Culture

Almost 80% of South Africans speak one of the SEB family languages as their first language. Their origins can be traced to farmers of West-Central Africa whose descendants over the past two millennia spread south of the equator and finally into Southern Africa.

Since then, varying degrees of sedentism [the practice of living in one place for a long time], population movements and interaction with Khoe and San communities, as well as people speaking other SEB languages, ultimately generated what are today distinct Southern African languages such as isiZulu, isiXhosa and Sesotho.

Despite these linguistic differences, these groups are treated mostly as a single group in genetic studies.

Understanding genetic diversity in a population is critical to the success of disease genetic studies. If two genetically distinct populations are treated as one, the methods normally used to find disease genes could become error prone.

Consideration of these genetic differences is critical to providing a reliable understanding of the genetics of complex diseases, such as diabetes and hypertension, in South Africans.

Dr Dhriti Sengupta and Dr Ananyo Choudhury in the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at the University of the Witwatersrand, Johannesburg, South Africa, were joint lead authors of the paper published in Nature Communications on 7 April 2021.

The study comprised a multidisciplinary team of geneticists, bioinformaticians, linguists, historians and archaeologists from Wits University (Michèle Ramsay, Scott Hazelhurst, Shaun Aron and Gavin Whitelaw), the University of Limpopo, and partners in Belgium, Sweden and Switzerland.

"South Eastern Bantu-speakers have a clear linguistic division - they speak more than nine distinct languages - and their geography is clear: some of the groups are found more frequently in the north, some in central, and some in southern Africa. Yet despite these characteristics, the SEB groups have so far been treated as a single genetic entity," says Choudhury.

The study found that SEB speaking groups are too different to be treated as a single genetic unit.

"So if you are treating say, Tsonga and Xhosa, as the same population - as was often done until now - you might get a completely wrong gene implicated for a disease," says Sengupta.

ABOUT THE STUDY

The study, titled: "Genetic substructure and complex demographic history of South African Bantu speakers" aimed to find out whether the SEB speakers are indeed a single genetic entity or if they have enough genetic differences to be grouped into smaller units.

Genetic data from more than 5000 participants speaking eight different southern African languages were generated and analysed.

These languages are isiZulu, isiXhosa, siSwati, Xitsonga, Tshivenda, Sepedi, Sesotho and Setswana.

Participants were recruited from research sites in Soweto in Gauteng, Agincourt in Mpumalanga, and Dikgale in Limpopo province.

Genetic differences reflect geography, language and history

The study detected major variations in genetic contribution from the Khoe and San into SEB speaking groups; some groups have received a lot of genetic influx from Khoe and San people, while others have had a very little genetic exchange with these groups.

This variation ranged on average from about 2% in Tsonga to more than 20% in Xhosa and Tswana.

This suggests that SEB speaking groups are too different to be treated as a single genetic unit.

"The study showed that there could be substantial errors in disease gene discovery and disease risk estimation if the differences between South-Eastern-Bantu speaking groups are not taken into consideration," says Sengupta.

The genetic data also show major differences in the history of these groups over the last 1000 years. Genetic exchanges were found to have occurred at different points in time, suggesting a unique journey of each group across the southern African landscape over the past millennium.

These genetic differences are strong enough to impact the outcomes of biomedical genetic research.

Sengupta emphasises, however, that ethnolinguistic identities are complex and cautioned against extrapolating broad conclusions from the findings regarding genetic differences.

"Although genetic data showed differences [separation] between groups, there was also a substantial amount of overlap [similarity]. So while findings regarding differences could have huge value from a research perspective, they should not be generalised," she says.

A GENETIC BLUEPRINT FOR FUTURE HEALTH

A common approach to identify if a genetic variant causes or predisposes us to a disease is to take a set of individuals with a disease (e.g., high blood pressure or diabetes) and another set of healthy individuals without the disease, and then compare the occurrence of many genetic variants in the two sets.

If a variant shows a notable frequency difference between the two sets it is assumed that the genetic variant could be associated with the disease.

"However, this approach depends entirely on the underlying assumption that the two groups consist of genetically similar individuals. One of the major highlights of our study is the observation that Bantu-speakers from two geographic regions - or two ethnolinguistic groups - cannot be treated as if they are the same when it comes to disease genetic studies," says Choudhury.

Future studies, especially those testing a small number of variants, need to be more nuanced and have balanced ethnolinguistic and geographic representation, he says.

This study is the second landmark study in African population genetics, published in the last six months, led by researchers in the Sydney Brenner Institute for Molecular Bioscience in the Faculty of Health Sciences at Wits University.

Professor Michèle Ramsay, director of the SBIMB and corresponding author of the study, says: "The in-depth analysis of several large African genetic datasets has just begun. We look forward to mining these datasets to provide new insights into key population histories and the genetics of complex diseases in Africa".

The Cyclostomata is an ancient group of aquatic colonial suspension-feeders from the phylum Bryozoa. The fact that they have unique placentae has been discovered by researchers at St Petersburg University and the University of Vienna. The coenocytes, i.e. large multinucleate cell structures, originate via nuclear multiplication and cytoplasmic growth among the cells surrounding the early embryo. Interestingly, the coenocytes are commonly found among fungi and plants, yet are quite rare in animals. It is the first time coenocytes have been discovered in placenta.

Biologists are well aware that the cells of the living organisms are incredibly different in the way that they behave. They may happen to form a multinucleate structure resulting from cell fusion, i.e. so-called syncytium with a single membrane. Such 'behaviour' ensures nutrient circulation with no resources and time spent on transporting between the cells. Yet similar structures can be formed through ways other than fusion, e.g. coenocytes originate via nuclear multiplication and cytoplasmic growth. Cell fusion is mainly typical of animals. For instance, in human placenta, syncytium covers embryonic placental villi, which invades the wall of the uterus to establish nutrient circulation between the embryo and the mother. In contrast, formation of coenocytes is typical of plants and fungi. Yet what these processes - cell fusion and cell growth, have in common is that they result in quite large irregular structures that resemble tissues.

'Initially, my postgraduate student Uliana Nekliudova, who is the first author of the article, and I expected to see syncytium in the Cyclostomata. Yet what we came across was coenocytes, i.e. multinucleate structures that were previously unknown in animal placentas,' said the head of the project and Professor at the Department of Invertebrate Zoology at St Petersburg University Andrew Ostrovsky. 'The embryos in this group of Bryozoa are not just abut the placenta, as happens normally, but embedded into it. The placenta consists of several large coenocytes, and the coenocytic "elements" are interconnected via cytoplasmic bridges and various cell contacts. Coenocytes have different ultra-structure. This tissue shows evidence of both nutrient synthesis and transport.'

Additionally, as the scientist said, forming such a structurally complex placenta may have contributed to evolving polyembryony in this group of animals. Polyembryony is a condition in which over a hundred embryos develop from a single fertilised egg, forming larvae. Yet, the unique combination of placentation, viviparity, and polyembryony is known to occur only in the nine-banded armadillo Dasypus.

The samples were collected near the Marine Biological Station of St Petersburg University at the White Sea. The scientists also discovered that placentation originated from the organ that was responsible for pushing off tentacles. All bryozoans release sperm into water column where zooids from other colonies catch it using tentacles. The membranous sac, i.e. an organ that contains circular muscles, pushes the tentacles off. After internal fertilisation, the membranous sac becomes part of the placenta transforming to coenocytes that provide embryonic nourishment. Evolution of the cyclostome placenta, involving transformation of the hydrostatic apparatus (membranous sac) and substitution of its function to embryonic nourishment, is an example of exaptation.

Most bryozoans eject a fertilised egg and then transport it into a special brood cavity for incubation. Yet the cyclostome bryozoans do it differently. The larvae develop inside the gonozooids, i.e. colony members that serve as a placental incubator. Larval production lasts almost all summer. Developed larvae gradually leave the gonozooids.

'Polyembryony is a so-called evolutional dead-end. You have offspring, yet they are clones. There is no genetic diversity', said Andrew Ostrovsky. 'The fact that the offspring are different is essential for the ability to survive. The question is why is polyembryony - that has been typical to Cyclostomata for about 200 million years according to the fossil evidence we have - resisted? What is the catch? Presumably, the bryozoans, producing clone-larvae during several months, "collide" them with a constantly changing environment. As a result, it is not genomes that change, but conditions where these genomes happen to find themselves.'

Although the problem of gender discrimination is already found in the music industry, music recommendation algorithms would be increasing the gender gap. Andrés Ferraro and Xavier Serra, researchers of the Music Technology research group (MTG) of the UPF Department of Information and Communication Technologies (DTIC), with Christine Bauer, of the University of Utrecht (Netherlands), have recently published a paper on gender balance in music recommendation systems in which they ask themselves how the system should work to avoid gender bias.

At the outset, the authors identified that gender justice was one of the artists' main concerns

Initially, the work by Ferraro, Serra and Bauer aimed to understand the fairness of music platforms available online from the artists' point of view. In interviews conducted with music artists, they identified that gender justice was one of their main concerns.

Women have less exposure

The authors tested a commonly used music recommendation algorithm based on collaborative filtering and analysed the results of two datasets. In both cases, they found that the algorithm reproduces the existing bias in the dataset, in which only 25% of artists are women. In addition, the algorithm generates a ranking with artists to recommend to the user. The authors saw that on average the first recommendation of a woman artist comes in 6th or 7th position, while that of a man artist is in first position. Ferraro, first author of the paper adds: "The bias in exposure comes from the way recommendations are generated". This means that women have less exposure based on the recommendations of the system.

The situation worsens when taking into account that as users listen to recommended songs, the algorithm learns. This creates a feedback loop.

With the help of the reordered algorithm, users begin to change their behaviour so that they listen to more female artists

A new approach to compensate for gender bias

The authors of the study propose a new approach that would allow greater exposure of female artists and would consist of reordering the recommendation, which would move a specified number of positions downwards in order to solve the existing gender bias.

In a simulation, the authors studied how classified recommendations would affect user behaviour in the long run. The results showed that, with the help of the reclassified algorithm, users would begin to change their behaviour and thus listen to more female artists than with other music recommendation algorithms and, moreover, the new algorithm, based on machine learning, would consolidate this change in behaviour.

MINNEAPOLIS/ST.PAUL (04/20/2021) -- University of Minnesota Medical School researchers have offered new ways to think about the immune system thanks to a recent study published in Nature. Their research, which indicates organ tissues become increasingly immune throughout life, may begin to alter fundamental ideas regarding the rules of vaccination and the immune system's function within the body.

Saythi Wijeyesinghe, PhD, the lead author on the study is a researcher in the Masopust Lab at the U of M Medical School, which focuses on T cell immunity. His research began with the goal to understand the lifespan of T cells in organ tissues, which are known to fight off viruses while also protecting from reinfection by the same virus.

"Historically, studies of the immune system have emphasized its renewable nature through bone marrow, lymphoid organs and blood. Our work shows how much this model fails to account for the many immune cells distributed throughout other organs of the body, where most infections and tumors arise," Wijeyesinghe said. "What we found ends up painting a much broader picture of how the immune system accomplishes surveillance of the entire body for pathogens, tissue damage and tumors."

The study's major findings, include:

- Antiviral T cells that reside in most organs of the body persist over time and in the face of extensive infectious exposures;

- Unlike other organ systems, the immune system becomes increasingly immune throughout life, which is a natural response to accumulated microbial exposures over time;

- Up to 25% of the cells in organs were immune cells, indicating that the immune system significantly contributes to the cellular makeup of the body;

- And, along with antiviral T cells, most other immune cells are durably tissue-resident in organs as well.

Wijeyesinghe hopes this study can further advance the ongoing change in how the broader scientific community conceptualizes the immune system and immune homeostasis.

During this study, Wijeyesinghe also unexpectedly discovered how tissue-resident T cells may serve as the origin for memory T cells in blood. As a next step in this research, the Masopust Lab is developing new techniques to trace the fate of these immune cells, hoping to further dissect the relationship between blood-borne and tissue-based immunity.

PHILADELPHIA - Renter protection policies that have curbed mass evictions during the COVID-19 pandemic have played a key role in preventing the spread of SARS-CoV-2 in U.S. cities, according to a new study published in Nature Communications.

Using an epidemiological model to predict how evictions and eviction moratoria would impact the epidemic, the researchers found, for instance, that in a city of 1 million in which 1 percent of households experience eviction monthly, this could lead to up to 49,000 excess COVID-19 infections. In Philadelphia alone, a fivefold increase in evictions, predicted by some economic analyses, could lead to 53,000 extra infections. The study was led by researchers in the Perelman School of Medicine at the University of Pennsylvania, Johns Hopkins University, and the University of Illinois at Urbana-Champaign.

"Our model shows clearly that policies to stem evictions are not only a warranted but a necessary component of COVID control. As long as the virus is circulating, ending these protections could have devastating implications in the United States," said co-senior author Michael Z. Levy, PhD/a>, an associate professor of Epidemiology in Penn's Perelman School of Medicine.

Record levels of unemployment have put millions of Americans at risk of losing their homes throughout 2020 and 2021. At the start of the pandemic, many cities and states enacted temporary legislation banning evictions, some of which have since expired. On September 4, 2020, the Centers for Disease Control and Prevention (CDC) imposed a national moratorium on evictions, which was extended in March 2021. This order is currently being challenged in various courts.

In addition to a number of well-documented adverse outcomes, evictions would also have outsized repercussions on the growth rate of the COVID-19 epidemic, Levy and his research team predicted in the summer of 2020. The effect emerges from increases in household sizes -- data suggest that, once evicted, households tend to "double-up," moving in with friends or family. Household transmission can also limit or delay the effects of measures like lockdowns, which aim to decrease the contact rate in the general population.

"Evictions were particularly concerning for us, because a growing number of contact tracing studies have shown that households are a major source of SARS-CoV-2 transmission. When households get bigger, that gives the virus a greater opportunity to get inside the home, and then, a greater chance to spread outside of it -- to coworkers, friends, and other family members," study co-author Alison Hill, PhD, an assistant professor at the Johns Hopkins University School of Medicine.

To quantify this effect, the research team modified an epidemiological model known as SEIR (susceptible, exposed, infectious, and recovered) to track the transmission of SARS-CoV-2 through a hypothetical metropolitan area of 1 million individuals. They then used a two-layer "network model" to show the contacts within a city population over which infection can spread: One layer described contacts within the household, estimated from the 2019 American Community Survey of the U.S. Census, and the second layer constituted contacts outside the household, such as work colleagues, classmates, and friends.

The researchers modeled evictions that resulted in the "doubling up" of households by merging each evicted household with one randomly selected household in the network. They then adjusted the number of contacts outside the household over the course of the simulations to capture the effects of lockdown measures and their subsequent relaxation.

The research team found that with a low monthly eviction rate of 0.25 percent, an estimated 0.5 percent more of the population could become infected with COVID-19 -- or about 5,000 excess cases per 1 million residents -- compared to if there were no evictions. A 1 percent monthly eviction rate could lead to 19,000 to 49,000 excess cases. With an eviction rate of 2 percent per month, that number jumps to 50,000 to 100,000 excess infections in a single city.

"Our results suggest that the CDC-mandated national order prohibiting evictions from Sept 4 - Dec 31, 2020 likely prevented thousands of excess COVID-19 infections for every million metropolitan residents," according to the study authors.

Their initial model assumed that mixing between households occurs randomly throughout a city and that evictions are uniformly distributed. However, data throughout the pandemic has consistently showed that both COVID-19 and evictions disproportionately affect poorer, minority communities. The research team therefore adjusted their model to evaluate the effect of evictions in a specific, diverse city - Philadelphia, Pennsylvania, which has one of the highest eviction rates among large U.S. cities.

In July 2020, Philadelphia's City Council passed the Emergency Housing Protection Act, in an effort to prevent evictions during the pandemic. The city was sued by a lobbyist group, which questioned whether the legislation was of broad societal interest, rather than protecting a narrow class of residents. This prompted Levy's team to assess the claim.

Their simulations showed that allowing evictions to resume in Philadelphia could substantially increase the number of COVID infections in the city, and that these increases would be felt among various socioeconomic populations, including those experiencing a low number of evictions. With evictions occurring at only their pre-pandemic rates, the epidemic would infect an extra 0.3 percent of the Philadelphia population, or 4,700 individuals. However, the researchers point out, many economic analyses predict the eviction crisis could be much higher if allowed to resume, due to the economic fallout associated with COVID-19. With a five-fold increase in evictions, excess infections would increase by 53,000 in the city.

"These simulations show that a change that seemingly only affects a small proportion of the population can have a great impact across interconnected communities," Levy said. "Evictions not only affect the evicted, but they can endanger an entire city."

An overgrowth of yeast in the gut within the first few months of life may cause changes to the immune system that increase the risk of asthma later on, shows a study published today in eLife.

Asthma is a common and sometimes difficult-to-manage, life-long lung condition that affects one in 10 children in developed countries. The findings explain a possible cause of asthma and may help scientists develop new strategies to prevent or treat the condition.

The period just after birth is a critical window for the development of a healthy immune system and gut microbiome. Disruptions to gut bacteria that produce anti-inflammatory compounds called short-chain fatty acids (SCFAs) early in life have previously been linked to asthma.

"We recently showed that overgrowth of a type of gut yeast called Pichia kudriavzevii in newborns in Ecuador is associated with an increased risk of asthma," says first author Rozlyn Boutin, an MD/PhD student in the Department of Microbiology and Immunology at the University of British Columbia, Vancouver, Canada. "In this study, we wanted to see if we could replicate these findings in children from an industrialised setting and identify how fungi of the gut microbiota affect the development of the immune system."

Boutin and colleagues began with a study of 123 newborns in Canada, who are part of the CHILD Cohort Study. They again found that an overgrowth of Pichia kudriavzevii in the stools of the newborns during the first three months of life was associated with a higher risk of asthma.

To understand how this yeast overgrowth might contribute to asthma later in life, the team applied Pichia kudriavzevii to newborn mice with immature gut microbiota communities. In this mouse model of asthma, the team found that the newborns exposed to the yeast experienced more lung inflammation than those who were unexposed. Applying Pichia kudriavzevii to an adolescent mouse model, however, did not cause this excess inflammation.

"Our findings show that there is a critical window in early life where disruptions in the gut microbiota caused by Pichia kudriavzevii affect the development of the immune system and increase the risk and severity of asthma later in life," Boutin says.

Previous studies have shown that bacterial SCFAs have beneficial effects on immune development that protect against asthma. In this study, the team also showed that anti-inflammatory SCFAs produced by gut bacteria inhibit the growth of Pichia kudriavzevii.

"Immune responses to gut microbe disruptions early in life have long-term consequences for diseases of the immune system later in life," concludes senior author Brett Finlay, Professor at the Michael Smith Laboratories and the Departments of Biochemistry and Molecular Biology, and Microbiology and Immunology, University of British Columbia. "Our study adds to our understanding of microbiota-associated asthma and suggests that inhibiting yeast overgrowth with SCFAs in early life could be an effective approach to preventing this condition."

FAYETTEVILLE, Ark. - The fearsome tyrannosaur dinosaurs that ruled the northern hemisphere during the Late Cretaceous period (66-100 million years ago) may not have been solitary predators as popularly envisioned, but social carnivores similar to wolves, according to a new study.

The finding, based on research at a unique fossil bone site inside Utah's Grand Staircase-Escalante National Monument containing the remains of several dinosaurs of the same species, was made by a team of scientists including Celina Suarez, University of Arkansas associate professor of geosciences.

"This supports our hypothesis that these tyrannosaurs died in this site and were all fossilized together; they all died together, and this information is key to our interpretation that the animals were likely gregarious in their behavior," Suarez said.

The research team also include scientists from the U.S. Bureau of Land Management, Denver Museum of Nature and Science, Colby College of Maine and James Cook University in Australia. The study examines a unique fossil bone site inside Grand Staircase-Escalante National Monument called the "Rainbows and Unicorns Quarry" that they say exceeded the expectations raised even from the site's lofty nickname.

"Localities [like Rainbows and Unicorns Quarry] that produce insights into the possible behavior of extinct animals are especially rare, and difficult to interpret," said tyrannosaur expert Philip Currie in a press release from the BLM. "Traditional excavation techniques, supplemented by the analysis of rare earth elements, stable isotopes and charcoal concentrations convincingly show a synchronous death event at the Rainbows site of four or five tyrannosaurids. Undoubtedly, this group died together, which adds to a growing body of evidence that tyrannosaurids were capable of interacting as gregarious packs."

In 2014, BLM paleontologist Alan Titus discovered the Rainbows and Unicorns Quarry site in Grand Staircase-Escalante National Monument and led the subsequent research on the site, which is the first tyrannosaur mass death site found in the southern United States. Researchers ran a battery of tests and analyses on the vestiges of the original site, now preserved as small rock fragments and fossils in their final resting place, and sandbar deposits from the ancient river.

"We realized right away this site could potentially be used to test the social tyrannosaur idea. Unfortunately, the site's ancient history is complicated," Titus said. "With bones appearing to have been exhumed and reburied by the action of a river, the original context within which they lay has been destroyed. However, all has not been lost." As the details of the site's history emerged, the research team concluded that the tyrannosaurs died together during a seasonal flooding event that washed their carcasses into a lake, where they sat, largely undisturbed until the river later churned its way through the bone bed.

"We used a truly multidisciplinary approach (physical and chemical evidence) to piece the history of the site together, with the end-result being that the tyrannosaurs died together during a seasonal flooding event," said Suarez.

Using analysis of stable carbon and oxygen isotopes and concentrations of rare earth elements within the bones and rock, Suarez and her then-doctoral student, Daigo Yamamura, were able to provide a chemical fingerprint of the site. Based on the geochemical work, they were able to conclusively determine that the remains from the site all fossilized in the same environment and were not the result of an attritional assemblage of fossils washed in from a variety of areas.

"None of the physical evidence conclusively suggested that these organisms came to be fossilized together, so we turned to geochemistry to see if that could help us. The similarity of rare earth element patterns is highly suggestive that these organisms died and were fossilized together," said Suarez.

Excavation of the quarry site has been ongoing since its discovery in 2014 and due to the size of the site and volume of bones found there the excavation will probably continue into the foreseeable future. In addition to tyrannosaurs, the site has also yielded seven species of turtles, multiple fish and ray species, two other kinds of dinosaurs, and a nearly complete skeleton of a juvenile (12-foot-long) Deinosuchus alligator, although they do not appear to have all died together like the tyrannosaurs.

"The new Utah site adds to the growing body of evidence showing that tyrannosaurs were complex, large predators capable of social behaviors common in many of their living relatives, the birds," said project contributor, Joe Sertich, curator of dinosaurs at the Denver Museum of Nature & Science. "This discovery should be the tipping point for reconsidering how these top carnivores behaved and hunted across the northern hemisphere during the Cretaceous."

Future research plans for the Rainbows and Unicorns Quarry fossils include additional trace element and isotopic analysis of the tyrannosaur bones, which paleontologists hope will determine with a greater degree of certainty the mystery of Teratophoneus' social behavior.

In stark contrast to the social interaction between humans and among many species of animals, paleontologists have long debated whether tyrannosaurs lived and hunted alone or in groups.

Based on findings at a site in Alberta, Canada, with over 12 individuals, the idea that tyrannosaurs were social with complex hunting strategies was first formulated by Philip Currie over 20 years ago. This idea has been widely debated, with many scientists doubting the giant killing machines had the brainpower to organize into anything more complex than what is observed in modern crocodiles. Because the Canadian site appeared to be an isolated case, skeptics claimed it represented unusual circumstances that did not reflect normal tyrannosaur behavior. Discovery of a second tyrannosaur mass death site in Montana again raised the possibility of social tyrannosaurs, but this site was still not widely accepted by the scientific community as evidence for social behavior. The researcher's findings at the Unicorns and Rainbows Quarry provides even more compelling evidence that tyrannosaurs may have habitually lived in groups.

TAMPA, Fla (April 20, 2021) — Chaperone protein imbalance can play a significant role in initiating toxic accumulation of tau in the aging brain – an early step in the development of Alzheimer’s disease and related neurodegenerative disorders known as tauopathies, a new preclinical study by University of South Florida Health (USF Health) neuroscientists suggests.

In humans, misfolding of the protein tau leads to its toxic accumulation inside brain cells, the formation of these tau aggregates into hallmark neurofibrillary tangles, neuron death, and eventually symptoms of cognitive decline such as memory loss and diminished thinking skills.

In this study the USF Health Morsani College of Medicine researchers used mice that were not genetically modified (wild-type mice) to examine the effects of Aha1 and FKBP52, two co-chaperone proteins of heat shock protein Hsp90, in the aging brain. They modeled molecular chaperone imbalance by overexpressing production of Aha1 and FKBP52 in these old, wide-type mice. The findings, highlighted below, were reported April 8 in Acta Neuropathologica Communications.

Hsp90 is a chaperone protein abundant in neurons and other cells in the brain. Normally, co-chaperone proteins assist chaperone proteins in monitoring and sustaining the balance (homeostasis) of proteins critical to cell health.

“The chaperone protein network is your cell’s natural defense to maintain homeostasis throughout life, and this study emphasizes the importance of protecting that balance in the aging brain,” said principal investigator Laura Blair, PhD, an assistant professor of molecular medicine at the USF Health Byrd Alzheimer’s Center, Morsani College of Medicine. “We’re excited about using this new model of tauopathy in finding ways to restore chaperone protein balance to delay or stop the progression of Alzheimer’s and other neurodegenerative diseases.”

Among their many quality-control functions, chaperone protein networks ensure proteins are folded to conform to the proper 3D shapes, transported precisely where needed to do their jobs, and pushed toward degradation if they are abnormally modified or no longer useful. Heat shock proteins like Hsp90, triggered when a cell is under stress, play a particularly important “triage” role in correcting protein misfolding to prevent aggregation.

“But in the aging brain, the balance of the chaperone proteins shifts and creates a system not working as efficiently as it normally would. Large numbers of the chaperone molecules decrease in expression, and a smaller but significant number increase in their expression,” Dr. Blair said.

Increasing age is the greatest known risk factor for Alzheimer’s disease. So, the USF Health team investigated whether increased levels of FKBP52 and Aha1 alone could initiate pathological features mimicking human Alzheimer’s disease in aged wild-type mice – those with no genetic manipulations predisposing their brains to abnormally increase tau aggregation.

Key findings from their new mouse model of tauopathy include:

High levels of FKBP52, and to a lesser extent elevated levels of Aha1, increased tau accumulation over time in the aged, wild-type mice.

The tau accumulation promoted by overexpression of FKBP52, but not Aha1, correlated with increased neuroinflammation through exaggerated activation of neuronal support cells, namely microglia and astrocytes. This was complemented by loss of neurons and cognitive impairments.

Existing mouse models, including those that add or subtract genes, introduce tau mutations, and seed mice brains with human tau, help scientists learn more about the underlying causes of Alzheimer’s disease and other tauopathies. However, they tend to be limited in capturing the physiological aspects of neurodegeneration in the context of both normal and abnormal aging.

“We hope this (chaperone imbalance) model will help us better understand the dynamics of tau aggregation and neuroinflammation, including the timing and connections among pathological events, without directly regulating one pathway or the other,” Dr. Blair said.

Dr. Blair’s team has designed follow-up studies to help unravel if, and when, tau accumulation or neuroinflammation is more influential in causing brain cell toxicity during aging. That could help determine which chaperones — FKBP52, Aha1, or others — may be the best therapeutic target options for restoring protein balance, she said.

Co-lead authors for the USF Health study were postdoctoral fellow Marangelie Criado-Marrero, PhD, and doctoral student Niat Gebru. The research was supported by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, National Institute on Aging, and the National Institute of Mental Health.

DOI

10.1186/s40478-021-01159-w

With alarms sounding about the declining diversity of plants and animals, a related concern with equally profound implications is posed: is the variety of microbial life, including viruses, changing too -- and if so, in which direction and how fast?

In a paper published today, David S. Thaler of the University of Basel, Switzerland, and Guest Investigator at The Rockefeller University's Programme for the Human Environment (PHE), notes the well-documented, "clearly downwards" trajectory of plant and animal diversity, constituting "a key issue of the Anthropocene."

Whether change is underway also in the world of microbes -- the tiniest cogs in planetary functioning -- is "a complete unknown. We have no idea whether global microbial diversity is increasing, decreasing, or staying the same," says Dr. Thaler.

"Most scientific papers tell us new facts. This is a different kind of paper; it does not answer anything but asks a new question," says Dr. Thaler.

"Socrates called ignorance of what we do not know 'profound ignorance.' This kind of ignorance was also famously termed 'unknown unknowns' (youtu.be/GiPe1OiKQuk) by former US Defence Secretary Donald Rumsfeld. Today's paper identifies what is (or was, as of now) a biological 'unknown unknown'."

Dr. Thaler points out that assessing plant and animal biodiversity involves counting different species within a given timeframe, and then comparing a subsequent count. By doing so, we learned that some species have recently become extinct, and many exist in fewer numbers, with an estimated one million at risk of extinction within decades.

The same approach has been used to monitor, for example, changes in microbial diversity in an intestine due to dietary changes.

Unfortunately, says Dr Thaler, it may be impossible to "count everything at different times" to figure out the direction of change in global microbial biodiversity because:

The extent of current microbial biodiversity is unknown, and a large fraction of the microbial world may exist in hard-to-access, rare, or extreme environments -- the deeper the depth, the less we know. Previous research has theorized that the deep hot biosphere may contain the majority of our planet's microbial biodiversity. Resolving this problem might require 20 years before there is a sufficient understanding of the deep biosphere and other hard-to-access environments.

A possible 'chicken and egg' paradox may prove hard to resolve: Establishing a baseline sequence library may never be finished because new diversity is generated more rapidly than it is measured. If some or all parts of microbial diversity are rapidly increasing, then survey approaches may never catch up to this dynamic process.

Says Dr. Thaler: The world is finding hundreds of variants of the SARS-CoV-2 virus that causes COVID-19, one of a very roughly estimated 10 billion different kinds of microbes each evolving in its own ways.

(Dr. Thaler cites a Harvard Medical School video, at https://youtu.be/plVk4NVIUh8, documenting how quickly bacteria can mutate to overcome increasing higher concentrations of antibiotics. Meanwhile, a recent study (bit.ly/IPBESpandemics) also estimates that there are more than 1 million animal viruses, about half of them potentially infectious to humans.)

"Microbial evolution is not always toward greater diversity, microbes can also become extinct, smallpox virus being an example," he adds. "Countless other viruses and bacteria probably have also come and gone without our ever having known of their existence. Some microbes are specific in their associations with certain animals and plants. As these plants and animals become extinct, it seems likely that specialized microbes associated with them have also vanished."

"The key point is that with plants and animals we know that the current overall trajectory of Earth's biosphere is toward fewer species, but there is no comparable understanding of the overall trajectory or detailed fine-structure trajectories of microbial evolution."

Possible implications in the trajectory of microbial evolution are not limited to the evolution of pathogens that attack humans or the few species we depend on for our food.

Changes in non-pathogenic microbial life might also have major implications for the biosphere. The importance of these complex communities of microorganisms -- with estimates of up to 10 billion types of microbes alone -- is hard to overstate: They maintain Earth's habitability.

(In 2011, scientists estimated that Earth's plant and animal species (or "macrobes") numbered almost 10 million, meaning therefore that for every "macrobe" species there are 1,000 kinds of microbes, with the same macrobe/microbe ratio applicable to both terrestrial and marine species.)

Humanity depends on the ecological services performed by bacteria, archaea, fungi and protists, which recycle nutrients, nurture plant growth, purify water, make cheese and wine, and decompose wastes. And, by turning atmospheric carbon dioxide back into carbon to be stored in soils or the ocean depths (and doing likewise with nitrogen, sulfur, iron, manganese and more), microbes are key to Earth's atmosphere and climate.

Globally today, heritable DNA sequence information "is probably dominated by microbes, including viruses," Dr. Thaler says. "The intriguing possibility is that macroscopically visible animals and plants may constitute an ever-shrinking proportion of the biosphere's heritable information. We really don't know."

"We probably ought to know if we are on the losing end of a biological information race, however, and might even want to take practical steps to increase the information content of 'our team.' There is also a purely intellectual interest to learn more about our place in the universe of biological information, perhaps analogous to our place in an expanding physical universe."

This is a hard question but hard does not mean impossible, he adds, "what approaches at least begin to address it?"

DNA technologies are an obvious place to look. How might current technologies be applied and how might future developments help?

Two approaches suggest themselves, says Dr. Thaler.

One is to focus on "modulators and vectors" of microbial evolution such as bacterial sex. Other new approaches that might be harnessed include single molecule or single cell (DNA) sequencing.

DNA barcodes and other sequence-based methods used to identify species of plants and animals and to assess the amount of variation within species "invite comparison to measures of microbial biodiversity," Dr Thaler says.

"The clustering pattern seen in macroscopic life seems in a general way also a property of microscopic forms of life. The details of comparison are of interest. There might be quantitative general principles behind the truism that 'life is lumpy'."

In both the microbial and the macroscopic world of visible plants and animals, a 'species' may be considered a cluster "in sequence space," which can be thought of in terms of stars and galaxies, where individuals are stars and species are galaxies.

Concludes Jesse Ausubel, Director of The Rockefeller University's PHE, a sponsor of the study: "Linnaeus started his Systema Naturae in 1735, almost 300 years ago, and we still do not have a complete list of the species of plants and animals that he started to catalogue. It will not be easy to do something similar with probably 1,000 times as many microbes, and measure the changes!"

Visual images from the laboratories of Gary Borisy (Forsyth Institute) and Jessica Mark Welch (Marine Biological Laboratory) show the difficulty of direct counts. A few tens of micrometers, the width of a human hair, span entire diverse, populous communities of microbes.

Dr. Thaler says this paper does not offer "protocols to solve the problem," but tries "to frame the rate of change of microbial biodiversity as an interesting and possibly important question on which progress is possible. I hope that someone reading this paper is stimulated to think of new approaches better than the ones suggested in it."

Adds Mr. Ausubel: "There is no agency yet monitoring the state of the microbial world, and no World Wildlife Fund, no Nature Conservancy for microbes. Perhaps one day soon we will realize and rectify our neglect and lift our respect for the diversity of microbial life."

Two studies led by Baylor College of Medicine shed new light on the unanswered question of why estrogen receptor-positive (ER+) breast cancer sometimes grows back in the bone and spreads to other tissues despite effective endocrine therapies directed at ER.

Working with animal models that include patient tumor samples, the team discovered that the bone microenvironment surrounding ER+ breast cancer cells reduced ER expression in these cells, leading to resistance to ER-targeting endocrine therapy (findings published in the journal Developmental Cell DOI: 10.1016/j.devcel.2021.03.008). Furthermore, the bone microenvironment triggered reprogramming of the cancer cells that promoted their ability to metastasize or spread to other tissues (findings published in Cell DOI: 10.1016/j.cell.2021.03.011 ).

"Metastasis to other organs is the major cause of cancer-related deaths, and my lab has been interested in this phenomenon for many years," said corresponding author Dr. Xiang H.-F. Zhang, the William T. Butler, M.D., Endowed Chair for Distinguished Faculty and professor of molecular and cellular biology at Baylor. "Breast cancer mostly metastasizes to the bone; however, it has remained a mystery why, in more than two-thirds of cases, metastases will not be limited to the bone, but rather subsequently occur in other organs and eventually cause death."

In these two papers, Zhang and his colleagues applied a series of models and techniques they had previously developed to investigate cancer-bone interactions at a single cell resolution to see what happens to ER+ breast cancer cells when they metastasize to the bone. They wanted to find out what might contribute to their resistance to endocrine treatment and enhance metastasis to other organs.

"Surprisingly, we discovered that when ER+ breast cancer cells locate in the bone, they reduce their expression of ER, which makes them less susceptible to endocrine therapies directed at ER," said co-first author Dr. Igor Bado, a postdoctoral fellow in the Zhang lab. "We determined that osteogenic cells, the cells that make new bone, promoted this change in the cancer cells both by releasing factors and by direct physical interaction with the cells."

Interestingly, the interaction with osteogenic cells also triggered changes in gene expression that gave the cancer cells stem cell-like properties, such as unchecked self-renewal and differentiation into various cell types. Having these properties, the authors explain, makes cancer cells more capable of generating new metastasis.

The team identified a number of metabolic pathways that were altered in cancer cells by the bone microenvironment. "Among these pathways, the EZH2-mediated pathway drives ER+ breast cancer cells toward a stem-like state. Inhibiting EZH2 reversed endocrine resistance," Bado said.

"EZH2 is emerging as a leading candidate for therapeutic intervention," said Zhang, a McNair Scholar and member of Baylor's Dan L Duncan Comprehensive Cancer Center.

These findings readily connected with the work Dr. Weijie Zhang was conducting in the Zhang lab. "We were studying whether bone metastases, as compared to a primary tumor, were more likely to further disseminate to other organs," said Weijie Zhang, co-first author of the work and a postdoctoral fellow in the Xiang Zhang lab. "We found that the bone microenvironment is like a 'powering station' for cancer cells, enhancing their ability to further disseminate to other organs. Our findings support the idea that many metastases may be initiated, not by primary tumors, but by further spread of other metastases."

The researchers also showed that the bone microenvironment can empower other types of cancer, such as prostate cancer.

"This is something that other people have not observed before," Weijie Zhang said. "We were able to discover this thanks to our unique model in which we can confine cancer cells to the bone to start with, which allows us to follow subsequent dissemination."

"Taken together, these studies revealed an unappreciated role of the bone microenvironment in metastasis progress and elucidated a reprogramming process driving terminal-stage, multi-organ metastases that provides new insight into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies," Xiang Zhang said.

April 19, 2021--(BRONX, NY)--Researchers at Albert Einstein College of Medicine have developed a topical drug that regenerates and restores the function of erectile nerves damaged by radical prostatectomy, the most common treatment for localized prostate cancer. The drug was tested in rats, and the findings were published online today in JCI Insight.

"Erectile dysfunction (ED) after radical prostatectomy has a major impact on the lives of many patients and their partners," said study co-leader David J. Sharp, Ph.D., professor of physiology & biophysics and of ophthalmology and visual sciences and professor in the Dominick P. Purpura Department of Neuroscience at Einstein. "Since rats are reliable animal models in urologic research, our drug offers real hope of normal sexual function for the tens of thousands of men who undergo this surgery each year."

Radical prostatectomy--surgery to remove the prostate gland--is considered the definitive treatment for localized prostate cancer. "Despite the advent of so-called nerve-sparing procedures, the surgery can damage the cavernous nerves, which control erectile function by regulating blood flow to the penis," said study co-leader Kelvin P. Davies, Ph.D., professor of urology and of physiology & biophysics at Einstein. He notes that about 60% of patients report having ED 18 months after surgery, and fewer than 30% have erections firm enough for intercourse after five years. Viagra and similar ED treatments are rarely effective in these patients, he said.

A decade ago, Dr. Sharp and colleagues discovered that the enzyme fidgetin-like 2 (FL2) puts the brakes on skin cells as they migrate towards wounds to heal them. To speed wound healing, the researchers developed an "anti-FL2" drug: small interfering RNA molecules (siRNAs) that inhibit the gene that codes for FL2. Packaged in gel nanoparticles and sprayed on mice, the siRNAs not only healed wounds twice as fast as untreated wounds but also regenerated damaged tissue. A February 2021 study in rats found that the siRNAs also aided the healing of corneal alkaline burns.

Dr. Sharp, Dr. Davies, and their teams realized that injured nerves might be especially amenable to this gene-silencing drug: For unknown reasons, the FL2 gene becomes over-active after injury to nerve cells, causing the cells to produce copious amounts of FL2 enzyme.

The Einstein team evaluated the drug using rat models of peripheral nerve injury in which the cavernous nerves were either crushed or severed, mimicking the nerve damage associated with radical prostatectomy. The siRNA gel was applied to the nerves immediately after injury.

When treatment was applied following a nerve crush injury, siRNA treatment enhanced nerve regeneration (regrowth) and restored nerve function as shown by cavernosometry, a test in which blood pressure within the penile shaft is measured after cavernous nerves are electrically stimulated. At three and four weeks post-therapy, the treated animals had significantly better erectile function compared to controls. After a month, the blood pressure response of the treated animals was comparable to that of normal animals.

Remarkably, even after nerves were severed, the drug treatment induced nerve regeneration and partial recovery of erectile function. Regenerated nerves were observed in 7 out of 8 treated animals, but not in any of the control animals (severed nerves treated with nonfunctioning siRNAs). The siRNA drug was able to heal gaps of several millimeters between the severed nerve ends--a result previously achieved only by nerve grafting, according to Dr. Sharp. "Functionally, the result from siRNA treatment was equivalent to or better than nerve grafting," he added.

The researchers also found that penile shafts of treated animals had higher levels of the enzyme nitric oxide synthase compared to controls. The enzyme produces the nitric oxide needed to trigger the sequence of events leading to erections. "This is important because drugs like Viagra don't work if there's no nitric oxide to kick things off," said Dr. Sharp. "But if we can restore even some of the nitric oxide in these nerves, Viagra and other ED drugs may then be able to exert their effects."

Dr. Sharp's team is currently studying whether the siRNAs can promote nerve regeneration after spinal cord injuries.

Having an epidural during childbirth is not associated with a greater risk of autism in the child, according to a study led by researchers at the Stanford University School of Medicine and the University of Manitoba.

The study, which will publish online April 19 in JAMA Pediatrics, helps resolve questions raised by an earlier, widely criticized report on the topic.

"We did not find evidence for any genuine link between having an epidural and putting your baby at increased risk of autism spectrum disorder," said the study's senior author, Alexander Butwick, MD, associate professor of anesthesiology, perioperative and pain medicine at Stanford. The study should help reassure both physicians and pregnant women about the favorable safety profile of epidurals, he added.

Epidurals are the most common form of pain relief for childbirth, used by about three-quarters of women in labor in the United States. Autism is a developmental disorder that affects one in every 54 children nationwide.

"The epidural is the gold standard in labor pain management," said the study's lead author, Elizabeth Wall-Wieler, PhD, assistant professor at the University of Manitoba. "The vast majority of evidence around epidurals, including that from our new study, shows that they are the most effective means of providing pain relief to women during labor and that serious complications are rare."

Questions raised by prior study

During an epidural, anesthetic is given by catheter into the space around the woman's spinal cord. Epidurals relieve pain from labor contractions while allowing women to stay alert and push during birth. They also have other important, yet underappreciated, advantages. For example, epidurals can provide anesthesia to laboring women who require unplanned, and often urgent, cesarean sections. They also pose a lower risk to the mother and baby than general anesthesia, which may be necessary if a woman who has not already had an epidural needs an emergency C-section.

In October 2020, a study of California births said epidural use was associated with a 37% greater risk of later autism diagnosis for children. But the study was widely criticized for failing to account for many socioeconomic, genetic and medical risk factors for autism -- separate from the epidural -- that could be more common among women who choose epidurals. Experts also noted that it was biologically implausible for epidurals to raise autism risk. Shortly after that study's release, several professional societies issued a statement saying that the study did not provide credible scientific evidence that epidurals cause autism.

Controlling for social, medical and family factors

The new research examined epidural use during childbirth and later diagnoses of autism in Manitoba, Canada. It included 123,175 children who were born between 2005 and 2016 and were followed until 2019.

"Manitoba has these wonderful, linked data sets that are population-wide," Butwick said, noting that the research team was able to access information that linked together individuals' medical records, prescriptions, other health-related data, socioeconomic information, and information about children's academic achievements. "It's extraordinary information that is super rich," he said.

All of the children in the study were born via vaginal delivery and were single births -- not twins or other multiples. Of those studied, 38.2% of the children were exposed to epidural anesthesia during labor; the rest were not. Of children exposed to epidurals during labor, 2.1% were later diagnosed with autism spectrum disorder, compared with 1.7% of children not exposed to epidurals.

But then the researchers controlled for factors thought to potentially influence autism risk -- many more such factors than in the prior study. Those included socioeconomic factors (mothers' education, marital status, neighborhood socioeconomic level and receipt of welfare during pregnancy); mothers' pre-pregnancy medical history (including diabetes, hypertension, anxiety and depression); medical conditions during pregnancy; mothers' smoking, alcohol and recreational drug use; mothers' hospitalization for mental illness during pregnancy; mothers' use of several types of prescription medications (benzodiazepines, antidepressants and antiepileptics); medical complications of delivery; and factors related to the mothers' pregnancy and labor, including the length of the pregnancy, whether labor was induced or augmented and whether the fetus was large or in distress during labor.

The researchers also analyzed pairs of siblings in which the mother received an epidural during one child's birth but not the other. This comparison gave a way to account for genetic and familial factors, which influence autism risk.

Once the researchers had adjusted for all the confounding factors, there was no statistically significant difference in autism risk between children whose mothers received epidurals during their birth and those who did not. Accounting for genetic and family-related factors reduced the difference between the groups even more.

The team conducted many different analyses, said Wall-Wieler, and repeatedly found a lack of association between epidurals and autism. "That makes us really confident in how robust our results were," she said.

"Our study has a stronger finding because we accounted for limitations the first study had," Butwick said. "An epidural remains a well-established and effective means of providing pain relief during labor, with several benefits associated with it."

What The Study Did: The association between hearing loss and level of physical activity among U.S. adults ages 60 to 69 was analyzed in this study.

Authors: Frank R. Lin, M.D., Ph.D., of the Johns Hopkins University School of Medicine in Baltimore, 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.2021.5484)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Animals are constantly moving and behaving in response to instructions from the brain. But while there are advanced techniques for measuring these instructions in terms of neural activity, there is a paucity of techniques for quantifying the behavior itself in freely moving animals. This inability to measure the key output of the brain limits our understanding of the nervous system and how it changes in disease.

A new study by researchers at Duke University and Harvard University introduces an automated tool that can readily capture behavior of freely behaving animals and precisely reconstruct their three dimensional (3D) pose from a single video camera and without markers.

The April 19 study in Nature Methods led by Timothy W. Dunn, Assistant Professor, Duke University, and Jesse D. Marshall, postdoctoral researcher, Harvard University, describes a new 3D deep-neural network, DANNCE (3-Dimensional Aligned Neural Network for Computational Ethology). The study follows the team's 2020 study in Neuron which revealed the groundbreaking behavioral monitoring system, CAPTURE (Continuous Appendicular and Postural Tracking using Retroreflector Embedding), which uses motion capture and deep learning to continuously track the 3D movements of freely behaving animals. CAPTURE yielded an unprecedented detailed description of how animals behave. However, it required using specialized hardware and attaching markers to animals, making it a challenge to use.

"With DANNCE we relieve this requirement," said Dunn. "DANNCE can learn to track body parts even when they can't be seen, and this increases the types of environments in which the technique can be used. We need this invariance and flexibility to measure movements in naturalistic environments more likely to elicit the full and complex behavioral repertoire of these animals."

DANNCE works across a broad range of species and is reproducible across laboratories and environments, ensuring it will have a broad impact on animal - and even human - behavioral studies. It has a specialized neural network tailored to 3D pose tracking from video. A key aspect is that its 3D feature space is in physical units (meters) rather than camera pixels. This allows the tool to more readily generalize across different camera arrangements and laboratories. In contrast, previous approaches to 3D pose tracking used neural networks tailored to pose detection in two-dimensions (2D), which struggled to readily adapt to new 3D viewpoints.

"We compared DANNCE to other networks designed to do similar tasks and found DANNCE outperformed them," said Marshall.

To predict landmarks on an animal's body DANNCE required a large training dataset, which at the outset seemed daunting to collect. "Deep neural networks can be incredibly powerful, but they are very data hungry," said senior author Bence Ölveczky, Professor in the Department of Organismic and Evolutionary Biology, Harvard University. "We realized that CAPTURE generates exactly the kind of rich and high-quality training data these little artificial brains need to do their magic."

The researchers used CAPTURE to collect seven million examples of images and labeled 3D keypoints in rats from 30 different camera views. "It worked immediately on new rats, even those not wearing the markers," Marshall said. "We really got excited though when we found that it could also track mice with just a few extra examples."

Following the discovery, the team collaborated with multiple groups at Duke University, MIT, Rockefeller University and Columbia University to demonstrate the generality of DANNCE in various environments and species including marmosets, chickadees, and rat pups as they grow and develop.

"What's remarkable is that this little network now has its own secrets and can infer the precise movements of animals it wasn't trained on, even when large parts of their body is hidden from view," said Ölveczky.

The study highlights some of the applications of DANNCE that allow researchers to examine the microstructure of animal behavior well beyond what is currently possible with human observation. The researchers show that DANNCE can extract individual 'fingerprints' describing the kinematics of different behaviors that mice make. These fingerprints should allow researchers to achieve standardized definitions of behaviors that can be used to improve reproducibility across laboratories. They also demonstrate the ability to carefully trace the emergence of behavior over time, opening new avenues in the study of neurodevelopment.

Measuring movement in animal models of disease is critically important for both basic and clinical research programs and DANNCE can be readily applied to both domains, accelerating progress across the board. Partial funding for CAPTURE and DANNCE was provided by the NIH and the Simons Foundation Autism Research Initiative (SFARI) and the researchers note the value of these tools hold for autism-related and motor-related studies, both in animal models and in humans.

"Because we've had very poor ability to quantify motion and movement rigorously in humans this has prevented us from separating movement disorders into specialized subtypes that potentially could have different underlying mechanisms and remedies. I think any field in which people have noticed but have been unable to quantify effects across their population will see great benefits from applying this technology" said Dunn.

The researchers open sourced the tool and it is already being put to use in other labs. Going forward, they plan to apply the system to multiple animals interacting. "DANNCE changes the game for studying behavior in free moving animals," said Marshall. "For the first time we can track actual kinematics in 3D and learn in unprecedented detail what animals do. These approaches are going to be more and more essential in our quest to understand how the brain operates."

New research is shining light on the importance of farmers' markets' ability to mitigate potential disruptions to distribution networks in the face of system shocks like the COVID-19 pandemic.

In a recent study, the researchers found the markets' regional characteristics play a key role in the decision to move all or parts of their operations online -- and how that decision can help or hinder its surrounding community.

"By building online communities through their social media and website tools, farmers' markets can play a role in keeping the community connected and supporting a sustainable and just food system through the pandemic and beyond," said researcher Josalyn Radcliffe, a PhD student in Waterloo's School of Public Health and Health Systems.

"The decision to transition online must always be anchored in the unique context of the organization."

That is why many southern farmers' markets across Canada were able to go online during the pandemic, but many in the North opted to stay in-person. The Yellowknife Farmers Market was one such case, choosing to pursue an adapted outdoor market, albeit with a "Shop, Don't Stop" message that fits with the emphasis on community expressed by patrons and the event-like atmosphere valued by many.

"While areas south of Yellowknife have more capacity to grow food, challenges regarding equitable access to electricity and internet and the potential for disruption in food access are common issues to markets in the Northwest Territories," said Kelly Skinner, a professor in the School of Public Health and Health Systems.

"Still, online spaces may be a valuable tool to mitigate potential disruptions to distribution networks due to the impacts of climate change and help facilitate the growth of the local food sector in the North."

Skinner collaborated with other researchers at Waterloo, Wilfrid Laurier University and the Yellowknife Farmers Market on a study of the market, which typically runs from June to September and attracts hundreds of people per week.

They conducted surveys during the 2019 market season, offering both a short flipchart dot survey, completed by 59 patrons and a longer questionnaire, completed by 31 patrons. A vendor survey was postponed due to COVID-19.

The results of the two patron surveys showed that this farmers' market was distinct: 58 per cent of Yellowknife consumers came to eat dinner, enjoy the atmosphere and support local businesses. At other markets across Canada, only two per cent attend primarily for the dining options, prioritizing instead the purchase of fresh and local foods. Most patrons at the Yellowknife market attended as couples and spent more than half their time talking to others.

The study also noted that online farmers' markets can be great opportunities to complement in-person relationships, share knowledge and maintain connections.