Culture

Adolescents and young adults (AYA) who have survived cancer often continue to suffer from insomnia long after treatment ends, interfering with a range of daily activities. In a study published today by Pediatric Blood and Cancer, researchers at Dana-Farber Cancer Institute show that an online program developed specifically for AYA cancer survivors can significantly alleviate insomnia and improve overall quality of life.

The program, which consists of six, 20-30 minute sessions, shows how sleep habits that may have helped patients cope with their intensive cancer treatments can become obstacles to healthy sleep as survivors move beyond treatment. Its automated format makes it particularly well-suited to the moment, as telehealth and online programs that are already adopted by many hospitals and clinics, are becoming even more widely used as a result of the COVID-19 crisis.

"Cognitive-behavioral therapy for insomnia (CBT-I), which helps patients understand the behavioral and thought patterns that lead to long-term troubles with falling or staying asleep, has been shown to be very effective in adult cancer survivors. However, it has not been widely tested in the AYA survivor group. We wanted to explore whether a CBT-I program, specifically tailored to AYA survivors and available online, could be helpful in this population," said Eric Zhou, PhD, who conducted the study with Dana-Farber colleague Christopher Recklitis, PhD, MPH.

"People who survived cancer as adolescents or young adults face a variety of sleep-related issues unique to their age group," Zhou commented. "These include the constraints placed on young people's sleep schedules by their parents or disruptive roommates. Teens and young adults also undergo normal developmental changes in circadian timing, naturally going to bed later and sleeping later than younger children and older adults. Insomnia treatments for AYA cancer survivors need to take account of these factors, as well as addressing their long-term cancer-related issues such as pain or fatigue."

The insomnia intervention tested in the study is known as SHUTi (Sleep Healthy Using the Internet) was developed by researchers at the University of Virginia and adapted for AYA cancer survivors by Zhou and Recklitis. The interactive program uses text, images, and video to explain how insomnia develops and how it can be overcome. In adapting the program, Dana-Farber researchers replaced vignettes - brief stories of individuals struggling with insomnia - from the original version with ones more relatable to young people.

The program discusses how sleep behaviors that helped patients weather cancer treatment can become maladaptive when they return to normal life. "During treatment, people may stay in bed because they're not feeling well or haven't gotten enough sleep. They may take naps and their sleep at night can be fragmented," said Zhou. As people move into recovery, these habits can make it difficult to resume healthy sleep patterns.

"SHUTi trains people to recalibrate their sleep so their sleep habits are no longer addressing the problems they experienced during treatment and are, instead, focused on improving long-term sleep," Zhou remarked.

In the study, 22 AYA cancer survivors - mean age 20.4 years - with insomnia enrolled to use the specially adapted SHUTi. As part of the program, participants kept a sleep diary, tracking when they slept, and entered the information into SHUTi, which adjusted its sleep recommendations accordingly.

At eight and 16 weeks after starting to use SHUTi, participants reported a significant lessening in insomnia severity, daytime sleepiness, and fatigue, and an overall improvement in quality of life.

"Our results demonstrate that an internet-delivered CBT-I program targeting AYA cancer survivors reduced their insomnia and improved their quality of life," Recklitis remarked. "Notably, our participants' insomnia severity continued to get better after the intervention had ended, suggesting that the continued to make sleep-related decisions that helped their sleep even after they had finished using the program."

Sometimes, when something is broken, the first step to fixing it is to break it even more.

In a recent example, scientists seeking to understand the mechanism of a DNA-repairing enzyme have discovered that the molecule performs its functions by first marking and then further breaking damaged DNA. The team's surprising findings on the protein, called XPG, have provided much-needed insight into how DNA repair works in healthy cells, as well as how different mutations can translate into different diseases and cancer.

"We saw that XPG makes a beeline for discontinuous DNA - places where the hydrogen bonds between bases on each strand of the helix have been disrupted - and then it very dramatically bends the strand at that exact location, breaking the interface that connects bases stacked on top of each other," said Susan Tsutakawa, a structural biologist in the Biosciences Area at Lawrence Berkeley National Laboratory (Berkeley Lab) and first author on the work, published this month in PNAS. "The bending activity adds to an already impressive arsenal, as XPG was first identified as a DNA chopping enzyme, responsible for cutting out nucleotide bases with chemical and UV radiation damage."

Yet despite this knack for destruction, the team notes that XPG is more like a master sculptor than a demolition crew.

"An unexpected finding from our imaging data is that the flexible parts of the protein - which were previously impossible to examine - have the ability to recognize perturbations associated with many different types of DNA damage," said co-author Priscilla Cooper, a biochemist senior scientist in the Biosciences Area. "XPG then uses its sculpting properties to bend the DNA in order to recruit and load into place the proteins that can fix that type of damage."

A protein with many jobs

Although the extent of what XPG does in human cells is still only partially understood, scientists have long known that the protein is essential to human health by observing the devastating symptoms that occur when it is missing or not functioning normally. Cockayne syndrome, a disease characterized by a progressive and ultimately fatal neurological decline that begins in infancy, and xeroderma pigmentosum, a condition of varying severity characterized by extreme sun sensitivity and greatly elevated risk of skin cancer, are both known to be caused by mutations in the gene that encodes XPG.

Fascinated by its many roles, Tsutakawa, Cooper, and John Tainer, the director of structural biology at the University of Texas MD Anderson Cancer Center and visiting faculty in the Biosciences Area, have been collaborating on studies of XPG for 20 years. The trio, and their many colleagues, pool their expertise in structural biology, molecular imaging, biochemistry, and cell biology so that they can map the protein's structure and interpret how its three-dimensional form interacts with DNA and other proteins. They had previously discovered that XPG often binds to damaged DNA without engaging its DNA cutting activity, but could not examine the protein in great enough detail to find out what it actually does in these instances.

After many years spent developing technology that could catch up with their ambitions, the team was finally able to build a precise model of XPG's catalytic core - the region responsible for the DNA cutting activity - and produce images of the large, multiple-unit molecule's overall structure using a trifecta of cutting-edge imaging technology.

They performed X-ray crystallography at Stanford Synchrotron Radiation Laboratory, and small angle X-ray scattering (SAXS) at the SIBYLS beamline of Berkeley Lab's Advanced Light Source. SAXS is a technique that has recently evolved to allow scientists to analyze flexible molecules moving freely between their natural states rather than in static or frozen conformations, as necessitated by crystallography. Such an approach is sorely needed for a protein like XPG, whose catalytic core is only one-quarter of the total structure and the rest is made of highly flexible "disordered" regions with no default shape.

To visualize the XPG-bound DNA, the scientists recruited Jack Griffith, a pioneer of rotary shadowing electron microscopy at the Lineberger Comprehensive Cancer Center at UNC Chapel Hill. Rotary shadowing electron microscopy allows direct visualization of individual DNA molecules with proteins bound to them, including how they were bent by XPG.

"The ability to see the shapes of individual DNA molecules gave us an essential clue as to how XPG works to identify and process damaged DNA," said Griffith, a professor of biochemistry and biophysics and expert in protein-DNA interactions.

The electron microscopy imaging also provided visual evidence supporting the scientists' previous surprising finding that XPG plays a role in homologous recombination - a DNA repair process frequently used by cells to fix dangerous double-strand breaks before replication. This means that XPG could be at the right place to help known homologous recombination proteins such as BRCA1 and BRCA2, defects in which are known to cause cancer.

Meanwhile, crystallography performed on the catalytic core shed light on how inherited patient mutations in the gene for XPG can translate into severe protein dysfunction and different diseases. The team made and tested catalytic core proteins having each of the 15 known point mutations that cause either xeroderma pigmentosum or Cockayne syndrome, and found that these single amino acid substitutions can destabilize the entire protein, but to different extents. The properties of the residual mutant protein will determine which disease results. "This structure helps us understand the distinction between the two diseases," said Cooper, "and it reinforces how complex the protein is."

Invigorated by the new information, the team has already begun a study looking at XPG's role in different cancers, as well as a follow-up structural study of the protein's disordered regions to learn more about its DNA sculpting properties.

"The superb technical and collaborative strengths of Berkeley Lab and our partners made this multi-disciplinary breakthrough feasible," noted Tainer.

"But we would also like to highlight the contribution of patients and patients' families," added Tsutakawa. "So much of what we have discovered was made possible by them choosing to share their DNA sequences with the scientific community."

The severity of knee joints damage in soccer players depends on their age and career duration, and the condition of articular cartilage and meniscus of the dominant (which has a higher mechanical load) and the non-dominant leg does not differ. However, even pronounced changes can be asymptomatic and do not impair knee joint mobility, as shown by a group of scientists, which included researchers from the Sechenov University. The findings which will help interpret the results of players clinical examination more accurately, were published in Sports Medicine - Open.

Regular strenuous training is not harmless for professional athletes. They often get injured and, as previous research shows, pathological joint changes are more common than among people of the same age who are not active in sports. Legs experience the major mechanical load in soccer. The dominant, kicking leg is particularly subject to uneven strain and, thus, injuries.

The authors of the study evaluated whether the prevalence and severity of joint damage depends on the age and experience of athletes, as well as if there is any difference in knee injuries between the dominant and the non-dominant leg. They examined 47 professional soccer players aged 19-31. The sample did not include goalkeepers, athletes who previously underwent knee surgery or those who suffered a knee injury in the past three months or were experiencing joint pain at the time of the examination.

Participants were divided into two groups: one included athletes who played soccer for more than 20 years (including sports schools and groups), and the other comprised less experienced players. MRI was used to examine the joints and allowed to obtain the high-resolution images of the joint structures and evaluate the changes in bone and cartilage tissues.

The imaging showed that absolutely all patients had asymptomatic cartilage or meniscus damages. Certain tissue changes were significantly more common in experienced athletes, the others were observed more often in younger players. The condition of the joint was identical in the dominant and non-dominant legs.

Coauthors of the paper included researchers from Sechenov University: Alexey Lychagin, the head of the Department of Traumatology and Orthopaedic Surgery, Eduard Bezuglov, assistant professor of the Department of Sport Medicine and Medical Rehabilitation and the chief doctor of the Russian national football team, and Artemii Lazarev, a 6th-year student of the Faculty of Medicine.

'In my view, the most significant finding of our study is that the vast majority of professional soccer players have asymptomatic cartilage or meniscus damages of the knee joint. These changes are often rather pronounced. For instance, 12.7% of knee joints have grade 4 cartilage damage, and 13.8% have grade 3 meniscus damage. This data can be extrapolated to almost all professional athletes from game sports; it should be considered by doctors when interpreting MRI data after an acute injury and choosing treatment tactics. All studies conducted in this group of players have shown that the surgery negatively affects professional performance and the progression of osteoarthritis. No wonder many well-known sports medicine specialists say that the best surgery is the surgery that did not take place,' said Artemii Lazarev.

The study will help to assess the impact of athletes' experience and leg dominance on the condition of the knee joints, and allow to develop injury prevention programmes and make injuries diagnostics more accurately.

Forest conservation areas in oil palm plantations play a vital role in storing carbon and boosting rainforest biodiversity, a new study on palm oil agriculture in Borneo has revealed.

The study, led by the University of York, found that patches of protected forest play an important role in helping to conserve endangered species including hornbill birds and dipterocarp trees.

The study revealed that plantations, where a tenth of the land is protected as natural forest, store up to 20% more carbon than plantations with no protected forest.

Oil palm agriculture is a key driver of deforestation, causing widespread biodiversity loss and carbon emissions - particularly in Indonesia and Malaysia, where 85% of the world's palm oil is produced.

Lead author of the study, Susannah Fleiss, a PhD student in the Department of Biology at the University of York, said: "Our study found that these forest areas do increase carbon stored in oil palm plantations, helping to mitigate the carbon emissions associated with oil palm agriculture.

"We also found that the protected forest sites which stored the most carbon also contained the highest plant diversity, so by choosing to protect forest areas with high carbon stocks, oil palm plantations will also protect rainforest biodiversity."

For the study, the researchers measured trees and other vegetation in 14 forest areas protected in Roundtable on Sustainable Palm Oil (RSPO)-certified oil palm plantations in Malaysian Borneo.

A key requirement for oil palm plantations to be certified as sustainable, under the RSPO certification scheme, is that the plantations must protect areas of natural forest within their land.

The researchers found that, in comparison to primary rainforest, the forest areas protected within oil palm plantations had low numbers of tree seedlings, meaning they may contain fewer trees in the years to come.

Oil palm plantation owners must act to manage protected areas of forest in order to conserve them for the future, the researchers urge.

Susannah Fleiss added: "We recommend that oil palm plantations manage their protected forest to improve the potential for the trees to produce seedlings and for the seedlings to survive. This could include planting additional seedlings or cutting back vines."

Professor Jane Hill, who co-supervised the project added: "Palm oil is a key ingredient in many supermarket products and it is crucial that it comes from sustainable sources. Our study highlights the importance of retaining forest patches in sustainable cultivation practices."

'Conservation set-asides improve carbon storage and support associated plant diversity in certified sustainable oil palm plantations' is published in Biological Conservation. The research was jointly funded by Unilever and the University of York.

How do plants know when it is time to flower? Researchers at Martin Luther University Halle-Wittenberg (MLU) have studied this question and identified two genes that are key to this process. They were able to show that the ELF3 and GI genes control the internal clock of the plants that monitors the length of daylight and determine when it is the right time to flower. The findings could help to breed plants that are better adapted to their environments. The study was published in The Plant Journal.

Plants also have an internal clock that prepares internal cellular mechanisms in anticipation of the upcoming environmental changes. This ensures that plants only perform specific tasks at the most suitable time of the day. For instance, during the day they carry out photosynthesis, extracting energy from sunlight. However, completely different processes occur at night when the sun is no longer shining. Many plants grow significantly more than during the day. So, in order to tell the difference between day and night, plants have special receptors in their cells that can sense sunlight and start and stop different processes as needed.

"Just like humans, plants also have a so-called circadian clock. This is a complex network of genes and proteins that enables plants to control different processes in relation to time so that their biorhythm is perfectly synchronised to the day-night cycle," explains Dr Usman Anwer from the Institute for Agricultural and Nutritional Sciences at MLU. Like humans, plants react to more than just external influences; the circadian clock regulates metabolism and other processes in the plant cells so that they take place at the right time throughout the day and year. That means plants are able to anticipate certain regularities in their environment, such as the alternation of day and night, and adjust accordingly. This also includes the ability by the plants to begin flowering at the right time. "Plant orient themselves to the ratio between the hours of sunlight and darkness. Some plants only flower when the days are particularly long. Others only flower when the nights exceed a certain length of time," explains the plant scientist. This is not surprising; after all, different plant species flower at different times of the year when the days have different lengths.

In this new study, the MLU researchers wanted to understand which genes control a plant's internal clock, thereby influencing the flowering process. They did this by investigating two genes that were already known to play a crucial role in the circadian clock: ELF3 and GI. "These two genes have always been studied separately. Our goal was to understand how the two genes work together and how they jointly influence the circadian clock, for example by regulating when a plant flowers," says Anwer. The team investigated how the two genes functioned in the model plant, the thale cress, also known as the Arabidopsis thaliana. The scientists bred plants that had various genetic defects. In one group, the ELF3 gene was defective, in the second group it was the GI gene. In the third group, both genes were switched off. The researchers then observed how the plants reacted to different periods of light. They found that when one of the two genes was defective, the plants' circadian clock still functioned on a rudimentary basis. When both genes were switched off, the plant no longer reacted at all. "The plants could still perceive the light, but they could no longer tell how long the light lasted. This explains why the mutants with the double gene defect produced flowers at the same time under different lengths of light period ," Answer concludes.

However, light is not the only external source of information for the circadian clock, says the researcher. The ambient temperature also changes during the course of the day and year. In a follow-up project, the scientists want to understand how temperature influences plant flowering and whether temperature can compensate for the lack of information about light. The findings could also be important for plant breeding. Most plants have adapted to their original environment in such a way that they require a specific ratio between hours of sunlight and darkness in order to flower. The new findings could allow plants to be bred that can also flower in other places and produce good yields.

Even the toughest coffee trees may be no match for climate change. A new study of the plant that produces robusta coffee suggests its heat tolerance has been consistently overestimated. Worse yet, when temperatures just slightly cross this point, yields plummet. The findings suggest the multibillion-dollar coffee industry could be facing a much tougher future on even a slightly warmer planet.

The study, published in Global Change Biology, was built on 10 years of yield observations on almost 800 farms across Southeast Asia. The analysis suggests that the optimal temperature range for robusta is 20.5 degrees C, which is markedly lower than the temperatures currently considered optimal. For every 1-degree increase over this new optimal range, yields decrease by 14 percent.

"Our results suggest that robusta coffee is far more sensitive to temperature than previously thought," said the authors. "Its production potential could decline considerably as temperatures increase under climate change, jeopardizing a multibillion-dollar coffee industry and the livelihoods of millions of farmers."

Scientists from the Alliance of Bioversity International and CIAT and the University of Southern Queensland (USQ) and ECOM Agroindustrial, a global commodity merchant and sustainable supply chain management company, conducted the research on farms in Vietnam and Indonesia, which supply about half the world's robusta beans.

The study's findings contrast with current estimates, based on historical botanical explorations in Central Africa, that had suggested robusta had a higher temperature tolerance.

"This should make us reassess the viability of some of our current options, like switching from arabica to robusta coffee as the climate warms to adapt production to climate change," said Jarrod Kath, the study's lead author from USQ.

Arabica coffee, which is preferred by coffee connoisseurs for its superb taste, is even more sensitive to temperature change. Coffee farmers at lower altitudes around the tropics have been switching out their arabica trees for robusta trees, while arabica farmers have been searching for higher altitudes and lower temperatures to maintain production.

"These findings provide baseline information for coffee farmers, private sector investors and governments to adapt their coffee production plans under climate change," said Alessandro Craparo, a co-author with the Alliance.

"Precipitation changes have long been a concern of the coffee industry," said co-author Laurent Bossolasco of ECOM. "Now it's clear that we need more in-depth analysis of temperature variations in the robusta region."

The research adds a new dimension to how the researchers and industry understand coffee, said Kath.

It highlights the importance of testing assumptions about agricultural production sensitivity to climate variability with large field-based datasets.

"Theory is only as good as the data used to test it," said Craparo.

What did the very first proteins look like -- those that appeared on Earth around 3.7 billion years ago? Prof. Dan Tawfik of the Weizmann Institute of Science and Prof. Norman Metanis of the Hebrew University of Jerusalem have reconstructed protein sequences that may well resemble those ancestors of modern proteins, and their research suggests a way that these primitive proteins could have progressed to forming living cells. Their findings were published in the Proceedings of the National Academy of Sciences (PNAS).

The proteins encoded in a cell's genetic material are the screws, springs and cogs of a living cell -- all of its moving parts. But the first proteins, we assume, appeared well before cells and thus life as we know it. Modern proteins are made of 20 different amino acids, all of them essential to protein-building, and all arranged in the form of a polymer - a long, chain-like molecule - in which the placement of each amino acid is crucial to the protein's function. But there is a paradox in thinking about how the earliest proteins arose. Because the amino acids needed to make proteins are themselves produced by other proteins - enzymes. It's a chicken-and-egg kind of question, and it has only been partially answered until now.

Scientists believe that the very first true proteins materialized from shorter protein segments called peptides. The peptides would have been sticky assemblies of the amino acids that were spontaneously created in the primeval chemical soup; the short peptides would have then bound to one another, over time producing a protein capable of some sort of action. The spontaneous generation of amino acids had already been demonstrated in 1952, in the famous experiment by Miller and Urey, in which they replicated the conditions thought to exist on Earth prior to life and added energy like that which could come from lightning or volcanoes. Showing amino acids could, under the right conditions, form without help from enzymes or any other mechanism in a living organism suggested that amino acids were the "egg" that preceded the enzyme "chicken."

Tawfik, who is in the Institute's Biomolecular Sciences Department, says that is all well and good, "but one vital type of amino acid has been missing from that experiment and every experiment that followed in its wake: amino acids like arginine and lysine that carry a positive electric charge." These amino acids are particularly important to modern proteins, as they interact with DNA and RNA, both of which carry net negative charges. RNA is today presumed to be the original molecule that could both carry information and make copies of itself, so contact with positively-charged amino acids would theoretically be necessary for further steps in the development of living cells to occur.

But there was one positively-charged amino acid that appeared in the Miller-Urey experiments, an amino acid called ornithine that is today found as an intermediate step in arginine production, but is not, itself, used to build proteins. The research team asked: What if ornithine was the missing amino acid in those ancestral proteins? They designed an original experiment to test this hypothesis.

The scientists began with a relatively simple protein from a family that binds to DNA and RNA, applying phylogenetic methods to infer the sequence of the ancestral protein. This protein would have been rich in positive charges - 14 of the 64 amino acids being either arginine or lysine. Next, they created synthetic proteins in which ornithine replaced these as the positive charge carrier.

The ornithine-based proteins bound to DNA, but weakly. In Metanis' lab, however, the researchers found that simple chemical reactions could convert ornithine to arginine. And these chemical reactions occurred under those conditions assumed to have prevailed on Earth at the time the first proteins would have appeared. As more and more of the ornithine was converted to arginine, the proteins came more and more to resemble modern proteins, and to bind to DNA in a way that was stronger and more selective.

The scientists also discovered that in the presence of RNA, that the ancient form of the peptide engaged in phase separation (like oil drops in water) - a step that can then lead to self-assembly and "departmentalization." And this, says Tawfik, suggests that such proteins, together with RNA, could form proto-cells, from which true living cells might have evolved.

During the pandemic lockdown, as couples have been forced to spend days and weeks in one another's company, some have found their love renewed while others are on their way to divorce court. Oxytocin, a peptide produced in the brain, is complicated in that way: a neuromodulator, it may bring hearts together or it can help induce aggression. That conclusion arises from unique research led by Weizmann Institute of Science researchers in which mice living in semi-natural conditions had their oxytocin producing brain cells manipulated in a highly precise manner. The findings, which were published in Neuron, could shed new light on efforts to use oxytocin to treat a variety of psychiatric conditions, from social anxiety and autism to schizophrenia.

Much of what we know about the actions of neuromodulators like oxytocin comes from behavioral studies of lab animals in standard lab conditions. These conditions are strictly controlled and artificial, in part so that researchers can limit the number of variables affecting behavior. But a number of recent studies suggest that the actions of a mouse in a semi-natural environment can teach us much more about natural behavior, especially when we mean to apply those findings to humans.

Prof. Alon Chen's lab group in the Institute's Neurobiology Department have created an experimental setup that enables them to observe mice in something approaching their natural living conditions - an environment enriched with stimuli they can explore - and their activity is monitored day and night with cameras and analyzed computationally. The present study, which has been ongoing for the past eight years, was led by research students Sergey Anpilov and Noa Eren, and Staff Scientist Dr. Yair Shemesh in Prof. Chen's lab group. The innovation in this experiment, however, was to incorporate optogenetics - a method that enables researchers to turn specific neurons in the brain on or off using light. To create an optogenetic setup that would enable the team to study mice that were behaving naturally, the group developed a compact, lightweight, wireless device with which the scientists could activate nerve cells by remote control. With the help of optogenetics expert Prof. Ofer Yizhar of the same department, the group introduced a protein previously developed by Yizhar into the oxytocin-producing brain cells in the mice. When light from the wireless device touched those neurons, they became more sensitized to input from the other brain cells in their network.

"Our first goal," says Anpilov, "was to reach that 'sweet spot' of experimental setups in which we track behavior in a natural environment, without relinquishing the ability to ask pointed scientific questions about brain functions."

Shemesh adds that, "the classical experimental setup is not only lacking in stimuli, the measurements tend to span mere minutes, while we had the capacity to track social dynamics in a group over the course of days."

Delving into the role of oxytocin was sort of a test drive for the experimental system. It had been believed that this hormone mediates pro-social behavior. But findings have been conflicting, and some have proposed another hypothesis, termed "social salience" stating that oxytocin might be involved in amplifying the perception of diverse social cues, which could then result in pro-social or antagonistic behaviors, depending on such factors as individual character and their environment.

To test the social salience hypothesis, the team used mice in which they could gently activate the oxytocin-producing cells in the hypothalamus, placing them first in the enriched, semi-natural lab environments. To compare, they repeated the experiment with mice placed in the standard, sterile lab setups.

In the semi-natural environment, the mice at first displayed heightened interest in one another, but this was soon accompanied by a rise in aggressive behavior. In contrast, increasing oxytocin production in the mice in classical lab conditions resulted in reduced aggression. "In an all-male, natural social setting, we would expect to see belligerent behavior as they compete for territory or food," says Anpilov. "That is, the social conditions are conducive to competition and aggression. In the standard lab setup, a different social situation leads to a different effect for the oxytocin."

If the "love hormone" is more likely a "social hormone," what does that mean for its pharmaceutical applications? "Oxytocin is involved, as previous experiments have shown, in such social behaviors as making eye contact or feelings of closeness," says Eren, "but our work shows it does not improve sociability across the board. Its effects depend on both context and personality." This implies that if oxytocin is to be used therapeutically, a much more nuanced view is needed in research: "If we want to understand the complexities of behavior, we need to study behavior in a complex environment. Only then can we begin to translate our findings to human behavior," she says.

Researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) have shed light on the reproductive role of 'dark matter' DNA - non-coding DNA sequences that previously seemed to have no function.

Their findings, published today in Nature Communications, have revealed that a specific non-coding genomic region is essential for the proper development of the male and female reproductive organs in rice.

"Rice is one of the major global crops and is the staple food in many countries, including Japan," said Dr. Reina Komiya, senior author of the research paper and associate researcher from the OIST Science and Technology Group. "Further research into how these genomic regions affect plant reproduction could potentially lead to increased productivity and more stable yields of rice."

Many previous developmental studies have focused on genes - the sections of DNA that provide instructions for making proteins. But in complex creatures like plants and animals, a large fraction of the genome - typically between 90-98% - doesn't actually code for proteins.

The vast expanse of this 'junk DNA' has long puzzled biologists, with many dubbing it the 'dark matter' of the genome. But recent research suggests that many of these non-coding genomic regions may have a function after all, giving rise to non-coding RNA.

Scientists have now identified numerous types of non-coding RNA, ranging from small molecules only 20-30 nucleotide bases in length to long molecules of over 200 nucleotides. Although studies show that non-coding RNA plays a vital role in the regulation of gene expression - the process where a gene's instructions are used to make RNA or protein - the precise function of each specific non-coding RNA remains poorly understood.

Dr. Komiya is particularly interested in reproduction-specific RNAs. "These are non-coding RNAs that are produced as the reproductive system forms. I wanted to uncover what role they play in the development of stamens and pistils, the male and female reproductive organs in plants."

Making mutants

In the study, Dr. Komiya's group focused on a reproduction-specific microRNA - a major class of small non-coding RNAs - called microRNA2118.

The scientists created mutant rice strains by deleting a region of the genome that contains multiple copies of the specific DNA sequence that gives rise to microRNA2118. They found that the mutant strains were sterile and showed abnormalities in the structure of the stamens and pistils.

"This means that the role of microRNA2118 in the proper development of the stamens and pistils is essential for plant fertility," said Dr. Komiya.

Revealing RNA and probing proteins

In order to delve deeper into how microRNA2118 controlled development of the anther, the scientists then identified which other molecules were affected by microRNA2118.

They found that microRNA2118 triggered the cleavage of long non-coding RNA, producing many tiny RNA molecules, called secondary small RNAs.

"Interestingly, these small RNAs were rich in uracil, one of the four nucleotide bases found in RNA, which is very unusual compared to other small RNAs," said Dr. Komiya. "We hope to find out the exact function of these small RNAs - and whether this difference in nucleotide composition is important - in further research."

The scientists also discovered that two Argonaute proteins that were only produced in the stamen were dependent on the presence of microRNA2118. Previous research has shown that Argonaute proteins team up with small RNAs to carry out many regulatory functions, such as silencing genes and cleaving RNA.

Dr. Komiya's group therefore proposes that the Argonaute proteins may interact with microRNA2118 to trigger production of the secondary small RNAs. The proteins may also interact with the secondary small RNAs to silence specific regions of the genome. The team hopes to elucidate exactly how the Argonaute proteins and secondary small RNAs affect development of the plant reproductive system in further research.

"Reproduction is an important phenomenon of passing genetic information to the next generation and is essential for maintaining a stable yield supply. However, development of the reproductive system is complicated, and many aspects remain unknown," concluded Dr. Komiya. "This study shows that non-coding RNAs, derived from regions of the genome that were thought to be non-functional, are vital for plant reproduction. Exploring non-coding RNAs further is an exciting and important area of research."

Differences in the rate that genetic mutations accumulate in healthy young adults could help predict remaining lifespan in both sexes and the remaining years of fertility in women, according to University of Utah Health scientists. Their study, believed to be the first of its kind, found that young adults who acquired fewer mutations over time lived about five years longer than those who acquired them more rapidly.

The researchers say the discovery could eventually lead to the development of interventions to slow the aging process.

"If the results from this small study are validated by other independent research, it would have tremendous implications," says Lynn B. Jorde, Ph.D., chair of the Department of Human Genetics at U of U Health and a co-author of the study. "It would mean that we could possibly find ways to fix ourselves and live longer and better lives."

The study appears online in the journal Scientific Reports.

Scientists have long known that DNA damage constantly occurs in the body. Typically, various mechanisms repair this damage and prevent potentially harmful mutations, according to lead and corresponding author Richard Cawthon, M.D., Ph.D., a U of U Health research associate professor of human genetics.

As we get older, these mechanisms become less efficient and more mutations accumulate. Older parents, for instance, tend to pass on more genetic mutations through their germline (egg and sperm) to their children than younger parents.

However, Cawthon and colleagues theorized that these mutations could be a biomarker for rates of aging and potentially predict lifespan in younger individuals as well as fertility in women.

The researchers sequenced DNA from 61 men and 61 women who were grandparents in 41 three-generational families. The families were part of the Centre d'Etude du Polymorphisme Humain (CEPH) consortium, which was central to many key investigations that have contributed toward a modern understanding of human genetics.

The researchers analyzed blood DNA sequences in trios consisting of pairs of grandparents from the first generation and one of their children from the second generation. That's because germline mutations are passed on to their offspring. Mutations found in the child's blood DNA that were not present in either parent's blood DNA were then inferred to have originated in the parents' germlines. The researchers were then able to determine which parent each germline mutation came from, and, therefore, the number of such mutations each parent had accumulated in egg or sperm by the time of conception of the child.

Knowing that allowed the researchers to compare each first-generation parent to others of the same sex and estimate their rate of aging.

"So, compared to a 32-year-old man with 75 mutations, we would expect a 40-year-old with the same number of mutations to be aging more slowly," Cawthon says. "We'd expect him to die at an older age than the age at which the 32-year-old dies."

The scientists found that mutations began to occur at an accelerating rate during or soon after puberty, suggesting that aging begins in our teens.

Some young adults acquired mutations at up to three times the rate of others. After adjusting for age, the researchers determined that individuals with the slowest rates of mutation accumulation were likely to live about five years longer than those who accumulated mutations more rapidly. This is a difference comparable to the effects of smoking or lack of physical activity, Cawthon says.

Women with the highest mutation rates had significantly fewer live births than other women and were more likely to be younger when they gave birth to their last child. This suggests that the high rate of mutation was affecting their fertility.

"The ability to determine when aging starts, how long women can stay fertile, and how long people can live is an exciting possibility," Cawthon says. "If we can get to a point where we better understand what sort of developmental biology affecting mutation rates is happening during puberty, then we should be able to develop medical interventions to restore DNA repair and other homeostatic mechanisms back to what they were before puberty. If we could do that, it's possible people could live and stay healthy much longer."

A group of researchers, led by a UNSW sustainability scientist, have reviewed existing academic discussions on the link between wealth, economy and associated impacts, reaching a clear conclusion: technology will only get us so far when working towards sustainability - we need far-reaching lifestyle changes and different economic paradigms.

In their review, published today in Nature Communications and entitled Scientists' Warning on Affluence, the researchers have summarised the available evidence, identifying possible solution approaches.

"Recent scientists' warnings have done a great job at describing the many perils our natural world is facing through crises in climate, biodiversity and food systems, to name but a few," says lead author Professor Tommy Wiedmann from UNSW Engineering.

"However, none of these warnings has explicitly considered the role of growth-oriented economies and the pursuit of affluence. In our scientists' warning, we identify the underlying forces of overconsumption and spell out the measures that are needed to tackle the overwhelming 'power' of consumption and the economic growth paradigm - that's the gap we fill.

"The key conclusion from our review is that we cannot rely on technology alone to solve existential environmental problems - like climate change, biodiversity loss and pollution - but that we also have to change our affluent lifestyles and reduce overconsumption, in combination with structural change."

During the past 40 years, worldwide wealth growth has continuously outpaced any efficiency gains.

"Technology can help us to consume more efficiently, i.e. to save energy and resources, but these technological improvements cannot keep pace with our ever-increasing levels of consumption," Prof Wiedmann says.

Reducing overconsumption in the world's richest

Co-author Julia Steinberger, Professor of Ecological Economics at the University of Leeds, says affluence is often portrayed as something to aspire to.

"But our paper has shown that it's actually dangerous and leads to planetary-scale destruction. To protect ourselves from the worsening climate crisis, we must reduce inequality and challenge the notion that riches, and those who possess them, are inherently good."

In fact, the researchers say the world's affluent citizens are responsible for most environmental impacts and are central to any future prospect of retreating to safer conditions.

"Consumption of affluent households worldwide is by far the strongest determinant - and the strongest accelerator - of increased global environmental and social impacts," co-author Lorenz Keysser from ETH Zurich says.

"Current discussions on how to address the ecological crises within science, policy making and social movements need to recognize the responsibility of the most affluent for these crises."

The researchers say overconsumption and affluence need to be addressed through lifestyle changes.

"It's hardly ever acknowledged, but any transition towards sustainability can only be effective if technological advancements are complemented by far-reaching lifestyle changes," says co-author Manfred Lenzen, Professor of Sustainability Research at the University of Sydney.

"I am often asked to explain this issue at social gatherings. Usually I say that what we see or associate with our current environmental issues (cars, power, planes) is just the tip of our personal iceberg. It's all the stuff we consume and the environmental destruction embodied in that stuff that forms the iceberg's submerged part. Unfortunately, once we understand this, the implications for our lifestyle are often so confronting that denial kicks in."

No level of growth is sustainable

However, the scientists say responsibility for change doesn't just sit with individuals - broader structural changes are needed.

"Individuals' attempts at such lifestyle transitions may be doomed to fail, because existing societies, economies and cultures incentivise consumption expansion," Prof Wiedmann says.

A change in economic paradigms is therefore sorely needed.

"The structural imperative for growth in competitive market economies leads to decision makers being locked into bolstering economic growth, and inhibiting
necessary societal changes," Prof Wiedmann says.

"So, we have to get away from our obsession with economic growth - we really need to start managing our economies in a way that protects our climate and natural resources, even if this means less, no or even negative growth.

"In Australia, this discussion isn't happening at all - economic growth is the one and only mantra preached by both main political parties. It's very different in New Zealand - their Wellbeing Budget 2019 is one example of how government investment can be directed in a more sustainable direction, by transforming the economy rather than growing it."

The researchers say that "green growth" or "sustainable growth" is a myth.

"As long as there is growth - both economically and in population - technology cannot keep up with reducing impacts, the overall environmental impacts with only increase," Prof Wiedmann says.

One way to enforce these lifestyle changes could be to reduce overconsumption by the super-rich, e.g. through taxation policies.

"'Degrowth' proponents go a step further and suggest a more radical social change that leads away from capitalism to other forms of economic and social governance," Prof Wiedmann says.

"Policies may include, for example, eco-taxes, green investments, wealth redistribution through taxation and a maximum income, a guaranteed basic income and reduced working hours."

Modelling an alternative future

Prof Wiedmann's team now wants to model scenarios for sustainable transformations - that means exploring different pathways of development with a computer model to see what we need to do to achieve the best possible outcome.

"We have already started doing this with a recent piece of research that showed a fairer, greener and more prosperous Australia is possible - so long as political leaders don't focus just on economic growth.

"We hope that this review shows a different perspective on what matters, and supports us in overcoming deeply entrenched views on how humans have to dominate nature, and on how our economies have to grow ever more. We can't keep behaving as if we had a spare planet available."

Many countries are failing to comply with the non-binding commitments of the Paris Agreement, making it increasingly clear that we have to reconsider how to ensure collective action to limit global warming to less than 2°C above preindustrial levels. A new IIASA-led study supports a different approach to designing an international climate agreement that would incentivize countries to cooperate.

Although there is general consensus that global greenhouse gas emissions are too high, most governments would prefer other countries to reduce their emissions rather than reducing their own. The Paris Agreement is intended to solve this collective action problem, but according to a 2017 United Nations Environment Programme report, this landmark accord is likely insufficient. The authors of the study published in Scientific Reports explored one proposed solution to this problem, namely matching-commitment agreements. In such an agreement, each country can commit to reducing its emissions by an amount that depends on the emissions reductions of other countries. Using these commitments to conditional emissions reductions allows countries to incentivize other countries to reduce their emissions.

"Much of the current discussion around international climate agreements centers on how to induce countries to accede to a global carbon price, and prevent countries who do not impose such a tax from gaining an economic advantage over those who do. One prominent approach to doing so is the "climate club" approach, which incentivizes countries to cooperate by imposing trade sanctions on those who do not. While this approach is compelling and may avoid some of the shortcomings of the Paris Agreement, its implementation would be difficult, as international-trade law would need to be amended to allow for penalties on non-participants," explains study lead author Chai Molina, a researcher at IIASA, Princeton University, and the University of Pennsylvania. "We wanted to understand if it's possible to incentivize countries to cooperate by using a matching-commitment agreement rather than trade sanctions or asking them to make binding commitments to unilateral actions."

The study results indicate that such an agreement incentivizes countries to make matching commitments that in turn incentivize emissions reductions and reduce emissions from those expected without an agreement. In the one-shot "climate game" analyzed in the study, matching-commitment agreements successfully diverted two heterogeneous countries from a rational, stable outcome from which no country has an incentive to deviate, to a unique new, efficient equilibrium at which their emissions are lower than they would be in the absence of an agreement. At this new equilibrium, both countries are better off in terms of their economic payoffs than they would have been without the matching-commitment agreements.

The authors say that one of the aspects that makes their study different from other studies on matching-commitment agreements, is that most of them treat countries as if they were identical, assuming that they would suffer the same damages from climate change, and that they have the same selfish economic incentives to keep greenhouse gas emissions high. This research was inspired by a previous study that analyzed matching-commitment agreements between countries whose incentives may be different from one another. That study, however, considered a business-as-usual scenario in which some countries act irrationally, in the sense that they have an incentive to lower their emissions unilaterally, but do not do so. In this setting, it is unclear whether the matching-commitment agreement results in emissions reductions beyond those that would have been achieved without any agreement, if countries simply heeded their selfish incentives.

In their study, the authors analyzed a more realistic scenario in which countries consistently respond rationally to their incentives, both in the business-as-usual scenario and under a matching-commitment agreement. This new choice of business-as-usual is important, not just because it changes the payoffs countries obtain for different emissions reductions, but also because it allowed the authors to show that the matching-commitment agreement still results in reduced emissions, even if countries heed their economic incentives in the absence of an agreement.

The researchers emphasize that their work is a "proof of concept", and that further work on the subject will help to determine whether these agreements would work in practice. Nonetheless, the study results suggest that matching-commitment agreements are a promising approach to constructing an international environmental agreement. Moreover, a similar approach could in principle be used to tackle other public goods problems in situations in which enforcement is problematic.

BEER-SHEVA, Israel...June 19, 2020 - Chronic traumatic encephalopathy (CTE), a neurodegenerative disease caused by repeated head injuries often affecting athletes, can only be diagnosed currently through brain tissue analysis post-mortem. However, in a new study published in Brain, a Journal of Neurology, Ben-Gurion University of the Negev (BGU) researchers present a new test methodology. Using brain imaging techniques and analytical methods, they can determine whether football players have CTE by measuring leakage of the blood-brain barrier.

The blood-brain barrier (BBB) is a specialized interface between the blood and the brain environment that prevents the transfer of unwanted molecules or infectious organisms from the blood to the brain. Evidence shows that breaching the integrity of this barrier causes many brain diseases and neurodegeneration as a result of aging.

"Since a leaky BBB is also found in CTE and causes brain dysfunction and degeneration, it now seems that this test could provide the first (and so far the only) evidence for brain injury in the players we studied on the Israel football team," says Prof. Alon Friedman, M.D., a neurosurgeon and researcher at BGU and Dalhousie University in Canada.

"Importantly, we believe that those with persistent leak encompassing months or years are more likely to develop CTE. Many players seem to repair their BBB quickly, and if they do not suffer from repeated TBIs [traumatic brain injuries] or are not sensitive to brain injury, they are not likely to develop CTE."

The study population included 42 Israelis who play amateur American football in the Israeli Football League (IFL), and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. Magnetic resonance scans were also performed on 51 patients with malignant brain tumors, ischemic stroke or traumatic brain injury (TBI). The NFL sideline concussion assessment tool was used to document history of previous head injuries, including concussions, as well as symptoms assessment and Standardized Assessment of Concussion (SAC) tests.

The researchers developed a modified dynamic contrast-enhanced-MRI (DCE-MRI) protocol and analytical methods to investigate vascular pathology and blood-brain barrier disorder (BBBD) associated with repeated mild TBI in American football players. For the first time, using human brain imaging, they distinguished between fast and slow leakage through the pathological BBB and showed that localized, specific post-traumatic vascular pathology may persist for months in a subset of players.

"We generated maps that visualized the permeability value for each 3D section (voxel), Prof. Friedman says. "Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in the control group. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with alterations in white matter tracts. Importantly, increased permeability persisted for months, as seen in players who were scanned both on- and off-season.

"Not less important is the observation that few players who did not complain of severe symptoms also showed a leaky BBB. This suggests that DCE-MRI should be used in conjunction with symptom questionnaires before return to play is approved."

Football players were three times more likely to display a leaky BBB than controls as BBBD was detected in a subgroup (27.4%) of players. This individual variability may explain the wide range of cognitive deficits and neuropsychiatric impairments observed in players, likely reflecting differences in affected brain networks.

"Our findings show that DCE-MRI can be used to diagnose specific vascular pathology after traumatic brain injury and other brain pathologies," Prof. Friedman says.

The researchers note that while the present study was performed in otherwise-healthy amateur players, future studies are recommended to determine the prevalence and spatial-temporal characteristics of BBBD in professional players and/or retired players with and without CTE clinical signs and symptoms. Differences, if found, may improve the understanding of the effects of impact strength and frequency, age of onset, player's skill and extent of vascular injury.

Today's modern cities, from Denver to Dubai, could learn a thing or two from the ancient Pueblo communities that once stretched across the southwestern United States. For starters, the more people live together, the better the living standards.

That finding comes from a study published today in the journal Science Advances and led by Scott Ortman, an archaeologist at the University of Colorado Boulder. He's one of a growing number of antiquarians who argue that the world's past may hold the key to its future. What lessons can people living today take from the successes and failures of civilizations hundreds or thousands of years ago?

Recently, Ortman and Jose Lobo from Arizona State University took a deep dive into data from the farming towns that dotted the Rio Grande Valley between the 14th and 16th centuries. Modern metropolises should take note: As the Pueblo villages grew bigger and denser, their per capita production of food and other goods seemed to go up, too.

Busy streets, in other words, may lead to better-off citizens.

"We see an increasing return to scale," said Ortman, an assistant professor in the Department of Anthropology who is also affiliated with the Santa Fe Institute in New Mexico. "The more people work together, the more they produce per person."

Whether the same thing is true today remains an open question, especially amid the unprecedented impacts of the COVID-19 pandemic on cities and human proximity. But the results from the sunny Southwest suggest that it's an idea worth exploring.

"The archaeological record can help us to learn about issues we care about today in ways that we can't do using the data available to us from modern societies," Ortman said.

The good dishes

The research is an offshoot of an effort that Ortman leads called the Social Reactors Project, which has explored patterns of growth in civilizations from ancient Rome to the Incan world.

It's an attempt to chase down an idea first proposed in the 18th century by Adam Smith, often known as the father of modern economics. In The Wealth of Nations, Smith made the case for the fundamental benefits of market size--that if you make it easier for more people to trade, the economy will grow.

Just look at any city in the U.S. where you might find a hair salon next to a bakery next to a doggie daycare.

"As people interact more frequently, a person can make and do fewer things themselves and get more of what they need from their social contacts," Ortman said.

The problem, he explained, is that such "agglomeration-driven" growth is difficult to isolate in today's big and complex cities. The same isn't true for the Rio Grande Valley.

Before the arrival of the Spaniards in the 16th century, hundreds of villages spanned the region near what is now Santa Fe. These settlements ranged in size from a few dozen residents to as many as 3,000 people, most of whom made their living by growing crops like maize and cotton.

Such a subsistence lifestyle didn't mean that these communities were simple.

"The traditional view in ancient history was that economic growth didn't happen until the onset of the industrial revolution," Ortman said.

He and Lobo decided to put that assumption to the test. The duo pored through an exhaustive database of archaeological finds from the region--capturing everything from the number and size of rooms in Pueblo communities to the pottery from rubbish heaps.

They unearthed a clear trend: When villages got more populous, their residents seemed to get better off on average--exactly as Smith predicted. Living spaces grew in size and families collected more painted pottery.

"You might think of it as more sets of dishes for sharing meals together," Ortman said.

Social connection

That growth, the team discovered, also seemed to follow a pattern that researchers on the Social Reactors Project have seen in a range of civilizations throughout history. Every time villages doubled in size, markers of economic growth increased by about 16% on average.

Ortman said that the effect doesn't happen in the same way everywhere. Factors like inequality and racism, for example, can keep urban residents from working together even when they live in cramped spaces.

But, Ortman added, these Pueblo communities hold an important lesson for modern-day societies: the more people can connect with others, the more prosperous they become.

"All other things being equal, urbanization should lead to improvements in the material conditions of life for people everywhere," he said. "We suspect this is why the world continues to urbanize, despite all of the associated problems."