Culture

Higher levels of ozone from air pollution are linked to an increased risk of developing fibroids among Black American women according to a large study published today (Friday) in Human Reproduction [1], one of the world's leading reproductive medicine journals.

Fibroids are non-cancerous growths that develop in and around the womb. They are diagnosed in 25-30% of pre-menopausal women, but the true incidence is thought to be between 70-80%. Many fibroids do not cause symptoms but when they do, they are one of the main reasons women are admitted to hospital for inpatient care. Symptoms can include heavy or painful periods, stomach and back pain, constipation, frequent need to urinate, and pain or discomfort during sex. In some cases they can affect fertility and pregnancy. Women of African-Caribbean origin are diagnosed with fibroids two to three times more often than white women, and they tend to experience earlier onset of symptoms and more severe disease.

Previous research has shown that Black people are exposed to higher levels of air pollution than white people in the USA but, until now, there has been no investigation into the association between air pollution and fibroids in Black women.

The study published today investigated concentrations of three environmental pollutants in the air in 56 US metropolitan areas between 1997 and 2011: particulate matter smaller than 2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3). The 21,998 premenopausal Black women who lived in these areas and were included in the research were part of the ongoing Black Women's Health Study. They answered questionnaires every two years and were followed up until 2019.

During the 14-year follow-up period, 6238 (28.4%) of women reported having fibroids diagnosed by a doctor and confirmed by ultrasound or surgery. Average (median) concentrations of ozone were 36.9 parts per billion (ppb), with a range of 25.4 to 55 ppb.

After adjusting for factors that could affect the results, such as education, smoking, body mass index, diet and whether or not the women had been pregnant, the researchers found that the risk of self-reported fibroids increased with increasing levels of ozone in the atmosphere, but not with PM2.5 or NO2.

Ozone was linked to a 35% increased risk of fibroids among the 20% of women exposed to the highest levels of ozone (42-55 ppb) - a rate of 33.6 cases per 1000 women, compared with the 20% exposed to the lowest levels (25-33 ppb) - a rate of 31.4 cases per 1000 women [2]. The association was stronger among women aged less than 35 years and for women who had been pregnant.

First author of the study, Dr Amelia Wesselink, an Assistant Professor in the Department of Epidemiology at Boston University School of Public Health (Massachusetts, USA), said: "We were surprised to see an association for ozone but not for PM2.5 and NO2. The mechanisms that we think could explain the association between ozone and fibroids are also relevant for the other pollutants, so this was an unexpected finding. It may reflect that there is a mechanism unique to ozone that we are missing, but it might also mean that there is factor that we've not been able to measure that could affect the results. For example, we were unable to account for vitamin D exposure and vitamin D deficiency is a suspected risk factor for fibroids."

Biological mechanisms that might be involved in the link between ozone and fibroids include an immune inflammatory response; oxidative stress (an imbalance between molecules in the body, leading to cell and DNA damage); high blood pressure that could lead to fatty deposits on artery walls; and activation of the body's stress response.

Dr Wesselink said that the increased risk of fibroids among Black women was not explained by known risk factors, or by socioeconomic status, or access to or quality of health care.

"We are still trying to figure out what specific exposures explain this disparity. Possible explanations that are under investigation include stress throughout life due to systematic oppression and racism; vitamin D deficiency; and environmental factors like air pollution, which we know are inequitably distributed across populations in the United States.

"There have now been three studies suggesting a link between air pollution and fibroids, but ours is the first to show this in Black women. Because Black women are inequitably exposed to air pollution, these findings have important implications for racial disparity in fibroids."

The study has some limitations. These include the way exposure to air pollution was measured; the fact that women reported doctors' diagnoses of fibroids, which could have led to an under-estimation of the problem; and that the researchers were unable to measure factors that could affect the results, such as vitamin D exposure.

Dr Wesselink said: "Vitamin D deficiency is a key hypothesis that is under investigation to explain the racial disparity in fibroids. It is certainly possible that our findings could be explained by vitamin D. This is something that should be considered in future work on this topic."

She concluded: "Further research and additional funding is needed to understand the role of air pollution in fibroid development. For instance, a prospective, ultrasound-based study could identify fibroids, regardless of whether or not they are causing symptoms that lead to women seeking medical care. In addition, we need to consider the role of other features in the physical and built environment in the development of fibroids; factors such as environmental noise, access to green spaces and other neighbourhood exposures."

People with healthier heart structure and function appear to have better cognitive abilities, including increased capacity to solve logic problems and faster reaction times, according to research led by Queen Mary University of London and the Radcliffe Department of Medicine at University of Oxford.

Dr Zahra Raisi-Estabragh, BHF Clinical Research Training Fellow at Queen Mary University of London said: "Heart disease and dementia are important and growing public health problems, particularly in ageing populations.

"We already knew that patients with heart disease were more likely to have dementia, and vice versa, but we've now shown that these links between heart and brain health are also present in healthy people. We demonstrated for the first time, in a very large group of healthy people, that individuals with healthier heart structure and function have better cognitive performance.

"With more research, these findings may help us to establish strategies for early prevention and reduce the burden of heart and brain disease in the future."

The brain has previously been proposed as a target for damage from heart disease, and the risk factors leading to heart disease have also been associated with both vascular and Alzheimer's dementia. However, the mechanisms by which these associations occur are not well understood, and studies had not been carried out in large groups of people or those without disease.

The new study, published in the European Heart Journal Cardiovascular Imaging, examined links between heart health and cognitive function in over 32,000 UK Biobank participants. The team assessed heart health using measures of anatomy and function obtained from MRI scans. Cognitive function was assessed using tests of fluid intelligence (the capacity to solve logic-based problems) and reaction time.

The results show that, in this large group of mostly healthy individuals, those with healthier heart structure and function performed significantly better in tests of cognitive ability.

To investigate underlying mechanisms for the observed relationships, the team also considered whether the links between heart and brain health may be related to shared risk factors for vascular disease, such as diabetes, smoking, high blood pressure and obesity.

They found that although these factors were important in determining both heart and brain health, they did not provide a complete explanation for the observed associations. This suggests that alternative mechanism may be important in mediating interactions across the heart and brain.

For instance, other studies have shown that proteins which are abnormally deposited in the brain in Alzheimer's disease may also accumulate and cause disease in the heart muscle. Another possibility is that poorer brain and heart health may both be a consequence of accelerated ageing.

The researchers caution that, as this was an observational study, it is not possible to make any definitive inferences about causality and it cannot be stated that heart disease causes impaired cognition, or vice versa. It is also possible that there may be residual confounding (i.e. that brain and heart health may appear to be connected due to their common association with a third factor).

Cooperation as a successful strategy has evolved in both nature and human society, but understanding its emergence can be a difficult task. Researchers have to abstract interactions between individuals into mathematical formulas to be able to create a model that can be used for predictions and simulations.

In the field of evolutionary game theory, they often investigate strategies of players in a simple game of giving and receiving benefits. Such strategies tell players how to behave in a given interaction. The scientists' findings counter the narrative that only the strongest and most selfish flourish and survive. Instead, they show how cooperation can be a successful and stable strategy.

Researchers, spearheaded by Laura Schmid from the Chatterjee group at IST Austria, have created a new mathematical framework that combines so far incompatible descriptions of cooperation. In their simulations of many interactions between players, they show how prior experiences with and reputation of a potential partner affect the willingness of a players to cooperate with them.

Scratched Backs and Flawless Reputation

The central concept in the researchers' work is that of interactions based on direct and indirect reciprocity. "An interaction based on direct reciprocity simply means 'I'll scratch your back if you scratch mine'," Laura Schmid explains, "It can be found both among humans and several animal species."

On the other hand, indirect reciprocity is based on the reputation of an individual. "This means that if they behave well towards others, I will cooperate with them, even if I have not interacted with that individual before," Schmid continues, "So far this has conclusively only been shown among humans."

Resolving conflicts that arise when these two kinds of reciprocity lead to competing suggestions is not straightforward. Should the player cooperate with a person who behaves well towards others, even if they have treated them unfairly in the past? The strategies adopted by the players then answer this kind of question.

One of the key insights the researchers gained from their unified model of both direct and indirect reciprocity was that the evolution of strategies, the amount of cooperation, as well as which kind of reciprocity individuals prefer all depend on the environment: factors like how often players interact and whether they know the truth about their partner's reputation.

Stabilized Cooperation

This model can help researchers understand the fundamental dynamics of how cooperative strategies evolve and stabilize. "Using mathematical tools that were developed only recently, we explored which strategies of direct or indirect reciprocity give rise to a Nash equilibrium," Schmid points out. "Once the evolving population of players in our simulation adopts such strategies, none of them has an incentive to divert."

These findings shed some light on how the evolution of cooperation in early human societies could have been influenced by their social norms based on experience and reputation. A more current application would be the modeling of rating systems of online stores based on both a buyer's personal experience and the reputation of a seller.

Bridging different fields such as game theory and evolutionary modeling has been a topic for Laura Schmid for some time. Growing up in Vienna, she first studied physics at TU Wien as well as piano at the Music and Arts University of the City of Vienna before joining the Chatterjee group at IST Austria for her PhD. After completing her degree later this year, she plans to continue her research career abroad.

In her future work, Laura Schmid wants to look into how many players in a group have to use a strategy based on indirect reciprocity for it to become successful. With this, she will be able to investigate the effect of the spread of social norms within a society.

The majority of children infected with SARS-CoV-2 may not show typical symptoms such as fever, cough or shortness of breath, according to a study published in Scientific Reports, which examined data on 12,306 children with laboratory-confirmed COVID-19 across the United States.

Pakaj Arora and colleagues found that 18.8% of the children included in the study were recorded as having symptoms such as fever, malaise, muscle or joint pain, and disturbances of smell or taste. . 16.5% of children had respiratory symptoms including cough and shortness of breath, 13.9% had gastrointestinal symptoms such as nausea, vomiting and diarrhea, 8.1% had dermatological symptoms (rash), and 4.8% had headaches.

5.5% (672) of children included in the study were hospitalized. Of those, 118 (17.6%) and 38 (4.1%) required critical care services and mechanical ventilation, respectively. The risk of hospitalization was similar between males and females, but higher in non-Hispanic Black and Hispanic children compared with non-Hispanic White children. The risk of requiring critical care and mechanical ventilation was similar across all groups.

The findings suggest that children and adolescents with COVID-19 may have a milder course of illness than adults, but disparities in severity appear to exist between non-Hispanic Black, Hispanic and non-Hispanic White children in the US. Given the high frequency of cases without typical symptoms, increased vigilance, innovative screening, and frequent testing may be required among school-going children and their immediate contacts as schools reopen. Implementation of these strategies may need to be enhanced among children from racial/ethnic minorities to curtail the existing COVID-19 related health disparities.

New research led by the University of Kent has found that adolescents and older adults pay less attention to social cues in real-world interactions than young adults.

The findings published by Nature Human Behaviour show that social attention undergoes age-related change, which has potential implications for how successfully we can interpret social interactions in daily life and throughout the lifespan.

Interpreting the facial expression, tone of voice and gestures of others is a vital element of social interaction that allow us to make rapid inferences about others' mental states, such as their intentions, emotions, desires and beliefs. Successful social interaction prompts perspective-taking and empathy along with other essential social skills, and plays an important role in enhancing our wellbeing.

The research led by PhD student, Martina De Lillo, alongside Professor Heather Ferguson and other colleagues at the University of Kent's School of Psychology, is the first of its kind to examine how social attention is allocated during adolescence and whether it differs from adulthood. Furthermore, no previous research has examined the lifespan developmental differences of social attention while people actively participate in real-world interactive situations.

The researchers recorded participants in two real-world social interaction situations (a face-to-face conversation and navigating an environment) using mobile eye-tracking glasses to monitor their attention to social and non-social information. Adolescents (10-19 years old), young (20-40 years old) and older (60-80 years old) adults were assessed in both scenarios.

In the first experiment adolescents and older adults spent less time looking at the experimenter's face during conversation, and more time fixating the background, compared to young adults. In the second experiment adolescents and older adults spent less time looking at people while navigating a busy University environment, compared to young adults. This is likely because adolescents and older adults found the social situation more challenging to maintain than young adults, and they managed this difficulty by avoiding the complex social information of the face.

Martina De Lillo said: 'Using mobile eye-tracking technology allowed us to gain a unique understanding into social interaction and the everyday use of social cognition in real-world contexts. It can play a critical role in further understanding how social interaction develops across the lifespan.'

Professor Ferguson said: 'Focusing less on people and their faces means that adolescents and older adults miss important cues, and this could lead to larger impairments in social interaction, or less opportunities to engage in social interaction with others.

'During adolescence, 10-19-year-olds are still learning and developing peer relationships, so they are experiencing a rapid change in their social experiences and preferences. For older adults, a substantial decline in social participation can lead to isolation, loneliness and poor health. Both groups can therefore be significantly impacted by a lack of social engagement.'

Multiple studies have shown that African American women with breast cancer have lower survival rates than white women with the disease. But the association between race or ethnicity and treatment outcomes in triple-negative breast cancer -- an aggressive type of tumor that does not respond to hormonal or other targeted therapies -- has not been well defined.

Now, new research from Washington University School of Medicine in St. Louis shows that non-Hispanic African American women with triple-negative breast cancer also do not fare as well as non-Hispanic white women with this type of breast cancer. The study demonstrates the need for additional research to address disparities in cancer care and understand whether tumor biology or nonbiological reasons such as systemic racism -- or a combination of such factors -- may prevent African American women from receiving the same quality of care as white women.

The study appears online May 13 in JAMA Oncology.

Among women with triple-negative breast cancer, the researchers found that African Americans had a 28% increased risk of death compared with Americans of European descent, and that this disparity was at least partially due to lower rates of surgery and chemotherapy among African American patients.

"Regardless of subtypes of breast cancer, many studies have shown that African American patients have lower survival than white patients," said epidemiologist and senior author Ying Liu, MD, PhD, an assistant professor of surgery in the Division of Public Health Sciences. "But there have been conflicting studies on triple-negative breast cancer outcomes. Some of these studies have shown no disparity in survival, but these were smaller studies with fewer triple-negative or African American patients. Our research uses a large study from a national dataset demonstrating that African American patients also have lower survival for this type of breast cancer. If we want to eliminate these disparities, we must first identify what they are and work to understand what drives them."

Breast cancer is classified into categories based on whether the tumor's growth is driven by hormones such as estrogen or progesterone or by proteins such as HER2, called growth factors. Hormonal therapies that block or reduce these hormones and drugs that target HER2 can be effective in treating these tumor types. In contrast, triple-negative breast cancer continues to grow even in the absence of all these hormones and growth factors, forcing doctors and patients to rely on surgery, chemotherapy and, less often, radiation.

About 10% to 12% of all invasive breast cancer diagnoses in the U.S. are triple-negative. And for reasons that remain unclear, African American women are at higher risk of developing triple-negative breast cancer than white American women.

For the study, researchers mined a large database maintained by the National Cancer Institute that included over 23,000 women diagnosed with triple-negative breast cancer from 2010 to 2015. Twenty-five percent of the patients were African American, and patients' tumors were stages 1, 2 or 3, but not stage 4, meaning they had not yet spread to other parts of the body. In a follow-up 3½ years later, 3,276 patients had died from breast cancer. The five-year survival rate was about 77% for African American women and about 83% for white women.

Compared with white patients, African American patients had 31% lower odds of receiving surgery and 11% lower odds of receiving chemotherapy. Radiation therapy is used less often for this type of cancer, but the researchers found no difference between the two groups. After adjusting for socioeconomic factors, tumor stage and size, treatment differences and other factors, the risk of death among African Americans remained increased by 16%.

Even when chemotherapy was given, there was some evidence that the treatment was less effective in African American patients. "This suggests there may be differences in tumor biology or tumor environment between African American and white patients," said Liu, also a research member of Siteman Cancer Center. "We need more research to understand if any differences exist between these tumors in their molecular biology or in their immune landscape, for example, so we can try to address them with different targeted therapies."

On average, African American patients were diagnosed at younger ages (56 years) than white patients (59 years). Tumors of African American patients also tended to be larger, diagnosed at more advanced stages and included more lymph node involvement, which is a sign the cancer is beginning to spread.

Additionally, African American patients were more likely to have health insurance through Medicaid and to live in urban areas and in counties that were more socioeconomically disadvantaged.

"There are a lot of factors beyond tumor biology that are likely contributing to these disparities," Liu said. "Our study couldn't measure many of these factors, but we know, for example, that African American patients are more likely to have unsatisfying communications with their doctors, experience discrimination in the health-care system, and have more difficulty with transportation to and from their appointments."

Curiously, researchers said the racial disparity in mortality was not found among triple-negative breast cancer patients over age 65 or those living in rural or socioeconomically poorer counties.

"Some of these associations are difficult to explain because data is limited," Liu said. "We can speculate that perhaps health care in rural or poorer communities is more difficult for cancer patients to access in general, so perhaps disparities are less apparent. But at this point, we don't know. We will need more research to understand what factors are causing these differences in treatment and survival, so that we can find ways to address them."

University of Massachusetts Amherst neuroscientists examining genetically identified neurons in a songbird's forebrain discovered a remarkable landscape of physiology, auditory coding and network roles that mirrored those in the brains of mammals.

The research, published May 13 in Current Biology, advances insight into the fundamental operation of complex brain circuits. It suggests that ancient cell types in the pallium - the outer regions of the brain that include cortex - most likely retained features over millions of years that are the building blocks for advanced cognition in birds and mammals.

"We as neuroscientists are catching on that birds can do sophisticated things and they have sophisticated circuits to do those things," says behavioral neuroscientist Luke Remage-Healey, associate professor of psychological and brain sciences and senior author of the paper.

For the first time, the team of neuroscientists, including lead author Jeremy Spool, who worked as a National Institutes of Health (NIH) postdoctoral fellow in Remage-Healey's lab, used viral optogenetics to define the molecular identities of excitatory and inhibitory cell types in zebra finches (Taeniopygia guttata) and match them to their physiological properties.

"In the songbird community, we've had a hunch for a long time that when we record the electrical signatures of these two cell types, we say - 'that's a putative excitatory neuron, that's a putative inhibitory neuron.' Now we know that these features are grounded in molecular truth," Remage-Healey says. "Without being able to pinpoint the cell types with these viruses, we wouldn't be able to learn how the cell and network features bear resemblance to those in mammals, because the brain architectures are so different."

The research team used viruses from a collection curated by co-author Yoko Yazaki-Sugiyama at the Okinawa Institute of Science and Technology in Japan to conduct viral optogenetic experiments in the brain. With optogenetics, the team used flashes of light to manipulate one cell type independent of the other. The team targeted excitatory vs. inhibitory neurons (using CaMKIIα and GAD1 promoters, respectively) in the zebra finch auditory pallium to test predictions based on the mammalian pallium.

"There's so much work out there on the physiology of these different cell types in the mammalian cortex that we were able to line up a series of predictions about what features birds may or may not have," Spool says.

The CaMKIIα and GAD1 populations in the songbird were distinct "in exactly the proportions you would expect from the mammalian brain," Spool says. With the cell type populations isolated, the researchers then examined systematically whether each population would correspond to the physiology of their mammalian counterparts.

"As we kept moving forward, again and again these cell populations were acting as if they were essentially from the mammalian cortex in a lot of physiological ways," Spool says.

Remage-Healey adds, "The correspondence between the cortex in mammals and what we're pulling out with molecularly identified cell types in birds is pretty striking."

In both birds and mammals, these neurons are thought to support advanced cognitive functions, such as memory, individual recognition and associative learning, Spool says.

Remage-Healey says the research, supported by NIH grants, helps delineate "the basic nuts and bolts of how the brain operates." Knowing the nuts and bolts builds foundations necessary to develop breakthroughs that could lead to neurological interventions for brain disorders.

"This can help us figure out what brain diversity is out there by unpacking these circuits and the ways they can go awry," Remage-Healey says.

A new approach to genomic species delineation could impact policy and lend clarity to legislation for designating a species as endangered or at risk.

The coastal California gnatcatcher is an unassuming little gray songbird that's been at the epicenter of a legal brawl for nearly 28 years, ever since U.S. Fish and Wildlife Service listed it as threatened under the Endangered Species Act.

Found along the Baja California coast, from down south in El Rosario, Mexico to Long Beach, Calif., its natural habitat is the rapidly declining coastal sagebrush that occupies prime, pristine real estate along the West Coast. When this particular gnatcatcher, Polioptila californica, was granted protection, the region's real estate developers went to court to get it delisted.

Central to their argument, which was dismissed in a federal court, was whether it was an independent species or just another population of a more widely found gnatcatcher. This distinction would dictate its threatened status. Evolutionary biologists have developed a new approach to genomic species delineation that improves upon current methods and could impact similar policy in the future.

This approach is based on the fact that in many groups of organisms it can be problematic to decide where one species begins and another ends.

"In the past, when it was challenging to distinguish species based on external characters, scientists relied on approaches that diagnosed signatures in the genome to identify 'breaks' or 'structure' in gene flow indicative of population separation. The problem is this method doesn't distinguish between two populations separated geographically versus two populations being two different species," said Jeet Sukumaran, computational evolutionary biologist at San Diego State University and lead author of a study published May 13 in PlOS Computational Biology.

"Our method, DELINEATE, introduces a way to distinguish between these two factors, which is important because most of the natural resources management policy and legislature in our society rests on clearly defined and named species units."

Typically, scientists will use a range of different methods to identify boundaries between different species, including statistical analysis and qualitative data to distinguish between population-level variation and species-level variation in their samples, to complete the classification of an organism. In cases where it is difficult to sort the variation between individuals into differences due to variation within a species as opposed to between two species, they often turn to genomic data based approaches for the answer. This is when scientists often use a model that generates a population phylogeny, or an evolutionary tree relating different populations.

Sukumaran and co-authors evolutionary biologists L. Lacey Knowles with the University of Michigan, Ann Arbor and Mark Holder with the University of Kansas, Lawrence add a second layer of information to the population phylogeny, to explicitly model the actual speciation process. This allows them to understand how these separate populations sometimes evolve into distinct species, which is the basis for distinguishing between populations and species in the data.

"Our method allows researchers to make statements about how confident they are that two populations are members of the same species,” Holder said. “That is an advance over just making a best estimate of species assignments."

Whether some of the population lineages in the sample are assigned to existing species or classified as entirely new species depends on two factors. One is the age of the population isolation events such as the splitting of an ancestral population into multiple daughter populations, which is how species are "born" in an extended process of speciation. The other is the rate of speciation completion, which is the rate at which the nascent or incipient species "born" from population splitting events develop into true full species.

"We're coming to realize now that many organisms are cryptic species," Sukumaran said. "Many of them are similar looking even though they are actually distinct species separated by many tens or hundreds of thousands or even millions of years of evolution."

This is either due to strong selection pressures to maintain the same morphology, or, more typically, due to very recent speciation resulting in insufficient time for external differences to develop.

"When rivers change course, when terrain changes, previously cohesive populations get fragmented, and the genetic makeup of the two separate populations, now each a population in their own right, can diverge," Sukumaran said. "Eventually, one or both these populations may evolve into separate species, and may (or may not) already have reached this status by the time we look at them.

"Yet individuals of these two populations may look identical to us based on their external appearances, as differences in these may not have had time to 'fix' in either population. This is when we turn to genomic data to help guide us toward deciding whether we are looking at two populations of the same species, or two separate species."

Currently, scientists apply a model based on multispecies coalescent theory to genomic data to identify the disruption of gene flow between different groups of organisms. This disruption is fundamental to species formation, but it can also occur between two different populations as well as two different species.

While scientists agree that it is critical to distinguish between populations and species boundaries in genomic data, there is not always a lot of agreement on how to go about doing it. "If you ask ten biologists, you will get twelve different answers," Sukumaran said.

By modeling the dynamics of speciation itself in the species delimitation analysis, something previous methods did not do, the researchers' approach allows for distinguishing between interpopulation boundaries to gene flow versus interspecies boundaries, based on the predicted pace of the speciation events.

With this framework, scientists can have a better understanding of the status of any species, but especially of species that are members of a species complex -- multiple independent species that all look alike.

Many fields of science and medicine depend on the accurate demarcation and identification of species, including ecology, evolution, conservation and wildlife management, agriculture and pest management, epidemiology and vector-borne disease management etc. These fields also intersect government, legislature and policy, with major implications for the day-to-day lives of broader human society.

The DELINEATE model is a first step in a process that will need to be further refined. Funding for this research came from the National Science Foundation.

SAN FRANCISCO, CA--May 12, 2021--Following the minuscule movements of every cell in a petri dish would be a painstaking task for any human. But teach a set of computer programs to do the job, and they can complete it quickly and even observe things that the human eye would miss.

Scientists at Gladstone Institutes have developed such an approach, which uses "neural nets"--artificial intelligence programs that can detect patterns--to analyze the locations of hundreds of cells growing together in a colony. When they applied the technique to a group of stem cells, the program revealed that a small number of cells act as "leaders," able to direct the movements of their neighbors.

"This technique gives us a much more comprehensive view of how cells behave, how they work cooperatively, and how they come together in physical space to form complex organs," says Gladstone Senior Investigator Todd C. McDevitt, PhD, senior author of a new paper published in the journal Stem Cell Reports.

Clusters of stem cells have the ability to form any tissue in the human body when exposed to the right mixture of signaling molecules. But researchers have a poor understanding of how those cells form patterns in space to eventually give rise to complex three-dimensional organs.

Traditionally, to study how cells move in space over time, cell biologists tag cells with fluorescent molecules that make them easy to track. Then, they watch those cells under a microscope to see how they divide and migrate. However, a human observer can only follow a small handful of cells at a time before it becomes too challenging to distinguish different cells and track their movements. This means scientists often have to extrapolate how an entire colony moves based on the movements of just a few of its members.

In the new paper, McDevitt's group trained three different neural networks to follow the motions of individual cells within colonies of thousands of cells. Each network had its own strengths and weaknesses, and individually none of them outperformed a person. But combined, the three neural networks were slightly more effective at tracking cells--they were able to find 94 percent of all cells in sequential frames, meaning they could follow their movements over time. Humans could only track 90 percent of all cells between frames; a scientist trying to follow cell movements could only figure out where nine of every ten cells moved. What's more, the combined neural networks were 500 times faster than a person, averaging 0.35 seconds per frame to identify all cells, while a human averaged about 3 minutes per frame.

When the researchers used the networks to study new colonies of stem cells, they were surprised to see lots more action than previous cell-tracking techniques had identified. While the colonies looked fairly static to the naked eye, the neural networks showed that nearly every cell was on the move--and much of the movement looked random.

"Going in, we didn't really expect there to be that much cell motion, so we had to come up with new approaches to understand the apparent chaos of the cells," says Gladstone Graduate Student David Joy, first author of the new paper.

Cells nearest the edges of each colony moved the most, McDevitt's group discovered. And cells tended to start and stop more than researchers would have guessed--on average, each cell moved for approximately 15 minutes, followed by a quiescent, motionless 10-minute period before another active phase began.

The researchers went on to show how changing the conditions of the cells' environment--by exposing the cells to different nutrients or drugs--can change how cells move. They also used the neural networks to track stem cell colonies over 24 hours as they began to form the multiple layers of different cell types that appear in an early embryo. The team found that cells have a wide range of movement profiles.

"Some cells move with a lot of persistence in once direction, while others move around and around but never get far from where they started," says Ashley Libby, PhD, a former graduate student in McDevitt's lab who helped lead the work. The diversity surprised the team; they had expected most cells to follow similar patterns of movement, she says.

What's more, some cells acted as "leaders" while others behaved more like "followers," the researchers say. The motion of a small number of cells spread outward to their neighbors, eventually shifting the dynamics of the entire colony. It's a pattern that wouldn't have been obvious if just a few cells had been tracked over time by a human observer.

The new findings are just a small sampling of the kinds of observations that will be possible as artificial intelligence approaches are applied to cell tracking, says McDevitt. And the knowledge that comes from these future experiments will be useful to researchers trying to coax cells to come together into complex organoids and organs--for both research and therapeutic purposes.

"If I wanted to make a new human heart right now, I know what types of cells are needed, and I know how to grow them independently in dishes," says McDevitt, who is also a professor of bioengineering and therapeutic sciences at UC San Francisco. "But we really don't know how to get those cells to come together to form something as complex as a heart. To accomplish that, we need more insights into how cells work cooperatively to arrange themselves."

As a next step, McDevitt's team is planning future studies that use the neural networks to analyze movements within stem cell cultures that have genetic mutations, to help show the effect of different genes on cell organization.

Numerous compelling evidences from astroparticle physics and cosmology indicate that the major matter component in the Universe is dark matter, accounting for about 85% with the remaining 15% is the ordinary matter. Nevertheless, people still know little about the dark matter, including its mass and other properties. Many models predict dark matter particles could couple to ordinary particle at weak interaction level, so it is possible to capture the signal of dark matter particle in the direct detection experiment. The scientific goals of the China Dark matter Experiment (CDEX) are on direct detection of light dark matter and neutrino-less double beta decay with p-type point contact germanium (PPCGe) detectors at the China Jinping Underground Laboratory (CJPL). The measurable energy spectra induced by the elastic scattering between dark matter particles and target nucleons in CDEX detector system could give us the information of dark matter mass, spin and other properties.

The analysis of the current dark matter experiments is usually model dependent, and many models beyond the standard model have predicted the existence of dark matter, such as super-symmetry model and extra-dimension model. Due to the variety of physics models, the constraints obtained from same experimental data cannot be applied directly to other models, which brings complications to physical interpretations. Cosmology observations have verified that the major part of dark matter is the non-relativistic cold dark matter, and as a result, the momentum transfer in the scattering process between dark matter particles and nucleons is only about hundreds of MeV, much lower than the electroweak scale (~250 GeV). It is therefore suitable to use effective field theory to analyze the interaction between dark matter and ordinary matter. Two alternative schemes have been proposed in recent years to study different possible interactions, namely non-relativistic effective field theory (NREFT) and chiral effective field theory (ChEFT). An effective theory contains all possible interactions allowed by given symmetric principles, so it can model-independently reduce the complicacy of analysis.

In the dark matter direct detection experiments, what are mostly focused on are the spin-independent (SI) and spin-dependent (SD) scattering analysis, while EFT can give more momentum-dependent or velocity-dependent interaction which are not taken into consideration usually. Benefiting from the low electrical noise of PCCGe, the analysis threshold of CDEX-1B and CDEX-10 both reach 160 eV, which can largely improve the detection sensitivity for light dark matter.

Based on the data set of CDEX-1B and CDEX-10, CDEX collaboration presents new limits for the couplings of WIMP-nucleon arising from NREFT and ChEFT. In the nonrelativistic effective field theory approach, they improve over the current bounds in the low mχ region. In the chiral effective field theory approach, they for the first time extended the limit on WIMP-pion coupling to the mχRelated results have been published online entitled "First experimental constraints on WIMP couplings in the effective field theory framework from CDEX" on Science China-Physics, Mechanics & Astronomy (Sci. China-Phys. Mech. Astron. 64, 281011 (2021))[1]. Prof. Y. F. Zhou from the Institute of Theoretical Physics, Chinese Academy of Sciences wrote a review article for this publication[2].

The operation and analysis of CDEX-1B and CDEX-10 are coming to the end, and the next generation of experiments CDEX-100/CDEX-1T are under preparation now. The lower background level and improvement of PPCGe performance can raise the sensitivity of direct detection experiment. While the next generation experiment of CDEX can discover dark matter remains unknown, but the mystery of dark matter will encourage more and more researchers to pursue its studies until the day when this profound mystery of the Universe will be solved.

The evolution of ankle and foot bones into different shapes and sizes helped mammals adapt and thrive after the extinction of the dinosaurs, a study suggests.

A surge of evolution following the mass extinction 66 million years ago enabled mammals to diversify and prosper during a period of major global change, researchers say.

Analysis of bones that form part of the ankle and the heel of the foot reveal that mammals during this time - the Paleocene Period - were less primitive than previously thought.

Palaeontologists from the University of Edinburgh made the discovery by comparing the anatomy of Paleocene mammals with species from the earlier Cretaceous Period and those that exist today.

They analysed foot and ankle bone measurements - which provide insights into animals' lifestyle and body size - of 40 Paleocene species. The team contrasted the results with data from living mammal species and mammals that existed during the Cretaceous Period.

Their findings show that Paleocene mammals had stockier, more muscular builds than those from the Cretaceous or present day. The animals' joints were also very mobile, supported by ligaments and tendons - rather than bony features as in some living mammals - which the team hypothesise enabled them to adapt and evolve more rapidly following the extinction.

Many species' ankles and feet closely resembled those of ground-dwelling and burrowing mammals that exist today, indicating that these lifestyles were key to surviving and thriving after the mass extinction, which was caused by an asteroid impact.

The ability to dig underground, for example, is likely to have helped mammals survive the initial devastation, while a loss of tree habitats after the extinction period may have favoured ground-dwelling species, the team says.

The study is published in the journal Proceedings of the Royal Society B. An Open Access version of the paper is available here: https://www.research.ed.ac.uk/en/publications/quantitative-assessment-of-tarsal-morphology-illuminates-locomoto. It was funded by a Marie Curie Career Integration Grant, the Natural Environment Research Council, National Science Foundation and European Research Council.

Dr Sarah Shelley, from the University of Edinburgh's School of GeoSciences, who led the study, said: "At the core of our study, we wanted to figure out what Paleocene mammals were doing in terms of their anatomy and how this related to aspects of their lifestyle and evolution in the wake of the dinosaur extinction. Paleocene mammals have this tendency to combine unusual mish-mashes of anatomy but are often seen as 'archaic' and unspecialised precursors to living mammal groups. What we found was this incredible diversity - they're adapting and evolving their robustly built bodies in ways that are different to living mammals. Our results show one of the many ways mammals were able to adapt and thrive following the catastrophic devastation of the end-Cretaceous extinction."

Arizona! The sunsets. The saguaros. The snakes.

All of them are part of life in the sunny Southwest, but keeping cool when the latter is holed up in a golf bag, air compressor or swimming pool pump house is a big ask for a lot of people.

Not as big as you'd think, however.

The first study to analyze snake removals in a social-ecological context was recently published by an Arizona State University conservation biologist working with a local rattlesnake removal company.

"I think one of the surprises was that people don't hate snakes," said researcher Heather Bateman of the College of Integrative Sciences and Arts. "A lot of them responded that the snakes are important to the desert ecosystem and the snake belongs in the desert, just not in my garage."

Snakes were most frequently removed from neighborhoods with wealthier and more highly educated residents, a greater proportion of Hispanic residents and recently constructed homes.

Bateman studied the records from 2,000 snake removals in metro Phoenix between 2018 and 2019. More than 68% of removals were venomous Western diamondback rattlesnake, the most common species in the area.

The contact zone for rattlesnakes and other species tends to be on the Valley fringes, said Bryan Hughes, owner of Rattlesnake Solutions. He gets the most calls from north of the Loop 101 freeway in Phoenix, Scottsdale and Cave Creek.

"A lot of that (area) has this very deep penetration zone where you can find rattlesnakes miles into areas that have been developed," Hughes said. "And that's just because of the way that the properties are developed. They leave natural waterways in place. They tend to use xeric landscaping on larger lots."

They also turn up in Phoenix around the mountain preserves. "That contact zone is razor thin," he said. "It's basically just that first row of houses that surround those parks."

Snake removal was high in neighborhoods with high income, the study found. But in high-income and high-education areas, snake removal was lower.

"That might indicate that there is an understanding that snakes play these important roles in ecosystems and maybe they're OK to be left in place or handled a different way," Bateman said. "Maybe it's because ... they understand the positive benefits of snakes and are less concerned and maybe decide against removal."

Snakes rarely get inside houses. If they do, they came in through an open door, Hughes said.

"We do have a lot of people that move here from cooler environments where a nice spring day means you leave the back patio unlocked and open a little bit and rattlesnakes will come in there occasionally that way, but very rarely," he said. "Most of the time when we get snakes at people's houses, it's in the backyard or the front yard where a lot of the landscaping, as the paper shows, is something that can be useful or mimics in some ways native landscaping that they use."

Hughes grew up in Idaho catching snakes for fun. He moved to Arizona 22 years ago.

"My interest in snakes changed from garter snakes to rattlesnakes at that point," he said.

He has been in business for about 10 years. He has about 25 employees positioned around the Valley and Tucson, who can usually show up for a call in half an hour.

"We have a massive data set just because we're out there and able to collect a lot of information," he said. "So I'm really excited about this type of collaboration."

The amount of data Hughes had on hand was a delight to Bateman.

"There's a lot that ecologists can gain and by partnering with the business community," she said. "What a great relationship to pair scientists with this business who also is using science. They understand their snakes. And they're contributing to what we know just about the natural history of these species. ... If I look at other sources of information of snakes in Maricopa County, I can go to the scientific literature and there's a couple of papers. And they studied snakes for years. They used road writing surveys (where biologists walk or drive down roads and record what they find) and other types of surveys. And they found on the order of hundreds of snakes, not thousands of snakes."

The published study will be of use to Hughes in his work as well.

"One of the biggest things that I saw that is going to have a lot of use for me just dealing with the public is the fact that how people felt about snakes was not meaningfully impacted by whether or not it's an area that a lot of snakes are removed," he said. "I've always thought that our culture has a lot to do with whether or not people feel positively or negatively about snakes. And a lot of what's in there suggests that, which gives me a lot of lessons about how, when I'm talking to somebody that is scared of snakes, how I can talk with them and how I might be able to change their mind."

The Indian public blamed foreigners, minority groups and doctors for the rapid spread of COVID-19 across the country during the first wave, due to misinformation, rumour and long-held discriminatory beliefs, according to an international study led by Monash University.

This resulted in people refusing to get tested for fear of humiliation or public reprisals, which included attacks on Muslims and health care workers.

However, when presented with accurate and reliable information about the virus spread, the Indian public back-pedalled on those negative sentiments and were more likely to get tested and seek medical help, highlighting the importance of health advice from credible sources.

A world-first study by researchers in the Monash Business School, Indian Institute of Technology Kanpur and University of Southampton found the prevalence of accurate information decreased the stigmatisation of COVID-19 patients and reduced the belief that infection was confined to religious minorities, lower-caste groups and frontline workers.

Led by Professor Asad Islam, Director of the Centre for Development Economics and Sustainability in the Monash Business School, the study surveyed 2,138 people across 40 localities in the Indian state of Uttar Pradesh on their views about spread of COVID-19.

Ninety-three per cent of respondents blamed foreigners for the spread of COVID-19, while 66 per cent also blamed the Muslim population. Surprisingly, 34 per cent and 29 per cent of people blamed health care workers and police respectively for failing to contain the virus spread.

The social and physical consequences of stigmatisation were found to be severe, as those with symptoms refused to step forward and get tested for fear of public humiliation.

Other examples included the refusal of non-Hindu doctors and patients to have a dignified burial; attacks on Muslims during and after religious events; health care workers being assaulted and asked to vacate their residences due to fear of virus spread; and incidents of COVID-19 patients leaving self-isolation early.

As India comes to grips with a devastating second wave, with an average of 350,000 new cases and 4,000 deaths daily, researchers say these incidents during the first wave are happening again.

"We believe the results are as relevant today, as widespread stigmatisation is visible even during this wave," Dr Islam said.

"Cases of stigmatisation during the second wave have resulted in doctors being verbally abused and prevented from taking a lift in their own residential flat, old parents being abandoned, several patients fleeing medical facilities across the country, and dead bodies being dumped in rivers.

"Most importantly, we found that stigmatisation of COVID-19 can have negative public health implications as it may lead people to avoid getting tested and respecting prevention measures. This is essential if India is to get on top of this second wave."

During the study, which took place in June 2020 at the height of the first wave, researchers surveyed individuals by phone and followed up with a randomised controlled test. The treatment group received information about COVID-19 and preventive strategies.

Researchers followed up with participants about one month later to assess if the information intervention was effective in improving knowledge about the transmission and prevention of COVID-19.

More than half of the participants who received the information brief were less likely to believe that any particular group was to be blamed for the spread of the disease and thus reduced stigmatisation of COVID-19 patients, frontline workers (health care workers, sanitary workers, and the police), and marginalised groups such as religious minorities.

Furthermore, researchers identified a significant increase in the self-reporting of COVID-related symptoms and subsequent medical treatment in the Indian population, including treatment for mental health. There was a 75 percentage point reduction in stress and anxiety experienced by participants in the treatment group.

An additional 10 per cent of participants reported a greater quality of life as a result of heightened information awareness and consumption.

"Health advice from credible sources in simple language is of utmost importance as individuals are still taking the pandemic lightly, not wearing their masks and are reluctant to get vaccinated due to widespread ignorance and misconception, even when the numbers are soaring," research co-author Associate Professor Liang Choon Wang from the Monash Business School's Department of Economics said.

"Raising awareness and reducing stress and stigmatisation could lead to encouraging vaccination rates, following prescribed quarantine or lockdown guidelines, coming forward and getting tested if symptoms are visible (or in early stages of infection) and getting help at the earliest time."

Traffic noise leads to inaccuracies and delays in the development of song learning in young birds. They also suffer from a suppressed immune system, which is an indicator of chronic stress. A new study by researchers of the Max Planck Institute for Ornithology and colleagues shows that young zebra finches, just like children, are particularly vulnerable to the effects of noise because of its potential to interfere with learning at a critical developmental stage.

Traffic noise is a pervasive pollutant that adversely affects the health and well-being of millions of people. In addition to severe noise-induced diseases in adults, traffic noise has also been linked to learning impairments and language deficits in children. In order to analyse the causal mechanisms connecting chronic noise exposure to cognitive deficiencies, researchers of the Max Planck Institute for Ornithology with colleagues at the University of Paris Nanterre and the Manchester Metropolitan University studied the song learning and immune function of young zebra finches exposed to traffic noise. Like children, songbirds must learn their vocalizations from adult tutors during a sensitive period early in life. Under normal conditions, the songs of the finches become stable and stereotyped at an age of around 90 days, and remain the same for the rest of their adult life, a process called "crystallization".

For the study, the researchers raised male zebra finch chicks in two groups. During their sensitive song learning period, the chicks in both groups were tutored with recorded song of adult males. In one group, the birds were additionally exposed to traffic noise that had been recorded in bird habitats close to busy roads in the city of Munich, Germany. The scientists monitored the singing activity of each male and compared their song development and learning success. Furthermore, they measured the immune responses of the chicks while they grew up.

Noise weakens immune response

The researchers found that juvenile zebra finches exposed to realistic levels of city noise had weaker immune responses than chicks from quiet nests, suggesting that noise was a source of chronic stress in these young birds. Furthermore, the birds in the noise treatment were significantly delayed in their vocal development - crystallizing their songs more than 30% later than controls, and with significantly lower accuracy in their song learning. "Our findings indicate that young songbirds, just like human children, are particularly vulnerable to the effects of noise because of its potential to interfere with learning at a critical developmental stage", says Henrik Brumm, who led the international research project.

The results of the study suggest that traffic noise even has the potential to affect the cultural evolution of bird song since noise-induced copying errors are likely to accumulate as song passes from one bird to another. "Our paper marks a breakthrough in the study of the effects of anthropogenic noise," Sue Anne Zollinger of the research team concludes, "it establishes bird song as an experimental paradigm for future studies on noise-related cognitive and developmental impairments, especially in regard to vocal learning deficiencies and speech development".

New Orleans, LA - Research conducted by an international team of scientists discovered a mechanism that leads to Herceptin resistance, representing a significant clinical obstacle to successfully treating HER2-positive breast cancer. They also identified a new approach to potentially overcome it. The work is published online in Nature Communications, available here.

"This work attempts to understand why some HER2-positive breast cancer patients do not benefit from treatment with Herceptin, which is a generally effective HER2-targeted therapy," explains Bolin Liu, MD, Professor of Genetics at LSU Health New Orleans' School of Medicine and Stanley S. Scott Cancer Center.

The researchers found increased signaling by IGF2/IRS1 (genes involved in regulating cell proliferation, growth, migration, differentiation and survival) in the HER2-positive breast cancer cells poorly responding to Herceptin. Further studies showed that disruption of a negative feedback loop formed by an important protein, FOXO3a, and several miRNAs that are controlled by FOXO3a causes abnormal activation of the IGF2/IRS1 signal, thereby leading to Herceptin resistance.

"Resistance to Herceptin frequently occurs and currently represents a major clinical challenge for successful treatment of HER2-positive breast cancer," notes Dr. Liu. "Data presented in the study not only improve our understanding of the molecular mechanism through which IGF-1R signaling activation leads to Herceptin resistance, but also promote identification of precision therapies to reverse the resistance phenotype."

The researchers write, "Breast cancer is the leading cause of cancer-related deaths in women worldwide. HER2-positive breast cancer is defined as a breast cancer subtype with amplified and/or overexpressed HER2 (or erbB2) gene. Amplification/overexpression of HER2 is observed in approximately 20-25% of breast cancers and is significantly associated with poor prognosis in breast cancer patients. Herceptin (or trastuzumab), a humanized anti-HER2 monoclonal antibody (Ab), is an effective HER2-targeted therapy against early and metastatic HER2-positive breast cancers. It has dramatically improved the survival of breast cancer patients with HER2-positive tumors, but not all HER2-positive breast cancers respond to Herceptin-based regimens. To date, we lack validated biomarkers predictive for Herceptin response."

"Our results may provide new avenues to identify useful biomarkers predictive for Herceptin efficacy and facilitate the development of novel approaches to enhance HER2-targeted therapy, thereby improving the survival of refractory breast cancer patients," Dr. Liu concludes.