Earth

Cells have a big decision: Should they replicate or sleep? Healthy cells can go either way. Cancer cells' replication switches are stuck in the 'on' position. Now a study by University of Colorado Cancer Center researchers working at CU Boulder's BioFrontiers Institute and published today in the journal Science overturns the conventional wisdom of how these switches work - a model accepted since 1974 and included in current textbooks.

Many biological systems have evolved ways to adapt their reproductive behavior to their surroundings. Take wild jackdaws - when ecosystem resources are limited, jackdaws hatch fewer eggs. Of course, jackdaws have to sense their ecosystems to make this adjustment. Cells do the same thing, with cell-surface receptors acting like tiny grasping hands reaching out into the ecosystem surrounding the cell to see what they can grab. When a specialized receptor/hand grabs a growth factor molecule it relays the signal inside the cell, telling the cell to initiate another pass through the cycle of cellular replication. When these growth factors are absent, cells enter a sleep-like state called quiescence.

Since 1974, scientists have thought that cells make the decision to replicate or quiesce only in a short window during the phase of the cell cycle called G1, as if cells make their go/no-go decision based on a snapshot of their surroundings. The current study, by the lab of Sabrina Spencer, PhD, CU Cancer Center investigator and assistant professor in the CU Boulder Department Biochemistry, together with lead author Mingwei Min, PhD, postdoctoral fellow in Dr. Spencer's lab, shows that cells do not, in fact, depend on a snapshot to decide whether to replicate - it's more like a movie.

"Cells are continuously integrating the availability of growth factors," Spencer says. "Since the environment is continuously fluctuating, it makes sense that cells would continuously sense their surroundings throughout the cell cycle to enable them to adapt appropriately."

But don't blame scientists of the 70s. The snapshot-vs-movie misunderstanding is a function old-vs-new technology. In the 1970s, scientists couldn't see single live cells and instead had to study populations of cells. To look at how growth factors affect cell proliferation, scientists had to synchronize cells by taking away growth factors to force them into quiescence, and then add growth factors back to see if they could initiate replication. What they found is a "restriction point" at which time taking away growth factors would no longer stop replication - making it seem as if growth factor sensing occurs only right before the restriction point in G1.

Spencer is a pioneer in the use of a new technology called single-cell microscopy. Basically, she can watch a single, live cell as it goes about its business. This means that she no longer has to synchronize a population of cells and can instead watch how single cells within a messy population of cells spanning the replication cycle react to these growth factors.

"The biochemistry of what people previously discovered is correct, but the timing is not," she says. The synchronization performed in earlier experiments wipes out cells' previous experience of growth factors - like pushing a reset button - and then providing growth factors to these reset cells made it seem as if they only sense growth factors before the restriction point in G1 phase of the current cell cycle. But Spencer didn't need to synchronize cells and so didn't need push reset by restricting growth factors.

What she saw is that cells remember.

Spencer found that cells sense growth factors throughout their previous cell cycle, such that taking away growth factors for one hour early in the previous cell cycle results in a lower percentage of cells choosing to launch back into replication 15 hours later.

"Cells are continuously taking stock of not only present growth factor signaling but past growth factor signaling, as well," Spencer says. "Normally 80 percent of cells commit to replication, but with a one-hour lapse in growth factors, you're down to 65 percent, with three-hour lapse you're down to 40 percent, and with a six-hour lapse you're down to only 10-20 percent making the decision to reenter the cell cycle. From a basic science point of view, this means they have a memory."

This memory seems linked to a cell's rate of protein production. When Spencer removed growth factors, protein production was drastically reduced, and along with it, the production of an important protein called Cyclin D, which in large part controls the entry into the cell cycle. With lower Cyclin D (also a major target for anti-cancer medicines), fewer cells chose to replicate.

"We think the basic science is pretty exciting. And in addition, the good news in the context of cancer is that cells are continuously sensitive to growth factor signaling - for example, in a disease like melanoma, you wouldn't have to only hit cells in G1 to block that cycle," Spencer says. "Understanding when cells care about receiving those signals, and when cells are sensitive to drugs that block these signals, can fine tune how people utilize those drugs."

Researchers from the Moscow Institute of Physics and Technology, working with Spanish, French, and German colleagues, have determined and analyzed the high-resolution structure of a protein from the recently discovered heliorhodopsin family. Microbial rhodopsins play a key role in optogenetics -- a technique that uses light to control nerve and muscle cells in living tissue. The findings were published in PNAS.

Optogenetics, a technique developed in 2005, involves the introduction of special photosensitive proteins, rhodopsins, into the membranes of neurons. It presents new possibilities for treating Parkinson's disease, depression, anxiety, and epilepsy.

Rhodopsins: Key tool for optogenetics

What made optogenetics possible was the discovery of a protein subfamily known as channelrhodopsins. Rhodopsins are activated by light, which they capture using a compound called retinal. That property makes rhodopsins crucial for animal vision.

In the 20th century, only archaeal rhodopsins found in the genomes of halobacteria were known. However, genomic and metagenomic studies have since led to the discovery of more than 10,000 rhodopsin genes across all three domains of life -- bacteria, archaea, and eukaryotes -- as well as in giant viruses. Among other things, these proteins are responsible for most of the solar energy captured in the ocean.

The diversity, biological significance, and possibilities for the applied use of rhodopsins prompt research into their structure. This in turn provides insights into their mechanisms of action and functions. Scientists from the Research Center for Molecular Mechanisms of Aging and Age-Related Diseases at MIPT make regular contributions to the field. Last year, for instance, they determined the structure of the KR2 protein as well as that of a rhodopsin from a giant virus.

'Inverted' protein structure examined

Despite the many differences in structure and function among rhodopsins, their orientation in the membrane is usually the same, with the so-called N-terminus positioned on the outside of the cell. The N-terminus refers to the end of a protein carrying an amino group, the other end being the C-terminus, carrying a carboxyl group.

However, in the recently discovered family of heliorhodopsins, it is the other way around: The N-terminus faces the cytoplasm, that is, the inside of the cell.

The MIPT researchers are among the first to have solved the structure of a heliorhodopsin -- namely, the 48C12 protein (fig. 1) -- showing the key differences from other known rhodopsins. In the recent paper, the team also suggests the possible functions of heliorhodopsins.

Kirill Kovalev, one of the first authors of the study and MIPT doctoral student, said: "Heliorhodopsins are unusual proteins. The high-resolution structures we obtained demonstrate both their unique overall architecture and the details of their internal configuration and the interactions between key amino acid residues."

In their study, the researchers analyzed the structure of the 48C12 protein in two states and compared it with the structures of other microbial rhodopsins. The team demonstrated that there is a large cavity inside the protein's cytoplasmic part, which accommodates a cluster of water molecules. In one of the obtained protein states, an acetate molecule was detected in the cavity. This means that the cavity might act as the protein's active site, where the binding of a substrate such as a nitrate or a carbonate occurs.

Though the precise function and biological role of heliorhodopsins remain unknown, the authors have put forward a hypothesis. "The unusual structure and properties of the protein leads us to suggest an enzymatic function for heliorhodopsins. Our work has also shown that protein groups with distinct functions may be identified within the family," explained Valentin Gordeliy, the scientific coordinator of MIPT's Research Center for Molecular Mechanisms of Aging and Age-Related Diseases.

The discovery of the heliorhodopsin 48C12 structure has thus allowed the biologists to demonstrate its fundamental difference from other microbial rhodopsins, opening up new possibilities for further research into heliorhodopsins.

Materials -- Molding molecular matter

Scientists at Oak Ridge National Laboratory used a focused beam of electrons to stitch platinum-silicon molecules into graphene, marking the first deliberate insertion of artificial molecules into a graphene host matrix.

While scientists have already used the beam of a high-resolution electron microscope to intentionally rearrange graphene's carbon-based molecular structure, this new development greatly enhances scientists' ability to control matter at the atomic scale.

"This technique allows us to insert foreign molecules into the graphene lattice to change its physical properties," said ORNL's Ondrej Dyck.

He explained that this process is generally applicable and could be especially useful for prototyping quantum-based devices -- including solid state qubits for quantum computers -- from graphene and other ultra-thin materials.

The research was published in Carbon. ¬- Gage Taylor

Media Contact: Sara Shoemaker, 865.576.9219; shoemakerms@ornl.gov

Image: https://www.ornl.gov/sites/default/files/2020-04/Ebeam_IMAGE_Final.jpg

Caption: Researchers insert a platinum-silicon molecule into a graphene lattice with a focused electron beam. Credit: Ondrej Dyck/Oak Ridge National Laboratory, U.S. Dept. of Energy

Nuclear -- Seeing inside particles

Oak Ridge National Laboratory researchers working on neutron imaging capabilities for nuclear materials have developed a process for seeing the inside of uranium particles - without cutting them open.

Nuclear materials experts and neutron scientists collaborated on the process, which creates image-based 3D reconstructions of the particles. Researchers can even view "slices" of different layers of particles to learn the effects of various conditions on elemental distribution, density and other properties.

Other methods to characterize these particles require they be cut in half, put in epoxy and mounted for viewing with an electron microscope. The new technique allows for characterization of the entire particle, not just a single cross section. ORNL's Kristian Myhre said the process is broadly applicable and already is being used to study other materials.

"Unlike electron microscopy, the neutron imaging allows you to take a unique picture without destroying your sample," Myhre said. "It's such a versatile technique."

Media Contact: Kristi Nelson Bumpus, 865.253.1381; bumpuskl@ornl.gov

Image: https://www.ornl.gov/sites/default/files/2020-04/Kernels-nuclear%20materials-2.jpg

Caption: Neutron imaging can non-destructively view important characteristics to develop advanced nuclear materials, such as the overall shape and defects shown in this example 3D image of uranium TRISO kernels. Credit: Kristian Myhre/Oak Ridge National Laboratory, U.S. Dept. of Energy

A storm nears the coast, stirring up wind and waves. Along the boardwalk that lines the beach, a row of oversize concrete umbrellas begins to tilt downward, transforming from a convenient canopy to a shield against the coming onslaught.

In a new approach to storm surge protection, a Princeton team has created a preliminary design for these dual-purpose kinetic umbrellas. In a study published Mar. 28 in the Journal of Structural Engineering, the researchers used computational modeling to begin evaluating the umbrellas' ability to withstand an acute storm surge.

As sea levels rise and storms grow stronger, coastal communities are building more seawalls to help protect people and property from extreme flooding. These barriers can be unattractive and restrict access to beaches, but the Princeton team's umbrellas would provide shade during fair weather and could be tilted in advance of a storm to form a flood barrier.

"This is so much more than just your typical coastal defensive structure," said lead study author Shengzhe Wang, a Ph.D. student in civil and environmental engineering. "It's the first time that anyone has really tried to integrate architecture as an inherent component to a coastal countermeasure."

The proposed umbrellas are shells of reinforced concrete about 4 inches thick, built in the shape of a hyperbolic paraboloid (shortened to hypar), a saddle-like structure that curves inward along one axis and outward along the other. The structure takes inspiration from the work of the Spanish-born architect Félix Candela, who designed hundreds of buildings with thin-shelled hypar roofs in Mexico in the 1950s and 1960s.

Study co-author Maria Garlock, a professor of civil and environmental engineering, has long studied Candela's designs; she co-wrote a book on Candela and helped create an archive and exhibition exploring his work. In the fall of 2017, she and co-author Branko Gliši?, an associate professor of civil and environmental engineering, were considering a project to study the potential of hypar umbrellas as "smart" structures to capture energy and rainwater. Then, a new idea came to her: In addition to adding sensors, "why not tip them and use them in a completely different way --as a kind of seawall?" she asked.

Garlock and Gliši? obtained funding from Project X, which enables engineering faculty members to pursue unconventional ideas. Wang took on the task of testing whether the umbrellas would be a viable strategy for coastal protection.

Wang analyzed the geometry and structural strength of the proposed umbrellas, thin shells of concrete measuring 8 meters (about 26 feet) on each side and supported by 10-foot-tall, 20-inch-square columns. In these simulations, he also tested the functionality of a hinge at the vertex where the column meets the middle of the umbrella.

To investigate how the umbrellas might fare during a coastal storm surge, the team compiled storm surge data from hurricanes between 1899 and 2012 along the U.S. East Coast, then modeled a storm surge height of 18 feet, encompassing all but the highest storm surge in the data set. Adapting established numerical methods for modeling fluid-structure interactions to study hypar structures, they showed that the umbrellas would remain stable when faced with a wall of water about 75% of their deployed height.

"These shells are so thin that anyone looking at this would not be inclined to believe that these structures would be capable of stopping such large forces from water," said Wang. "But we're able to take advantage of the geometry of the hypar shape that gives the structure the additional strength that's required."

Wang has now built physical models of the umbrellas (measuring about 6 inches across) to validate the results of the numerical approach, and is beginning to test the models' responses to the dynamic forces of turbulent flows inside a 10-foot-long water channel. Wind forces characteristic of landfalling hurricanes will also be captured via wind tunnel testing.

"In reality, you're not going to just have a pile of static water. You're going to have waves, you're going to have wind that generates those waves," he said. "That's what we're trying to capture in our next step: How do we physically simulate these waves and how would these waves affect our structures?"

Wang noted that most previous studies have evaluated the ability of vertical walls or slanted barriers to withstand storms, but the hypar's complex geometry required the team "to come up with a whole new set of rules that govern how the structure will perform." Due to the complexity of the solution, another graduate student, Vanessa Notario, will study the flow of forces in the shell as a part of her M.S.E. thesis.

In addition to optimizing the structures to resist high winds and waves, designs for coastal protection must take other practical considerations into account. The 10-foot height of the columns, Garlock said, is good for shading pedestrians while restricting access to the umbrellas' hinges and preventing vandalism.

The team plans to investigate the potential of using more sustainable materials, as well as adding sensors and actuators to control the umbrellas, and incorporating systems for capturing solar energy and storm water.

"Sensors would verify that umbrellas are performing properly before, during and after deployment, while actuators would enable not only automatic deployment but also tracking the sun and wind for the best power and storm water harvesting purposes," said Gliši?, who has expertise in structural health monitoring and smart structures.

"This is a completely new way of thinking about coastal defense structures," said Garlock. "Moving forward, our goal is to make these umbrellas part of a smart, sustainable community."

To help integrate the new design into holistic plans for coastal resilience, the researchers will collaborate with Ning Lin, an associate professor at Princeton whose team recently produced updated 21st-century flood maps for the U.S. Atlantic and Gulf Coasts. They also have plans to work with a geotechnical engineer and are consulting with the New York City Mayor's Office of Resiliency.

Branching allows plants to occupy space in 3D, an innovation considered essential for their adaption. Stem cells are key to this process because they promote the establishment of new growth axes. But where do these stem cells come from?

New research led by investigators from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences (CAS) helps answer this question.

The study, which will be published in Current Biology on April 2, describes how a key shoot stem cell-promoting gene activates its own expression, thus maintaining a stem cell lineage in the leaf axil that enables branching. This knowledge may help scientists optimize crop architecture and boost yields, which is especially important in an era of global climate change.

Unlike animals, plants form lateral organs throughout their life from a specialized stem cell-containing tissue - the meristem. Shoot apical meristems form leaves, while buds established at the leaf axil enable branching. Importantly, buds are formed by axillary meristems that have the same developmental potential as the shoot apical meristem.

In previous research, the IGDB-led team showed that a meristematic cell lineage is maintained in the leaf axil in order to provide progenitor cells for axillary meristem initiation. In the current study, they show how cell fate is maintained in this cell lineage.

"Meristematic cells use a very simple mechanism to keep their identification," said Prof. JIAO Yuling, corresponding author of the paper.

Specifically, leaf axil meristematic cells maintain the expression of SHOOT MERISTEMLESS (STM), a transcription factor promoting shoot meristems. This expression is important because it keeps the STM locus accessible to other binding proteins, according to first author CAO Xiuwei, a postdoctoral fellow in JIAO's lab. Binding the STM locus to other transcription factors is needed before axillary meristem initiation.

The scientists' key finding, however, is that maintenance of STM expression relies on self-activation. In other words, STM binds to its own promoter and then activates gene expression.

The researchers also discovered that STM works in cooperation with the STM-interacting partner protein ATH1. The former is responsible for transcriptional activation, while the latter is responsible for DNA binding.

Although the current study focuses on plants, it may also be applicable to animal research. "Plant cells do not migrate, providing a more tractable system for studying cell lineage and fate determination," said JIAO. "This research helps us to understand how cell fate can be maintained, and this regulatory circuit may also be utilized by animal stem cells," he noted.

Overall, this study inspires future investigation into the molecular mechanisms underlying stem cell fate maintenance in both plants and in animals.

PITTSBURGH, April 2, 2020 - University of Pittsburgh School of Medicine scientists today announced a potential vaccine against SARS-CoV-2, the new coronavirus causing the COVID-19 pandemic. When tested in mice, the vaccine, delivered through a fingertip-sized patch, produces antibodies specific to SARS-CoV-2 at quantities thought to be sufficient for neutralizing the virus.

The paper appeared today in EBioMedicine, which is published by The Lancet, and is the first study to be published after critique from fellow scientists at outside institutions that describes a candidate vaccine for COVID-19. The researchers were able to act quickly because they had already laid the groundwork during earlier coronavirus epidemics.

"We had previous experience on SARS-CoV in 2003 and MERS-CoV in 2014. These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We knew exactly where to fight this new virus," said co-senior author Andrea Gambotto, M.D., associate professor of surgery at the Pitt School of Medicine. "That's why it's important to fund vaccine research. You never know where the next pandemic will come from."

"Our ability to rapidly develop this vaccine was a result of scientists with expertise in diverse areas of research working together with a common goal," said co-senior author Louis Falo, M.D., Ph.D., professor and chair of dermatology at Pitt's School of Medicine and UPMC.

Compared to the experimental mRNA vaccine candidate that just entered clinical trials, the vaccine described in this paper -- which the authors are calling PittCoVacc, short for Pittsburgh Coronavirus Vaccine -- follows a more established approach, using lab-made pieces of viral protein to build immunity. It's the same way the current flu shots work.

The researchers also used a novel approach to deliver the drug, called a microneedle array, to increase potency. This array is a fingertip-sized patch of 400 tiny needles that delivers the spike protein pieces into the skin, where the immune reaction is strongest. The patch goes on like a Band-Aid and then the needles -- which are made entirely of sugar and the protein pieces -- simply dissolve into the skin.

"We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient," Falo said. "And it's actually pretty painless -- it feels kind of like Velcro."

The system also is highly scalable. The protein pieces are manufactured by a "cell factory" -- layers upon layers of cultured cells engineered to express the SARS-CoV-2 spike protein -- that can be stacked further to multiply yield. Purifying the protein also can be done at industrial scale. Mass-producing the microneedle array involves spinning down the protein-sugar mixture into a mold using a centrifuge. Once manufactured, the vaccine can sit at room temperature until it's needed, eliminating the need for refrigeration during transport or storage.

"For most vaccines, you don't need to address scalability to begin with," Gambotto said. "But when you try to develop a vaccine quickly against a pandemic that's the first requirement."

When tested in mice, PittCoVacc generated a surge of antibodies against SARS-CoV-2 within two weeks of the microneedle prick.

Those animals haven't been tracked long term yet, but the researchers point out that mice who got their MERS-CoV vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year, and so far the antibody levels of the SARS-CoV-2 vaccinated animals seem to be following the same trend.

Importantly, the SARS-CoV-2 microneedle vaccine maintains its potency even after being thoroughly sterilized with gamma radiation -- a key step toward making a product that's suitable for use in humans.

The authors are now in the process of applying for an investigational new drug approval from the U.S. Food and Drug Administration in anticipation of starting a phase I human clinical trial in the next few months.

"Testing in patients would typically require at least a year and probably longer," Falo said. "This particular situation is different from anything we've ever seen, so we don't know how long the clinical development process will take. Recently announced revisions to the normal processes suggest we may be able to advance this faster."

If the energy supply of a cell is disturbed by damage, it can protect itself from functional losses and repair itself in a kind of workshop mode. That is the result of a new study conducted by Professor Dr. Aleksandra Trifunovic and Dr. Karolina Szcepanowska as a leading scientist in her team, at the CECAD Cluster of Excellence in Aging Research at the University of Cologne. The findings have been published in Nature Communications under the title 'A salvage pathway maintains highly functional respiratory complex I'.

Trifunovic's lab works on mitochondria, the powerhouses of every cell. The tasks of mitochondria include very basic processes such as the constant energy supply of the cell. The power machinery in mitochondria consists of five components, the so-called complexes I-V. In them, the food we eat is ultimately converted into energy for the cell. If the cellular energy supply is no longer guaranteed due to disturbances in signalling processes, this has serious consequences for the entire organism, and can cause diseases.

'In our most recent work, we have discovered a rescue route that enables cells to repair damage of a particularly sensitive part of complex I', said Trifunovic. 'Repairing something is a far more energy-efficient self-help mechanism compared to the effort that would be required to completely destroy and rebuild this entire complex.'

The specific rescue route Trifunovic identified also acts as a safety valve for the cell. If the rescue route becomes active, the dysfunctional component quickly switches to a shutdown mode and 'goes to the workshop'. This way, the cells prevent harmful reactive oxygen species from being produced and released in the powerhouse engine. Trifunovic remarked: 'So far, very little is known about how this machinery is maintained and regulated. Our results shed light on this process and allow us to explore further therapeutic possibilities.'

Trifunovic and her team are already developing further research questions. In addition to the general novelty of the entire mechanism, she was particularly surprised to see that it is often better for the organism to keep some powerhouse machine components running despite damage, and not to put all damaged components into 'workshop mode' at the same time or to dismantle them completely. It is possible that functions of individual components, which go beyond energy supply, also play a role. Trifunovic would like to further investigate the scope and versatility of the molecular repair pathway she discovered in order to identify its full potential for possible therapies.

Trifunovic insisted that this study would not be possible without work of Dr. Karolina Szczepanowska, who was a driving force behind this project, and important collaboration with groups from our and other universities.

A new study, published in Environmental Health Perspectives, has found that clean cooking with liquified petroleum gas (LPG) could avert 28,000 premature deaths and reduce global temperatures through successful implementation of a new national household energy strategy in Cameroon.

Researchers from the University of Liverpool, in collaboration with the CICERO Centre for International Climate Research, conducted the study that found these deaths could be avoided by 2030, following successful implementation of a national Master Plan to increase adoption of LPG for clean cooking. This is in addition to positive impacts on deforestation and actual reductions in global temperature from switching from biomass to LPG projected to reach -0.70 milli °C in 2100.

Major risk factor

Household air pollution (HAP) is a major risk factor for disease and disability in low- and middle-income countries. HAP is caused by incomplete combustion of solid fuels and kerosene in inefficient stoves and devices, which are used for household energy, including cooking, lighting, and heating. HAP is the leading environmental risk factor for the global burden of disease responsible for almost 4 million annual deaths for approximately 2.8 billion people who rely on these polluting traditional fuels.

The reliance on solid fuels for household energy poses risks to health and the environment and contributes to holding back economic development. These risks include: death and illness from respiratory conditions and cardiovascular disease due to high levels of smoke inhalation, environmental harms from deforestation and air pollution, and adverse impacts on society from sub-optimal health, leading to reduced quality of life and a less economically active population. Reliance on solid fuel also has a detrimental effect on individuals and households from time lost and safety risks resulting from gathering fuel and through inefficient cooking.

Master Plan

In response to concerns about deforestation, environment and health, the Cameroon Government has set a target that by 2030, 58% of the population currently relying on biomass will be using LPG as a cooking fuel, compared to less than 20% in 2014. A National Master Plan was developed and published to help implement scale of access and adoption of LPG by the sector to achieve this target.

Through funding from the African Development Bank, the University of Liverpool and CICERO led a study to estimate the potential impacts that planned LPG expansion (Master Plan) would have on population health and climate change mitigation assuming primary, sustained use of LPG for daily cooking.

Researchers utilised existing and new mathematical models to calculate the health and climate impacts of expanding LPG primary adoption for household cooking in Cameroon over two potential time horizons (short term (2017-2030) and longer term (up to 2100)).

Results

It was estimated that by 2030 (the national target), successful implementation of the Master Plan would avert about 28,000 deaths and 770,000 disability-adjusted life years (DALYs).

For the same period, modelling demonstrated no impact on global temperatures from additional carbon dioxide (CO2) from expanding use of LPG, compensated by reductions of more than a third of short-term climate forcing emissions (e.g. methane and black carbon). The findings (estimated global cooling of 0.1 milli °C in 2030 to 0.70 milli °C in 2100) are aligned with the IPCC Special Report on Climate Warming of 1.5° where gas-based cooking is being recommended as a black-carbon mitigation measure.

The lead health data scientist from the University of Liverpool, Dr Chris Kypridemos, said: "Timely implementation of the National LPG Master Plan for clean cooking in Cameroon could have substantial health benefits for the population as well as favourable climate impacts contributing to a reduction in global warming, of which the magnitude is dependent on the time perspective.

LPG for cooking, by contrast to other fossils fuels, has the potential to protect forests as well as offering substantial health and societal benefits. Further research is needed to explore how to best support national policy and achieve effective implementation of the LPG Master Plan to ensure long-term sustainability and favour equitable adoption of LPG at scale."

This research was funded by the African Development Bank and by the National Institute for Health Research (NIHR) using UK aid from the UK government to support global health research.

Cover crop impacts on soil properties depends on cover crop productivity. Planting cover crops early and in a diverse mix of species could be an option to boost biomass production and enhance benefits to soils. However, the impacts of early planting and species mixes on soil properties are not well understood.

In a recent article in Agronomy Journal, researchers investigated how broadcasting cover crops pre-harvest or drilling post-harvest affected biomass production and soil properties after four years. Cover crops were cereal rye, a mix of rye, legumes, and brassicas, and a no cover crop control. These were studied under no-till rainfed and irrigated continuous corn and corn-soybean rotations at three sites in the eastern Great Plains.

Cover crop biomass was low (

Genetic variations in the skin can create a natural sunscreen, according to University of Queensland researchers investigating the genes linked with vitamin D.

Professor John McGrath from UQ’s Queensland Brain Institute said this was one of a number of ways vitamin D affected the body in a collaborative study that looked at the genomes of more than half a million people from the United Kingdom.

“This study has implicated several new skin-related genes that impact on our vitamin D status — distinct from skin colour which affects our ability to make vitamin D depending on the concentration of the pigment melanin in the skin,” Professor McGrath said.

“Vitamin D is the sunshine hormone and we need bright sunshine on the skin to make it, but variations in our genes also influence how efficient we are at doing that.

“Our findings suggest that genetic variants in the HAL (histidine ammonia-lyase) gene can vary the concentration of a small molecule in the skin which acts like an internal Sun Protection Factor, or SPF.

This molecule soaks up UVB light – the light our bodies use to make vitamin D — and the amount of it in our skin influences how much of the vitamin we can make.

Professor Naomi Wray from UQ’s Institute for Molecular Bioscience and Queensland Brain Institute said the team found 143 gene locations linked to vitamin D concentration.

“Previously we only knew about six regions, so these findings will provide new insights into how our body handles vitamin D,” Professor Wray said.

“The study has found many interesting new candidates that can help our understanding of factors that influence vitamin D concentration.

“Our findings are a treasure trove of clues which will keep researchers busy for a long time.”

The study supports the hypothesis that low vitamin D may be the consequence of poor health, rather than contributing to the risk.

This study was published in Nature Communications and funded by the NHMRC and the Danish National Research Foundation (Niels Bohr Professorship).

Professor John McGrath has a joint position at Aarhus University, Denmark and University of Queensland.

Journal

Nature Communications

DOI

10.1038/s41467

Washington, DC, April 2, 2020 - A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that an entirely parent-based treatment, SPACE (Supportive Parenting for Anxious Childhood Emotions), is as efficacious as individual cognitive-behavioral therapy (CBT) for the treatment of childhood and adolescent anxiety disorders.

Anxiety disorders, including social phobia, separation anxiety, generalized anxiety, are the most common mental health problems in childhood, causing significant distress to the child and family. With up to one-third of youth experiencing a clinically impairing anxiety disorder by the time they reach adulthood, such disorders lead to impairment in personal, social and academic functioning. When not treated successfully, anxiety disorders in childhood can cause long term impairment and an increased risk of additional physical and mental health problems.

This new study enrolled 124 children with existing clinical anxiety disorders and randomly assigned them to receive either the current front-line CBT treatment, or SPACE--developed by Yale researcher, Dr. Eli Lebowitz and his team at the Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA.

SPACE teaches parents to reduce their accommodation and to respond to a child's anxiety symptoms in a supportive manner that conveys acceptance of the child's genuine distress along with confidence in the child's ability to cope with anxiety.

The authors found that children whose parents participated in 12 sessions of SPACE were as likely to overcome their anxiety disorder as children who participated in 12 sessions of CBT, the best-established evidence-based treatment for child anxiety.

Anxious children look to their parents for help in coping with their anxiety and avoiding the things that make them feel afraid. Parents of anxious children typically become entangled in their child's symptoms through a process known as family accommodation. For example, a child who is chronically worried may rely on a parent for constant reassurance, or a child with separation anxiety may require a parent to stay at home with them or sleep next to them at night.

For children with social phobia, parents often speak in place of the child or avoid having guests over to the home. Research indicates that family accommodation can contribute to maintaining the child's anxiety symptoms over time.

For both treatments, approximately 60 percent of children no longer met diagnostic criteria for any anxiety disorder following treatment, based on assessments conducted by independent evaluators who were unaware of which treatment children received. An even greater proportion (87.5 percent for SPACE and 75.5 percent for CBT) showed significant improvement in their symptoms. Anxiety symptom questionnaires completed by children and by their parents also showed equivalent improvement for SPACE and CBT. Parents and children rated both treatments as highly satisfactory.

Overconfidence in one's own abilities despite clear evidence to the contrary is present and persistent in children as young as four, a new study by the University of Sussex Business School has revealed.

The cognitive bias has been consistently observed among a number of professions including business executives, bankers and physicians across different countries and cultures but a new study led by Dr Dominik Piehlmaier indicates that overconfidence is persistent and widespread during early childhood.

The research also found that girls were more successful than boys at a card game in the study thanks to a more low-risk strategy but also experienced greater swings between overconfidence and lack of confidence in their abilities.

Dr Dominik Piehlmaier, Lecturer in Marketing at the University of Sussex Business School and the study's author, said: "Much of our knowledge on judgment and decision-making is based on adult participants but there is no reason to believe that humans only develop such an omnipresent cognitive illusion once we reach adulthood.

"My findings indicate that effective interventions that increase an individual's knowledge about their own knowledge and its boundaries might be needed to target much younger individuals if one wants to efficiently calibrate a person's irrational confidence."

In the study, children were asked to play a card game known as the Children's Gambling Task where they choose cards from one of two packs.

The card is then turned over to reveal how many stickers the participant has won and lost. One pack had cards with significantly higher wins and losses than the other.

At intervals, children had to decide whether they thought they would win more, about the same, or fewer stickers than previously in the game.

Each participant started off with four stickers after the initial six practice trials. On average, every participant gained 0.3 stickers per turn and left the game with an average of 6.67 stickers, ranging from zero to 33.

The study showed that more than 70% of four-year-olds and half of all five and six-year-olds were overconfident in their expectations after playing ten turns and six practice trials.

Dr Piehlmaier said: "A vast number of repetitions, learning, and feedback in the study did not diminish the misplaced confidence in the success of the majority of participants.

"The children played more than 60 turns and saw their payoff balance rose and fell, yet every third child still thought that they could do better than they had done in the previous 50 turns.

"The Children's Gambling Task closely resembles a very simplified version of the financial markets with relatively safe options providing low but steady average return rates and highly risky assets that promise much higher short-term gains with a catastrophic long-term yield.

"The finding that overconfidence is persistent even in the face of own shortcomings mirrors results from previous studies that looked at the performance of investors."

Overconfidence is widely seen as a male trait but the study also had interesting findings when it came to the general performance of boys and girls.

In general, girls outperformed boys by an average of 2.87 stickers thanks to a less high-risk strategy of choosing relatively more safe cards which offered smaller but more sustainable gains.

Dr Piehlmaier added: "Boys seem to follow a negative trend line that indicates slow but steady learning on what might be considered 'reasonable expectations'.

"Girls' behaviour is much more unpredictable. When the girls' overconfidence plot is compared to their payoffs, it can be noticed that they closely align.

"This indicates that girls overestimate their abilities if they have a winning streak and underestimate themselves whenever they lose a few times in a row.

"By the end of the experiment, there were relatively more overconfident girls than boys; a finding that contradicts previous reports regarding more calibrated girls in metamemory tasks."

Different surfaces and organs of the body are covered by epithelial tissue, which is composed of cells tightly connected to each other. The cells can be attached through junctions that are in direct contact with the cytoskeletal network inside the cells.

This network, composed of actin and myosin proteins that together form contractile actomyosin bundles, maintain the epithelial cells close to each other.

Recent studies have shown that physical alterations in the growth environment of cells have a significant impact on tissue function. Therefore, such changes are also connected to the onset of a number of diseases, including cancer.

Now, a research group working at the University of Helsinki's Faculty of Veterinary Medicine under the direction of Sari Tojkander has found that extracellular forces regulate the formation of epithelia-integrating actomyosin bundles.

"Contacts between neighbouring epithelial cells generate mechanical tension, which activates a certain intracellular signalling pathway. This, in turn, drives the assembly of epithelial actomyosin structures. If components involved in the signalling pathway are disturbed, epithelial cells are detached from each other and become mobile," says Sari Tojkander.

The study utilised breast and kidney epithelial cell lines, but the researchers assume that the same mechanisms also apply to other types of epithelial cells.

"Another important factor is that, in the case of cancer, the proteins associated with this signalling pathway that is sensitive to mechanical tension are regulated erroneously. In other words, our findings have a direct association with means that cancer cells may use to break away from the area of the original tumour, enabling them to scatter to healthy tissues," says postdoctoral researcher Kaisa Rajakylä, who is the principal author of the article.

Think about traffic flow in a city - there are stop signs, one-way streets, and traffic lights to organize movement across a widespread network. Now, imagine what would happen if you removed some of the traffic signals.

Among your brain's 86 billion neurons are the brain's own version of stop signals: inhibitory neurons that emit chemicals to help regulate the flow of ions traveling down one cell's axon to the next neuron. Just as a city without traffic signals would experience a spike in vehicle accidents, when the brain's inhibitory signals are weakened, activity can become unchecked, leading to a variety of disorders.

In a new study published in GLIA on March 11, Virginia Tech neuroscientists at the Fralin Biomedical Research Institute at VTC describe how the common Toxoplasma gondii parasite prompts the loss of inhibitory signaling in the brain by altering the behavior of nearby cells called microglia.

The Centers for Disease Control and Prevention estimates that 40 million Americans have varying levels of Toxoplasma infection, although most cases are asymptomatic. Commonly passed to humans via exposure to farm animals, infected cat litter, or undercooked meat, the parasitic infection causes unnoticeable or mild, to flu-like symptoms in most healthy people. But for a small number of patients, these microscopic parasites hunker down inside of neurons, causing signaling errors that can result in seizures, personality and mood disorders, vision changes, and even schizophrenia.

"After the initial infection, humans will enter a phase of chronic infection. We wanted to examine how the brain circuitry changes in these later stages of parasitic cyst infection," said Michael Fox, a professor at the Fralin Biomedical Research Institute and the study's lead author.

The parasite forms microscopic cysts tucked inside of individual neurons.

"The theory is that neurons are a great place to hide because they fail to produce some molecules that could attract cells of the immune system," said Fox, who is also director of the research institute's Center for Neurobiology Research.

Fox and his collaborator, Ira Blader, recently reported that long-term Toxoplasma infections redistribute levels of a key enzyme needed in inhibitory neurons to generate GABA, a neurotransmitter released at the specialized connection between two neurons, called a synapse.

Building on that discovery, the scientists revealed that persistent parasitic infection causes a loss of inhibitory synapses, and they also observed that cell bodies of neurons became ensheathed by other brain cells, microglia. These microglia appear to prevent inhibitory interneurons from signaling to the ensheathed neurons.

"In neuropsychiatric disorders, similar patterns of inhibitory synapse loss have been reported, therefore these results could explain why some people develop these disorders post-infection," Fox said.

Fox said the inspiration for this study started years ago when he met Blader, a collaborating author and professor of microbiology and immunology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, after he delivered a seminar at Virginia Tech. Blader studied Toxoplasma gondii and wanted to understand how specific strands of the parasite impacted the retina in mouse models.

Working together, the two labs found that while the retina showed no remarkable changes, inhibitory interneurons in the brain were clearly impacted by the infection. Mice - similar to humans - exhibit unusual behavioral changes after Toxoplasma infection. One hallmark symptom in infected mice is their tendency to approach known predators, such as cats, displaying a lack of fear, survival instincts, or situational processing.

"Even though a lot of neuroscientists study Toxoplasma infection as a model for immune response in the brain, we want to understand what this parasite does to rewire the brain, leading to these dramatic shifts in behavior," Fox said.

Future studies will focus on further describing how microglia are involved in the brain's response to the parasite.

Among the research collaborators is Gabriela Carrillo, the study's first author and a graduate student in the Translational Biology, Medicine, and Health Program. Previously trained as an architect before pursuing a career in science, Carrillo chose this topic for her doctorate dissertation because it involves an interdisciplinary approach.

"By combining multiple tools to study infectious disease and neuroscience, we're able to approach this complex mechanistic response from multiple perspectives to ask entirely new questions," Carrillo said. "This research is fascinating to me because we are exposing activated microglial response and fundamental aspects of brain biology through a microbiological lens."

Researchers in Japan have succeeded in creating a new type of helicoidal supramolecular polymer. The process and mechanism of the generation of its structure were observed using atomic force microscopy (AFM); the helicoidal structure grew spontaneously after two different monomers were mixed. The findings of the study, which was published in Nature Communications on April 1st, 2020 may lead to the design of original soft materials.

In recent years, researchers have paid attention to supramolecular polymers formed through non-covalent bonds with the aim of developing smart soft materials. Shiki Yagai, a professor at Chiba University says, "Supramolecular polymers have various functions. They have self-repair capability and are easily degraded, so through precise design of their molecular structures we will be able to create materials having higher environmental responsiveness."

For many years, Prof. Yagai and his research team have been working on designing supramolecular polymers that have unique features. Good examples of these new polymers are self-foldable supramolecular polymers and chimera fibers which combine helixes and linear chains.

In this research, the team succeeded in creating a supramolecular polymer whose helicoidal structure extends spontaneously. Extension is started by only mixing two molecules differing in one oxygen atom. By observing its degradation process, they discovered that the new supramolecular polymer has the unique property of changing its chemical structure in response to temperature.

When they mixed two naphthalene molecules, six-membered hydrogen-bonded supramolecular complexes (rosettes) consisting of monomer subunits formed an amorphous coaggregate (Fig. 1-A). However, when left at room temperature, integrated rosette subunits in which two molecules are alternately arranged gradually formed in the mixture, and this spontaneously developed into a beautiful helical structure (Fig.1-B). The team succeeded in controlling the copolymerization using electrostatic interaction between the two molecules, and observed the formation of the helicoid using AFM.
Spectral measurements revealed that this higher-order structural change was due to the composition of the rosette units that make up the polymer. Homopolymers consisting only of electron-rich molecules (red molecules in Fig. 1) are energetically stabilized by forming a stable ring structure, and integrated rosettes are further stabilized by coaggregation. Bonds between the rosettes are strengthened by energetic stabilization and they grow into a helicoidal structure rather than stopping at rings.

In addition, a unique thermal response in which the helicoidal supramolecular copolymers rapidly collapsed at 45 ºC to 50 ºC was discovered. This phenomenon is entirely different from the thermal decomposition behavior of general supramolecular polymers, which gradually disintegrate from the terminal or defect site.

"Using this self-sorting structural change, it should be possible to create new soft materials that quickly respond to various environments," says Prof. Yagai.