Culture

A team led by researchers at Weill Cornell Medicine and Children's National Hospital has developed a unique pre-clinical model that enables the study of long-term HIV infection, and the testing of new therapies aimed at curing the disease.

Ordinary mice cannot be infected with HIV, so previous HIV mouse models have used mice that carry human stem cells or CD4 T cells, a type of immune cell that can be infected with HIV. But these models tend to have limited utility because the human cells soon perceive the tissues of their mouse hosts as "foreign," and attack--making the mice gravely ill.

By contrast, the new mouse model, described in a paper in the Journal of Experimental Medicine on May 14, avoids this problem by using a subset of human CD4 cells that mostly excludes the cells that would attack mouse tissue. The researchers showed that the mice can usefully model the dynamics of long-term HIV infection, including the virus's response to experimental therapies.

"We expect this to be a valuable and widely used tool for studying the basic science of HIV infection, and for speeding the development of better therapies," said co-first author Dr. Chase McCann. During the study, Dr. McCann was a Weill Cornell Graduate School student in the laboratory of senior author Dr. Brad Jones, associate professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine. Dr. McCann, who was supported at Weill Cornell by a Clinical and Translational Science Center (CTSC) TL1 training award, is now the Cell Therapy Lab Lead in the Center for Cancer and Immunology Research at Children's National Hospital in Washington, DC. The other co-first authors of the study are Dr. Christiaan van Dorp of Los Alamos National Laboratory and Dr. Ali Danesh, a senior research associate in medicine at Weill Cornell Medicine.

The invention of the new mouse model is part of a wider effort to develop and test cell therapies against HIV infection. Cell therapies, such as those using the patient's own engineered T cells, are increasingly common in cancer treatment and have achieved some remarkable results. Many researchers hope that a similar strategy can work against HIV and can potentially be curative. But the lack of good mouse models has hampered the development of such therapies.

Drs. Jones and McCann and their colleagues showed in the study that the cell-attacks-host problem found in prior mouse models is chiefly due to so-called "naïve" CD4 cells. These are CD4 cells that have not yet been exposed to targets, and apparently include a population of cells that can attack various mouse proteins. When the researchers excluded naïve CD4 cells and instead used only "memory" CD4 cells, which circulate in the blood as sentinels against infection following exposure to a specific pathogen, the cells survived indefinitely in the mice without causing major damage to their hosts.

The researchers observed that the human CD4 cells also could be infected and killed by HIV, or protected by standard anti-HIV drugs, essentially in the same way that they are in humans. Thus, they showed that the mice, which they termed "participant-derived xenograft" or PDX mice, served as a workable model for long-term HIV infection. This term is akin to the "patient-derived xenograft" PDX models used to study cancer therapies, while recognizing the contributions of people with HIV as active participants in research.

Lastly, the researchers used the new model to study a prospective new T-cell based therapy, very similar to one that is now being tested against cancers. They put memory CD4 T cells from a human donor into the mice to permit HIV infection, and then, after infection was established, treated the mice with another infusion of human T cells, these being CD8-type T cells, also called "killer T cells."

The killer T cells were from the same human donor and could recognize a vulnerable structure on HIV--so that they attacked the virus wherever they found it within the mice. To boost the killer T cells' effectiveness, the researchers supercharged them with a T cell-stimulating protein called IL-15.

The treatment powerfully suppressed HIV in the mice. And although, as often seen in human cases, the virus ultimately evolved to escape recognition by the killer T cells, the ease of use of the mouse model allowed the researchers to monitor and study these long-term infection and viral escape dynamics in detail.

"I think that the major impact of this model will be its acceleration of the development of T cell-based therapies that can overcome this problem of viral escape," Dr. Jones said.

He and his laboratory are continuing to study such therapies using the new mouse model, with engineered T cells from Dr. McCann's laboratory and others.

May 14, 2021 - Two thirds of all pediatric spinal fractures, especially in the adolescent population, occur in motor vehicle accidents (MVAs) where seatbelts are not utilized, reports a study in Spine. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Over 60 percent of pediatric spinal fractures occur in children ages 15 to 17, coinciding with the beginning of legal driving," according to the new research by Dr. Vishal Sarwahi, MD, of Cohen Children's Medical Center, New Hyde Park, NY, and colleagues. They emphasize the need for measures to increase seatbelt usage, particularly by younger drivers, and outline the potential trauma that can be avoided through proper seatbelt use.

Seatbelts save lives... and spines

Motor vehicle accidents are the leading cause of death amongst teenagers in the United States. Many previous studies have reported rising rates of pediatric spinal injuries, especially in teens aged 15 and older. This new study confirms that MVAs, in fact, cause most spinal fractures in children and adolescents, with high rates of other injuries. Spinal fractures in young patients are also associated with a three percent mortality rate, with many deaths occurring in unrestrained drivers and passengers.

Using the American College of Surgeons' National Trauma Data Bank, Dr. Sarwahi and his colleagues studied 34,563 pediatric patients (younger than 18 years) who sustained spinal fractures between 2009 and 2014. Many of the patients had multiple spinal fractures, with a total of 45,430 fractured vertebrae.

Overall, teenagers between age 15 and 17 years accounted for about 63 percent of spinal fractures, two-thirds of which occurred in MVAs. These findings show that around the time teens get their drivers' license, drivers and passengers are at highest risk for MVA resulting in spinal fracture.

Fifty-eight percent of the injured patients were male. Pediatric spinal fractures were found to be most common in the South: 38 percent, probably due to a lack of public transport resulting in more vehicles on the road.

The study also shows the impact of seatbelt use on these devastating injuries. "Nearly two-thirds of pediatric spinal fractures sustained in MVAs occurred in children who did not use belts," Dr. Sarwahi and co-authors write. Without seatbelts, the risks of severe or multiple injuries and death are substantially increased, with a significantly increased death rate from 29.3 percent to 70.7 percent - more than doubled.

Data on seatbelt use was available for nearly 19,000 patients, with approximately two-thirds of patients (65.9 percent) unrestrained. Almost half (44.2 percent) of unrestrained patients in MVAs were teenagers. Despite a larger percentage of MVAs occurring in the South overall, the percentage of spinal fractures from MVAs for unrestrained drivers and passengers was similar across all regions of the United States; approximately two-thirds of all teenagers across all regions - Northeast, Midwest, West, South - involved in MVAs did not wear seatbelts. This demonstrates the universality of teenage risk-taking behavior and identifies at-risk groups for risk modification strategies.

When seatbelts were worn, the rate of spinal fractures was substantially lower for all drivers and passengers. Seatbelt use lowered the risk of death by more than 20 percent. For young patients in MVAs, wearing seatbelts was also associated with lower rates of multiple vertebral fractures, other types of fractures in addition to spinal fracture, and head and brain injury.

While the percentage of drivers wearing seatbelts has risen steadily over the years, adolescents and young adults remain less likely to use these lifesaving devices. Dr. Sarwahi and colleagues discuss targeted approaches using technology and media awareness campaigns to increase seatbelt use among young people, as well as studies showing the importance of societal and cultural norms related to seatbelts. The researchers conclude: "Ensuring our new, young drivers wear protective devices can greatly reduce morbidity/mortality associated with MVA and can help save lives, and spines."

ITHACA, NY, May 13, 2021 -- Cyanobacteria are one of the unsung heroes of life on Earth. They first evolved to perform photosynthesis about 2.4 billion years ago, pumping tons of oxygen into the atmosphere - a period known as the Great Oxygenation Event - which enabled the evolution of multicellular life forms.

Led by BTI faculty member Fay-Wei Li, researchers have discovered a new species of cyanobacteria, Anthocerotibacter panamensis, which could help illuminate how photosynthesis evolved to create the world as we know it. The work was published in Current Biology on May 13.

"We never intended to discover a new species," said Li. "It was a total accident."

His lab was working on a project to isolate cyanobacteria from hornwort plants, and noticed something weird in a sample from a rainforest in Panama. The researchers sequenced the cyanobacterium's DNA, and found that it belonged to a group called Gloeobacteria, which is extremely rare.

"Prior to this discovery, only two species of Gloeobacteria had been isolated," Li said. "There is also a third group of uncultured species from the Arctic and Antarctic regions, but no one knows how many species are in that group."

Gloeobacteria diverged from the more commonly studied Phycobacteria about 2 billion years ago. The two groups have many differences, and A. panamensis shares some traits with each.

Similar to other Gloeobacteria, the new species lacks thylakoids - the membrane-bound compartments that are the site of the light-dependent reactions of photosynthesis in Phycobacteria and plants.

"Now we can be pretty sure that the thylakoid evolved in Phycobacteria," Li said.

On the other hand, A. panamensis makes carotenoids - a group of compounds that help protect an organism from sun damage - in a fashion similar to Phycobacteria and plants, but different from the other Gloeobacteria.

"These results suggest that this particular carotenoid biosynthesis pathway evolved in the ancestor of all cyanobacteria, and then was lost in some Gloeobacteria," said Li.

Li said one of the more interesting findings is that A. panamensis has very few genes that encode the proteins that perform light-dependent reactions. The researchers found that the new species could still perform photosynthesis, but very slowly, which could be of interest to synthetic biologists.

"If you want to build a complete set of photosynthetic machinery with the fewest necessary components, then this species could inform how to do that," said Li. "Anthocerotibacter has a minimal set of photosystem subunits, but it still functions."

The United States has witnessed a steep rise in reports, arrests, and media coverage of teachers' sexual misconduct with students. A new study investigated the impact of perpetrators' gender, sexuality, and age on perceptions of teacher sexual misconduct. The study found that
responses to teachers' misconduct varied according to certain characteristics, which can influence whether victims report the misconduct.

The study, by researchers at Prairie View A&M University and the University of Nevada, Reno, appears in Feminist Criminology.

"Because sexual abuse of a child or adolescent in any context has substantial psychological, emotional, and physical consequences for the victim, teachers' sexual misconduct is a serious public health concern," says Kristan N. Russell, assistant professor of justice studies at Prairie View A&M University, who led the study. "Yet very little research has been done to examine the factors that affect how these cases are perceived."

Public perceptions are important, Russell argues, because they may contribute to the stigma experienced by victims, and also affect the willingness of victims to disclose or report these types of cases. Public perceptions also inform legal decision making regarding these cases.

The study's 495 respondents were recruited through a crowdsourcing website in 2019. They were over the age of 18 (average age was 36 years old) and predominantly White (60 percent), male (60 percent), and heterosexual (74 percent).

Respondents were asked to read one of eight randomly assigned fictional newspaper articles describing a case of a local teacher who engaged in sexual misconduct with a 17-year-old student. The articles described forms of nonsexual contact (sending nude photos and sexting) and forcible rape. Then the respondents answered questions about their perceptions of the case and their general attitudes toward cases of this type.

The articles varied by gender of the teacher (male or female), gender pairing of the teacher and student (opposite gender/heterosexual or same gender/homosexual), and age of the teacher (26 or 52 years). The pictures of the teacher, which were stock photos, varied by gender and age.

Although the study did not find evidence of significant interactions between gender, sexuality, and age, it did find that each of these factors affected respondents' perceptions. Specifically:

When the teacher was a woman, respondents perceived the relationship to be less detrimental to the student, the student to be more mature and responsible, and the relationship to be more acceptable.

Heterosexual pairings were perceived as more acceptable than same-sex pairings, with the student perceived as more mature and responsible in heterosexual pairings.

When the teacher was older, respondents perceived the teacher as more responsible and the student as having psychological issues contributing to the reasons for participating in the interaction. The age of the teacher did not relate significantly to respondents' perceptions of the impact of the relationship on the student.

The findings suggest that harmful aspects of teachers' sexual misconduct may be downplayed when the teacher is a woman, leading to underreporting of this type of misconduct by victims, the authors note. In addition, gender pairing affects perceptions, with heterosexual relationships less likely to be reported than homosexual relationships. This illustrates the persistence of stereotypes that depict gay people as predatory or pedophilic, and this, too, may contribute to reduced disclosure by victims in an effort to avoid stigmatization.

"Our findings can be used to develop trainings to inform teachers and students about the factors that influence perceptions and may contribute to underreporting, and strategies for intervening and reporting," suggests Kjerstin Gruys, assistant professor of sociology at the University of Nevada, Reno, coauthor of the study. "We hope that by educating people about what to be aware of in terms of laws and consent, and by allowing systematic and anonymous forms of reporting, students and staff can feel comfortable and safe reporting crimes."

What if you could predict which cells might become cancerous? Breast tissue changes dramatically throughout a woman's life, so finding markers for sudden changes that can lead to cancer is especially difficult. Cold Spring Harbor Laboratory (CSHL) Associate Professor Camila dos Santos and her team identified and cataloged thousands of normal human and mouse breast cell types. The new catalog redefines healthy breast tissue so that when something goes awry, scientists can pinpoint its origin.

Any breast cell could become cancerous. Dos Santos says:

"To understand breast cancer risk, you have to understand normal breast cells first, so when we think about preventive and even targeting therapies, you would be preventing the right cell types from developing to cancer cells."

A traditional way to catalog cells is by tracking a few signature genes related to the cell's function. To classify cells more extensively, dos Santos' team turned to a technique known as single-cell RNA sequencing. They tracked the activity of several genes in over 15,000 cells in mouse and human breast tissue. Samantha Henry, a Stony Brook University graduate student-in-residence in dos Santos' lab, says:

"We really created a whole catalog of many genes for each cell population to better define them. And when I say there were a lot of genes, there were a lot of genes and it took a long time to get through."

One cell group included estrogen receptor-positive cells, which are generally amenable to treatment. But dos Santos' team found that this group could be split into several subpopulations, where each one might have different responses to therapies.

The team, in collaboration with computational biologist CSHL Professor Adam Siepel and his team, learned that mice and human breast cells had similar genetic profiles, demonstrating why studies in mice are likely to be relevant to humans. Marygrace Trousdell, a computational science developer in the dos Santos lab, says:

"We're always finding ourselves struggling with definitive classifications of certain cell types. Sometimes I think I've seen every gene out there, and then something else will pop up."

Currently, the lab is trying to distinguish normal genetic shifts from those associated with cancer. Dos Santos hopes that her catalog of breast cell types will point to which kinds of cells to monitor and point researchers toward treatment options in the future.

Next-generation sequencing technology has made it easier than ever for quick diagnosis of plant diseases. "It's really exciting to see how sequencing technologies have evolved and how this new technology facilitates sequencing of entire genomes in such a short amount of time," said Yazmín Rivera, a plant pathologist with the United States Department of Agriculture's Plant Protection and Quarantine program, who recently published a research paper on the efficacy of Oxford Nanopore Technologies protocols.

"We wanted to provide an unbiased assessment of the technology and protocols available for long read sequencing," Rivera explained. Along with other plant pathologists, Rivera used the company's protocols to prepare RNA and DNA libraries from virus-infected plant material and from a plant pathogenic bacterium, respectively. After one hour of data sequencing, scientists had enough data to assemble small genomes.

"Diagnosticians will welcome an objective review of this technology," Rivera said. Rivera and her colleagues published their findings in Plant Health Progress, presenting a side-by-side comparison of the protocols that will allow the reader to identify which library preparation kit is best suited for their needs.

The ability to quickly obtain the entire genome of an organism has great implications for the plant pathology field. "Having more information readily available facilitates identification of emerging pathogens and of pathogens that are difficult to identify," explains Rivera. For more information, read "Comparison of Nanopore Sequencing Protocols and Real-Time Analysis for Phytopathogen Diagnostics"? published in the March issue of Plant Health Progress.

Dozens of commonly used drugs, including antibiotics, antinausea and anticancer medications, have a potential side effect of lengthening the electrical event that triggers contraction, creating an irregular heartbeat, or cardiac arrhythmia called acquired Long QT syndrome. While safe in their current dosages, some of these drugs may have a more therapeutic benefit at higher doses, but are limited by the risk of arrhythmia.

Through both computational and experimental validation, a multi-institutional team of researchers has identified a compound that prevents the lengthening of the heart's electrical event, or action potential, resulting in a major step toward safer use and expanded therapeutic efficacy of these medications when taken in combination. The team found that the compound, named C28, not only prevents or reverses the negative physiological effects on the action potential, but does not cause any change on the normal action potential when used alone at the same concentrations. The results, found through rational drug design, were published online Friday, May 14 in the Proceedings of the National Academy of Sciences.

The research team was led by Jianmin Cui, professor of biomedical engineering in the McKelvey School of Engineering at Washington University in St. Louis; Ira Cohen, MD, PhD, Distinguished Professor of Physiology and Biophysics, professor of medicine, and director of the Institute for Molecular Cardiology at the Renaissance School of Medicine at Stony Brook University; and Xiaoqin Zou, professor of physics, biochemistry, and a member of the Dalton Cardiovascular Research Center and Institute for Data Science and Informatics at the University of Missouri.

The drugs in question, as well as several that have been pulled from the market, cause a prolongation of the QT interval of the heartbeat, known as acquired Long QT Syndrome, that predisposes patients to cardiac arrhythmia and sudden death. In rare cases, Long QT also can be caused by specific mutations in genes that code for ion channel proteins, which conduct the ionic currents to generate the action potential. Although there are several types of ion channels in the heart, a change in one or more of them may lead to this arrhythmia, which contributes to about 200,000 to 300,000 sudden deaths a year, more than deaths from stroke, lung cancer or breast cancer.

The team selected a specific target, IKs, for this work because it is one of the two potassium channels that are activated during the action potential: IKr (rapid) and IKs (slow).

"The rapid one plays a major role in the action potential," said Cohen, one of the world's top electrophysiologists. "If you block it, Long QT results, and you get a long action potential. IKs is very slow and contributes much less to the normal action potential duration."

It was this difference in roles that suggested that increasing IKs might not significantly affect normal electrical activity but could shorten a prolonged action potential.

Cui, an internationally renowned expert on ion channels, and the team wanted to determine if the prolongation of the QT interval could be prevented by compensating for the change in current and inducing the Long QT Syndrome by enhancing IKs. They identified a site on the voltage-sensing domain of the IKs potassium ion channel that could be accessed by small molecules.

Zou, an internationally recognized expert who specializes in developing new and efficient algorithms for predicting protein interactions, and the team used the atomic structure of the KCNQ1 unit of the IKs channel protein to computationally screen a library of a quarter of a million small compounds that targeted this voltage-sensing domain of the KCNQ1 protein unit. To do this, they developed software called MDock to test the interaction of small compounds with a specific protein in silico, or computationally. By identifying the geometric and chemical traits of the small compounds, they can find the one that fits into the protein -- sort of a high-tech, 3D jigsaw puzzle. While it sounds simple, the process is quite complicated as it involves charge interactions, hydrogen bonding and other physicochemical interactions of both the protein and the small compound.

"We know the problems, and the way to make great progress is to identify the weaknesses and challenges and fix them," Zou said. "We know the functional and structural details of the protein, so we can use an algorithm to dock each molecule onto the protein at the atomic level."

One by one, Zou and her lab docked the potential compounds with the protein KCNQ1 and compared the binding energy of each one. They selected about 50 candidates with very negative, or tight, binding energies.

Cui and his lab then identified C28 using experiments out of the 50 candidates identified in silico by Zou's lab. They validated the docking results by measuring the shift of voltage-dependent activation of the IKs channel at various concentrations of C28 to confirm that C28 indeed enhances the IKs channel function. They also studied a series of genetically modified IKs channels to reveal the binding of C28 to the site for the in silico screening.

Cohen and his lab tested the C28 compound in ventricular myocytes from a small mammal model that expresses the same IKs channel as humans. They found that C28 could prevent or reverse the drug-induced prolongation of the electrical signals across the cardiac cell membrane and minimally affected the normal action potentials at the same dosage. They also determined that there were no significant effects on atrial muscle cells, an important control for the drug's potential use.

"We are very excited about this," Cohen said. "In many of these medications, there is a concentration of the drug that is acceptable, and at higher doses, it becomes dangerous. If C28 can eliminate the danger of inducing Q-T prolongation, then these drugs can be used at higher concentrations, and in many cases, they can become more therapeutic."

While the compound needs additional verification and testing, the researchers say there is tremendous potential for this compound or others like it and could help to convert second-line drugs into first-line drugs and return others to the market. With assistance from the Washington University Office of Technology Management, they have patented the compound, and Cui has founded a startup company, VivoCor, to continue to work on the compound and others like it as potential drug candidates. The work was accelerated by a Leadership and Entrepreneurial Acceleration Program (LEAP) Inventor Challenge grant Washington University in St. Louis in 2018 funded by the Office of Technology Management, the Institute of Clinical and Translational Sciences, the Center for Drug Discovery, the Center for Research Innovation in Biotechnology, and the Skandalaris Center for Interdisciplinary Innovation and Entrepreneurship.

"This work was done by an effective drug design approach: identifying a critical site in the ion channel based on understanding of structure-function relation, using in silico docking to identify compounds that interact with the critical site in the ion channel, validating functional modulation of the ion channel by the compound, and demonstrating therapeutic potential in cardiac myocytes," Zou said. "Our three labs form a great team, and without any of them, this would not be possible."

Even the mention of lavender evokes the distinct fragrance of the flower. This beautiful flower has been used to make perfumes and essential oils since time immemorial. The aesthetics of the flower have captured the imagination of hundreds, worldwide. So, what makes this flower so special? What are the "magical" compounds that gives it its unique fragrance? What is the genetic basis of these compounds? These questions have long puzzled scientists.

To find out the answers, a group of scientists from China have sequenced the genome of lavender, which is known in the scientific world as Lavandula angustifolia. The team headed by Dr. Lei Shi, Professor at the Key Laboratory of Plant Resources and Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, was specifically interested in the genetics and diversity of a class of volatile terpenoids produced by lavender.

Terpenoids play important roles in the biology of fragrant flowers including lavender. In the environment, terpenoids have been shown to attract potential insect pollinators. In real-life applications, terpenoids lend their potential benefits, including stress relief and skin conditioning, through products like essential oils. Keeping these in mind, it is essential to understand the fundamentals of terpenoid biosynthesis at the genetic level to manipulate lavender to produce better quality of these compounds.

The team began by analyzing the high-quality reference genome data of the Chinese variety of lavender 'Jingxun 2'. Through phylogenetic analysis, they identified genomic events through the evolutionary history of lavender that led to the expansion of terpenoid biosynthetic genes in this species. Their analysis also yielded important insights into changes in these genes with respect to changes in the environment under which they grew.

Firstly, the scientists assembled the genetic sequences of the Chinese lavender cultivar. Next, they identified and named, or "annotated," the genomic regions in the lavender sequence and performed phylogenetic analysis on these sequences to better understand the evolutionary history of the lavender. Then they identified the events that affected the entire lavender genome and specifically the terpenoid producing genes. Finally, they associated genes on the lavender genome sequences with different terpenoids found in the plant, to construct gene-terpenoid networks.

Their results, published in a recent issue of Horticulture Research, reported the successful assembly of the 894.5 Mb lavender genome sequence distributed across 27 chromosomes, and could possibly be the best quality lavender sequence assembly, so far. In addition, the scientists were able to show that lavender has exclusively undergone major genetic events, including two whole genome duplications, which allowed them to better adapt and thrive in colder Mediterranean weather conditions.

Explaining their observations, Dr. Shi says, "Plants have the capacity to duplicate their genomes and when this happens there is freedom for the duplicated genes to evolve to do other things. This has allowed plants to develop new machinery to make a diverse array of chemical compounds that are used to defend against attack from harmful microbes and herbivores, and to attract beneficial species such as bees to assist in pollination." In fact, this explanation by Dr. Shi is supported by the findings of the team's study. His team identified gene duplications caused by the previously mentioned genetic events, which in turn led to terpenoid diversification. Upon further analysis, they also observed gene clusters specifically corresponding to attractive and defensive terpenoids.

Dr. Shi is excited about the potential real-life applications of this work. "The introduction of lavender into China can be traced back to the 1950s by pioneers of the Institute of Botany, The Chinese Academy of Sciences. Degradation of the cultivated species is of concern; hence, improved varieties are urgently needed. With a better understanding of the lavender genome, scientists will have an easier time developing new varieties, which may produce high-quality essential oils, have strong ornamental uses, and are resistant to pathogens and climate fluctuations.", he exclaims.

Sharing Dr. Shi's enthusiasm, we can indeed hope this study paves the way for better varieties of lavender and provide a template for research in plant volatile-environmental interactions.

Psychology researchers at UC Santa Cruz have found that playing games in virtual reality creates an effect called "time compression," where time goes by faster than you think. Grayson Mullen, who was a cognitive science undergraduate at the time, worked with Psychology Professor Nicolas Davidenko to design an experiment that tested how virtual reality's effects on a game player's sense of time differ from those of conventional monitors. The results are now published in the journal Timing & Time Perception.

Mullen designed a maze game that could be played in both virtual reality and conventional formats, then the research team recruited 41 UC Santa Cruz undergraduate students to test the game. Participants played in both formats, with researchers randomizing which version of the game each student started with. Both versions were essentially the same, but the mazes in each varied slightly so that there was no repetition between formats.

Participants were asked to stop playing the game whenever they felt like five minutes had passed. Since there were no clocks available, each person had to make this estimate based on their own perception of the passage of time.

Prior studies of time perception in virtual reality have often asked participants about their experiences after the fact, but in this experiment, the research team wanted to integrate a time-keeping task into the virtual reality experience in order to capture what was happening in the moment. Researchers recorded the actual amount of time that had passed when each participant stopped playing the game, and this revealed a gap between participants' perception of time and the reality.

The study found that participants who played the virtual reality version of the game first played for an average of 72.6 seconds longer before feeling that five minutes had passed than students who started on a conventional monitor. In other words, students played for 28.5 percent more time than they realized in virtual reality, compared to conventional formats.

This time compression effect was observed only among participants who played the game in virtual reality first. The paper concluded this was because participants based their judgement of time in the second round on whatever initial time estimates they made during the first round, regardless of format. But if the time compression observed in the first round is translatable to other types of virtual reality experiences and longer time intervals, it could be a big step forward in understanding how this effect works.

While there are many informal descriptions of time compression in virtual reality from people who have experienced it first-hand, it's still an active area of research. One particularly well-known prior study applied virtual reality time compression to shorten the perceived duration of treatment for chemotherapy patients, but that experiment didn't compare virtual reality with conventional screen formats.

"This is the first time we can really isolate that it's not just that you're playing a video game, or the content of whatever you're seeing," Mullen said. "It's really the fact that it is virtual reality versus a conventional screen that contributes to this time compression effect."

Time compression could be useful in some situations--like enduring an unpleasant medical treatment or passing the time on a long flight--but in other circumstances, it could have harmful consequences.

"As virtual reality headsets get more comfortable to wear for longer periods of time, and as more immersive games are made for this format, I think it would be good to avoid having it become like a virtual casino, where you end up playing more because you don't realize how much time you're spending," Mullen said.

Research on game addiction shows that losing track of time during gameplay can negatively affect a player's sleep cycle and mood. These effects could be more pronounced in virtual reality, but Mullen says game designers can help to minimize the risk, perhaps by integrating a clock that would appear at regular intervals during gameplay.

It will also be important to discover why virtual reality seems to contribute to time compression. In the paper, Mullen describes one possibility, which relates to the fact that, in virtual reality, a player has less body awareness. Psychology Professor Nicolas Davidenko, a coauthor and advisor on the paper, explained why this might be important.

"In virtual reality, when you look down, you might see nothing where your body normally would be, or you might see a schematic of a body, but it won't feel like your body," Davidenko said. "There are theories that we may rely on our heartbeat and other bodily rhythms to help our brain track the passage of time, so if you have a less vivid sense of your body in virtual reality, you might be missing the pulses of this timekeeping mechanism."

Future experiments to test this theory could yield new insights to help designers maximize benefits and minimize harm from time compression as virtual reality technology continues to grow.

A new study with zebrafish shows that a deadly form of skin cancer -- melanoma -- alters the metabolism of healthy tissues elsewhere in the body. The research from Washington University in St. Louis suggests that these other tissues could potentially be targeted to help treat cancer.

"Tumors rely on a constant supply of nutrients to grow. Instead of competing with tumors for nutrients, other tissues can reprogram their metabolism to be complementary. In some instances, this may even allow healthy tissues to feed the tumor," said Gary Patti, the Michael and Tana Powell Professor of Chemistry in Arts & Sciences at Washington University and a professor of chemistry and medicine at the School of Medicine.

Patti is the corresponding author of the study published May 13 in Cell Metabolism.

Cancer consumes tremendous amounts of glucose, a key source of energy for cells in the body. Glucose, or blood sugar, is derived from food and transported around the body through the bloodstream after eating. Tumors actively soak up glucose as a fuel to support their rapid growth.

This trait is so well known that physicians regularly use it as a diagnostic test for cancer, where patients are administered a specific form of glucose that can be monitored with a PET scan. What is less clear is how a tumor's penchant for glucose affects other tissues.

"Glucose levels are tightly regulated," Patti said. "When glucose levels get too low, it's dangerous. We wanted to know whether a tumor with a high avidity for glucose might influence glucose levels in the blood."

Even when healthy people go a long period of time without eating, blood glucose levels are kept relatively constant. That is because glucose can be made by the liver when it cannot be obtained directly from food.

"As it turns out, the liver counters the impact of the tumor by synthesizing glucose," Patti said. "It's very similar to what occurs during a fast."

Working with zebrafish, Patti and co-authors including other researchers at the School of Medicine developed a new approach to study melanoma's impact on different tissues in the body that uses a technology called metabolomics.

The scientists fed the zebrafish special versions of nutrients tagged with isotope labels. These labels allowed the scientists to track where nutrients go and into what molecules they get broken down. They found that a molecule being spit out by the tumor was being taken up by the liver to make glucose.

By applying metabolomics to individual zebrafish, the scientists observed that melanoma tissues in the body consume about 15 times more glucose than the other tissues they measured. Despite this burden, the zebrafish were able to maintain circulating glucose levels, apparently by making glucose in the liver through a process that is ordinarily triggered when we go without eating.

But it was clear that otherwise healthy tissues were affected in many ways by the presence of melanoma.

The scientists examined tissues in the liver, intestine, fin, muscle, brain, blood, and eye of the zebrafish. They observed metabolic dysregulation across most of the tissues -- indicating that melanoma broadly impacts whole-body metabolism.

"There is clear metabolic crosstalk between melanoma and other tissues," Patti said. "The metabolic relationship between melanoma and liver is partly characterized by a gene called BCAT1 in the cancer cells. BCAT1 goes from essentially being turned off in healthy skin cells to being highly expressed in zebrafish melanoma. By looking at melanoma from human patients, we were able to confirm that the same pattern holds in people."

Much of the previous research on cancer has focused on the metabolism of the tumor itself.

"Our work shows that a lot of interesting metabolic changes are also occurring beyond the tumor," Patti said. "We have demonstrated that, at least in some cases, these metabolic changes in non-malignant tissues occur to support the tumor. This is exciting because it means that we might be able to target the metabolism of healthy tissues as a potential treatment for cancer."

A group of the world's leading experts in the transmission of airborne pathogens is calling for a tightened regulatory system to control air quality in buildings - as a way of reducing the spread of covid-19 and other illnesses.

Writing in the journal Science, the 40 scientists say: "A paradigm shift is needed on the scale that occurred when Chadwick's Sanitary Report in 1842 led the British government to encourage cities to organise clean water supplies and centralised sewage systems.

"In the 21st century we need to establish the foundations to ensure that the air in our buildings is clean with a significantly reduced pathogen count, contributing to the building occupants' health, just as we expect for the water coming out of our taps."

The scientists who have contributed to the analysis include Cath Noakes, Professor of Environmental Engineering for Buildings at the University of Leeds and a member of SAGE, the body that advises the UK Government on scientific emergencies.

Professor Noakes said: "Over the years, we have neglected the role that the air circulating inside a building plays in the way germs and viruses may spread between people. The pandemic has exposed that deficiency in our understanding and the way we seek to make buildings safer to use.

"We need to introduce new mechanisms that keep pathogen levels in the air flow in buildings and other enclosed spaces to a minimum. That approach can be achieved with technology backed-up with a requirement to meet new standards."

"Action to improve ventilation to reduce exposure to airborne pathogens will bring other benefits, including reducing exposure to other air pollutants and improved performance and wellbeing."

Recognising the risk of aerosol pathogen spread

Historically, public health regulations have concentrated on sanitation, drinking water and food safety, whereas the risk from airborne pathogens whether it is flu or covid-19 is "... addressed fairly weakly, if at all, in terms of regulations, standards, and building design and operation, pertaining to the air we breathe", say the scientists.

But research during the covid-19 pandemic has underlined the role that aerosols play in spreading disease. When a person who has a respiratory infection speaks, coughs or sneezes, tiny infective particles are emitted from their nose and mouth. Indoors, those tiny particles are carried in the air and infect other people.

The paper says: "... community outbreaks for COVID-19 infection in particular most frequently occur at larger distances through inhalation of airborne virus-laden particles in indoor spaces shared with infected individuals.

"Such airborne transmission is potentially the dominant mode of transmission of numerous respiratory infections. We also have strong evidence on disease transmission, for example in restaurants, ships, and schools, suggesting that the way we design, operate, and maintain buildings influences transmission."

That risk of people becoming cross infected inside a building can be reduced through ventilation coupled with air disinfection and air filtration systems. However, the scientists note: "... almost no engineering-based measures to limit community respiratory infection transmission had been employed in public buildings - excluding health care facilities - or transport infrastructure anywhere in the world."

Tighter controls

There are ventilation guidelines and standards which architects and builders must follow but the focus is on reducing odours and carbon dioxide levels and in maintaining thermal comfort. None provide recommendations on how to control the spread of pathogens.

The scientists are calling for World Health Organisation indoor air-quality guidelines, which cover pollutants such as carbon monoxide and other chemicals, to be extended to include airborne pathogens. The experts say individual governments need to introduce and enforce domestic regulations.

"None of this means that every indoor space should become a biosafety facility. It means that a building should be designed and operated according to its purpose and the activities conducted there, so that airborne infection risk is maintained below an acceptable level," the scientists write in the paper.

That would mean different standards for a gym where people may be breathing heavily as opposed to people relaxing in a cinema.

The lead author of the paper, Lidia Morawska, Distinguished Professor in the School of Earth and Atmospheric Sciences at Queensland University of Technology in Australia, said: "For decades, the focus of architects and building engineers was on thermal comfort, odour control, perceived air quality, initial investment cost, energy use, and other performance issues, while infection control was neglected."

Quotes from other authors of the paper

Trish Greenhalgh, Professor of Primary Care Health Sciences at the University of Oxford, said: " It's no exaggeration to call this a paradigm shift. Up to now, most of the efforts to prevent transmission of Covid-19 and other airborne respiratory diseases such as tuberculosis has focused on influencing individual behaviour such as mask-wearing, cough hygiene and handwashing. These measures are still important, but they will be relatively ineffective in the indoor environment until we ensure that the air we inhale contains far fewer particles that have been exhaled by others in the room.

"We need to re-think the practice, currently common in many countries, of keeping windows closed and recycling stale air in air-conditioning. Windows should be opened and draughty rooms welcomed; if air is recycled it must be filtered and disinfected; and monitoring air quality--for example using CO2 monitors--should become commonplace. In short, we need to re-think--and re-regulate--what counts as a 'healthy' building."

Stephanie Dancer, Professor of Microbiology at Edninburgh Napier University and Consultant Medical Microbiologist at NHS Lanarkshire, in Scotland, said: "Even just opening the windows provides more than a gesture towards reducing the risk of infection."

Costs

The scientists challenge the argument that costs of air quality control in buildings would be prohibitively expensive. They say the monthly cost of covid-19 is conservatively estimated at $1 trillion. Installing ventilation and air-quality systems designed to remove airborne pathogens would add about one percent to the construction costs of a typical building.

Improving air quality in buildings would bring benefits beyond reducing sickness levels due to respiratory infections. It is likely to reduce allergens and the number of people who experience 'sick building syndrome'.

Scientists exploring the drivers of Antarctic climate change have discovered a new and more efficient pathway for the creation of natural aerosols and clouds which contribute significantly to temperature increases.

The Antarctic Peninsula has shown some of the largest global increases in near-surface air temperature over the last 50 years, but experts have struggled to predict temperatures because little was known about how natural aerosols and clouds affect the amount of sunlight absorbed by the Earth and energy radiated back into space.

Studying data from seas around the Peninsula, experts have discovered that most new particles are formed in air masses arriving from the partially ice-covered Weddell Sea - a significant source of the sulphur gases and alkylamines responsible for 'seeding' the particles.

A new study shows that increased concentrations of sulphuric acid and alkylamines are essential for the formation of new particles around the northern Antarctic Peninsula. High concentrations of other acids and oxygenated organics coincided with high levels of sulphuric acid, but by themselves did not lead to measurable particle formation and growth.

An international team of researchers from the University of Birmingham; Institute of Marine Science, Barcelona, Spain; and King Abdulaziz University, Jeddah, Saudi Arabia studied summertime open ocean and coastal new particle formation in the region, based on data from ship and land stations, and today published its findings in Nature Geoscience.

The researchers revealed that the newly discovered pathway is more efficient than the ion-induced sulphuric acid-ammonia pathway previously observed in Antarctica and can occur rapidly under neutral conditions.

Study co-author Roy Harrison OBE, Professor of Environmental Health at the University of Birmingham, commented: "New particle formation is globally one of the major sources of aerosol particles and cloud condensation nuclei. This previously overlooked pathway to natural aerosol formation could prove a key tool in predicting the future climate of polar regions.

"The key to unlocking Antarctica's climate change lies in examining particles created in the atmosphere by the chemical reaction of gases. These particles start tiny and grow bigger, becoming cloud condensation nuclei leading to more reflective clouds which direct outgoing terrestrial radiation back to earth and warm the lower atmosphere."

New particle formation is globally one of the major sources of aerosol particles and cloud condensation nuclei. Existing research suggests that natural aerosols contribute disproportionately to global warming, whilst sulphuric acid is thought to be responsible for most aerosol seeding observed in the atmosphere.

The research team identified numerous sulphuric acid-amine cluster peaks during new particle formation events - providing evidence that alkylamines provided the basis for sulphuric acid nucleation.

"We found that sulphuric acid-amine-water nucleation is a dominant process in the Antarctic Peninsula, with the amines coming from regions of sea ice in the Antarctic Peninsula-western Weddell Sea region," added Professor Harrison. "Waters in this region with significant amounts of sea ice are rich in amines, and aerosols originating from such regions show a near five-fold enhancement in amine concentrations."

Today, the rocks of the Hanna Formation in south-central Wyoming are hundreds of miles away from the nearest ocean. But around 58 million years ago, Wyoming was oceanfront property, with large hippo-like mammals traipsing through nearshore lagoons.

In a study published in Scientific Reports, geologist Anton Wroblewski, an adjunct associate professor in the Department of Geology and Geophysics, and applied biodiversity scientist Bonnie Gulas-Wroblewski of the Texas A&M Natural Resources Institute, report the discovery of several sets of fossilized tracks, likely from the brown bear-sized Coryphodon, that represent the earliest known evidence of mammals gathering near an ocean.

"Trace fossils like footprints record interactions between organisms and their environments, providing information that body fossils alone cannot," Wroblewski says. "In this case, trace fossils show that large- bodied mammals were regularly using marine environments only eight million years after non-avian dinosaurs went extinct."

The tracks that the Drs. Wroblewski found in the Hanna Formation of Wyoming include underprints, impressions in soft sediment made when heavy animals walk on overlying sediment layers, as well as prints pressed into the surfaces of ancient tidal flats. Now preserved in sandstone, the tracks are more than half a mile (one kilometer) long and were made by two different animals, one with four toes and one with five. The five-toed tracks are consistent with Coryphodon, a semi-aquatic mammal similar to a hippopotamus. The owner of the four-toed tracks remains a mystery.

"Paleontologists have been working in this area for thirty years, but they've been looking for bones, leaf fossils, and pollen, so they didn't notice footprints or trackways," Wroblewski says. He first saw the tracks in September 2019. "When I found them, it was late afternoon and the setting sun hit them at just the right angle to make them visible on the tilted slabs of sandstone. At first, I couldn't believe what I was seeing; I had walked by this outcrop for years without noticing them. Once I saw the first few, I followed out the ridge of sandstone and realized they were part of a much larger, more extensive trackway."

Fossilized plants and pollen helped the researchers determine the age of the tracks to be around 58 million years old, during the Paleocene epoch. Before this finding, the earliest known evidence of mammals interacting with marine environments came from the Eocene epoch, around 9.4 million years later. Wroblewski says that the Hanna Formation tracks are the first Paleocene mammal tracks found in the USA and only the fourth in the world, with two sets of tracks previously found in Canada and one in Svalbard, Norway. It's also the largest accumulation of Paleocene mammal tracks in the world in both aerial extent and the absolute number of tracks, he says. With at least two species leaving the tracks, it's also the most taxonomically diverse.

Today's large mammals congregate near marine environments for a variety of reasons, including protection from predators and biting insects, foraging for unique foods, and access to salt sources, which may have been limited in the tropical forests of North America during the Paleocene. The researchers say ancient mammals may have had similar reasons for seeking out a day at the beach.

The research shows, Wroblewski says, that hypotheses of behavior and evolution based on isotopic, molecular and body fossil data can be empirically tested using trace fossils. "No other line of evidence directly records behaviors of extinct organisms preserved in their preferred habitats," he says. "There's still a lot of important information out there in the rocks, waiting for somebody to spot it when the lighting is just right!"

What The Study Did: This survey study examined differences between male and female physicians in the use of social media and reported career and professional benefits.

Authors: Shikha Jain, M.D., of the University of Illinois at Chicago, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.9834)

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Scientists reveal that the deterioration of modern concrete and asphalt structures is due to the presence of trace quantities of organic matter in these structures.

Cement and asphalt are vital to modern construction materials; cement is used for the construction of various buildings and structures, while asphalt is primarily used for highways and runways. They have been widely used for these purposes since the 1800s. It has been observed modern concrete structures and asphalt structures tend to deteriorate much faster than historical structures, but the reason for this phenomenon was unknown.

A team of scientists from six institutions, including Akihiro Moriyoshi, Emeritus Professor Hokkaido University, have revealed that the presence of trace quantities of organic matter in modern concrete structures and asphalt pavements drive the deterioration of these structures. Their findings, which include novel methods to assess deterioration, were published in the journal PLOS ONE.

The deterioration of modern concrete structures and asphalt pavements are a major issue. The features that lead to deterioration include cracks, disaggregation (breakdown into fine white powder) and delamination (separation into layers). These deteriorated structures are unsafe for their intended purposes; rapid deterioration reduces the expected lifespan of structures, thereby increasing the costs for maintenance or replacement.

The scientists set out to develop a new method to assess the rate of deterioration in concrete. The current method is based on the width of surface cracks in concrete and a simple chemical test; however, it only gives an incomplete picture of the level of damage. During their experiments, the scientists happened to notice that a strange odor developed when commercial cement was mixed with water. They hypothesized that organic matter was responsible for the odor, and investigated the effect it has on deterioration of concrete.

The scientists developed the one-dimensional transient moisture permeation apparatus to accurately reproduce the field environmental conditions that concrete structures and asphalt pavements are exposed to, in the laboratory, over a period of 24 hours. When combined with CT scans, this method can be used to evaluate the precise extent of the damage. They tested a variety of asphalt samples from Japan dating back to 1960; a number of concrete samples from across the world were also tested, and a 120-year-old concrete sample was used as a reference.

The scientists showed that there are a number of organic molecules, from diverse sources, present in modern concrete structures and asphalt pavements: phthalates, diesel exhaust particulates, surfactants, and windshield washer fluids. These molecules are either introduced during the manufacturing process -- the contents of phthalates, phosphate compounds, and AE water reducing agents present in commercially available cements are 0.0012%, 0.12%, and 0.25%, respectively -- or absorbed from the environment, and cause rapid deterioration of concrete structures and asphalt pavements.

Of the organic matter present in cement, phthalates have the highest effect on deterioration more than phosphates and AE water reducing agents. Organic matter in water accelerates deterioration of asphalt pavements. The scientists also showed that crack width and length is the best determinant of concrete damage, while the degree of formation of amorphization is the best determinant of deterioration. They believe that their findings can be used to develop novel formulations for long-lasting concrete structures and asphalt pavements.