Harnessing an innate protection against Ebola

School of Veterinary Medicine researchers have identified a cellular pathway that keeps Ebola virus from exiting human cells, with implications for developing new antivirals.

Peer-Reviewed Publication

UNIVERSITY OF PENNSYLVANIA

 

IMAGE: AN INNATE MECHANISM IN HUMAN CELLS MAY PREVENT EBOLA VIRUS FROM SPREADING, ACCORDING TO NEW PENN VET-LED RESEARCH. USING POWERFUL CONFOCAL MICROSCOPY, THEY TRACKED THE BUDDING OF VIRUS-LIKE PARTICLES FROM CELLS (SHOWN IN THE FILAMENTOUS PROJECTIONS IN THE CELL IN THE UPPER RIGHT) AND HOW AUTOPHAGY, A “SELF-EATING” CELLULAR PROCESS, BY WHICH VIRAL PROTEINS ARE SEQUESTERED IN VESICLES (SHOWN IN THE CELL IN THE LOWER LEFT), INHIBITS VIRUS-LIKE PARTICLES FROM EXITING. view more 

CREDIT: COURTESY OF THE HARTY LABORATORY

In their evolutionary battle for survival, viruses have developed strategies to spark and perpetuate infection. Once inside a host cell, the Ebola virus, for example, hijacks molecular pathways to replicate itself and eventually make its way back out of the cell into the bloodstream, where it can spread further.

But our own cells, in the case of Ebola and many other viruses, aren’t without defenses. In a study published in the Proceedings of the National Academy of Sciences, a team led by University of Pennsylvania School of Veterinary Medicine scientists discovered a way human cells hamper the Ebola virus’ ability to exit.

An interaction between viral and host proteins prompts host cells to ramp up activity of a pathway responsible for digesting and recycling proteins, the team found. This activity, known as autophagy “self-eating,” allows fewer viral particles to reach the surface of a host cell, thus reducing the number that can exit into the bloodstream and further propagate infection.

“This interaction seems to be part of an innate defense mechanism,” says Ronald N. Harty, a professor at Penn Vet and senior author on the study. “Human cells appear to specifically target a key Ebola virus protein and direct it into the autophagy pathway, which is how cells process and recycle waste.”

The investigation emerged from a longtime area of focus for Harty’s lab: the interaction between the viral protein VP40, found in both Ebola and Marburg viruses, and various human proteins. In the group’s previous work, they’ve found that one area of VP40, known as a PPXY motif, binds corresponding motifs known as WW domains on specific host proteins.

In many instances, this PPXY-WW interaction causes more viral particles to exit the cell in a process called “budding.” But in screening various host proteins thought to play a role in the process, Harty and postdoc Jingjing Liang, the study’s lead author, uncovered some that did the opposite upon binding VP40, causing budding to decrease. One of these was a protein called Bag3, on which they reported in a PLOS Pathogens paper in 2017.

Though Ebola is a potentially deadly virus, Harty and colleagues can safely study its workings in a Biosafety Level 2 laboratory, substituting virus-like particles (VLPs) that express VP40 for the virus itself. These VP40 VLPs are not infectious but can bud out from host cells like the real thing.

In the new work, the Penn Vet researchers and colleagues from the Texas Biomedical Research Institute dug deeper to learn about the mechanism by which Bag3 reduced budding. Bag3 is known as a “co-chaperone” protein, involved in forming a complex with other proteins and chaperoning them on their trip to be digested, ultimately in organelles called autolysosomes, part of the process of autophagy. Using VP40 VLPs, Harty’s group confirmed that VP40 bound to Bag3 and formed the protein complex. When the researchers added a compound that is known to block formation of this complex, they saw VP40 being released; VLP budding activity subsequently increased.

To follow the activity of VP40 in real time, the team used powerful confocal microscopy, labeling each actor of interest with a different fluorescent tag. They observed that Bag3 was involved in sequestering VP40 in vesicles in the cell that would go on to undergo autophagy. Stuck in these vesicles and destined for the cellular “recycling center,” VP40 was unable to move to the cell membrane and bud.

“I think one of the most interesting things that we showed is the selectivity of the cargo,” Liang says. “We show that autophagy doesn’t just happen passively. Bag3 acts through the PPXY-WW interaction to specifically target VP40 to undergo autophagy.”

When the researchers added the drug rapamycin, which enhances autophagy, VP40 sequestration went up and VLP budding went down. Rapamycin works by inhibiting the activity of a pathway governed by a protein complex called mTORC1, a cellular sensor that turns on protein synthesis when a cell needs raw material to grow. The researchers found this pathway appeared to be important in regulating Ebola infection; in experiments with live virus conducted in a Biosafety Level 4 laboratory, they observed that the virus could activate mTORC1 signaling, causing the cellular “factory” to produce materials the virus would need to expand and spread. In contrast, inhibiting mTORC1 with rapamycin directed the virus toward the autophagy pathway, where it would be digested by the cell’s autolysosomes.

“The virus wants the cell growing so it activates mTORC1,” says Harty. “Autophagy does the opposite, keeping the cellular materials in balance.”

Autophagy is important for normal cellular processes, ensuring that the cell doesn’t become cluttered with unnecessary or misfolded proteins and other materials floating around. But this work also suggests autophagy can be harnessed by the body to defend against harmful infection.

“Our conception is that this is part of the arms race between our bodies and the virus,” Liang says. “The virus wants to shape its environment to benefit itself and its own survival, so it evolved to manipulate mTORC1. But the cell can also use this pathway to defend against viral infection.”

With these insights into the human body’s innate defenses against Ebola, the researchers hope to see if autophagy may be a factor in other hemorrhagic viral infections, such as those that cause Marburg and Lassa fever. And while the current experiments were primarily conducted using human liver cell lines, the team would also like to test whether autophagy and the mTORC1 pathway are involved in viral defense in other cell types, such as the immune system’s macrophages, the primary cells involved in propagating infection.

Ultimately, Harty, Liang, and colleagues hope to find as many viral vulnerabilities as possible, helping inform drugs that could be one component of a therapeutic cocktail, each targeting different stages of infection, from viral entry to exit.

“This all ties together in our overall goal of understanding viral-host interactions and, by understanding them, working to intervene to slow or stop infection,” Harty says.

Ronald N. Harty is professor of pathobiology and microbiology at the University of Pennsylvania School of Veterinary Medicine.

Jingjing Liang is a postdoctoral fellow in Penn’s School of Veterinary Medicine.

Harty and Liang’s coauthors were the Texas Biomedical Research Institute’s Marija A. Djurkovic and Olena Shtanko. Liang was lead author on the study and Harty was corresponding author.

The work was supported in part by the National Institutes of Health (grants AI138052, AI139392, AI153815, and EY031465 to Harty and AI154336 and AI151717 to Shtanko.)

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2210690120 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Chaperone-assisted selective autophagy targets filovirus VP40 as a client and restricts egress of virus particles

During dolphin research, UH engineer discovers new method to possibly improve pharmaceuticals

Controlling Crystal Growth Has Implications for Array of Medicines

Peer-Reviewed Publication

UNIVERSITY OF HOUSTON

 

IMAGE: JEFFREY RIMER, UNIVERSITY OF HOUSTON ABRAHAM E. DUKLER PROFESSOR OF CHEMICAL ENGINEERING, KNOWN GLOBALLY FOR HIS SEMINAL BREAKTHROUGHS USING INNOVATIVE METHODS TO CONTROL CRYSTALS TO HELP TREAT MALARIA AND KIDNEY STONES, IS REPORTING A NEW METHOD TO CONTROL THE GROWTH OF AMMONIUM URATE CRYSTALS, THE SUBSTANCE KNOWN TO CAUSE KIDNEY STONES IN DOLPHINS, WITH IMPLICATIONS IN THE PHARMACEUTICAL INDUSTRY. view more 

CREDIT: UNIVERSITY OF HOUSTON

In the body, crystals – made of things such as calcium or a collection of urine – form masses that can cause pain and serious health conditions. A University of Houston crystals expert, Jeffrey Rimer, Abraham E. Dukler Professor of Chemical Engineering, known globally for his seminal breakthroughs using innovative methods to control crystals to help treat malaria and kidney stones, is reporting a new method to control the growth of ammonium urate crystals, the substance known to cause kidney stones in dolphins. 

Yes, dolphins get kidney stones, too. And how did we find this out? You can thank the Navy. 

In fact, move over Navy SEAL – the bottlenose dolphin is another marine mammal working hard defending our shores. With their highly evolved ability to detect objects, the dolphins have been helping the U.S. Navy find underwater mines for decades as part of the U.S. Navy Marine Mammal Program.  

As part of that program, the Navy takes good care of its dolphin friends, funding research on such matters as dolphin kidney stones. Rimer has been riding the wave of dolphin research for a while, previously reporting on crystals associated with dolphin kidney stones made of ammonium urate, rarely found in humans. Now he’s leading an international team of researchers from Tianjin University China, Stockholm University Sweden, University of Pittsburgh, University of Strathclyde, Glasgow Scotland, Texas A&M University, Purdue University, Instituto Politecnico Nacional Mexico and The Molecular Foundry at Lawrence Berkeley National Laboratory. 

On behalf of the team, Rimer has published new work in Nature Communications on their discovery of a method to control the crystal growth of ammonium urate by manipulating isomers of urate called tautomers. The findings may not only help dolphins but may also have implications for the pharmaceutical industry. 

“We found that a small fraction of urate existing as a minor tautomer can control the rate at which crystals grow to the point they can completely block crystallization,” said Rimer. “It was the most unexpected and remarkable thing to find that as you increase the concentration of urate, all of a sudden the rate of crystallization drops to almost zero and crystals do not grow in that region.” 

Rimer thinks it may be possible to mimic those results by diet control to get the concentration in the kidney in that range, so then the possibility exists that crystal growth would be inhibited, and medicine would be unnecessary.  

That goes for dolphins and humans, alike, but more on that in future research.   

Examining urate crystals, Rimer also found that tautomers get incorporated into crystals as defects, and that is where the findings have implications for pharmaceuticals.  

Among the top 200 drugs, there are 33 (including allopurinol, used to treat kidney stones) that are tautomers. These medications impact millions worldwide, prescribed for HIV, epilepsy, COVID-19, schizophrenia and cancer (skin, lung and pancreatic). 

“When we produced crystals with very few defects, they dissolved much slower whereas crystals with a higher percentage of defects dissolve faster,” said Rimer. “That is critical for pharmaceuticals because when you put medicine into your body, their effectiveness is related to how fast they dissolve,” said Rimer. 

“We are asking the question about these 33 pharmaceuticals – do companies really know the extent to which they develop defects? The same question can be posed for nature where tautomers may impact unique properties in species that are vital to their intended function like optical properties in fish or color change in chameleons,” he said. 

With Rimer’s continued research, these questions may soon be answered. 

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JOURNAL

Nature Communications

ARTICLE TITLE

Tautomerism unveils a self-inhibition mechanism of crystallization

ARTICLE PUBLICATION DATE

2-Feb-2023

A new understanding of reptile coloration

Python study identifies gene involved in creating piebald traits

Peer-Reviewed Publication

MCGILL UNIVERSITY

 

IMAGE: A SMALL SAMPLE OF THE VARIATIONS IN COLORING AND PATTERNING SEEN AMONG CAPTIVE-BRED BALL PYTHONS (PYTHON REGIUS). view more 

CREDIT: MCGILL UNIVERSITY AND HEATHER ROFFEY

Snakes and mice don’t look alike. But much of what we know about skin coloration and patterning in vertebrates generally, including in snakes, is based on lab mice. However, there are limits to what mice can tell us about other vertebrates because they don’t share all of the same types of color-producing cells, known as chromatophores. For example, snakes have a type of chromatophore called iridophores that can generate iridescent colours by reflecting light.

To gain a better understanding of the genetic basis of coloration in vertebrates, a McGill University-led research team combined a range of techniques (whole gene sequencing, gene-editing, and electron microscopy) to look more closely at color variations and patterning in the skin shed by ball pythons bred in captivity. They were able to identify a particular gene (tfec) that plays a crucial role in reptile pigmentation generally and more specifically in a classic color variant found across vertebrates and distinguished by blotches of white, the piebald.

Crowdsourcing biological data with the help of snake breeders

The sale of captive-bred reptiles is a $1.4 billion industry within the U.S. alone. Over 4.5 million American households keep reptiles, and close to one in five of these are snakes bred in captivity. Due to the spectacular color variations produced through captive breeding, an individual ball python (Python regius – originally found in West and Central Africa) can sell for tens of thousands of dollars.

“Ball pythons show incredible variation in skin coloring and patterning, which is part of their appeal for hobbyists, but also makes them really useful for researchers who want to understand the genetic basis of coloration,” says Rowan Barrett, Interim Director of McGill University’s Redpath Museum, the Canada Research Chair in Biodiversity Science, and the senior author on the recent paper in Current Biology. “The pet trade has created a huge pool of colour variation that would not have existed otherwise. This provides a catalogue for us to figure out the many ways that genes produce the amazing diversity of colors, spots, and stripes we see across different animals.”

Gene-editing confirms role of mutation in reptile colouration

To identify the genes that control a particular trait, scientists look for genetic variants that are present in animals that have the trait and absent in animals that don’t. Using shed skin collected from snake breeders, Barrett’s team found that piebald snakes carried the same mutation in the tfec gene.

But a common problem for scientists is that finding a correlation between a gene and a particular trait, such as the piebaldism, does not imply causation. To make that functional link, the McGill researchers collaborated with Doug Menke’s lab at the University of Georgia to modify tfec in a different reptile species, the brown anole lizard, using the gene-editing technology CRISPR. They found that genetically modified lizards do indeed show altered colouration, proving that mutations to tfec cause changes to color-producing cells. 

“Our research advances knowledge of the genetics of vertebrate colouration generally and particularly of the development of iridescent cells, which haven’t been studied as much as other color pathways” adds Alan Garcia-Elfring, a PhD student in McGill’s Biology Department and the first author on the paper. “It also highlights the potential benefits of working with non-academic communities like ball python breeders to accelerate discoveries in fundamental science. Our job, at this point, is to figure out what other mutations underlie all this variation seen in captivity, and how these mutations interact. It’s an exciting time for both researchers and reptile hobbyists.”

 

“Piebaldism and chromatophore development in reptiles are linked to the tfec gene” in Current Biology by Alan Garcia-Elfring et al

https://doi.org/10.1016/j.cub.2023.01.004

Researchers have been able to pinpoint a mutation in a specific gene that they believe plays a crucial role in creating piebald reptiles.

CREDIT

CREDIT: Heather Roffey

JOURNAL

Current Biology

DOI

10.1016/j.cub.2023.01.004 

ARTICLE TITLE

Piebaldism and chromatophore development in reptiles are linked to the tfec gene

Autonomous driving: New algorithm distributes risk fairly

Software makes more ethically differentiated decisions

Peer-Reviewed Publication

TECHNICAL UNIVERSITY OF MUNICH (TUM)

Technical realization is not the only obstacle to be mastered before autonomously driving vehicles can be allowed on the street on a large scale. Ethical questions play an important role in the development of the corresponding algorithms: Software has to be able to handle unforeseeable situations and make the necessary decisions in case of an impending accident. Researchers at TUM have now developed the first ethical algorithm to fairly distribute the levels of risk rather than operating on an either/or principle. Approximately 2,000 scenarios involving critical situations were tested, distributed across various types of streets and regions such as Europe, the USA and China. The research work published in the journal "Nature Machine Intelligence" is the joint result of a partnership between the TUM Chair of Automotive Technology and the Chair of Business Ethics at the TUM Institute for Ethics in Artificial Intelligence (IEAI).

Maximilian Geisslinger, a scientist at the TUM Chair of Automotive Technology, explains the approach: "Until now, autonomous vehicles were always faced with an either/or choice when encountering an ethical decision. But street traffic can't necessarily be divided into clear-cut, black and white situations; much more, the countless gray shades in between have to be considered as well. Our algorithm weighs various risks and makes an ethical choice from among thousands of possible behaviors – and does so in a matter of only a fraction of a second."

More options in critical situations

The basic ethical parameters on which the software's risk evaluation is oriented were defined by an expert panel as a written recommendation on behalf of the EU Commission in 2020. The recommendation includes basic principles such as priority for the worst-off  and the fair distribution of risk among all road users. In order to translate these rules into mathematical calculations, the research team classified vehicles and persons moving in street traffic based on the risk they present to others and on the respective willingness to take risks. A truck for example can cause serious damage to other traffic participants, while in many scenarios the truck itself will only experience minor damage. The opposite is the case for a bicycle. In the next step the algorithm was told not to exceed a maximum acceptable risk in the various respective street situations. In addition, the research team added variables to the calculation which account for responsibility on the part of the traffic participants, for example the responsibility to obey traffic regulations.

Previous approaches treated critical situations on the street with only a small number of possible maneuvers; in unclear cases the vehicle simply stopped. The risk assessment now integrated in the researchers' code results in more possible degrees of freedom with less risk for all. An example will illustrate the approach: An autonomous vehicle wants to overtake a bicycle, while a truck is approaching in the oncoming lane. All the existing data on the surroundings and the individual participants are now utilized. Can the bicycle be overtaken without driving in the oncoming traffic lane and at the same time maintaining a safe distance to the bicycle? What is the risk posed to each respective vehicle, and what risk do these vehicles constitute to the autonomous vehicle itself? In unclear cases the autonomous vehicle with the new software always waits until the risk to all participants is acceptable. Aggressive maneuvers are avoided, while at the same time the autonomous vehicle doesn't simply freeze up and abruptly jam on the brakes. Yes and No are irrelevant, replaced by an evaluation containing a large number of options.

"The sole consideration of traditional ethical theories resulted in a dead end"

"Until now, often traditional ethical theories were contemplated to derive morally permissible decisions made by autonomous vehicles. This ultimately led to a dead end, since in many traffic situations there was no other alternative than to violate one ethical principle," says Franziska Poszler, scientist at the TUM Chair of Business Ethics. "In contrast, our framework puts the ethics of risk at the center. This allows us to take into account probabilities to make more differentiated assessments."

The researchers emphasized the fact that even algorithms that are based on risk ethics – although they can make decisions based on the underlying ethical principles in every possible traffic situation - they still cannot guarantee accident-free street traffic. In the future it will additionally be necessary to consider further differentiations such as cultural differences in ethical decision-making.

Software now to be tested in street traffic

Until now the algorithm developed at TUM has been validated in simulations. In the future the software will be tested on the street using the research vehicle EDGAR. The code embodying the findings of the research activities is available as Open Source software. TUM is thus contributing to the development of viable and safe autonomous vehicles.

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JOURNAL

Nature Machine Intelligence

DOI

10.1038/s42256-022-00607-z 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

An ethical trajectory planning algorithm for autonomous vehicles

ARTICLE PUBLICATION DATE

2-Feb-2023

Living in a violent setting can result in a shorter, but also a more unpredictable lifespan, according to new research from NYU Abu Dhabi social scientists

While widespread violence has long been known to exert a heavy toll on life expectancy, these findings highlight an even stronger association with lifetime uncertainty

Peer-Reviewed Publication

NEW YORK UNIVERSITY

 

IMAGE: GLOBAL LIFETIME UNCERTAINTY (STANDARD DEVIATION) AND LEVEL OF VIOLENCE (GPI INTERNAL PEACE) FOR MEN AND WOMEN CONDITIONAL ON SURVIVING TO AGE 10 IN 2017 view more 

CREDIT: COURTESY OF NYU ABU DHABI

Abu Dhabi, UAE, February 3, 2023 – A team of researchers at the NYU Abu Dhabi (NYUAD) Social Science Division and Oxford University have published a new study that explores the extent that violence in a country affects uncertainty of the age at death, also referred to as lifetime uncertainty, a key – yet often underappreciated – public health indicator. After hypothesizing that violence is a key predictor of lifetime uncertainty cross-nationally, the researchers found cross-national evidence of a direct link between living in a violent setting and both a shorter and less predictable lifespan.

Uncertainty about the future, specifically uncertainty about survival, influences human behavior and practical life-course decision making, from choices about investing in education, following healthy living habits, and even whether or not to have children. At the population level, lifetime uncertainty can be measured as the spread, or inequality, in age at death. In the study titled A global assessment of the impact of violence on lifetime uncertainty published in the journal Science Advances, the researchers analyzed mortality data for 162 countries between 2008-2017 from the Global Burden of Disease Study and the Internal Peace Index. The researchers found that the most violent countries are those with the lowest life expectancy – with an estimated gap of approximately 14 years in remaining life expectancy with peaceful settings – and the highest lifetime uncertainty. Violence was shown to be a key predictor of lifetime uncertainty cross-nationally, a relationship that was especially strong in countries with ongoing conflicts and/or high levels of violence.

In the Middle East, the researchers found that conflict-related deaths at young ages are the largest contributor to lifetime uncertainty. In Latin America, a similar pattern can be attributed to high rates of homicide and interpersonal violence. Gender is also a factor. Although the effects are larger in magnitude for men, the consequences remain considerable for adolescent girls and women in their early reproductive years. It was also found that in contexts of high violence, lifetime uncertainty is linked to high premature mortality, and such early deaths are the driving factor behind the gap with peaceful nations.

An empirical link between prevailing levels of violence and lifetime uncertainty has not yet been comprehensively established worldwide. As exposure to violence entails a fundamental state of vulnerability with significant social and psychological implications, such as the increased risk of depression, alcohol abuse, suicidal behavior, and posttraumatic stress disorder, understanding the long-term impacts is critical.

“Our study has shown that the impact of violence on mortality goes beyond cutting lives short,” said Orsola Torrisi, a Post-doctoral Associate at the NYUAD Social Science Division. “To live in a violent country is to experience a double burden: lives are both shorter and less predictable. In turn, higher levels of uncertainty make individuals more likely to engage in violent behavior, creating a vicious cycle that is difficult to break.  The magnitude of lifetime uncertainty attributed to violence – even as other historical causes like disease continue to decline – highlights that it is a significant, but largely unaddressed, public health crisis in many parts of the world.”

 

ENDS

 

About NYU Abu Dhabi

www.nyuad.nyu.edu
NYU Abu Dhabi is the first comprehensive liberal arts and research campus in the Middle East to be operated abroad by a major American research university. NYU Abu Dhabi has integrated a highly selective program with majors in the sciences, engineering, social sciences, arts, and humanities with a world center for advanced research. Its campus enables students to succeed in an increasingly interdependent world, and to advance cooperation and progress on humanity’s shared challenges. NYU Abu Dhabi’s high-achieving students have come from some 120 countries and speak over 115 languages. Together, NYU's campuses in New York, Abu Dhabi, and Shanghai form the backbone of a unique global university, giving faculty and students opportunities to experience varied learning environments and immersion in other cultures at one or more of the numerous study-abroad sites NYU maintains on six continents. 

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JOURNAL

Science Advances

ARTICLE TITLE

A global assessment of the impact of violence on lifetime uncertainty

Life in a violent country can be years shorter and much less predictable – even for those not involved in conflict

How long people live is less predictable and life expectancy for young people can be as much as 14 years shorter in violent countries,compared to peaceful countries, according to a new study today [3/2] from an international team, led by Oxford’s Leverhu

Peer-Reviewed Publication

UNIVERSITY OF OXFORD

How long people live is less predictable and life expectancy for young people can be as much as 14 years shorter in violent countries compared to peaceful countries, according to a new study today [3/2] from an international team, led by Oxford’s Leverhulme Centre for Demographic Science. It reveals a direct link between the uncertainty of living in a violent setting, even for those not directly involved in the violence, and a ‘double burden’ of shorter and less predictable lives.

According to the research, violent deaths are responsible for a high proportion of the differences in lifetime uncertainty between violent and peaceful countries. But, the study says, ‘The impact of violence on mortality goes beyond cutting lives short. When lives are routinely lost to violence, those left behind face uncertainty as to who will be next.’

Lead author Dr José Manuel Aburto from Oxford's Leverhulme Centre for Demographic Science and the London School of Hygiene and Tropical Medicine, adds, ‘What we found most striking is that lifetime uncertainty has a greater association with violence than life expectancy. Lifetime uncertainty, therefore, should not be overlooked when analysing changes in mortality patterns.’

Using mortality data from 162 countries, and the Internal Peace Index between 2008-2017, the study shows the most violent countries are also those with the highest lifetime uncertainty. In the Middle East, conflict-related deaths at young ages are the biggest contributor to this, while in Latin America, a similar pattern results from homicides and interpersonal violence.

But lifetime uncertainty was ‘remarkably low’ between 2008-2017, in most Northern and Southern European countries. Although Europe has been the most peaceful region over the period, the Russian invasion of Ukraine will impact this.

In high-income countries, reduced cancer mortality has recently helped to reduce lifetime uncertainty. But, in the most violent societies, lifetime uncertainty is even experienced by those not directly involved in violence. The report states, ‘Poverty-insecurity-violence cycles magnify pre-existing structural patterns of disadvantage for women and fundamental imbalances in gender relations at young ages. In some Latin American countries, female homicides have increased over the last decades and exposure to violent environments brings health and social burdens, particularly for children and women.’

Study co-author Professor Ridhi Kashyap, from the Leverhulme Centre, says, ‘Whilst men are the major direct victims of violence, women are more likely to experience non-fatal consequences in violent contexts. These indirect effects of violence should not be ignored as they fuel gender inequalities, and can trigger other forms of vulnerability and causes of death.’

According to the report, lower life expectancy is usually associated with greater lifetime uncertainty. In addition, living in a violent society creates vulnerability and uncertainty – and that, in turn, can lead to more violent behaviour. 

Countries with high levels of violence experience lower levels of life expectancy than more peaceful ones, ‘We estimate a gap of around 14 years in remaining life expectancy at age 10 between the least and most violent countries…In El Salvador, Honduras, Guatemala and Colombia the gap in life expectancy with high income countries is predominantly explained by excess mortality due to homicides.’

Study co-author Vanessa di Lego, from the Wittgenstein Centre for Demography and Global Human Capital, adds, ‘It is striking how violence alone is a major driver of disparities in lifetime uncertainty. One thing is for certain, global violence is a public health crisis, with tremendous implications for population health, and should not be taken lightly.’

 

About the Leverhulme Centre for Demographic Science

This major new interdisciplinary research centre, funded by the Leverhulme Trust and directed by Professor Melinda Mills, is tackling the most challenging demographic problems of our time. Based at the University of Oxford, the Centre is at the forefront of demographic research that impacts academia, society and policy. Together with academic and industry partners, our researchers use new types of data, methods and unconventional approaches to disrupt conventional thinking across important issues such as COVID-19, climate change, and life expectancy. More information on the Centre can be found here.

About the University of Oxford

Oxford University has been placed number one in the Times Higher Education World University Rankings for the seventh year running, and ​number two in the QS World Rankings 2022. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer.

Oxford is world-famous for research and teaching excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research alongside our personalised approach to teaching sparks imaginative and inventive insights and solutions.

 

 

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JOURNAL

Science Advances

DOI

10.1126/sciadv.add9038 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

A global assessment of the impact of violence on lifetime uncertainty

ARTICLE PUBLICATION DATE

3-Feb-2023

A subtitled world: Uncovering the secrets of tickertape synesthesia

Peer-Reviewed Publication

INSTITUT DU CERVEAU (PARIS BRAIN INSTITUTE)

 

IMAGE: EMPLOYEES OF THE WALDORF-ASTORIA HOTEL OPERATING TICKERS AND STOCK EXCHANGE BOARDS, 1918. view more 

CREDIT: WIKIMEDIA.

The anthropologist Francis Galton, Charles Darwin's cousin, was interested in the most notable faculties of the human mind. In 1883, he observed that some people visualized the speech of their interlocutor in their internal mental space. "Some few people see mentally in print every word that is uttered […], and they read them off usually as from a long imaginary strip of paper, such as is unwound from telegraphic instruments". The ticker tape no longer exists today, but this particularity – called tickertape synesthesia (TTS), remains.

Synesthesia is a neurological phenomenon in which different senses are stimulated simultaneously while processing sensory information. It allows some artists to hear colors, see sounds, or even taste music. In the case of TTS, synesthetes can read someone's voice.

"This phenomenon goes far beyond the anecdote. It opens a window to understand better the mechanisms at work in processing written language and their neural bases," explains Fabien Hauw, a doctoral student at Paris Brain Institute. He and Laurent Cohen, who co-leads the Neuropsychology and Functional Neuroimaging team, interviewed 26 people with TSS. Their goal? To find out in which conditions the subtitles appeared, in what form, and whether they could present an advantage or a handicap in everyday life. "We think that TTS occurs when the translation of phonemes into graphemes, i.e., sounds into letters, is too efficient," explains Laurent Cohen. In these people, the connection between the mental representations of phonology and spelling is exaggerated, and the reading mechanism is somehow 'forced' as soon as they are exposed to vocal sounds."

Indeed, even though this characteristic was described more than a century ago, it is still poorly understood. A previous study estimated that up to 1.4% of the population could experience involuntary subtitles when hearing a human voice, but this figure remains uncertain. It's challenging to detect TTS subjects, who are generally unaware that they are distinguishable from the average person. "Several participants in the study were shocked to learn that not everyone has built-in subtitles," laughs Laurent Cohen. We taught them through our recruitment ad. Like most forms of synesthesia, TTS is a subjective phenomenon. We don't know how to measure it objectively, as we would evaluate visual acuity, for example. Nor is it associated with outstanding abilities or incapacitating cognitive impairments. This makes it an exciting but invisible quality.

A thousand transcripts

To better understand the subjective experience of tickertape synesthesia, Fabien Hauw, and Laurent Cohen asked the 26 participants, whose native language was French, to fill out a questionnaire. Indeed, many questions were left answered: can SST be triggered by a foreign language, new words, or noises (sneezing, meowing, motor humming)? Are the subtitles formatted in a specific way (size, color, capitalization, special characters) for each individual?

The researchers' results indicate that for 73% of the participants, synesthesia appeared during the acquisition of reading in childhood. With almost half of them, this characteristic proved to be both an advantage and a nuisance; it helps them memorize words but disrupts their attention in crowded places where many conversations occur simultaneously. Indeed, for 70% of the participants, TTS is an automatic process that cannot be controlled.

Some synesthetes report that the appearance of the captions can be affected by the context of verbalization, especially when the speaker is emotional; the words may then change color or size, depending on the intensity of the emotion. "Letters may be blurred or shaking when I'm moved," said one participant.

Even more surprising: some subjects report that when they watch a foreign movie, a second level of subtitles – a product of their synesthesia – appears above the subtitles embedded in the video. Others have subtitled dreams and nightmares, which provide their oneiric activity with a cinematic dimension. Finally, since one-third of the participants knew of other cases of TTS in their family, the emergence of this form of synesthesia might have a genetic basis.

Powerful super-readers?

In literate people, specific mental processes make it possible to interpret words, sounds, and letters and give them meaning. To be effective, these processes are fine-tuned under genetic and environmental constraints during development. Thus, we can observe a wide variety in reading performance across individuals, ranging from dyslexia...to synesthesia. In that sense, researchers believe that TTS results from a very atypical development of literacy.

"In a previous MRI study, we showed that when a synesthete listens to a monologue, certain areas of the left hemisphere are activated more strongly than in a control subject, notably, regions responsible for speech analysis and a specific area involved in spelling – the VFWA (Visual Word Form Area)," Fabien Hauw explains. These areas are identical to those related to reading. The observations support the idea that tickertape synesthesia is a form of upended reading: instead of simply translating written words into sounds, these people automatically convert sounds into written words."

The researchers' observations must be reproduced with a more extensive and diverse sample of subjects. "Thanks to this study, we can map the spectrum of perceptions that exist in TTS. Now, we want to ensure that it is related to an overdeveloped access to orthographic representations", says Laurent Cohen. We will never know if synesthetic scribes in ancient Egypt subtitled their interlocutors in hieroglyphics. But by illuminating the mechanisms of reading, we may be able to help children for whom this acquisition remains challenging.

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Publication:

Hauw, F et al., Subtitled speech: Phenomenology of tickertape synesthesia, 

Cortex. https://doi.org/10.1016/j.cortex.2022.11.005  

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JOURNAL

Cortex

DOI

10.1016/j.cortex.2022.11.005 

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Subtitled speech: Phenomenology of tickertape synesthesia

Black South Africans report higher life satisfaction and are at less risk for depression post-migration, MU study finds

Findings may help policymakers tailor mental health resources to underprivileged migrants, those seeking economic mobility

Peer-Reviewed Publication

UNIVERSITY OF MISSOURI-COLUMBIA

 

IMAGE: ROAD view more 

CREDIT: UNIVERSITY OF MISSOURI

COLUMBIA, Mo. -- Although relocating can be stressful, a new study at the University of Missouri found Black South Africans who migrated far away from home to find work reported better emotional well-being and were at lower risk for depression after the move on average.

As mental health and internal migration continue to be understudied components of public health research compared to physical health outcomes and international immigration, the findings of the study can help policymakers tailor resources toward underprivileged migrants after they move, as well as toward those who get left behind and are still seeking upward mobility.

“Eighty percent of South Africans are Black, yet they have a very small share of the country’s overall wealth as the legacy of Apartheid continues to be felt,” said Tyler Myroniuk, an assistant professor in the MU School of Health Professions and lead author on the study. “South Africa offers a prime example of inequality and the potential struggles that migrants undergo trying to move to overcome such inequalities, so we wanted to better understand how migrants fare after they move.”

The collapse of Apartheid in 1994 opened the floodgates of migrants throughout South Africa, mainly from rural areas to urban cities in search of economic opportunities.

“We have seen throughout history, not just in South Africa but here in the United States and all over, most migrants don’t move just for fun, they move because they have to as they seek upward mobility and economic opportunities that they often lack wherever they are from,” Myroniuk said. “Refugees who are forced to relocate tend to have far worse mental health outcomes after they move, but we know far less about the emotional well-being of those who move voluntarily.”

Myroniuk traveled to the University of Cape Town in South Africa in 2017 and 2018 to analyze internal migration data from the National Income Dynamic Study from 2008 to 2015. Nearly 2,300 Black South African migrants were studied, and on average, the further away from home the migrants moved, the higher levels of emotional well-being they self-reported after the move compared to before the move.

By using longitudinal data — where researchers repeatedly examine the same individuals to detect changes that might occur over a long period of time — in this study, Myroniuk and his team were able to determine the self-reported improvements in life satisfaction came after the migration.

“Given how stressful moving can be, I was a bit surprised by the findings,” Myroniuk said. “This research can help us gain insight into why people move, and it also shows that when people move, they typically know what is best for them. They move to make things better for not just themselves but for their family as well. So, we also need to start thinking more about those who were possibly left behind and how to best help them as well.”

In 2010, Myroniuk traveled to rural Malawi in southeast Africa to research family health. It was while talking with migrants about their experiences moving long distances from other parts of the country that sparked his interest in researching this understudied population.

“As they described their motives for moving, all the hurdles they faced along the way and all the risk and uncertainty involved, I admired their resilience in the midst of such highly unequal circumstances,” Myroniuk said. “In the context of public health research, physical health outcomes and international immigrants tend to be studied quite often, but the emotional well-being of voluntary, internal migrants is an understudied topic as they move within their home country. Yet it happens all the time, far more often than international immigration, and I think people worldwide can relate to the stress and uncertainty that comes with moving.”

While conducting research in 2012, Myroniuk remembers seeing migrants on the move away from an isolated township outside of Johannesburg, South Africa. The isolated township offered few services and was not on the electric grid. The migrants' personal belongings were stacked 12 feet high in the back of a pickup truck as they travelled to their next destination.

“While those who moved may have found work and were able to send some money back home to support their families, this study also indirectly highlights those who were potentially left behind, those who may have wanted to move but could not for financial or other reasons,” Myroniuk said. “As migrants and their families tend to be a vulnerable, insecure population, this research can hopefully lead to policymakers identifying vulnerable individuals in local primary care settings and tailoring support and resources to help those in need who are searching for upward mobility.”

As a public health researcher, Myroniuk has previously studied barriers and facilitators to accessing HIV treatment for older adults in South Africa, where HIV is more prevalent than other parts of the world.

“Whether it’s HIV or COVID-19, the pandemic has definitely put a spotlight on the spread of infectious diseases and the physical health impacts of these diseases,” Myroniuk said. “However, as medicine improves and people are living longer, it is also important to think about the mental health and emotional well-being of vulnerable populations, so this research is a small step in the right direction to spark further conversations.”

“Post-migration emotional well-being among Black South Africans” was recently published in Social Science and Medicine – Mental Health. Co-authors on the study include Michael White at Brown University and Sangeetha Madhavan at the University of Maryland.

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JOURNAL

SSM - Mental Health

DOI

10.1016/j.ssmmh.2022.100173 

METHOD OF RESEARCH

Data/statistical analysis

ARTICLE TITLE

Post-migration emotional well-being among Black South Africans