Earth

Latest findings from expanded research on Antarctic meteorology and climate

image: Featured on the cover is China's first homemade icebreaker (Xuelong 2, left-hand vessel), which was designed to break 1.5-m-thick ice and 0.2-m-thick snow at a speed of 2-3 knots. It completed its testing by breaking through the shelf ice forwardly and backwardly near the Chinese station Zhongshan during the 36th Antarctic expedition. The icebreaker Xuelong (right-hand vessel) also joined this expedition, marking the first time for two Chinese icebreakers to have worked together and setting a new milestone for China's polar research.

Image: 
Advances in Atmospheric Sciences

The April 18 special issue of Advances in Atmospheric Sciences, titled, "Antarctic Meteorology and Climate: Past, Present and Future," presents the latest findings from expanded and ongoing research efforts in Antarctic meteorology, weather prediction, climate variability and climate change.

The issue presents research conducted during the recent Year of Polar Prediction (YOPP, https://www.polarprediction.net)--an international effort by the World Meteorological Organization to improve predictions of weather, climate and sea-ice conditions in the Arctic and Antarctic. This collection of peer-reviewed papers provides evidence of variability and change in Antarctic environmental conditions, mostly based on enhanced observations carried out during the YOPP Special Observing Period in the Southern Ocean, the most extensive period of observations ever conducted in and around Antarctica.

YOPP efforts in the Southern Hemisphere stimulated additional research in Antarctic meteorology and climate by enabling increased data collection and enhanced computing power for modeling. The AAS special issue suggests that future Antarctic weather forecasts and climate predictions will be more reliable based on the combined new insights into the atmosphere, land surface, ocean conditions and sea ice variability--ultimately making operations in Antarctica and the Southern Ocean safer.

"These studies make important contributions to our understanding of the weather and climate systems in the polar regions and can improve future climate projections while producing important information for policymakers," said Ming Xue, an AAS editor-in-chief, and professor and director of the Center for Analysis and Prediction of Storms at the University of Oklahoma in Norman, Oklahoma.

The special issue also indicates that long-term weather and climate changes are already underway across Antarctica and the Southern Ocean with potentially far-reaching consequences, which will be the object of future research.

"Climate change research in the Antarctic is relatively neglected compared to the Arctic," said Jiping Liu, the issue's lead editor and associate professor at the University at Albany in Albany, New York. "However, it's clear that climate change is already impacting the Antarctic and that studying the changes is vital, because it enables us to predict the future climate more accurately."

Signs of climate change in the Antarctic, added Liu, include a strong warming over the Antarctic Peninsula, a deepening of the Amundsen Sea low, rapid warming of the upper ocean north of the circumpolar current, an increase of sea ice since the late 1970s followed by a recent rapid decrease and accelerated ice loss from ice shelf/sheet during the same period.

Some of the highlights from the issue include:

Lazzara et al. summarize the challenges and outcomes of five themes discussed during the 13th (2018) and 14th (2019) workshops on Antarctic meteorology and climate, including meteorological observations, atmospheric numerical modeling, meteorological and climate research, weather forecasting and operational services, and the YOPP in the Southern Hemisphere effort (YOPP-SH).

Sato et al. assess forecasts with and without including radiosonde data obtained from the Japanese icebreaking research vessel and Antarctic Dome Fuji station.

Bozkurt et al. analyze recent near-surface temperature trends and identify a windward warming over the Peninsula (except during summer).

Ding et al. analyze precipitation at the Chinese station and identify a change in summer precipitation (rainfall vs. snowfall) that occurred around the early 2000s.

"This is the second special issue published by AAS highlighting scientific progress in important areas addressed by the YOPP," said Thomas Jung, professor at the Alfred Wegener Institute in Bremerhaven, Germany, and YOPP coordinator. " In 2018, AAS also published a special issue focusing on the impact of Arctic change on Eurasian climate and weather."

Credit: 
Institute of Atmospheric Physics, Chinese Academy of Sciences

Business-to-business customers expect personal service in online chat

For a long time, companies have used cost-effective chat services in their business-to-customer (B2C) sales. Companies engaged in business-to-business (B2B) sales are also increasingly moving their activities online, but their online chat services and customer interaction have not been studied much yet. A new study from the University of Eastern Finland shows that the nature of social presence in B2B online chat dialogues varied depending on the stage of the customer relationship.

Published in European Journal of Marketing, the study explored social presence in a B2B online chat service. In technology-mediated communication, social presence refers to a feeling of interaction with a real, authentic person. The data was collected at a case company specialising in SaaS services, and it comprised 157 chat dialogues between buyers and sellers.

"A lack of social presence can be one reason why a company's online sales aren't growing. Many companies want to invest in elements that ooze social presence, since anonymous, asynchronous and text-based technology-mediated communication can reduce the creation of trust between the parties," University Lecturer Jonna Koponen from the University of Eastern Finland notes.

New customers are looking for solutions to their business problems, existing customers maintain their customer relationship

The study showed that the behaviour and goals of customers in online chat dialogues varied depending on the stage of the customer relationship. New customers and potential buyers were looking for solutions to their business problems, asked for more information on SaaS services or gave feedback to the company. In a best-case scenario, they had decided to purchase the service or wanted to continue their dialogue with the company's solution sales representative in another communication channel.

The company's long-term customers, on the other hand, used the chat service for obtaining information, solving problems, giving feedback and booking appointments with the company's solution sales representative. They also used the chat service to maintain the customer relationship. Sometimes they even brought in new customers by recommending the company to others.

"Social presence plays a key role in e-commerce. Earlier studies have shown that social presence increases the customer's trust in the website and in the seller, and it also provides support for the customer's decision to purchase," Koponen says.

The study is the first to show how an online chat service can help to build customer relationships in B2B e-commerce. The chat service was also one of the channels B2B customers used for making complaints. The findings of the study can be used in the development of chat bots, in sales and marketing training, as well as in the development of companies' e-commerce.

Credit: 
University of Eastern Finland

Stem cells in human embryos commit to specialization surprisingly early

The point when human embryonic stem cells irreversibly commit to becoming specialised has been identified by researchers at the Francis Crick Institute.

Our biological history can be traced back to a small group of cells called embryonic stem cells, which through cell division, give rise to cells that specialise to perform a specific role in the body - a process known as differentiation.

Understanding when and how embryonic stem cells specialise provides insights into healthy differentiation and how cells 'remember' what type of cell they are. This process can go wrong in cancer, when cells 'forget' their identity and change into the wrong type.

As part of the research, published in Cell Stem Cell, Crick scientists found that embryonic stem cells differentiate unexpectedly early, irreversibly committing to become each of the more than 200 cell types in the body.

They showed this was as a result of a newly identified small group of genes becoming activated, which they named 'early-commitment genes'.

"Working with stem cells and mathematical models, we've identified a new class of genes which are responsible for regulating one of the earliest stages of human development," says Silvia Santos, author and group leader in the Quantitative Cell Biology Laboratory at the Crick.

"Once these genes are activated, it's a question of minutes before the cells fully commit to differentiation. The speed of this is incredibly surprising, especially if you consider how the first signs of differentiation, that's the embryo developing the first embryonic germ layers, take about three days. These layers ultimately give rise to all the tissues in the growing foetus weeks later."

The researchers focused on one early-commitment gene, called GATA3. When this gene was activated experimentally in the lab, embryonic stem cells quickly committed to differentiation. On the other hand, when this gene was deleted, this process was sluggish and not quite right.

"GATA3 is crucial to the healthy, timely differentiation of stem cells. Once it's switched on, this gene triggers a positive feedback loop, which helps it stay active. In turn, this ensures that the cells remain differentiated, and do not reverse back to a stem cell state," says Alexandra Gunne-Braden, co-lead author and postdoc in the Quantitative Cell Biology Laboratory at the Crick.

This research used stem cells taken from embryos donated by people undergoing IVF. The donated embryos were not needed in the course of their fertility treatment and would have otherwise been destroyed.

"When embryonic stem cells commit to specialisation is a fundamental and yet until now, unanswered question," continues Silvia Santos.

"It's important we understand more about this, as the healthy function of cells is underpinned by the process of how cells acquire and remember their identity during the process of differentiation. This valuable insight into early human development could open up new avenues for research into diseases that occur when this process goes wrong."

Credit: 
The Francis Crick Institute

A key brain region for controlling binge drinking has been found

image: A magnified image of cells in the extended amygdala. The green color indicates cells that produce the kappa opioid receptor activating protein. Image courtesy of JR Haun, Medical University of South Carolina.

Image: 
JR Haun, Medical University of South Carolina

A team of National Institutes of Health-funded researchers at the Medical University of South Carolina has found that deactivating a stress-signaling system in a brain area known for motivation and emotion-related behaviors decreases binge drinking. The study, which was published online in February and is to appear in the May issue of Neuropharmacology, pinpoints a particular system in a specific brain region that can be manipulated to reduce harmful binge drinking.

The MUSC team was led by Howard C. Becker, Ph.D., director of the Charleston Alcohol Research Center and professor in the Department of Psychiatry & Behavioral Sciences.

"Binge drinking is one of the most common patterns in which alcohol is consumed," explained Becker. "It's a risky behavior, and one consequence of repeated binge drinking is increasing risk for developing an alcohol use disorder."

Further, according to Becker, those who consistently binge drink, particularly during adolescent and college years, have almost 10 times the risk of developing an alcohol use disorder.

But how much alcohol must be consumed to qualify a drinking session as a binge?

A binge, as defined by the National Institute on Alcohol Abuse and Alcoholism, or NIAAA, means drinking to the legal limit of intoxication within two hours. Becker put this into perspective.

"This is four standard drinks for a woman or five drinks for a male - consumed over about a two-hour period," he explained.

JR Haun, a graduate student in the Becker laboratory and first author on the article, described what the NIAAA considers 'standard' related to certain beverage types.

"A drink is defined as roughly one 12-ounce can of beer, a five-ounce glass of wine or a standard 1.5 ounce shot of distilled spirits," he explained, adding that the serving sizes can vary based on the percentage of pure alcohol in the drink.

In their study, Becker and Haun tested a potential strategy for reducing risky binge drinking.

"Binge drinking is a destructive behavior," said Haun. "And our goal was to curb that. Through our investigation, we found a brain region and a system that we can manipulate to decrease binge drinking."

The system that Becker's team investigated - the opioid receptor system - is well-recognized in the addiction field.

Notorious narcotic drugs of abuse, such as morphine, heroin and oxycontin/oxycodone act on the opioid-receptor system, producing the pleasurable effects that make these drugs so addictive.

However, there is an odd opioid receptor out, so to speak, that is not involved in signaling pleasure.

"The kappa opioid-receptor system is the antithesis to other opioid receptors," explained Haun. "It's often referred to as an anti-reward system."

Instead of feelings of pleasure, the kappa opioid receptor produces stress and discontent.

When people drink and experience positive effects, that is partially due to pleasurable opioid receptors being activated. However, after they have finished drinking and nausea, headache, and the stress of withdrawal start to set in, the kappa opioid receptor system has been activated.

Becker's team found that turning off the kappa opioid receptors in the brain decreased binge drinking. This finding suggests that the kappa opioid receptor system is important not only in the negative state of withdrawal but also in driving binge drinking itself.

At first glance, this finding might sound counterintuitive. How does turning off the negative effects of the kappa opioid receptor decrease drinking?

"It's not entirely clear why," said Haun. "But what we do know is that kappa opioid receptors play an important role in the negative emotional state that drives drinking when it becomes compulsive in alcohol use disorders."

Becker and Haun hypothesize that the kappa opioid receptor system may drive binge and compulsive alcohol use in a similar way, in addition to contributing to stress and unease during withdrawal.

To begin testing their hypothesis, Becker and Haun first identified the exact region in the brain that is involved in binge drinking driven by kappa opioid receptors.

Becker's team homed in on a network of structures called the extended amygdala. According to Haun, it is a part of the brain that's involved in motivational behavior, is very responsive to stress, and is implicated in compulsive drinking. This network of circuits in the brain also contains a number of kappa opioid receptors, making it the team's top candidate to investigate for its role in regulating excessive drinking.

To determine how kappa opioid receptors in the extended amygdala affect binge drinking, Becker's team specifically inactivated kappa opioid receptors in this region in mice.

"Haun actually introduced a drug that blocks kappa opioid receptors right into the extended amygdala," explained Becker.

This study used a binge-drinking mouse model, which allowed the mice to drink freely for four hours each night.

"The mice will drink enough alcohol in this relatively short period of time to achieve blood alcohol levels that would define it as a binge episode," said Becker.

After blocking the kappa opioid receptors in these mice, the team tested how much alcohol the animals voluntarily consumed. What they found could have important implications for future treatments of chronic binge drinking, according to Haun.

"Blocking these kappa receptors in the extended amygdala didn't completely abolish drinking," explained Haun. "It brought it down to a more moderate level, the equivalent being a glass of wine at dinner opposed to a bottle."

This finding supports Becker and Haun's hypothesis that the kappa opioid receptor system in the extended amygdala promotes binge drinking.

Blocking kappa opioid receptors in the extended amygdala, therefore, could act as a therapy to taper binge drinking.

So will there soon be a pill to curb the urge to binge?

According to Becker, if such a therapy were developed, he believes it would be best tailored for those who have difficulty controlling more chronic heavy drinking, such as those with an alcohol use disorder.

"I think the ultimate goal is to better understand new potential treatment targets and how new therapeutics may have some value in helping to quell the desire and motivation to drink excessively in those who have developed an alcohol use disorder or are on the threshold of doing so," explained Becker.

Credit: 
Medical University of South Carolina

Nanoparticles: Acidic alert

Researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich have synthesized nanoparticles that can be induced by a change in pH to release a deadly dose of ionized iron within cells. This mechanism could potentially open up new approaches to the targeted elimination of malignant tumors.

Ions play crucial roles in all aspects of cell biology. They trigger signaling cascades, regulate enzyme activities and control the pH of the intra- and extracellular media. The concentrations of free ions are therefore tightly regulated, and sudden changes in their intracellular levels can induce programmed cell death. However, this very fact has made it difficult to elucidate the complex mechanisms that control ion concentrations in cells. Because cells act rapidly to block the import of excess ions, they effectively resist attempts to manipulate intracellular ion levels. A research team led by Hanna Engelke and Evelyn Ploetz (Faculty of Chemistry and Pharmacy, LMU) has now synthesized nanoparticles that make it possible - for the first time - to rapidly trigger the large-scale release of ionic iron within cells in a controlled manner. This in turn precipitates a form of inflammatory cell death known as pyroptosis, a type of reaction that is specific to cells of the innate immune system. According to the new study, which appears in the journal Advanced Materials, the ability to induce pyroptosis on demand could in principle be utilized to eliminate malignant cells, and to trigger an immune reaction that is specifically directed against cancers.

The rapid-release effect is a direct result of the structural properties of the nanoparticles, which belong to a class of substances known as metal-organic frameworks (MOFs). The interstices formed by these frameworks provide identical binding sites to which other substances - in this case, iron-oxygen complexes - can be specifically attached. "Structurally, these binding sites are tiny hexagons that are connected to each other by organic linker molecules," Ploetz explains. "MOFs can be thought of as scaffolds, and the pores within each nanoparticle are large enough to allow reaction partners to diffuse into them." In addition the nanoparticles are coated with lipids, which enables them to be taken up by cells.

Once inside the cell, the nanoparticles are transported into organelles called lysosomes, where they are degraded. "We were able to demonstrate that the rate of degradation depends on the pH of the extracellular medium. If the pH value is relatively low, as it is in an acidic milieu, degradation occurs rapidly, which results in a sudden and massive release of iron ions," Ploetz says. She and her colleagues suspect that this effect is attributable to the fact that, under mildly acidic conditions, the reduced form of the amino acid cysteine - which promotes the dissolution of the nanoparticles - is present in excess.

"We were particularly surprised to find that the release of iron from the nanoparticles did not induce ferroptosis, as one might expect in the presence of excess iron. Instead, they trigger a reaction known as pyroptosis," says Ploetz. Induction of pyroptosis in cells of the innate immune system results in a strong inflammatory reaction, which kills the cell concerned, but may serve as a signal that activates anti-tumor immunity.

The authors point out that these nanoparticles have great potential as therapeutic agents, particularly in the treatment of malignant tumors. "The extracellular medium within tumors is more acidic than that associated with normal cells. In principle, this pH difference could be exploited for the targeted release of the iron within the tumor environment. That would enable the nanoparticles to attack the primary tumor directly, while inducing pyroptosis to activate the immune system," says Ploetz. "But because their properties can be readily controlled by altering the pH, they are also ideally suited for application in other contexts."

Credit: 
Ludwig-Maximilians-Universität München

Mysterious tuft cells found to play role in pancreatitis

image: Pancreatitis tuft cells (red, microvilli and actin rootlets) in the injured pancreas (green); nuclei (blue).

Image: 
Salk Institute

LA JOLLA--(April 17, 2020) Persistent inflammation of the pancreas (chronic pancreatitis) is a known risk factor for developing pancreatic cancer, the third-deadliest cancer in the United States. Tuft cells--cells sensitive to chemical (chemosensory) changes typically found in the intestines and respiratory tract--had previously been discovered in the pancreas, but their function has largely remained a mystery. Now, a team of Salk scientists led by Professor Geoffrey Wahl and Staff Scientist Kathleen DelGiorno has uncovered the formation of tuft cells during pancreatitis and the surprising role of tuft cells in immunity, using mouse models of pancreatitis. The findings, published in Frontiers in Physiology on February 14, 2020, could lead to the development of new biomarkers to test for pancreatitis and pancreatic cancer.

"By understanding these early stages of pancreas disease, we hope our work will lead to the development of new strategies to diagnose and treat pancreatitis and pancreatic cancer early on," says Wahl, co-corresponding author and holder of the Daniel and Martina Lewis Chair in Salk's Gene Expression Laboratory.

The pancreas is an abdominal organ that plays a role in digestion and blood sugar regulation. Yet, scientists know little about how the pancreas recovers from injuries, such as pancreatitis, or fights off pancreatic cancer. Most of the pancreas is composed of acinar cells, which produce and secrete digestive enzymes. Acinar cells also have the ability to transform into another type of cell called a tuft cell. Scientists do not know all of the functions of tuft cells, but previous work showed that intestinal tuft cells secrete the protein IL-25 to support the immune response during parasitic infections.

"Since cancer has been called 'the wound that never heals,' we wanted to investigate how the pancreas heals from pancreatitis to better understand pathways that may be co-opted by cancer," says Razia Naeem, co-first author and laboratory technician in the Wahl lab.

The researchers used a combination of techniques including histology, imaging and molecular strategies to characterize tuft cell populations in pancreatitis mouse models. They found that, although the pancreas does not normally contain tuft cells, during pancreatitis acinar cells undergo complex changes to become tuft cells, as a normal part of pancreatic injury and recovery. This transformation is similar to a reserve soldier (acinar cell) who must then change from their civilian clothes into that of a soldier (tuft cell) to fight off the enemy of inflammation.

The researchers also observed that the pancreatitis-induced tuft cells secreted IL-25 to promote the immune response, similar to what had previously been found in the intestine. Thus, tuft cells may play a role modulating the immune system during pancreatitis.

The scientists examined tuft cell formation in seven strains of mice to see if there were any differences during the development of pancreatitis. Surprisingly, the team found that tuft cell formation did not occur in all strains of mice. The most genetically diverse animals produced the most tuft cells, suggesting that tuft cell formation is either controlled genetically or by influences on gene expression (epigenetics).

"The genetic susceptibility of tuft cell formation may represent a critical factor in pancreatitis formation, severity and progression to cancer in humans," says Kathleen DelGiorno, first and co-corresponding author of the paper and staff scientist in the Wahl lab. "Our work demonstrates that it's important to use the right mouse model to study pancreatitis and pancreatic cancer for there to be relevance to humans."

The team's work shows that using genetically diverse mice may better represent the complex human genome, allowing for more translatable modeling of disease in the lab, according to Wahl. The findings could mean that some people may be more susceptible to getting pancreatitis than others.

Next, the group plans to follow up on their gene expression analyses to pinpoint which genes control tuft cell formation in pancreatitis and whether tuft cells affect progression to pancreatic cancer. Their biggest hope is that their results will help pave the way for more targeted treatments for pancreatitis and cancer.

Credit: 
Salk Institute

Climate-driven megadrought is emerging in western US, says study

image: Areas of southwestern North America affected by drought in the early 2000s; darker colors are more intense. Yellow box shows the study area.

Image: 
Adapted from Williams et al., Science, 2020

With the western United States and northern Mexico suffering an ever-lengthening string of dry years starting in 2000, scientists have been warning for some time that climate change may be pushing the region toward an extreme long-term drought worse than any in recorded history. A new study says the time has arrived: a megadrought as bad or worse than anything even from known prehistory is very likely in progress, and warming climate is playing a key role. The study, based on modern weather observations, 1,200 years of tree-ring data and dozens of climate models, appears this week in the leading journal Science.

"Earlier studies were largely model projections of the future," said lead author Park Williams, a bioclimatologist at Columbia University's Lamont-Doherty Earth Observatory. "We're no longer looking at projections, but at where we are now. We now have enough observations of current drought and tree-ring records of past drought to say that we're on the same trajectory as the worst prehistoric droughts."

Reliable modern observations date only to about 1900, but tree rings have allowed scientists to infer yearly soil moisture for centuries before humans began influencing climate. Among other things, previous research has tied catastrophic naturally driven droughts recorded in tree rings to upheavals among indigenous Medieval-era civilizations in the Southwest. The new study is the most up-to-date and comprehensive long-term analysis. It covers an area stretching across nine U.S. states from Oregon and Montana down through California and New Mexico, and part of northern Mexico.

Using rings from many thousands of trees, the researchers charted dozens of droughts across the region, starting in 800 AD. Four stand out as so-called megadroughts, with extreme aridity lasting decades: the late 800s, mid-1100s, the 1200s, and the late 1500s. After 1600, there were other droughts, but none on this scale.

The team then compared the ancient megadroughts to soil moisture records calculated from observed weather in the 19 years from 2000 to 2018. Their conclusion: as measured against the worst 19-year increments within the previous episodes, the current drought is already outdoing the three earliest ones. The fourth, which spanned 1575 to 1603, may have been the worst of all -- but the difference is slight enough to be within the range of uncertainty. Furthermore, the current drought is affecting wider areas more consistently than any of the earlier ones -- a fingerprint of global warming, say the researchers. All of the ancient droughts lasted longer than 19 years -- the one that started in the 1200s ran nearly a century -- but all began on a similar path to to what is showing up now, they say.

Nature drove the ancient droughts, and still plays a strong role today. A study last year led by Lamont's Nathan Steiger showed that among other things, unusually cool periodic conditions over the tropical Pacific Ocean (commonly called La Niña) during the previous megadroughts pushed storm tracks further north, and starved the region of precipitation. Such conditions, and possibly other natural factors, appear to have also cut precipitation in recent years. However, with global warming proceeding, the authors say that average temperatures since 2000 have been pushed 1.2 degrees C (2.2 F) above what they would have been otherwise. Because hotter air tends to hold more moisture, that moisture is being pulled from the ground. This has intensified drying of soils already starved of precipitation.

All told, the researchers say that rising temperatures are responsible for about half the pace and severity of the current drought. If this overall warming were subtracted from the equation, the current drought would rank as the 11th worst detected -- bad, but nowhere near what it has developed into.

"It doesn't matter if this is exactly the worst drought ever," said coauthor Benjamin Cook, who is affiliated with Lamont and the Goddard Institute for Space Studies. "What matters is that it has been made much worse than it would have been because of climate change." Since temperatures are projected to keep rising, it is likely the drought will continue for the foreseeable future; or fade briefly only to return, say the researchers.

"Because the background is getting warmer, the dice are increasingly loaded toward longer and more severe droughts," said Williams. "We may get lucky, and natural variability will bring more precipitation for a while. But going forward, we'll need more and more good luck to break out of drought, and less and less bad luck to go back into drought." Williams said it is conceivable the region could stay arid for centuries. "That's not my prediction right now, but it's possible," he said.

Lamont climatologist Richard Seager was one of the first to predict, in a 2007 paper, that climate change might eventually push the region into a more arid climate during the 21st century; he speculated at the time that the process might already be underway. By 2015, when 11 of the past 14 years had seen drought, Benjamin Cook led a followup study projecting that warming climate would cause the catastrophic natural droughts of prehistory to be repeated by the latter 21st century. A 2016 study coauthored by several Lamont scientist reinforced those findings. Now, says Cook, it looks like they may have underestimated. "It's already happening," he said.

The effects are palpable. The mighty reservoirs of Lake Mead and Lake Powell along the Colorado River, which supply agriculture around the region, have shrunk dramatically. Insect outbreaks are ravaging dried-out forests. Wildfires in California and across wider areas of the U.S. West are growing in area. While 2019 was a relatively wet year, leading to hope that things might be easing up, early indications show that 2020 is already on a track for resumed aridity.

"There is no reason to believe that the sort of natural variability documented in the paleoclimatic record will not continue into the future, but the difference is that droughts will occur under warmer temperatures," said Connie Woodhouse, a climate scientist at the University of Arizona who was not involved in the study. "These warmer conditions will exacerbate droughts, making them more severe, longer, and more widespread than they would have been otherwise."

Angeline Pendergrass, a staff scientist at the U.S. National Center for Atmospheric Research, said that she thinks it is too early to say whether the region is at the cusp of a true megadrought, because the study confirms that natural weather swings are still playing a strong role. That said, "even though natural variability will always play a large role in drought, climate change makes it worse," she said.

Tucked into the researchers' data: the 20th century was the wettest century in the entire 1200-year record. It was during that time that population boomed, and that has continued. "The 20th century gave us an overly optimistic view of how much water is potentially available," said Cook. "It goes to show that studies like this are not just about ancient history. They're about problems that are already here."

Credit: 
Columbia Climate School

Study: Cultural variables play important role in perceptions of status, power

image: Cultural variables play an important role in perceptions of status and power in business, according to research co-written by Carlos Torelli, a professor of business administration and the James F. Towey Faculty Fellow at the Gies College of Busines at Illinois.

Image: 
Photo by Gies College of Business

CHAMPAIGN, Ill. -- Are powerful individuals such as politicians necessarily viewed by others as having high status? And conversely, are high-status individuals such as tech moguls always seen as powerful? According to new research co-written by a University of Illinois at Urbana-Champaign expert in consumer behavior and global marketing, the answer depends on one's cultural orientation.

Cultures with a "vertical collectivist orientation," in which the individual willingly submits to authority by subordinating personal goals and accepting hierarchy, respond differently to the power-status dynamic than cultures with a more egalitarian "horizontal collectivistic orientation" that emphasizes communality and pro-social cooperation, said Carlos Torelli, a professor of business administration and the James F. Towey Faculty Fellow at Illinois.

"Power and status are different sources of social hierarchy with distinct consequences," he said. "Power equates to control over resources, while status broadly means respect and admiration. A bill collector has power but doesn't have high status. An Olympic athlete, on the other hand, has high status but doesn't have power. Our paper seeks to advance understanding of social hierarchies by proposing that this variation can be explained, at least in part, by one's cultural orientation."

Across six studies, Torelli and his co-authors used a range of methodologies to investigate the perceptions of the power-status dynamic to better understand the established effects on fairness.

"Power and status are distinct bases of social hierarchy with unique effects," said Torelli, also the executive director of Executive and Professional Education at the Gies College of Business. "Yet evidence suggests wide variation in whether perceptions of status and power are highly correlated versus relatively distinct. We use a cross-cultural lens to explain this variation and suggest that cultural orientation shapes the effect of power on perceived status, and vice versa."

These cultural contingencies, in turn, have implications for established effects of power and status.

Because vertical collectivism - common in east Asia - is associated with a tendency to automatically respect those in positions of power and authority, the extent to which individuals perceive high-power individuals as also having high status increases, according to the research.

"In those cultures, it's not uncommon for powerful leaders - say, a Bill Gates type - to be widely respected and also seen as a high-status individual," Torelli said.

On the other hand, cultures with a horizontal collectivistic orientation - common in some parts of Latin America - view hierarchy in a much dimmer light, he said. As a result, horizontal collectivists don't automatically submit to authority, and believe goals are best achieved via cooperation and pro-sociality toward others. Accordingly, these cultures foster perceptions that high-status individuals - say, a LeBron James type - also have power.

The insights gleaned from the research have practical relevance for organizations and individuals in the global economy, Torelli said.

"The results have important implications for navigating social hierarchies in different cultural settings," he said. "If you're a manager or other high-level executive and you're transferred to a vertical-collectivist culture, you'll automatically be respected. But you also need to exercise that power. You can't lurk in the background. You have to be out front and assert yourself."

If you move to a more horizontal-collective environment, you shouldn't assume that "just because you're the boss, people will automatically respect you," Torelli said.

"You have to earn their respect by showing your employees your interpersonal ability - your empathy, your concern about your subordinates, your level of cooperation. That becomes more important in a horizontal-collectivistic environment, less so in a vertical-hierarchical environment. It's more important to perform in that environment."

Although the U.S. is an individualistic country that doesn't in aggregate subscribe to vertical or horizontal collectivism, pockets of collectivism exist in the southern U.S., Torelli said.

"Immigration patterns are also bringing more cultural diversity to the workplace - for example, collectivism associated with Latin American and east Asian immigrants - and younger generations are increasingly endorsing a horizontal-collectivist orientation," he said. "Managers operating in these settings should also pay attention to perceptions of the power-status dynamics."

Torelli said the research has direct consequences for American managers operating in global environments.

"There are important consequences for C-level executive types who are looking to break into markets in certain parts of east Asia or Latin America," Torelli said. "And that's important because the east Asian market is going to define the global economy for many years to come."

Torelli's co-authors are Lisa M. Leslie, of New York University; Jennifer L. Stoner, of the University of North Dakota; and Christopher To, of Northwestern University.

The paper was published in the journal Organizational Behavior and Human Decision Processes.

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

New universal Ebola vaccine may fight all four virus species that infect humans

image: The highly infectious and deadly Ebola virus is shown in this research photo from the National Institute of Allergy and Infectious Diseases. Ebola virus disease has an average fatality rate of about 50%, although rates in certain recent outbreaks have reached close to 90%, according to the World Health Organization. Researchers report in the Journal of Virology early development of a potential universal vaccine for Ebola. Preclinical tests show it may neutralize all four species of the virus infecting people.

Image: 
NIAID

CINCINNATI - Infectious disease scientists report early development of a potential universal vaccine for Ebola viruses that preclinical tests show might neutralize all four species of these deadly viruses infecting people in recent outbreaks, mainly in Africa.

Scientists at Cincinnati Children's Hospital Medical Center report their preclinical results in the Journal of Virology, published by the American Society for Microbiology.

Although still in early preclinical testing, researchers report that their data indicate that the prospective vaccine has potential to be a stand-alone protection from Ebola. It also could broaden and extend the durability of protective immunity induced by current live vaccines already being tested in clinical trials against individual Ebola virus species, said Karnail Singh, PhD, the study's co-principal investigator in the Division of Infectious Diseases.

"This could be a significant advancement in the global effort to prevent or manage Ebola outbreaks, especially if this vaccine used alone or in combination with another Ebola vaccine results in long-term and durable protective immunity against different Ebola viruses," Singh said.

A deadly Ebola outbreak in West Africa between 2013 and 2016 accelerated international efforts to develop vaccines for these highly infectious and harmful viruses. This led to development of recombinant Ebola vaccines in which glycoprotein from Zaire Ebola virus is engineered into another modified live viral vector. When administered, these live vaccines induce immune responses against the Ebola glycoprotein that, in turn, protect against any subsequent attack by the Ebola virus.

Singh and colleagues report that while the live-vector vaccines are producing encouraging results in clinical trials, until the current study none of the new vaccines under development have been shown to induce immune responses that cross-react against multiple Ebola virus species that cause the deadly disease in humans.

A Different Approach

The new vaccine takes a novel approach, according to the study. The researchers designed a bivalent, spherical Ebola virus-like particle (VLP) that incorporates two genetically diverse glycoproteins (one each from the Zaire Ebola virus and Sudan Ebola virus) on a spherical core.

This approach will not cause illness in the recipient as the VLPs lack the genetic material and do not multiply. The vaccine works by stimulating immune responses against Ebola that generate virus-fighting antibodies to attack the different virus species.

When the researchers administered their new Ebola VLP vaccine to appropriate animal models, it produced robust immune responses against Ebola virus species known to be pathogenic in humans.

Although the new vaccine uses glycoproteins from two Ebola virus species, Singh said it might work against all four known pathogenic Ebola viruses as responses to one of the glycoproteins generates cross-reactive responses against two other Ebola virus species.

More Testing Needed

The researchers emphasize that extensive additional preclinical testing of the prospective Ebola VLP vaccine is needed before it could potentially be tested in clinical trials.

A key collaborator on the multi-institutional study -- which included the University of Cincinnati College of Medicine, the Emory University School of Medicine, and the University of Louisiana's New Iberia Research Center - was Paul Spearman, MD, Division Director of Infectious Diseases at Cincinnati Children's.

Spearman said at the moment, vaccine challenge experiments are in the planning stages. They will involve working in collaboration with an institution that has Level 4 biosafety facilities and will require additional external funding to move this promising research forward.

"If the data from those studies is equally encouraging, the vaccine should be ready to progress to generation of clinical grade material for human trials," he said.

The study was funded in part by a pilot grant to Singh and Spearman by Innovation Ventures, the technology commercialization arm of Cincinnati Children's, the Cincinnati Children's Research Foundation and support from the New Iberia Research Center, University of Louisiana at Lafayette. Partial support for the study's use of virus-like-particle (VLP) platforms to conduct Ebola vaccine research was provided by the National Institutes of Health.

Credit: 
Cincinnati Children's Hospital Medical Center

High-efficiency catalyst enhancing the electric reduction performance of CO2

Electrochemical conversion of carbon dioxide (CO2) into fuels and value-added feedstocks, ideally if powered by renewable electricity, provides a route to reduce greenhouse gas emissions and simultaneously close the carbon loop. At present, the rational design and controllable synthesis of more efficient catalysts, combined with the understanding of the catalytic mechanism, in order to achieve the industrial application of CO2 electric reduction technology has become the research focus and difficulty.

Recently, a team led by Prof. YU Shuhong and Prof. GAO Minrui from University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) developed a microwave heating strategy for synthesizing a transition metal chalcogenide nanostructure that efficiently catalyzes CO2 electroreduction to carbon monoxide (CO). The series of research results were published in Angewandte Chemie and Journal of the American Chemical Society.

A considerable challenge in the conversion of CO2 into useful fuels comes from the activation of CO2 to CO2- or other intermediates, which often requires precious metallic catalysts, high overpotentials, and/or the electrolyte additives (e.g., ionic liquids).

In this study, the researchers reported a microwave heating strategy for synthesizing a transition metal chalcogenide nanostructure that efficiently catalyzes CO2 electroreduction to CO. They achieved a record CO2-to-CO conversion current of 212 mA cm-2 at selectivity of ~95.5% and potential of -1.2 V versus a reversible hydrogen electrode (RHE) in a flow cell configuration by using the cadmium sulfide (CdS) nanoneedle arrays as electrocatalysts.

Experimental and computational studies showed that the high-curvature CdS nanostructured catalyst with pronounced proximity effect gives rise to large electric field enhancement, which can concentrate alkali metal cations and thereby results in the enhanced CO2 electroreduction efficiency.

In addition to using the "near neighbor effect" of the nano multi-needle tip to achieve the enrichment of target ions, Prof. GAO Minrui's group and academician YU Shuhong's team further proposed to use the "confined-area effect" of the nanocavity to enrich the reaction intermediates and realize the high-efficiency conversion from CO2 to multi-carbon fuels.

The results introduced a simple confinement route for new CO2 reduction reaction (CO2RR) catalyst design. Spatial confinement of the in situ generated carbon intermediates within Cu2O cavities was found to be sufficient for preventing Cu+ reduction under CO2RR and to stabilize Cu oxidation state.

They experimentally showed that the as-designed Cu2O with multi-cavities yields C2+ compounds with a Faradaic efficiency of over 75% and a C2+ partial current density of 267 ± 13 mA cm-2. Such notable C2+ production enabled by the catalyst demonstrated here suggested a material structuring way to boosting CO2RR activity and selectivity for value-added carbon-based fuels powered by renewable energy.

The above research shows that the design of the catalyst nanostructure in the CO2 electroreduction reaction has an important impact on the catalytic performance. The nanoscale "enrichment effect" can effectively enhance the adsorption of key intermediates, thereby promoting the efficient operation of the reaction. This new design concept provides new ideas for the design of related electrocatalysts and the synthesis of high value-added carbon-based fuels in the future.

Credit: 
University of Science and Technology of China

NASA reports Arctic stratospheric ozone depletion hit record low in March

image: The Antarctic ozone hole that occurs annually in September and October during the Southern Hemisphere spring typically sees much lower ozone levels in than the Arctic. The purples and deep blues show the extent of low ozone levels on Oct. 12, 2018, when they dropped to 104 Dobson units.

Image: 
Credits: NASA's Goddard Space Flight Center

Ozone levels above the Arctic reached a record low for March, NASA researchers report. An analysis of satellite observations show that ozone levels reached their lowest point on March 12 at 205 Dobson units.

While such low levels are rare, they are not unprecedented. Similar low ozone levels occurred in the upper atmosphere, or stratosphere, in 1997 and 2011. In comparison, the lowest March ozone value observed in the Arctic is usually around 240 Dobson units.

"This year's low Arctic ozone happens about once per decade," said Paul Newman, chief scientist for Earth Sciences at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "For the overall health of the ozone layer, this is concerning since Arctic ozone levels are typically high during March and April."

Ozone is a highly reactive molecule comprised of three oxygen atoms that occurs naturally in small amounts. The stratospheric ozone layer, roughly 7 to 25 miles above Earth's surface, is a sunscreen, absorbing harmful ultraviolet radiation that can damage plants and animals and affecting people by causing cataracts, skin cancer and suppressed immune systems.

The March Arctic ozone depletion was caused by a combination of factors that arose due to unusually weak upper atmospheric "wave" events from December through March. These waves drive movements of air through the upper atmosphere akin to weather systems that we experience in the lower atmosphere, but much bigger in scale.

In a typical year, these waves travel upward from the mid-latitude lower atmosphere to disrupt the circumpolar winds that swirl around the Arctic. When they disrupt the polar winds, they do two things. First, they bring with them ozone from other parts of the stratosphere, replenishing the reservoir over the Arctic.

"Think of it like having a red-paint dollop, low ozone over the North Pole, in a white bucket of paint," Newman said. "The waves stir the white paint, higher amounts of ozone in the mid-latitudes, with the red paint or low ozone contained by the strong jet stream circling around the pole."

The mixing has a second effect, which is to warm the Arctic air. The warmer temperatures then make conditions unfavorable for the formation of polar stratospheric clouds. These clouds enable the release of chlorine for ozone-depleting reactions. Ozone depleting chlorine and bromine come from chlorofluorocarbons and halons, the chemically active forms of chlorine and bromine derived from man-made compounds that are now banned by the Montreal Protocol. The mixing shuts down this chlorine and bromine driven ozone depletion.

In December 2019 and January through March of 2020, the stratospheric wave events were weak and did not disrupt the polar winds. The winds thus acted like a barrier, preventing ozone from other parts of the atmosphere from replenishing the low ozone levels over the Arctic. In addition, the stratosphere remained cold, leading to the formation of polar stratospheric clouds which allowed chemical reactions to release reactive forms of chlorine and cause ozone depletion.

"We don't know what caused the wave dynamics to be weak this year," Newman said. "But we do know that if we hadn't stopped putting chlorofluorocarbons into the atmosphere because of the Montreal Protocol, the Arctic depletion this year would have been much worse."

Since 2000, levels of chlorofluorocarbons and other man-made ozone-depleting substances have measurably decreased in the atmosphere and continue to do so. Chlorofluorocarbons are long-lived compounds that take decades to break down, and scientists expect stratospheric ozone levels to recover to 1980 levels by mid-century.

NASA researchers prefer the term "depletion" over the Arctic, since despite the ozone layer's record low this year, the ozone loss is still much less than the annual ozone "hole" that occurs over Antarctica in September and October during Southern Hemisphere spring. For comparison, ozone levels over Antarctica typically drop to about 120 Dobson units.

NASA, along with the National Oceanic and Atmospheric Administration, monitors stratospheric ozone using satellites, including NASA's Aura satellite, the NASA-NOAA Suomi National Polar-orbiting Partnership satellite and NOAA's Joint Polar Satellite System NOAA-20. The Microwave Limb Sounder aboard the Aura satellite also estimates stratospheric levels of ozone-destroying chlorine.

Credit: 
NASA/Goddard Space Flight Center

Molecular networks serve as cellular blueprints

image: Researchers have found that unique types of networks underlie the structures of membraneless organelles such as stress granules and processing bodies. Image from the researchers.

Image: 
The researchers

Networks are at the heart of everything from communications systems to pandemics. Now researchers have found that a unique type of network also underlies the structures of critical cellular compartments known as membraneless organelles. These findings may provide key insights into the role of these structures in both disease and cellular operations.

"Prior to this study, we knew the basic physical principle by which these protein-rich compartments form - they condense from the cytoplasm into liquid droplets like dew on a blade of grass," said David Sanders, a post-doctoral researcher in Chemical and Biological Engineering at Princeton University. "But unlike dew drops, which are composed of a single component (water), cellular droplets are intimidatingly complex. Our work uncovers surprisingly simple principles that we think are universal to the assembly of liquid organelles, and opens new frontiers into studying their role in health and disease."

Sanders is the lead author in an article in the journal Cell describing a blueprint for the assembly of these liquid structures, also called condensates. The researchers looked closely at two types of condensates, stress granules and processing bodies ("P-bodies"). In the Cell paper, researchers directed by Clifford Brangwynne, a professor of Chemical and Biological Engineering at Princeton and the Howard Hughes Medical Institute, combined genetic engineering and live cell microscopy approaches to reveal the rules underlying the assembly and structure of stress granules, and why they remain distinct from their close relatives, P-bodies.

Stress granules earn their namesake by appearing when cells are removed from their comfort zone--for example, following heat or detection of noxious chemicals. Both stress granules and P-bodies are tied to an influx of RNA, genetic material that acts as the messenger between the cell's permanent genetic code (DNA) and its principal workhorses (protein). Although the function of these condensates is unclear, some scientists believe both play a role in supervising the cellular actions of the RNA messenger. Regardless of function, stress granules are hijacked by viral infections and have been implicated in diseases of aging. Understanding their assembly is thus critical to the development of new therapeutics.

In healthy cells, cellular machines called ribosomes continually move along the RNA assembly line, insulating the genetic message from its environment and manufacturing proteins essential for the cell's survival. When an external stress halts the assembly line, however, RNA is stripped bare and clumps together into stress granules and P-bodies. Brangwynne's team developed an approach to determine how this clumping occurs and why certain clumps prefer to associate, yet keep their components from mixing into a uniform droplet.

From previous studies by co-authors at Harvard University, the researchers knew a protein called G3BP, which is specifically targeted in many viral infections, is necessary for stress granules to form. But what makes G3BP special? To determine this, the researchers used gene-edited cells that lack G3BP and are unable to form stress granules following the addition of a chemical.

"This allowed us to add back components, one by one, to see what was necessary for their formation," Sanders said. "The first step was to add the G3BP back with various parts of the protein missing."

This approach identified two parts of the protein that were essential: one part that binds RNA and another which binds to specific proteins. Remarkably, the researchers were able to reverse engineer this molecular rescue by linking together similar parts from unrelated proteins. The team showed that stress granule protein scaffolds required a specific collection of building blocks, with a requisite number of chemical connectors that grabbed onto RNA strands and clumped them together. The connectors, called RNA-binding domains, are found on many types of proteins, but come in different flavors that specify their biological function.

"It was remarkably simple to reconstruct this," Sanders said. "All you needed was a scaffolding. Any RNA-binding domain would work as long as there were enough of them."

Eventually, the researchers were able to form identical condensates using more than a dozen different scaffolds.
"What really mattered was whether there were enough binding domains to contact RNA and then connect them together in space," Sanders said. "Similar ideas have been used to understand the assembly of non-living materials, which inspired our thinking about the problem from a network perspective."

The researchers realized that the formation of the condensates was at heart a networking problem. When there were sufficient binding domains available to grab hold of RNA strands, the condensates rapidly formed. At the cellular level, concentrations of proteins with binding domains determined whether stress granules would or would not occur at any spot in the cell.

This understanding also provided insight about the well-known tendency of stress granules and P-bodies to stick together. The tendency, which is the subject of intense inquiry by numerous research groups, is related to the internal networks of stress granules and P-bodies, and the way those networks intersect.

"It just so happens that G3BP has the greatest abundance and network affinity of stress granule proteins," Sanders said. "It likes to interact with other proteins that similarly grab hold of RNA. The reason why stress granules and P-bodies stick together is that they overlap in their networks, forming an adhesive glue. What's interesting is that the two liquids have enough network overlap to stick together, but are different enough that they don't fully mix. If you increase the degree of network overlap, you can collapse the droplets into a single condensate. Moreover, if you remove the overlapping network glue, they detach. Thus, describing condensates as stress granules or P-bodies is really a false dichotomy. What matters is network connectivity and this will be determined by distinct cellular states."

Brangwynne shared his excitement about future work building from these studies, determining whether the blueprint for stress granules and P-bodies applies to other condensates such as nucleoli. "Our group had previously shown that nucleoli exhibit a similar structure, like different types of oil droplets that do not mix, all floating within a water solution. But we didn't understand the molecular rules. Using the stress granule system, we may have uncovered a general framework for understanding this problem, which is exciting to think about in the context of different areas of biology, and for exploiting in biomedical applications such as organelle engineering and therapeutics."

Credit: 
Princeton University, Engineering School

Solving the puzzle of Mitchell disease

image: Dr. Hugo J. Bellen (right) talks with a colleague in a lab.

Image: 
Baylor College of Medicine

When a patient with puzzling neurological symptoms enrolled in the Undiagnosed Diseases Network, researchers led by Dr. Hugo J. Bellen were set on solving the mystery. The patient presented with an unidentified late-onset neurodegenerative disorder. The team named this new syndrome "Mitchell disease" in reference to the first patient to be diagnosed with this disorder and looked to identify its genetic basis.

"On comparing the patient's and his parents' DNA, the team identified a mutation in the patient that resulted in a single amino acid substitution (N237S) in the ACOX1 protein. This change was seen only in the patient and was not present in either of his parents' DNA, indicating that the patient had a de novo, or new, mutation on this gene,' said Bellen, professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and also a Howard Hughes Medical Institute investigator. "With the help of the online gene-matching tool GeneMatcher, we found two more patients who had the same new mutation in the ACOX1 gene."

All three patients, who ranged from 3 to 12 years old at the time of disease onset, had remarkably similar clinical features, including degeneration of peripheral nerves that caused a progressive loss of mobility and hearing. The three individuals had identical gene variants, a clear indication that ACOX1 dysfunction likely was the cause of the symptoms.

A medical mystery

The finding that an ACOX1 mutation was linked to Mitchell disease initially baffled the researchers. The only known ACOX1-related disorder described in the medical literature at that time presented earlier in infancy with seizures, severe cognitive decline, neuro-inflammation and accumulation of very-long-chain-fatty acids in plasma and, more importantly, was caused by the lack of the ACOX1 protein - none of which was true for these three patients.

"The brain has large amounts of lipids, which are critical for the proper functioning of the nervous system. Abnormal breakdown of lipids in the brain and peripheral nervous system is associated with several neurodegenerative diseases," Bellen said.

The gene ACOX1 is involved in lipid breakdown. It produces an enzyme called Acyl-CoA oxidase 1 that initiates a series of reactions that break down very-long-chain-fatty acids in small intracellular organelles called peroxisomes.

Fruit flies help solve the medical mystery

To resolve this conundrum, the Bellen team turned to fruit flies. The first surprising discovery made by the lead author, Hyunglok Chung, was that the ACOX1 protein is abundant and critical for the maintenance of glia, cells that support neurons. This uncovered a previously unknown role of peroxisomes in glial cells and paved the way for further experiments.

To understand how ACOX1 variants affect the function of glia, they generated two mutant fly lines, the first one lacked both the copies of ACOX1 gene and the second, carried the substitution mutation (N237S) found in one of the ACOX1 genes in the Mitchell disease patients.

"Flies lacking ACOX1 mimicked the symptoms of ACOX1 deficiency in humans, including elevated levels of very-long-chain-fatty acids along with dramatic loss of glia and neurons and progressively impaired neuronal function. When we reduced the synthesis of very-long-chain-fatty acids in these flies by administering the drug bezafibrate, we observed significant improvement in lifespan, vision, motor coordination and neuronal function, implicating elevated levels of these lipids and their excessive accumulation in glia as an important contributor," said Chung, postdoctoral fellow in the Bellen lab.

"It is remarkable how well bezafibrate suppressed the symptoms of ACOX1 deficiency, suggesting a new therapeutic avenue for patients with this condition," Bellen said.

In contrast to the loss of ACOX1, the introduction of the single amino acid substitution (N237S) in ACOX1 gene resulted in a hyperactive ACOX1 protein. Typically, breakdown of very-long-chain-fatty acids by the enzymatic action of ACOX1 produces small amounts of highly reactive oxygen species, but glial cells quickly neutralize them. However, in Mitchell's disease, hyperactive ACOX1 produces copious amounts of toxic reactive oxygen species, leading to the destruction of glia and their neighboring neurons.

The harmful effects due to hyperactive ACOX1 were potently reversed with the antioxidant N-acetyl cysteine amide (NACA). However, NACA did not suppress the lethality or toxic effects in flies that lacked ACOX1, a clear indication that the two diseases act via entirely different pathways and would need to be treated with two distinct therapeutic strategies.

"This study is a prime example of how combining UDN's unique team science approach with power of fruit fly genetics is facilitating rapid and phenomenal progress in rare diseases research. We take on cases of patients with conditions never described before, uncover new diseases and find definitive molecular diagnosis for them. We make significant progress in unraveling the causes of these novel diseases and rapidly identify and test promising new treatment options," Bellen said. "We have successfully identified more than 25 disease-causing genes within the past three years - a task that typically takes many years."

Credit: 
Baylor College of Medicine

Male ring-tail lemurs exude fruity-smelling perfume from their wrists to attract mates

image: This image shows a male lemur with clearly visible antebrachial glands on its wrists.

Image: 
Chigusa Tanaka, Japan Monkey Centre

Humans aren't the only primates who like smelling nice for their dates. In the journal Current Biology on April 16, scientists report that male ring-tailed lemurs (Lemur catta) become more attractive to females by secreting a fruity and floral aroma from their wrists. Using detailed chemical analysis, the researchers identified three compounds responsible for this sweet scent, marking the first time that pheromones have been identified in a primate.

"During the yearly breeding season, male lemurs rub the glands on their wrists against their fluffy tails and then wave them at females in a behavior called 'stink flirting,'" says senior author Kazushige Touhara, professor and biochemist at the University of Tokyo.

Ring-tailed lemurs have well-developed scent glands on their shoulders and wrists. These glands are typically used to designate social rank, territory, and reproductive status. However, behavioral observations show they also use their scent glands to catch the attention of females. "Since only ring-tailed lemurs have these wrist glands and exhibit 'stink flirting' behavior, we reasoned that specific odorants for sexual communication must be involved," Touhara says.

At the Japanese Monkey Center (JMC) in Aichi and The Research Institute of Evolutionary Biology in Tokyo, Japan, Touhara and his team tracked the behavior of a conspiracy of ring-tailed lemurs. They observed that female lemurs sniffed the scent markings left by males more often and for longer periods of time during the breeding season--when females are sexually receptive. Furthermore, when researchers isolated the primate perfume from four males and presented it to females individually, they found that females sniffed the fruity-smelling odor for roughly twice as long as the bitter-smelling gland secretions produced off-season.

"Females sniff the floral and fruity scent for a few more seconds than the controls and occasionally even lick it. Although this sounds like a very short time, it's enough to recognize or evoke curiosities in the male," says Touhara.

Using gas chromatography-mass spectrometry analysis on the of the wrist-gland secretions produced during breeding and non-breeding seasons, Touhara determined the major chemical components making up the male scents. Three aldehyde compounds--dodecanal, 12-methyltridecanal, and tetradecanal--were present in both odors but showed substantially higher concentrations during the breeding season. Moreover, when the compounds were individually presented to females in the JMC enclosure, researchers found that only the mixture of all three had a significant ability to hold a female's attention.

"All three compounds have been suggested to be involved in the recognition of newborn sheep by their mothers, and tetradecanal is known as a sex pheromone in some insect species. Although this is the first time 12-methyltridecanal has been identified in primate species, all three aldehydes appear to be used as communication tools widely throughout the animal kingdom," says Touhara.

Young, sexually mature males naturally produce more of these compounds than their senior male counterparts--most likely because aged males produce less testosterone. Furthermore, scientists have observed that females past their reproductive prime are altogether unimpressed by the fruity-smelling odors males exude. These findings suggest that the three compounds are, indeed, pheromones, but more work is required to determine whether they directly influence sexual behavior. "While we have not examined behavioral changes after the sniff in detail, this is an area for future work to determine whether these pheromones impact mating success."

Credit: 
Cell Press

Odor experts uncover the smelly chemistry of lemur love

image: A research team led by the University of Tokyo analyzed the odors that male ring-tailed lemurs use when stink flirting with females. The odor molecules they identified could be the first known primate sex pheromones.

Image: 
Illustration by Caitlin E. Devor, University of Tokyo, CC BY 4.0

Three chemicals with floral, fruity scents are likely essential ingredients in the natural cologne male ring-tailed lemurs use to attract a mate. Experts in odor communication say these chemicals could be the first fully identified sex pheromones in primates.

During the yearly breeding season, male lemurs rub glands on their wrists against their fluffy tails and then wave their tails at females, a behavior called "stink flirting." Only ring-tailed lemurs (Lemur catta) have these wrist glands and exhibit "stink flirting" behavior. The wrist glands produce a clear liquid, never before examined in detail.

"What made our study different is that we have expertise in chemistry, while most studies of animal communication are done by ecologists," said Professor Kazushige Touhara, an expert studying olfaction, the sense of smell, at the University of Tokyo and leader of the recent research study, published in Current Biology.

Recipe for lemur cologne

Researchers collected the clear liquid from males' wrist glands during both the breeding and nonbreeding seasons, then analyzed its chemical components.

The analytical technique gas chromatography-mass spectrometry can identify chemicals based on their electrical charge, molecular weight and other aspects. The research team also benefited from newer technology that can analyze small samples without complicated pretreatment.

Three odor compounds (dodecanal, 12-methyltridecanal and tetradecanal) were more abundant and one (acetamide) was less abundant in the wrist gland liquid collected during the breeding season.

Male lemurs' testosterone levels are naturally higher during the breeding season and at younger ages.

When researchers artificially increased the testosterone of a healthy, young male lemur during the nonbreeding season, the amount of the odor compounds tended to increase, similar to breeding season levels.

"This increase really supports the connection between testosterone and these odor compounds," said Project Assistant Professor Mika Shirasu, a member of the Touhara lab and co-first author of the research publication.

Females' sniff test

Researchers also saved males' breeding season wrist gland secretions to soak in cotton pads and present to females during the nonbreeding season.

"Outside of the breeding season, females had no special interest in any of the male odors we tested," said Shirasu.

To discover if any of the three odor compounds are more important for attracting females' attention, researchers presented females with cotton pads soaked in the individual odor compounds, a blend of the three compounds to mimic normal male breeding season wrist gland secretions, or a neutral control liquid.

When tested in their normal social environment, female lemurs showed no increased interest in any of the three individual male odor compounds. The more natural blend of the three compounds did capture their interest, measured as a longer time spent sniffing that cotton pad.

Although researchers can observe female lemurs' interest, the outcomes of that interest are more complicated to study.

"Curiosity does not necessarily mean sexual attraction. We cannot say for certain yet if a female spending a longer time interested in the scent means that a male will be more successful at mating," said Touhara.

Fragrance for lemurs only

It remains impossible to predict what the three likely lemur sex pheromones might mean for other primates, including humans.

"There are no humans waving tails at each other," said Touhara.

Lemurs are part of a different evolutionary lineage called the wet-nosed strepsirrhines, which have a greater sense of smell than the dry-nosed haplorhine group that includes humans and apes.

"Maybe there are no sex pheromones in humans, but there are probably odors - like parents smelling their baby's heads - that we use to affect each other's emotions," said Touhara.

Researchers cannot yet refer to the odors identified in lemurs as official sex pheromones due to the scientific definition that a pheromone must be used for communication only between members of a single species. The research team hopes that ecologists and zoologists may be able to use these new details about likely sex pheromones to increase understanding of primate behavior.

This research project was conducted over seven years, led by the University of Tokyo in collaboration with partners at Kyoto University, the Research Institute of Evolutionary Biology and the Japan Monkey Centre.

Credit: 
University of Tokyo