As common as roe deer may seem in Swiss forests, one of their characteristics is unique among deer species. After mating and fertilisation of the egg in midsummer, the pinhead-sized embryo does not implant in the uterus, but enters into a period of dormancy, called embryonic diapause. This period lasts for over four months until December. Only then does the embryo continue its development at normal pace and implants in the uterus. In May, after four and a half months of “real” gestation, the doe gives birth to one to three fawns.

Although the phenomenon has been known for more than 150 years, it still puzzles. Various forms of embryonic diapause are known to occur in over 130 mammalian species. However, they rarely last as long as observed in the roe deer. And, most importantly, almost no other species shows such a pronounced, continuous deceleration instead of a complete halt. In mice, scientists can artificially induce diapause. However, in roe deer it is still unclear which factors control diapause while keeping the embryo alive.

The research group led by Susanne Ulbrich, Professor of Animal Physiology at ETH Zurich, has been investigating the mystery of roe deer diapause for some time. In a new study, the researchers show which molecular processes take place in the embryo while it is dormant: embryonic cells continue to divide during diapause, albeit very slowly. The number of cells, including embryonic stem cells, doubles only every two to three weeks. The study, which has just been published in the journal PNAS, involved not only the ETH group, but also researchers from the Universities of Zurich and Bern, as well as German and French research institutions.

Gene transcripts and signalling molecules studied

To answer the question of what prevents the embryonic cells from dividing at a normal pace, the researchers first examined the molecular composition of the uterine fluid. Next, they took a closer look at the transcriptome, i.e., the sum of all messenger RNA molecules, of the embryos and the uterine epithelial cells.

In the uterine fluid, the researchers found signalling substances that could regulate the cell division rate. The amino acid serine was particularly conspicuous. The ETH researchers showed that towards the end of diapause, the concentration of certain amino acids in the uterine fluid changes. The cell proliferation rate then concomitantly returns to a normal rate.

This process involves the molecular complex mammalian target of rapamycin (mTOR). mTOR reacts to amino acids and plays a crucial role in many metabolic signalling pathways in mammalian cells, including those associated with cancer. mTORC1, for example, regulates protein synthesis and thus cell growth and division.

According to the new findings, the activity of only mTORC1, but not mTORC2, is suppressed in roe deer embryos throughout diapause. This is in contrast to diapausing mice, where cell division is completely halted upon inhibition of both mTORC1 and mTORC2.

Towards the end of diapause, the significant increase in the amino acid level in the uterine fluid activates mTORC1. This, in turn, increases the expression of metabolic and cell cycle genes, driving embryo development forwards. Meanwhile, since mTORC2 is not inhibited during diapause in roe deer embryos, the researchers hypothesise that this could explain why cell division slowly continues.

In this study, the researchers did not investigate whether other signalling molecules are involved alongside the various amino acids. It also remains unclear whether the amino acids are actually responsible for the resumption of embryonic development or whether the embryo itself also secretes molecules that act on maternal cells and signalling pathways. The embryo may indicate its presence to its mother through specific signalling molecules. Ulbrich would like to close this knowledge gap in future studies.

New light on reproductive biology

These new findings shed light on reproductive and developmental biology in general. One fundamental question is how pregnancy is established in mammals. For example, in women and in domestic cattle, embryos often fail to implant in the uterus and die. “This has to do with complex interactions between the embryo and the mother,” Ulbrich says.

She adds that a successful pregnancy calls for precise timing. The embryo must make itself known at the right time through appropriate (molecular) signals and interrupt the mother’s cycle. “We want to better understand this interaction between embryo and mother,” Ulbrich explains. For this, she says, the roe deer is an ideal model. Embryonic development in roe deer is very similar to that of cattle but takes place in slow motion. “This allows us to better temporally resolve the sequence of events and find causal relationships.”

The findings could also help improve in vitro fertilisation in humans so that embryos may no longer need to be frozen. Moreover, natural factors could be used to control the rate at which cells, including embryonic stem cells, divide.

However, important seabed habitats and species recover more quickly following extreme storms than in the wake of such fishing activity.

That is one of the key findings of a first-of-its-kind study which examined the impact of the 2013/14 winter storms on the Lyme Bay Marine Protected Area (MPA), off the coast of southern England.

Academics from the University of Plymouth have been monitoring the area using underwater cameras and other techniques since 2008, when a ban on bottom towed fishing was introduced as part of a range of conservation measures.

They have previously demonstrated that several species have returned to the area since the MPA was introduced, resulting in the significant recovery of seabed life and fish and shellfish stocks.

However, there have been no previous studies looking at how extreme storms impact seabed habitats or the potential for MPAs to increase ecosystem resilience from storms.

To address that, researchers analysed the impacts of the 2013/14 series of storms, which separate studies by the University found to be the most energetic to hit western Europe since 1948.

Through annual surveys of seabed life in the MPA, they were able to see the immediate impact of the storms but also how the seabed was able to recover in subsequent years.

Writing in Frontiers in Marine Science, the researchers say that with extreme events likely to become more frequent and severe as a result of climate change, up to 29% of coastal reef MPAs around the UK may be similarly impacted by extreme storms.

Dr Emma Sheehan, Associate Professor of Marine Ecology at the University of Plymouth, is the study’s lead author. She said: “In our assessments in 2014, it appeared the previous winter’s storms had devastated the MPA. Loose sediments and other debris were prolific where life and biogenic reef habitat had been observed the year before. However, by 2016, large numbers of adult pink sea fans and other species were being observed once again with more juvenile pink sea fans than ever before. It showed the MPA’s recovery had begun almost immediately whereas, by contrast, it took more than three years for such patterns to be seen following its initial designation.”

The University’s work in Lyme Bay has been carried out in conjunction with local fishers and other community groups along the Dorset and Devon coastline.

In addition to assessing the effects of a ban on bottom-towed fishing, it has shown that limits on crab and lobster pot fishing could offer long-term benefits to fishermen and the environment.

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A research team from Tohoku University has unveiled more about the evolutionary process of the Marinoan-Ediacaran transition. Using biomarker evidence, they revealed possible photosynthetic activity during the Marinoan glaciation. This was followed by photosynthetic organisms and bacteria entering a period of low productivity. However, as eukaryotes expanded during the early Ediacaran period, they blossomed.

Dr. Kunio Kaiho, who co-authored a paper with Atena Shizuya, said, “Our findings help clarify the evolution of primitive to complex animals in the aftermath of the Snowball Earth.” Their paper online was published in the journal Global and Planetary Change on August 8, 2021.

The late Neoproterozoic era (650-530 million years ago) witnessed one of the most severe ice ages in the Earth’s 4.6-billion-year history. Researchers believe that ice sheets covered the entire earth since glaciogenic units, such as ice-rafted debris, are distributed globally. Overlaying these glaciogenic formations are cap carbonates. These precipitate under warm conditions and therefore suggest that the glacial environment changed rapidly into a greenhouse environment.

The Snowball Earth hypothesis purports the atmospheric carbon dioxide concentration controlled the change from a frozen state to an ice-free state. Ice sheet-covered oceans prevented the dissolution of carbon dioxide into seawater during the Marinoan ice age, meaning greenhouse gas concentration, emitted by volcanic activity, increased gradually. Once the extreme greenhouse effect kicked in, glaciers melted and excess carbon dioxide precipitated on glaciogenic sediments as cap carbonates.

Whilst the Snowball Earth theory explains the wide distributions of glacial formations, it fails to shed light on the survival of living organisms. To counteract this, some researchers argue that sedimentary organic molecules, a molecular clock, and fossils from the late Neoproterozoic era are evidence that primitive eukaryotes such as sponges survived this severe ice age. Alternative models also propose that an ice-free open sea existed during the glaciation and acted as an oasis for marine life.

But what is understood is that the Marinoan glaciation and the succeeding extreme climatic transition likely had a marked impact on the biosphere. Shortly after the ice age, the Lantian biota, the earliest-known complex macroscopic multicellular eukaryotes, emerged. The Lantian biota includes macrofossils that are phylogenetically uncertain but morphologically and taxonomically diverse. Meanwhile, pre-Marinoan species have simple body plans with limited taxonomic variety.

Bacteria and eukaryote biomarkers demonstrate that bacteria dominated before the glaciation, whereas steranes/hopanes ratios illustrate that eukaryotes dominated just before it. However, the relationship between the biosphere changes and the Marinoan glaciation is unclear.

In 2011, Kaiho and his team traveled to Three Gorges, China under the guidance of China University of Science’s Dr. Jinnan Tong to take sedimentary rock samples from the deeper outcrops of marine sedimentary rocks. From 2015 onwards, Shizuya and Kaiho analyzed the biomarkers of algae, photosynthetic activity, bacteria, and eukaryotes from the rock samples.

They found photosynthetic activity based on n-C₁₇ + n-C₁₉ alkanes for algae and pristane + phytane during the Marinoan glaciation. Hopanes within the early and late carbonate deposition showed photosynthetic organisms and other bacteria entering a state of low productivity before recovering. And steranes from carbonates and mudstones after the cap carbonate deposition from the early Ediacaran period indicated the expansion of eukaryotes. The expansion of eukaryotes corresponded to the Lantian biota being morphologically diverse when compared to pre-Marinoan species.

Kaiho believes we are one step closer to understanding the evolutionary process that occurred before and after Snowball Earth. “The environmental stress of closed ocean environments for the atmosphere followed by high temperatures around 60°C may have produced more complex animals in the aftermath.” Their findings show that bacterial recovery preceded eukaryotes’ domination.

Kaiho’s team is doing further studies to clarify the relationship between climate change and the biosphere in other locations. They are also studying the relationship between atmospheric oxygen increases and animal evolution from the late Cryogenian to early Cambrian (650 to 500 million years ago).

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Soon after the Big Bang 13.8 billion years ago, the Universe was an unruly place. Galaxies constantly collided. Stars formed at an enormous rate inside gigantic gas clouds. However, after a few billion years of intergalactic chaos, the unruly, embryonic galaxies became more stable and over time matured into well-ordered spiral galaxies. The exact course of these developments has long been a mystery to the world’s astronomers. However, in a new study published in Monthly Notices of the Royal Astronomical Society, researchers have been able to provide some clarity on the matter.

“Using a supercomputer, we have created a high-resolution simulation that provides a detailed picture of a galaxy’s development since the Big Bang, and how young chaotic galaxies transition into well-ordered spirals” says Oscar Agertz, astronomy researcher at Lund University.

In the study, the astronomers, led by Oscar Agertz and Florent Renaud, use the Milky Way’s stars as a starting point. The stars act as time capsules that divulge secrets about distant epochs and the environment in which they were formed. Their positions, speeds and amounts of various chemical elements can therefore, with the assistance of computer simulations, help us understand how our own galaxy was formed.

“We have discovered that when two large galaxies collide, a new disc can be created around the old one due to the enormous inflows of star-forming gas. Our simulation shows that the old and new discs slowly merged over a period of several billion years. This is something that not only resulted in a stable spiral galaxy, but also in populations of stars that are similar to those in the Milky Way,” says Florent Renaud, astronomy researcher at Lund University.

The new findings will help astronomers to interpret current and future mappings of the Milky Way. The study points to a new direction for research in which the main focus will be on the interaction between large galaxy collisions and how spiral galaxies’ discs are formed. The research team in Lund has already started new super computer simulations in cooperation with the research infrastructure PRACE (Partnership for Advanced Computing in Europe).

“With the current study and our new computer simulations we will generate a lot of information which means we can better understand the Milky Way’s fascinating life since the beginning of the Universe,” concludes Oscar Agertz.

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Now, halfway through 2021, the first official research results are in — and it’s good news: The show can go on.

Published today in the journal ACS Environmental Au, University of Colorado Boulder and University of Maryland researchers have found that while playing musical instruments can emit the same levels of potentially COVID-laden airborne particles as singing, simple safety measures, such as masking instruments, social distancing and implementing time limits, significantly reduce this risk.

“COVID has shown people that aerosol transmission of respiratory diseases is something that happens. But just because it goes into the air doesn’t mean that everyone is going to contract this disease. We found that there are ways to mitigate these aerosols in a space and ways to reduce your risk,” said Tehya Stockman, lead author of the paper and graduate student in mechanical engineering.

This research began in earnest in 2020 at CU Boulder and the University of Maryland to find out if playing musical instruments carried the same risks of COVID-19 transmission as singing is shown to have. While there have been no reported outbreaks from instrumental ensembles, these published findings echo the researchers’ initial hypotheses and recommendations that were eagerly accepted early on in the pandemic by musicians and performing groups worldwide.

“I want to acknowledge the courage of the music directors and the teachers to go ahead and follow our suggestions in the face of all of this adversity, fear and worry,” said Shelly Miller, co-author of the study and professor of mechanical and environmental engineering. “That really meant a lot to us because they trusted our very good research methods, our researchers and the evolution of science as it moves from: we don’t know, to, let’s find out, to OK — now we know this.”

These findings not only apply to the specific musical applications in which they have been tested, they also further validate that masking works as an effective mitigation technique, and ventilation and social distancing are important to reduce transmission, said Miller. Miller said she hopes these findings will further inspire a paradigm shift focused on mitigation measures and ventilation in order to reduce airborne transmission of infectious diseases.

Mitigation matters

The researchers tested three mitigation strategies on a variety of woodwind, reed and brass instruments, as well as with two singers and an actor. They evaluated these strategies, different lengths of performance time and the differences between indoor and outdoor locations by measuring aerosols, carbon dioxide levels and visualizing the flow of the air using various modeling techniques.

First, they found that masks work — even on instruments — and the quality of the filtering material and their fit are important. Masks worn securely over a singer’s mouth and nose, as well as bell covers (made of MERV13 filter material) placed over the ends of instruments significantly decreased the speed and amount of particles produced from both sources.

For woodwind and reed instruments, they found that the amount of air that escapes from the keyholes does not significantly contribute to any increased risk. This means that clarinetists and flautists do not have to place a bag around their entire instrument to play safely.

Second, time together matters. To keep risk low (at 10% chance of transmission), instrumentalists should spend less than 30 minutes indoors and less than 60 minutes outdoors playing together at a time. No matter the amount of social distancing, “infection risk continuously increases with the duration regardless of the distance to the singer or the player,” the researchers found.

They also found that spacing out does pay off: Leaving several feet of distance between players and singers reduces aerosol concentrations, which are highest closest to each person producing them. And while playing outdoors is best, a layered approach with all the other mitigation measures makes it much safer to play indoors.

Finally, no Plexiglass or face shields are needed. The airborne particles that transmit COVID-19 can easily flow around these barriers and mix with the air in a room.

Quantifying carbon dioxide

So how then, can a musician or audience member now know it’s safe to attend a concert?

Carbon dioxide has been shown to be great indicator of how well ventilated — or not — an indoor space is, and therefore its level of risk for catching COVID-19.

But in this study, the researchers showed that when somebody wears a mask, carbon dioxide passes through the mask with the air that a person is exhaling, but the particles which can carry the virus get stuck. This means that when someone puts on a mask or a bell cover, the carbon dioxide emissions continue, but the particle emissions (which could carry the virus) are reduced.

“Carbon dioxide concentration is a measure of the ventilation in the room. But if everybody’s wearing a mask, the carbon dioxide in that room is still going to be high, but the respiratory droplets that may contain the virus are going to be much lower,” Marina Vance, co-author on the study and assistant professor in the Paul M. Rady Department of Mechanical Engineering and the Environmental Engineering Program. “So in that case, it’s not a direct representation of your risk.”

So, if a concert hall requires all audience members to wear masks and that all performers place a bell cover on their instrument, the risk of COVID transmission in that room would be reduced — even if the measured carbon dioxide levels are high. But carbon dioxide is still a great proxy for risk indoors in restaurants, where most people are not masked and are often speaking loudly.

Such direct application of this research to real-life scenarios has been an extremely rewarding experience for Vance and the other researchers.

“The best part of the study was that all of this technical knowledge and all of this scientific understanding was getting translated almost in real-time and getting into the hands of the people that needed it the most. I’ve never been a part of anything like that,” said Vance. “It was nerve-wracking, exciting and important all at once.”

The safe return of music

When lead author Stockman first learned to play clarinet years ago, she didn’t do so with the intent to advance scientific research. But her personal musical experience allowed the work to advance quickly, as she performed calibration tests by herself in the lab during the pandemic.

She understands the frustrations of musicians who may need to follow these protocols. She also knows how important it is to keep people safe.

“What we’ve shown is that there’s easy measures to take that make life still be relatively normal — and you don’t have to fear the air,” said Stockman.

This sentiment is echoed by co-authors Mark Spede, national president of the College Band Directors National Association and director of bands at Clemson University, and James Weaver, director of Performing Arts and Sports for the National Federation of State High School Associations, who point out that the mitigation strategies tested in this study can be implemented not only during the lingering COVID-19 pandemic, but in the face of any future pathogen that may come along.

“Although we may not know how the end of the pandemic will play out, this important study has allowed performing arts educators to advocate for the safe return of live music to the classroom,” said Spede.

This research was conducted in partnership and collaboration with the National Federation of State High School Associations and College Band Directors National Association.

Additional authors on this publication include: Abhishek Kuma, Lingzhe Wang, Sameer Patel, Darin Toohey and Jean Hertzberg of CU Boulder; and Shengwei Zhu, Don Milton and Jelena Srebric of the University of Maryland.

Results from the registry indicated that in addition to more severe or critical infections, pediatric cancer patients were more likely to be hospitalized and die than were other children. The pandemic also disrupted cancer treatment. These effects were observed more significantly in low- and middle-income countries, where the odds of severe or critical disease from COVID-19 were nearly 6 times higher than in high-income countries.

“The results clearly and definitively show that children with cancer fare worse with COVID-19 than children without cancer,” said corresponding author Sheena Mukkada, M.D., St. Jude Departments of Global Pediatric Medicine and Infectious Diseases. “This global collaboration helps clinicians make evidence-based decisions about prevention and treatment, which, unfortunately, remain relevant as the pandemic continues.”

A greater burden for childhood cancer patients

This is the first multinational study to describe the outcomes of a large cohort of children and adolescents with cancer or hematopoietic stem cell transplantation and laboratory diagnosis of COVID-19. The registry remains open and is enrolling children younger than 19 years old.

The analysis looked at 1,500 children from 131 hospitals in 45 countries from April 15, 2020, to February 1, 2021. This is prior to vaccinations becoming available to older children in some areas of the globe, as well as prior to the emergence of certain disease variants, including delta, which are responsible for the new surge and have become a major global concern.

The study found that 65% of patients were hospitalized and 17% required admission or transfer to a higher level of care. It also showed that 4% of patients died due to COVID-19 infections, compared to 0.01-0.7% mortality reported among general pediatric patients. Cancer care was also affected. Cancer therapy was modified in 56% of patients and 45% had chemotherapy withheld while their infections were treated.

“By working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer,” said the paper’s co-author, Professor Kathy Pritchard-Jones, SIOP president. “The results are reassuring that many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”

A global pandemic and a global response

The registry suggests biologic factors that likely influence how children with cancer respond to COVID-19. Those include immune system function and the underlying disease. Analysis also showed that outcomes vary around the world, although the registry does not pinpoint causes. This variation may be due to a multitude of factors, including disruptions from the pandemic, access to care and resources, or delays in infection diagnosis.

Results from the registry are a call to action to address inequities in access to protective and effective treatment measures against the COVID-19 pandemic worldwide.

“Understanding a global crisis like COVID-19 requires our entire childhood cancer community around the world to come together to respond,” said senior author Carlos Rodriguez-Galindo, M.D., St. Jude Global director. “The impact of this disease has been felt in every corner of the world, but particularly in low- and middle-income countries compared to high-income countries. There are critical differences based on where a child lives. This registry is a tool that is helping us understand what that means for children with cancer everywhere.”

The registry (http://covid19childhoodcancer.org/) is still enrolling patients and continues to add new countries. It includes freely available data-visualization tools so that anyone, anywhere, can access the information.

Learn more about COVID-19 and vaccination

Vaccinations against COVID-19 have been demonstrated to be safe and effective in preventing severe forms of the disease, helping patients avoid hospitalizations and the need for mechanical ventilation. In the United States, vaccines are available and encouraged for children 12 years of age and older. Vaccination is one way to protect not only yourself but your community, including those who are at high risk of severe disease such as children with cancer.

Learn more about how Vaccines Bring Us Closer (https://www.stjude.org/media-resources/special-announcements/get-vaccinated.html) and check out COVID-19 resources from St. Jude (https://www.stjude.org/treatment/patient-resources/covid-19-resources-from-st-jude.html).

Authors and Funding

The study’s other authors are Guillermo Chantada, Hospital San Joan de Deu Barcelona, Spain; Rashmi Dalvi, Bombay Hospital Institute of Medical Sciences Mumbai, India; Laila Hessissen, Mohammed V University Rabat, Morocco; Michael Sullivan, University of Melbourne, Australia; Eric Bouffet, Hospital for Sick Children Toronto, Canada; Nickhill Bhakta, Yichen Chen, Yuvanesh Vedaraju, Lane Faughnan, Maysam Homsi, Hilmarie Muniz-Talavera, Radhikesh Ranadive, Monika Metzger, Paola Friedrich, Asya Agulnik, Sima Jeha, Catherina Lam, Daniel Moreira, Victor Santana, Miguela Caniza and Meenakshi Devidas of St. Jude; and more than 150 members of the Global Registry of COVID-19 in Childhood Cancer.

The study was funded by the National Institutes of Health (Cancer Center Support grant CA21765), and ALSAC, the fundraising and awareness organization of St. Jude.

Although COVID-19 is primarily considered a respiratory disease, experts recognize it also affects the nervous system, sometimes causing severe neurological symptoms. Some COVID-19 survivors also experience long-term mental health problems, including anxiety, depression and post-traumatic stress disorder.

Few studies have examined functional abnormalities in the brain, which might reveal the physiological processes that underlie prolonged mental health symptoms in COVID-19 survivors.

In this paper, published in Neurobiology of Stress, the researchers set out to determine whether survivors experience functional disruption of large-scale brain networks, collections of discrete and widespread regions of the brain that work together to perform complex cognitive tasks. They collected functional MRI (fMRI) data and self-reported post-traumatic stress symptoms from 50 COVID-19 survivors, along with matched control subjects. The COVID-19 survivors were discharged between February and March 2020 from hospitals in Wuhan, China, and were tested about six months after their discharge.

The findings showed COVID-19 survivors self-reported significantly more symptoms of post-traumatic stress than the controls. The study also revealed COVID-19 survivors exhibited abnormal patterns of brain connectivity over time, which were significantly associated with greater post-traumatic stress symptoms.

“Until recently,” said Calhoun, a Georgia Research Alliance Eminent Scholar, “analysis approaches used for fMRI data assumed that the brain’s functional connectivity was static. But we now have approaches that can capture dynamic functional brain connectivity, showing the way brain patterns change over time in fundamental and reoccurring ways.”

The researchers identified three distinct, reoccurring states of functional connectivity in the subjects’ brains. The COVID-19 survivors showed an increased occurrence of a particular state marked by patterns of connections between brain networks involving sensorimotor functions and visual networks.

“When we looked within the COVID-19 survivor group, we also found a significant relationship between the severity of their post-traumatic stress symptoms and how often their brain patterns are in that state,” said Calhoun. “If they spend more time in that state, they tend to have higher values on those symptom scales.”

“Our findings provide evidence that COVID might affect transient brain dynamics rather than its ongoing activity,” said Zening Fu, the study’s first author and a research scientist at TReNDS.

The results highlight the importance of evaluating transient, time-varying functional network changes among COVID-19 survivors, although Calhoun notes there are still many unanswered questions, including why this one brain state is linked to post-traumatic stress. The research team is also interested in replicating the study using other data and looking at changes within subjects before and after contracting COVID-19.

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