Fingerprints are one of the best-recognised examples of pattern formation by epithelial cells. The primary cells in the epithelium are the keratinocytes, and they are known to form patterns at the microscopic and macroscopic levels. While factors affecting this pattern formation have been reported, the exact mechanisms underlying the process are still not fully understood.

A team of researchers, led by Associate Professor Ken Natsuga at the Faculty of Medicine, Hokkaido University, have revealed that cell-cell adhesion governs pattern formation in keratinocytes. Their findings were published in the journal Life Science Alliance.

“In this study, we used an immortalized keratinocyte cell line, called HaCaT, which retains all the properties of normal keratinocytes,” Natsuga explained. “In order to ensure that our findings were accurate, we established single-cell cultures from this cell line.”

The team observed pattern formation in both the original heterogeneous cell line, as well as in single-cell-derived cultures. During culturing, the keratinocytes moved randomly and spontaneously formed high- and low-density regions, leading to pattern formation.

The pattern formation was markedly influenced by starvation. When the culture medium was renewed, patterns were obscured, but reappeared as the nutrients in the culture medium were consumed by the keratinocytes.

The team then examined the gene expression in the keratinocytes, which revealed that cell adhesion proteins and keratinocyte differentiation proteins were upregulated in high-density regions. “As cell adhesion is necessary for the development of high-cell-density regions, we specifically investigated the expression of adherens junction (AJ) molecules such as E-cadherin and actin,” Natsuga elaborated. “We found that these molecules were localized at the intercellular junctions of high-density regions.”

The authors then used a mathematical model to confirm that, under spatially uniform density and stress, strong cell adhesion leads to the formation of density patterns. They were also able to demonstrate that the keratinocyte patterns influenced cell proliferation and differentiation, and that serum starvation influences epidermal stratification (a type of differentiation) in skin cells from mice.

“Our study presents a novel and robust model of cell-cell adhesion-induced patterning (CAIP),” concludes Natsuga. “We have deepened our mechanistic insight into cellular organization and its consequences for cell fate decisions and epithelial stratification.” The team demonstrated that epithelial cell-cell adhesion is essential and sufficient for patterning. Future work will focus on adding more variables to the model to understand other processes that occur concurrently during development.

The work, led by scientists at the Department of Energy’s Pacific Northwest National Laboratory, published today in the journal Geophysical Research Letters.

Regulations put into effect in 2020 by the International Maritime Organization required a roughly 80 percent reduction in the sulfur content of shipping fuel used globally. That reduction meant fewer sulfur aerosols flowed into Earth’s atmosphere.

When ships burn fuel, sulfur dioxide flows into the atmosphere. Energized by sunlight, chemical intermingling in the atmosphere can spur the formation of sulfur aerosols. Sulfur emissions, a form of pollution, can cause acid rain. The change was made to improve air quality around ports.

In addition, water likes to condense on these tiny sulfate particles, ultimately forming linear clouds known as ship tracks, which tend to concentrate along maritime shipping routes. Sulfate can also contribute to forming other clouds after a ship has passed. Because of their brightness, these clouds are uniquely capable of cooling Earth’s surface by reflecting sunlight.

The authors used a machine learning approach to scan over a million satellite images and quantify the declining count of ship tracks, estimating a 25 to 50 percent reduction in visible tracks. Where the cloud count was down, the degree of warming was generally up.

Further work by the authors simulated the effects of the ship aerosols in three climate models and compared the cloud changes to observed cloud and temperature changes since 2020. Roughly half of the potential warming from the shipping emission changes materialized in just four years, according to the new work. In the near future, more warming is likely to follow as the climate response continues unfolding.

Many factors — from oscillating climate patterns to greenhouse gas concentrations — determine global temperature change. The authors note that changes in sulfur emissions aren’t the sole contributor to the record warming of 2023. The magnitude of warming is too significant to be attributed to the emissions change alone, according to their findings.

Due to their cooling properties, some aerosols mask a portion of the warming brought by greenhouse gas emissions. Though aerosols can travel great distances and impose a strong effect on Earth’s climate, they are much shorter-lived than greenhouse gasses.

When atmospheric aerosol concentrations suddenly dwindle, warming can spike. It’s difficult, however, to estimate just how much warming may come as a result. Aerosols are one of the most significant sources of uncertainty in climate projections.

“Cleaning up air quality faster than limiting greenhouse gas emissions may be accelerating climate change,” said Earth scientist Andrew Gettelman, who led the new work.

“As the world rapidly decarbonizes and dials down all anthropogenic emissions, sulfur included, it will become increasingly important to understand just what the magnitude of the climate response could be. Some changes could come quite quickly.”

The work also illustrates that real-world changes in temperature may result from changing ocean clouds, either incidentally with sulfur associated with ship exhaust, or with a deliberate climate intervention by adding aerosols back over the ocean. But lots of uncertainties remain. Better access to ship position and detailed emissions data, along with modeling that better captures potential feedback from the ocean, could help strengthen our understanding.

In addition to Gettelman, Earth scientist Matthew Christensen is also a PNNL author of the work. This work was funded in part by the National Oceanic and Atmospheric Administration.

The research team’s findings show that when decision makers quickly come to a conclusion, the decision is more influenced by their initial bias, or a tendency to err on the side of one of the choices presented. If decision makers wait to gather more information, the slower decision will be less biased. The work was published today in Physical Review E.

“The basic result might seem sort of intuitive, but the mathematics we had to employ to prove this was really non-trivial,” said co-author Bhargav Karamched, an assistant professor in the FSU Department of Mathematics and the Institute of Molecular Biophysics. “We saw that for the first decider in a group, the trajectory of their belief is almost a straight line. The last decider hovers around, going back and forth for a while before making a decision. Even though the underlying equation for each agent’s belief is the same except for their initial bias, the statistics and behavior of each individual is very different.”

The researchers built a mathematical model that represented a group of agents required to decide between two conclusions, one which was correct and one which was incorrect. The model assumed each actor within a group was acting rationally, that is, deciding based off their initial bias and the information they are presented, rather than being swayed by the decisions of individuals around them.

Even with evidence and assuming perfect rationality, bias toward a particular decision caused the earliest deciders in the model to make the wrong conclusion 50% of the time. The more information actors gathered, the more likely they were to behave as if they weren’t biased and to arrive at a correct conclusion.

Of course, in the real world, people are swayed by all sorts of inputs, such as their emotions, the decisions their friends made and other variables. This research offers a metric showing how individuals within a group should make decisions if they are acting rationally. Future research could compare real-world data against this metric to see where people are diverting from optimally rational choices and consider what might have caused their divergence.

The researchers’ model is known as a drift diffusion model, so called because it combines two concepts: individual actor’s tendency to “drift,” or move toward an outcome based on evidence, and the random “diffusion,” or variability of the information presented.

The work could be used, for example, to understand when people are being unduly swayed by early decisions or falling victim to groupthink. It even helps describe other complex scenarios with many individual actors, such as the immune system or the behavior of neurons.

“There is still a lot of work to do to understand decision making in more complicated situations, such as cases where more than two alternatives are presented as choices, but this is a good starting point,” Karamched said.

This research was a multi-institution collaboration involving doctoral candidate Samantha Linn and Associate Professor Sean D. Lawley of the University of Utah, Associate Professor Zachary P. Kilpatrick of the University of Colorado, and Professor Krešimir Josic of the University of Houston.

This research was supported by the National Science Foundation and the National Institutes of Health.

But while the American public quickly learned about the disease during the summer of 2022, as the number of cases declined and media attention waned, much of that knowledge appears to have been lost, according to new survey data from the Annenberg Public Policy Center of the University of Pennsylvania.

In a nationally representative survey of about 1,500 U.S. empaneled adults conducted in July 2024, the policy center finds that knowledge about mpox — which increased from July to August 2022 — has declined, along with fear of the disease (which was previously called monkeypox). This wave of the Annenberg Science and Public Health (ASAPH) knowledge survey finds that:

• Only 1 in 20 Americans (5%) are worried about contracting mpox in the next three months, down from 21% in August 2022. In addition, fewer than 1 in 10 (9%) are worried that they or their families will contract mpox.

• Fewer than 1 in 5 people (17%) know that mpox is less contagious than Covid-19, down from 41% in August 2022. Nearly two-thirds (63%) are not sure.

• Just a third of people (34%) know that men who have sex with men are at a higher risk of infection with mpox, down from nearly two-thirds (63%) in August 2022.

• Less than half (45%) know that a vaccine for mpox exists, down from 61% in August 2022.

• Fewer people (58%) know that it’s false to say that getting a Covid-19 vaccine increases your chances of getting mpox, down from 71%.

“The speed with which the public learned needed information about mpox in the summer of 2022 was a tribute to effective communication by the public health community,” said Kathleen Hall Jamieson, director of the Annenberg Public Policy Center (APPC) and director of the survey. “That same expertise should now be deployed to ensure that those at risk remember mpox’s symptoms, modes of transmission, and the protective power of vaccination.”

Mpox outbreaks in 2024 and 2022

Discovered in 1958, mpox is a rare disease caused by an orthopox virus, and is a less deadly member of the family of viruses that cause smallpox, according to the CDC. Mpox may cause fever, chills, headaches, muscle aches, swollen lymph nodes, and painful rashes, particularly on the hands, feet, face, chest, mouth, or near the genitals. According to the CDC, the disease can spread through contact with infected wild animals, close (including sexual) contact with an infected individual, including contact with scabs or body fluids, or contact with contaminated materials such as towels or bedding.

The current outbreak involves an mpox strain known as clade I, which is especially virulent and dangerous to infants and children under the age of 5, according to the World Health Organization (WHO), whose director general announced this week that he was convening a panel of experts to advise him whether the outbreak should be declared a global health emergency. (The WHO called an end to the 2022 mpox global health emergency in May 2023.) The WHO says there have been over 14,000 cases this year, with at least 511 deaths, according to STAT News. In the Democratic Republic of Congo (DRC), 62% of the deaths involved children under age 5. The current subtype appears to be spread through routine close contact between individuals, though in November 2023 the WHO confirmed that this strain was also being sexually transmitted.

This deadlier strain of monkeypox has not been reported outside central and east Africa, the CDC said.

A different strain of mpox in the 2022 outbreak, known as the clade II subtype, which spread across the United States, was less deadly and largely transmitted through sexual contact, and men who have sex with men were at higher risk of the disease. That earlier strain never disappeared entirely, though new cases are at a much lower level, according to the CDC. The majority of cases are in people who are not vaccinated against mpox or have received only one of the two recommended doses, the CDC reported.

Vaccination against mpox

While knowledge concerning mpox has declined significantly, there has been a less pronounced drop in people’s intentions to get vaccinated against the disease. The CDC has urged individuals to be vaccinated with two doses of the vaccine Jynneos four weeks apart — both for people who have been exposed to mpox virus to help prevent its spread and for people with risk factors for mpox, including men who have sex with men.

An earlier APPC survey, in October 2022, found that 76% of respondents said they were “very likely” or “somewhat likely” to get an mpox vaccine if they were exposed to mpox. The current survey, in July 2024, found a slight decline — 70% of respondents reported that they were either very/somewhat likely to get the vaccine (68%) or were already vaccinated against mpox (2%). However, 3 in 10 (30%) said they were “not too likely” or “not at all likely” to get vaccinated against mpox if exposed to the virus. In addition, 70% reported in July 2024 that they thought the benefits of vaccination against mpox outweighed the risks.

APPC’s ASAPH survey

The survey data come from the 20^th wave of a nationally representative panel of 1,496 U.S. adults, first empaneled in April 2021, conducted for the Annenberg Public Policy Center by SSRS, an independent market research company. This wave of the Annenberg Science and Public Health Knowledge (ASAPH) survey was fielded July 11-18, 2024, and has a margin of sampling error (MOE) of ± 3.6 percentage points at the 95% confidence level. All figures are rounded to the nearest whole number and may not add to 100%.

The researchers developed a method to measure three-dimensional shape changes and analyze how cells behave during this process. Using a physical model based on shape-programming, they found that the movements and rearrangements of cells play a key role in shaping the tissue. This study, published in Science Advances, shows that the shape programming method could be a common way to show how tissues form in animals.

Epithelial tissues are layers of tightly connected cells and make up the basic structure of many organs. To create functional organs, tissues change their shape in three dimensions. While some mechanisms for three-dimensional shapes have been explored, they are not sufficient to explain the diversity of animal tissue forms. For example, during a process in the development of a fruit fly called wing disc eversion, the wing transitions from a single layer of cells to a double layer. How the wing disc pouch undergoes this shape change from a radially symmetric dome into a curved fold shape is unknown.

The research groups of Carl Modes, group leader at the MPI-CBG and the CSBD, and Natalie Dye, group leader at PoL and previously affiliated with MPI-CBG, wanted to find out how this shape change occurs. “To explain this process, we drew inspiration from “shape-programmable” inanimate material sheets, such as thin hydrogels, that can transform into three-dimensional shapes through internal stresses when stimulated,” explains Natalie Dye, and continues: “These materials can change their internal structure across the sheet in a controlled way to create specific three-dimensional shapes. This concept has already helped us understand how plants grow. Animal tissues, however, are more dynamic, with cells that change shape, size, and position.”

To see if shape programming could be a mechanism to understand animal development, the researchers measured tissue shape changes and cell behaviors during the Drosophila wing disc eversion, when the dome shape transforms into a curved fold shape. “Using a physical model, we showed that collective, programmed cell behaviors are sufficient to create the shape changes seen in the wing disc pouch. This means that external forces from surrounding tissues are not needed, and cell rearrangements are the main driver of pouch shape change,” says Jana Fuhrmann, a postdoctoral fellow in the research group of Natalie Dye. To confirm that rearranged cells are the main reason for pouch eversion, the researchers tested this by reducing cell movement, which in turn caused problems with the tissue shaping process.

Abhijeet Krishna, a doctoral student in the group of Carl Modes at the time of the study, explains: “The new models for shape programmability that we developed are connected to different types of cell behaviors. These models include both uniform and direction-dependent effects. While there were previous models for shape programmability, they only looked at one type of effect at a time. Our models combine both types of effects and link them directly to cell behaviors.”

Natalie Dye and Carl Modes conclude: “We discovered that internal stress brought on by active cell behaviors is what shapes the Drosophila wing disc pouch during eversion. Using our new method and a theoretical framework derived from shape-programmable materials, we were able to measure cell patterns on any tissue surface. These tools help us understand how animal tissue transforms their shape and size in three dimensions. Overall, our work suggests that early mechanical signals help organize how cells behave, which later leads to changes in tissue shape. Our work illustrates principles that could be used more widely to better understand other tissue-shaping processes.”