Culture

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.

A COVID-19 vaccine that could provide protection against existing and future strains of the COVID-19 coronavirus, and other coronaviruses, and cost about $1 a dose has shown promising results in early animal testing.

Vaccines created by UVA Health's Steven L. Zeichner, MD, PhD, and Virginia Tech's Xiang-Jin Meng, MD, PhD, prevented pigs from being becoming ill with a pig model coronavirus, porcine epidemic diarrhea virus (PEDV). The vaccine was developed using an innovative approach that Zeichner says might one day open the door to a universal vaccine for coronaviruses, including coronaviruses that previously threatened pandemics or perhaps even coronaviruses that cause some cases of the common cold.

Their coronavirus vaccine offers several advantages that could overcome major obstacles to global vaccination efforts. It would be easy to store and transport, even in remote areas of the world, and could be produced in mass quantities using existing vaccine-manufacturing factories.

The UVA and Virginia Tech scientists created the vaccine using a new platform Zeichner invented to rapidly develop new vaccines. So the testing success bodes well for both the COVID-19 vaccine and Zeichner's vaccine-development approach.

"Our new platform offers a new route to rapidly produce vaccines at very low cost that can be manufactured in existing facilities around the world, which should be particularly helpful for pandemic response," Zeichner said.

New Vaccine Approach

Zeichner's new vaccine-production platform involves synthesizing DNA that directs the production of a piece of the virus that can instruct the immune system how to mount a protective immune response against the virus.

That DNA is inserted into another small circle of DNA called a plasmid that can reproduce within bacteria. The plasmid is then introduced into bacteria, instructing the bacteria to place pieces of proteins on their surfaces. The technique uses the common bacteria E. coli.

One major innovation is that the E. coli have had a large number of its genes deleted. Removing many of the bacteria's genes, including genes that make up part of its exterior surface or outer membrane, appears to substantially increase the ability of the immune system to recognize and respond to the vaccine antigen placed on the surface of the bacteria.

To produce the vaccine, the bacteria expressing the vaccine antigen are simply grown in a fermenter, much like the fermenters used in common microbial industrial processes like brewing, and then killed with a low concentration of formalin.

"Killed whole-cell vaccines are currently in widespread use to protect against deadly diseases like cholera and pertussis. Factories in many low-to-middle-income countries around the world are making hundreds of millions of doses of those vaccines per year now, for a $1 per dose or less," Zeichner said. "It may be possible to adapt those factories to make this new vaccine. Since the technology is very similar, the cost should be similar too."

The entire process, from identifying a potential vaccine target to producing the gene-deleted bacteria that have the vaccine antigens on their surfaces, can take place very quickly, in only two to three weeks, making the platform ideal for responding to a pandemic.

Targeting Coronavirus

Zeichner and Meng's vaccine takes an unusual approach in that it targets a part of the spike protein of the virus, the "viral fusion peptide," that is essentially universal among coronaviruses. The fusion peptide has not been observed to differ at all in the many genetic sequences of SARS-CoV-2, the virus that causes COVID-19, that have been obtained from thousands of patients around the world during the pandemic.

Meng and Zeichner made two vaccines, one designed to protect against COVID-19, and another designed to protect against PEDV. PEDV and the virus that causes COVID-19 are both coronaviruses, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share several of the amino acids that constitute the fusion peptide. PEDV infects pigs, causing diarrhea, vomiting and high fever, and has been a large burden on pig farmers around the world. When PEDV first appeared in pig herds in the US, it killed almost 10% of US pigs - a pig pandemic.

One advantage of studying PEDV in pigs is that Meng and Zeichner could study the ability of the vaccines to offer protection against a coronavirus infection in its native host - in this case, pigs. The other models that have been used to test COVID-19 vaccines study SARS-CoV-2 in non-native hosts, such as monkeys or hamsters, or in mice that have been genetically engineered to enable them to be infected with SARS-CoV-2. Pigs are also very similar in physiology and immunology to people - they may be the closest animal models to people other than primates.

In some unexpected results, Meng and Zeichner observed that both the vaccine against PEDV and the vaccine against SARS-CoV-2 protected the pigs against illness caused by PEDV. The vaccines did not prevent infection, but they protected the pigs from developing severe symptoms, much like the observations made when primates were tested with candidate COVID-19 vaccines. The vaccines also primed the immune system of the pigs to mount a much more vigorous immune response to the infection. If both the PEDV and the COVID-19 vaccines protected the pigs against disease caused by PEDV and primed the immune system to fight the disease, it is reasonable to think that the COVID-19 vaccine would also protect people against severe COVID-19 disease, the scientists say.

Next Steps

Additional testing - including human trials - would be required before the COVID-19 vaccine could be approved by the federal Food and Drug Administration or other regulatory agencies around the world for use in people, but the collaborators are pleased by the early successes of the vaccine-development platform.

Zeichner added that he was encouraged that a collaboration between UVA and Virginia Tech, schools with a well-known sports rivalry, has produced such promising results.

"XJ is just an amazing collaborator and a wonderful scientist. And he is incredibly generous with his time and the resources he has available," Zeichner said. "If UVA and Virginia Tech scientists can work together to try to do something positive to address the pandemic, then maybe there is some hope for collaboration and cooperation in the country at large."

A new study from the UBC Sauder School of Business finds a subtle shift in organ donor messaging can lead to a big boost in registration.

Organ donation saves countless lives every year, and most people think it's the right thing to do -- but when it comes to people actually registering to donate, the numbers around the world are surprisingly low. This is particularly so in countries that rely on informed consent and require people to learn about organ donation before they opt-in to register as a donor.

In fact, in Canada, just 32 per cent of people have registered to become organ donors.

Transplant agencies have tried a range of strategies to increase donation levels, including the introduction of in-hospital organ donation coordinators, greater public education and marketing campaigns.

Some campaigns emphasize how low organ donation rates are and plead with people to sign up, hoping the meagre numbers will motivate people to help. In marketing, this is known as a low descriptive norm. Others take the opposite tack, and emphasize how positive people feel about organ donation, which encourages people to conform to the expectations of others, a high injunctive norm. For example, one UK government advertisement stated, "96 per cent believe donating organs is the right thing to do."

But what happens when you combine the two approaches? According to the new study, titled Everybody Thinks We Should But Nobody Does: How Combined Injunctive and Descriptive Norms Motivate Organ Donation Registration, highlighting the incongruence between what people believe and what they do -- or don't do -- can spur their willingness to register.

According to UBC Sauder PhD candidate Rishad Habib (she/her), who co-authored the study with UBC Sauder colleagues Dr. Katherine White and Dr. JoAndrea Hoegg, by focusing on how low registration numbers are, some agencies may be unknowingly alienating potential donors.

"If you tell people that nobody is doing something, does that really motivate them to register?" says Habib. "By communicating that the numbers are low, they might be inadvertently communicating that it's not very important, or not worthwhile."

On the flipside, if marketers focus on how many people support organ donation, they risk making people feel like they don't need to act.

For the study, the researchers tested all three approaches -- focusing on the low rates, the high support, and a combination of the two -- in online surveys, lab surveys and in a public field study.

In one study, research assistants set up a table at the UBC student centre and regularly rotated banners encouraging passersby to register. They also asked people if they were already registered, and if they weren't, they would show them an iPad displaying the different messaging on the banners.

For example, one read, "Only 20 per cent of Canadians are registered as organ donors" while another said, "90 per cent of Canadians believe people should register as organ donors." The people were then offered the chance to sign up.

Roughly 20 per cent of people who were given only the individual messages signed up; but when people were given the combined message, registrations jumped to 33 per cent, which represents an almost 70 per cent increase -- a leap that could help save lives.

"It motivates responsibility," explains Habib. "When the two messages are combined, people think, 'No one's doing it, but it's important. So I need to step up and register."

Habib hopes the findings, which were published in the Journal of Consumer Psychology, will help transplant organizations create more effective communication strategies; in fact, the study has already influenced at least one organ donation registry's online and TV campaigns.

"You could apply this to other situations where there's a positive behaviour, but there aren't a lot of people doing it -- like mask wearing at the start of the pandemic," she says. "If the behaviour levels are low, but the support for the behaviour is high, then it makes sense to communicate both."

A forest looks like a hotbed of randomness, with trees and plants scattered in wild and capricious diversity. But appearances can be deceiving, say a trio of complexity researchers at the Santa Fe Institute (SFI). Underneath that apparent messiness lurk extraordinary regularities, governed by the biological mechanisms that drive universal forces of growth, death, and competition.

In a paper published April 9 in the journal PNAS, the SFI group, led by Program Postdoctoral Fellow and now Complexity Science Hub Vienna Postdoctoral Scientist Eddie Lee, describes a new framework that can reproduce those spatial and temporal patterns that emerge in places and spaces where plants grow together. The framework uses computational and statistical tools to connect metabolic principles, which control how an individual organism lives and thrives, to the diverse arrangements of trees, shrubs, and other vegetation readily observed in landscapes, forests and beyond.

"This paper goes a long way in showing how things that look arbitrary and capricious can in fact be understood within a mathematical framework," says SFI Distinguished Shannan Professor and former President Geoffrey West, who collaborated with Lee and Chris Kempes, SFI Professor, on the model.

Scientists have long sought mathematical laws that connect the similar patterns that emerge at large and small scales of existence. "If you look at the microscopic structure of multicellular life, you see a lot of the same patterns playing out," says Lee. The metabolic rate of an organism follows a power scaling law with its mass, for example. Previous attempts at establishing such mathematical laws for the assemblage of plants in a forest have been a source of vociferous debate.

In previous work, West and others have developed models that start with the metabolic constraints on a single, optimized tree to make predictions about patterns that might emerge in a community of such trees. The model accurately showed how features like growth rate or canopy size might change with plant size -- and how those features might affect competition with other organisms or change the structure of the entire forest.

Kempes says that this idealized model paved the way for connecting biological principles like metabolism to mathematical, macro-level patterns, but over time researchers began to focus on how real-world situations differ in detail from that model. Not every tree or population follows the optimal rules, though, leading researchers like Lee to investigate new ways to generalize the core tenets.

"What happens when that law for scaling deviates for individual species, or for different contexts? How does that work?" says Kempes. "How do all those fit together?"

The new model extends essential ideas from earlier works for how to set up a model informed by the biological principles of growth, death, and resource competition, but it also allows a user to generalize those ideas to a wide range of species and situations, says Kempes. A user might relax certain assumptions about tree allometries -- relationships between size and shape -- or incorporate ideas about how trees interact with other organisms, like termites.

By turning these "knobs" on the simulation, Lee says, researchers can more closely reproduce the diverse ways that forests diverge from the idealized model. They can also clearly connect biological principles at the level of the organism to how forest structure plays out on larger scales.

West says the new approach will not only reveal scaling laws that have been previously gone unnoticed but also shine a light on new areas of investigation. "One of the great things about having an analytical model of this kind is that it points to where data is missing, or where data is poor," he says, "and the kinds of things people should be measuring."

The model also shows how a physics-inspired approach -- which often focuses on idealized situations -- can contribute to advances in understanding biological complexity. "There is this marvelous interplay between the fields," West says.

Osaka, Japan - As humans, we each have a powerful ability to easily recognize our own face. But now, researchers from Japan have uncovered new information about how our cognitive systems enable us to distinguish our own face from those of others, even when the information is presented subliminally.

In a study published this month in Cerebral Cortex, researchers from Osaka University have revealed that a central element of the dopamine reward pathway in the brain was activated when participants were subliminally shown images of their face. This provides new clues regarding the underlying processes of the brain involved in self-facial recognition.

When we are exposed to a subliminal image of our face—meaning we are not fully aware of it—many brain regions are activated in addition to those that process face information. Furthermore, our brain responds differently to supraliminal (conscious) and subliminal (subconscious) images of our face compared to faces of others. However, whether we use the same or different neural networks to process subliminal versus supraliminal faces has not been established, something the researchers at Osaka University aimed to address with this research.

"We are better at recognizing our own face compared to faces of others, even when the information is delivered subliminally," says lead author of the study Chisa Ota. "However, little is known about whether this advantage involves the same brain or different areas that are activated by supraliminal presentation of our face."

To address this, the researchers used functional magnetic resonance imaging (fMRI) to examine the differences between brain activity elicited by subliminally presented images of the faces of participants and faces of others. They also examined brain activation produced by subliminally presented images of faces with modified features.

"The results provided us with new insights regarding the neural mechanisms of the self-face advantage," explains Tamami Nakano, senior author. "We found that activation in the ventral tegmental area, which is a central component of the dopamine reward pathway, was stronger for subliminal presentations of the participant's face compared with faces of others."

Instead, subliminal presentation of the faces of others induced activation in the amygdala of the brain, which is known to respond to unfamiliar information. This difference in brain responses to the face of the participant or those of others was consistent even when the faces were modified, as long as the shapes of the facial features were retained.

"Our findings indicate that the dopamine reward pathway is involved in enhanced processing of one's own face even when the information is subliminal", says Tamami Nakano. "Furthermore, discrimination of one's own face from those of others appear to rely on the information of facial parts."

These findings advance the understanding of the neural mechanisms of subliminal self-facial processing. Given that the dopamine reward pathway is automatically involved in unconscious self-facial processing, this research may have applications in efforts to unconsciously manipulate motivation.

With its more than 40 million articles in 301 different languages, Wikipedia is one of the largest human collaboration efforts in history. One of the main pillars on which this wish to bring together the sum of all knowledge is based is the achievement of a neutral space. However, several studies suggest that the site suffers from a persistent gender bias as regards both content and the composition of its community. An analysis of the gender gap in the Spanish-language version of Wikipedia by an interdisciplinary team at the UOC has revealed that only 11.6% of its registered editors are women.

According to the new study, which has been published in the journal PLOS ONE, the difference could be partially due to female editors being less persistent. "Women edit less and give up sooner. This is part of the reason the gap is not narrowing," note the authors. In spite of this, the results reveal a small group of veteran female editors, some of whom have edited more than men, a fact that could help design measures to highlight and increase women's participation in this space.

The paper is signed by UOC researchers Julià Minguillón of the Learning Analytics for Innovation and Knowledge Application in Higher Education group (LAIKA), of the Faculty of Computer Science, Multimedia and Telecommunications, Julio Meneses and Sergi Fàbregues of the Gender and IT group (GenTIC), of the Internet Interdisciplinary Institute (IN3) and of the Faculty of Psychology and Education Sciences, and by Professor Eduard Aibar of the Philosophy for Contemporary Challenges group (MUSSOL) of the Faculty of Arts and Humanities. Núria Ferran, a researcher at the Faculty of Audiovisual Media of the University of Barcelona, also took part.

A new method for identifying gender

With over 1.58 million pages, the Spanish version of Wikipedia is the ninth largest, as well as the fourth largest by number of registered editors (around 17,000). One of the challenges facing the new study has been identifying these people's gender, as many of them have chosen not to reveal it in their Wikipedia personal profiles. To ascertain this, in addition to collecting the information published by the users themselves, the researchers also created a systematic method to establish their gender based on their names and the use of grammatical gender in the descriptions appearing in their profiles. This procedure made it possible to identify the gender of 49% of editors, as compared with only 38.8% who had specified it on their personal page.

According to the results of this innovative process, the number of active female editors in the Spanish-language version of Wikipedia accounts for 7.4% of all existing profiles, a figure that rises to 11.6% if you take into account only those profiles whose genders we know for certain. "These differences mean that the Spanish-language Wikipedia site is a male-dominated territory that may plausibly be considered a misogynistic place by female editors. Additionally, the high percentage of unknown profiles hinders efforts to reduce this perception, as women perceive anonymous editors as more critical of their contributions," the researchers highlight.

Lower retention rates among female editors

In general, the study also found differences in editing practices, as women have lower retention rates. According to the authors, this can be explained "partly by female editors being less persistent and tending to leave Wikipedia much more quickly, particularly in the first few weeks." However, an analysis of the most active people on the site revealed the disappearance or even reversal of gender differences between men and women in some cases: "There is a small group of veteran female editors who have edited more than male editors in terms of editing practices and involvement in different parts of Wikipedia," they highlight.

The types of contributions made are another differentiating factor between men and women. According to the study, female editors edit a higher percentage of non-article pages; in other words, in places whose specific purpose is to interact with other participants, particularly discussion pages, where articles' flaws and possible improvements are discussed. These findings seem to corroborate those of previous studies suggesting that men tend to be contributors while women tend to behave more as collaborators. However, the researchers highlight that "when taking into account only the most active editors, although women have a higher average number of edits in all namespaces, the differences between women and the most active men are not statistically significant."

Greater interest in gender-related matters

The researchers also found differences between the two groups' interests based on an analysis of the categories used by Wikipedia to group articles by subject area. Although the authors describe these categories as "too general," the study suggests that women are "slightly less" interested in editing science and nature pages.

As for content pages, men always outperform women by three to one. In fact, women often do not contribute at all or contribute significantly less, although with one exception: gender gap-related pages and WikiProjects. "We found only two groups of pages in which women seem more active than men: the 'Women' and 'Feminism' WikiProjects and another group of pages relating to gender issues. It therefore appears that women are more interested in making contributions in this field," they stress.

Highlighting the work of the most active female editors

In view of this bias, the researchers suggest a variety of measures to encourage participation by women. Firstly, they propose changes to the way the website works, such as facilitating editing -- particularly regarding the management of references -- to "avoid incomplete or erroneous edits that are almost certain to be subsequently deleted." They also recommend improving the identification of "abusive behaviours," particularly by veteran editors who may be "less than fully impartial in relation to gender issues, a problem that is not exclusive to women and may also affect other minority groups," they note.

They additionally emphasize the importance of supporting female editors for longer after taking part in Wikipedia welcome activities such as WikiProjects or Wikimarathons, where they get together in one place to edit and improve a subject matter or group of articles. Highlighting the involvement of the group of most active female editors is another recommendation made by the researchers, who assert that "raising awareness of women's successful experiences could provide a good starting point to encourage other women to continue editing and thus promote their long-term commitment to Wikipedia." Finally, the conclusions of the paper also stress the need to research why women stop editing Wikipedia and take a closer look at the role of Wikimarathons to encourage more women to take up and maintain the editing habit over time.

Singapore, 19 April, 2021 - Researchers at the Future Urban Mobility (FM) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have created a synthetic framework known as theory-based residual neural network (TB-ResNet), which combines discrete choice models (DCMs) and deep neural networks (DNNs), also known as deep learning, to improve individual decision-making analysis used in travel behaviour research.

In this research paper, Theory-based residual neural networks: A synergy of discrete choice models and deep neural networks, recently published in established transportation science journal Transportation Research: Part B, SMART researchers explain their developed TB-ResNet framework and demonstrate the strength of combining the DCMs and DNNs methods, proving that they are highly complementary.

As machine learning is increasingly used in the field of transportation, the two disparate research concepts, DCMs and DNNs, have long been viewed as conflicting methods of research.

By synergising these two important research paradigms, TB-ResNet takes advantage of DCMs' simplicity and DNNs' expressive power to generate richer findings and more accurate predictions for individual decision-making analysis, which is important for improved travel behaviour research. The developed TB-ResNet framework is more predictive, interpretable, and robust as compared to DCMs and DNNs, with findings consistent over a wide range of data sets.

Accurate and efficient analysis of individual decision-making in the everyday context is critical for mobility companies, governments and policy makers seeking to optimise transport networks and tackle transport challenges, especially in urban cities. TB-ResNet will eliminate existing difficulties faced in DCMs and DNNs, and allow stakeholders to take a holistic, unified view towards transport planning.

Postdoctoral Associate at MIT Urban Mobility Lab and lead author of the paper, Shenhao Wang, said, "Improved insights to how travellers make decisions about travel mode, destination, departure time, and planning of activities are crucial to urban transport planning for governments and transport companies worldwide. I look forward to further developing TB-ResNet and its applications for transport planning now that it has been acknowledged by the transport research community."

SMART FM Lead Principal Investigator and Associate Professor at MIT Department of Urban Studies and Planning, Jinhua Zhao, said, "Our Future Urban Mobility research team focuses on developing new paradigms and innovating future urban mobility systems in and beyond Singapore. This new TB-ResNet framework is an important milestone that could enrich our investigations for impacts of decision-making models for urban development."

The TB-ResNet can also be widely applied to understand individual decision-making cases as illustrated in this research, whether it is about travels, consumption, voting, among many others.

The TB-ResNet framework was tested in three instances in this study. Firstly, researchers used it to predict travel mode decisions between transit, driving, autonomous vehicles, walking, and cycling, which are major travel modes in an urban setting. Secondly, they evaluated risk alternatives and preferences when monetary payoffs with uncertainty are involved. Examples of such situations include insurance, financial investment, and voting decisions.

Lastly, they examined temporal alternatives, measuring the trade-off between current and future money payoffs. A typical example of when such decisions are made would be in transport development where shareholders analyse infrastructure investment with large down payment and long-term benefits.

A team of researchers from the Hebrew University of Jerusalem has proven the linkages between ultra-processed foods and reduced bone quality, unveiling the damage of these foods particularly for younger children in their developing years. The study, led by Professor Efrat Monsonego-Ornan and Dr. Janna Zaretsky from the Department of Biochemistry, Food Science and Nutrition at the University's Faculty of Agriculture, was published in the journal Bone Research and serves as the first comprehensive study of the effect of widely-available food products on skeleton development.

Ultra-processed foods--aka, junk food--are food items products that undergo several stages of processing and contain non-dietary ingredients. They're popular with consumers because they are easily accessible, relatively inexpensive and ready to eat straight out of the package. The increasing prevalence of these products around the world has directly contributed to increased obesity and other mental and metabolic impacts on consumers of all ages.

Children tend to like junk food. As much as 70% percent of their caloric consumption are estimated to come from ultra-processed foods. While numerous studies have reflected on the overall negative impact of junk food, few have focused on its direct developmental effects on children, particularly young children.

The Hebrew University study provides the first comprehensive analysis for how these foods impact skeletal development. The study surveyed lab rodents whose skeletons were in the post embryonic stages of growth. The rodents that were subjected to ultra-processed foods suffered from growth retardation and their bone strength was adversely affected. Under histological examination, the researchers detected high levels of cartilage buildup in the rodents' growth plates, the "engine" of bone growth. When subjected to additional tests of the rodent cells, the researchers found that the RNA genetic profiles of cartilage cells that had been subjected to junk food were showing characteristics of impaired bone development.

The team then sought to analyze how specific eating habits might impact bone development and replicated this kind of food intake for the rodents. "We divided the rodents' weekly nutritional intake--30% came from a 'controlled' diet, 70% from ultra-processed foods", shared Monsonego-Ornan. They found that the rodents experienced moderate damage to their bone density albeit there were fewer indications of cartilage buildup in their growth plates. "Our conclusion was that even in reduced amounts, the ultra-processed foods can have a definite negative impact on skeletal growth."

These findings are critical because children and adolescents consume these foods on a regular basis to the extent that 50 percent of American kids eat junk food each and every day. Monsonego-Ornan added. "when Carlos Monteiro, one of the world's leading experts on nutrition, said that there is no such thing as a healthy ultra-processed food, he was clearly right. Even if we reduce fats, carbs nitrates and other known harmful substances, these foods still possess their damaging attributes. Every part of the body is prone to this damage and certainly those systems that remain in the critical stages of development."