Anti-depressant repurposed to treat childhood cancer

A new study has found that a commonly prescribed antidepressant may halt growth of a type of cancer known as childhood sarcoma, at least in mice and laboratory cell experiments. The findings, from researchers at Karolinska Institutet in Sweden and MD Anderson Cancer Center in Texas, ignite hope of novel treatment strategies against this disease. The study is published in the journal Cancer Research.

“Although this study was done in mice and we do not yet know how translatable the results are to humans, it gives us hope for repurposing common drugs for young cancer patients desperately requiring better treatment options,” says the study’s first author, Caitrín Crudden, a former Ph.D. student in the receptor signaling pathology group at the Department of Oncology-Pathology at Karolinska Institutet.

The study examined commonalities between two large groups of cell surface receptors, the so-called G protein-coupled receptors (GPCRs) and the receptor tyrosine kinases (RTKs). GPCRs are targeted by more than half of all developed drugs to treat conditions such as allergies, asthma, depression, anxiety and hypertension, but have so far not been widely used to treat cancers.

RTKs, on the other hand, are targeted by drugs against cancers, such as breast and colon cancers, due to their implication in a variety of cellular abnormalities. One receptor in the RTK family that plays a key role in many cancers, including childhood sarcoma, is the insulin-like growth factor receptor (IGF1R). However, previous attempts to develop anti-cancer drugs against this receptor have failed.

In this study, the researchers scrutinized the IGF1R and found that it shares a signaling module with the GPCRs, meaning it may be possible to affect its function through drugs targeting the GPCRs. This strategy opens new possibilities of repurposing well-tolerated drugs to silence this tumor-driving receptor and thereby halt cancer growth.

To test their hypothesis, the researchers treated childhood (Ewing) sarcoma cells and mouse models with Paroxetine, an anti-depressant drug that impairs a serotonin reuptake receptor that is part of the GPCR-family. They found that this drug significantly decreased the number of IGF1R receptors on the malignant cells and thereby suppressed the growth of the tumor. The researchers also uncovered the molecular mechanism behind this cross-targeting.

“We have developed a novel strategy to control the activity of these tumor-driving receptors by striking the GPCRs,” says Leonard Girnita, researcher in the Department of Oncology-Pathology, Karolinska Institutet, and principle investigator of the study. “To our knowledge this represents a new paradigm for the entire class of cancer-relevant RTKs and could be used as a starting point for the rational design of specific therapeutics in virtually any pathological conditions. This is especially important considering the huge number of GPCR-targeting medicines already in clinical use and with low toxicity.”

Next, the researchers plan to develop their strategy to selectively cross-target multiple RTKs and to verify their findings in a clinical setting.

More information: Crudden et al., Inhibition of G protein-coupled receptor kinase 2 promotes unbiased downregulation of IGF-1 receptor and restrains malignant cell growth. Cancer Research (2020). DOI: 10.1158/0008-5472.CAN-20-1662

https://medicalxpress.com/news/2020-11-anti-depressant-repurposed-childhood-cancer.html

An Amazonian Tea Stimulates the Formation of New Neurons

DMT, a natural component of ayahuasca tea, promotes neurogenesis, a new study reports. Researchers found DMT was capable of activating neural stem cells and promoted the formation of new neurons.

One of the main natural components of ayahuasca tea, dimethyltryptamine (DMT), promotes neurogenesis (the formation of new neurons) according to research led by the Complutense University of Madrid (UCM).

In addition to neurons, the infusion used for shamanic purposes also induces the formation of other neural cells such as astrocytes and oligodendrocytes.

“This capacity to modulate brain plasticity suggests that it has great therapeutic potential for a wide range of psychiatric and neurological disorders, including neurodegenerative diseases”, explained José Ángel Morales, a researcher in the UCM and CIBERNED Department of Cellular Biology.

The study, published in Translational Psychiatry, reports the results of four years of in vitro and in vivo experimentation on mice, demonstrating they exhibit “a greater cognitive capacity when treated with this substance”, according to José Antonio López, a researcher in the Faculty of Psychology at the UCM and co-author of the study.

Ayahuasca is produced by mixing two plants from the Amazon: the ayahuasca vine (Banisteriopsis caapi) and the chacruna shrub (Psychotria viridis).

The DMT in ayahuasca tea binds to a type-2A serotonergic brain receptor, which enhances its hallucinogenic effect. In this study, the receptor was changed to a sigma type receptor that does not have this effect, thus “greatly facilitating its future administration to patients”.

In neurodegenerative diseases, it is the death of certain types of neuron that causes the symptoms of pathologies such as Alzheimer’s and Parkinson’s. Although humans have the capacity to generate new neuronal cells, this depends on several factors and is not always possible.

“The challenge is to activate our dormant capacity to form neurons and thus replace the neurons that die as a result of the disease. This study shows that DMT is capable of activating neural stem cells and forming new neurons”, concluded Morales.

N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo” by Jose A. Morales-Garcia, Javier Calleja-Conde, Jose A. Lopez-Moreno, Sandra Alonso-Gil, Marina Sanz-SanCristobal, Jordi Riba & Ana Perez-Castillo. Translational Psychiatry.

Scientists find Madagascar chameleon last seen 100 years ago

Scientists say they have found an elusive chameleon species that was last spotted in Madagascar 100 years ago.

Researchers from Madagascar and Germany said Friday that they discovered several living specimens of Voeltzkow’s chameleon during an expedition to the northwest of the African island nation.

In a report published in the journal Salamandra, the team led by scientists from the Bavarian Natural History Collections ZSM said genetic analysis determined that the species is closely related to Labord’s chameleon.

Researchers believe that both reptiles only live during the rainy season — hatching from eggs, growing rapidly, sparring with rivals, mating and then dying during a few short months.

“These animals are basically the mayflies among vertebrates,” said Frank Glaw, curator for reptiles and amphibians at the ZSM.

Researchers said the female of the species, which had never previously been documented, displayed particularly colorful patterns during pregnancy, when encountering males and when stressed.

The scientists say that the Voeltzkow’s chameleon’s habitat is under threat from deforestation.

___

https://apnews.com/article/madagascar-chameleon–3d70ac4d74fa9d32b86962b9e8b5e2db

Thanks to Pete C for bringing this to the It’s Interesting community.

Unconscious Exposure to a Feared Stimulus Can Reduce Fear, Study Shows

For many years, exposure therapy has been a first-line behavioral treatment for people diagnosed with anxiety disorders such as social phobia and PTSD that involve a paralyzing or disabling fear. War veterans, for example, whose trauma may be linked in memory with the sound of an explosion can sometimes be helped by being exposed under controlled clinical conditions to loud sounds that have the power to trigger their fear response even when no threat is really present.

Exposure therapy is well known to be effective for many PTSD and anxiety disorder patients. But it has a significant drawback: some fearful or anxious people find it hard to endure even controlled exposures to feared stimuli. This can lead them to drop out of exposure therapy, or to avoid treatment entirely.

Paul Siegel, Ph.D., of Purchase College, the State University of New York, devoted his 2014 BBRF Young Investigator project to exploring a phenomenon called the “Very Brief Exposure Effect.” In a paper newly published in Lancet Psychiatry, Dr. Siegel and associates report early success in a clinical experiment that sought to make use of this effect, hoping it might one day help people with fear and anxiety disorders who are unable to endure exposure therapy. The team’s senior member was Bradley Peterson, M.D., of the University of Southern California, a 2010 BBRF Distinguished Investigator, 2002 Independent Investigator and 1996 Young Investigator.

Drs. Siegel, Peterson and colleagues recruited a group of 82 women—half of them with a specific phobia, half with no phobias or other disorders—to test if exposure might still be effective even when the person receiving it is not conscious of undergoing exposure to the stimulus that triggers their fear. Their hypothesis was that the brain’s fear mechanisms, including those governing the extinction of fear, rely on automatic processes that occur when one is exposed to a phobic stimulus, be it conscious or not.

This is where the “very brief exposure effect” comes into play. The idea is to present repeated sequences of very brief exposures to the feared stimulus, followed immediately by what psychologists call a “masking” stimulus, which conceals the feared stimulus. Through such repeated exposure to the feared stimulus without the person’s conscious perception, “the fear response is desensitized at an unconscious level of processing,” Dr. Siegel explains.

The women recruited for the study had a carefully assessed, and intense, fear of spiders. This is not usually a disabling fear, the researchers noted—and this was by design. The study would test whether people with a very pronounced fear of something specific could be unconsciously exposed to that stimulus as a way of learning to overcome their fear.

An intense fear of spiders—or a relative absence of that fear—was documented via a test which gauged participants’ willingness to move progressively closer to a live tarantula in a terrarium. Phobic participants met diagnostic criteria for specific phobia, while controls did not meet criteria for any psychiatric disorder. The women were randomly assigned to subgroups: those who would receive very brief exposure (spider images) followed by masking, and those who would receive a placebo stimulus (pictures of flowers) followed by masking. Ten minutes after these exposures were conducted, the women received a functional MRI brain scan, so the researchers could observe, in real time, the changes in brain activity caused by the masked exposures.

Very brief exposure (VBE) via masking had two crucial effects, the team said. First, VBE activated brain circuits known to support the regulation of fear and its associated behavioral responses. Second, after the exposures, participants with phobias were able to move closer to the tarantula; their fear of spiders was reduced.

These results were not inconsistent with the theory behind exposure therapy, the researchers stressed. Just as in standard exposure therapy, the VBE method involves fear-extinction learning. It differs in that the learning in VBE follows from exposures that are not conscious.

For this reason, the researchers propose that if their results are replicated in clinical trials, and in individuals who suffer from more serious and disabling conditions such as PTSD and acute anxiety, VBE might be used as an adjunct to conventional exposure therapy—as a pretreatment, perhaps, that might promote the ability of patients receiving conventional exposure therapy to tolerate the fear that the treatment engenders under controlled conditions.

The fMRI scans of study participants who were helped by VBE suggested that its therapeutic effects may have been mediated by specific brain regions important in automatic (i.e., non-conscious) fear extinction and emotional salience processing. “Our findings challenge the clinical belief that direct confrontation of feared situations—and thus conscious arousal and emotional distress—are necessary to reduce fear,” they wrote.

Royal mystery unravelled: Hidden Henry VIII palace that ‘led to his death’ discovered

ROYAL FAMILY historians have discovered one of King Henry VIII’s hidden palaces, a site where he is believed to have taken part in the final joust that ultimately led to his death.

By CLIVE HAMMOND

Experts at the University of Greenwich, working alongside Royal Museums Greenwich, were stunned as they pinpointed the exact location of the tiltyard where Henry VIII’s last joust occurred. Historians have long argued that as a result of an injury he sustained while jousting, Henry VIII‘s movement was severely hampered, which led to the monarch’s massive weight gain. This weight gain, it is believed, would ultimately lead to his demise.

But the experts were amazed as they unearthed the tiltyard, as they had long believed the location of the area was completely different to where it was found.

Simon Withers, who is in charge of the research team, said: “When people ask me how I spent lockdown, I say ‘well, we found a palace’.

“It was always known to be underfoot but, until our find, the tiltyard towers had been believed to be elsewhere.

“Ground-penetrating radar sends pulses into the ground which are reflected back giving an image of what lies below.

“The images recorded on the radargrams are tantalisingly ambiguous and it has taken some time to reconcile these with what had long been considered to be the location of the tiltyard.”

The scans were from the National Maritime Museum, and found that one of the palace’s octagonal towers was actually further east than experts had originally thought.

The university said it was the site where Henry VIII famously was thrown off his horse in 1536, 11 years before he passed away.

In order to pinpoint the location, the researchers were able to use high-resolution ground penetrating radar, which allowed them to survey around two metres below the ground’s surface.

The research group, called Captivate, is aiming to continue its work on the project after the RMG gave access to work on the estate.

After his riding accident, Henry VIII – known to be athletic in his youth – saw his waistline grow and despite not carrying out any more exercise, he would still eat around 5,000 calories a day, mainly consisting of meat and wine.

Henry VIII’s waist measured at around 54 inches (137cm), and historians say his body became covered in “painful, pus-filled boils” and it was likely he suffered from gout.

In his earlier years, Henry VIII suffered a leg injury, which would be reopened as a result of his last joust in Greenwich.

The joust also reportedly led to Henry VIII’s mood swings, which became a trademark of his reign.

He was renowned for being short-tempered and it was estimated that by the time he had died he ordered the execution of more than 70,000 people.

He died on January 28, 1547 – on what would have been his father’s 90th birthday.

New insight into how brain neurons influence choices

By studying animals choosing between two drink options, researchers at Washington University School of Medicine in St. Louis have discovered that the activity of certain neurons in the brain leads directly to the choice of one option over another. The findings could lead to better understanding of how decision-making goes wrong in conditions such as addiction and depression. Credit: Mike Worful

When you are faced with a choice—say, whether to have ice cream or chocolate cake for dessert—sets of brain cells just above your eyes fire as you weigh your options. Animal studies have shown that each option activates a distinct set of neurons in the brain. The more enticing the offer, the faster the corresponding neurons fire.

Now, a study in monkeys by researchers at Washington University School of Medicine in St. Louis has shown that the activity of these neurons encodes the value of the options and determines the final decision. In the experiments, researchers let animals choose between different juice flavors. By changing the neurons’ activity, the researchers changed how appealing the monkeys found each option, leading the animals to make different choices. The study is published Nov. 2 in the journal Nature.

A detailed understanding of how options are valued and choices are made in the brain will help us understand how decision-making goes wrong in people with conditions such as addiction, eating disorders, depression and schizophrenia.

“In a number of mental and neuropsychiatric disorders, patients consistently make poor choices, but we don’t understand exactly why,” said senior author Camillo Padoa-Schioppa, Ph.D., a professor of neuroscience, of economics and of biomedical engineering. “Now we have located one critical piece of this puzzle. As we shed light on the neural mechanisms underlying choices, we’ll gain a deeper understanding of these disorders.”

In the 18th century, economists Daniel Bernoulli, Adam Smith and Jeremy Bentham suggested that people choose among options by computing the subjective value of each offer, taking into consideration factors such as quantity, quality, cost and the probability of actually receiving the promised offer. Once computed, values would be compared to make a decision. It took nearly three centuries to find the first concrete evidence of such calculations and comparisons in the brain. In 2006, Padoa-Schioppa and John Assad, Ph.D., a professor of neurobiology at Harvard Medical School, published a groundbreaking paper in Nature describing the discovery of neurons that encode the subjective value offered and chosen goods. The neurons were found in the orbitofrontal cortex, an area of the brain just above the eyes involved in goal-directed behavior.

At the time, though, they were unable to demonstrate that the values encoded in the brain led directly to choosing one option over another.

“We found neurons encoding subjective values, but value signals can guide all sorts of behaviors, not just choice,” Padoa-Schioppa said. “They can guide learning, emotion, perceptual attention, and aspects of motor control. We needed to show that value signals in a particular brain region guide choices.”

To examine the connection between values encoded by neurons and choice behavior, researchers performed two experiments. The study was conducted by first authors Sébastien Ballesta, Ph.D., then a postdoctoral researcher, and Weikang Shi, a graduate student, with the help of Katherine Conen, Ph.D., then a graduate student, who designed one of the experiments. Ballesta is now an associate professor at the University of Strasbourg in Strasbourg, France; Conen is now at Brown University.

In one experiment, the researchers repeatedly presented monkeys with two drinks and recorded the animals’ selections. The drinks were offered in varying amounts and included lemonade, grape juice, cherry juice, peach juice, fruit punch, apple juice, cranberry juice, peppermint tea, kiwi punch, watermelon juice and salted water. The monkeys often preferred one flavor over another, but they also liked to get more rather than less, so their decisions were not always easy. Each monkey indicated its choice by glancing toward it, and the chosen drink was delivered.

Then, the researchers placed tiny electrodes in each monkey’s orbitofrontal cortex. The electrodes painlessly stimulate the neurons that represent the value of each option. When the researchers delivered a low current through the electrodes while a monkey was offered two drinks, neurons dedicated to both options began to fire faster. From the perspective of the monkey, this meant that both options became more appealing but, because of the way values are encoded in the brain, the appeal of one option increased more than that of the other. The upshot is that low-level stimulation made the animal more likely to choose one particular option, in a predictable way.

In another experiment, the monkeys saw first one option, then the other, before they made a choice. Delivering a higher current while the monkey was considering one option disrupted the computation of value taking place at that time, making the monkey more likely to choose whichever option was not disrupted. This result indicates that values computed in the orbitofrontal cortex are a necessary part of making a choice.

“When it comes to this kind of choices, the monkey brain and the human brain appear very similar,” Padoa-Schioppa said. “We think that this same neural circuit underlies all sorts of choices people make, such as between different dishes on a restaurant menu, financial investments, or candidates in an election. Even major life decisions like which career to choose or whom to marry probably utilize this circuit. Every time a choice is based on subjective preferences, this neural circuit is responsible for it.”

More information: Values encoded in orbitofrontal cortex are causally related to economic choices, Nature (2020). DOI: 10.1038/s41586-020-2880-x , www.nature.com/articles/s41586-020-2880-x

https://medicalxpress.com/news/2020-11-insight-brain-neurons-choices.htm

First Alzheimer’s Blood Test Rolled Out for Clinical Use in US

The test will be a cheaper and more accessible alternative to currently available diagnostic tools, researchers say.

By Shawna Williams

The first blood test designed to assist physicians in determining whether a patient has Alzheimer’s disease is now available in most US states, the company C2N Diagnostics announced October 29. The test measures biomarkers that frequently reflect the presence of amyloid plaques in the brain—a hallmark of Alzheimer’s—as well as the presence of a gene variant that increases the risk of the disease.

“I’m very excited about it,” says Suzanne Schindler, a neurologist at the Washington University School of Medicine in St. Louis who was involved in testing an earlier version of the assay but is not connected to C2N. While there are two other tests for Alzheimer’s-associated brain changes, she notes, both have logistical and financial challenges: one that collects biomarkers in the cerebrospinal fluid (CSF) requires a spinal tap, while the other, a scan called amyloid PET, involves injecting a radioactive tracer, costs thousands of dollars, and is only performed at specialized centers. “I think patients really like the idea of a blood test,” she says. “And I think that it really has the potential to allow us to do a lot more testing than we have done in the past.”

The price of the test is $1,250, says C2N CEO Joel Braunstein, but patients who qualify for financial assistance will be charged between $25 and $400. Health insurance companies don’t currently pay for the test, he adds, but qualifying for this reimbursement “is a very high priority” for the company.

“If you asked me [five or ten] years ago if there would ever be a blood test for Alzheimer’s, I would have been very skeptical,” says Howard Fillit, the executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, which invested in C2N’s development of the test. “So the fact that this is on the market now is just amazing.” 

Fillit wasn’t alone in thinking that, due to the blood-brain barrier, biomarkers from the brain wouldn’t be found in peripheral blood in sufficient quantities to deliver a diagnosis. But analytical techniques have advanced in sensitivity in recent years, allowing small amounts of biomarkers in the blood to be detected. 

The C2N test relies on the ratio of two isoforms of the amyloid-β protein, Aβ42 and Aβ40, that aggregate to form amyloid plaques in the brain, combined with the presence of isoforms of apolipoprotein E (ApoE) that reflect whether the patient caries a genetic variant associated with Alzheimer’s risk. The results are combined into a score that indicates the probability that a patient would be found to have amyloid plaques if they were to undergo an amyloid PET scan. Doctors can then consider the test results along with other information about the patient to arrive at a diagnosis. According to data posted on the company’s website, a study in 686 patients with cognitive impairment found that those with scores above a certain cutoff point had a positive amyloid PET scan 92 percent of the time, while those with scores below a certain cutoff had a 77 percent chance of having a negative result on the PET scan.

While no drugs have yet been approved to treat Alzheimer’s, being able to distinguish it from other possible causes of cognitive impairment is nonetheless valuable, Fillit and Schindler say. As a clinician, Schindler says, “I want to know what my patients have.” That can be complicated because in many cases, “they don’t just have memory impairment, they’re taking multiple medications, they have all sorts of health issues,” she says. “And sometimes it’s really hard to know whether the symptoms they’re experiencing are due to something like Alzheimer’s or something else.” 

Symptom-based diagnosis of Alzheimer’s disease is only about 70 percent accurate, notes Colin Masters of the Florey Institute of Neuroscience and Mental Health in Australia who was part of the team that first characterized the amyloid plaques in the disease. If a clinician suspects the disease but the blood test returns a negative result, this “will force the clinicians to go and look harder for other causes of dementia,” says Masters, who collaborates with one of the test’s developers but has no ties to C2N. He adds that once an amyloid-targeting Alzheimer’s drug is approved, the test will be useful in determining who should receive it. Such a treatment may not be far off: the Biogen drug candidate aducanumab is set for review by a US Food and Drug Administration panel later this week.

The blood test is also likely to be a boon for clinical trials to develop other drugs, as it will make it easier to screen patients for recruitment, Fillit says. “Screening and enrollment represents up to fifty percent of the cost of clinical trials in Alzheimer’s disease, and one Phase 3 trial costs three to four hundred million dollars,” he says, calling the blood test a “huge advance in clinical trials.”

Spiders can detect sound through the same organ that allows them to detect vibration

The tropical net-casting spider Deinopis spinosa joinsseveral other arachnid species that can hear sounds from afar without the help of a web, or even ears—an ability that aids its unique hunting tactics.

by Katarina Zimmer

If you were able to find the ogre-faced spider Deinopis spinosa during the daytime, you wouldn’t see much movement. Looking like a dead leaf on a branch, it doesn’t move at all, hiding from predators and silently waiting out the day. But during the night, it transforms into one of the most agile of arachnid hunters.

Holding a net stretched between its four front legs, it springs down onto the ground to ensnare insect prey, making use of its hypersensitive, night-vision eyes—the largest of any spider, at nearly 5 mm across together. Using a different maneuver, it strikes out with its web grasped between its front legs to snatch mosquitoes, moths, and flies passing above it in a rapid, athletic, backbend. Yet how it detects these prey overhead has long been a mystery.

A new study published yesterday (October 29) in Current Biology demonstrates that D. spinosa can hear sounds from two meters away, which allows it to catch prey without relying on vision. The findings place the ogre-faced spiderin the ranks of certain jumping spiders, cob-web spiders, and fishing spiders, which have been previously shown to be capable of “hearing.” The study’s results add to evidence that help debunk an old yet persistent myth that spiders, which have no ears, can only detect mechanical vibrations, say, through their webs, and not airborne sound. The new data on D. spinosa confirm earlier clues that spiders can hear through the same organ they use to detect mechanical vibration.

“There have been several hints and actual documentations of acoustic sensitivity in spiders over the years, but this one’s [particularly] interesting,” remarks neuroethologist Andrew Mason of the University of Toronto Scarborough who has worked in one of the coauthor’s labs as a postdoc but wasn’t involved in the current study. “The really new piece of it is providing evidence that the spider’s leg can function as an acoustic transducer and that can be mediated by the sensory organ that’s normally associated with substrate vibration.”

Sensory ecologist Jay Stafstrom, a postdoc in neuroethologist and bioacoustician Ronald Hoy’s lab at Cornell University, had learned in earlier experiments that D. spinosa uses vision for its forward-striking, net-casting maneuvers but not for its back-bending twists. Individuals whose eyes were temporarily blinded couldn’t catch insects off the ground, but they could still catch prey out of the air, suggesting that “they’re probably using some other sensory system” for the backwards maneuver, Stafstrom says.

Deinopis spinosa uses its ability to hear from afar to snatch prey out of the air with a rapid overhead back-twist that unfolds within 60 milliseconds. 

Stafstrom, Hoy, and colleagues set out to investigate whether the ogre-faced arachnids were capable of picking up acoustic cues produced by the flapping of insect prey. Using techniques developed by lab neuroethologist Gil Menda, the team inserted tiny tungsten electrodes into the brains of living spiders in regions thought to be important for processing sensory information, and separately, into detached legs to detect neural activity of peripheral nerves. To the team’s surprise, neurons both in the brain and legs were responsive to a wide range of tonal frequencies—from 100 to 10,000 Hz—emitted from a loudspeaker 2 meters away. That range goes well beyond the typical wingbeat frequencies of their prey—which would be roughly between 150 and 750 Hz—into the kilohertz range, which would include the calls of passerine birds, for instance, that have been observed foraging around palm plants that ogre-faced spiders live on.

The researchers wondered if the metatarsal organ—an instrument situated at the lowest leg joint that senses mechanical vibration through movements in the spider’s exoskeleton—could play a role in detecting sound. Indeed, further experiments in which the researchers experimentally restricted the movement of detached legs demonstrated that the organ plays a role in detecting a subset of the frequencies they detect.

That suggests that, at least for some frequencies, the metatarsal organ of ogre-faced spiders can pick up airborne sounds that propagate through the air in pressure waves that deflect the tips of their legs, Stafstrom explains. “Even such a small amount of information, like air particles actually deflecting off of this leg, is enough for the spiders to functionally hear,” Stafstrom says.

The team suspects that sensitive leg hairs known as trichobothria—which Hoy’s team has previously shown enable jumping siders to hear from afar—play a role in detecting lower frequencies.

The scientists followed up with behavioral experiments to test if the spiders would respond to sounds. And sure enough, 13 of 25 spiders performed back-twists when they heard frequencies between 150 and 750 Hz, as if an insect had whizzed passed them. Stafstrom also flew out to Florida to find spiders in the wild and repeated the experiments with a Bluetooth speaker—with similar results, he says.

Curiously, the spiders didn’t react behaviorally to higher frequency tones, even though the previous experiments indicated that their central and peripheral neurons are responsive to tones as high as five octaves above a middle A. Perhaps the spiders have the ability to hear those frequencies not in order to hunt but so they can hide from avian predators, which tend to produce high-frequency sounds.

To Natasha Mhatre, a sensory biologist at Western University in Canada who wasn’t involved in the study, the findings address a long-standing mystery. Some previous research in other spider species in which researchers recorded the neural responses to experimental vibrations of the leg suggested that they were in fact more sensitive to frequencies greater than 1,000 Hz than to frequencies below that. That observation was puzzling because most of the vibrations spiders encounter on their web would be below 1,000 Hz, Mhatre says. “For the longest time, we didn’t really know why on Earth spiders were more sensitive to things that are above 1,000 hertz and not sensitive to the things that they’re actually interested in,” she says.

The team’s results suggest that ogre-faced spiders may be sensitive to those higher frequencies because they’re listening to airborne sounds, possibly to avoid birds. “What this study shows is that yes, some sounds are sufficient . . .  to generate joint bending large enough to actually produce a nervous response and therefore for the spider to hear it,” Mhatre adds.

Both Mason and Mhatre say they’re curious about the precise mechanisms involved, such as which leg in the hunting posture “hears” the sound, and whether and how the spider’s webs could play an auxiliary role in hearing by modifying the spider’s sensitivity to certain sounds.

To Mason, the findings also raise a philosophical question about how spiders perceive the world. Scientists tend to think about airborne sound and substrate vibration as two distinct entities. But for the spider, are they two different categories of stimulus, or are they part of a continuous realm of sensory information? “It may be that it’s just all vibration, and the boundary between the air and the web is just not a real boundary.”

For a spider with such a unique Jekyll-and-Hyde lifestyle, still by day and acrobatic at night, Stafstrom says, he’s not surprised they have an advanced sensory toolkit. “Their behavior requires some really impressive sensory equipment to be able to survive and be successful as an animal. Trying to figure out how [exactly] they’re doing it is a question that I’ll be trying to answer for many years to come.”

J.A. Stafstrom et al., “Ogre-faced, net-casting spiders use auditory cues to detect airborne prey,” Current Biology, doi:10.1016/j.cub.2020.09.048.

Hard Physical Work Significantly Increases the Risk of Dementia

hose who work in physically demanding jobs have a 55% higher risk of developing dementia than those who have more sedentary careers.

The muscles and joints are not the only parts of the body to be worn down by physical work. The brain and heart suffer too. A new study from the University of Copenhagen shows that people doing hard physical work have a 55-percent higher risk of developing dementia than those doing sedentary work. The figures have been adjusted for lifestyle factors and lifetime, among other things.

The general view has been that physical activity normally reduces the risk of dementia, just as another study from the University of Copenhagen recently showed that a healthy lifestyle can reduce the risk of developing dementia conditions by half.

Here the form of physical activity is vital, though, says associate professor Kirsten Nabe-Nielsen from the Department of Public Health at the University of Copenhagen.

“Before the study we assumed that hard physical work was associated with a higher risk of dementia. It is something other studies have tried to prove, but ours is the first to connect the two things convincingly,” says Kirsten Nabe-Nielsen, who has headed the study together with the National Research Centre for the Working Environment with help from Bispebjerg-Frederiksberg Hospital.

“For example, the WHO guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not. Guides from the health authorities should therefore differentiate between physical activity in your spare time and physical activity at work, as there is reason to believe that the two forms of physical activity have opposite effects,” Kirsten Nabe-Nielsen says and explains that even when you take smoking, blood pressure, overweight, alcohol intake and physical activity in one’s spare time into account, hard physical work is associated with an increased occurrence of dementia.

One of the study’s co-authors is Professor MSO Andreas Holtermann from the National Research Centre for the Working Environment. He hopes the dementia study from the University of Copenhagen will contribute to shine a spotlight on the importance of prevention, as changes in the brain begin long before the person leaves the labour market.

“A lot of workplaces have already taken steps to improve the health of their staff. The problem is that it is the most well-educated and resourceful part of the population that uses these initiatives. Those with a shorter education often struggle with overweight, pain and poor physical fitness, even though they take more steps during the day and to a larger extent use their body as a tool. For workmen, it is not enough for example to avoid heavy lifts if they wish to remain in the profession until age 70. People with a shorter education doing manual labour also need to take preventive steps by strengthening the body’s capacity via for example exercise and strength training,” he says.

The study is based on data from the Copenhagen Male Study (CMS), which included 4,721 Danish men, who back in the 1970s reported data on the type of work they did on a daily basis. The study included 14 large Copenhagen-based companies, the largest being DSB, the Danish Defence, KTAS, the Postal Services and the City of Copenhagen.

Through the years, the researchers have compiled health data on these men, including data on the development of dementia conditions.

According to Kirsten Nabe-Nielsen, previous studies have suggested that hard physical work may have a negative effect on the heart blood circulation and thus also on the blood supply to the brain. This may for example lead to the development of cardiovascular diseases like high blood pressure, blood clots in the heart, heart cramps and heart failure.

The National Research Centre for the Working Environment continues to work on the results with a view to identifying healthier ways of doing hard physical work. They have therefore begun to collect data from social and healthcare assistants, child care workers and packing operatives, among others, in order to produce interventions meant to organise hard physical work in such a way that it has an ‘exercise effect’.

They thus hope to see companies successfully change work procedures, ensuring for example that heavy lifts will have a positive effect rather than wear down the workers. The results will be published on an ongoing basis.

Scientists Discover New Human Salivary Glands

The findings may have implications for radiotherapy, a cancer treatment that can cause damage to salivary glands and leave lasting complications.

Doctors don’t regularly come across undiscovered bits of human anatomy, but a team of physicians recently reported a never-before-described set of salivary glands in patients’ necks. The first hint of this new gland emerged while Wouter Vogel, a radiation oncologist at the Netherlands Cancer Institute (NCI), was probing for damage to salivary glands after radiotherapy for cancer in the head, neck, or brain—injuries that can lead to issues such as problems with digestion, speech, and an increase in oral infections. While going through these scans, he found something usual.

Vogel was using a new technique for detecting cells in the salivary glands—PSMA PET/CT, a form of combined positron emission tomography (PET) and computed tomography (CT) that uses a radioactive tracer that binds to a prostate-specific membrane antigen (PSMA). This method is typically used to detect prostate cancer, but in a prior study, Vogel and his colleagues had found that it also labels salivary gland cells, where PSMA is also expressed. Humans have three major salivary glands and approximately 1,000 minor ones. “This scan is extremely sensitive for the salivary glands,” Vogel says. “So we can see more than ever before.”

What he saw was an unexpectedly high level of labeling in the upper section of the throat known as the nasopharynx, where only minor salivary glands are supposed to be found.

When Vogel first observed the unanticipated signal, he says he was confused—salivary gland cells were not thought to be abundant in this location. Immediately, he sought a second opinion from his colleague Matthijs Valstar, an oral and maxillofacial surgeon at the NCI. “You never believe something until you have some feedback from others,” Vogel tells The Scientist. “But we agreed that it really was an unexpected and significant signal that requires further investigation.”

To examine further, Vogel and Valstar assembled a team of more than a dozen researchers from NCI and three other medical centers in the Netherlands. Together, they went through the PSMA PET/CT scans of more than 100 patients with prostate or urethral gland cancer and found similar signals in the nasopharynx region in those individuals as well. This assessment also revealed that the glands existed as a pair and had an average length of four centimeters. The group then dissected two human cadavers to confirm that this was, indeed, salivary gland tissue. They dubbed these newly identified glands as “tubarial glands,” based on their location above the torus tubarius, the section of the nasopharynx just behind the pharynx. These findings appeared last week (October 16) in Radiotherapy & Oncology.

According to Vogel, there are likely two main reasons the tubarial glands haven’t been found before: researchers had not previously used PSMA PET/CT to look for salivary glands, and the newly discovered glands are located in a region that’s hard to access with standard surgical procedures. “With the other salivary glands, you can just feel them by either with your hand or see them during surgery,” Vogel explains. “The location we’re describing now, you can only see it with a nasal endoscopy.” Nasal endoscopy is a method in which a tube with a tiny camera and light are used to image the nose and sinuses. Based on the tubarial glands’ similarities to the volume and draining system of the sublingual gland—one of the three major salivary glands—the authors suggest that the new glands should be classified as a fourth major gland. However, they also note that some might disagree with this categorization, because the new glands share similarities with minor glands as well.

Because salivary glands are at risk of damage from radiotherapy, the team also set out to investigate whether radiotherapy exposure to the tubarial glands would affect patients. After examining data from a cohort of more than 700 head and neck cancer patients, they reported that the radiotherapy dose to the gland area was associated with dry mouth and swallowing difficulties after treatment.

Vincent Vander Poorten, an otorhinolaryngologist at University Hospital Leuven (UZ Leuven) in Belgium who was not involved in this study but has collaborated with the authors on other projects, says that while he agrees that the authors have found a new cluster of minor glands, whether the tubarial gland is truly a separate, major gland is somewhat controversial. “Of course, you could say that it’s just a cluster of minor salivary glands that are all over the place in the mucous membranes of the head and neck.”

See “New Discoveries in Human Anatomy

“I don’t think there is any doubt this is new salivary tissue that has been discovered.” Chris Nutting, an oncologist at the Royal Marsden Hospital in the UK who was not involved in this study, tells The Scientist. “One of the areas that we are very keen on pursuing is trying to identify salivary tissue and avoiding it because it causes one of the main complications of radiotherapy.” The question is how much sparing this gland will actually improve patient outcomes, he adds. The authors conducted a retrospective study, which looks back at previously collected data, but Nutting says a prospective study, which enrolls participants and observes the outcomes of an exposure over time, will be important.

Vogel, too, notes that whether radiotherapy to spare the tubarial glands will actually make a difference in patient outcomes is an open question. “That is the reason that we cannot just implement this new finding into treatment today,” he adds. “We have to do prospective evaluations to see if it really helps patients. This is something that we envision [doing in] the coming years.”

M. Valstar et al., “The tubarial salivary glands: A potential new organ at risk for radiotherapy,” Radiotherapy & Oncology, doi:10.1016/j.radonc.2020.09.034, 2020.