Earth

Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells. Their findings are published in the Biophysical Journal.

A cell's identity is driven by which DNA is "read" or "not read" at any point in time. Signalling in the cell to start or stop reading DNA happens through proteins called transcription factors. Identity changes happen naturally during development as cells transition from an undesignated cell to a specific cell type. As it turns out, these transitions can also be reversed. In 2012, Japanese researchers were awarded the Nobel prize for being the first to push a regular skin cell backwards to a stem cell.

A fuller understanding of molecular processes towards stem cell therapies

Until now, it is unknown how the conversion of a skin cell into a stem cell happens exactly, on a molecular scale. "Fully understanding the processes with atomic details is essential if we want to produce such cells for individual patients in the future in a reliable and efficient manner", says research leader Vlad Cojocaru of the Hubrecht Institute. "It is believed that such engineered cell types may in the future be part of the solution to diseases like Alzheimer's and Parkinson's, but the production process would have to become more efficient and predictable."

Pioneer transcription factor

One of the main proteins involved in the stem cell generation is a transcription factor called Oct4. It induces gene expression, or activity, of the proteins that 'reset' the adult cell into a stem cell. Those genes induced are inactive in the adult cells and reside in tightly packed, closed states of chromatin, the structure that stores the DNA in the cell nucleus. Oct4 contributes to the opening of chromatin to allow for the expression of the genes. For this, Oct4 is known as a pioneer transcription factor.

The data from Cojocaru and his PhD candidate - and first author of the publication - Jan Huertas show how Oct4 binds to DNA on the so-called nucleosomes, the repetitive nuclear structures in chromatin. Cojocaru: "We modelled Oct4 in different configurations. The molecule consists of two domains, only one of which is able to bind to a specific DNA sequence on the nucleosome in this phase of the process. With our simulations, we discovered which of those configurations are stable and how the dynamics of nucleosomes influence Oct4 binding. The models were validated by experiments performed by our colleagues Caitlin MacCarthy and Hans Schöler in Münster."

One step closer to engineered factors

This is the first time computer simulations show how a pioneer transcription factor binds to nucleosomes to open chromatin and regulate gene expression. "Our computational approach for obtaining the Oct4 models can also be used to screen other transcription factors and to find out how they bind to nucleosomes", Cojocaru says.

Moreover, Cojocaru wants to refine the current Oct4 models to propose a final structure for the Oct4-nucleosome complex. "For already almost 15 years now, we know that Oct4 together with three other pioneer factors transforms adult cells into stem cells. However, we still do not know how they go about. Experimental structure determination for such a system is very costly and time consuming. We aim to obtain one final model for the binding of Oct4 to the nucleosome by combining computer simulations with different lab experiments. Hopefully, our final model will give us the opportunity to engineer pioneer transcription factors for efficient and reliable production of stem cells and other cells needed in regenerative medicine."

Copper has been essential to human technology since its early days--it was even used to make tools and weapons in ancient times. It is widely used even today, especially in electronic devices that require wiring. But, a challenge with using copper is that its surface oxidizes over time, even under ambient conditions, ultimately leading to its corrosion. And thus, finding a long-term method to protect the exposed surfaces of copper is a valuable goal. One common way of protecting metal surfaces is by coating them with anti-corrosive substances. Graphene is studied extensively as a candidate for anti-corrosive coating, as it serves as a barrier to gas molecules. But, despite these properties, graphene sheets are seen to protect copper from corrosion only over short periods (less than 24 hours). In fact, surprisingly, after this initial period, graphene appears to increase the rate of copper corrosion, which is completely in contrast to its anti-corrosive nature.

To shed light on the peculiar nature of graphene seen in copper, a research team from Chung-Ang University, Korea, led by Prof Hyungbin Son, studied graphene islands on a copper substrate to analyze the patterns of its corrosion. Prof Son explains, "Graphene is known to be mechanically very strong and impermeable to all gases, including hydrogen. Following studies claiming that the corrosion of copper substrates was accelerated under graphene through various defects, these properties have attracted great attention as an oxidation barrier for metals and have been controversial for over a decade. However, they have not been qualitatively investigated over longer time scales. Thus, we were motivated to study the role of graphene as a corrosion-resistant film at the graphene-copper interface." Prof Son and his team used Raman spectroscopy, scanning electron microscopy, and white light interferometry to observe the trends in copper corrosion for 30 days.

At first, the team detected corrosion developing at the edges, spreading the oxidized form of copper, copper oxide (Cu2O), at various defects such as edges, grain boundaries, and missing atoms. This resulted in the splitting of water vapor, supplying oxygen for the oxidation process, until the entire barrier seemed to be rendered useless and copper was fully corroded underneath. Owing to graphene's effect on ambient water vapor, the protected portion of the copper substrate was more corroded than the unprotected portion. Over time, the formation of Cu2O underneath the graphene sheet dispersed the strain and caused p-doping in graphene--creating a hybrid-like structure. But, after 13 days of exposure to ambient conditions, the team discovered something new. They observed that that the corrosion had significantly slowed down where a new hybrid of graphene and Cu2O layer had formed. Meanwhile, the unprotected copper continued to corrode at a consistent rate, until it had penetrated far deeper than the corrosion under the graphene shield.

These findings show that graphene, in fact, protects copper from deep, penetrating oxidation, unlike what previous studies had concluded. Prof Son explained, "We observed that over a longer time scale (more than 1 year), the graphene-Cu2O hybrid structure became a protective layer against oxidation. The area beyond the graphene was heavily oxidized with CuO, with a depth of ?270 nm."

This study has finally managed to settle the debate on whether graphene can be used to protect copper against oxidation. Prof Son concludes, "For nearly a decade, graphene's anti-corrosive properties have been controversial, with many studies suggesting that graphene accelerates the oxidation of copper (resulting in its corrosion). We have shown for the first time that the graphene-Cu2O hybrid structure, which forms over a long period, significantly slows down the oxidation of copper in the long term, as compared to bare copper."

Only time will reveal more about further applications of graphene as an anti-corrosive material. But one thing is certain--this research has potentially taken down several barriers in using graphene to extend the life of copper.

Standard comfort measurements used to design buildings' heating and cooling systems share a common flaw, according to new research. The researchers said the findings could mean that designers have relied on inaccurate measurements for decades when building their systems.

In findings reported February 14 in the journal Scientific Reports, the researchers said the error was caused by the standard instrument used to measure temperature effects of radiant heating and cooling. The instrument, called a globe thermometer, and associated formulas used to calculate comfort based on the sensor's readings do not properly account for air flow called free convection. In experiments, the failure led to temperature errors of more than two degrees Celsius, the researchers said.

Forrest Meggers, an assistant professor at Princeton University's Andlinger Center for Energy and the Environment and one of the lead researchers, said the team uncovered problems with traditional measurements while building an outdoor exhibit in Singapore. While the team had no issues keeping the exhibit participants comfortable using a radiant cooling system, using standard measurement techniques, the team had difficulty demonstrating these cooling effects.

Meggers, also an assistant professor of architecture, said designers take basic measurements with the globe thermometer and use formulas to determine how the radiant system affects occupant comfort levels in various environments. Although the participants remained comfortable and the system was able to keep them feeling cool, the calculations showed the system was not working and that the environment should feel uncomfortable.

"That's when we realized the formula was wrong. We had a hard time accepting it," Meggers said.

The notion of using radiative heat exchange cooling or heating walls and surfaces to keep people nearby comfortable has been identified as an energy efficient design feature, but air conditioning is still the primary solution for keeping people comfortable in buildings in the United States and other places. Radiant systems have not always been seen as effective. The researchers say this miscalculation could help to explain why. Understanding and effectively capturing the impact of radiant systems on comfort can have a major impact on energy savings. Letting the air reach five degrees warmer while cooling surfaces, the researchers say, can lower cooling demand by up to 40% and maintain occupant comfort.

A new innovation makes it possible, for the first time, to quantitatively assess children's spontaneous movement in the natural environment.

Researchers have developed a smart jumpsuit, or a garment that accurately measures the spontaneous and voluntary movement of infants from the age of five months. Details on their motility help in assessing abnormal neurological development, among other things.

The study on the smart jumpsuit and the related analysis method applied to 7-month-old infants was published in the Scientific Reports journal. In the future, the jumpsuit can also be used to study older children.

The assessment of spontaneous and voluntary movements is part of the neurological examination of infants. Previously, the quantitative tracking of children's spontaneous motility in the natural environment has not been possible. Instead, children have been primarily qualitatively assessed at the physician's or physiotherapist's practice, which requires taking into account the fact that the infant's behaviour in the practice setting does not necessarily entirely match that seen at home.

"The smart jumpsuit provides us with the first opportunity to quantify infants' spontaneous and voluntary movements outside the laboratory. The child can be sent back home with the suit for the rest of the day. The next day, it will be returned to the hospital where the results will then be processed," explains Sampsa Vanhatalo, professor of clinical neurophysiology at the University of Helsinki.

Vanhatalo says that the new analysis method quantifies infant motility as reliably as a human being would be able to do by viewing a video recording. After the measurement, the infant's actual movements and physical positions will be known to the second, after which computational measures can be applied to the data.

"This is a revolutionary step forward. The measurements provide a tool to detect the precise variation in motility from the age of five months, something which medical smart clothes have not been able to do until now."

Neurological abnormalities should be detected early on

The data gleaned by the smart jumpsuit is valuable, since the detection of abnormalities in the neurological development of infants at an early stage enables early support. Brain plasticity is at its strongest in early childhood, and is benefited by measures supporting development, which are targeted at recurring everyday activities.

At least 5% of Finnish children suffer from problems associated with language development, attention regulation and motor development. Often, such problems overlap. The pathogenic mechanisms underlying developmental disorders are complex, but preterm birth, perinatal brain damage and the lack of early care, as well as insufficient stimulation in the growth environment aggravate the risk of developmental problems.

According to Leena Haataja, professor of paediatric neurology, developmental disorders in today's pressure-dominated world pose a considerable risk that can lead to learning difficulties and obstacles in the competition for education and jobs. Furthermore, they are a risk factor associated with exclusion from contemporary society.

"The early identification of developmental disorders and support for infants' everyday functional capacity in interaction with the family and the growth environment constitute a significant factor on the level of individuals, families and society," Haataja notes.

In the future, the smart jumpsuit can be used for the objective measurement of how various therapies and treatments affect children's development.

"This is the million-dollar question in Western healthcare. In addition, we may be able to quantify how early motor development associates with later cognitive development," Vanhatalo says.

[Points]

Transmission of 10.66 Pb/s with a spectral efficiency of 1158.7 bit/s/Hz over a 38-core 3-mode fiber

A low-DMD, high core-count few-mode fiber, adoption of 256- and 64-QAM modulation

Drastic increase of data-rate per fiber for intra- and inter data-center communication

[Abstract]

The National Institute of Information and Communications Technology (NICT, President: TOKUDA Hideyuki, Ph.D.), Sumitomo Electric Industries, Ltd. (Sumitomo Electric, President: INOUE Osamu) and Optoquest Co., Ltd. (Optoquest, President: HIGASHI Noboru) succeeded in experimental transmission at 10.66 peta-bit per second, achieving a spectral efficiency of 1158.7 bits per second/Hz. This result exceeded the previous record of 10.16 peta-bit per second.

In this experiment, we develop an optical fiber that supports the transmission of three transverse modes in 38 cores with reduced relative propagation delays between modes, and demonstrated its suitability for high spectral efficiency modulation, namely 256- and 64-quadrature amplitude modulation (QAM). The achieved data rate per fiber increased by a factor of more than 100 over existing commercial transmission systems, demonstrating a potential to significantly reduce the number of fibers required for data transmission over short distances, such as intra- and inter data-center traffic. This result will be presented at the Optical Fiber Communication Conference (OFC 2020) to be held on March 8-12, 2020, in San Diego.

[Background]

In 2008, NICT established a study group on Extremely Advanced Optical Transmission Technologies to enhance collaboration between industry, universities and the government, engaging in pioneering research and development. The research by the collaborative group is at a high level in fierce global competition, exemplified by a past data-rate demonstration record of 10.16 peta-bit per second in a 19-core 6-mode fiber. To achieve larger capacities, a fiber with a larger number of cores or modes is required. However, there are several technical challenges in increasing them, such as the mechanical reliability of fibers or the complexity of signal processing.

[Achievements]

For this transmission experiment, Sumitomo Electric developed a 38-core 3-mode fiber, Optoquest developed a 38-core multiplexer, and NICT performed a transmission experiment of 10.66 peta-bit per second over 13 km distance.

When transmitting different data-streams over different transverse modes in each core, the signals typically experience strong mixing and require digital signal processing (DSP) to separate the signals at the receiver. To reduce the complexity of the DSP, it is important to reduce the propagation delay differences between the modes (DMD: Differential Mode Delay). For this experiment, we fabricated a 38-core 3-mode fiber with reduced propagation delays between modes in each core for simplifying DSP and achieved a delay difference of 0.6-3.0 nanoseconds. Furthermore, loss variation between different modes (MDL: Mode-Dependent Loss), can impair signal quality and reduce achievable data-rate. In the experiment, both the optical fiber and the core- and mode-multiplexers were optimized for a reduced MDL of 5-8.5 dB for most of the fiber cores. Depending on the MDL and DMD in each core, highly spectrally efficient modulation formats of 256- and 64-QAM were selected for transmission leading to data-rates between 279 tera-bit per second and 298 tera-bit per second in each of the 38 cores.

Due to the transmission of a total of 114 spatial channels (38 cores x 3 modes), we increased the transmission capacity by a factor of more than 100 compared to the current standard transmission systems and hence these results demonstrate a potential to significantly reduce the number of fibers required in short-range, ultra-high-capacity systems, such as those for intra- and inter data-center connections.

[Future Prospects]

NICT will continue to promote the effort for early social implementation of the technologies, and the cutting-edge/innovative research and development toward the realization of the ultimate performance of the multi-core/multi-mode optical fiber transmission systems.

Forget counting sheep. If you really want a good night's sleep, all you may need is your romantic partner's favorite T-shirt wrapped around your pillow.

New research accepted for publication in the journal Psychological Science suggests that the scent of a romantic partner can improve your quality of sleep. This is true regardless of whether or not you are consciously aware that the scent is even present.

"A growing body of evidence has shown that close relationships are essential to our health and well being," said Frances Chen, a researcher at the University of British Columbia, Vancouver, and co-author on the paper. "But far less is known about the role of scent in relationships and social support processes. The current study provides new evidence that the mere scent of a romantic partner improves sleep efficiency."

Previous research has shown that romantic relationships and close physical contact can provide many physical and mental benefits, including aiding in a good night's sleep. Other research has shown that scents can have profound and evocative effects on the brain. What has not yet been clearly demonstrated is a direct connection between the two.

Chen and graduate student Marlise Hofer set out to investigate this intersection and to understand how romance, scent, and sleep interact.

Chen and Hofer began their research by asking one member of a heterosexual couple in a long-term (three or more months) relationship to wear a plain cotton T-shirt for 24 hours. During this time, the wearer was to avoid typical scent-producing behaviors, like eating spicy food or doing vigorous exercise. They were also told to avoid perfume, cologne, and antiperspirants. The T-shirt was then hermetically sealed and frozen.

Afterward, the second member of the couple was given two identical shirts, one previously worn by their partner and another that either had been previously worn by a stranger or was scent free.

When a participant used their partner's worn, scent-bearing T-shirt as a pillowcase, they experienced an average of over nine additional minutes of sleep per night. This equates to more than one hour of additional sleep per week, achieved without spending any more time in bed. The increase was due to participants sleeping more efficiently, meaning they spent less time tossing and turning. Sleep efficiency was measured using a wrist-worn sleep monitor that tracked movement throughout the night.

Participants also gave self-reported measures of sleep quality each morning, which increased on nights they thought they were sleeping with their partner's scent.

"The effect we observed in our study was similar in magnitude to that reported for melatonin supplements--a commonly used sleep aid. The findings suggest that the scent of our loved ones can affect our health in powerful ways," noted Hofer.

This research suggests that simple strategies such as taking a partner's scarf or shirt along when traveling may have measurable effects on our sleep. Future research might determine if the scent of a romantic partner has additional health benefits beyond the domains of stress and sleep.

"These findings reveal that--whether or not we are aware of it--a fascinating world of communication is happening right under our noses!" concludes Hofer.

The brains of most fish and amphibian species contain a pair of conspicuously large nerve cells. These are the largest cells found in any animal brain. They are called Mauthner cells and trigger lightning-fast escape responses when predators approach. Biologists at the University of Bayreuth have now shown that these cells have unique functions essential for survival, the loss of which cannot be compensated for by other nerve cells. In addition, they have discovered that Mauthner cells remain functional for a long time without their cell bodies (soma). The researchers have published their findings in the journal "PNAS".

The new findings contradict the widespread view that vital functions of nervous systems are not dependent on individual cells specifically equipped for the purpose. "For some years now, there has been a tendency in biology to assume that there are only weakly developed hierarchies in animal nervous systems. Therefore, one could basically assume that any vital functions are at least partially taken over by other areas of the nervous system in case of failure of the nerve cells that are primarily responsible for a given function. However, Mauthner cells in fish and amphibians are examples of a strong hierarchical dependence. In our experiments, we were able to show that a loss of these cells leads to a lifelong failure of the escape reflexes they control that can never be compensated for", explains the Bayreuth animal physiologist Prof. Dr. Stefan Schuster, who directed the investigations.

This central function of Mauthner cells was long misunderstood. It was believed that a Mauthner cell was condemned to die without its cell body, the soma, and was therefore non-functional. This assumption led to incorrect interpretations of experiments in which the somata of the Mauthner cells had been removed. Here, rapid escapes were still present and these were erroneously explained by other nerve cells compensating for the supposed failure of the Mauthner cells. But in fact, as the Bayreuth researchers have now shown, Mauthner cells are extraordinarily tough. The structure that is crucial for the transmission of excitation in such a cell, the axon, is able to transmit signals to the nervous system and trigger reflex movements even after the cell body has been removed. Only when an important substructure of the axon - the Axon Initial Segment (AIS) - is missing, does a complete functional failure actually occur.

"This observation is not really surprising, given the central importance of the Mauthner cells. It is precisely because of their unique function that evolution has ensured that they are able to fulfil important tasks even after relatively severe damage to the cell body," says Alexander Hecker M.Sc., the first author of the new study. With high-precision experiments on fish larvae, which did not result in them being killed, he was able to demonstrate the unusual toughness of these nerve cells.

"Our results show that Mauthner cells deserve more attention in biomedicine. In particular, the structures and mechanisms that maintain important functions in these nerve cells even after serious damage to their cell body should be studied in as much detail as possible. This might provide a valuable starting point for investigations that focus on the maintenance and regeneration of damaged nerve cells," added Schuster.

Everything a cell does, from dividing in two to migrating to a different part of the body, is controlled by enzymes that chemically modify other proteins in the cell. Researchers at Princeton University have devised a new mathematical technique to describe the behavior of many cellular enzymes. The approach, which will be published February 13 in the journal Current Biology, will help researchers determine how genetic mutations change the behavior of these enzymes to cause a range of human diseases, including cancer.

Enzymes called kinases can add phosphate molecules to multiple sites on other proteins (including other kinases), altering their activity within the cell. Studying these "multisite phosphorylation reactions" is complicated because the phosphate groups can be added rapidly and in different orders, which may affect how the modified proteins behave within the cell. This makes it difficult to understand exactly what goes wrong when a kinase is mutated.

A team of Princeton researchers led by Martin Wühr, an assistant professor of molecular biology, and Stanislav Shvartsman, a professor of chemical and biological engineering at Princeton and an Investigator at the Flatiron Institute, developed a mathematical model of how a kinase called MEK adds two phosphate molecules to a kinase called ERK. This double phosphorylation activates ERK so that it can drive numerous cellular processes, including cell growth and division. Mutations in MEK and ERK can cause several diseases, including cancer.

"There are many mutations in MEK that affect the overall levels of dually phosphorylated ERK," Wühr said. "But the effects of these mutations on the mechanism of ERK activation remain unknown."

The researchers' model revealed how fast each phosphate group is added and how often both phosphates are added by the same enzyme. Most of the time, a single MEK enzyme binds to ERK and adds one phosphate molecule before it detaches and allows a second MEK enzyme to bind and add the second phosphate.

The researchers then used their model to analyze a mutant version of MEK that is found in human cancers. This mutant MEK was twice as fast at adding the first phosphate to ERK, and was much more likely to remain attached and add the second phosphate group itself. Together, this enhances ERK activation and accelerates cancer cell growth.

The researchers then analyzed two other MEK mutations that cause a variety of developmental abnormalities, including congenital heart defects and stunted growth. These mutations did not affect MEK's ability to add phosphate molecules to ERK. Instead, they enhance the activation of MEK by another kinase, called Raf, which adds two phosphate molecules onto MEK.

"Our analysis therefore reveals which of the multiple steps in this cascade of multisite phosphorylation are affected by each mutation," Shvartsman said. "We expect that our mathematical models will allow a deeper, more quantitative understanding of cell regulation systems, including their responses to mutations of constituent proteins."

Uncovering exactly how mutations alter enzyme function can help researchers develop new therapeutic strategies that restore their function back to normal.

"Our approach is not limited to kinases and is applicable to a broad class of biochemical mechanisms where one enzyme modifies multiple sites on its substrate," Wühr said.

Experts at the Center for Tobacco Research and The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) are making a case for why the U.S. Food and Drug Administration's (FDA) proposed rule to add 13 new graphic warnings for cigarette packages and advertisements should be allowed to go into effect. This is the second time the FDA has tried to add graphic warning labels; the previous attempt was ruled in violation of the First Amendment in 2012.

In a Viewpoints article titled New Graphic Tobacco Warnings and the First Amendment, published in the medical journal JAMA Oncology, Patricia J. Zettler, JD, and Theodore L. Wagener, PhD, both with the OSUCCC - James, and co-author Tony Yang of George Washington University outlined why the graphic labels can--and should--survive constitutional scrutiny.

The experts argue the images on the proposed labels are factual representations of the potential negative health effects of smoking and are based on research that demonstrates the warnings promote an improved understanding of the consequences of smoking by increasing consumers' attention to the knowledge of potential consequences.

The experts conclude: "The fate of the FDA's latest attempt to require graphic warnings has implications not just for the agency's efforts to address the negative public health effects of smoking, but also for efforts to educate the public about newer tobacco technologies, such as e-cigarettes, and any efforts to assist consumers to make informed choices by requiring industry to provide information."

In August, the FDA revealed the proposed designs that highlight the negative health effects of tobacco use. The labels include text warnings as well as such graphic images as diseased lungs, feet with amputated toes, and a chest scar from heart surgery.

"Many of the tools that the FDA uses to achieve its public health mission focus on informing patients and consumers. The fate of the agency's latest graphic warnings effort is important because these warnings have potential to help reduce smoking," says Zettler, a member of the OSUCCC - James Cancer Control Research Program and assistant professor at Ohio State's Moritz College of Law. "This effort may serve as a bellwether for the fate of the FDA's regulatory efforts in other areas."

In warm coastal waters around the world, swimmers can often spot large groups of jellyfish pulsing rhythmically on the seafloor. Unless properly prepared with protective clothing, it is best to steer clear of areas that Cassiopea, or upside-down jellyfish inhabit: getting too close can lead to irritating stings, even without direct contact.

Now, researchers have taken a close look at the cause of the "stinging water" encountered near these placid-looking creatures: a toxin-filled mucus the jellyfish release into the water. In the Feb. 13 issue of the journal Communications Biology, a journal from Nature Research, a team led by scientists at the Smithsonian's National Museum of Natural History, the University of Kansas and the U.S. Naval Research Laboratory reports on microscopic structures they have discovered inside the mucus--gyrating balls of stinging cells that they call cassiosomes.

"This discovery was both a surprise and a long-awaited resolution to the mystery of stinging water," said Cheryl Ames, museum research associate and associate professor at Tohoku University. "We can now let swimmers know that stinging water is caused by upside-down jellyfish, despite their general reputation as a mild stinger." The jellyfish is commonly found in calm, sheltered waters such as lagoons and mangrove forests.

The study, a multidisciplinary exploration of cassiosomes conducted over several years, grew out of the curiosity that Ames, National Oceanic and Atmospheric Administration (NOAA) zoologist Allen Collins and colleagues had about the discomfort they had all experienced firsthand after swimming near upside-down jellyfish. It began when Ames was a graduate student in the invertebrate zoology lab that Collins heads at the museum and culminated when Ames, as a postdoctoral fellow at the U.S. Naval Research Laboratory, investigated the question further as an issue of safety for scientists, the military and recreationists. Initially, Ames said, she and her colleagues were not even sure jellyfish were responsible for their stinging, itching skin, since several other ideas had been put forward about the phenomena, including severed jellyfish tentacles, "sea lice," anemones and other stinging marine animals. But they knew that the upside-jellyfish in the museum's aquarium-room lab tanks released clouds of mucus when they were agitated or feeding, and they wondered if they might find the culprit there.

When Ames and Smithsonian interns Kade Muffett and Mehr Kumar first placed a sample of the jellyfish mucus under a microscope, they were surprised to see bumpy little balls spinning and circulating in the slimy substance. Together with Anna Klompen, a graduate student at the University of Kansas and former museum and NOAA fellow, they turned to several more sophisticated imaging methods to examine the mysterious masses closely, and eventually a clearer picture emerged. The bumpy blobs, they discovered, were actually hollow spheres of cells, probably filled with the same jelly-like substance that gives jellyfish their structure. Most of the outer cells were stinging cells known as nematocytes. Other cells were present, too, including some with cilia--waving, hairlike filaments that propel the cassiosomes' movements. Puzzlingly, inside the jelly-filled center of each sphere was a bit of ochre-colored symbiotic algae--the same sort that lives inside the jellyfish itself.

Taking another look at the jellyfish themselves, the team was able to detect cassiosomes clustered into small spoon-like structures on the creatures' arms. When they gently provoked a jellyfish, they could see cassiosomes slowly break away, steadily leaving the appendages until thousands of them mingled with the animal's mucus. They also found that the cassiosomes were efficient killers of lab-fed brine shrimp, and videos that the team produced show tiny crustaceans succumbing quickly to the venomous spheres in the lab. Molecular analyses conducted at the museum and the U.S. Naval Research Laboratory identified three different toxins within the cassiosomes.

While its exact role in the ocean is not yet known, Ames said cassiosome-packed mucus may be an important part of upside-down jellyfishes' feeding strategy. While the photosynthetic algae that live inside upside-down jellyfish provide most of the animals' nutritional resources, the jellyfish likely need to supplement their diet when photosynthesis slows--and toxic mucus appears to keep incapacitated critters close at hand.

"Venoms in jellyfish are poorly understood in general, and this research takes our knowledge one step closer to exploring how jellyfish use their venom in interesting and novel ways," Klompen said.

Collins said the team's discovery was particularly exciting because Cassiopea jellyfish have been recognized for more than 200 years, but cassiosomes have remained unknown until now. "They're not the most venomous critters, but there is a human health impact," he said. "We knew that the water gets stingy, but no one had spent the time to figure out exactly how it happens." Already, the team has identified cassiosomes in four additional closely related jellyfish species, reared at the National Aquarium, and they are eager to learn whether they might be even more widespread.

"This study shows the power of harnessing multi-institution collaboration to solve a problem that has baffled scientists and swimmers around the world," said Gary Vora, deputy laboratory head at the U.S. Naval Research Laboratory. "What stood out most was the team's ability to experimentally pursue where the data was taking us, given the breadth of the tools that were required to come to these conclusions."

We all have our varying mental emphases, inclinations, and biases. These individual dispositions are dynamic in that they can change over time and context. In a study published today in the journal Trends in Cognitive Sciences, Prof. Moshe Bar, a neuroscientist at the Gonda (Goldschmied) Multidisciplinary Brain Research Center at Bar-Ilan University (BIU), together with Noa Herz, of Tel Aviv University, and Shira Baror, of BIU, introduces a new theory that brings us closer to understanding how the mind adapts to various situations.

The authors propose that changing states of mind (SoMs) are holistic in that they exert all-encompassing and coordinated effects simultaneously on our perception, attention, thought, affect, and behavior. They provide evidence and a framework for the concept of SoM, proposing a unifying principle for the underlying cortical mechanism whereby SoM is determined. This novel global account gives rise to unique hypotheses and opens new horizons for understanding the human mind.

According to the theory, the principle dimensions of SoM are directly related to one another and cause one another to change in order to adapt to a particular situation. The SoM aligns them together like a web over a host of mental processes. While SoM are aligned, a single mechanism triggers the synchronous dynamic that gives rise to its all-encompassing nature. Bar and team propose that SoM is determined by the balance between prior experience, or top-down (TD) processing, and input from our senses, or bottom-up (BU) cortical processing. The ratio between the two acts as a 'steering' mechanism whereby the brain combines TD and BU signals to varying degrees depending on state, enabling us to adapt in different contexts.

SoM influences the way we experience our environment perceptually and cognitively, how we feel, how we decide, and how we act. Changing SoMs exert all-encompassing and coordinated effects simultaneously on our perception, attention, thought, affect and behavior. They are dynamic states that are flexible within the same individual, an idea that places much less significance on the traditional concept of personality and how it makes us work.

Manipulating SoM can prove beneficial. By acknowledging the dimensions of our SoM and the connections between them, we can influence performance to best match the demands of a given situation. For example, a computer programmer might encounter different tasks that require different cognitive skills. Some of these might include detailed planning of an algorithm that requires attention to detail, reliance on previously acquired knowledge, and narrowed associative thinking. But if the programmer encounters a problem that suddenly calls for new ideas, alternative ways of thinking, and novel programming skills, engaging in tasks that induce broad SoM can assist in fostering the necessary transition.

A state of mind is dynamic and allows us to look at the same situation in different ways. The optimal state of mind is one that best fits a particular context, according to Bar. Because our mood, breadth of thought, and scope of attention are inter-linked, changing one changes the others accordingly. Since the brain can easily switch from one state to another, understanding that we can adapt our state of mind to a particular situation can prove quite beneficial and might just lead to a healthier state of mind. "We are dynamic and versatile organisms, adapted to fit multiple scenarios and numerous situations. Unlike what intuition might have us believe, our mind is not fixed, and our operation is not consistent. Just like our pupils can dilate to best match a specific amount of light, our entire mind can change depending on task and context," says Bar. Understanding that the mind works on the same principle will allow us to control our state of mind to the extent that this is possible, he concludes.

What The Study Did: Patients with facial palsy completed questionnaires to help identify socioeconomic, personality and mental health factors associated with their health-related quality of life, information that may be beneficial in interpreting treatment outcomes.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Tessa E. Bruins, B.Sc., of the University Medical Center Groningen, in Groningen, the Netherlands, is the corresponding author.

(doi:10.1001/jamaoto.2019.4559)

Editor's Note: The article includes conflict of interest disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

There are more than 100 different autoimmune diseases. But what unites them all is that they arise from an individual's own cells - rare and mysterious immune cells that target not external viruses and bacteria but the body's own healthy organs and tissues.

For the first time, a team led by researchers at the Garvan Institute of Medical Research have pinpointed individual cells that cause autoimmune disease from patient samples. They also uncovered how these cells 'go rogue' by evading checkpoints that normally stop immune cells from targeting the body's own tissues.

The findings could have significant implications for the diagnosis and treatment of autoimmune disease, which affects one in eight individuals in Australia.

"Current treatments for autoimmune disease address only the symptoms, but not the cause. To make more targeted treatments that address disease development and progression, we first need to understand the cause," says Professor Chris Goodnow, co-senior author of the published work, Executive Director of the Garvan Institute and Director of the UNSW Sydney Cellular Genomics Futures Institute.

"We have developed a technique that allows us to look directly at the cells that cause autoimmune disease - it's as though we're looking through a new microscope lens for the first time, learning more about autoimmune disease than was ever possible before."

The findings, published in the journal Cell today, are part of the visionary Hope Research program.

Tracing autoimmune disease to its origins

Because 'rogue' immune cells are so rare in a blood sample - less than one in 400 cells - studying them has been a challenge. Analysis to date has at best revealed 'averages' of the vast mix of cells in a patient's sample, says Dr Mandeep Singh, first author of the published paper.

"Using cellular genomics, we developed a method to 'zoom in' on these disease-causing immune cells in the blood samples of four patients with cryoglobulinemic vasculitis - a severe inflammation of the blood vessels," says Dr Singh.

By first separating individual cells, and then separating their genetic material, the researchers isolated immune cells that produced 'rheumatoid factors' - antibody proteins that target healthy tissues in the body and are associated with the most common autoimmune diseases, including rheumatoid arthritis.

Once isolated, the researchers then analysed the DNA and messenger RNA of each of these 'rogue' cells, scanning more than a million positions in the genome to identify DNA variants that may be at the root of disease.

The evolution of autoimmune disease

Through their analysis, the researchers discovered that the disease-causing immune cells of the vasculitis patients had accumulated a number of mutations before they produced the damaging rheumatoid factors.

"We identified step-wise genetic changes in the cells at the root of an autoimmune disease for the first time, tracing an 'evolutionary tree' of how normal immune cells develop into disease-causing cells," says co-senior author Dr Joanne Reed, who heads the Rheumatology and Autoimmunity Group at the Garvan Institute.

Remarkably, the researchers found that some of the first gene mutations that occurred in these rogue cells were known to drive lymphomas (cancerous immune cells).

"We uncovered 'lymphoma driver mutations', including a variant of the CARD11 gene, which allowed the rogue immune cells to evade immune tolerance checkpoints and multiply unchecked," explains Professor Goodnow, who first hypothesised that disease-causing autoimmune cells employ this cancer tactic in 2007.

Further, the researchers found that cells with the lymphoma driver mutations accumulated further mutations that caused the rheumatoid factors they produced to aggregate, or 'clump together', at lower temperatures.

"This explains the patients' cryoglobulinemic vasculitis, a severe condition that develops in some people with Sjögren's syndrome, systemic lupus, rheumatoid arthritis, or hepatitis C virus infection. In these individuals, rheumatoid factors in the blood aggregate at colder temperatures closer to the skin and also in the kidneys, nerves, and other organs, which damages blood vessels and often proves very difficult to treat," says Dr Reed.

New hope for personalised diagnosis and treatments

Not only have the research findings uncovered the root cause of an autoimmune disease - the ability to identify and investigate specific immune cells at such resolution has vast potential for future treatments to target the cause of all autoimmune diseases.

"In our study, we uncovered specific mutations that mark early stages of autoimmune disease. If we can diagnose a patient at these stages, it may be possible to combine our knowledge of these mutations with new targeted treatments for lymphoma to intervene in disease progression or to track how well a patient is responding to treatments," says Dr Reed.

The researchers are now planning follow-up studies to investigate mutations of autoimmune cells in a range of other diseases, including lupus, celiac disease and type 1 diabetes.

"Identifying these rogue immune cells is a significant step forward for how we study autoimmune disease - and crucially the first step to finding ways to eliminate them from the body entirely," says Professor Goodnow.

A study published Feb. 13 in Cell provides an unprecedented look at the dozens of molecular steps that occur to bring about endometrial cancer, commonly known as uterine cancer. The study offers insights about how physicians might be able to better identify which patients will need aggressive treatment and which won't, and offers clues about why a common treatment is not effective with some patients.

The study, funded by the National Cancer Institute, also suggests a potential new role for already-approved drugs that target proteins known as CDK12, SMARCA4 and PML in other types of cancer.

One could say that the work is a detailed molecular snapshot of endometrial cancer. However, the information is so vast, touching upon tens of thousands of molecular actors taking part in thousands of interactions at different times, that the work is more like a frame-by-frame video, documenting steps that play out over years in patients' bodies.

"This is like the Google Earth of endometrial cancer," said Karin Rodland, one of five corresponding authors of the paper and a cancer biologist at the U.S. Department of Energy's Pacific Northwest National Laboratory. "It's a very comprehensive portrait of this particular cancer type. We tried to measure everything we possibly could. Then we searched for patterns."

Rodland and PNNL's Tao Liu are two of five corresponding authors of the paper; the others come from New York University School of Medicine, Washington University in St. Louis, and Baylor College of Medicine. Overall, scientists from more than a dozen institutions contributed. The senior author is David Fenyo of NYU Langone Health.

Endometrial cancer: beyond genes

The research builds on work by The Cancer Gene Atlas, or TCGA, which identified some of the genetic underpinnings of the disease in 2013.

But genes are only the start of the story when it comes to cancer. When and where are those genes turned on, turned off, or mutated? What do they produce and how do those products interact?

The team studied 95 uterine tumors and 49 normal uterine tissue samples. Scientists measured the abundance and modifications of a dizzying array of molecular players, including genes, messenger RNAs, circular RNAs, micro RNAs and proteins. The measurements of what scientists call "post-translational modifications," including phosphorylation and acetylation, are key to determining when and where proteins, the molecular workhorses of every cell, are active or inactive.

"This unique, rich resource of high-quality data about all these molecular players from the same set of samples provides cancer researchers with a precious view of protein activity and regulation," said Liu.

Altogether the team took more than 12 million measurements.

What did they learn from the painstaking process? Here are the top takeaways.

Identifying the most aggressive endometrial cancers

Scientists developed a promising new way to identify tumors that are not currently classified as aggressive but which turn out to be just as invasive as serous tumors, which grow quickly and are more likely than other tumors to kill patients.

Right now the aggressiveness of an endometrial tumor is determined largely by viewing the cells under a microscope. The team showed that activity levels of certain proteins clearly differentiate more-aggressive from less-aggressive tumors. For example, the team showed how the protein beta-catenin, a well-known actor in many types of cancer, interacts with a signaling pathway known as Wnt to evade detection, accumulate and spur cells to grow out of control.

"What was a disciplined army of interacting proteins now becomes a mob, wreaking havoc," said Rodland.

Unexpectedly, the team also found that a process that involves packing and unpacking genes happens more often than expected in tumor cells. There's more than 7 feet of DNA squeezed into nearly every one of our cells, and it's packed super efficiently, but cells need to unspool the DNA so that other molecular machinery can access it. The team's measures indicate that a key part of the process, known as histone acetylation, is very active in endometrial cancer.

"Imagine a librarian holding a book very tight to the chest, not allowing anyone else to read it," said Rodland. "If you want to read the book - or in this case, access a gene and turn it on - you have to have a way to loosen the librarian's grip and open the book."

Identifying patients who will or won't benefit from checkpoint therapy

The team created a new way to determine which patients are most likely to benefit from a treatment known as checkpoint therapy, where drugs like pembrolizumab and nivolumab are used to dodge the barriers that some cancer cells use to evade the immune system. It's one of many ways that physicians are exploring the use of immunotherapy to spur the body's natural defenses to fight cancer.

Currently in endometrial cancer, physicians use a measurement known as tumor mutation burden to determine which patients are most likely to benefit. Based on the measurements of immune activity in this study, the scientists have proposed a new measure focused on a patient's antigen presentation machinery, known as the APM. The APM describes how well the body flags cancer cells and presents them to the body's immune system for destruction - a key function for checkpoint inhibitors to be effective.

Better insight into exactly who would benefit from the drugs would allow physicians to avoid their use in patients who are unlikely to benefit, sparing those patients severe and unnecessary side effects.

"This work contributes to the personalized medicine we need to deliver for patients who have endometrial cancer," said Bing Zhang of Baylor College of Medicine, a corresponding author. "Such work will help us to know which patients will benefit most from which therapies."

The team also discovered that small, oft-overlooked molecules known as circular RNAs seem to be involved in the transformation that cells undergo when they gain the ability to spread. The transition is called the endothelial-mesenchymal transition, or EMT; it's what makes endometrial cancer deadly.

The study is the fifth publication in a series of studies funded by the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium to tackle the biological pathways involved in cancer. Previously published papers have focused on ovarian cancer and colon cancer.

"This is hypothesis-generating research," said Rodland. "It's like the Moon mission, where the crew brought back rocks for study by many other scientists. Here, we are providing the raw information for scores of scientists to pore over, to study, and to generate new hypotheses. Eventually we hope this information will lead to clinical trials and perhaps new ways to treat this disease."

The Chinese puzzle ball is an ornate decorative artwork consisting of several concentric shells that move independently of each other. In the recent decade, Chinese scientists provided a universal method for the fabrication of a conceptually similar micronanoscale structure, called the hollow multishell structure (HoMS).

A new study led by Prof. WANG Dan from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences proposes a novel concept of temporal-spatial ordering and dynamic smart behavior in HoMSs. It was published in Nature Reviews Chemistry on Feb. 11.

Unlike the single shell hollow sphere or nanoparticles, HoMS has potential applications in fields ranging from energy conversion and storage to catalysis, since it avoids easy agglomeration of nanoparticles, maintains the advantage of effective surface area, and benefits the mass transmission.

In the first phase of their work, the group developed a facile sequential templating approach (STA) for the fabrication of HoMS. This approach realized precise control of the shell number, thickness, distance, and facet exposure, thus modulating surface properties and the interface of HoMS materials.

Specifically, multishells separate space into various, relatively isolated subspaces. At the same time, the heterogeneous pores on each shell facilitate the transmission of small molecules.

"When a molecule or electromagnetic wave diffuses through HoMS, it experiences a set order of environments and spends a controllable time in each one," said WANG. "Based on the understanding of structure property relationship, we name this specific feature of HoMS as 'temporal-spatial ordering'."

Interestingly, in the antenna system of cyanobacteria, different antenna pigments are loaded in a certain order to realize the sequential collection of light energy, which is the example for natural temporal-spatial ordering. This specific structure ensures the fast and precise route to accumulate large amount of oxygen to significant amounts for oxygenic life.

"Inspired by nature, we believe the unique structure suggests promising applications for HoMS in sequential electromagnetic wave harvesting, cascade catalytic reactions, sustained drug release, and hybrid energy storage technologies," said WANG.

The group also proposed another promising proposition: HoMS with isolated spaces in multiple chemical environments could express dynamic smart behavior.

Through chemical modification, HoMSs can bind the target and perhaps also self-evolve to have desired properties at a desired time, which would be highly desirable in chemical engineering and biochemistry fields.