Brain

Heart disease more likely for adults with dysfunctional childhoods

High family adversity in childhood tied to heart attacks, strokes as adult

Childhood adversity can lead to lifelong stress, smoking, anxiety, depression, sedentary lifestyle in adulthood

Social, economic support for young children has biggest 'bang for the buck' to combat issues

CHICAGO --- Children who experience trauma, abuse, neglect and family dysfunction are at increased risk of having heart disease in their 50s and 60s, according to a new Northwestern Medicine study.

Results from the study showed people exposed to the highest levels of childhood family environment adversity were more than 50 percent more likely to have a cardiovascular disease event such as a heart attack or stroke over a 30-year follow-up.

The longitudinal study of more than 3,600 participants is among the first to describe the trajectory of cardiovascular disease and death based on family environment ratings from young adulthood into older middle age.

The findings were published today, April 28, in the Journal of the American Heart Association.

Children who experience this type of adversity are predisposed to higher rates of lifelong stress, smoking, anxiety, depression and sedentary lifestyle that persist into adulthood. These can lead to increased body mass index (BMI), diabetes, increased blood pressure, vascular dysfunction and inflammation.

"This population of adults is much more likely to partake in risky behaviors - for example, using food as a coping mechanism, which can lead to problems with weight and obesity," said first author Jacob Pierce, a fourth-year medical student at Northwestern University Feinberg School of Medicine. "They also have higher rates of smoking, which has a direct link to cardiovascular disease."

Adults who were exposed to these risk factors as children may benefit from counseling on the link between coping with stress and controlling smoking and obesity, but more research is needed, Pierce said.

"Early childhood experiences have a lasting effect on adult mental and physical well-being, and a large number of American kids continue to suffer abuse and dysfunction that will leave a toll of health and social functioning issues throughout their lives," said senior author Joseph Feinglass, research professor of medicine and of preventive medicine at Feinberg. "Social and economic support for young children in the United States, which is low by the standards of other developed countries, has the biggest 'bang for the buck' of any social program."

The study used the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort that has followed participants from recruitment in 1985-1986 through 2018, to determine how childhood psychosocial environment relates to cardiovascular disease incidence and mortality in middle age.

To get a broad idea of what a study participant's family environment was like during their childhood, participants answered survey questions that asked questions such as, "How often did a parent or other adult in the household make you feel that you were loved, supported, and cared for?" or "How often did a parent or other adult in the household swear at you, insult you, put you down or act in a way that made you feel threatened?"

The most predictive of cardiovascular disease later in life was "Did your family know what you were up to as a kid?" Pierce said.

While the study didn't specifically address attentiveness of parents, the findings indicate parents' involvement in their children's lives could impact their health later in life.

Credit: 
Northwestern University

How animals 'dial up' the pain they experience from certain stimuli

Scientists have - for the first time - shown how chemical triggers in the nervous system can amplify the pain experienced by mammals in response to certain stimuli.

The pain system probably evolved to alert them to life-threatening dangers. As they approach objects that are extremely hot or cold or are biting them, they experience intense pain - allowing them to get out of harm's way.

But in certain diseases, that defence mechanism malfunctions and rather than providing a short, sharp shock - it produces long-term, chronic pain, seen with some conditions affecting humans such as neuropathies, arthritic pains or migraines.

Researchers at the University of Leeds, in collaboration with colleagues in the US and China, have discovered that, under certain conditions, the molecular sensors that make nerves respond to physical stimuli can be turbo charged - to intensify the electrical signals reaching the brain. The brain interprets those signals as pain.

In animal studies using rat nerve cells, they found that the normal chemical messaging system utilized by the nerves to detect heat and involving calcium ions as 'messengers' was supplemented by what is known as the calcium-activated chlorine channel. It is this combination that amplifies the electrical signal to the brain.

Their research findings are published today (28/4) in the journal Science Signaling.

The research team used a technique called super-resolution microscopy which allowed them to see in exceptional detail the interaction of the molecules involved in nerve signalling.

Nikita Gamper, Professor of Neuroscience in the Faculty of Biological Sciences at Leeds, supervised the research. He said: "Our findings show how environmental threats are detected and then processed by the nervous system.

"And of course, this understanding is also important for us to be able to combat the flip side of the pain sensation - when people begin to experience pain that is no longer protective or beneficial, such as pain from inflammation, cancer and many other conditions.

"These are conditions that damage the quality of life experience by many people."

This pain amplification mechanism happens in the peripheral nervous system which feeds into - but is separate from - the central nervous system, made up of the spinal column and brain. For Professor Gamper, that division opens-up the possibility that drug therapies to reduce chronic pain could be targeted on the peripheral nervous system rather than the brain.

He said: "The painkillers that we currently use act on the central nervous system and brain. Developing painkillers that work on brain function is very hard because the brain is a complex organ and although you might solve one problem, you often get unwanted side effects.

"Opioids are standard analgesics, but they are highly addictive. Therapies based on the peripheral nervous system would potentially have less effect on the brain."

Although the study was conducted on nerve cells from rats and the applicability to the human nervous system is yet to be confirmed, there are reasons to believe that while there is a big difference between the human and rat brains, the peripheral nervous systems bear much closer similarity.

Credit: 
University of Leeds

How animals 'dial up' the pain they experience from certain stimuli

Scientists have - for the first time - shown how chemical triggers in the nervous system can amplify the pain experienced by mammals in response to certain stimuli.

The pain system probably evolved to alert them to life-threatening dangers. As they approach objects that are extremely hot or cold or are biting them, they experience intense pain - allowing them to get out of harm's way.

But in certain diseases, that defence mechanism malfunctions and rather than providing a short, sharp shock - it produces long-term, chronic pain, seen with some conditions affecting humans such as neuropathies, arthritic pains or migraines.

Researchers at the University of Leeds, in collaboration with colleagues in the US and China, have discovered that, under certain conditions, the molecular sensors that make nerves respond to physical stimuli can be turbo charged - to intensify the electrical signals reaching the brain. The brain interprets those signals as pain.

In animal studies using rat nerve cells, they found that the normal chemical messaging system utilized by the nerves to detect heat and involving calcium ions as 'messengers' was supplemented by what is known as the calcium-activated chlorine channel. It is this combination that amplifies the electrical signal to the brain.

Their research findings are published today (28/4) in the journal Science Signaling.

The research team used a technique called super-resolution microscopy which allowed them to see in exceptional detail the interaction of the molecules involved in nerve signalling.

Nikita Gamper, Professor of Neuroscience in the Faculty of Biological Sciences at Leeds, supervised the research. He said: "Our findings show how environmental threats are detected and then processed by the nervous system.

"And of course, this understanding is also important for us to be able to combat the flip side of the pain sensation - when people begin to experience pain that is no longer protective or beneficial, such as pain from inflammation, cancer and many other conditions.

"These are conditions that damage the quality of life experience by many people."

This pain amplification mechanism happens in the peripheral nervous system which feeds into - but is separate from - the central nervous system, made up of the spinal column and brain. For Professor Gamper, that division opens-up the possibility that drug therapies to reduce chronic pain could be targeted on the peripheral nervous system rather than the brain.

He said: "The painkillers that we currently use act on the central nervous system and brain. Developing painkillers that work on brain function is very hard because the brain is a complex organ and although you might solve one problem, you often get unwanted side effects.

"Opioids are standard analgesics, but they are highly addictive. Therapies based on the peripheral nervous system would potentially have less effect on the brain."

Although the study was conducted on nerve cells from rats and the applicability to the human nervous system is yet to be confirmed, there are reasons to believe that while there is a big difference between the human and rat brains, the peripheral nervous systems bear much closer similarity.

Credit: 
University of Leeds

Glacier detachments: A new hazard in a warming world?

image: View into the detachment zone: Flat Creek glacier used to occupy the central trough visible in the image. Within just a few years, the surrounding ice flowed into space previously filled by the glacier, masking the full extent of the damage left by the detachments. Wrangell-St. Elias National Park and Preserve.

Image: 
Photo Mylène Jacquemart.

Boulder, Colo., USA: On the evening of 5 August 2013, a startling event occurred deep in the remote interior of the United States' largest national park. A half-kilometer-long tongue of Alaska's Flat Creek glacier suddenly broke off, unleashing a torrent of ice and rock that rushed 11 kilometers down a rugged mountain valley into the wilderness encompassed by Wrangell-St. Elias National Park and Preserve.

After National Park Service geologist Michael Loso documented a similar event in the same location in 2015, he recruited Mylène Jacquemart, a Ph.D. student at the University of Colorado Boulder, to investigate. "We were aware of glacier detachments that had happened in Tibet, Russia, and Argentina, but started out thinking we were investigating a regular landslide," says Jacquemart. "Then we noticed that the entire glacier was missing."

The results, published in Geology, indicate the Alaskan detachments occurred at the height of the summer melt seasons and suggest these highly destructive events could occur more frequently in a warming world.

After National Park Service geologist Michael Loso conducted preliminary research that ruled out a seismic trigger for these events, he, Jacquemart, and other experts began a research project to investigate what had happened at Flat Creek. The team used a variety of tools, including satellite imagery, field measurements, digital elevation models, and meltwater modeling, to piece together the sequence of events. "This project was a real sleuthing challenge," says Jacquemart, "and the pieces finally fell into place when we discovered the bulge on the Flat Creek glacier."

Although the researchers were aware that an odd ice bulge existed on the glacier's tongue prior to the first detachment in 2013, it wasn't until they obtained 10-year-old, high-resolution satellite images and estimated that the bulge was an impressive 70 meters high that they began to understand its implications. "Our data indicate that the lowermost part of the glacier tongue was very thin, stagnant, and firmly frozen to the glacier bed," Jacquemart says. "We believe this frozen tongue did two things: it blocked ice flowing down from higher on the glacier, forcing it to bulge; and it slowed meltwater drainage, allowing the water to pool under the glacier." The resulting increase in subglacial water pressure, she says, eventually caused the glacier tongue to suddenly detach, resulting in two mass flows so large that they each buried about 3 square kilometers of 400-year-old forest.

Glaciers are primarily disappearing as a result of their ice melting at a faster pace, says Jacquemart. "But the new insights we're gaining from places like Flat Creek show that we also need to consider new processes we weren't previously aware of." Ultimately, says Jacquemart, scientists will need to develop a better understanding of these new processes and potentially reevaluate hazard assessments in mountain communities.

"Flat Creek is fortunately in a very remote place," says Jacquemart, "but the detachments that occurred in Russia and Tibet claimed numerous lives." Given that the mass flows produced by glacier detachments appear to travel quite far, she says, emergency planners also need to consider possible cascading hazards, such as the temporary damming of a river followed by the water's release. "Suddenly, a remote event can have far-reaching impacts downstream," says Jacquemart.

The similarity of the glacier detachments in Alaska with those that occurred in Tibet suggest that all of these events shared a common cause. Other detachments elsewhere in the world have also been recently discovered, says Jacquemart, suggesting that large-scale glacier detachments may be exacerbated by global warming. "We conclude that the meltwater produced by increasingly warmer summers has the potential to create unexpected consequences in the form of hazards that we didn't previously know about", says Jacquemart, "and that we are only just beginning to understand."

Credit: 
Geological Society of America

Study reveals pharmacy-level barriers to treatment for opioid use disorder in Appalachian Kentucky

image: Young worked with Trish Freeman, director of the Center for the Advancement of Pharmacy Practice in the UK College of Pharmacy, to interpret the study results.

Image: 
Pete Comparoni, University of Kentucky Public Relations & Strategic Communications

LEXINGTON, Ky. (April 28, 2020) - A new study led by University of Kentucky researcher April Young and Emory University researcher Hannah Cooper shows that a number of pharmacies in the Appalachian region of Kentucky are limiting the dispensing of buprenorphine, a medication used to treat opioid use disorder (OUD). This study arose from work funded by the Kentucky Communities and Researchers Engaging to Halt the Opioid Epidemic (CARE2HOPE) grant, led by Young and Cooper.

Published in the International Journal of Drug Policy, the study looked at buprenorphine dispensing practices in 12 Kentucky counties. The research team interviewed 14 pharmacists operating 15 pharmacies throughout these counties to explore dispensing practices and perceived influences on these practices and teamed up with Trish Freeman, director of the Center for the Advancement of Pharmacy Practice in the UK College of Pharmacy, to interpret the results.

Buprenorphine is in a class of drugs known as a mixed opioid agonist/antagonist. Also known as an opioid analgesic, it provides pain relief but additionally stops the symptoms caused by other opioids. Buprenorphine is an effective medication to treat OUD, yet studies show that fewer than two in 10 people with opioid use disorder receive any treatment.

Results showed that 12 of the 15 pharmacies limited buprenorphine dispensing in several ways. Analysis of the interviews showed three major factors in the limiting of buprenorphine dispensing, including concerns about exceeding a Drug Enforcement Administration (DEA) cap on opioid dispensing, distrust of pharmaceutical companies and prescribers of opioid analgesics, and a general stigma against people who use drugs and/or against the medications to treat substance use disorder.

In an effort to reduce fraudulent opioid prescribing and dispensing, the DEA has established rules requiring pharmaceutical wholesalers to monitor and report any "suspicious" orders of controlled substances they receive from pharmacies. In response, pharmaceutical wholesalers have developed algorithms that will flag a pharmacy for investigation if they place a "suspicious" order for a controlled substance - for example, an order of unusual size or frequency or that deviates substantially from a normal pattern.

Because buprenorphine is classified as a controlled substance, it is subject to this monitoring. As a result of these policies, many pharmacies are afraid to stock it or are reluctant to increase the amount they typically order to avoid raising any red flags.

"Unfortunately, the wholesalers' algorithms are proprietary, which means we don't know the specifics of what types of controlled substance orders may trigger an investigation," said April Young, associate professor of epidemiology in the UK College of Public Health and faculty member of UK's Center on Drug and Alcohol Research. "Moving forward, we recommend that buprenorphine be removed from opioid monitoring systems, and if it must be tracked, it should be tracked separately."

Ultimately, the researchers note that all the initiatives that are underway to increase buprenorphine prescribing must also come with policy changes that help increase dispensing of the life-saving medication.

As one pharmacist quoted in the study noted, "You can have all the funding in the world to have all these programs to [prescribe] all of these medicines. If your pharmacies can't physically get it [from the wholesalers], it ain't doing no good."

Credit: 
University of Kentucky

Potential autism biomarker found in babies, Stanford-led study reports

A biological marker in infants that appears to predict an autism diagnosis has been identified in a small study led by researchers at the Stanford University School of Medicine.

The study of 33 individuals showed that the biomarker, a hormone called vasopressin, was present at lower levels during infancy in the cerebrospinal fluid of babies who were later diagnosed with autism than those who were not. CSF surrounds the brain and spinal cord.

The results will be published April 27 in the Proceedings of the National Academy of Sciences.

"When young children aren't appropriately processing basic social stimuli early in life, it puts their brains on a different developmental trajectory," said Karen Parker, PhD, associate professor of psychiatry and behavioral sciences. Although autism can be diagnosed from behavioral symptoms around 2 years of age, shortages of autism specialists often delay diagnosis until age 4 or later, causing children to miss the benefits of early treatment. "If we could identify these children earlier, we could intervene earlier," Parker said.

The study's lead author is Ozge Oztan, PhD, a research scientist in psychiatry and behavioral sciences at Stanford. Parker shares senior authorship of the paper with John Constantino, MD, professor of psychiatry and pediatrics at Washington University in St. Louis.

A small protein hormone

Autism is a developmental disorder characterized by impaired social skills, repetitive behavior patterns and restricted interests. Early intervention can have lasting benefits for affected children.

Vasopressin is a protein hormone that's just nine amino acids long. It affects social behaviors in male mammals, such as pair-bonding and fathering, and differs by only two amino acids from another, better-known protein hormone with social roles: oxytocin.

Vasopressin appears to play an important role in autism. In previous research, Parker's team found that CSF levels of vasopressin are lower in children and teens with autism than in those without the disorder, and that individuals with the lowest CSF vasopressin levels had the most severe autism symptoms. CSF oxytocin levels, however, were not associated with autism. Parker's team also previously demonstrated that administering vasopressin to kids with autism improves their social ability, whereas trials of oxytocin for autism have had inconsistent results.

The new study was conducted using a rare archive of CSF samples collected from infants during routine medical care. If an infant younger than 3 months develops a fever, doctors typically collect CSF via a spinal tap to rule out brain infections. The study used CSF that was left over from such procedures and had been frozen for subsequent research purposes.

After matching 913 archived CSF samples to medical records, the researchers identified 11 infants who were later diagnosed with autism in childhood. The CSF samples from nine of them were large enough for testing. Each of these samples was compared with two control samples obtained from children whose medical records did not show an autism diagnosis by age 12.

The researchers found significantly lower CSF vasopressin levels in infants who were later diagnosed with autism than in those who were not. Individual vasopressin levels correctly predicted which children would develop autism in seven of the nine autism cases. The two samples that did not correctly predict autism were from infants who also later were diagnosed with attention deficit hyperactivity disorder. The researchers also measured oxytocin levels in the CSF samples but did not find they differed between children with and without autism.

Need for a larger study

The findings need to be replicated in a larger group, Parker said. Her team would also like to study CSF samples from children with other disorders -- such as neuromuscular diseases that have a neurologic component but do not impair social skills -- to determine whether the finding of low CSF vasopressin is specific to autism. They also hope to study whether a blood biomarker exists for autism in infants, as obtaining CSF samples is difficult.

Prior studies of infants at high risk for autism, such as those with an autistic sibling, have demonstrated that babies who later develop autism do not show behavioral symptoms very early in life. That means there is likely a window of time before symptoms first appear when behavioral therapies to maintain social responsiveness could be maximally effective, Parker said.

"If we could intervene when kids still look at faces, smile and respond to their names, that could potentially change the trajectory of the disorder," she said.

Credit: 
Stanford Medicine

New species of moths discovered in the Alps named after three famous alpinists

image: A Curved-horn moth of the genus Caryocolum feeding on a carnation plant. This genus feeds exclusively on plants in the carnation family (Caryophyllaceae).

Image: 
P. Buchner / Tiroler Landesmuseen

The discovery of new, still unnamed animal species in a well-researched European region like the Alps is always a small sensation. All the more surprising is the description of a total of three new to science species previously misidentified as long-known alpine moths.

During a genetic project of the Tyrolean State Museums in Innsbruck (Austria), Austrian entomologist and head of the Natural Science Collections Peter Huemer used an integrative research approach that relies on molecular methods to study four European moths. Despite having been known for decades, those species remained quite controversial, because of many unknowns around their biology.

At the end, however, it turned out that the scientist was not dealing with four, but seven species. The three that were not adding up were indeed previously unknown species. Therefore, Huemer described the moths in a paper in the open-access, peer-reviewed journal Alpine Entomology. Curiously, all three species were given the names of legendary alpinists: Reinhold Messner, Peter Habeler and David Lama.

Tribute to three legends in alpinism

"The idea to name the new species in honour of three world-renowned climbers was absolutely no coincidence," explains Huemer.

One of the newly described species, Caryocolum messneri, or Messner's Curved-horn moth, is dedicated to Reinhold Messner. Messner is a famous alpinist who was the first to reach Mount Everest without additional oxygen, but also the first climber to ascend all fourteen peaks over 8,000 metres. For decades, he has been inspiring followers through lectures and books. His is also the Messner Mountain Museum project, which comprises six museums located at six different locations in South Tyrol, northern Italy, where each has the task to educate visitors on "man's encounter with mountains" by showcasing the science of mountains and glaciers, the history of mountaineering and rock climbing, the history of mythical mountains, and the history of mountain-dwelling people.

"So what could have been a better fit for a name for the species that flutters on the doorstep of his residence, the Juval Castle in South Tyrol?" says Huemer.

The second new species, Caryocolum habeleri, or Habeler's Curved-horn moth, honours another extraordinary mountaineer: Peter Habeler. Having joined Messner on his expedition to Mount Everest, he also climbed this mountain without additional oxygen in a first for history. Another achievement is his climbing the famous Eiger North Face in mere 10 hours. Additionally, together with the study's author, he sits on the advisory board of the nature conservation foundation "Blühendes Österreich". However, the species' name is also a nod to Peter Habeler's cousin: Heinz Habeler, recognised as "the master of butterfly and moth research in Styria". His collection is now housed in the Tyrolean State Museums.

The third alpinist, whose name is immortalised in a species name, is David Lama, specially recognised by Huemer for his commitment to conservation. Once, in order to protect endangered butterflies along the steep railway embankments in Innsbruck, Lama took care to secure volunteers in a remarkable action. Nevertheless, Lama earned his fame for his spectacular climbing achievements. His was the first free ascent of the Compressor route on the south-eastern flank of Cerro Torre.

"Unfortunately, David lost his life far too soon in a tragic avalanche accident on 16 April 2019 in Banff National Park, Canada. Now, Caryocolum lamai (Lama's Curved-horn moth) is supposed to make him 'immortal' also in the natural sciences," says Huemer.

Many unresolved questions

The newly described moth species are closely related and belong to the genus Caryocolum of the so-called Curved-horn moths (family Gelechiidae).

As caterpillars, the species of this genus live exclusively on carnation plants. Even though the biology of the new moths is still unknown, because of their collection localities, it could be deduced that plants such as the stone carnation are likely their hosts. All species are restricted to dry and sunny habitats and sometimes inhabit altitudes of up to 2,500 m. So far, they have only been observed with artificial light at night.

While Messner's Curved-horn moth occurs from northern Italy to Greece, the area of ??Habeler´s Curved-horn Moth is limited to the regions between southern France, northern Switzerland and southeastern Germany. On the other hand, Caryocolum lamai, only inhabits a small area in the western Alps of Italy and France.

Research on alpine butterflies and moths has been an important scientific focus at the Tyrolean state museums for decades. In 30 years, Peter Huemer discovered and named over 100 previously unknown to science species of lepidopterans. All these new discoveries have repeatedly shown the gaps in the study of biodiversity, even in Central Europe.

"How could we possibly protect a species that we don't even have a name for is one of the key questions for science that derives from these studies," says Huemer in conclusion.

Credit: 
Pensoft Publishers

Disappearance of animal species takes mental, cultural and material toll on humans

For thousands of years, indigenous hunting societies have subsisted on specific animals for their survival. How have these hunter-gatherers been affected when these animals migrate or go extinct?

To answer this and other questions, Tel Aviv University (TAU) researchers conducted a broad survey of several hunter-gatherer societies across history in a retrospective study published on January 30 in Time and Mind. The study, led by Eyal Halfon and Prof. Ran Barkai of TAU's Department of Archeology and Ancient Near Eastern Cultures, sheds new light on the deep, multidimensional connection between humans and animals.

"There has been much discussion of the impact of people on the disappearance of animal species, mostly through hunting," explains Halfon. "But we flipped the issue to discover how the disappearance of animals -- either through extinction or migration -- has affected people."

The research reveals that these societies expressed a deep emotional and psychological connection with the animal species they hunted, especially after their disappearance. The study will help anthropologists and others understand the profound environmental changes taking place in our own lifetimes.

Halfon and Prof. Barkai conducted a survey of different historical periods and geographical locations, focusing on hunter-gatherer societies that hunted animals as the basis for their subsistence. They also investigated situations in which these animals became extinct or moved to more hospitable regions as a result of climate change.

"We found that humans reacted to the loss of the animal they hunted -- a significant partner in deep, varied and fundamental ways," Halfon says.

The new research explores hunter-gatherer societies throughout human history, from those dating back hundreds of thousands of years to modern-day societies that still function much the way prehistoric groups did. Ten case studies illustrate the deep connection -- existential, physical, spiritual and emotional -- between humans and animals they hunted.

"Many hunter-gatherer populations were based on one type of animal that provided many necessities such as food, clothing, tools and fuel," Prof. Barkai says. "For example, until 400,000 years ago prehistoric humans in Israel hunted elephants. Up to 40,000 years ago, residents of Northern Siberia hunted the woolly mammoth. When these animals disappeared from those areas, this had major ramifications for humans, who needed to respond and adapt to a new situation. Some had to completely change their way of life to survive."

According to the study, human groups adapted in different ways. Siberian residents seeking sustenance after the disappearance of mammoths migrated east and became the first settlers of Alaska and northern Canada. Cave dwellers in central Israel's Qesem Cave (excavated by Prof. Barkai) hunted fallow deer, far smaller than elephants, which required agility and social connections instead of robust physical strength. This necessitated far-reaching changes in their material and social culture and, subsequently, physical structure.

Halfon stresses the emotional reaction to an animal group's disappearance. "Humans felt deeply connected to the animals they hunted, considering them partners in nature, and appreciating them for the livelihood and sustenance they provided," he says. "We believe they never forgot these animals -- even long after they disappeared from the landscape."

An intriguing example of this kind of memory can be found in engravings from the Late Paleolithic period in Europe, which feature animals like mammoths and seals. Studies show that most of these depictions were created long after these two animals disappeared from the vicinity.

"These depictions reflect a simple human emotion we all know very well: longing," says Halfon. "Early humans remembered the animals that disappeared and perpetuated them, just like a poet who writes a song about his beloved who left him."

According to Prof. Barkai, another emotional response was a sense of responsibility -- even guilt. "Indigenous hunter-gatherer societies have been very careful to maintain clear rules about hunting. As a result, when an animal disappears, they ask: 'Did we behave properly? Is it angry and punishing us? What can we do to convince it to come back?'" he concludes. "Such a reaction has been exhibited by modern-day hunter-gatherer societies as well."

Credit: 
American Friends of Tel Aviv University

3D tissue models provide unprecedented insight into human brain function and disease

Bethesda, MD - Researchers have created 3D tissue structures that recapitulate many aspects of specific human brain regions. These tiny, brain-region specific spheroids are allowing scientists to study previously inaccessible aspects of human brain development and function.

"Truly understanding the processes involved in development, assembly and dysfunction of the human brain has been difficult because we can't directly investigate or manipulate functioning human brain tissue," said Sergiu P. Pasca from Stanford University. "To overcome this challenge, we developed a way to create self-organizing 3D tissue structures from pluripotent stem cells derived noninvasively from a single patient."

Pasca and colleagues have shown that these brain-region specific spheroids can be maintained for years, which allows the study of advanced stages of brain maturation and function.

Pasca, the recipient of the 2020 C.J. Herrick Award in Neuroanatomy, was scheduled to present this research at the American Association for Anatomy annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

The researchers have used the new stem-cell derived 3D platform to create organoids resembling several brain regions. For example, spheroids resembling the cerebral cortex show many features of in utero neural development.

"Moreover, we have demonstrated that regionalized brain spheroids can be put together to form fused structures called brain assembloids," said Pasca. "The assembloids can then be used to investigate developmental processes that were previously inaccessible such as cell migration, long-distance connections and the formation of neural circuits."

The researchers are now using the organoids to study neuropsychiatric diseases such as a rare form of autism known as Timothy syndrome and to examine the cellular and molecular consequences of mutations associated with neuropsychiatric disorders.

Credit: 
Experimental Biology

Warming climate undoes decades of knowledge of marine protected areas

image: A recovering reef in Seychelles.

Image: 
Nick Graham, Lancaster University

Climate change and warming seas are transforming tropical coral reefs and undoing decades of knowledge about how to protect these delicate and vital ecosystems.

Many of the world's coral reefs are seeing biodiversity plunge in the face of repeated coral bleaching events.

Protected areas, called marine reserves, are an effective and long-established tool in the conservation toolbox. Marine reserves have been used for decades to enhance biodiversity and fish biomass by preventing damage and over-exploitation by fishing.

However, a new study highlights that tropical coral reef marine reserves can offer little defence in the face of climate change impacts. And the changes that are being observed will force scientists, conservationists and reserve managers to rethink the role these protected areas can bring.

"Climate change is so fundamentally changing the structure and composition of coral reef ecosystems, that the way the ecosystem functions and responds to common management and conservation approaches needs to be carefully re-evaluated," explains Professor Nick Graham of Lancaster University and lead author of the study. "The rules we have come to rely on, no longer apply."

Bleaching occurs when seas become too warm, causing corals to expel their colourful algae. This disrupts the ecosystem and reduces the availability of food and shelter for many fish species.

Some coral reefs are able to recover over time, while others are transformed and become dominated by seaweed.

The new study, published in the journal Nature Communications, focused on reefs and marine reserves in Seychelles. Coral reefs in Seychelles were badly affected by a bleaching event in 1998, when around 90% of the coral died. Scientists used data from 21 reefs over a 20-year time period, spanning the 1998 bleaching event, to explore how reefs have changed and how this has affected the role of marine reserves.

Professor Graham explains: "Our long-term records of Seychelles' coral reefs show that before the bleaching event marine reserves contained high coral cover, a very biodiverse range of fish, and high biomass of carnivorous and herbivorous fish.

"Following the bleaching event, the role of the marine reserves changed substantially. They no longer supported higher coral cover compared to adjacent fished areas, and their role in enhancing biodiversity decreased. Plant-loving fish, such as rabbitfish and parrotfish, dominated fish communities. This was the case for reefs where corals were recovering, as well as reefs transformed and dominated by seaweed."

Reduced numbers of carnivorous predators, such as grouper and snapper species, show reserves are much less effective at protecting the tops of food webs in the years following bleaching events. These population drops are likely due to fewer fish for them to prey on after the loss of coral reef structures.

Dr Shaun Wilson, of the Department of Biodiversity, Conservation and Attractions in Western Australia, a co-author on the study, said: "Despite these climate-driven transformations, marine protected areas still have a role to play in ocean conservation. It is encouraging that marine reserves continue to protect some species, especially when these species are critical for local fisheries."

Gilberte Gendron of the Seychelles National Parks Authority, adds: "Although these reordered marine reserves are less biodiverse, they are still important to maintain. This is because, when compared to openly fished areas, they still protect higher levels of fish biomass of species that are important to our local fisheries. For example, the protected herbivorous fish can spill out into openly fished areas and help support adjacent fisheries."

If the goal is to protect biodiversity then it may be better to target new marine reserves around those coral reefs where the rate of warming is slowest, or those where recovery from bleaching is more likely.

While the scientists say marine reserves still have an important role to play in protecting fish biomass, they call in their paper for urgent reductions in global greenhouse gas emissions, as well as other pressures such as poor land practices that input nutrients and pollutants to coastal waters, to protect tropical coral reefs.

Credit: 
Lancaster University

Paleontologists reveal 'the most dangerous place in the history of planet Earth'

image: Predator paradise - The giant predatory dinosaur Carcharodontosaurus eyes a group of Elosuchus - crocodile-like hunters - near a carcass. Artwork by Davide Bonadonna

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Artwork by Davide Bonadonna

100 million years ago, ferocious predators, including flying reptiles and crocodile-like hunters, made the Sahara the most dangerous place on Earth.

This is according to an international team of scientists, who have published the biggest review in almost 100 years of fossil vertebrates from an area of Cretaceous rock formations in south-eastern Morocco, known as the Kem Kem Group.

The review, published in the journal ZooKeys, "provides a window into Africa's Age of Dinosaurs" according to lead author Dr Nizar Ibrahim, an Assistant Professor of Biology at the University of Detroit Mercy and Visiting Researcher from the University of Portsmouth.

About 100 million years ago, the area was home to a vast river system, filled with many different species of aquatic and terrestrial animals. Fossils from the Kem Kem Group include three of the largest predatory dinosaurs ever known, including the
sabre-toothed Carcharodontosaurus (over 8m in length with enormous jaws and long, serrated teeth up to eight inches long) and Deltadromeus (around 8m in length, a member of the raptor family with long, unusually slender hind limbs for its size), as well as several predatory flying reptiles (pterosaurs) and crocodile-like hunters. Dr Ibrahim said: "This was arguably the most dangerous place in the history of planet Earth, a place where a human time-traveller would not last very long."

Many of the predators were relying on an abundant supply of fish, according to co-author Professor David Martill from the University of Portsmouth. He said: "This place was filled with absolutely enormous fish, including giant coelacanths and lungfish. The coelacanth, for example, is probably four or even five times large than today's coelacanth. There is an enormous freshwater saw shark called Onchopristis with the most fearsome of rostral teeth, they are like barbed daggers, but beautifully shiny."

Researchers from the Universities of Detroit, Chicago, Montana, Portsmouth (UK), Leicester (UK, David Unwin), Casablanca (Morocco), and McGill (Canada), as well as the Paris Museum of Natural History, have produced the first detailed and fully illustrated account of the fossil-rich escarpment, previously known as the "Kem Kem beds". The researchers now define this sedimentary package as the Kem Kem Group, which consists of two distinct formations, the Gara Sbaa Formation and the Douira Formation.

To assemble the huge datasets and fossil images, which were originally included in his PhD thesis, Dr Ibrahim visited Kem Kem collections on several continents.

Shedding light on Africa's ancient past is important says Professor Martill, "This is the most comprehensive piece of work on fossil vertebrates from the Sahara in almost a century, since the famous German palaeontologist Ernst Freiherr Stromer von Reichenbach published his last major work in 1936."

Credit: 
University of Portsmouth

A 'corset' for the enzyme structure

image: Tobias Hett (left) and Nico Fleck (right) at the spectrometer in the laboratory of the Institute of Physical and Theoretical Chemistry at the University of Bonn.

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© Foto: Hamed Alaei

The structure of enzymes determines how they control vital processes such as digestion or immune response. This is because the protein compounds are not rigid, but can change their shape through movable "hinges". The shape of enzymes can depend on whether their structure is measured in the test tube or in the living cell. This is what physicochemists at the University of Bonn discovered about YopO, an enzyme of the plague pathogen. This fundamental result, which has now been published in the journal Angewandte Chemie, is potentially also of interest for drug research.

All living cells contain proteins, which are essential for the maintenance of body functions. Proteins consist primarily of amino acids and, as catalysts (enzymes), enable biochemical reactions that would otherwise not take place. Enzymes control for example the digestion and the immune system. "The type of biochemical reactions and how they occur depends on the structure of the proteins," says Prof. Dr. Olav Schiemann from the Institute of Physical and Theoretical Chemistry at the University of Bonn. Proteins are not rigid, but can change their shape through movable "hinges". This interplay between structure and dynamics determines what happens. The enzyme and the substance to be transformed must fit together like a key and lock in order to catalyze a specific process.

YopO is anchored in the membrane and therefore particularly stable

The scientists used a protein from plague pathogens (Yersinia) for their research. These trick the immune system by injecting proteins such as YopO (Yersinia outer protein O) into the attacking macrophages. YopO binds to the actin of the defending cells, causing the immune cells to no longer be able to envelop and digest the pathogens. "We used YopO because this enzyme is medically interesting and can be anchored or immobilized in a membrane," explains Schiemann. "The latter is an important prerequisite for our measurements at room temperature."

Nico Fleck from Schiemann's research group developed spin labels for this purpose that were specifically adapted to investigations within the cell. These are tiny "flags" that team member Caspar A. Heubach attached to different positions of the protein. Using the DQC (Double Quantum Coherence) method, which works like a ruler at the molecular level, team member Tobias Hett then measured the distances between the flags. "If we know the distances between the spin labels, we can deduce which structures a certain enzyme is able to assume," says Hett. This works somewhat like a "sat nav" for molecules; after all, the guidance system for vehicles is also based on distance measurements.

The researchers applied the DQC method to YopO in the test tube and, for comparison, in eggs of the African clawed frog, which are frequently used as model organisms in science. For the measurements in the cell, the YopO tagged with the flags was injected into the eggs with a syringe, "very similar to the way the plague pathogens do at the molecular level," explains Nico Fleck. This showed that YopO was able to take up a larger number of different structures when in aqueous solution in the test tube than in the eggs. "YopO is structurally more mobile in the test tube than in living cells," says Schiemann. "In cells, structures such as membranes and interactions with other proteins reduce the structural diversity of YopO."

Fundamental principle

This finding not only applies to YopO, but is a fundamental principle: In the test tube there is no "corset" imposed by other cell structures, the unfolding possibilities for enzymes are greater. The researchers believe that this has consequences for all studies involving biomolecules. "Investigations of the isolated biomolecules are certainly essential. For a complete picture, however, such structures and dynamics should be studied under as natural conditions as possible," says Schiemann. Caspar Heubach adds: "If the results of a study refer to biomolecular processes in cells, one should, as in this case, also investigate the structure and dynamics of proteins in living cells."

Results are interesting for pharmaceutical research

As proteins control different cellular processes, they are also the focus of the search for new treatments. The researchers are therefore confident that the results presented by the research team at the University of Bonn are also of potential interest for pharmaceutical research. "The interactions in the cell are important for the structure and dynamics of proteins," says Schiemann. "It therefore makes a difference how the structure of enzymes is determined in the search for active substances."

Credit: 
University of Bonn

Adsorbent material developed with PET bottles for the removal of antibiotics from water

image: The KIST research team extracted high-purity organic ligand from PET waste bottles and used it to synthesize a high-efficiency adsorbent material that could effectively remove antibiotics from water in an environmentally and economically beneficial way. During the development of this adsorbent material, an alkaline hydrolysis process was used to induce a neutralization reaction, resulting in the production of a high-purity terephthalic acid.

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Korea Institute of Science and Technology (KIST)

South Korea with its high antibiotic use is categorized as a country at high risk of the emergence of *multi drug-resistant bacteria, or so-called "super bacteria." According to the Ministry of Environment, antibiotic substances have been detected at livestock wastewater treatment facilities, sewage treatment plants, and in rivers.

*Multi drug-resistant bacteria: Bacteria resistant to different antibiotics. Also called super-bacteria.

The Korea Institute of Science and Technology announced that a research team, led by researchers Jung Kyung-won and Choi Jae-woo, at KIST's Water Cycle Research Center, has developed a high-efficiency, adsorbent material using PET waste bottles. The new material is expected to help solve the problem of environmental toxins and antibiotic-resistant bacteria which are caused by leaks of antibiotics into water.

Currently, the most well-known method of effectively removing antibiotics from water uses porous carbon composite, synthesized by pyrolyzing **metal-organic frameworks(MOF). Porous carbon composites adsorb antibiotics in the water, thereby removing them. However, since the ***organic ligand generally used to synthesize MOF is very expensive, the cost is a major obstacle to this method's widespread, practical application through mass production.

**Metal-organic frameworks(MOF): Crystalline porous substances bonded in two or three dimensions through a coordination bond between metal ions and organic ligand

***Organic ligand: Essential element for the syntheses of MOF. Serves to link metal ions.

In order to develop a more cost-effective solution, the KIST research team turned its attention to the PET bottles that people use in their everyday lives. PET is a high-molecular compound obtained by polymerizing ethylene glycol and terephthalic acid, the latter of which is used as organic ligand for the syntheses of MOF. The KIST research team extracted high-purity organic ligand from PET waste bottles and used it to synthesize a high-efficiency adsorbent material that could effectively remove antibiotics from water in an environmentally and economically beneficial way.

During the development of this adsorbent material, an alkaline hydrolysis process was used to induce a neutralization reaction, resulting in the production of a high-purity terephthalic acid. To maximize the efficiency of the alkaline hydrolysis process, the research team incorporated an ultrasound-assisted ****phase transfer catalyst process. By optimizing this process, the team was able to successfully extract 100% high-purity terephthalic acid, which they then used to develop a porous carbon composite. Iron-based MOF was used as a precursor in order to impart magnetism to the adsorbent material. In this way, the team was able to develop an eco-material that can be easily separated from the mixture after the adsorption process, using an external magnetic field.

****Phase transfer catalyst: When two different phases coexist, a phase transfer catalyst that facilitates the transport of a reactant from one phase to the other.

The KIST research team tested the efficiency of the porous carbon composite in terms of its ability to adsorb "tetracycline," or the antibiotic used to treat bacterial infections, from the water. Tests showed that the newly developed material was able to remove 100% of the tetracycline in about 90 minutes under general water conditions (pH 6), with an adsorption rate of 671.14 mg/g, which is a rate superior to that of previously developed adsorbents. In order to assess the reusability of the porous carbon composite, the adsorption-desorption process was conducted five times. Even after repeated use, the material maintained 90% of its adsorption properties, indicating a high degree of stability and wide applicability for water treatment.

Dr. Jung Kyung-won at KIST said, "This porous carbon composite is applicable to a wide range of water treatment areas as it uses waste plastics to prevent environmental pollution and maintains its high adsorption properties even after repeated use." KIST's Dr. Choi Jae-woo also commented, "The porous carbon composite developed through this research is applicable to various fields, ranging from eco-materials to energy materials, and I expect that it will soon be highly regarded as a value-added eco-material."

Credit: 
National Research Council of Science & Technology

Researchers explore ocean microbes' role in climate effects

A new study shows that "hotspots" of nutrients surrounding phytoplankton -- which are tiny marine algae producing approximately half of the oxygen we breathe every day -- play an outsized role in the release of a gas involved in cloud formation and climate regulation.

The new research quantifies the way specific marine bacteria process a key chemical called dimethylsulfoniopropionate (DMSP), which is produced in enormous amounts by phytoplankton. This chemical plays a pivotal role in the way sulfur and carbon get consumed by microorganisms in the ocean and released into the atmosphere.

The work is reported in the journal Nature Communications, in a paper by MIT graduate student Cherry Gao, former MIT professor of civil and environmental engineering Roman Stocker (now a professor at ETH Zurich, in Switzerland), in collaboration with Jean-Baptiste Raina and Professor Justin Seymour of University of Technology Sydney in Australia, and four others.

More than a billion tons of DMSP is produced annually by microorganisms in the oceans, accounting for 10 percent of the carbon that gets taken up by phytoplankton -- a major "sink" for carbon dioxide, without which the greenhouse gas would be building up even faster in the atmosphere. But exactly how this compound gets processed and how its different chemical pathways figure into global carbon and sulfur cycles had not been well-understood until now, Gao says.

"DMSP is a major nutrient source for bacteria," she says. "It satisfies up to 95 percent of bacterial sulfur demand and up to 15 percent of bacterial carbon demand in the ocean. So given the ubiquity and the abundance of DMSP, we expect that these microbial processes would have a significant role in the global sulfur cycle."

Gao and her co-workers genetically modified a marine bacterium called Ruegeria pomeroyi, causing it to fluoresce when one of two different pathways for processing DMSP was activated, allowing the relative expression of the processes to be analyzed under a variety of conditions.

One of the two pathways, called demethylation, produces carbon and sulfur based nutrients that the microbes can use to sustain their growth. The other pathway, called cleavage, produces a gas called dimethylsulfide (DMS), which Gao explains "is the compound that's responsible for the smell of the sea. I actually smelled the ocean a lot in the lab when I was experimenting."

DMS is the gas responsible for most of the biologically derived sulfur that enters the atmosphere from the oceans. Once in the atmosphere, sulfur compounds are a key source of condensation for water molecules, so their concentration in the air affects both rainfall patterns and the overall reflectivity of the atmosphere through cloud generation. Understanding the process responsible for much of that production could be important in multiple ways for refining climate models.

Those climate implications are "why we're interested in knowing when bacteria decide to use the cleavage pathway versus the demethylation pathway," in order to better understand how much of the important DMS gets produced under what conditions, Gao says. "This has been an open question for at least two decades."

The new study found that the concentration of DMSP in the vicinity regulates which pathway the bacteria use. Below a certain concentration, demethylation was dominant, but above a level of about 10 micromoles, the cleavage process dominated.

"What was really surprising to us was, upon experimentation with the engineered bacteria, we found that the concentrations of DMSP in which the cleavage pathway dominates is higher than expected -- orders of magnitude higher than the average concentration in the ocean," she says.

That suggests that this process hardly takes place under typical ocean conditions, the researchers concluded. Rather, microscale "hotspots" of elevated DMSP concentration are probably responsible for a highly disproportionate amount of global DMS production. These microscale "hotspots" are areas surrounding certain phytoplankton cells where extremely high amounts of DMSP are present at about a thousand times greater than average oceanic concentration.

"We actually did a co-incubation experiment between the engineered bacteria and a DMSP-producing phytoplankton," Gao says. The experiment showed "that indeed, bacteria increased their expression of the DMS-producing pathway, closer to the phytoplankton."

The new analysis should help researchers understand key details of how these microscopic marine organisms, through their collective behavior, are affecting global-scale biogeochemical and climatic processes, the researchers say.

Credit: 
Massachusetts Institute of Technology

Being fun is no laughing matter

image: Children and adolescents are, quite literally, fun-seekers. A new study is the first to directly tie perceptions of children who are fun with changes in peer status.

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Florida Atlantic University

With children currently cooped up at home with limited access to their friends, a new study shows just how important it is to have fun and what that means in a child's social circles. Children who are well-liked and children who are popular enjoy tremendous advantages in the peer group. After decades of research, experts know something about the characteristics of children who enjoy high status in the peer group. Children who are well-liked tend to be outgoing, assertive, prosocial, and academically competent; they are neither aggressive nor withdrawn. Children who are popular are outgoing, assertive, and prosocial or aggressive (or both); they too are not withdrawn.

What about being fun? It's a characteristic that is conspicuously missing from these lists - an omission that is odd when you consider how much time and energy children devote to having fun.

Researchers at Florida Atlantic University in collaboration with Concordia University in Montreal, Canada, find that being fun is a serious matter because it imparts special benefits on children. They recently published a first-of-its-kind longitudinal study in the Journal of Personality that explored the importance of being fun.

The purpose of the study was to examine whether children who are well-liked and children who are popular got that way by being fun to hang around with. Data from children living in Florida and children living in Colombia, South America, examined the degree to which peer perceptions of being fun predict increases in being liked by classmates and being popular with classmates. Their findings are the first to directly tie perceptions of children who are fun with changes in peer status.

The results clearly underscore the importance of being fun. Across a two-month period, primary school children perceived by classmates as someone who is fun to be around experienced an increase in the number of classmates who liked them and the number who rated them as popular. Importantly, these associations remained after removing the contribution of variables known to contribute to peer status, such as prosocial behavior, leadership, physical attractiveness, fairness, athletic ability, disruptiveness, and aggression. Being well-liked and being popular also anticipated changes in classmate perceptions of a child as fun, suggesting that, in the eyes of peers, "fun begets status and status begets fun."

"Our study is novel in that no research has unambiguously measured peer perceptions of classmates who are fun and no longitudinal studies have examined whether being fun uniquely anticipates subsequent changes in peer social status," said Brett Laursen, Ph.D., lead author and a professor in the Department of Psychology in FAU's Charles E. Schmidt College of Science. "The findings also are important because until now only prosocial behavior and leadership have been demonstrated to prospectively predict changes in both likeability and popularity."

The investigators focused on the late primary school and early middle school years, a time when peer reputations consolidate and peer status assumes outsized importance in the lives of children.

"We had good reasons to suspect that being fun would uniquely contribute to a child's social status. Obviously, fun is intrinsically rewarding. Fun peers are rewarding companions and rewarding companions enjoy higher social status than non-rewarding companions," said Laursen. "But the benefits of fun probably extend well beyond their immediate rewards. Fun experiences provide positive stimulation that promotes creativity. Being fun can protect against rejection insofar as it raises the child's worth to the group and minimizes the prospect that others will habituate to the child's presence. Finally, changes in the brain in the early middle school years increase the salience of rewards derived from novelty, in general, and fun, in particular. Children and adolescents are, quite literally, fun-seekers."

What makes a child fun? The researchers say that some children who are fun are undoubtedly equipped with a constellation of traits that combine to make them rewarding companions.

"One potential combination is surgency and ego resilience, which make the child a novel and exciting companion," said Laursen. "Fun children are probably also socially adept, and have high levels of perspective?taking and social skills."

Why does that matter? Laursen says that adults tend to forget the importance of peer status in the classroom. Being well-liked and being popular are huge assets.

"Well-liked children present few adjustment difficulties and tend to succeed where others do not," said Laursen. "Popularity is highly coveted by children and adolescents; many value it above being liked."

This finding raises the possibility of a reputational halo effect. Age-mates assume that children with high social status have desirable attributes, which may turn into a self-fulfilling prophesy as high status children are given more opportunities to have fun and thereby hone their skills around others who are fun.

The study involved two sets of children in grades 4 to 6 (ages 9 to 12): the first included 306 girls and 305 boys attending school in northern Colombia; the second included 363 girls and 299 boys attending school in southern Florida. All of the data came in the form of peer nominations - an important strategy that avoids the use of self-report data. The same pattern of results emerged in different samples, in different locations, and from different children of different ages.

Credit: 
Florida Atlantic University