targets for developing new treatments.

The immune system keeps us healthy by fighting infections. However, if something goes wrong, the cells in our immune system can mistakenly cause inflammation, leading to immune diseases like asthma, multiple sclerosis and inflammatory bowel disease (IBD). These diseases affect millions of people worldwide, with more than 5 million asthma patients in the UK alone*, yet it is not known what triggers the immune system to respond in this way, or even the exact cell types involved.

Previous research found that there are thousands of genetic changes - known as genetic variants - that are more common in patients with immune diseases than in healthy people. Understanding these genetic changes could provide clues to the causes and biological pathways involved in immune disease, and in time, lead to identifying new drug targets.

Many of these genetic variants are in poorly understood areas of the genome and are thought to be involved in regulating functions of immune cells. Add to this, cytokines - the signalling proteins released to allow communication between the immune cells during inflammation - and the picture becomes even more complex, making it extremely difficult to pinpoint what is causing the disease.

Researchers at the Sanger Institute and their collaborators aim to understand which immune cell states are most important for immune diseases, in an effort to hone in on potential new drug targets for diseases like asthma and IBD.

In this new study, the team looked at which parts of the genome were active in three types of immune cells from healthy volunteers, and cross-checked these positions against all the genetic variants implicated in different immune diseases. They also added different cytokines, creating a total of 55 different cell states, to mimic immune disease inflammation and understand the effects of the signalling chemicals in these cells.

The study revealed that one particular cell type and cell state - early activation of memory T cells - had the most active DNA across the same regions as the genetic variants implicated in immune diseases. This pointed towards the initial activation of these T cells being important in disease development. Surprisingly, the research showed that the cytokines generally only had subtle effects on the DNA activity, and played a lesser role in most of the diseases studied.

Dr Blagoje Soskic, a lead author on the paper from the Wellcome Sanger Institute and Open Targets, said: "Our study is the first in depth analysis of immune cells and cytokine signals in the context of genetic differences linked to immune diseases. We found links between the disease variants and early activation of memory T cells, suggesting that problems with regulating this early T cell activation could lead to immune diseases."

Dr Rab Prinjha, Chair of the Open Targets Governance Board and Head of Adaptive Immunity and Immuno-Epigenetics Research Unit, GSK said: "At GSK, we deploy both genetics and genomics to identify which parts of the immune system are central to a range of human diseases and to yield better validated targets that could become transformational medicines. To investigate the science of the immune system, functional genomics helps us better understand the role that individual genes may or may not play in triggering pathogenic immune mechanisms. This paper is yet another result from our 5-year collaboration with Open Targets to advance the field and shows our focus on advanced technologies to drive our science."

To enable this complex analysis, the researchers developed a new computational method, called CHEERS, which enabled them to identify cell states relevant for immune diseases. Openly available**, this resource could also be used to find links between genetic variation and mechanisms for other complex diseases.

Dr Gosia Trynka, the senior author from the Wellcome Sanger Institute and Open Targets, said: "There are thousands of different cell types and states in the body, and finding the cause of autoimmune diseases is like finding a needle in a haystack. We have identified early activation of memory T cells as being particularly relevant to immune diseases, and will now be able to dive deeper into studying how this is regulated, to discover genes and pathways that could be used as drug targets."

New Iridium compounds effective towards killing cancer cells even without the presence of oxygen - expanding the range of tumours that can be targeted

When activated by light, compound cuts off the cancer cell's 'power source'

Technique could reduce side effects of cancer treatment and potentially immunise against future cancer

Most Iridium is believed to have come from the meteorite that wiped out dinosaurs, and uses include in spacecraft and satellites

A space-age metal that formed part of the asteroid that destroyed the dinosaurs could provide a new method of treating cancer tumours selectively using light.

Scientists at the University of Warwick in collaboration with colleagues in China, France, Switzerland and Heriot-Watt University have developed a technique that uses light to activate a cancer-killing compound of Iridium that attacks, for the first time, a vital energy source in cancer cells even under hypoxia, significantly opening up the range of cancers that can be treated using the technique.

The technique is detailed in a paper published today (23 September 2019) in Nature Chemistry and could lead to another tool for clinicians to use in the fight against cancer, and potentially even vaccinate patients against future cancers.

Photodynamic therapy (PDT) uses light to kill cancer tumours in the body by activating a chemical compound called a photosensitiser, which creates species that can attack cancer cells in the presence of light. Using this method, clinicians can direct the light to specific regions of the cancer tumour and spare normal tissue from damage.

Current methods mainly rely on the presence of oxygen and many tumours are 'hypoxic', which means that they are deficient in normal oxygen often due to poor blood supplies. The international team of scientists have now developed a compound of the metal Iridium that will kill cancer cells in culture even when oxygen concentration is low.

The technique can treat any tumours where light can be administered, and would be particularly suited to treat bladder, lung, oesophageal, brain and skin cancers. There are around 10,000 bladder cancer cases in the UK per year, of which about 5,000 might potentially benefit from this kind of treatment.

Professor Peter Sadler from the University of Warwick's Department of Chemistry said: "All the time in cancer treatment, clinicians are trying to fight resistance. Drugs can kill the cancer cells initially, but with repeated treatment the cells become resistant, they learn how to chemically modify the drug or counteract its mechanism of action. Researchers are looking for novel ways in which the cancer cell will die. If they have become resistant to other cancer drugs, they may not be resistant to this treatment because the way it kills the cancer cells is different.

"There is an increasing interest in reducing the side effects of cancer treatment as much as possible and anything that can be selective in what it targets will help with that. The compound that we have developed would not be very toxic at all, we would give it to the cancer cells, allow a little time for it to be taken up, then we would irradiate it with light and activate it in those cells. We would expect killing of those cancer cells to occur very quickly compared with current methods."

Once light-activated, the Iridium compound attacks the energy producing machinery in the cancer cells - a vital co-enzyme called nicotinamide adenine dinucleotide (NADH) - and catalytically destroys that co-enzyme or changes it into its oxidised form. This upsets the energy-producing machinery in a cancer cell and effectively cuts off the tumour's power source.

Our bodies need coenzyme nicotinamide adenine dinucleotide (NADH) to generate energy. Cancer cells have a very high requirement for NADH, because they need a lot of energy to divide and multiple rapidly.

The researchers even found that the compound still works in the presence of oxygen, by converting it into a 'toxic' type of oxygen that will kill the cancer cells.

The team of scientists also noted that as the cancer cells die, they change their chemistry in such a way that they will generate an immune reaction in the body, what is known as an immunotherapeutic response. This suggests that those treated by this technique might be immunised against attack by that cancer, and will be investigated further in future research.

Professor Vas Stavros (University of Warwick) commented: "The power of light to change the reactivity of chemical molecules dramatically within a thousandth of a millionth of a second can now be harnessed to treat resistant cancers."

Professor Martin Paterson (Heriot-Watt University) commented: "This breakthrough illustrates the power of modern computation to understand the effects of light on chemical molecules to provide drugs of the future with truly unique mechanisms of action."

Professor Hui Chao (Sun Yat-Sen University) commented: "Now we have a potential new drug which can not only selectively kill cancer cells with normal oxygen supplies, but also hypoxic cancer cells which often resist treatment by photodynamic therapy."

Professor Peter Sadler added: "The ability of metal compounds to induce an immunogenic response in the body that may effectively vaccinate a person against future attack by cancer is an exciting development. It is very speculative, but we are looking further into the hallmarks of that.

"Importantly we were fortunate to have had 3 highly talented young Royal Society Newton International Fellows in our team working on this challenging interdisciplinary project, who will undeniably contribute towards the future of this crucially important research."

Iridium was first discovered in 1803, and its name comes from the Latin for 'rainbow'. From the same family as platinum, it is hard, brittle, and is the world's most corrosion-resistant metal. Yellow in colour, its melting point is more than 2400° Celsius. It is used in satellites and spacecraft due to its resistance to extreme environments, and is commonly believed to have been enriched in the earth's crust by a meteorite that wiped out the dinosaurs 66 million years ago.

HOUSTON - (Sept. 23, 2019) - Rice University researchers have found a way to track the formation of soluble amyloid beta peptide aggregates implicated in the onset of Alzheimer's disease.

The Rice lab of Angel Martí reported its development of a ruthenium-based fluorescent complex that binds to soluble, oligomeric amyloid beta peptides. As the peptides come together to form the large biomolecules called oligomers, the fluorescent additive binds and labels them.

That will allow researchers to easily track the progress and movements of aggregates as they grow over time. Details of the work appear in the Journal of the American Chemical Society.

Amyloid plaques have long been suspected as the root cause of Alzheimer's, but recent studies suggest that oligomers -- floating molecules with repeating peptide units -- do far more damage.

"There's a view in the field that soluble oligomers are the main cause of neuronal degeneration, because these oligomers are toxic to neurons," said Martí, an associate professor of chemistry, of bioengineering and of materials science and nanoengineering.

"These oligomers are definitely associated with Alzheimer's pathology, so there's been a need for tools to help us study them."

He said oligomers are "virtually invisible" to Thioflavin T dyes commonly used to tag amyloid fibrils in lab studies. The ruthenium complexes solve that problem.

The complexes take advantage of fluorescence anisotropy, in which the fluorescent response is polarized, glowing brighter in some directions than others. "It's a very old technique related to the rotation of molecules," Martí said. "When the molecule is in solution, it moves and is constantly rotating. When it's very small, it rotates very fast and the anisotropy is nearly zero.

"But when the same probe binds to a big macromolecule, it rotates more slowly," he said. "That's how we know we have oligomers, and then we can track their growth and propagation."

Lab tests showed oligomers forming in solution at different temperatures over hours. Martí noted cold solutions slow the process, but at body temperatures, oligomers form "very fast and in large amounts. The speed at which they form at physiological temperatures is remarkable."

The Rice lab also used its probes to see how neuroblastoma cells were affected in real time when injected with amyloid beta peptides. They revealed only 60% of cells injected with oligomers remained viable, while those treated with amyloid fibrils and monomers had higher viability, about 80%, suggesting the oligomers are indeed toxic, Martí said.

For now, he said, the ruthenium probes are meant for use only in the laboratory. "It will be difficult to use these in the brain because there's too much scattering of light," Martí said. "They are made to take advantage of polarized light, and scattering would dampen that."

"But as a lab tool, they will allow researchers around the world to test the effects of other molecules on the rate of oligomer formation, and that's a big deal," he said. "They can quickly see if a drug delays or halts the formation of oligomers."

INFORMS Journal Marketing Science New Study Key Takeaways:

Artificial intelligence can increase sales by four times more than inexperienced workers.

If a customer is told about the use of artificial intelligence before purchasing, sales drop by nearly 80%.

The majority of the problem in using artificial intelligence is customer pushback.

CATONSVILLE, MD, September 23, 2019 - Chatbots, which use artificial intelligence to simulate human conversation through voice commands or text chats, incur almost zero marginal costs and can outsell some human employees by four times, so why aren't they used more often? According to new research, the main contributor is customer pushback.

Service industry outlets like American Eagle Outfitters and Domino's Pizza use chatbots, as well as online services like Amazon and eBay. The machines don't have "bad days" and never get frustrated or tired like humans, and they can save money for consumers, but new research in the INFORMS journal Marketing Science says if customers know about the chatbot before purchasing, sales rates decline by more than 79.7%.

The study authors, Xueming Luo and Siliang Tong (both of Temple University), Zheng Fang of Sichuan University, and Zhe Qu of Fudan University, targeted 6,000 customers from a financial services company. They were randomly assigned to either humans or chatbots, and disclosure of the bots varied from not telling the consumer at all, to telling them at the beginning of the conversation or after the conversation, or telling them after they'd purchased something.

"Our findings show when people don't know about the use of artificial intelligence (AI) chatbots they are four times more effective at selling products than inexperienced workers, but when customers know the conversational partner is not a human, they are curt and purchase less because they think the bot is less knowledgeable and less empathetic," said Luo, a professor and Charles Gilliland Distinguished Chair at Temple University.

"Chatbots offer enhanced technological benefits, reduced customer hassle costs and increased consumer welfare (offering the product at lower cost because bots save money on labor)," added Luo. "This data empowers marketers to target certain customer segments to cultivate customer trust in chatbots."

A study published today in Drugs & Aging found that older adults in Ontario with chronic obstructive pulmonary disease (COPD) were twice as likely to use prescription synthetic oral cannabinoids compared to older adults without COPD.

Using provincial health administrative databases, researchers found that while synthetic oral cannabinoid use was relatively low among adults over the age of 66 with COPD (0.6 per cent), this group was twice as likely to be using these drugs compared to adults of the same age without COPD (0.3 per cent).

The research led by St. Michael's Hospital in Toronto and the not-for-profit research institute ICES raises concerns about the use of synthetic cannabinoids, man-made versions of tetrahydrocannabinol (THC) - a key chemical in marijuana. When ingested, THC activates receptors in the central nervous system, producing a variety of potential effects including sedation, anxiety, muscle weakness and pain relief.

COPD is a progressive lung disease that causes breathing difficulty, but it can be associated with a variety of other problems too, like chronic muscle pain and insomnia. Psychoactive drug classes, like cannabinoids, are often prescribed to help reduce pain, promote sleep and decrease difficult-to-control breathlessness.

"Our study showed that patients and clinicians are turning to cannabinoids more frequently to manage the symptoms associated with COPD, but little is known about the potential dangers associated with this medication class," said Dr. Nicholas Vozoris, lead author, a respirologist at St. Michael's and an associate scientist at the hospital's Li Ka Shing Knowledge Institute and ICES.

"Previous studies by our team found that other psychoactive drugs, like opioids and benzodiazepines, are frequently used in COPD. We wanted to find out if this was the case too for synthetic oral cannabinoids."

Researchers also found that synthetic oral cannabinoids were used more frequently in subgroups of older adults with COPD at heightened risk for adverse events, such as those with psychiatric disease and those receiving other sedating psychoactive medications.

"Safety recommendations provided for these medications advise against prescribing cannabinoids in these groups," said Dr. Vozoris. "And yet these individuals with COPD are being exposed at greater rates."

The team also found that synthetic oral cannabinoids were used more often in potentially concerning ways among older adults with COPD, including more frequently at higher doses and for longer durations of time.

"Though the use of these drugs isn't too frequent today, without careful monitoring of the way they're being prescribed and used now, we could end up with larger problems in the future," Dr. Vozoris said.

As one of the first studies to describe the use of this drug class in individuals with COPD, Dr. Vozoris said these results provide a basis for future research to examine the effects of oral synthetic cannabinoid use on respiratory outcomes among individuals with COPD.

The results also provide a foundation for clinicians to make more informed decisions regarding the use of this drug class.

"We hope that clinicians read our paper and walk away with a better understanding of this drug class," said Dr. Vozoris. "We'd like them to reflect on their own prescribing practices and ensure cannabinoid drugs are used and prescribed with vigilance."

PHILADELPHIA (September 23, 2019) - Nurse burnout impacts both nurses and patients, and significantly influences the retention of nurses in the healthcare setting, research shows. But could burnout be a symptom of something larger?

A commentary by a University of Pennsylvania School of Nursing (Penn Nursing) nurse-bioethicist explores the effects of ethical issues faced by clinicians in practice and how moral distress may play a larger role in the loss of clinicians in the workplace.

"Moral distress may be inevitable in the multifaceted and ethically complicated arena of meeting the healthcare needs and preferences of diverse patients, but such distress need not inevitably lead to negative outcomes," wrote Connie M. Ulrich, PhD, RN, FAAN, the Lillian S. Brunner Chair in Medical and Surgical Nursing and Professor of Bioethics and Nursing , co-author of the commentary.

Moral distress results from managing the complex ethical issues in healthcare practice and patient care. Those morally stressing situations can make clinicians feel unable to provide the care they think is best based on their professional standards of practice and their values. While the confidence, moral clarity, and self-efficacy that come with moral strength can help clinicians make difficult ethical decisions, moral strength can likewise be eroded in the healthcare environment.

While support and training efforts to help clinicians develop coping skills, resiliency, and enhanced moral strength are important, the authors caution that it is imperative to also address organizational and systemic factors that contribute to moral distress and ways to support clinicians' capacity to act with moral strength.

"More research into the subject is needed in order to prioritize educational and institutional change that address the ethical complexities in healthcare institutions, as well as interventions to prevent the experience of moral distress from leading to self-doubt and to the erosion of moral strength," said Ulrich.

Researchers at the University of Illinois at Urbana-Champaign have constructed a quantum-mechanical state in which the colors of three photons are entangled with each other. The state is a special combination, called a W state, that retains some entanglement even if one of the three photons is lost, which makes it useful for quantum communication. Such entangled states also enable novel quantum applications and tests of fundamental physics.

The uniqueness of this work is that the researchers used color, or the energy of the photons, as the entangling degree of freedom, while previous work used polarization. The energy of a photon cannot be easily changed, which reduces the possibility of errors when the energy-entangled W state is propagating over a long distance. The state was verified for the first time by measuring information about the two-photon sub-systems.

"People have created polarization-entangled W states before," noted Bin Fang, the graduate student on the project. "However, this is the first discrete energy-entangled W state and the first three-photon entangled state created in optical fiber."

To create the state, the researchers shine a laser into a glass fiber. Through a process called spontaneous four-wave mixing, four laser photons interact with the fiber and are annihilated to create two pairs of photons at different colors (for example, two pairs of red and green photons). These four photons are used to construct the 3-photon W state. One of them is detected to be green, leaving the other three entangled as a W state, which is comprised of all possible iterations of two red photons and a green photon at once.

The illustration that the researchers use is that of traffic lights.

"Like three traffic lights that always signal two stops and a go, the photons' colors always end up being two reds and a green, but the specific combination is not set until we make a measurement - a feature of the quantum mechanical nature of photons," said Virginia Lorenz, associate professor of physics and the principal investigator.

Compared to other types of three-particle entanglement, the W state is useful for quantum communication in that, if one of the photons is lost, the other two retain some entanglement, meaning the communication is able to continue.

"Another new aspect of this research is that we found a path to verify the state is the one we aimed for that circumvents a complicated color conversion step, " said Lorenz. "Our theorist collaborators came up with a way to fairly straightforwardly show that the W state exists."

What does it take for a human to trust a robot? That is what Army researchers are uncovering in a new study into how humans and robots work together.

Research into human-agent teaming, or HAT, has examined how the transparency of agents--such as robots, unmanned vehicles or software agents--influences human trust, task performance, workload and perceptions of the agent. Agent transparency refers to its ability to convey to humans its intent, reasoning process and future plans.

New Army-led research finds that human confidence in robots decreases after the robot makes a mistake, even when it is transparent with its reasoning process. The paper, "Agent Transparency and Reliability in Human-Robot Interaction: The Influence on User Confidence and Perceived Reliability," has been published in the August issue of IEEE-Transactions on Human-Machine Systems.

To date, research has largely focused on HAT with perfectly reliable intelligent agents--meaning the agents do not make mistakes--but this is one of the few studies that has explored how agent transparency interacts with agent reliability. In this latest study, humans witnessed a robot making a mistake, and researchers focused on whether the humans perceived the robot to be less reliable, even when the human was provided insight into the robot's reasoning process.

"Understanding how the robot's behavior influences their human teammates is crucial to the development of effective human-robot teams, as well as the design of interfaces and communication methods between team members," said Dr. Julia Wright, principal investigator for this project and researcher at U.S. Army Combat Capabilities Development Command's Army Research Laboratory, also known as ARL. "This research contributes to the Army's Multi-Domain Operations efforts to ensure overmatch in artificial intelligence-enabled capabilities. But it is also interdisciplinary, as its findings will inform the work of psychologists, roboticists, engineers, and system designers who are working toward facilitating better understanding between humans and autonomous agents in the effort to make autonomous teammates rather than simply tools.

This research was a joint effort between ARL and the University of Central Florida Institute for Simulations and Training, and is the third and final study in the Autonomous Squad Member (ASM) project, sponsored by the Office of Secretary of Defense's Autonomy Research Pilot Initiative. The ASM is a small ground robot that interacts with and communicates with an infantry squad.

Prior ASM studies investigated how a robot would communicate with a human teammate. Using the Situation awareness-based Agent Transparency model as a guide, various visualization methods to convey the agent's goals, intents, reasoning, constraints, and projected outcomes were explored and tested. An at-a-glance iconographic module was developed based on these early study findings, and then was used in subsequent studies to explore the efficacy of agent transparency in HAT.

Researchers conducted this study in a simulated environment, in which participants observed a human-agent Soldier team, which included the ASM, traversing a training course. The participants' task was to monitor the team and evaluate the robot. The Soldier-robot team encountered various events along the course and responded accordingly. While the Soldiers always responded correctly to the event, occasionally the robot misunderstood the situation, leading to incorrect actions. The amount of information the robot shared varied between trials. While the robot always explained its actions, the reasons behind its actions and the expected outcome of its actions, in some trials the robot also shared the reasoning behind its decisions, its underlying logic. Participants viewed multiple Soldier-robot teams, and their assessments of the robots were compared.

The study found that regardless of the robot's transparency in explaining its reasoning, the robot's reliability was the ultimate determining factor in influencing the participants' projections of the robot's future reliability, trust in the robot and perceptions of the robot. That is, after participants witnessed an error, they continued to rate the robot's reliability lower, even when the robot did not make any subsequent errors. While these evaluations slowly improved over time as long as the robot committed no further errors, participants' confidence in their own assessments of the robot's reliability remained lowered throughout the remainder of the trials, when compared to participants who never saw an error. Furthermore, participants who witnessed a robot error reported lower trust in the robot, when compared to those who never witnessed a robot error.

Increasing agent transparency was found to improve participants' trust in the robot, but only when the robot was collecting or filtering information. This could indicate that sharing in-depth information may mitigate some of the effects of unreliable automation for specific tasks, Wright said. Additionally, participants rated the unreliable robot as less animate, likable, intelligent, and safe than the reliable robot.

"Earlier studies suggest that context matters in determining the usefulness of transparency information," Wright said. "We need to better understand which tasks require more in-depth understanding of the agent's reasoning, and how to discern what that depth would entail. Future research should explore ways to deliver transparency information based on the tasking requirements."

Findings from an innovative new study led by researchers at Dartmouth's Geisel School of Medicine and published this week in Nature Microbiology reveal that the way in which human fungal pathogens form colonies can significantly impact their ability to cause disease.

Highly diverse and adaptable, these colonies, known as biofilms, allow invasive fungal pathogens such as Aspergillus fumigatus to grow and thrive, infecting the lungs of patients, even under demanding environmental circumstances.

"It's a type of infection that most people don't have to be concerned about, since our immune systems have evolved to allow us to be resistant to fungi in the environment," explains Robert Cramer, PhD, a professor of microbiology and immunology at Geisel and senior author on the study.

But for patients with diseases like cancer, who are on drugs or therapies that suppress their immune systems, the infections can be lethal. "Since fungi are some of our closest relatives genetically, the drugs we have for treatment are limited and very toxic," says Cramer. "The big challenge we face is trying to develop new therapies that target these infections in critically ill patients, that don't make them sicker but also can prevent these organisms from causing morbidity and mortality."

To this end, in the study the researchers sought to assess how an important environmental stressor impacts disease progression in invasive aspergillosis, a disease caused by the mold Aspergillus fumigatus, and to identify fungal genetic factors involved in this process.

"Our project was based on some previous work Robb had done, which showed that within the lesions in the lung where the fungus is growing there's actually very little oxygen available," says Caitlin Kowalski, Guarini '20, a PhD candidate in the Cramer Lab at Geisel and first author on the study. "This puts a lot of stress on the fungus, but some strains are able to grow in a hypoxic (oxygen deficient) environment better than others."

Collaborating with Jason Stajich, PhD, a genomics expert at the University of
California-Riverside, the team used an experimental evolution approach, exposing the pathogen to low oxygen conditions to identify genes and mechanisms involved in low oxygen fitness. They then screened for and identified a specific mutation that caused key changes in gene function.

"Not only did the strain that we isolated end up growing better in low oxygen, it was better able to cause disease in a murine model of infection where we know (from previous studies) that the lungs become hypoxic," says Kowalski. "In the process we were able to ascribe function to a gene that was previously unknown to have any role in Aspergillus physiology and virulence."

Working with Carey Nadell, PhD, an assistant professor of biological sciences at Dartmouth College, Kowalski and her colleagues were also able to use advanced microscopy techniques that revealed differences in the strain's filamentous architecture.

"I think that's the other big takeaway from Caitlin's project, in addition to the novel gene finding," says Cramer. "That is, that the appearance of the organism can actually tell us something about how it's going to behave in the lung--in this case, how this particular morphology gives the organism the ability to be more virulent and to cause more host damage."

Understanding these characteristics is an important step in developing more effective therapies for patients. "For these strains that look different and cause more inflammation, we may need to incorporate more host-targeted therapeutics--and our field is moving in this direction--to dampen down the immune response and allow antifungals more time to actually work," he explains.

Cramer credits the Burroughs Wellcome Fund, of which he is an Investigator in the Pathogenesis of Infectious Diseases, as a key source of support for the research.

"The fellowship allows me to take some risks with certain projects, where you're sort of in unchartered territory and you don't know what you're going to find," he says. "It paid off very handsomely in that it allowed us to generate some valuable data, which is already helping us secure other grant funding, such as from the NIH, that will help support Caitlin's career and our overall efforts to reduce the disease burden caused by this organism."

Athens, Ga. - If children are exposed to bias against one person, will they develop a bias against that person's entire group? The answer is yes, according to new research from University of Georgia social psychologist Allison Skinner. The study's results are the first to demonstrate that nonverbal signals can produce new biases that generalize to entire groups and classes of people.

"Our findings indicate that the process of acquiring bias based on nonverbal signals--and extending that bias to a larger group--is already in operation in early childhood, prior to the start of first grade," said Skinner, first author and assistant professor of psychology in the Franklin College of Arts and Sciences. "Exposure to biased nonverbal signals may be an important process through which group biases are rapidly and unintentionally transmitted within our culture."

Her study, published in the Journal of Personality and Social Psychology, explores bias generalization in preschoolers aged 4 and 5.

With co-authors Kristina R. Olson and Andrew N. Meltzoff (both University of Washington), Skinner tested whether preschool children seeing one individual receive more positive nonverbal signals than another would lead them to develop bias in favor of that individual's group--and whether such biases would be generalized to large classes of people, for example, those of the same nationality.

In the experiments, children watched video in which an adult actor displayed positive nonverbal signals--appearing warm and friendlier--toward an unknown adult from one fictitious place and negative nonverbal signals toward an unknown adult from another place. The preschoolers were then asked questions to assess their biases toward the adults in the videos and toward other people of their "nationality."

"Children's biases went beyond simply preferring people from one place relative to another," Skinner said. "They were more likely to imitate the words and actions demonstrated by the target of positive nonverbal signals, and they preferred to interact with members of that individual's group."

This study follows on the heels of her previously published work on the role of nonverbal signals in spreading attitudes and biases among adults. In a study published in Personality and Social Psychology Bulletin, Skinner found that adults formed conscious attitudes toward an individual based on witnessing positive or negative nonverbal signals displayed toward that person. They also formed unconscious attitudes, but they were likely to misattribute the cause, according to Skinner.

"People were more likely to attribute their attitude to how the individual behaved, rather than how the individual was treated by others," she said. "It didn't matter if the individual responded neutrally. If people treated him as if he was behaving like a jerk, then that was their inference."

A new imaging study of the mummified arteries of people who lived thousands of years ago revealed that their arteries were more clogged than originally thought, according to a proof-of-concept study led by a researcher with The University of Texas Health Science Center at Houston (UTHealth). It is in the October print edition of the American Heart Journal.

"I wanted to see if heart disease is a modern-day problem. It appears to have been a problem for a very long time," said Mohammad Madjid, MD, MS, the study's lead author and an assistant professor of cardiovascular medicine with McGovern Medical School at UTHealth.

In the past when researchers analyzed the hearts and arteries of mummies, they used an imaging technique called computed tomography (CT scan) that creates meticulous images of blood vessels, organs, and bones. However, these scans detect only accumulated calcium in the arteries, not buildup of cholesterol.

Madjid said his team is the first to examine mummified arterial remains from different parts of the world with an imaging technique that detects cholesterol. It is called near-infrared spectroscopy.

"A catheter is placed on the sample and it sends out signals. The signals bounce off the tissue and come back. You can tell the difference between various tissue components because each has a unique molecular signature like a fingerprint," Madjid said.

Madjid's samples included mummified arterial tissue from three men and two women ranging in age from 18 to 55-60. Three died presumably of pneumonia and one of renal failure. The cause of death for the fifth person is unknown. Four lived in South America and one in the Middle East. They lived from the late Chinchorro era, 2000 B.C., to Cabuza, 350 to 1000 A.D.

The type of arterial disease detected is the result of cholesterol plaque buildup in arteries and is formally called atherosclerosis. It limits the flow of oxygen-rich blood to various parts of the body, and it can lead to a heart attack.

Cholesterol buildup is a hallmark of atherosclerosis from the very early stages, while calcium accumulation is a sign of late stages of the disease. Therefore, relying only on calcium by CT scan underestimates the true prevalence of the disease, Madjid said.

Madjid, who is affiliated with UT Physicians and the Memorial Hermann Heart & Vascular Institute -Texas Medical Center, said factors such as exposure to smoke from fire pits, viral infections, bacterial infections, and bad genes might have contributed to the plaque buildup in people living centuries ago.

The buildup was also present in people at a relatively young age, he said.

The study offers new insight into the earlier pathological stages of atherosclerosis, showing a prevalence of cholesterol-rich plaques even in ancient times, the authors reported.

Madjid plans to examine additional mummified remains to see how widespread the arterial problems were.

The authors concluded, "Noninvasive near-infrared spectroscopy is a promising technique for studying ancient mummies of various cultures to gain insight into the origins of atherosclerosis."

Phoenix, Arizona, USA: Mosasaurs were true sea monsters of late Cretaceous seas. These marine lizards -- related to modern snakes and monitor lizards -- grew as long as fifty feet, flashed two rows of sharp teeth, and shredded their victims with enormous, powerful jaws.

Now, new research suggests that mosasaurs had yet another potent advantage: a muscular breast stroke that may have added ambush-worthy bursts of speed.

"We know that mosasaurs most likely used their tails for locomotion. Now we think that they also used their forelimbs, or their tail and forelimbs together," explains lead author Kiersten Formoso, a Ph.D. student in vertebrate paleontology at the University of Southern California. That dual swimming style, she says, could make mosasaurs unique among tetrapods (four limbed creatures), living or extinct.

Previous studies noted that mosasaurs had an unusually large pectoral girdle--the suite of bones that support the forelimbs. But most assumed the creature's swimming was mainly driven by their long tails, something like alligators or whales. That smooth, long distance-adapted swimming style is called "cruising," as opposed to "burst" motion. "Like anything that swims or flies, the laws of fluid dynamics mean that burst versus cruising is a tradeoff," explains co-author Mike Habib, Assistant Professor of Anatomical Sciences at USC. "Not many animals are good at both."

To dive in more closely on whether mosasaurs were burst-adapted, cruise-adapted, or an unusual balance of both, Formoso and co-authors focused on the oversized pectoral girdle. They studied a fossil Plotosaurus, a type of mosasaur, at the Natural History Museum of Los Angeles County. In addition, they used measurements of mosasaur pectoral girdles published in other studies.

They determined that the mosasaurs' unusually large and low-placed pectoral girdle supported large muscle attachments. In addition, says Habib, asymmetry in the bone structure is a telltale sign of the strong, inward pull-down motion called adduction. These analyses suggest that mosasaurs used their forelimbs to swim, breast-stroke style, adding powerful bursts of propulsion to their ability to cruise.

The team continues to model bone structure, morphology, measurements, and fluid dynamics such as drag to learn exactly how, and how fast, these sea monsters swam. Along with applications to biomechanics, and even robotics, say Formoso and Habib, the study also sheds light on how evolution and ecosystems are affected by fluid dynamics.

Formoso points out that it's a challenge to study kinematics on extinct animals, considering that the subjects are missing flesh, skin, and many bones. But one thing is nearly certain, she says. "Mosasaurs swam unlike anything else."

BUFFALO, N.Y. -- Onions and garlic are key ingredients in sofrito, a condiment that's a staple of Puerto Rican cuisine. They may also be a recipe for reducing the risk of breast cancer.

That's according to the findings of a study led by University at Buffalo and University of Puerto Rico researchers. It's the first population-based study to examine the association between onion and garlic consumption and breast cancer in Puerto Rico. The results were published in the journal Nutrition and Cancer.

"We found that among Puerto Rican women, the combined intake of onion and garlic, as well as sofrito, was associated with a reduced risk of breast cancer," said Gauri Desai, the study's lead author, who is an epidemiology PhD student in UB's School of Public Health and Health Professions.

In fact, those who consumed sofrito more than once per day had a 67% decrease in risk compared to women who never ate it. The idea for the study stemmed from previous scientific evidence showing that eating onions and garlic may have a protective effect against cancer.

"Studying Puerto Rican women who consume a lot of onions and garlic as sofrito was unique," Desai said, adding that it was total intake of onions and garlic, not sofrito alone, that was associated with breast cancer risk.

Puerto Rico was a perfect place to study, because women there consume larger amounts of onions and garlic than in Europe and the U.S., due largely to the popularity of sofrito, Desai noted. Onions and garlic also are eaten regularly in "guisos" (stews), as well as in bean- and rice-based dishes in Puerto Rican cuisine.

In addition, "Puerto Rico has lower breast cancer rates compared to the mainland U.S., which makes it an important population to study," Desai said.

"There is very little research on breast cancer in Puerto Rico. This study was a collaboration between my colleagues here at UB and at the University of Puerto Rico to help us understand why rates there are lower than in the rest of the U.S., and why rates there are continuing to increase while they are decreasing in the rest of the United States," said study co-author Jo Freudenheim, PhD, chair of epidemiology and environmental health at UB.

So, why the focus on these two ingredients? "Onions and garlic are rich in flavonols and organosulfar compounds," Desai said.

In particular, garlic contains compounds such as S-allylcysteine, diallyl sulfide and diallyl disulfide, while onions contain alk(en)yl cysteine sulphoxides. "These compounds show anticarcinogenic properties in humans, as well as in experimental animal studies," said Lina Mu, the study's senior author, who is an associate professor of epidemiology and environmental health at UB.

Study participants were enrolled in the Atabey Study of Breast Cancer, a case-control study named after the Puerto Rican goddess of fertility. The study was conducted between 2008 and 2014 and included 314 women with breast cancer and 346 control subjects.

A new report highlights the latest advances in cell-based therapies for the treatment of disorders of the musculoskeletal system, such as arthritis and osteoporosis, and it identifies key unanswered questions that should be addressed through ongoing research. The report is published in the Journal of Bone and Mineral Research and concurrently in the Journal of Orthopaedic Research, and was issued by a joint Task Force of the American Society for Bone and Mineral Research and the Orthopaedic Research Society.

With cell-based therapies, cells are injected, grafted, or implanted into a patient. Due to the lack of rigorous clinical studies and randomized clinical trials, however, these treatments should be considered experimental. The Task Force provides specific recommendations and ethical considerations for preclinical and clinical investigations of cell-based therapies, and it highlights the importance of determining the direct and indirect effects of these therapies on disease.

"This is an area of enormous public interest and scientific importance," said lead author and task force co-chair Regis O'Keefe, MD, PhD, of Washington University School of Medicine in St. Louis. "Musculoskeletal diseases such as osteoarthritis, intervertebral disc degeneration, and tendinopathies cause pain, impair function, and can lead to a sense of helplessness. Currently a large number of unproven cell-based therapies are marketed to a vulnerable population of patients that suffer from musculoskeletal disease." "The goal of the task force was to provide, in an unbiased way, a balanced assessment of the current state of cell-based therapies and to define the scientific agenda needed to develop more proven and effective approaches to treatment in the future," said task force co-chair Rocky Tuan, PhD, of the Chinese University of Hong Kong.

Current obesity rates in adults in the United States could be the result of dietary changes that took place decades ago, according to a new study published by researchers at the University of Tennessee, Knoxville.

"While most public health studies focus on current behaviors and diets, we took a novel approach and looked at how the diets we consumed in our childhood affect obesity levels now that we are adults," said Alex Bentley, head of UT's Department of Anthropology and lead researcher of the study, which was published in Economics and Human Biology.

Consumption of excess sugar, particularly in sugar-sweetened beverages, is a known contributor to both childhood and adult obesity. Many population health studies have identified sugar as a major factor in the obesity epidemic. One problem with this theory, however, has been that sugar consumption in the US began to decline in the late 1990s while obesity rates continued to rise well into the 2010s.

That increase shows in the numbers: By 2016, nearly 40 percent of all adults in the US--a little over 93 million people--were affected by obesity. In Tennessee alone, the adult obesity rate more than tripled, from about 11 percent in 1990 to almost 35 percent in 2016. By 2017, however, obesity in Tennessee had fallen 2 percent from the previous year.

If high-sugar diets in childhood have long-lasting effects, the changes we see now in adult obesity rates may have started with diets decades ago, when those adults were children.

"Since the 1970s, many available infant foods have been extremely high in sugar," said Hillary Fouts, coauthor of the study and cultural anthropologist and professor in the UT Department of Child and Family Studies. "Other independent studies in medicine and nutrition have suggested that sugar consumption during pregnancy can cause an increase in fat cells in children," she added.

"Up to this point, no studies had explicitly explored the temporal delay between increased sugar consumption and rising obesity rates," says Damian Ruck, postdoctoral research fellow in the Department of Anthropology and coauthor of the study. To address the problem, the authors modeled the increase in US adult obesity since the 1990s as a legacy of the increased excess sugar consumption measured among children in the 1970s and 1980s.

The researchers tested their model using national obesity data collected between 2004 and 1990 by the Centers for Disease Control and Prevention. They compared those obesity rates with annual sugar consumption since 1970 using the median per capita rates issued by the US Department of Agriculture.

The model also roughly captures how obesity rates vary by age group among children and teenagers.

"Our results suggest that the dietary habits learned by children 30 or 40 years ago could explain the adult obesity crisis that emerged years later," said Ruck.

A large portion of the sugar increase before 2000 was from high fructose corn syrup (HFCS), which after 1970 quickly become the main sweetener in soft drinks and a common ingredient in processed foods. At peak sugar consumption, in 1999, each person in the US consumed on average around 60 pounds of HFCS per year and more than 400 calories per day in total excess sugars.

US sugar consumption has declined since 2000. "If 2016 turns out to be the peak in the obesity rate," Bentley added, "that is coincidentally one generation after the peak in excess sugar consumption."

The researchers are planning to continue their studies in the area by exploring the effect of sugar-sweetened beverages. "This is important because obesity disproportionately affects the poor," said Bentley.

In a paper published in Palgrave Communications in 2018, Bentley and his colleagues found that the relationship between low income and high rates of obesity became noticeable on a national scale in the early 1990s. The 2018 study shows that the correlation between household income and obesity rate has grown steadily, from virtually no correlation in 1990 to a very strong correlation by 2016.