DNA from archaeological remains shows that immigration to Scandinavia was exceptional during the Viking period

A new study based on 297 ancient Scandinavian genomes analysed together with the genomic data of 16,638 present day Scandinavians resolve the complex relations between geography, ancestry, and gene flow in Scandinavia -- encompassing the Roman Age, the Viking Age and later periods. A surprising increase of variation during the Viking period indicates that gene flow into Scandinavia was especially intense during this period.

An international study coordinated from Stockholm and Reykjavik investigates the development of the Scandinavian gene pool over the latest 2000 years. In this effort the scientists relied on historic and prehistoric genomes, and from material excavated in Scandinavia. These ancient genomes were compared with genomic data from 16,638 contemporary Scandinavians. As the geographical origin and the datings were known for all these individuals, it was possible to resolve the development of the gene pool to a level never realised previously.

Dr Ricardo Rodríguez Varela at the Centre for Palaeogenetics*, who analysed all the data and extracted some of the ancient DNA used in the study, explains: "With this level of resolution we not only confirm the Viking Age migration. We are also able to trace it to the east Baltic region, the British-Irish Isles and southern Europe. But not all parts of Scandinavia received the same amounts of gene flow from these areas. For example, while British-Irish ancestry became widespread in Scandinavia the eastern-Baltic ancestry mainly reached Gotland and central Sweden."

The gene pool bounced back after the Viking period

Another new discovery in this study was what happened to the gene pool after the Viking period. The scientists were surprised to find that it bounced back in the direction of what it looked like before the Viking period migration.

Professor Anders Götherström at the Centre for Palaeogenetics, who is a senior scientist on the study, is intrigued: "Interestingly, the non-local ancestry peaks during the Viking period while being lower before and after. The drop in current levels of external ancestry suggests that the Viking-period migrants got less children, or somehow contributed proportionally less to the gene pool than the people who were already in Scandinavia."

Yet a new discovery was the history of the northern Scandinavian gene pool. There is a genetic component in northern Scandinavia that is rare in central and western Europe, and the scientists were able to track this component in northern Scandinavia through the latest 1000 years.

Dr Ricardo Rodríguez Varela comments, "We suspected that there was a chronology to the northern Scandinavian gene pool, and it did indeed prove that a more recent influx of Uralic ancestry into Scandinavia define much of the northern gene pool. But if it is recent, it is comparatively so. For example, we know that this Uralic ancestry was present in northern Scandinavia as early as during the late Viking period."

Based on well-known Swedish archaeological sites

The study is based on a number of well-known Swedish archaeological sites. For example, there are genomes from the 17th century warship Kronan, from the Viking and Vendel period boat burials in the lake Mälaren Valley, and from the migration period ring fortress Sandby borg on Öland.

Anders Götherström conclude: "We were working on a number of smaller studies on different archaeological sites. And at some point it just made sense to combine them into a larger study on the development of the Scandinavian gene pool.

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Two out of three glaciers could be lost by 2100

Assistant Professor David Rounce of Civil and Environmental Engineering led an international effort to produce new projections of glacier mass loss through the century under different emissions scenarios. The projections were aggregated into global temperature change scenarios to support adaptation and mitigation discussions, such as those at the recent United Nations Conference of Parties (COP 27). His work showed that the world could lose as much as 41 percent of its total glacier mass this century -- or as little as 26 percent -- depending on today's climate change mitigation efforts.

Specifically, Rounce and his team found that in a future scenario with continued investment in fossil fuels, over 40 percent of the glacial mass will be gone within the century, and over 80 percent of glaciers by number could well disappear. Even in a best-case, low-emissions scenario, where the increase in global mean temperature is limited to +1.5° C relative to pre-industrial levels, over 25 percent of glacial mass will be gone and nearly 50 percent of glaciers by number are projected to disappear. A majority of these lost glaciers are small (less than one km2) by glacial standards, but their loss can negatively impact local hydrology, tourism, glacier hazards, and cultural values.

His work provides better context for regional glacier modeling, and he hopes it will spur climate policymakers to lower temperature change goals beyond the 2.7° C mark that pledges from COP-26 are projected to hit. Smaller glacial regions like Central Europe and Western Canada and the United States will be disproportionately affected by temperatures rising more than 2° C. At a 3° C rise, glaciers in these regions almost disappear completely.

Rounce noted that the way in which glaciers respond to changes in climate takes a long time. He describes the glaciers as extremely slow-moving rivers. Cutting emissions today will not remove previously emitted greenhouse gasses, nor can it instantly halt the inertia they contribute to climate change, meaning even a complete halt to emissions would still take between 30 and 100 years to be reflected in glacier mass loss rates.

Many processes govern how glaciers lose mass and Rounce's study advances how models account for different types of glaciers, including tidewater and debris-covered glaciers. Tidewater glaciers refer to glaciers that terminate in the ocean, which causes them to lose a lot of mass at this interface. Debris-covered glaciers refer to glaciers that are covered by sand, rocks, and boulders. Prior work by Rounce has shown that the thickness and distribution of debris cover can have a positive or negative effect on glacial melt rates across an entire region, depending on the debris thickness. In this newest work, he found that accounting for these processes had relatively little impact on the global glacier projections, but substantial differences in mass loss were found when analyzing individual glaciers.

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Riddle solved: Why was Roman concrete so durable?

The ancient Romans were masters of engineering, constructing vast networks of roads, aqueducts, ports, and massive buildings, whose remains have survived for two millennia. Many of these structures were built with concrete: Rome's famed Pantheon, which has the world's largest unreinforced concrete dome and was dedicated in A.D. 128, is still intact, and some ancient Roman aqueducts still deliver water to Rome today. Meanwhile, many modern concrete structures have crumbled after a few decades.

Researchers have spent decades trying to figure out the secret of this ultradurable ancient construction material, particularly in structures that endured especially harsh conditions, such as docks, sewers, and seawalls, or those constructed in seismically active locations.

Now, a team of investigators from MIT, Harvard University, and laboratories in Italy and Switzerland, has made progress in this field, discovering ancient concrete-manufacturing strategies that incorporated several key self-healing functionalities. The findings are published in the journal Science Advances, in a paper by MIT professor of civil and environmental engineering Admir Masic, former doctoral student Linda Seymour, and four others.

For many years, researchers have assumed that the key to the ancient concrete's durability was based on one ingredient: pozzolanic material such as volcanic ash from the area of Pozzuoli, on the Bay of Naples. This specific kind of ash was even shipped all across the vast Roman empire to be used in construction, and was described as a key ingredient for concrete in accounts by architects and historians at the time.

Under closer examination, these ancient samples also contain small, distinctive, millimeter-scale bright white mineral features, which have been long recognized as a ubiquitous component of Roman concretes. These white chunks, often referred to as "lime clasts," originate from lime, another key component of the ancient concrete mix. "Ever since I first began working with ancient Roman concrete, I've always been fascinated by these features," says Masic. "These are not found in modern concrete formulations, so why are they present in these ancient materials?"

Previously disregarded as merely evidence of sloppy mixing practices, or poor-quality raw materials, the new study suggests that these tiny lime clasts gave the concrete a previously unrecognized self-healing capability. "The idea that the presence of these lime clasts was simply attributed to low quality control always bothered me," says Masic. "If the Romans put so much effort into making an outstanding construction material, following all of the detailed recipes that had been optimized over the course of many centuries, why would they put so little effort into ensuring the production of a well-mixed final product? There has to be more to this story."

Upon further characterization of these lime clasts, using high-resolution multiscale imaging and chemical mapping techniques pioneered in Masic's research lab, the researchers gained new insights into the potential functionality of these lime clasts.

Historically, it had been assumed that when lime was incorporated into Roman concrete, it was first combined with water to form a highly reactive paste-like material, in a process known as slaking. But this process alone could not account for the presence of the lime clasts. Masic wondered: "Was it possible that the Romans might have actually directly used lime in its more reactive form, known as quicklime?"

Studying samples of this ancient concrete, he and his team determined that the white inclusions were, indeed, made out of various forms of calcium carbonate. And spectroscopic examination provided clues that these had been formed at extreme temperatures, as would be expected from the exothermic reaction produced by using quicklime instead of, or in addition to, the slaked lime in the mixture. Hot mixing, the team has now concluded, was actually the key to the super-durable nature.

"The benefits of hot mixing are twofold," Masic says. "First, when the overall concrete is heated to high temperatures, it allows chemistries that are not possible if you only used slaked lime, producing high-temperature-associated compounds that would not otherwise form. Second, this increased temperature significantly reduces curing and setting times since all the reactions are accelerated, allowing for much faster construction."

During the hot mixing process, the lime clasts develop a characteristically brittle nanoparticulate architecture, creating an easily fractured and reactive calcium source, which, as the team proposed, could provide a critical self-healing functionality. As soon as tiny cracks start to form within the concrete, they can preferentially travel through the high-surface-area lime clasts. This material can then react with water, creating a calcium-saturated solution, which can recrystallize as calcium carbonate and quickly fill the crack, or react with pozzolanic materials to further strengthen the composite material. These reactions take place spontaneously and therefore automatically heal the cracks before they spread. Previous support for this hypothesis was found through the examination of other Roman concrete samples that exhibited calcite-filled cracks.

To prove that this was indeed the mechanism responsible for the durability of the Roman concrete, the team produced samples of hot-mixed concrete that incorporated both ancient and modern formulations, deliberately cracked them, and then ran water through the cracks. Sure enough: Within two weeks the cracks had completely healed and the water could no longer flow. An identical chunk of concrete made without quicklime never healed, and the water just kept flowing through the sample. As a result of these successful tests, the team is working to commercialize this modified cement material.

"It's exciting to think about how these more durable concrete formulations could expand not only the service life of these materials, but also how it could improve the durability of 3D-printed concrete formulations," says Masic.

Through the extended functional lifespan and the development of lighter-weight concrete forms, he hopes that these efforts could help reduce the environmental impact of cement production, which currently accounts for about 8 percent of global greenhouse gas emissions. Along with other new formulations, such as concrete that can actually absorb carbon dioxide from the air, another current research focus of the Masic lab, these improvements could help to reduce concrete's global climate impact.

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Newly discovered anatomy shields and monitors brain

From the complexity of neural networks to basic biological functions and structures, the human brain only reluctantly reveals its secrets. Advances in neuro-imaging and molecular biology have only recently enabled scientists to study the living brain at level of detail not previously achievable, unlocking many of its mysteries. The latest discovery, described today in the journal Science, is a previously unknown component of brain anatomy that acts as both a protective barrier and platform from which immune cells monitor the brain for infection and inflammation.

The new study comes from the labs of Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at University of Rochester and the University of Copenhagen and Kjeld Møllgård, M.D., a professor of neuroanatomy at the University of Copenhagen. Nedergaard and her colleagues have transformed our understanding of the fundamental mechanics of the human brain and made significant findings to the field of neuroscience, including detailing the many critical functions of previously overlooked cells in the brain called glia and the brain's unique process of waste removal, which the lab named the glymphatic system.

"The discovery of a new anatomic structure that segregates and helps control the flow of cerebrospinal fluid (CSF) in and around the brain now provides us much greater appreciation of the sophisticated role that CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defenses," said Nedergaard.

The study focuses on the membranes that encase the brain, which create a barrier from the rest of the body, and keep it bathed in CSF. The traditional understanding of what is collectively called the meningeal layer, a barrier comprised of individual layers known as the dura, arachnoid, and pia matter.

The new layer discovered by the U.S. and Denmark-based research team further divides the space below the arachnoid layer, the subarachnoid space, into two compartments, separated by the newly described layer, which the researchers name the SLYM, an abbreviation of Subarachnoidal LYmphatic-like Membrane. While much of the research in the paper describes the function of SLYM in mice, they also report its actual presence in the adult human brain as well.

The SLYM is a type of membrane called mesothelium, which is known to line other organs in the body, including the lungs and heart. Mesothelia typically surround and protect organs, and harbor immune cells. The idea that a similar membrane might exist in the central nervous system was a question first posed by Møllgård, the first author of the study. His research focuses on developmental neurobiology, and on the systems of barriers that protect the brain.

The new membrane is very thin and delicate, and consists of only one or a few cells in thickness. Yet the SLYM is a tight barrier, and allows only very small molecules to transit; it seems to separate "clean" and "dirty" CSF. This last observation hints at the likely role played by SLYM in the glymphatic system, which requires a controlled flow and exchange of CSF, allowing the influx of fresh CSF while flushing the toxic proteins associated with Alzheimer's and other neurological diseases from the central nervous system. This discovery will help researchers more precisely understand the mechanics of the glymphatic system, which was the subject of a recent $13 million grant from the National Institutes of Health's BRAIN Initiative to the Center for Translational Neuromedicine at the University of Rochester.

The SLYM also appears important to the brain's defenses. The central nervous system maintains its own native population of immune cells, and the membrane's integrity prevents outside immune cells from entering. In addition, the SLYM appears to host its own population of central nervous system immune cells that use the SLYM for surveillance at the surface of brain, allowing them to scan passing CSF for signs of infection.

Discovery of the SLYM opens the door for further study of its role in brain disease. For example, the researchers note that larger and more diverse concentrations of immune cells congregate on the membrane during inflammation and aging. When the membrane was ruptured during traumatic brain injury, the resulting disruption in the flow of CSF impaired the glymphatic system and allowed non-central nervous system immune cells to enter the brain.

These and similar observations suggest that diseases as diverse as multiple sclerosis, central nervous system infections, and Alzheimer's might be triggered or worsened by abnormalities in SLYM function. They also suggest that the delivery of drugs and gene therapeutics to the brain may be impacted by SLYM function, which will need to be considered as new generations of biologic therapies are being developed.

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Scientists find key reason why loss of smell occurs in long COVID-19

The reason some people fail to recover their sense of smell after COVID-19 is linked to an ongoing immune assault on olfactory nerve cells and an associated decline in the number of those cells, a team of scientists led by Duke Health report.

The finding, publishing online Dec. 21 in the journal Science Translational Medicine, provides an important insight into a vexing problem that has plagued millions who have not fully recovered their sense of smell after COVID-19.

While focusing on the loss smell, the finding also sheds light on the possible underlying causes of other long COVID-19 symptoms -- including generalized fatigue, shortness of breath, and brain fog -- that might be triggered by similar biological mechanisms.

"One of the first symptoms that has typically been associated with COVID-19 infection is loss of smell," said senior author Bradley Goldstein, M.D., Ph.D., associate professor in Duke's Department of Head and Neck Surgery and Communication Sciences and the Department of Neurobiology.

"Fortunately, many people who have an altered sense of smell during the acute phase of viral infection will recover smell within the next one to two weeks, but some do not," Goldstein said. "We need to better understand why this subset of people will go on to have persistent smell loss for months to years after being infected with SARS-CoV2."

In the study, Goldstein and colleagues at Duke, Harvard and the University of California-San Diego analyzed olfactory epithelial samples collected from 24 biopsies, including nine patients suffering from long-term smell loss following COVID-19.

This biopsy-based approach -- using sophisticated single-cell analyses in collaboration with Sandeep Datta, M.D., Ph.D., at Harvard University -- revealed widespread infiltration of T-cells engaged in an inflammatory response in the olfactory epithelium, the tissue in the nose where smell nerve cells are located. This unique inflammation process persisted despite the absence of detectable SARS-CoV-2 levels.

Additionally, the number of olfactory sensory neurons were diminished, possibly due to damage of the delicate tissue from the ongoing inflammation.

"The findings are striking," Goldstein said. "It's almost resembling a sort of autoimmune-like process in the nose."

Goldstein said learning what sites are damaged and what cell types are involved is a key step toward beginning to design treatments. He said the researchers were encouraged that neurons appeared to maintain some ability to repair even after the long-term immune onslaught.

"We are hopeful that modulating the abnormal immune response or repair processes within the nose of these patients could help to at least partially restore a sense of smell," Goldstein said, noting this work is currently underway in his lab.

He said the findings from this study could also inform additional research into other long-COVID-19 symptoms that might be undergoing similar inflammatory processes.

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Rwandan tree carbon stock mapped from above

As the first country, Rwanda can now present a national inventory based on a mapping of the carbon stock of each individual tree. Researchers at University of Copenhagen have developed a method to achieve this task in collaboration with Rwandan authorities and researchers.

"Large uncertainties exist for the current forest assessments internationally. By mapping the carbon stock of all individual trees, accuracy is greatly improved. Further, the way different countries make their inventories is not consistent due to different contexts, goals, and available datasets. We hope that this method will establish itself as a standard, thereby enabling better comparisons between countries," says PhD Researcher Maurice Mugabowindekwe, Department of Geosciences and Natural Resources Management (IGN), University of Copenhagen. He is first author on the scientific article presenting the new method. The article has been accepted for publication by Nature Climate Change, one of the most prominent journals for the field.

Maurice Mugabowindekwe being Rwandan himself is helpful during the work, but the choice of Rwanda for development of the method was scientifically based, he emphasizes:

"The country has a rich landscape variation including savannas, woodlands, sub-humid and humid forests, shrubland, agro-ecosystem mosaics, and urban tree ecosystems which are representative of most tropical countries. We wanted to prove the method for all these landscape types. Moreover, Rwanda is a signatory to several international agreements on forest preservation and climate change mitigation. For instance, Rwanda has pledged to restore about 80 % of its surface area by 2030 under the Bonn Challenge. So, it is highly relevant to have a reliable method for monitoring tree carbon."

First method for mapping individual trees

Preservation of natural forests and planting of new trees are recognized as vital routes to limiting climate change. However, large uncertainties regarding the carbon content of the trees have made it hard to assess the efficiency of concrete initiatives. The University of Copenhagen researchers have overcome this problem.

The new method benefits from databases which give the relationship between the extent of the crown and the total carbon content of an individual tree.

"Mapping individual trees and calculating their carbon stocks has traditionally been done in forestry, albeit at a much smaller scale. Basically, what we do equals scaling up these approaches from a very local to a national level," says Researcher Ankit Kariryaa, working 50:50 at IGN and at the Department of Computer Sciences (DIKU). Scientists from these two University of Copenhagen departments have developed the method with IGN as lead, in collaboration with other international scientists.

The new method will support Rwanda in verifying fulfilment of commitments under schemes such as the global forestry climate change mitigation scheme REDD+ or the African Forest Landscape Restoration Initiative, AFR 100.

Many trees are found outside forests

Manually mapping the trees of an entire country would be a huge endeavor and excessively costly. Thus, the new method constitutes a breakthrough since no other method would realistically be able to provide the same information at the level of individual trees.

"It is important to take a holistic approach and also include trees which are outside forests," says Ankit Kariryaa, noting that 72 % of the mapped trees were in farmlands and savannas, and 17 % in plantations.

At the same time, the relatively small proportion of trees which are found in natural forests -- 11 % of the total tree count -- comprise about 51 % of the national carbon stock of Rwanda. This is possible mainly because natural forests have a very high carbon content per tree volume, thanks to the very low human disturbance secured through national legislation.

"This suggests that conservation, regeneration, and sustainable management of natural forests is more effective at mitigating climate change than plantation," Maurice Mugabowindekwe comments.

Rainforest appears to be "a huge green blanket"

It is paramount that the computer can distinguish the individual trees. This is because the relationship between the extent of the crown and the total carbon content of a tree is very different depending on the size of a tree. One very large tree will have a much higher carbon content than a group of trees with the same joint crown extent. So, if the group was mistaken for one tree, the carbon content would be significantly overestimated. A deep neural network is used for detecting the individual trees.

"Especially for the rainforest, it is highly challenging to determine how many different trees are present in an image. At first glance, the forest just appears to be one huge green blanket. But by using methods from Machine Learning and Computer Vision, our system can also be applied to identify the individual trees in overstory of dense forests," explains Christian Igel, Professor of Machine Learning at DIKU.

Training the computer on verified samples is at the core of Machine Learning. In the Rwandan study, the computer was trained on a set of some 97,500 manually delineated tree crowns representing the full range of biogeographical conditions across the country.

The study used publicly available aerial and satellite images of Rwanda at 0.25 x 0.25 m resolution. These images were collected in June-August 2008 and 2009 and were provided by the Rwanda Land Management and Use Authority and the University of Rwanda. More than 350 million trees were mapped.

Applications beyond Rwanda

Nine researchers from University of Copenhagen visited Rwanda in July 2022 with a dual purpose of field work and presenting results from the first nation-wide mapping to the Rwandan authorities and other stakeholders in the country's forestry sector.

"The presentation was well received," reports Maurice Mugabowindekwe. He was immediately tasked by the Rwandan authorities with an updated mapping based on newer aerial images acquired in 2019. This work is now ongoing.

Further, the method has already been tested for a handful of countries besides Rwanda. These include Tanzania, Burundi, Uganda, and Kenya.

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Unveiling the mysteries of senescent cells and their effect on aging and human health

Multiple researchers at the Jackson Laboratory are taking part in an ambitious research program spanning several top research institutions to study senescent cells. Senescent cells stop dividing in response to stressors and seemingly have a role to play in human health and the aging process. Recent research with mice suggests that clearing senescent cells delays the onset of age-related dysfunction and disease as well as all-cause mortality.

Could therapies that remove senescent cells -- called senotherapeutics -- also improve the health of humans as we age? Answering this question and more has the potential to significantly advance human health, and the National Institutes of Health (NIH) has launched an extensive research initiative for this very purpose.

The SenNet Consortium, a collaboration of institutions from throughout the United States, was initially launched in 2021 with centers established to gather and analyze human data. The researchers will collect and analyze 18 tissues from healthy humans across lifespan to discern the full scope of senescent cells and how they may contribute to the aging process. The work of the SenNet Consortium was recently presented in a paper published in Nature Aging.

Along with colleagues from Mayo Clinic, University of Texas Health Science center at San Antonio, and UConn Health, JAX Professor Paul Robson, Ph.D. is taking part in the mapping of four human tissue types (kidney, adipose, pancreas, and placenta) within the KAPP-Sen Tissue Mapping Center. The Robson Lab also leads the Biological Analysis Core, and the Data Analysis Core of KAPP-Sen TMC is led by JAX Associate Professor Duygu Ucar, Ph.D., and JAX Professor Jeff Chuang, Ph.D.

SenNet has also grown over the past year to add mouse-focused investigators, and JAX was designated as a Tissue Mapping Center (TMC) for SenNet in August 2022, supported by a four-year, $10.7 million grant from the National Institute on Aging. JAX-Sen is led by Professor and Maxine Groffsky Endowed Chair Nadia Rosenthal, Ph.D., FMedSci with co-principal investigators Robson, JAX Associate Professor Ron Korstanje, Ph.D., and UConn Health's Ming Xu, Ph.D. Associate Professor Sheng Li and Principal Computational Scientist Matt Mahoney lead the Data Analysis Core of the JAX-Sen TMC.

JAX is poised to make substantial contributions to SenNet by profiling senescent cells in kidney, placenta, pancreas, and heart, all tissues that are relevant to chronic diseases of aging. The team will draw upon its genetically diverse mouse resources, including Diversity Outbred mouse populations, to model a range of molecular senescence traits, as well as inbred mice specifically engineered to help visualize senescent cell subsets.

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Human brain organoids implanted into mouse cortex respond to visual stimuli for first time

A team of engineers and neuroscientists has demonstrated for the first time that human brain organoids implanted in mice have established functional connectivity to the animals' cortex and responded to external sensory stimuli. The implanted organoids reacted to visual stimuli in the same way as surrounding tissues, an observation that researchers were able to make in real time over several months thanks to an innovative experimental setup that combines transparent graphene microelectrode arrays and two-photon imaging.

The team, led by Duygu Kuzum, a faculty member in the University of California San Diego Department of Electrical and Computer Engineering, details their findings in the Dec. 26 issue of the journal Nature Communications. Kuzum's team collaborated with researchers from Anna Devor's lab at Boston University; Alysson R. Muotri's lab at UC San Diego; and Fred H. Gage's lab at the Salk Institute.

Human cortical organoids are derived from human induced pluripotent stem cells, which are usually derived themselves from skin cells. These brain organoids have recently emerged as promising models to study the development of the human brain, as well as a range of neurological conditions.

But until now, no research team had been able to demonstrate that human brain organoids implanted in the mouse cortex were able to share the same functional properties and react to stimuli in the same way. This is because the technologies used to record brain function are limited, and are generally unable to record activity that lasts just a few milliseconds.

The UC San Diego-led team was able to solve this problem by developing experiments that combine microelectrode arrays made from transparent graphene, and two-photon imaging, a microscopy technique that can image living tissue up to one millimeter in thickness.

"No other study has been able to record optically and electrically at the same time," said Madison Wilson, the paper's first author and a Ph.D. student in Kuzum's research group at UC San Diego. "Our experiments reveal that visual stimuli evoke electrophysiological responses in the organoids, matching the responses from the surrounding cortex."

The researchers hope that this combination of innovative neural recording technologies to study organoids will serve as a unique platform to comprehensively evaluate organoids as models for brain development and disease, and investigate their use as neural prosthetics to restore function to lost, degenerated or damaged brain regions.

"This experimental setup opens up unprecedented opportunities for investigations of human neural network-level dysfunctions underlying developmental brain diseases," said Kuzum.

Kuzum's lab first developed the transparent graphene electrodes in 2014 and has been advancing the technology since then. The researchers used platinum nanoparticles to lower the impedance of graphene electrodes by 100 times while keeping them transparent. The low-impedance graphene electrodes are able to record and image neuronal activity at both the macroscale and single cell levels.

By placing an array of these electrodes on top of the transplanted organoids, researchers were able to record neural activity electrically from both the implanted organoid and the surrounding host cortex in real time. Using two-photon imaging, they also observed that mouse blood vessels grew into the organoid providing necessary nutrients and oxygen to the implant.

Researchers applied a visual stimulus-an optical white light LED-to the mice with implanted organoids, while the mice were under two-photon microscopy. They observed electrical activity in the electrode channels above the organoids showing that the organoids were reacting to the stimulus in the same way as surrounding tissue. The electrical activity propagated from the area closest to the visual cortex in the implanted organoids area through functional connections. In addition, their low noise transparent graphene electrode technology enabled electrical recording of spiking activity from the organoid and the surrounding mouse cortex. Graphene recordings showed increases in the power of gamma oscillations and phase locking of spikes from organoids to slow oscillations from mouse visual cortex. These findings suggest that the organoids had established synaptic connections with surrounding cortex tissue three weeks after implantation, and received functional input from the mouse brain. Researchers continued these chronic multimodal experiments for eleven weeks and showed functional and morphological integration of implanted human brain organoids with the host mice cortex.

Next steps include longer experiments involving neurological disease models, as well as incorporating calcium imaging in the experimental set up to visualize spiking activity in organoid neurons. Other methods could also be used to trace axonal projections between organoid and mouse cortex.

"We envision that, further along the road, this combination of stem cells and neurorecording technologies will be used for modeling disease under physiological conditions; examining candidate treatments on patient-specific organoids; and evaluating organoids' potential to restore specific lost, degenerated or damaged brain regions," Kuzum said.

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Precise solar observations fed millions in ancient Mexico

Without clocks or modern tools, ancient Mexicans watched the sun to maintain a farming calendar that precisely tracked seasons and even adjusted for leap years.

Before the Spanish arrival in 1519, the Basin of Mexico's agricultural system fed a population that was extraordinarily large for the time. Whereas Seville, the largest urban center in Spain, had a population of fewer than 50,000, the Basin, now known as Mexico City, was home to as many as 3 million people.

To feed so many people in a region with a dry spring and summer monsoons required advanced understanding of when seasonal variations in weather would arrive. Planting too early, or too late, could have proved disastrous. The failure of any calendar to adjust for leap-year fluctuations could also have led to crop failure.

Though colonial chroniclers documented the use of a calendar, it was not previously understood how the Mexica, or Aztecs, were able to achieve such accuracy. New UC Riverside research demonstrates how they did it. They used the mountains of the Basin as a solar observatory, keeping track of the sunrise against the peaks of the Sierra Nevada mountains.

"We concluded they must have stood at a single spot, looking eastwards from one day to another, to tell the time of year by watching the rising sun," said Exequiel Ezcurra, distinguished UCR professor of ecology who led the research.

To find that spot, the researchers studied Mexica manuscripts. These ancient texts referred to Mount Tlaloc, which lies east of the Basin. The research team explored the high mountains around the Basin and a temple at the mountain's summit. Using astronomical computer models, they confirmed that a long causeway structure at the temple aligns with the rising sun on Feb. 24, the first day of the Aztec new year.

"Our hypothesis is that they used the whole Valley of Mexico. Their working instrument was the Basin itself. When the sun rose at a landmark point behind the Sierras, they knew it was time to start planting," Ezcurra said.

The sun, as viewed from a fixed point on Earth, does not follow the same trajectory every day. In winter, it runs south of the celestial equator and rises toward the southeast. As summer approaches, because of the Earth's tilt, sunrise moves northeast, a phenomenon called solar declination.

This study may be the first to demonstrate how the Mexica were able to keep time using this principle, the sun, and the mountains as guiding landmarks. Though some may be familiar with the "Aztec calendar," that is an incorrect name given to the Sun Stone, arguably the most famous work of Aztec sculpture used solely for ritual and ceremonial purposes.

"It did not have any practical use as a celestial observatory. Think of it as a monument, like Nelson's Column in Trafalgar Square or Lincoln's Memorial in Washington, D.C.," Ezcurra said.

Learning about Aztec tools that did have practical use offers a lesson about the importance of using a variety of methods to solve questions about the natural world.

"The same goals can be achieved in different ways. It can be difficult to see that sometimes. We don't always need to rely solely on modern technology," Ezcurra said. "The Aztecs were just as good or better as the Europeans at keeping time, using their own methods."

The Aztec observatory could also have a more modern function, according to Ezcurra. Comparing old images of the Basin of Mexico to current ones shows how the forest is slowly climbing up Mount Tlaloc, likely as a result of an increase in average temperatures at lower elevation.

Read more at Science Daily

Designing with DNA

Marvel at the tiny nanoscale structures emerging from research labs at Duke University and Arizona State University, and it's easy to imagine you're browsing a catalog of the world's smallest pottery.

A new paper reveals some of the teams' creations: itty-bitty vases, bowls, and hollow spheres, one hidden inside the other, like housewares for a Russian nesting doll.

But instead of making them from wood or clay, the researchers designed these objects out of threadlike molecules of DNA, bent and folded into complex three-dimensional objects with nanometer precision.

These creations demonstrate the possibilities of a new open-source software program developed by Duke Ph.D. student Dan Fu with his adviser John Reif. Described December 23 in the journal Science Advances, the software lets users take drawings or digital models of rounded shapes and turn them into 3D structures made of DNA.

The DNA nanostructures were assembled and imaged by co-authors Raghu Pradeep Narayanan and Abhay Prasad in professor Hao Yan's lab at Arizona State. Each tiny hollow object is no more than two millionths of an inch across. More than 50,000 of them could fit on the head of a pin.

But the researchers say these are more than mere nano-sculptures. The software could allow researchers to create tiny containers to deliver drugs, or molds for casting metal nanoparticles with specific shapes for solar cells, medical imaging and other applications.

To most people, DNA is the blueprint of life; the genetic instructions for all living things, from penguins to poplar trees. But to teams like Reif's and Yan's, DNA is more than a carrier of genetic information -- it's source code and construction material.

There are four "letters," or bases, in the genetic code of DNA, which pair up in a predictable way in our cells to form the rungs of the DNA ladder. It's these strict base-pairing properties of DNA -- A with T, and C with G -- that the researchers have co-opted. By designing DNA strands with specific sequences, they can "program" the strands to piece themselves together into different shapes.

The method involves folding one or a few long pieces of single-stranded DNA, thousands of bases long, with help from a few hundred short DNA strands that bind to complementary sequences on the long strands and "staple" them in place.

Researchers have been experimenting with DNA as a construction material since the 1980s. The first 3D shapes were simple cubes, pyramids, soccer balls -- geometric shapes with coarse and blocky surfaces. But designing structures with curved surfaces more akin to those found in nature has been tricky. The team's aim is to expand the range of shapes that are possible with this method.

To do that, Fu developed software called DNAxiS. The software relies on a way to build with DNA described in 2011 by Yan, who was a postdoc with Reif at Duke 20 years ago before joining the faculty at Arizona State. It works by coiling a long DNA double helix into concentric rings that stack on each other to form the contours of the object, like using coils of clay to make a pot. To make the structures stronger, the team also made it possible to reinforce them with additional layers for increased stability.

Fu shows off the variety of forms they can make: cones, gourds, clover leaf shapes. DNAxiS is the first software tool that lets users design such shapes automatically, using algorithms to determine where to place the short DNA "staples" to join the longer DNA rings together and hold the shape in place.

"If there are too few, or if they're in the wrong position, the structure won't form correctly," Fu said. "Before our software, the curvature of the shapes made this an especially difficult problem."

Given a model of a mushroom shape, for example, the computer spits out a list of DNA strands that would self-assemble into the right configuration. Once the strands are synthesized and mixed in a test tube, the rest takes care of itself: by heating and cooling the DNA mixture, within as little as 12 hours "it sort of magically folds up into the DNA nanostructure," Reif said.

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