“We know that AMD starts in the outer blood-retina barrier,” said Kapil Bharti, Ph.D., who heads the NEI Section on Ocular and Stem Cell Translational Research. “However, mechanisms of AMD initiation and progression to advanced dry and wet stages remain poorly understood due to the lack of physiologically relevant human models.”

The outer blood-retina barrier consists of the retinal pigment epithelium (RPE), separated by Bruch’s membrane from the blood-vessel rich choriocapillaris. Bruch’s membrane regulates the exchange of nutrients and waste between the choriocapillaris and the RPE. In AMD, lipoprotein deposits called drusen form outside Bruch’s membrane, impeding its function. Over time, the RPE break down leading to photoreceptor degeneration and vision loss.

Bharti and colleagues combined three immature choroidal cell types in a hydrogel: pericytes and endothelial cells, which are key components of capillaries; and fibroblasts, which give tissues structure. The scientists then printed the gel on a biodegradable scaffold. Within days, the cells began to mature into a dense capillary network.

On day nine, the scientists seeded retinal pigment epithelial cells on the flip side of the scaffold. The printed tissue reached full maturity on day 42. Tissue analyses and genetic and functional testing showed that the printed tissue looked and behaved similarly to native outer blood-retina barrier. Under induced stress, printed tissue exhibited patterns of early AMD such as drusen deposits underneath the RPE and progression to late dry stage AMD, where tissue degradation was observed. Low oxygen induced wet AMD-like appearance, with hyperproliferation of choroidal vessels that migrated into the sub-RPE zone. Anti-VEGF drugs, used to treat AMD suppressed this vessel overgrowth and migration and restored tissue morphology.

“By printing cells, we’re facilitating the exchange of cellular cues that are necessary for normal outer blood-retina barrier anatomy,” said Bharti. “For example, presence of RPE cells induces gene expression changes in fibroblasts that contribute to the formation of Bruch’s membrane — something that was suggested many years ago but wasn’t proven until our model.”

Among the technical challenges that Bharti’s team addressed were generating a suitable biodegradable scaffold and achieving a consistent printing pattern through the development of a temperature-sensitive hydrogel that achieved distinct rows when cold but that dissolved when the gel warmed. Good row consistency enabled a more precise system of quantifying tissue structures. They also optimized the cell mixture ratio of pericytes, endothelial cells, and fibroblasts.

Co-author Marc Ferrer, Ph.D., director of the 3D Tissue Bioprinting Laboratory at NIH’s National Center for Advancing Translational Sciences, and his team provided expertise for the biofabrication of the outer blood-retina barrier tissues “in-a-well,” along with analytical measurements to enable drug screening.

“Our collaborative efforts have resulted in very relevant retina tissue models of degenerative eye diseases,” Ferrer said. “Such tissue models have many potential uses in translational applications, including therapeutics development.”

Bharti and collaborators are using printed blood-retina barrier models to study AMD, and they are experimenting with adding additional cell types to the printing process, such as immune cells, to better recapitulate native tissue.

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Materials provided by NIH/National Eye Institute. Note: Content may be edited for style and length.

“To effectively prevent all tipping risks, the global mean temperature increase would need to be limited to no more than one degree — we are currently already at about 1.2 degrees,” Jonathan Donges, Co-Lead of the FutureLab on Earth Resilience in the Anthropocene at PIK adds. “The latest IPCC report is showing that we’re most likely on a path to temporarily overshoot the 1.5 degrees Celsius temperature threshold.”

Emergence of at least one tipping event increases with rising peak temperatures

To arrive at these results, the scientists, together with co-authors from the Earth Commission — a group of leading scientists convened by Future Earth — used different global warming overshoot scenarios with peak temperatures from two to four degrees and applied these to a set of four interacting tipping elements: the Greenland Ice Sheet, the West Antarctic Ice Sheet, the Atlantic Meridional Overturning Circulation AMOC, and the Amazon rainforest. The researchers applied a risk analysis approach based on millions of model simulations to reflect the uncertainties in relevant parameters such as the uncertainty in critical temperature thresholds as well as interaction strengths and interaction structure. Such an amount of simulations would be computationally too expensive to do based on fully coupled Earth System Model simulations. For the different overshoot scenarios, the research team then analyzed the risk of crossing critical thresholds and the potential for triggering cascading interactions between the four elements, depending on the magnitude and duration of the overshoot as well as the warming remaining on the long-term.

“We found that the risk for the emergence of at least one tipping event increases with rising peak temperatures — already at a peak temperature of three degrees Celsius, more than one third of all simulations showed a tipping event even when overshoot durations were limited strongly. At four degrees Celsius peak temperature, this risk extends to more than half of all simulations,” explains Nico Wunderling.

Tipping mechanisms under warming overshoots

“Especially the Greenland and the West Antarctic ice sheet are at risk of tipping even for small overshoots, underlining that they are among the most vulnerable tipping elements. While it would take a long time for the ice loss to fully unfold, the temperature levels at which such changes are triggered could already be reached soon,” says Ricarda Winkelmann, Earth Commissioner and Co-Lead of the FutureLab on Earth Resilience in the Anthropocene. “Our action in the coming years can thus decide the future trajectory of the ice sheets for centuries or even millennia to come.” The other two tipping elements considered in the study, the AMOC and Amazon rainforest, have higher critical temperature thresholds. Yet, they would react much faster once the tipping process has started. Therefore, it is much more difficult to stop their tipping process once initiated by a temporary global warming overshoot.

Current mitigation policies are expected to lead to 2-3.6 degrees Celsius of global warming by the end of this century. “This is not enough. Even though a temporary temperature overshoot would definitely be better than reaching a peak temperature and remaining there, some of the overshoot impacts may lead to irreversible damages in a high climate risk zone and this is why low-temperature overshoots are key here,” explains Jonathan Donges. Ricarda Winkelmann adds: “Every tenth of a degree counts. We must do what we can to limit global warming as quickly as possible.”

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Materials provided by Potsdam Institute for Climate Impact Research (PIK). Note: Content may be edited for style and length.

To better understand the magnitude of the gun violence crisis and put it in perspective, researchers at Brown University and the University of Pennsylvania compared the risk of firearm-related death for young adult men living in the most violent areas in four major U.S. cities with the risks of combat death and injury faced by U.S. military personnel who served in Afghanistan and Iraq during active periods of war.

The results were mixed: The study, published in JAMA Network Open, found that young men from zip codes with the most firearm violence in Chicago and Philadelphia faced a notably higher risk of firearm-related death than U.S. military personnel deployed to wartime service in Afghanistan and Iraq. But the opposite was true in two other cities: The most violent areas in New York and Los Angeles were associated with much less risk for young men than those in the two wars.

In all zip codes studied, risks were overwhelmingly borne by young men from minority racial and ethnic groups, the study found.

“These results are an urgent wake-up call for understanding, appreciating and responding to the risks and attendant traumas faced by this demographic of young men,” said Brandon del Pozo, an assistant professor of medicine (research) at Brown’s Warren Alpert Medical School and an assistant professor of health services, policy and practice (research) at the University’s School of Public Health.

Del Pozo conducts research at the intersection of public health, public safety and justice, focusing on substance use, the overdose crisis, and violence. His recently released book, “The Police and the State: Security, Social Cooperation, and the Public Good,” is based on his academic research as well as his 23 years of experience as a police officer in New York City and as chief of police of Burlington, Vermont.

“Working as a police officer, I witnessed the toll of gun violence, and how disruptive it was for families and communities,” del Pozo said. “It stood out to me that the burden was not distributed evenly by geography or demographic. Some communities felt the brunt of gun violence much more acutely than others. By analyzing publicly available data on firearm fatalities in cities and in war, we sought to place that burden in sharp relief.”

At the same time, del Pozo said, he and the other study authors were responding to oft-repeated inflammatory claims about gun violence in American cities.

“We often hear opposing claims about gun violence that fall along partisan lines: One is that big cities are war zones that require a severe crackdown on crime, and the other is that our fears about homicides are greatly exaggerated and don’t require drastic action,” del Pozo said. “We wanted to use data to explore these claims — and it turns out both are wrong. While most city residents are relatively safe from gun violence, the risks are more severe than war for some demographics.”

Illustrating the magnitude of the firearm crisis

To conduct their analysis, the researchers obtained information on all fatal and nonfatal shootings of 18- to 29-year-old men recorded as crimes in 2020 and 2021 in Chicago; Los Angeles; New York; and Philadelphia — the four largest U.S. cities for which public data on those who were shot were available. For New York, Chicago and Philadelphia, they used shooting death and injury data sets made public by each city; for Los Angeles, they extracted firearm death and injury data from a larger public data set of recorded crimes. Data were aggregated to the zip code level and linked to corresponding demographic characteristics from the U.S. Census Bureau’s 2019 American Community Survey.

The researchers acquired wartime combat-related mortality and injury counts for the conflicts in Iraq and Afghanistan from peer-reviewed analyses of U.S. military data covering the years 2001 to 2014 for the war in Afghanistan and 2003 to 2009 for the war in Iraq, both of which were periods of active combat. Because there is limited data about the risks of serving in different military units at different times during the Afghanistan and Iraq wars, the researchers considered the mortality and injury data of a single, de-identified Army brigade combat team engaged in combat during a 15-month period of the Iraq War that involved notably above-average combat death and injury rates at a time considered to be the height of the conflict.

The analysis included 129,826 young men residing in the four cities considered in the study.

The researchers found that compared to the risk of combat death faced by U.S. soldiers who were deployed to Afghanistan, the more dangerous of the two wars, young men living in the most violent zip code of Chicago (2,585 individuals) had a 3.23 times higher average risk of firearm-related homicide, and those in Philadelphia (2,448 people) faced a 1.9 times higher average risk of firearm-related homicide. Singling out the elevated dangers faced by the U.S. Army combat brigade in Iraq, the young men studied in Chicago still faced notably greater risks, and the ones faced in Philadelphia were comparable.

However, these findings were not observed in the most violent zip codes of Los Angeles and New York, where young men faced a 70% to 91% lower risk than soldiers in the Afghanistan war across fatal and nonfatal categories.

When the researchers looked at the demographics of the young men in the zip codes studied, they determined that the risk of violent death and injury observed in the zip codes studied was almost entirely borne by individuals from minority racial and ethnic groups: Black and Hispanic males represented 96.2% of those who were fatally shot and 97.3% of those who experienced nonfatal injury across all four cities.

In the study, the researchers make the point that the risk of firearm death is not the only thing that young men living in violent U.S. zip codes have in common with young men at war.

“Exposure to combat has been associated with stress-inducing hypervigilance and elevated rates of homelessness, alcohol use, mental illness and substance use, which, in turn, are associated with a steep discounting of future rewards,” they write. “Our findings — which show that young men in some of the communities we studied were subject to annual firearm homicide and violent injury rates in excess of 3.0% and as high as 5.8% — lend support to the hypothesis that beyond the deaths and injuries of firearm violence, ongoing exposure to these violent events and their risks are a significant contributor to other health problems and risk behaviors in many U.S. communities.”

Del Pozo added that the health risks are likely even higher for people in cities, because they need to face their “battles” every day over a lifetime, as opposed to military personnel in a tour of duty in Afghanistan, which typically lasted 12 months. The study results, del Pozo said, help illustrate the magnitude of the firearms crisis, a necessary understanding to municipalities seeking to formulate an effective public health response.

“The findings suggest that urban health strategies should prioritize violence reduction and take a trauma-informed approach to addressing the health needs of these communities,” del Pozo said.

Other Brown contributors included Dr. Michael J. Mello, a physician and researcher at the Warren Alpert Medical School and the Injury Prevention Center at Rhode Island Hospital.

The study was supported by the National Institute on Drug Abuse (K01DA056654) and the National Institute of General Medical Sciences (P20GM139664).

Imaging light in deep tissues is extremely difficult because as light travels into tissue, much of it is either absorbed or scattered. The MIT team overcame that obstacle by designing a sensor that converts light into a magnetic signal that can be detected by MRI (magnetic resonance imaging).

This type of sensor could be used to map light emitted by optical fibers implanted in the brain, such as the fibers used to stimulate neurons during optogenetic experiments. With further development, it could also prove useful for monitoring patients who receive light-based therapies for cancer, the researchers say.

“We can image the distribution of light in tissue, and that’s important because people who use light to stimulate tissue or to measure from tissue often don’t quite know where the light is going, where they’re stimulating, or where the light is coming from. Our tool can be used to address those unknowns,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering.

Jasanoff, who is also an associate investigator at MIT’s McGovern Institute for Brain Research, is the senior author of the study, which appears today in Nature Biomedical Engineering. Jacob Simon PhD ’21 and MIT postdoc Miriam Schwalm are the paper’s lead authors, and Johannes Morstein and Dirk Trauner of New York University are also authors of the paper.

A light-sensitive probe

Scientists have been using light to study living cells for hundreds of years, dating back to the late 1500s, when the light microscope was invented. This kind of microscopy allows researchers to peer inside cells and thin slices of tissue, but not deep inside an organism.

“One of the persistent problems in using light, especially in the life sciences, is that it doesn’t do a very good job penetrating many materials,” Jasanoff says. “Biological materials absorb light and scatter light, and the combination of those things prevents us from using most types of optical imaging for anything that involves focusing in deep tissue.”

To overcome that limitation, Jasanoff and his students decided to design a sensor that could transform light into a magnetic signal.

“We wanted to create a magnetic sensor that responds to light locally, and therefore is not subject to absorbance or scattering. Then this light detector can be imaged using MRI,” he says.

Jasanoff’s lab has previously developed MRI probes that can interact with a variety of molecules in the brain, including dopamine and calcium. When these probes bind to their targets, it affects the sensors’ magnetic interactions with the surrounding tissue, dimming or brightening the MRI signal.

To make a light-sensitive MRI probe, the researchers decided to encase magnetic particles in a nanoparticle called a liposome. The liposomes used in this study are made from specialized light-sensitive lipids that Trauner had previously developed. When these lipids are exposed to a certain wavelength of light, the liposomes become more permeable to water, or “leaky.” This allows the magnetic particles inside to interact with water and generate a signal detectable by MRI.

The particles, which the researchers called liposomal nanoparticle reporters (LisNR), can switch from permeable to impermeable depending on the type of light they’re exposed to. In this study, the researchers created particles that become leaky when exposed to ultraviolet light, and then become impermeable again when exposed to blue light. The researchers also showed that the particles could respond to other wavelengths of light.

“This paper shows a novel sensor to enable photon detection with MRI through the brain. This illuminating work introduces a new avenue to bridge photon and proton-driven neuroimaging studies,” says Xin Yu, an assistant professor radiology at Harvard Medical School, who was not involved in the study.

Mapping light

The researchers tested the sensors in the brains of rats — specifically, in a part of the brain called the striatum, which is involved in planning movement and responding to reward. After injecting the particles throughout the striatum, the researchers were able to map the distribution of light from an optical fiber implanted nearby.

The fiber they used is similar to those used for optogenetic stimulation, so this kind of sensing could be useful to researchers who perform optogenetic experiments in the brain, Jasanoff says.

“We don’t expect that everybody doing optogenetics will use this for every experiment — it’s more something that you would do once in a while, to see whether a paradigm that you’re using is really producing the profile of light that you think it should be,” Jasanoff says.

In the future, this type of sensor could also be useful for monitoring patients receiving treatments that involve light, such as photodynamic therapy, which uses light from a laser or LED to kill cancer cells.

The researchers are now working on similar probes that could be used to detect light emitted by luciferases, a family of glowing proteins that are often used in biological experiments. These proteins can be used to reveal whether a particular gene is activated or not, but currently they can only be imaged in superficial tissue or cells grown in a lab dish.

Jasanoff also hopes to use the strategy used for the LisNR sensor to design MRI probes that can detect stimuli other than light, such as neurochemicals or other molecules found in the brain.

“We think that the principle that we use to construct these sensors is quite broad and can be used for other purposes too,” he says.

The research was funded by the National Institutes of Health, the G. Harold and Leyla Y. Mathers Foundation, a Friends of the McGovern Fellowship from the McGovern Institute for Brain Research, the MIT Neurobiological Engineering Training Program, and a Marie Curie Individual Fellowship from the European Commission.

The team, which includes researchers from the University of York and the British Museum, analysed the remains of 1,226 pottery vessels from 156 hunter-gatherer sites across nine countries in Northern and Eastern Europe. They combined radiocarbon dating, together with data on the production and decoration of ceramic vessels, and analysis of the remains of food found inside the pots.

Their findings, published in the journal Nature Human Behaviour, suggest that pottery-making spread rapidly westwards from 5,900 BCE onwards and took only 300-400 years to advance over 3,000 km, equivalent to 250 km in a single generation.

Professor Oliver Craig, from the University of York’s Department of Archaeology, said: “Our analysis of the ways pots were designed and decorated as well as new radiocarbon dates suggests that knowledge of pottery spread through a process of cultural transmission.

“By this we mean that the activity spread by the exchange of ideas between groups of hunter-gatherers living nearby, rather than through migration of people or an expanding population as we see for other key changes in human history such as the introduction of agriculture.”

“That methods of pottery-making spread so far and so fast through the passing on of ideas is quite surprising. Specific knowledge may have been shared through marriages or at centres of aggregation, specific points in the landscape where groups of hunter-gatherers came together perhaps at certain times of the year.”

By studying traces of organic materials left in the pots, the team demonstrated that the pottery was used for cooking, so the ideas of pottery-making may have been spread through shared culinary traditions.

Carl Heron, from the British Museum, said: “We found evidence that the vessels were used for cooking a wide range of animals, fish and plants, and this variety suggests that the drivers for making the pottery were not in response to a particular need, such as detoxifying plants or processing fish, as has previously been suggested.

“We also found patterns suggesting that pottery use was transmitted along with knowledge of their manufacture and decoration. These can be seen as culinary traditions that were rapidly transmitted with the artefacts themselves.”

The world’s earliest pottery containers come from East Asia and may have spread rapidly eastwards through Siberia, before being taken up by hunter-gatherer societies across Northern Europe, long before the arrival of farming.

This research is funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme.

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Materials provided by University of York. Note: Content may be edited for style and length.

This scenario isn’t that far from reality, as AI chatbots are already taking over online commerce. By 2025, 95% of companies will have an AI chatbot, according to Finance Digest. AI might not be sentient yet, but it can be programmed to express emotions.

Humans displaying positive emotions in customer service interactions have long been known to improve customer experience, but researchers at the Georgia Institute of Technology’s Scheller College of Business wanted to see if this also applied to AI. They conducted experimental studies to determine if positive emotional displays improved customer service and found that emotive AI is only appreciated if the customer expects it, and it may not be the best avenue for companies to invest in.

“It is commonly believed and repeatedly shown that human employees can express positive emotion to improve customers’ service evaluations,” said Han Zhang, the Steven A. Denning Professor in Technology & Management. “Our findings suggest that the likelihood of AI’s expression of positive emotion to benefit or hurt service evaluations depends on the type of relationship that customers expect from the service agent.”

The researchers presented their findings in the paper, “Bots With Feelings: Should AI Agents Express Positive Emotion in Customer Service?,” in Information Systems Research in December.

Studying AI Emotion

The researchers conducted three studies to expand the understanding of emotional AI in customer service transactions. Although they changed the participants and scenario in each study, AI chatbots imbued with emotion used positive emotional adjectives, such as excited, delighted, happy, or glad. They also deployed more exclamation points.

The first study focused on whether customers responded more favorably to positive emotion if they knew the customer agent was a bot or person. Participants were told they were seeking help for a missing item in a retail order. The 155 participants were then randomly assigned to four different scenarios: human agents with neutral emotion, human agents with positive emotion, bots with neutral emotion, and bots with positive emotion. Then they asked participants about service quality and overall satisfaction. The results indicated that positive emotion was more beneficial when human agents exhibited it, but it had no effect when bots exhibited it.

The second study examined if customers’ personal expectations determined their reaction to the bot. In this scenario, the 88 participants imagined returning a textbook and were randomly assigned to either emotion-positive or emotion-neutral bots. After chatting with the bot, they were asked to rate if they were communal (social) oriented or exchange (transaction) oriented on a scale. If the participant was communal-focused, they were more likely to appreciate the positive emotional bot, but if they expected the exchange as merely transactional, the emotionally positive bot made their experience worse.

“Our work enables businesses to understand the expectations of customers exposed to AI-provided services before they haphazardly equip AIs with emotion-expressing capabilities,” Zhang said.

The final study explored why a bot’s positive emotion influences customer emotions, following 177 undergraduate students randomly assigned to emotive or non-emotive bots. The results explained why positive bots have less of an effect than anticipated. Because customers do not expect machines to have emotions, they can react negatively to emotion in a bot.

The results across the studies show that using positive emotion in chatbots is challenging because businesses don’t know a customer’s biases and expectations going into the interaction. A happy chatbot could lead to an unhappy customer.

“Our findings suggest that the positive effect of expressing positive emotion on service evaluations may not materialize when the source of the emotion is not a human,” Zhang said. “Practitioners should be cautious about the promises of equipping AI agents with emotion-expressing capabilities.”