“We’re very interested in understanding the meaning and origin of the portraits, and finding ways to connect them and come up with a cultural understanding of why they were even painted in the first place,” says materials scientist Darryl Butt, co-author of the study and dean of the College of Mines and Earth Sciences.

Faiyum mummies

The portrait that contained the purple pigment came from an Egyptian mummy, but it doesn’t look the same as what you might initially think of as a mummy — not like the golden sarcophagus of Tutankhamen, nor like the sideways-facing paintings on murals and papyri. Not like Boris Karloff, either.

The portrait, called “Portrait of a Bearded Man,” comes from the second century when Egypt was a Roman province, hence the portraits are more lifelike and less hieroglyphic-like than Egyptian art of previous eras. Most of these portraits come from a region called Faiyum, and around 1,100 are known to exist. They’re painted on wood and were wrapped into the linens that held the mummified body. The portraits were meant to express the likeness of the person, but also their status — either actual or aspirational.

That idea of status is actually very important in this case because the man in the portrait we’re focusing on is wearing purple marks called clavi on his toga. “Since the purple pigment occurred in the clavi — the purple mark on the toga that in Ancient Rome indicated senatorial or equestrian rank- it was thought that perhaps we were seeing an augmentation of the sitter’s importance in the afterlife,” says Glenn Gates of the Walters Art Museum in Baltimore, where the portrait resides.

The color purple, Butt says, is viewed as a symbol of death in some cultures and a symbol of life in others. It was associated with royalty in ancient times, and still is today. Paraphrasing the author Victoria Finlay, Butt says that purple, located at the end of the visible color spectrum, can suggest the end of the known and the beginning of the unknown.

“So the presence of purple on this particular portrait made us wonder what it was made of and what it meant,” Butt says. “The color purple stimulates many questions.”

Lake pigments

Through a microscope, Gates saw that the pigment looked like crushed gems, containing particles ten to a hundred times larger than typical paint particles. To answer the question of how it was made, Gates sent a particle of the pigment to Butt and his team for analysis. The particle was only 50 microns in diameter, about the same as a human hair, which made keeping track of it challenging.

“The particle was shipped to me from Baltimore, sandwiched between two glass slides,” Butt says, “and because it had moved approximately a millimeter during transit, it took us two days to find it.” In order to move the particle to a specimen holder, the team used an eyelash with a tiny quantity of adhesive at its tip to make the transfer. “The process of analyzing something like this is a bit like doing surgery on a flea.”

With that particle, as small as it was, the researchers could machine even smaller samples using a focused ion beam and analyze those samples for their elemental composition.

What did they find? To put the results in context, you’ll need to know how dyes and pigments are made.

Pigments and dyes are not the same things. Dyes are the pure coloring agents, and pigments are the combination of dyes, minerals, binders and other components that make up what we might recognize as paint.

Initially, purple dyes came from a gland of a genus of sea snails called Murex. Butt and his colleagues hypothesize that the purple used in this mummy painting is something else — a synthetic purple.

The researchers also hypothesize that the synthetic purple could have originally been discovered by accident when red dye and blue indigo dye mixed together. The final color may also be due to the introduction of chromium into the mix.

From there, the mineralogy of the pigment sample suggests that the dye was mixed with clay or a silica material to form a pigment. According to Butt, an accomplished painter himself, pigments made in this way are called lake pigments (derived from the same root word as lacquer). Further, the pigment was mixed with a beeswax binder before finally being painted on linden wood.

The pigment showed evidence suggesting a crystal structure in the pigment. “Lake pigments were thought to be without crystallinity prior to this work,” Gates says. “We now know crystalline domains exist in lake pigments, and these can function to ‘trap’ evidence of the environment during pigment creation.”

Bottom of the barrel, er, vat

One other detail added a bit more depth to the story of how this portrait was made. The researchers found significant amounts of lead in the pigment as well and connected that finding with observations from a late 1800s British explorer who reported that the vats of dye in Egyptian dyers’ workshops were made of lead.

“Over time, a story or hypothesis emerged,” Butt says, “suggesting that the Egyptian dyers produced red dye in these lead vats.” And when they were done dyeing at the end of the day, he says, there may have been a sludge that developed inside the vat that was a purplish color. “Or, they were very smart and they may have found a way to take their red dye, shift the color toward purple by adding a salt with transition metals and a mordant [a substance that fixes a dye] to intentionally synthesize a purple pigment. We don’t know.”

Broader impacts

This isn’t Butt’s first time using scientific methods to learn about ancient artwork. He’s been involved with previous similar investigations and has drawn on both his research and artistic backgrounds to develop a class called “The Science of Art” that included studies and discussions on topics that involved dating, understanding and reverse engineering a variety of historical artifacts ranging from pioneer newspapers to ancient art.

“Mixing science and art together is just fun,” he says. “It’s a great way to make learning science more accessible.”

And the work has broader impacts as well. Relatively little is known about the mummy portraits, including whether the same artist painted multiple portraits. Analyzing pigments on an atomic level might provide the chemical fingerprint needed to link portraits to each other.

“Our results suggest one tool for documenting similarities regarding time and place of production of mummy portraits since most were grave-robbed and lack archaeological context,” Gates says.

“So we might be able to connect families,” Butt adds. “We might be able to connect artists to one another.”

In findings recently published in the journal Science Advances, these boisterous, red-beaked songbirds, known as zebra finches, have been shown to pick one another out of a crowd (or flock) based on a particular peer’s distinct song or contact call.

Like humans who can instantly tell which friend or relative is calling by the timbre of the person’s voice, zebra finches have a near-human capacity for language mapping. Moreover, they can remember each other’s unique vocalizations for months and perhaps longer, the findings suggest.

“The amazing auditory memory of zebra finches shows that birds’ brains are highly adapted for sophisticated social communication,” said study lead author Frederic Theunissen, a UC Berkeley professor of psychology, integrative biology and neuroscience.

Theunissen and fellow researchers sought to gauge the scope and magnitude of zebra finches’ ability to identify their feathered peers based purely on their unique sounds. As a result, they found that the birds, which mate for life, performed even better than anticipated.

“For animals, the ability to recognize the source and meaning of a cohort member’s call requires complex mapping skills, and this is something zebra finches have clearly mastered,” Theunissen said.

A pioneer in the study of bird and human auditory communication for at least two decades, Theunissen acquired a fascination and admiration for the communication skills of zebra finches through his collaboration with UC Berkeley postdoctoral fellow Julie Elie, a neuroethologist who has studied zebra finches in the forests of their native Australia. Their teamwork yielded groundbreaking findings about the communication skills of zebra finches.

Zebra finches usually travel around in colonies of 50 to 100 birds, flying apart and then coming back together. Their songs are typically mating calls, while their distance or contact calls are used to identify where they are, or to locate one another.

“They have what we call a ‘fusion fission’ society, where they split up and then come back together,” Theunissen said. “They don’t want to separate from the flock, and so, if one of them gets lost, they might call out ‘Hey, Ted, we’re right here.’ Or, if one of them is sitting in a nest while the other is foraging, one might call out to ask if it’s safe to return to the nest.”

These days, Theunissen keeps a few dozen zebra finches in aviaries on and around campus, 20 of which were used in this latest experiment.

In a two-part experiment, 20 captive zebra finches were trained to distinguish between different birds and their vocalizations. At first, half the birds were tested on memorizing songs, while the other half were assessed on distance or contact calls. They then switched those tasks.

Next, the zebra finches were placed, one at a time, inside a chamber and listened to sounds as part of a reward system. The goal was to train them to respond to particular zebra finches by hearing several different renditions of those birds’ distinct vocalizations and memorizing them.

By pecking a key inside the chamber, the bird subjects triggered an audio recording of a zebra finch vocalization. If they waited until the six-second recording ended, and it was part of the reward group, they received birdseed. If they pecked before the recording was finished, they moved to the next recording. Over several trials, they learned which vocalizations would yield birdseed, and which ones to skip.

Next, the zebra finches were introduced to more audio recordings from new zebra finches, to teach them to distinguish which vocalizations belonged to which bird. They soon learned to differentiate between 16 different zebra finches.

In fact, the zebra finches, both male and female, performed so well in the tests that four of them were given the more challenging task of distinguishing between 56 different zebra finches. On average, they succeeded in recognizing 42 different zebra finches, based on their signature sounds. Plus, they were still able to identify the birds based on their unique sounds a month later.

“I am really impressed by the spectacular memory abilities that zebra finches possess in order to interpret communication calls,” Theunissen said. “Previous research shows that songbirds are capable of using simple syntax to generate complex meanings and that, in many bird species, a song is learned by imitation. It is now clear that the songbird brain is wired for vocal communication.”

In addition to Theunissen, co-authors of the study are Kevin Yu and Willam Wood at UC Berkeley.

Professor Ivan Huc (Department of Pharmacy, LMU) studies aspects of the self-organization processes that enable macromolecules to adopt defined folded shapes. The molecular structures found in nature provide him with models, whose properties he tries to reproduce in the laboratory with non-natural molecules that are neither proteins, nucleic acids or sugar-like. More specifically, he uses the tools of synthetic chemistry to elucidate the underlying principles of self-organization — by constructing molecules that are expressly designed to fold into predetermined shapes. Beginning with monomers that his group has developed, he sets out to produce what he calls ‘foldamers’, by assembling the monomers one by one to generate a folded macromolecule.

Structures with low degrees of symmetry

“The normal way to get the complex structure of proteins is to use different types of monomers, called amino acids,” as Huc reports. “And the normal method to connect different amino acids in the the correct order is to link them one by one.” The sequence of amino acids contains the folding information that allows different protein sequences to fold in different ways.

“But we discovered something unexpected and spectacular,” comments Huc. He and his colleagues in Munich, Groningen, Bordeaux and Berlin used organic, sulfur-containing monomers to spontaneously get cyclic macromolecules with a complex shape, as illustrated by their low degree of symmetry, without requiring a specific sequence. The macromolecules self-synthesize — no further conditions are necessary. “We only put one monomer type in a flask and wait,” Huc says. “This is typical for a polymerization reaction, but polymers from a single monomer usually don´t adopt complex shapes and don’t stop growing at a precise chain length.”

To further control the reaction, the scientists also used either a small guest molecule or a metal ion. The regulator binds within the growing macromolecule and causes monomers to arrange themselves around it. By choosing a regulator with the appropriate characteristics, the authors of the new study were able to produce structures with a predetermined number of subunits. The cyclic macromolecules exhibited low levels of symmetry. Some consisted of either 13, 17 or 23 subunits. Since 13, 17 and 23 are prime numbers, the corresponding folded shapes exhibit low degrees of symmetry.

A model for biological and industrial processes

Interest in the elucidation of such mechanisms is not restricted to the realm of basic research. Huc and his colleagues hope that their approach will lead to the fabrication of designer plastics. Conventional polymers usually consist of mixtures of molecules that vary in length (i.e. the number of monomers they contain). This heterogeneity has an impact on their physical properties. Hence, the ability to synthesize polymer chains of an exact length and/or geometry is expected to lead to materials with novel and interesting behaviors.

Furthermore, foldamers like those that have now been synthesized show close structural resemblances to biopolymers. They therefore offer an ideal model system in which to study the properties of proteins. Every protein is made up of a defined linear (i.e. unbranched) sequence of amino acids, which constitutes its ‘primary structure’. But most amino-acid chains fold into local substructures such as helically coiled stretches, or parallel strands that can form sheets. These units represent the protein’s secondary structure. The term ‘tertiary structure’ is applied to the fully folded single chain. This in turn can interact with other chains to form a functional unit or quaternary structure.

Huc’s ultimate goal is to mimic complex biological mechanisms using structurally defined, synthetic precursors. He wants to understand how, for example, enzymes fold into the correct, biologically active conformation following their synthesis in cells. Molecules whose properties can be precisely controlled in the laboratory provide ideal models with which to work out the answers and perhaps to go beyond enzymes themselves.

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The researchers found that a unique protocol of treatments with high-pressure oxygen in a pressure chamber can reverse two major processes associated with aging and its illnesses: the shortening of telomeres (protective regions located at both ends of every chromosome) and the accumulation of old and malfunctioning cells in the body. Focusing on immune cells containing DNA obtained from the participants’ blood, the study discovered a lengthening of up to 38% of the telomeres, as well as a decrease of up to 37% in the presence of senescent cells.

The study was led by Professor Shai Efrati of the Sackler School of Medicine and the Sagol School of Neuroscience at TAU and Founder and Director of the Sagol Center of Hyperbaric Medicine at the Shamir Medical Center; and Dr. Amir Hadanny, Chief Medical Research Officer of the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center. The clinical trial was conducted as part of a comprehensive Israeli research program that targets aging as a reversible condition.

The paper was published in Aging on November 18, 2020.

“For many years our team has been engaged in hyperbaric research and therapy — treatments based on protocols of exposure to high-pressure oxygen at various concentrations inside a pressure chamber,” Professor Efrati explains. “Our achievements over the years included the improvement of brain functions damaged by age, stroke or brain injury.

“In the current study we wished to examine the impact of HBOT on healthy and independent aging adults, and to discover whether such treatments can slow down, stop or even reverse the normal aging process at the cellular level.”

The researchers exposed 35 healthy individuals aged 64 or over to a series of 60 hyperbaric sessions over a period of 90 days. Each participant provided blood samples before, during and at the end of the treatments as well as some time after the series of treatments concluded. The researchers then analyzed various immune cells in the blood and compared the results.

The findings indicated that the treatments actually reversed the aging process in two of its major aspects: The telomeres at the ends of the chromosomes grew longer instead of shorter, at a rate of 20%-38% for the different cell types; and the percentage of senescent cells in the overall cell population was reduced significantly — by 11%-37% depending on cell type.

“Today telomere shortening is considered the ‘Holy Grail’ of the biology of aging,” Professor Efrati says. “Researchers around the world are trying to develop pharmacological and environmental interventions that enable telomere elongation. Our HBOT protocol was able to achieve this, proving that the aging process can in fact be reversed at the basic cellular-molecular level.”

“Until now, interventions such as lifestyle modifications and intense exercise were shown to have some inhibiting effect on telomere shortening,” Dr. Hadanny adds. “But in our study, only three months of HBOT were able to elongate telomeres at rates far beyond any currently available interventions or lifestyle modifications. With this pioneering study, we have opened a door for further research on the cellular impact of HBOT and its potential for reversing the aging process.”

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The researchers developed a model to test the effectiveness of measures such as physical distancing, masks or social bubbles when used in various settings.

Their paper was published Nov. 19 in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

They introduce the concept of “event R,” which is the expected number of people who become infected with COVID-19 from one individual at an event.

Tupper and Colijn look at factors such as transmission intensity, duration of exposure, the proximity of individuals and degree of mixing — then examine what methods are most effective at preventing transmission in each circumstance.

The researchers incorporated data from reports of outbreaks at a range of events, such as parties, meals, nightclubs, public transit and restaurants. The researchers say that an individual’s chances of becoming infected with COVID-19 depend heavily on the transmission rate and the duration — the amount of time spent in a particular setting.

Events were categorized as saturating (high transmission probability) or linear (low transmission probability). Examples of high transmission settings include bars, nightclubs and overcrowded workplaces while low transmission settings include public transit with masks, distancing in restaurants and outdoor activities.

The model suggests that physical distancing was effective at reducing COVID-19 transmission in all settings but the effectiveness of social bubbles depends on whether chances of transmission are high or low.

In settings where there is mixing and the probability of transmission is high, such as crowded indoor workplaces, bars and nightclubs and high schools, having strict social bubbles can help reduce the spread of COVID-19.

The researchers found that social bubbles are less effective in low transmission settings or activities where there is mixing, such as engaging in outdoor activities, working in spaced offices or travelling on public transportation wearing masks.

They note that masks and other physical barriers may be less effective in saturating, high transmission settings (parties, choirs, restaurant kitchens, crowded offices, nightclubs and bars) because even if masks halve the transmission rates that may not have much impact on the transmission probability (and so on the number of infections).

The novel coronavirus is relatively new but the science continues to evolve and increase our knowledge of how to effectively treat and prevent this highly contagious virus. There is still much that we do not know and many areas requiring further study.

“It would be great to start collecting information from exposures and outbreaks: the number of attendees, the amount of mixing, the levels of crowding, the noise level and the duration of the event,” says Colijn, who holds a Canada Research Chair in Mathematics for Evolution, Infection and Public Health.

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But, it turns out, ChIP-seq may have been quantitative all along, according to a recent report selected as an Editors’ Pick by and featured on the cover of the Journal of Biological Chemistry.

“ChIP-seq is the backbone of epigenetics research. Our findings challenge the belief that additional steps are required to make it quantitative,” said Brad Dickson, Ph.D., a staff scientist at Van Andel Institute and the study’s corresponding author. “Our new approach provides a way to quantify results, thereby making ChIP-seq more precise, while leaving standard protocols untouched.”

Previous attempts to quantify ChIP-seq results have led to additional steps being added to the protocol, including the use of “spike-ins,” which are additives designed to normalize ChIP-seq results and reveal histone changes that otherwise may be obscured. These extra steps increase the complexity of experiments while also adding variables that could interfere with reproducibility. Importantly, the study also identifies a sensitivity issue in spike-in normalization that has not previously been discussed.

Using a predictive physical model, Dickson and his colleagues developed a novel approach called the sans-spike-in method for Quantitative ChIP-sequencing, or siQ-ChIP. It allows researchers to follow the standard ChIP-seq protocol, eliminating the need for spike-ins, and also outlines a set of common measurements that should be reported for all ChIP-seq experiments to ensure reproducibility as well as quantification.

By leveraging the binding reaction at the immunoprecipitation step, siQ-ChIP defines a physical scale for sequencing results that allows comparison between experiments. The quantitative scale is based on the binding isotherm of the immunoprecipitation products.

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