Culture

Molecular changes in white blood cells can help diagnose 'the bends' earlier in divers

For over a century, researchers have known about "the bends", a serious condition affecting scuba divers. However, we still know relatively little about its physiological basis. Doctors do not yet have a definitive test for the bends, instead relying on symptoms to diagnose it. A new study in Frontiers in Physiology is the first to investigate genetic changes in divers with this condition, finding that genes involved in inflammation and white blood cell activity are upregulated. The findings cast light on the processes underlying the bends, and may lead to biomarkers that will help doctors to diagnose the condition more precisely.

The bends, more formally known as decompression sickness, is a potentially lethal condition that can affect divers. Symptoms include joint pain, a skin rash, and visual disturbances. In some patients, the condition can be severe, potentially leading to paralysis and death.

Researchers have known about the condition for a long time. A paper published in 1908 correctly hypothesized that it involves bubbles of gas forming in the blood and tissue because of a decrease in pressure. However, despite this, researchers do not yet fully understand the precise mechanisms underlying the condition. Animal studies have suggested that inflammatory processes may have a role in decompression sickness, but no-one had studied this in humans.

Divers have developed methods to reduce the risk of the bends, including controlled ascents from the depths, and it is now relatively rare. However, for suspected cases, doctors have no way to test for the condition, and instead rely on observing symptoms and seeing whether patients respond to hyperbaric oxygen therapy, which involves breathing oxygen at high pressures.

To investigate the basis of decompression sickness, the researchers behind this new study took blood samples from divers who had been diagnosed with decompression sickness and divers who had completed a dive without developing the condition. The researchers took blood samples at two distinct times: within 8 hours of the divers emerging from the water, and 48 hours afterwards, when the divers with decompression sickness had undergone hyperbaric oxygen treatment. They performed RNA sequencing analysis to measure gene expression changes in white blood cells.

"We showed that decompression sickness activates genes involved in white blood cell activity, inflammation and the generation of inflammatory proteins called cytokines," explained Dr Nikolai Pace of the University of Malta, a researcher involved in the study. "Basically, decompression sickness activates some of the most primitive body defense mechanisms that are carried out by certain white blood cells."

Interestingly, these genetic changes had diminished in samples taken at 48 hours after the dive, after the patients had been treated with hyperbaric oxygen therapy. The findings provide a first step towards potentially developing a diagnostic test for decompression sickness, and may also reveal new treatment targets.

"We hope that our findings can aid the development of a blood-based biomarker test for human decompression sickness that can facilitate diagnosis or monitoring of treatment response," said Prof Ingrid Eftedal of the Norwegian University of Science and Technology, who was also involved in the project. "This will require further evaluation and replication in larger groups of patients."

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Frontiers

Patient-provider discussions about bariatric surgery play pivotal role in weight loss outcomes

BOSTON -- Obesity increases one's risk for many diseases and often prevents patients from receiving other necessary medical procedures. One of the most effective ways for patients with severe obesity to lose weight is through bariatric surgery, but it's not clear how often this option is raised. In a new study published in Obesity, investigators from Brigham and Women's Hospital find that eligible patients who discuss bariatric surgery options with their primary care providers or specialists from disciplines ranging from cardiology to urology are more likely to undergo surgery and lose more weight than those who do not have such discussions. But the team also found that these pivotal discussions were exceedingly rare, with fewer than 10 percent of eligible patients having a conversation over the course of a year.

"Obesity is a very significant health problem in the United States and increases the risk of almost every disease, from heart disease to diabetes and kidney failure," said Alexander Turchin, MD, MS, Division of Endocrinology, Diabetes and Hypertension. "The most effective treatment for people with severe obesity is weight loss surgery. However, fewer than 1 percent of eligible patients every year undergo these operations in the U.S. We wanted to explore why that is."

Turchin and colleagues conducted an observational study from 2000 to 2015, collecting data from 30,560 patients with obesity. They looked at the frequency of patient-provider conversations about bariatric surgery and correlated patient weight-loss outcomes. Researchers analyzed clinicians' electronic notes through artificial intelligence, using natural language processing (NLP) software, and searched for provider documentation of conversations about weight loss surgery.

Many patients with a body mass index of 35 or greater are eligible for weight loss surgery. Notably, investigators found that less than 10 percent of potentially eligible patients had discussions about bariatric surgery with their providers. Patients who had these discussions were 10 times more likely to undergo weight loss surgery than those who did not. Patients who engaged in these conversations were also more likely to lose weight over time, even without surgery, and lost more weight than patients who did not talk with their providers about surgery options at all.

Authors note that one limitation of this study is that they do not know who initiated these discussions. In some cases, the providers may have first brought up bariatric surgery, while in others, patients may have first asked questions about it.

"Even without surgery, such discussions emphasize the seriousness of obesity and may prompt patients to explore ways to lose weight," said Turchin. "It's important for clinicians to initiate these discussions but also support them when patients bring them up themselves."

Looking forward, Turchin's team aims to investigate which medical specialists are most likely to have these discussions and evaluate whether prompting these conversations is an effective intervention for weight-related illnesses.

"Usually, when we talk about clinical outcomes, we look at whether we changed a patient's medication or started a new treatment," said Turchin. "What we miss, though, is that the first step in reaching a treatment goal is to talk to the patient. We need to talk to our patients more about the options available and help them to become better informed about their care."

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Brigham and Women's Hospital

Monoclonal antibody therapy for COVID-19 safe, effective for transplant patients

ROCHESTER, Minn. -- Treating transplant patients with mild to moderate cases of COVID-19 with monoclonal antibodies is safe and helps prevent serious illness, according to a Mayo Clinic study recently published in Open Forum Infectious Diseases. These results are especially important because transplant patients who are infected with COVID-19 have a higher risk of severe illness and death.

"Monoclonal antibody therapy is really important for the transplant population because they are less likely to develop their own immunity. Providing them with these antibodies helps them recover from COVID-19," says Raymund Razonable, M.D., a Mayo Clinic infectious diseases specialist and the study's senior author.

The retrospective study focused on the first 73 solid organ transplant patients who received monoclonal antibody infusions for treatment of mild to moderate COVID-19 between Nov. 19, 2020, and Jan. 23 at Mayo Clinic. Eleven patients had an emergency department visit and nine patients were hospitalized. Most significantly, no patients required mechanical ventilation, died or experienced organ rejection.

"While we expected monoclonal antibody therapy would be beneficial for patients, we were pleasantly surprised by the results. Only one patient required care in the ICU for non-COVID-19 indication, and, most importantly, there were no deaths," Dr. Razonable says.

Monoclonal antibodies help prevent the virus that causes COVID-19 from attaching to human cells, which helps block the spread of infection. In fall 2020, the Food and Drug Administration authorized the emergency use of bamlanivimab and casirivimab-imdevimab to treat mild to moderate COVID-19 in patients with a high risk of becoming seriously ill. But since the safety and efficacy of these therapies for transplant patients remained unknown due to the limited clinical data, many health care institutions initially hesitated to set up infusion centers, Dr. Razonable says.

The study's results highlight the important role monoclonal antibodies can play in treating transplant patients with mild to moderate COVID-19. Knowing how best to treat these patients remains crucial given that recent studies indicate that COVID-19 vaccines are not as effective for transplant patients.

"It is important that these patients have early access to monoclonal antibody treatment," Dr. Razonable says. "Our data show the outcomes for patients are better if they get infused earlier." The study's lead author is Zachary Yetmar, M.D., Mayo Clinic. Other co-authors are Elena Beam, M.D.; Jack O'Horo, M.D.; Ravindra Ganesh, M.B.B.S., M.D.; Dennis Bierle, M.D.; Lisa Brumble, M.D.; and Teresa Seville, M.D. ? all of Mayo Clinic.

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Mayo Clinic

Flickering screens may help children with reading and writing difficulties

image: Professor Goran Soderlund.

Image: 
Agneta Lundberg

Previous studies have shown that children with attention difficulties and/or ADHD solve cognitive tasks better when they are exposed to auditory white noise. However, this is the first time that such a link has been demonstrated between visual white noise and cognitive abilities such as memory, reading and non-word decoding in children with reading and writing difficulties.

"The white noise to which we exposed the children, also called visual pixel noise, can be compared with giving children glasses. The effect on reading and memory was immediate," explains Göran Söderlund, Senior Lecturer in Education at the University of Gothenburg and Professor of Special Education at the Western Norway University of Applied Sciences.

11-year-olds tested

The study was conducted on around 80 students in the Småland region of southern Sweden. The children who took part were selected following a word recognition test and were split into three groups: good readers, children with some reading difficulties and children with major reading difficulties (i.e. having phonological impairments).

In the study, the children were asked to read 12 words while being exposed to four different levels of visual white noise, from zero to high. The test involved assessing how many of the words the children could read correctly and how many words they were able to recall afterwards.

White noise improves reading skills and memory

The results showed that the group with major reading difficulties, particularly phonological difficulties, performed significantly better when exposed to visual pixel noise. They read more words correctly and also recalled more words in the moderate noise conditions. The white noise had no effect or negative effects on the good readers and those with only minor reading problems.

"This is the first evidence of visual white noise having effects on higher-level cognition, in this case both reading and memory," says Göran Söderlund.

Right amount of white noise key

The children were exposed to different levels of white noise, with the results showing that the amount of noise is critical for reading and memory.

"You can compare it with being shortsighted and needing glasses. We saw that when we exposed the children to a medium level of white noise, their reading improved. However, their reading skills were less good when there was no noise or a high level of noise," adds Göran.

"These results show that children with reading and writing difficulties can be helped with an incredibly simple intervention. By adjusting screens in school or at home, we hope to be able to resolve their problems at a stroke. This is the first study of its kind, and replications are needed."

Further research required

Göran Söderlund now wants to further investigate the effects of white noise. He hopes that new studies can answer the question of whether practising with white noise for a prolonged period can lead to lasting improvements.

"It's worth exploring, as we just don't know. This first study of ours is basic research. But our results show that the children improved immediately, so it's important to continue with new studies to establish whether this simple measure, which everyone can do on their own laptop, will actually provide enduring help for these children."

The study "Sensory white noise improves reading skills and memory recall in children with reading disability" was published in the scientific journal Brain and Behavior. The study was conducted by Göran Söderlund, Jakob Åsberg Johnels (Gillberg Neuropsychiatry Centre at the University of Gothenburg) and Andreas Magnusson, plus Bodil Rothén, Ellen Torstensson-Hultberg and Linda Fälth (Linnaeus University).

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University of Gothenburg

New research shows link between politics, boredom and breaking public-health rules

People who are more prone to boredom and who are socially conservative are more likely to break public-health rules, according to new psychology research.

While previous research demonstrated a connection between being highly prone to boredom and breaking social-distancing rules, this study demonstrated the association was more prominent as participants' social conservatism increased.

"Many public-health measures such as wearing a mask or getting a vaccine have become highly politicized," said James Danckert, professor of psychology at the University of Waterloo. "People who find these measures a threat to their identity, and who suffer from boredom a lot, find breaking the rules helps them re-establish a sense of meaning and identity. Boredom threatens our need to make meaning out of life and some things such as politics can strengthen our sense of identity and meaning."

For the study, researchers asked more than 900 people to respond to questions about boredom, political ideology and adhering to public-health measures such as wearing a mask or not socializing outside one's household. They then applied a variety of statistical analysis techniques to explore the relations that underly these elements.

As the pandemic continues, the work has implications for public-health policy and communications. For instance, focusing on what people can do rather than what they are restricted from doing. Such messaging could help provide a more positive framework to help people ground their sense of identity and control.

"Many of the restrictions have become heavily politicized and much of the messaging from governments has focused on personal responsibility," Danckert said. "But this can become finger pointing and blaming and most of us recoil from that. What we need is to promote our shared values - the things we all have in common and the positive things we can get back if we all pull together.

"It can be difficult for some people to cope with boredom and that can have serious consequences for an individual and for society at large. Boredom is not a trivial experience - it's worth paying attention to it."

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University of Waterloo

How gender norms and job loss affect relationship status

In cultures that place a high value on conventional gender norms, particularly those that prize men as the breadwinners in a family, their unemployment plays an outsized role in whether a romantic relationship ultimately succeeds or fails.

That's according to new research from sociologists Pilar Gonalons-Pons of the University of Pennsylvania and Markus Gangl of Goethe University Frankfurt. They published their findings in the journal American Sociological Review.

"This study is really about how the association between men's unemployment and divorce or separation varies across countries," says Gonalons-Pons, an assistant professor in the Department of Sociology. "It also points to how much views about gender really shape the length of romantic relationships."

For the past five years, Gonalons-Pons has been conducting research on gender, labor, families, and public policy. Though the literature includes plenty of work on predictors of relationship longevity, most of it focuses on economic conditions like financial stressors or on the psychological, determining whether two people actually make a good match.

"There were no studies showing empirically how gender culture is its own important determinant," she says. So Gonalons-Pons and Gangl took on this question.

Given the data available, they chose to concentrate on heterosexual couples from the United States and 28 high-income countries in Europe. These fell on a continuum, from the most gender-conservative, where about a third of the population believes a man's role is as primary breadwinner, to more gender-progressive, where that number drops to about 4%. In total, the researchers followed couples for four years, looking for events of unemployment as well as separation or divorce.

They hypothesized that in gender-conservative countries, the stress of men's unemployment wouldn't be solely financial but also related to cultural norms. "We thought that when a man loses his jobs and doesn't get another one right away it might cast this pressure, this feeling of failure or lack of a sense of status and social identity," Gonalons-Pons says.

The results played out as the researchers expected. Countries that place greater value on a man's role as breadwinner experience a stronger association between men's unemployment and relationship breakup, whether separation or divorce. In places where the idea of "man as head of household" isn't as pronounced, there's less criticism of masculine identity following a job loss.

The findings make sense to Gonalons-Pons. "In a more hostile context, a gender-conservative context, men's unemployment will leave a more negative psychological impact on the man, which reverberates within the couple," she says. "You'll have more friends, more family saying, 'What's wrong with your partner? What's happening here?' That doesn't make either person feel any better and leads to this cultural pressure that can accentuate stress and ultimately result in a breakup."

Interestingly, the researchers didn't see the effect to the same extent for cohabiting couples, a finding that aligns with previous research on non-married couples who live together. Gonalons-Pons suspects this stems from the fact that the pressure to conform to conventional gender norms increases with marriage.

Though the work as a whole focused on a subset of high-income countries and on heterosexual couples only, the researchers say it potentially has broader implications for other places and other kinds of relationships--though the questions may be slightly different. For example, how do those beliefs affect the longevity of a romantic partnership between two men or two women?

"These cultural ideas create support for those who conform to these norms," she says. "The flip side is they create pressure that can negatively affect people who do not."

Gonalons-Pons stresses that her work does not equate to a crystal ball for any single relationship. "None of this is to say that if you break a gender norm, you're destined to break up," she says. "It's to highlight that these norms do matter; they do influence a relationship. Social norms are part of what shapes the well-being of a couple."

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University of Pennsylvania

Diversity in research identifies more genomic regions linked to diabetes-related traits

Researchers at the Keck School of Medicine (KSOM) of USC are among the contributors to a large-scale ethnically diverse genetic study that has expanded what we know about potential causes of type 2 diabetes.

The research, published in Nature Genetics, was conducted by the international MAGIC collaboration, made up of 400 global academics and led by researchers at the University of Exeter.

The study, a genome-wide meta-analysis, has identified more regions of the genome that are linked to blood glucose and insulin levels, features that contribute to the risk of type 2 diabetes. The findings demonstrate that, while 80-85 percent of genes linked to glucose and insulin levels are the same across different ethnic groups, a significant minority are present in only one or two ethnic groups. Thus, including different multi-ethnic participants yields more and better results. This new approach may ultimately help researchers and health care providers move toward a more precise approach in the diagnosis and management of diabetes in diverse populations.

Making research more diverse

According to the GWAS Diversity Monitor, launched in Nature Genetics in 2020 as a way to track participants included across all published genome-wide association studies in real time, more than 88 percent of research has been conducted in Europeans. This means the results of these studies may not offer the same kind of benefit to people from non-European ancestry as they do people of European descent.

To help rectify this, the MAGIC team analyzed data from 280,000 people without diabetes across a wide range of ethnicities, including individuals of East Asian, Hispanic, African American, South Asian and sub-Saharan African origin. Researchers looked at glycemic traits, which are used to diagnose diabetes and monitor sugar and insulin levels in the blood.

By including multi-ethnic participants, the team discovered 24 more regions of the genome--called loci--that are linked to glycemic traits than if they had conducted the research on Europeans alone.

Research diversity key to precision medicine

Professor Inês Barroso, PhD, of the University of Exeter, who led the research, said,"Type 2 diabetes is an increasingly huge global health challenge--with most of the biggest increases occurring outside of Europe. While there are a lot of shared genetic factors between different countries and cultures, our research tells us that they do differ, in ways that we need to understand. It's critical to ensuring we can deliver a precision diabetes medicine approach that optimises treatment and care for everyone."

KSOM's Thomas Buchanan, MD, professor of medicine, Bernard J. Hanley Chair in Medicine, and vice dean for research, and Richard Watanabe, PhD, professor of preventive medicine and associate dean for health and population science programs, provided a large set of samples from Latino participants. Watanabe also plays a leadership role in MAGIC as a member of the steering committee.

"We have known for a very long time that some racial and ethnic groups have particularly high rates of diabetes in our current environment, which has easy access to food with little requirements for physical activity," Buchanan said. "This study begins to shed some light on the possible genetic contributors to racial/ethnic-specific diabetes risk."

"Genetic studies to date have primarily been in populations of northern European ancestry," Watanabe added. "So this study points to key genetic determinants that not only identify similarities across these diverse groups, but also key differences that may exist. These findings are the first step in moving us towards precision-based medicine, which may eventually improve the quality of life for our local Hispanic population from which the samples we contributed were obtained."

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Keck School of Medicine of USC

New method makes generic polymers luminescent

image: Ball-milling the mixture of polystyrene and pre-fluorescent radical reactants yielded luminescent polymers. Photos show the mixture before (left) and after (right) the reaction, under UV light. (Koji Kubota et al., Angewandte Chemie International Edition. May 14, 2021)

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Koji Kubota et al., <em>Angewandte Chemie International Edition</em>. May 14, 2021

Hokkaido University researchers have developed a simple method that converts existing generic polymers into luminescent polymers using mechanical force.

Researchers from Hokkaido University have successfully developed a new method to give luminescent properties to generic polymers, such as polystyrene and polyethylene. The technique, which was published in the journal Angewandte Chemie International Edition, makes it possible to easily prepare luminescent polymers without using complicated organic synthetic methods.

"Luminescent polymers are widely used in modern society, in applications such as organic lasers, solar cells, sensors and bioimaging, but their preparation often requires multiple chemical synthesis steps, which are both time and labor intensive," explains Professor Hajime Ito, one of the authors of the study and Vice Director of the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) at Hokkaido University.

To overcome this problem, the research team investigated whether luminescent polymers could be prepared using mechanical force as opposed to sophisticated chemical synthesis.

"It is well known that mechanically stimulating polymers, for example by grinding or crushing them, generates reactive species called free radicals," says Associate Professor Koji Kubota from Hokkaido University, a paper co-author. "Inspired by this phenomenon, as well as our previous research into mechanical-force-induced luminescence and reactions, we wanted to investigate whether we could find a simpler method for preparing functional luminescent materials."

In this study, the researchers placed the polymer and pre-fluorescent radical reactants together in a ball milling jar containing stainless steel balls. The jar was then shaken, causing the balls to grind the solid compounds and initiate a reaction. During this process, the covalent bonds in the polymer chains were cleaved and the pre-fluorescent molecules were inserted into the polymer, gaining significantly higher emission intensity. The researchers successfully applied this method to polystyrene, polyethylene, polyphenylene sulfide, polysulfone, and other generic polymers.

"With further development, the method could potentially be adapted to introduce other functions to generic polymers," says Hokkaido University Assistant Professor Mingoo Jin.

"In the future, we hope to use this method to develop novel sensing and recording materials that change colour in response to mechanical stimuli," Hajime Ito added.

This could pave the way for "smart" materials for a wide range of applications, such as bioimaging reagents and pressure-sensitive sensors.

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Hokkaido University

Breakthrough in brain imaging may offer future alternative to functional MRI

The gold standard in functional brain imaging for over two decades, functional magnetic resonance imaging (fMRI) has transformed the landscape of research and clinical care. Yet, because of its cost and functional limitations, scientists have continued to look for new ways to see into the human brain.

Researchers from the Keck School of Medicine of USC and the California Institute of Technology (Caltech), with the help of patients recovering from traumatic brain injury, have now demonstrated an alternative way to produce highly detailed images of the human brain. Their work, published in
Nature Biomedical Engineering, yielded the first pictures of human brain function ever produced using functional photoacoustic computerized tomography (fPACT) - a landmark in the history of functional brain imaging.

Technology meets technique

Imaging with fPACT works by emitting a beam of laser light into the area being imaged. The light is absorbed by oxygen-carrying hemoglobin molecules in the patient's red blood cells causing them to vibrate ultrasonically. The vibrations can then be scanned by sensors. Lihong Wang, PhD the Bren professor of medical and electrical engineering at the Andrew and Peggy Cherng Department of Medical Engineering at Caltech is a leader in the field of photoacoustic imaging.

The technology has previously been successful in animal and some human tissue models, but there are hurdles to applying it to the brain. "The human skull is an acoustic lens, but it distorts and attenuates our signals," Wang says. "It's like looking outside through a wavy window. The barrier impacts the clarity of the image rendered, a challenge our field is working to overcome."

Despite the challenges, this research collaboration has shown proof of concept that fPACT can be used for brain imaging. To establish the technology's effectiveness, Charles Liu, MD, PhD, director of the USC Neurorestoration Center and professor of clinical neurological surgery, and Jonathan Russin, MD, an associate director of the USC Neurorestoration Center and assistant professor of clinical neurological surgery, enlisted the aid of traumatic brain injury patients in the USC Neurorestoration Center.

"Our study subjects had undergone hemicraniectomy [the temporary removal of a large portion of the skull], which enabled us to test the technology without interference in fully awake humans prior to skull reconstruction surgery. Thanks to their participation, we discovered fPACT is capable of creating functional brain images that are superior in some ways to 7T fMRI," Liu says. "This may be something that will change neuroimaging forever."

The study subjects were recruited from Rancho Los Amigos National Rehabilitation Center where a large number of cranial reconstruction surgeries are performed. "It is terrific to work with patients to develop transformative tools to better understand how to treat their neurological disabilities", adds Liu, who also serves as chair of neurosurgery and orthopedics and chief of innovation and research at Rancho.

The benefits could be enormous. "fPACT costs less than MRI, is potentially portable, is accessible to patients with implants and eliminates the claustrophobic/magnetic MRI environment," Russin notes. "This study is a first for functional human brain imaging - and, we believe, a critical step forward in advancing the field."

Reactions to results

In order to complete the study, Liu, Russin and Wang solicited critical input from the USC Mark and Mary Stevens Institute for Neuroimaging and Informatics, which provided expertise and resources including access to a state-of-the-art 7-Tesla MRI. "To understand the potential of fPACT, the research team needed to compare it to the best current functional brain imaging," says Danny J.J. Wang, PhD, professor of neurology and radiology. "After reviewing the data, it seems clear that fPACT could have immense impact in neuroscience, with applications ranging from vessel and tumor imaging to localization of function and seizures."

Results from the study highlight fPACT's ability to produce accurate 3D maps of blood flow. Since blood flow increases to specific areas of the brain during cognitive tasks, a device that shows blood concentration and oxygenation changes can help researchers and medical professionals monitor brain activity. This is known as functional imaging.

The study offers key insight into fPACT's long-term potential. Today, Liu, Russin and their team are partnering with Caltech to develop workarounds to skull interference to further investigate the possibilities of fPACT technology.

Credit: 
Keck School of Medicine of USC

IPBES/IPCC: Tackling the biodiversity and climate crises together, and their combined social impacts

image: The peer-reviewed workshop report is the product of a four-day virtual workshop between experts selected by a 12-person Scientific Steering Committee assembled by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) and the Intergovernmental Panel on Climate Change (IPCC) - the first-ever collaboration between these two intergovernmental bodies.

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IPBES

BONN, 10 June - Unprecedented changes in climate and biodiversity, driven by human activities, have combined and increasingly threaten nature, human lives, livelihoods and well-being around the world. Biodiversity loss and climate change are both driven by human economic activities and mutually reinforce each other. Neither will be successfully resolved unless both are tackled together.

This is the message of a workshop report, published today by 50 of the world's leading biodiversity and climate experts.

The peer-reviewed workshop report is the product of a four-day virtual workshop between experts selected by a 12-person Scientific Steering Committee assembled by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) and the Intergovernmental Panel on Climate Change (IPCC) - the first-ever collaboration between these two intergovernmental bodies.

The report finds that previous policies have largely tackled biodiversity loss and climate change independently of each other, and that addressing the synergies between mitigating biodiversity loss and climate change, while considering their social impacts, offers the opportunity to maximize benefits and meet global development goals.

"Human-caused climate change is increasingly threatening nature and its contributions to people, including its ability to help mitigate climate change. The warmer the world gets, the less food, drinking water and other key contributions nature can make to our lives, in many regions" said Prof. Hans-Otto Pörtner, co-chair of the Scientific Steering Committee.

"Changes in biodiversity, in turn, affect climate, especially through impacts on nitrogen, carbon and water cycles," he said. "The evidence is clear: a sustainable global future for people and nature is still achievable, but it requires transformative change with rapid and far-reaching actions of a type never before attempted, building on ambitious emissions reductions. Solving some of the strong and apparently unavoidable trade-offs between climate and biodiversity will entail a profound collective shift of individual and shared values concerning nature - such as moving away from the conception of economic progress based solely on GDP growth, to one that balances human development with multiple values of nature for a good quality of life, while not overshooting biophysical and social limits."

The authors also warn that narrowly-focused actions to combat climate change can directly and indirectly harm nature and vice-versa, but many measures exist that can make significant positive contributions in both areas.

Among the most important available actions identified in the report are:

Stopping the loss and degradation of carbon- and species-rich ecosystems on land and in the ocean, especially forests, wetlands, peatlands, grasslands and savannahs; coastal ecosystems such as mangroves, salt marshes, kelp forests and seagrass meadows; as well as deep water and polar blue carbon habitats. The report highlights that reducing deforestation and forest degradation can contribute to lowering human-caused greenhouse gas emissions, by a wide range from 0.4-5.8 gigatonnes of carbon dioxide equivalent every year.

Restoring carbon- and species-rich ecosystems. The authors point to evidence that restoration is among the cheapest and quickest nature-based climate mitigation measures to implement - offering much-needed habitat for plants and animals, thus enhancing resilience of biodiversity in the face of climate change, with many other benefits such as flood regulation, coastal protection, enhanced water quality, reduced soil erosion and ensuring pollination. Ecosystem restoration can also create jobs and income, especially when taking into consideration the needs and access rights of indigenous peoples and local communities.

Increasing sustainable agricultural and forestry practices to improve the capacity to adapt to climate change, enhance biodiversity, increase carbon storage and reduce emissions. These include measures such as diversification of planted crop and forest species, agroforestry and agroecology. Improved management of cropland and grazing systems, such as soil conservation and the reduction of fertilizer use, is jointly estimated by the report to offer annual climate change mitigation potential of 3-6 gigatonnes of carbon dioxide equivalent.

Enhancing and better-targeting conservation actions, coordinated with and supported by strong climate adaptation and innovation. Protected areas currently represent about 15% of land and 7.5% of the ocean. Positive outcomes are expected from substantially increasing intact and effectively protected areas. Global estimates of exact requirements for effectively protected and conserved areas to ensure a habitable climate, self-sustaining biodiversity and a good quality of life are not yet well established but range from 30 to 50 percent of all ocean and land surface areas. Options to improve the positive impacts of protected areas include greater resourcing, better management and enforcement, and improved distribution with increased inter-connectivity between these areas. Conservation measures beyond protected areas are also spotlighted - including migration corridors and planning for shifting climates, as well as better integration of people with nature to assure equity of access and use of nature's contributions to people.

Eliminating subsidies that support local and national activities harmful to biodiversity - such as deforestation, over-fertilization and over-fishing, can also support climate change mitigation and adaptation, together with changing individual consumption patterns, reducing loss and waste, and shifting diets, especially in rich countries, toward more plant-based options.

Some focused climate mitigation and adaptation measures identified by the report as harmful to biodiversity and nature's contributions to people include:

Planting bioenergy crops in monocultures over a very large share of land areas. Such crops are detrimental to ecosystems when deployed at very large scales, reducing nature's contributions to people and impeding achievement of many of the Sustainable Development Goals. At small scales, alongside pronounced and rapid reductions in fossil-fuel emissions, dedicated bioenergy crops for electricity production or fuels may provide co-benefits for climate adaptation and biodiversity.

Planting trees in ecosystems that have not historically been forests and reforestation with monocultures - especially with exotic tree species. This can contribute to climate change mitigation but is often damaging to biodiversity, food production and other nature's contributions to people, has no clear benefits for climate adaptation, and may displace local people through competition for land.

Increasing irrigation capacity. A common response to adapt agricultural systems to drought that often leads to water conflicts, dam building and long- term soil degradation from salinization.

Any measures that focus too narrowly on climate change mitigation should be evaluated in terms of their overall benefits and risks, such as some renewable energies generating surges of mining activity or consuming large amounts of land. The same applies to some technical measures too narrowly focused on adaptation, such as building dams and sea walls. Although important options for mitigating and adapting to climate change exist, these can have large negative environmental and social impacts - such as interference with migratory species and habitat fragmentation. Such impacts can be minimized, for instance, by developing alternative batteries and long-lived products, efficient recycling systems for mineral resources, and approaches to mining that include strong considerations for environmental and social sustainability.

The report authors stress that while nature offers effective ways to help mitigate climate change, these solutions can only be effective if building on ambitious reductions in all human-caused greenhouse gas emissions. "Land and ocean are already doing a lot - absorbing almost 50% of CO2 from human emissions - but nature cannot do everything," said Ana María Hernández Salgar, Chair of IPBES. "Transformative change in all parts of society and our economy is needed to stabilize our climate, stop biodiversity loss and chart a path to the sustainable future we want. This will also require us to address both crises together, in complementary ways."

Highlighting the significance of the co-sponsored workshop, Dr. Hoesung Lee, Chair of the IPCC, said: "Climate change and biodiversity loss combine to threaten society - often magnifying and accelerating each other. By focusing on synergies and trade-offs between biodiversity protection and climate change mitigation and adaptation, this workshop advanced the debate on how to maximize benefits to people and the planet. It also represented an important step in collaboration between our two communities."

"It may be impossible to achieve win-win synergies, or even manage the tradeoffs between climate and biodiversity actions in every single patch of a landscape or seascape," said Prof. Pörtner, "But achieving sustainable outcomes becomes progressively easier when integrating a mix of actions at larger spatial scales, through cross-border collaboration and joint consultative spatial planning, which is why it is important to also address the lack of effective governance systems and mechanisms to improve integration between solutions for climate change and biodiversity."

Credit: 
Terry Collins Assoc

Lunar sample tells ancient story with help of Curtin's world-class facilities

video: Atom probe reconstruction of Mg atoms in deformed apatite.

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Curtin University

Curtin University researchers have helped uncover the four billion year old story of a lunar sample brought from the Moon to Earth, by the manned Apollo 17 mission more than 50 years ago.

The global research collaboration, involving scientists from the UK, Canada, Sweden and Australia, aimed to analyse the ancient rock sample through a modern lens to find out its age, which crater it came from and its geological trajectory.

That modern lens was provided, in part, by both Curtin's Geoscience Atom Probe Facility* and Space Science and Technology Centre* (SSTC) where the research team was able to use the most advanced analytical equipment to accurately date the sample and perform sophisticated numerical impact simulations to determine the source crater.

Co-author Associate Professor Katarina Miljkovic from the SSTC in Curtin's School of Earth and Planetary Sciences said Curtin's involvement ensured the international team had access to world-class facilities in order to shed new light about Earth-Moon origins.

"Through a truly international collaborative effort, we have connected a tiny lunar sample investigated on a microscopic scale with the moment when the Moon's surface was smashed by a major impact event. The study showcases the extent of Curtin's analytical and numerical capability to solve complex geological problems on a planetary scale," Associate Professor Miljkovic said.

"Dating techniques (Uranium-Lead geochronology) suggested this sample from the Moon's Serenitatis Basin is very old, around 4.2 billion years- that's only about 350 million years younger than the entire Solar System, making it a precious sample for learning about the Moon's early evolution and our planet's origins.

"The study also provides a new insight into the atomic scale processes that take place in minerals affected by extreme impact events. The analytical work done at Curtin's Geoscience Atom Probe Facility looked at the distribution of atoms in the sample and found that it experienced not one, but two impact events. The second impact transported the sample near to its resting place where it was collected by astronauts."

Numerical impact simulations made at Curtin's Space Science and Technology Centre, supported the analytical findings with detailed understanding of the fate of this sample as it was flung across the Moon during the impact events that caused the craters.

Director of the SSTC, Professor Phil Bland said Curtin is proud to have played an integral part in uncovering this important story which provides an invaluable reference point to understand the entire bombardment history of the Earth-Moon system.

"This research shows that even the tiniest sample brought back from space may yield profound results that advance our understanding of the origins and evolution of Earth and planetary bodies in our Solar System," Professor Bland said.

"It is also an excellent demonstration of the need for more space missions that aim to return samples to Earth, given that the scientific return is enormous."

The research team was led by Dr Ana Cernok from Open University (UK) and also involved the University of Portsmouth (UK), Royal Ontario Museum, University of Toronto and Université de Sherbrooke (Canada) and Swedish Museum of Natural History (Sweden).

Researchers from Curtin also included Professor Steven Reddy, Dr Denis Fougerouse, Dr William Rickard and Dr David Saxey.

Some aspects of the study were supported by the Australia Research Council, the Science and Industry Endowment Fund and The Institute for Geoscience Research (TIGeR).

The full paper, 'Lunar samples record an impact 4.2 billion years ago that may have formed the Serenitatis Basin' was published in Nature Communications Earth and Environment.

Credit: 
Curtin University

Ion and lipid transporters specialize for their niche

image: Alignment between LMCA1 G4 E2-BeF3- (red) and SERCA E2-AlF4- (pdb: 3b9r) (dark grey). Relevant Ca2+-coordinating residues are shown as sticks. The structures are aligned by the residues shown as sticks. SERCA Ca2+ binding site I and II are indicated.

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Sara Basse Hansen, Aarhus University

Cell viability require that a variety of functions at the cell membrane are maintained properly. P-type ATPases translocate substrates across the membrane, and they have evolved into different types taking care of specific substrates within a diverse range. Now, key structural aspects have been described on how two different types of P-type ATPases - a Ca2+ transporting Ca2+ -ATPase and a lipid transporting P4-ATPase - have adapted to different substrates and physical environments.

Many bacteria export intracellular calcium using active transporters homologous to the well-described mammalian Ca2+-ATPases such as plasma-membrane Ca2+-ATPase and sarco-endoplasmic reticulum Ca2+-ATPase (PMCA and SERCA, respectively). Crystal structures of Ca2+-ATPase 1 from Listeria monocytogenes (LMCA1) suggest that LMCA1 is pre-organized for dephosphorylation upon Ca2+ release, which can explain the rapid dephosphorylation observed earlier in single-molecule studies.

Also, variation in the architecture of the calcium binding sites explains why LMCA1 transports a single Ca2+ ion similar to PMCA, in contrast to two transported Ca2+ ions in SERCA. The LMCA1 structures provide insight into the evolutionary divergence and conserved features of this important class of ion transporters that also inform us on central mechanisms of mammalian Ca2+ -ATPases and how they can be regulated or affected by pathological conditions.

For the P4-ATPase study, researchers took a different perspective. The transport cycle of a P-type ATPase consist of two half-reactions. Phosphorylation where a phosphate is transferred from ATP to the transporter, and dephosphorylation, where the phosphate is again released. In contrast to ion transporters such as LMCA1, the P4-ATPases transport lipids and are known as lipid flippases. Importantly, the lipid transport is coupled to the dephosphorylation reaction of the cycle, where for ion transporting P-type ATPases it is mainly coupled to the phosphorylation reaction.

Through new structures determined by cryo-electron microscopy (cryo-EM) of a yeast lipid flippase, Drs2p/Cdc50p, it was investigated how the lipid flippases have diverged from ion transporters and have adapted the enzymatic mechanism for the "flipped" purpose. Cryo-EM was a critical technique for this study, and multiple structures of the transport cycle could be determined by locking Drs2p/Cdc50p using different inhibitors and electron microscopy data collected at the electron microscopy infrastructure facility at Aarhus University (EMBION).

The two studies have been spearheaded by PhD student Sara Basse Hansen and Postdoc Milena Timcenko - under the supervision of Professor Poul Nissen (and Sara also of Associate Professor Magnus Kjærgaard) - and are being published in Journal of Molecular Biology.

Credit: 
Aarhus University

The survivability of animal species depends on the number of offspring

image: Amphibians.

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Tel Aviv University

Researchers from Tel Aviv University took part in a new international study proposing an amendment to the widely accepted theory on the extinction of animal species - by moving the focus from the animal's body size to its reproductive capacity. The researchers found gaps and incompatibilities between mammals and amphibians in the relation between body size and extinction risk: Whereas large mammals bear a smaller number of offspring per birth, leading to higher risk of extinction, larger amphibian females lay more eggs, reducing the threat to the species.

The researchers analyzed data from databases on both extinction risks and reproductive capacities of various species of amphibians (e.g., frogs and salamanders). Contributors to the international study included Prof. Shai Meiri from the School of Zoology at the George S. Wise Faculty of Life Sciences at Tel Aviv University, alongside researchers from Queen's University Belfast, Nottingham Trent University, Exeter University, and the University of Lincoln. The paper was published in the scientific journal Global Ecology and Biogeography.

Prof. Meiri explains that the accelerated extinction of biodiversity worldwide is one of the most pressing challenges facing humanity today. Thus, for scientists in an age of global warming and rapid destruction of natural habitats, understanding the factors that drive the process of extinction is a very high priority.

The extinction theory that has prevailed so far in the scientific world claims that larger species are at greater risk of extinction. This approach is supported by the high number of large and familiar animals that are in fact on the verge of extinction, such as rhinos and whales. One contradictory fact, however, not explained by this theory, is that over 40% of the amphibian species, such as frogs, toads, salamanders, and newts, are endangered despite their small body size - in fact more so than any other vertebrate.

While in other animals the number of offspring decreases as the body size increases, this is not true for amphibians. The researchers found that the females of the smaller amphibians, such as rain frogs (Eleutherodactylus), produce fewer offspring per clutch, compared to larger species like the American bullfrog (Lithobates), that lays up to 80,000 eggs every time. Thus, harmful impact on one generation of small amphibians due to the destruction of their natural habitat can drastically reduce their population and increase the threat of extinction.

Prof. Shai Meiri: "Protecting nature begins with basic science, like this study which gives us more tools to understand the processes of extinction. As we learn more and understand these processes better, we can focus our preservation efforts and point to new, untried directions. An emphasis on the number of offspring rather than body size will help us examine which species and/or geographical regions require protection. In this way the present study can provide a basis for more effective activities in the global struggle against biodiversity loss."

Dr. Daniel Pincheira-Donoso, Lecturer in Evolutionary Biology & Macroecology from the School of Biological Sciences at Queen's University: "More babies per clutch or birth means more variety among the babies. To some extent, it is like playing the lottery: the more tickets you play the higher your chances to win. In this case, more numerous and diverse babies increase the chances that at least some can survive the stress of environmental alterations, such as progressive climatic changes."

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Tel-Aviv University

Trapping DNA damage

Even on a good day, DNA is constantly getting damaged.

Nicks, scratches, breaks: the delicate strands that carry life's genetic code take a beating as they jumble about in the course of their work. If left untreated, errors accumulate, with fatal consequences -- such as cancerous tumors -- for the cell and the organism.

This is where two key proteins come to the rescue: PARP -- or poly ADP ribose polymerase -- acts as a marker for a trouble spot, allowing XRCC1 -- or X-ray repair cross-complementing protein 1 -- to zoom in and begin a repair.

This much has been known for some time and was even recognized in the 2015 Nobel prizes for chemistry, resulting in the development of anti-cancer drugs known as PARP inhibitors that work to disrupt the growth of certain types of tumors.

But while these actors had been identified, their precise roles were not clear. Now a team of scientists at Tokyo Metropolitan University, the University of Sussex, and Kyoto University have revealed exactly how XRCC1 does its work.

"PARP turns out to be something of a villain," explains Kouji Hirota at Tokyo Metropolitan. "The spots it marks become 'PARP traps', which left un-repaired lead to disfunction and cell death."

XRCC1 therefore isn't simply repairing DNA, it is disarming PARP traps.

The scientists compared cells lacking the XRCC1 gene with those lacking PARP as well as with still others lacking both proteins. The team discovered that without XRCC1 on patrol, PARP traps accumulate like landmines.

"PARP exerts toxic effects in the cell and XRCC1 suppresses this toxicity," Hirota elaborates.

The team next seeks to delve even further into these processes, aiming to aid in the development of future cancer treatments.

KyotoU's Shunichi Takeda says: "These results indicate that XRCC1 is a critical factor in the resolution of PARP traps and may be a determinant of the therapeutic effect of PARP inhibitors used in the treatment of hereditary breast and ovarian cancer syndromes."

Credit: 
Kyoto University

'Bad fat' suppresses killer T cells from attacking cancer

LA JOLLA--(June 10, 2021) In order for cancer to grow and spread, it has to evade detection by our immune cells, particularly specialized "killer" T cells. Salk researchers led by Professor Susan Kaech have found that the environment inside tumors (the tumor microenvironment) contains an abundance of oxidized fat molecules, which, when ingested by the killer T cells, suppresses their ability to kill cancer cells. In a vicious cycle, those T cells, in need of energy, increase the level of a cellular fat transporter, CD36, that unfortunately saturates them with even more oxidized fat and further curtails their anti-tumor functions.

The discovery, published online in Immunity on June 7, 2021, suggests new pathways for safeguarding the immune system's ability to fight cancer by reducing the oxidative lipid damage in killer T cells. Identifying factors like these that cause immune suppression in the tumor microenvironment can lead to the development of novel immunotherapies for cancer.

"We know that tumors are a metabolically hostile environment for healthy cells, but elucidating which metabolic processes are altered and how this suppresses immune cell function is an important area of cancer research that is gaining a lot of attention," says Kaech, senior author and director of Salk's NOMIS Center for Immunobiology and Microbial Pathogenesis. "Our findings uncovered a novel mode of immunosuppression in tumors involving the import of oxidized fats (AKA lipids) in T cells via the cellular fat transporter CD36, which impairs their anti-tumor functions locally."

The burgeoning field of cancer immunometabolism studies how immune cell metabolism is reprogrammed within tumors and driven by alterations in nutrient availability. While scientists know that tumors accumulate fats--and that such accumulation is associated with immune dysfunction--the details of the relationship haven't been clear.

Working with Joseph Witztum's lab at UC San Diego and Antonio Pinto in the Salk Mass Spectrometry Core facility, the team established that tumors contain elevated amounts of several classes of lipid, and oxidized lipids in particular, which are generally found in oxidized low-density lipoproteins (LDLs), commonly considered "bad" fat. They then observed how killer T cells respond to the oxidized LDLs in tumors and found that killer T cells adapted to the tumor microenvironment by increasing CD36 on their surface and ingesting an abundance of oxidized lipids. Working with Brinda Emu's lab at Yale University, they found this process served as a catalyst to drive even greater amounts of lipid oxidation internally in the killer T cells and ultimately repressed their defenses.

Next, the team employed various methods to investigate how CD36 impaired killer T cell function. They created mouse models lacking CD36 on T cells and used antibodies to block CD36. They confirmed that CD36 promoted T cell dysfunction in tumors by increasing oxidized lipid import, which caused greater lipid oxidation and damage within the T cells and triggered the activation of a stress response protein, p38.

"We found that when the T cells get 'stressed out' by oxidized lipids, they shut down their anti-tumor functions," says Shihao Xu, a Salk postdoctoral fellow and the first author on the paper.

The team also found new therapeutic opportunities to reduce lipid oxidation and restore killer T cells' function in tumors through immunotherapy by blocking CD36 with an antibody therapy or by overexpressing glutathione peroxidase 4 (GPX4, a key molecule that removes oxidized lipids in cells).

Importantly, lipid oxidation doesn't just happen in T cells; it also happens in tumor cells, and too much of it can cause cell death. In fact, there is a lot of excitement in cancer research to increase lipid oxidation in tumor cells to a lethal level, but Kaech and her team urge some caution.

"Now that we've uncovered this vulnerability of T cells to lipid oxidation stress, we may need to find more selective approaches to inducing lipid oxidation in the tumor cells but not in the T cells," says Kaech, who holds the NOMIS Chair at Salk. "Otherwise, we may destroy the anti-tumor T cells in the process, and our work shows a few interesting possibilities for how to do this."

Credit: 
Salk Institute