Author: Futurity (National Geo)

Mothers struggling with depression tend to take longer to respond to their child during back-and-forth dialogue, according to a new study.

The findings provide the basis for further research to determine if the slower response time has any long-term effects on the children’s language development, vocabulary, or academic outcomes.

For the study, published in the journal Infant and Child Development, researchers listened to audio recordings of more than 100 families who were involved in the Early Head Start program, a federal child development program for children whose family’s income is at or below the federal poverty line.

Some of the moms involved were struggling with depression, and the researchers documented how much time passed in between responses for a mother and her child during back-and-forth dialogue.

“We found that the time gap in between responses, in general, gets shorter between mother and child as the child ages, and we also found the mom’s timing tended to predict the child’s timing and vice versa,” says Nicholas Smith, an assistant professor in the School of Health Professions at the University of Missouri.

“Mothers and children are in sync. Children who were slower to respond to their mom often had moms who were slower to respond to the child, and children who were faster to respond to their mom had moms who were faster to respond to the child. The significant new finding was that the moms who were more depressed took longer to respond to their child compared to moms who were less depressed.”

In the longitudinal study, using audio recordings, researchers compared the response time of back-and-forth dialogue between mothers and their children when the children were 14 months old and 36 months old.

Going forward, Smith plans to further study the dialogue response timing for the same individuals that were recorded in this study when the children were in pre-kindergarten and also when they were in fifth grade to examine how these effects play out later on in the children’s development.

“The overall objective we are hoping to accomplish is to better understand how mother-child interaction works as well as the underlying mechanisms and potential factors at play,” Smith says.

“Once we identify what factors drive successful development outcomes and what factors potentially impair development, we can better identify at-risk children and then tailor potential interventions toward those that can benefit from them the most.”

The Mizzou Alumni Association funded the work.

Source: University of Missouri

A new method allows researchers to control and follow in real time how tau protein changes from a benign protein essential for normal function in our brains to the toxic tangles that are a signature of Alzheimer’s.

The technique uses low voltage electricity as a surrogate for the natural signals that trigger the protein to fold and assemble, both for its normal function in the brain and in the runaway process leading to often fatal disease.

“This method provides scientists a new means to trigger and simultaneously observe the dynamic changes in the protein as it transitions from good to bad,” says Daniel E. Morse, professor emeritus of biochemistry and molecular genetics at the University of California, Santa Barbara and senior author of the study in the Journal of Biological Chemistry.

“The method should be widely useful to identify molecules and conditions that direct different trajectories of assembly in a number of different but related amyloid diseases,” says lead author Eloise Masqulier.

Under normal circumstances, tau is a soluble protein that starts out in an open, loose configuration, like a piece of string. In response to a signal, tau proteins fold up and progressively assemble with one another, enabling them to bind to tiny cylindrical structures—microtubules—that support the shape of the neurons and transport nutrients and molecules inside the cells.

However, in pathological cases, the signal goes too far, causing the protein to assemble uncontrollably, forming the insoluble amyloid filaments that become neurofibrillary tangles inside neurons, interrupting their function and eventually killing them.

Using their new method with the core portion (a peptide) of tau, the investigators were able to observe and analyze a critical “tipping point” between normal, reversible folding and assembly, and the irreversible, pathological assembly that underlies tauopathic, neurodegenerative diseases.

Using less than a volt of electrical potential to mimic hyperphosphorylation (the disease-promoting signal), the scientists triggered and finely tuned the tau-peptide’s folding in their lab experiments, using spectroscopic methods to reveal details of the folding and progressive assembly to form amyloid-like filaments.

Unlike other modes of examining protein folding and assembly, such as X-ray diffraction or cryo-electron microscopy that provide static snapshots of the processes as they occur in time, the new electrochemical method allows users to continuously witness and analyze details of the progressive, dynamical folding and assembly as they occur in real time, permitting the first direct observations of the critical earliest steps in these processes.

Also, unlike most techniques previously used for studies of tau and its core peptide, because the electrical trigger closely mimics the natural triggering signal, the method permits direct observation of these processes without the need for additional “helper” molecules.

The authors report that the technology can also be used as a tool to more rapidly test and identify drugs and antibodies potentially useful for prevention or treatment of Alzheimer’s and other amyloid diseases.

“Because we can turn on and fine-tune the process at will,” Morse says, “we can use this system to see what molecules could interdict or block specific stages of folding and assembly.”

Source: UC Santa Barbara

The cannabis component CBD inhibits the breakdown of THC, which may result in a stronger and longer high after using edibles, research finds.

Contrary to some common claims, the researchers found that relatively high doses of CBD may increase the adverse effects of THC, the main active ingredient in cannabis that can cause a mood alteration or a “high” sensation.

The results of the study, published in JAMA Network Open, show that the maximum amount of THC measured in participants’ blood samples was almost twice as high after consuming a brownie containing THC with CBD than after eating a brownie with only THC, even though the dose of THC in each brownie (20 mg) was the same. In addition, the maximum amount of 11-OH-THC (a metabolic byproduct of THC that produces drug effects similar to THC) was 10-fold greater after eating the brownie with the high CBD extract compared with the one containing high THC extract.

The work examines how the body absorbs, eliminates, and responds to cannabis extracts that varied with respect to THC and CBD concentrations.

“The fact that THC and CBD were orally administered was very important for the study and played a large role in the behavioral effects and drug interactions we saw,” says Austin Zamarripa, postdoctoral research fellow at the Johns Hopkins University School of Medicine and the study’s lead author.

Prior controlled human studies evaluating these interactions have predominantly administered THC and CBD by inhalation or intravenously, or have not administered them at the same time. For this reason, much of the existing data regarding interactions between THC and CBD may not apply to edible cannabis products such as baked goods, candies, and gummies, which get metabolized in the intestine and liver.

“Overall, we saw stronger subjective drug effects, greater impairment of cognitive [thinking] and psychomotor [moving] ability and greater increase in heart rate when the same dose of THC was given in a high CBD cannabis extract, compared with a high THC extract with no CBD,” says Zamarripa.

The new study, which tested each type of cannabis extract and a placebo within the same subjects rather than using different people for each drug type, took place from January 2021 to March 2022 at the Behavioral Pharmacology Research Unit at Johns Hopkins Bayview Medical Center. The researchers recruited 18 adult participants (11 men and 7 women) who had not used cannabis for at least 30 days prior to beginning the study.

Study volunteers took part in three sessions, each separated by at least one week. In each session, participants consumed a brownie containing either 20 mg of THC, 20 mg of THC and 640 mg of CBD, or no THC or CBD (placebo). Neither the participants nor the investigators knew in advance what was in the brownie that participants ate on a given session. Participants also took a drug cocktail consisting of five cytochrome, or CYP, probe drugs (100 mg caffeine, 25 mg losartan, 20 mg omeprazole, 30 mg dextromethorphan, and 2 mg midazolam) 30 minutes after eating each brownie. These drugs will help the scientists figure out how CBD and THC affect how participants’ bodies metabolize other commonly used medications and dietary supplements (in analyses that they will publish separately).

To create a basis for comparison, baseline blood samples were collected from all participants before each session, along with their vital signs, including heart rate and blood pressure, and measures of cognitive and psychomotor performance. Participants provided blood and urine samples at timed intervals for 12 hours and then again approximately 24 hours after drug dosing was completed. Self-reported drug effects were measured using the Drug Effect Questionnaire, or DEQ, a standardized tool used to assess aspects of subjective experiences after being given a psychoactive drug like THC or cannabis.

Although participants experienced the typical effects produced by cannabis with both the CBD and THC extracts, there were notable differences between the two, which are likely the result of the increased concentration of THC and 11-OH-THC in the blood after the CBD extract was consumed.

Using the DEQ tool, participants rated subjective drug effects with a scale from 0 to 100, with 0 being “not at all affected” and 100 being “extremely affected.” Among the subjective ratings, participants experienced greater increases in overall drug effects, unpleasant drug effects, feeling sick, dry/red eyes, and difficulty performing routine tasks when they consumed the brownie with both CBD and THC compared the THC-only brownie. After eating the brownie with the high CBD cannabis extract, participants showed significantly more impairment in performance on tests of memory and attention compared with when they consumed the brownie with the high THC extract.

Consuming the high CBD extract brownie also resulted in a greater increase in heart rate, from a 10 beats per minute increase from baseline [THC] to a 25 beats per minute increase from baseline [THC + CBD]. The placebo brownie did not increase the subjective drug effect ratings or alter the performance on any cognitive or psychomotor tasks.

“We have demonstrated that with a relatively high oral dose of CBD [640 mg] there can be significant metabolic interactions between THC and CBD, such that the THC effects are stronger, longer-lasting, and tend to reflect an increase in unwanted adverse effects,” says Ryan Vandrey, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and the study’s senior author.

Vandrey notes that another of his team’s recent studies found that CBD products don’t always have correct labels.

“Our new study suggests that it’s important for folks to be aware that if they’re going to take a high-dose CBD extract, they also need to be mindful about interactions with other medications. Individuals should discuss with their doctor whether they should consider dose adjustments of THC and other medications if they’re also taking CBD,” says Vandrey.

The researchers say that future studies are needed to further understand the impact of CBD and THC dose, relative concentration, frequency of use, and individual health differences on how our bodies metabolize commonly used medications. This kind of research is needed to inform clinical and regulatory decision-making regarding the therapeutic and nontherapeutic use of cannabis products.

Source: Johns Hopkins University

A newly identified tsetse fly pheromone reveals new insights into how the insects communicate—and may help in reducing disease spread.

The tsetse fly is a blood-sucking insect that spreads diseases in both humans and animals across much of sub-Saharan Africa.

Tsetse flies are known to carry parasites called African trypanosomes. When the insects bite humans or animals, they transmit these parasites, spreading diseases such as African sleeping sickness, which can be fatal to humans, and nagana, a disease that affects livestock and other animals.

“African sleeping sickness is a dreadful disease that’s hard to treat. Our immune systems have a hard time clearing trypanosomes and most of the drugs we have to kill them are toxic,” says John Carlson, professor of molecular, cellular, and developmental biology at Yale University and senior author of the new study. “And nagana, which affects livestock, has had terrible economic impacts in the region.”

Further, with climate change projected to expand the areas in which tsetse flies can survive, more humans and animals are expected to be affected by these diseases in the coming years.

One strategy identified as a way to control the spread of tsetse flies is to use their own pheromones—particularly volatile pheromones, or pheromones that work over distances rather than through direct contact—to attract and trap the insects.

To identify volatile pheromones that might be used for this purpose, the researchers took tsetse flies—of the species G. morsitans—and placed them in a liquid to collect any chemicals they might be emitting. They then ran those extracts through a device called a gas chromatograph-mass spectrometer, which can identify specific compounds from a mixed sample.

The researchers found several chemicals that had never previously been reported, including three that elicited responses from tsetse flies. One in particular, a chemical called methyl palmitoleate (MPO), had the strongest effects.

Specifically, in a series of experiments led by first author Shimaa Ebrahim, a postdoctoral fellow in Carlson’s lab, researchers found that MPO attracted male tsetse flies, caused them to stop and remain where they were for some time, and acted as an aphrodisiac. A drop of liquid containing MPO attracted male tsetse flies to knots in yarn that only resembled flies and to females of another tsetse fly species that they would not typically interact with.

To better understand how MPO mediated behavior, the researchers then tested whether neurons on the flies’ antennae responded to MPO. Indeed, they identified a subpopulation of olfactory neurons on the antennae that increased their firing rates when exposed to the pheromone.

Together, the findings indicate that MPO is a tsetse fly attractant, say the researchers, and therefore, it may be useful in slowing disease spread.

Currently, the most effective method of controlling tsetse fly populations is through traps that use odors from the animals the flies prefer to feed on.

“Now we’ve found this pheromone that could be used in combination with the host odors,” says Carlson. “Especially since MPO not only attracts the flies but causes them to freeze where they are.”

While animal odors have the benefit of attracting tsetse flies across large distances, they tend to fade quickly. MPO works at shorter distances but is effective for longer periods of time, Carlson adds.

“MPO could be one more tool in the toolbox when it comes to combatting tsetse flies and the diseases they spread,” he says.

The team is now working with collaborators in Kenya to test whether MPO is useful in traps in the real world, not just in a lab setting.

Additionally, the researchers want to understand what causes tsetse flies infected with trypanosomes to emit an entirely different set of chemicals—something else they identified in the study—and how that affects fly communication.

The study appears in the journal Science.

Source: Mallory Locklear for Yale University

Male whales along Australia’s eastern seaboard are giving up singing to attract a mate, switching instead to fighting their male competition.

Researchers analyzed almost two decades of data on humpback whale behavior and found singing may no longer be in vogue when it comes to seduction.

“…humans aren’t the only ones subject to big social changes when it comes to mating rituals.”

“In 1997, a singing male whale was almost twice as likely to be seen trying to breed with a female when compared to a non-singing male,” says Rebecca Dunlop, associate professor at the University of Queensland’s School of Biological Sciences.

“But by 2015 it had flipped, with non-singing males almost five times more likely to be recorded trying to breed than singing males. It’s quite a big change in behavior so humans aren’t the only ones subject to big social changes when it comes to mating rituals.”

The researchers believe the change has happened progressively as populations recovered after the widespread cessation of whaling in the 1960s.

“If competition is fierce, the last thing the male wants to do is advertise that there is a female in the area, because it might attract other males which could out-compete the singer for the female,” Dunlop says.

“By switching to non-singing behavior, males may be less likely to attract competition and more likely to keep the female. If other males do find them, then they either compete, or leave.

“With humpbacks, physical aggression tends to express itself as ramming, charging, and trying to head slap each other. This runs the risk of physical injury, so males must weigh up the costs and benefits of each tactic.”

“Male whales were less likely to sing when in the presence of other males. Singing was the dominant mating tactic in 1997, but within the space of seven years this has turned around,” she says.

“It will be fascinating to see how whale mating behavior continues to be shaped in the future.”

Celine Frere, an associate professor and study coauthor, says previous work from Professor Michael Noad found the whale population grew from approximately 3,700 whales to 27,000 between 1997 and 2015.

“We used this rich dataset, collected off Queensland’s Peregian Beach, to explore how this big change in whale social dynamics could lead to changes in their mating behavior,” Frere says.

“We tested the hypothesis that whales may be less likely to use singing as a mating tactic when the population size is larger, to avoid attracting other males to their potential mate.”

The research appears in Communications Biology.

Source: University of Queensland

A trio of faulty genes that fail to put the brakes on the immune system’s all-out assault on SARS-CoV-2 may help explain some severe COVID cases in kids.

One of the most terrifying aspects of the COVID pandemic has been its unpredictably severe impact on some children. While most infected kids have few or no symptoms, one in 10,000 fall suddenly and dramatically ill about a month after a mild infection, landing in the hospital with inflamed hearts, lungs, kidneys, and brains, spiked temperatures, skin rashes, and abdominal pain. Researchers call it MIS-C—multisystem inflammatory syndrome in children.

Some suspected that MIS-C is a SARS-CoV-2-specific form of Kawasaki disease, a rare childhood inflammatory condition that has long puzzled clinicians and seems to be triggered by many different viruses.

The new findings in Science constitute the first mechanistic explanation of any Kawasaki disease.

“The patients are sick not because of the virus,” says Rockefeller University geneticist Jean-Laurent Casanova. “They’re sick because they excessively respond to the virus.”

An enduring mystery of COVID has been its wildly varied impact on individuals, with one person getting a sore throat and another winding up on a ventilator—or worse. In February 2020, Casanova and his collaborators in the CHGE, an international consortium of researchers seeking the human genetic and immunological bases of all the different ways a SARS-CoV-2 infection can manifest, began searching for inborn errors (genetic mutations) of immunity among healthy people who had severe forms of COVID. Among their targets were children with MIS-C.

Casanova and his CHGE colleagues assembled an ever-growing database of hundreds of fully sequenced genomes of COVID victims from hospitals across North America, Asia, Europe, Latin America, Oceania, and the Middle East. They have since made several discoveries about the genetic predispositions of individuals who develop severe COVID.

For the current study, the researchers hypothesized that in some children, MIS-C could be caused by a gene defect that rendered them vulnerable to an inflammatory condition provoked by a SARS-CoV-2 infection, says Casanova, professor in and head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at Rockefeller.

To find out, they analyzed the genomes of 558 children who’d had MIS-C. Five unrelated kids from four countries—Turkey, Spain, the Philippines, and Canada—shared mutations in three closely related genes controlling the OAS-RNase L pathway, which is involved in viral response.

Normally, this pathway is induced by type 1 interferons and activated by viral infection, which induce OAS1, OAS2, and OAS3 molecules. These in turn activate RNase L, an antiviral enzyme that chops up single-strand viral and cellular RNA, shutting down the cell. When a cell goes dark, the virus can’t hijack its replication machinery to spread disease.

But in the five children with these mutations, the pathway failed to activate in response to the presence of SARS-CoV-2. The cell instead sensed the viral RNA using another pathway known as MAVS, which provokes an army of dendritic cells, phagocytes, monocytes, and macrophages to attack the viral invaders en masse. The MAVS pathway acts as a sort of accelerator of the immunological response.

The OAS-RNase L pathway, on the other hand, is supposed to act as the brake. But in MIS-C, the brake fails, and the response careens out of control.

“Phagocytes produce excessive levels of inflammatory cytokines and chemokines and growth factors and interferons—you name it,” Casanova says. Massive inflammation ensues.

Because MIS-C is clinically and immunologically so aligned with other examples of Kawasaki disease, the researchers believe that MIS-C is a variety of the disease driven by a SARS-CoV-2 infection—the first such provocateur of Kawasaki to be pinpointed.

Why this reaction only takes place about a month after infection remains unknown. “We now understand the molecular and cellular basis of the disease, but we don’t understand the timing,” Casanova says.

Although the findings shed light on how problem genes can kick off MIS-C in some populations, it only accounts for 1% of the children in the study. As for the rest of the children who had COVID only to wind up hospitalized weeks later—the vast majority of whom recover quickly with treatment—the researchers plan to seek out other mutations in the OAS-RNase L pathway or in related pathways.

“We clearly now have one pathway that is causal of disease when it’s disrupted,” he says. “There’s every good reason to believe that there will be many other patients with MIS-C who have mutated genes in this pathway. Is that going to be 5%, 10%, 50%, 100%? I don’t know. But for sure, there will be mutations in other genes controlling this pathway.”

Source: Rockefeller University

Cannabidiol or CBD inhibits the metabolism of nicotine, meaning it could help tobacco users curb the urge for that next cigarette, according to a new study.

Researchers tested the effects of CBD, a non-psychoactive component of cannabis, and its major metabolite on human liver tissue and cell samples, showing that it inhibited a key enzyme for nicotine metabolism.

For the nicotine-addicted, slowing metabolism of the drug could allow them to wait before feeling the need to inhale more of it along with all the other harmful things found in cigarette smoke.

More research is needed to confirm these effects in humans and determine dosage levels, but these findings show promise, says Philip Lazarus, professor of pharmaceutical sciences at Washington State University.

“The whole mission is to decrease harm from smoking, which is not from the nicotine per se, but all the carcinogens and other chemicals that are in tobacco smoke,” says Lazarus, senior author of the study in the journal Chemical Research in Toxicology. “If we can minimize that harm, it would be a great thing for human health.”

Cigarette smoking is still a major health problem with one in five people in the US dying every year from smoking-related causes. While often seen as less harmful, many other nicotine delivery methods including vaping, snuff, and chew also contain chemicals that can cause cancer and other illnesses.

For the current study, researchers tested CBD and its major metabolite, meaning what it converts to in the body, 7-hyroxycannabidiol, on microsomes from human liver tissue as well as on microsomes from specialized cell lines that allowed them to focus on individual enzymes related to nicotine metabolism.

They found that CBD inhibited several of these enzymes, including the major one for nicotine metabolism, identified as CYP2A6. Other research has found that more than 70% of nicotine is metabolized by this enzyme in the majority of tobacco users. The impact of CBD on this particular enzyme appeared quite strong, inhibiting its activity by 50% at relatively low CBD concentrations.

“In other words, it appears that you don’t need much CBD to see the effect,” says Lazarus.

Lazarus’ team is currently developing a clinical study to examine the effects of CBD on nicotine levels in smokers, measuring nicotine levels in their blood versus smokers taking a placebo over the course of six to eight hours. Then, they hope to do a much larger study looking at CBD and nicotine addiction.

Additional coauthors are from Penn State and Washington State. The National Institutes of Health supported the work.

Source: Washington State

Researchers offer the first description of the animal communities around the asphalt volcanoes about 10 miles off the coast of Santa Barbara, California.

Santa Barbara Channel’s natural oil seeps are a beach-goer’s bane, flecking the shores with blobs of tar. But the leaking petroleum also creates fascinating geologic and biologic features. These asphalt volcanoes, virtually unique in the world, provide a rare habitat in a region known for its underwater biodiversity.

The findings, published in the Bulletin of Marine Science, detail the different kinds of fishes that live on and around the volcanoes.

Scientists first discovered asphalt volcanoes in the Gulf of Mexico. These vents erupt hot tar instead of lava, slowly building up smooth mounds that can be several dozen feet tall. In 2010, a team led by UC Santa Barbara professor Dave Valentine documented two volcanoes in the Santa Barbara Channel, which they named Il Duomo and Il Duomito; the taller of the two, Il Duomo, is about 65 feet tall. The group published an account of the geology and characterized the habitat. Since then, scientists have found only one other site, off the coast of Angola.

“Even in our channel, that has lots of seeps, there’s only two asphalt volcanoes that we know of,” says lead author Milton Love, a researcher at UC Santa Barbara’s Marine Science Institute. “So it takes an almost unique set of circumstances to form these.”

Yet, virtually nothing was known about the animals living at asphalt volcanoes aside from a brief description Valentine and his coauthors provided in their 2010 paper. So, Love and his colleagues used footage from an autonomous underwater vehicle to characterize the fish communities that inhabit these remarkable features. Their goal was to figure out who lives where and why. The team combed through eight hours of surveys—encompassing 2,743 still images—gradually building up a roster of the neighborhood.

Although fish densities were low, the team found a relatively diverse assemblage of species. Altogether, they observed 1,836 fish representing no less than 43 species. And at least 53.5% of these species were rockfishes. “This is what you would expect to find if you surveyed a tall and fairly smooth rock reef in this location,” Love says.

Certain fish preferred the volcanoes’ uniform slopes, including rockfishes like the swordspine, greenblotched, and greenspotted. Meanwhile, a variety of poachers and flatfishes populated the muddy sea bottom surrounding the mounds. Oddly enough, there were haloes several meters wide around the volcanoes devoid of flatfishes. Love suspects those fish that ventured too close were spotted against the black tar and eaten.

The researchers observed a few taxa that moved between the mud and the edges of the asphalt, such as shortspine combfish, greenstriped rockfish, and spotted ratfish. Notably rare were the “sheltering guild” of fishes, such as bocaccio and cowcod, which require nooks and crannies that are absent on the asphalt volcanoes’ smooth slopes, as well as the surrounding sea floor. However, “Even small amounts of asphalt in an image had a substantial effect on the species that were observed,” the authors write, as soft-seafloor fishes kept away from the hard tar.

Although dormant now, the asphalt volcanoes are relatively new features. “They probably developed around 40,000 years ago,” Love says. And he was quick to point out that they were quite different just a few thousand years ago. “What we see now we wouldn’t have seen even 20,000 years ago, when you had these glacial maximums and sea level minimums,” he says. At that time, the highest of these features would have been just a few dozen feet below the surface. “It would’ve had an entirely different group of fishes and invertebrates, and it would’ve had algae all over it.”

Today, the volcanoes have a stark beauty. Colorful invertebrates pop out in sharp relief against the black substrate. “You have all kinds of sponges and deep-water corals,” Love says. A particularly striking orange animal seems to rim the edges of cracks and fissures. “Is it a sea anemone? Nobody seems to know.” The group hopes to publish an account of the invertebrate assemblages in the future.

Unfortunately, the team also found evidence of illegal fishing, including lost lines, weights, and even a rockfish carcass still on the hook. Although the fish communities are typical of the area, Love believes California should protect these sites given how unique they are. “Not only are there only three places known that have this habitat, but this is the only one in shallow water,” he says.

Source: UC Santa Barbara