Earth

A team of chemical engineers has developed a new way to produce medicines and chemicals on demand and preserve them using portable "biofactories" embedded in water-based gels called hydrogels. The approach could help people in remote villages or on military missions, where the absence of pharmacies, doctor's offices or even basic refrigeration makes it hard to access critical medicines, daily use chemicals and other small-molecule compounds.

Led by Hal Alper, professor at The University of Texas at Austin's Cockrell School of Engineering, in collaboration with chemist Alshakim Nelson and his research group at the University of Washington, this first-of-its-kind system effectively embeds microbial biofactories -- cells bioengineered to overproduce a product -- into the solid support of a hydrogel, allowing for portability and optimized production. It is the first hydrogel-based system to organize both individual microbes and consortia for in-the-moment production of high-value chemical feedstocks, used for processes such as fuel production, and pharmaceuticals. Products can be produced within a couple of hours to a couple of days.

The team describes their new approach in the Feb. 4 issue of Nature Communications.

"We have taken a completely different angle for fermentation by utilizing hydrogels," said Alper, whose research expertise is focused in biotechnology and cellular engineering. "Many of the chemicals, fuels, nutraceuticals and pharmaceuticals we use rely on traditional fermentation technology. Our technology addresses a strong limitation in the fields of synthetic biology and bioprocessing, namely the ability to provide a means for both on-demand and repeated-use production of chemicals and antibiotics from both mono- and co-cultures."

As a crosslinked polymer, the hydrogel used in this work can be 3D printed or manually extruded. The gel material, along with the cells inside, can flow like a liquid and then harden upon exposure to UV light. Molecularly, the resulting polymer network is large enough for molecules and proteins to move through it, but the space is too small for cells to leak out.

The team also found that by lyophilizing, or freeze-drying, the hydrogel system, it can effectively preserve the fermentation capacity of the biofactories until needed in the future. The result of the freeze-drying somewhat resembles an ancient mummy, shriveled up but well-preserved. To revive the hydrogel and enable the production of the chemical or pharmaceutical, one would simply add water, sugar and/or some other basic nutrients, and the cells will then convert into the product just as effectively as before the preservation process.

One of the novel aspects enabled by this platform is the ability to combine multiple different organisms, called consortia, together in a way that outperforms traditional, large-scale bioreactors. In particular, this system enables a plug-and-play approach to combining and optimizing chemical production. For example, if one set of enzymes works best in the bacteria E. coli, while the other works best in the yeast S. cerevisiae, the two organisms can work together to more efficiently go straight to the product. The research team tested both of these organisms.

This platform has the added benefit of multitasking, keeping different types of cells separated while they grow, preventing one from taking over and killing off the others. Likewise, by testing a range of temperatures, the team was able to control the dynamics of the system, keeping the growth of multiple cell types balanced.

Finally, the team was able to show continuous, repeated use of the system (with yeast cells) over the course of an entire year without a decrease in yields, indicating the sustainability of the process over time.

Medicines such as antibiotics have a certain shelf life and require particular storage conditions. The portability of the biofactory to make these molecules makes the hydrogel system especially useful in remote places, without access to refrigeration to store medications. It would also be a small and compact way to maintain access to several medications and other essential chemicals when there is no access to a pharmacy or a store, like during a military mission or a mission to Mars. Although not quite there yet, the possibilities are promising.

"This technology can be applied to a wide range of products and cell types. We see engineers and scientists being able to plug and play with different consortia of cells to produce diverse products that are needed for a specific scenario," Alper said. "That's part of what makes this technology so exciting."

Philadelphia, February 4, 2020 - Researchers shed new light on the genetic relationship between three mood disorders associated with depression--major depression and bipolar disorder types 1 and 2, in a new study in the journal Biological Psychiatry, published by Elsevier.

"The clearest findings are a genetic distinction between type 1 bipolar and type 2 bipolar, and the greater similarity of type 2 bipolar to major depressive disorder," said first author Jonathan Coleman, PhD, a statistical geneticist and postdoctoral fellow in the lab of senior author Gerome Breen, PhD at the Institute of Psychiatry, Neuroscience, and Psychology at Kings College London, UK.

Both types of bipolar disorder used to be referred to as 'manic-depressive disorder'. Mania is a behavioral state associated with behavioral activation, euphoric or irritable mood, reduced need for sleep, impulsive behavior, impaired judgement, racing disorganized thoughts, impulsive behaviors, and frequently strongly held false beliefs (delusions) or hallucinations. Bipolar disorder type 1 is associated with mania and depression, while bipolar 2 is predominately associated with depression marked by mild symptoms reminiscent of mania, called hypomania.

The insights came from several extremely large datasets analyzed together. For their meta-analysis, Coleman, Breen and their co-authors combined genome-wide association studies from three large datasets of people with major depression and bipolar disorder to evaluate shared and distinct molecular genetic associations. Most of the data came from the large international Psychiatric Genomics Consortium. Additional data came from the UK Biobank, a major health resource established by the Wellcome Trust, and the online genetic service platform, 23andMe.

There are significant racial and ethnic differences in the findings from genome-wide association studies (GWAS). The findings of this study pertain only to people of European ancestry and findings might be different in other groups.

The authors also report that the genetic risk for these disorders was predictive of other traits as well. For example, the genetic risk for bipolar disorder was correlated with more educational attainment, while the heritable risk for major depressive disorder was associated with less education.

In the mouse brain, the authors also mapped the genetic risk for these disorders on to particular brain cell types using a sophisticated analytic strategy building on the pattern of genes expressed. They implicated serotonin neurons in the risk for both depression and bipolar disorder, while bipolar disorder distinctively involved GABA and glutamate neurons (nerve cell types also implicated in schizophrenia).

"We have long known that mood disorders are highly heterogeneous and the boundaries between types of mood disorders are often difficult to define clinically," said John Krystal, MD, editor of Biological Psychiatry. "This new study suggests that there are aspects of genetic risk, and presumably brain function, that link forms of mood disorders, but there are also distinctions that may shed light on subtypes of depression that may have important implications for treatment."

Ultimately, the researchers want to develop clinical tools to help predict if a first episode of depression is likely to persist as a disorder or progress into bipolar disorder. "Genetic data won't ever replace clinical insight, but it might be a useful addition to clinical models," said Coleman.

Oncotarget Volume 11, Issue 4: Treatment of human oral squamous cell carcinoma cell lines HSC3 and HSC4 with Clostridium perfringens enterotoxin, induced CLDN4 nuclear translocation to enhance epithelial-mesenchymal transition, stemness, cell proliferation, and invasive ability.

Moreover, it was revealed that the complex of YAP1, CLDN4, and zona occludens-2 was formed by CPE treatment, further suppressing YAP1 phosphorylation by LATS1 and activating it.

Dr. Yi Luo from the Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China, Dr. Tadaaki Kirita from the Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara, Japan and Dr. Hiroki Kuniyasu from the Department of Molecular Pathology, Nara Medical University, Kashihara, Nara, Japan said in their Oncotarget research article, "More than 300 species of bacteria are found in the oral cavity, 10% of which are anaerobic in nature"

The number of bacteria in the oral cavity is determined by scraping the gingiva.

Mostly the normal count of bacteria is about 1011 to 1012 cfu/ml and of these 0.1% are anaerobic.

It is still unclear what role oral bacteria play exactly in the development of oral cancer.

In contrast, zonula occludens -1 and ZO-2, which are lining proteins in tight junctions, activate yes-associated protein and transcriptional coactivator with PDZ-binding motif by inhibiting the Hippo signaling pathway, promoting cancer cell growth and epithelial-mesenchymal transition to enhance cancer metastasis.

In this study, the authors examined the role of the bacteria in the oral cavity, especially anaerobic bacteria, in the development of oral cancer through the action on CLDN protein.

We showed that anaerobic bacteria impair tight junctions and promote cancer progression through YAP1 activation in oral squamous cell carcinomas.

The Luo/Kirita/Kuniyasu Research Team concluded that their Oncotarget study inferred that Clostridium induced YAP1 activation, which in turn suggested that the suppression of Clostridium by antibiotics and/or oral hygiene might contribute to the suppression of carcinogenesis and cancer progression. Extensive clinical studies are required to prove this hypothesis in the future.

If you feed the birds in your backyard, you may be doing more than just making sure they have a source of food: you may be helping baby birds give parasites the boot.

New research published in the Journal of Applied Ecology from UConn assistant professor of ecology and evolutionary biology Sarah Knutie shows that feeding bluebirds can have a significant impact on parasitic nest flies feeding on baby bluebirds.

Parasitic flies can be found in the nests of many bird species, and some can have significant impacts on nestling survival.

The flies lay eggs in the nests, and once the eggs hatch, the larvae feed on the blood of nestlings by drilling holes through the young birds' skin.

In the case of bluebirds, Knutie says it appears nestlings are generally tolerant of the flies, meaning they can sustain high loads of parasites but not suffer significant negative impacts on survival and growth. However, the parasite removes a lot of blood from the nestling, which could have lasting impacts.

"Bluebirds do not have a detectable immune response to the parasitic flies," says Knutie. "Since backyard bird feeding by humans is so popular, I was interested in how giving these birds food could influence their immune response against the parasite, and whether there is a particular time during the breeding season when supplemental feeding is most effective."

To perform the study, Knutie and her father set up 200 nest boxes in northern Minnesota. She followed each nest for the presence of bird eggs, and then, when the eggs hatched, fed some of the birds live mealworms.

The growth and survival of the nestlings was tracked until the birds fledged. After leaving the nest, the number of parasites was recorded.

Nestling birds that were fed had higher overall survival and less blood loss than birds that were not fed.

"When the nestlings were not fed, every nest had parasites, with up to 125 flies in a single nest," Knutie says. "When the nestlings had been fed, I found very few or no parasites. These results suggest that food supplementation could be increasing the birds' ability to kill the parasites."

Next, Knutie wanted to explore why this trend is seen with supplemented birds. She looked to the antibody response in the nestlings, which could be helping the birds kill the parasites.

"With unsupplemented nestlings, there is a low-to-no detectable antibody response. With supplemented nestlings, there was a significantly higher antibody response," she says. "Higher antibody levels mean fewer parasites."

This could be attributable to the birds having more nutrient resources to devote to mounting a response sooner in life than the un-supplemented cohort. With an immune response, the parasites are killed. The timing of the feeding therefore seems important, with feeding earlier in the breeding season benefiting the young birds more than later in the season.

"If food availability is driving the nestlings' immune response to parasites, feeding early could really help the birds," Knutie says.

The other aspect of the response Knutie explored was whether the antibody response could be related to the birds' gut microbiota. To study this, the microbial communities were analyzed. Knutie found that overall, the microbial communities between the supplemented and unsupplemented birds were similar, however, there were some slight differences.

"The relative abundance of Clostridium species was much higher in supplemented birds, and there were correlations with antibody levels and parasites. More Clostridium meant more antibodies and fewer parasites," she says.

Knutie is quick to point out that correlation does not mean causation, and that her research team is delving further into the question of the gut microbiota playing a role in mediating an immune response in the bluebirds.

"The interesting piece of this work suggests that if you feed your birds, it can really reduce the parasite load for the young birds, and that timing of feeding matters," says Knutie.

Even though they are inanimate objects, sand dunes can 'communicate' with each other. A team from the University of Cambridge has found that as they move, sand dunes interact with and repel their downstream neighbours.

Using an experimental dune 'racetrack', the researchers observed that two identical dunes start out close together, but over time they get further and further apart. This interaction is controlled by turbulent swirls from the upstream dune, which push the downstream dune away. The results, reported in the journal Physical Review Letters, are key for the study of long-term dune migration, which threatens shipping channels, increases desertification, and can bury infrastructure such as highways.

When a pile of sand is exposed to wind or water flow, it forms a dune shape and starts moving downstream with the flow. Sand dunes, whether in deserts, on river bottoms or sea beds, rarely occur in isolation and instead usually appear in large groups, forming striking patterns known as dune fields or corridors.

It's well-known that active sand dunes migrate. Generally speaking, the speed of a dune is inverse to its size: smaller dunes move faster and larger dunes move slower. What hasn't been understood is if and how dunes within a field interact with each other.

"There are different theories on dune interaction: one is that dunes of different sizes will collide, and keep colliding, until they form one giant dune, although this phenomenon has not yet been observed in nature," said Karol Bacik, a PhD candidate in Cambridge's Department of Applied Mathematics and Theoretical Physics, and the paper's first author. "Another theory is that dunes might collide and exchange mass, sort of like billiard balls bouncing off one another, until they are the same size and move at the same speed, but we need to validate these theories experimentally."

Now, Bacik and his Cambridge colleagues have shown results that question these explanations. "We've discovered physics that hasn't been part of the model before," said Dr Nathalie Vriend, who led the research.

Most of the work in modelling the behaviour of sand dunes is done numerically, but Vriend and the members of her lab designed and constructed a unique experimental facility which enables them to observe their long-term behaviour. Water-filled flumes are common tools for studying the movement of sand dunes in a lab setting, but the dunes can only be observed until they reach the end of the tank. Instead, the Cambridge researchers have built a circular flume so that the dunes can be observed for hours as the flume rotates, while high-speed cameras allow them to track the flow of individual particles in the dunes.

Bacik hadn't originally meant to study the interaction between two dunes: "Originally, I put multiple dunes in the tank just to speed up data collection, but we didn't expect to see how they started to interact with each other," he said.

The two dunes started with the same volume and in the same shape. As the flow began to move across the two dunes, they started moving. "Since we know that the speed of a dune is related to its height, we expected that the two dunes would move at the same speed," said Vriend, who is based at the BP Institute for Multiphase Flow. "However, this is not what we observed."

Initially, the front dune moved faster than the back dune, but as the experiment continued, the front dune began to slow down, until the two dunes were moving at almost the same speed.

Crucially, the pattern of flow across the two dunes was observed to be different: the flow is deflected by the front dune, generating 'swirls' on the back dune and pushing it away. "The front dune generates the turbulence pattern which we see on the back dune," said Vriend. "The flow structure behind the front dune is like a wake behind a boat, and affects the properties of the next dune."

As the experiment continued, the dunes got further and further apart, until they form an equilibrium on opposite sides of the circular flume, remaining 180 degrees apart.

The next step for the research is to find quantitative evidence of large-scale and complex dune migration in deserts, using observations and satellite images. By tracking clusters of dunes over long periods, we can observe whether measures to divert the migration of dunes are effective or not.

The threat of antimicrobial resistance to medication is a global health issue. Recent years have seen a surge in our awareness of resistance genes; and as a result of the prevalence of these genes, antibiotics are becoming less effective at treating microbial infections, such as TB and gonorrhoea.

Although much work has been done analysing the human gut microbiome and its associated genes, little is currently known about these genes in the mouth.

In a paper published today in Nature Communications, academics from King's College London have taken the first step to examine the antimicrobial resistance potential of the mouth - the oral resistome. As the mouth is the first point of entry for food and many medications, it has the potential to influence the spread of antimicrobial resistance in the human microbiome. Antimicrobial resistance arises when the microbe acquires genes that attempt to avoid or destroy the drugs.

"Given what we are beginning to discover about the sheer variety of microbial species in the human microbiome, if we are to stand any hope of getting to grips with the spread and persistence of antimicrobial resistance, we need to expand human resistome studies to sample other body areas," explains Dr David Moyes, Lecturer in Host-Microbiome Interactions at King's College London.

The research group accessed saliva, dental plaque and other oral data and analysed them using the Comprehensive Antibiotic Resistance Database (CARD). They included data from several different regions within the study, including Asia, Pacific, European and American locations.

They found that there were unique resistome profiles in the mouth compared to the gut. Further, whilst there was less diversity of antimicrobial resistance genes in the mouth, those genes present were more pervasive across the populations studied.

Dr Moyes asks: "If body sites have different resistomes, can a gut resistome represent the entirety of the human resistome? We must continue analysis of the microbiomes at other body sites to realise the huge potential for unlocking insights from open-source datasets of previously sampled cohorts. If we look hard enough, the answers could be right under our noses."

Scientists at the University of Alaska Fairbanks have identified a new species of thalattosaur, a marine reptile that lived more than 200 million years ago.

The new species, Gunakadeit joseeae, is the most complete thalattosaur ever found in North America and has given paleontologists new insights about the thalattosaurs' family tree, according to a paper published today in the journal Scientific Reports. Scientists found the fossil in Southeast Alaska in 2011.

Thalattosaurs were marine reptiles that lived more than 200 million years ago, during the mid to late Triassic Period, when their distant relatives -- dinosaurs -- were first emerging. They grew to lengths of up to 3-4 meters and lived in equatorial oceans worldwide until they died out near the end of the Triassic.

"When you find a new species, one of the things you want to do is tell people where you think it fits in the family tree," said Patrick Druckenmiller, the paper's lead author and director and earth sciences curator at the University of Alaska Museum of the North. "We decided to start from scratch on the family tree."

Prior to the discovery of Gunakadeit joseeae, it had been two decades since scientists had thoroughly updated thalattosaur interrelationships, Druckenmiller said. The process of re-examining a prehistoric animal's family tree involves analyzing dozens and dozens of detailed anatomical features from fossil specimens worldwide, then using computers to analyze the information to see how the different species could be related.

Druckenmiller said he and collaborator Neil Kelley from Vanderbilt University were surprised when they identified where Gunakadeit joseeae landed.

"It was so specialized and weird, we thought it might be out at the furthest branches of the tree," he said. Instead it's a relatively primitive type of thalattosaur that survived late into the existence of the group.

"Thalattosaurs were among the first groups of land-dwelling reptiles to readapt to life in the ocean," Kelley said. "They thrived for tens of millions of years, but their fossils are relatively rare so this new specimen helps fill an important gap in the story of their evolution and eventual extinction."

That the fossil was found at all is a remarkable. It was located in rocks in the intertidal zone. The site is normally underwater all but a few days a year. In Southeast Alaska, when extreme low tides hit, people head to the beaches to explore. That's exactly what Jim Baichtal, a geologist with the U.S. Forest Service's Tongass National Forest, was doing on May 18, 2011, when low tides of -3.7 feet were predicted.

He and a few colleagues, including Gene Primaky, the office's information technology professional, headed out to the Keku Islands near the village of Kake to look for fossils. Primaky saw something odd on a rocky outcrop and called over Baichtal, "Hey Jim! What is this?" Baichtal immediately recognized it as a fossilized intact skeleton. He snapped a photo with his phone and sent it to Druckenmiller.

A month later, the tides were forecasted to be almost that low, -3.1 feet, for two days. It was the last chance they would have to remove the fossil during daylight hours for nearly a year, so they had to move fast. The team had just four hours each day to work before the tide came in and submerged the fossil.

"We rock-sawed like crazy and managed to pull it out, but just barely," Druckenmiller said. "The water was lapping at the edge of the site."

Once the sample was back at the UA Museum of the North, a fossil preparation specialist worked in two-week stints over the course of several years to get the fossil cleaned up and ready for study.

When they saw the fossil's skull, they could tell right away that it was something new because of its extremely pointed snout, which was likely an adaptation for the shallow marine environment where it lived.

"It was probably poking its pointy schnoz into cracks and crevices in coral reefs and feeding on soft-bodied critters," Druckenmiller said. Its specialization may have been what ultimately led to its extinction. "We think these animals were highly specialized to feed in the shallow water environments, but when the sea levels dropped and food sources changed, they had nowhere to go."

Once the fossil was identified as a new species, it needed a name. To honor the local culture and history, elders in Kake and representatives of Sealaska Corp. agreed the Tlingit name "Gunakadeit" would be appropriate. Gunakadeit is a sea monster of Tlingit legend that brings good fortune to those who see it. The second part of the new animal's name, joseeae, recognizes Primaky's mother, Joseé Michelle DeWaelheyns.

Under severe environmental stresses such as high temperature, dryness and high salination, cells survive by responding appropriately through elaborate mechanisms, according to new cell biology research from the Laboratory of Molecular Genetics at The Institute of Medical Science, the University of Tokyo. The results are expected to be useful for conferring environmental stress resistance to animals and plants to survive in severe environmental conditions caused by global warming, and also for developing methods of treating human diseases such as cancer and autoimmune diseases caused by dysregulation of the stress response machinery. Their recent research has been published in THE EMBO JOURNAL.

This research was conducted by Associate Professor Kazuo Tatebayashi at the University of Tokyo, in collaboration with Drs. Taichiro Tomida and Satomi Adachi-Akahane at Toho University, and Dr. Yuji Tokunaga of the National Institute of Advanced Industrial Science and Technology (AIST).

Lead scientist Kazuo Tatebayashi said "Organisms live while adapting to various environmental stresses. Our discovery is a breakthrough that clarified the mechanism of how cell sensors recognize danger and respond appropriately at the molecular level using budding yeast (*1). "

When cells are exposed to high osmolarity

The research group has focused on what is called "high osmolarity" as one of the environmental stresses. It is a condition that can be caused by high temperatures and dryness, which are closely related to global warming. For many years the research group has been investigating how cell sensors respond to this high osmolarity from various angles.

Sensors that respond to high osmolarity were previously known to be located on the outer cell membrane among life scientists specializing in cells. However, the research group found that a cytoplasmic sensor for high osmotic pressure exists in the Hog1 MAP kinase (MAPK) pathway(*2), which responds appropriately to high osmolarity and regulates osmoadaptation in budding yeast.

When cells are exposed to high osmolarity, the functionally redundant Sho1 and Sln1 osmosensors, respectively, activate the Ste11-Pbs2-Hog1 MAPK cascade and the Ssk2/Ssk22-Pbs2-Hog1 MAPK cascade. In a canonical MAPK cascade, a MAPK kinase kinase (MAP3K) activates a MAPK kinase (MAP2K) by phosphorylating two conserved Ser/Thr residues in the activation loop. The Research Group discover that the MAP3K Ste11 phosphorylates only one activating phosphorylation site (Thr-518) in Pbs2, whereas the MAP3Ks Ssk2/Ssk22 can phosphorylate both Ser-514 and Thr-518 under optimal osmostress conditions. Mono-phosphorylated Pbs2 cannot phosphorylate Hog1 unless the reaction between Pbs2 and Hog1 is enhanced by osmostress. The lack of the osmotic enhancement of the Pbs2-Hog1 reaction suppresses Hog1 activation by basal MAP3K activities and prevents pheromone-to-Hog1 crosstalk in the absence of osmostress. Please see: https://www.embopress.org/doi/10.15252/embj.2019103444)

Water moving into and out of cells affects flower freshness

Under low and high environmental osmolarity conditions, water moves into or out of cells, respectively. "For example, when we put a drooping flower in water, it will regain freshness.

" This is because water moves from an area of lower osmotic pressure to an area of higher osmotic pressure. When placed in water, the osmotic pressure in the environment surrounding the flower becomes lower, and the cells in the flower take up water and become fresh. On the other hand, if the surrounding environment is hot and dry, and the osmotic pressure becomes high, the water in the cells will be drained and dehydrated, and it will be in danger of survival, "says Tatebayashi.

When in high osmolarity, the cell activates a sensor that says, "You are now in danger.". There are various types of sensors that detect different environmental stresses to transmit such information in cells. Each type of sensor plays a different role in transmission, and controls environmental stress responses in conjunction with each other.

"Usually, the sensor that responds to the high osmotic pressure is in the cell membrane, which triggers a chain reaction of enzymes (called kinases) that phosphorylate another protein in the cell. When the first kinase phosphorylates the second kinase, the second kinase is activated, and then the second kinase phosphorylates the third kinase sequentially, so that the information is propagated and amplified. Our new finding shows that the phosphorylation of the third kinase is directly boosted by osmotic pressure, ensuring a much more accurate and robust response than previously thought possible," says Tatebayashi. As described above, our environmental stress response control system works very regularly and cooperatively to help maintain our health and life.

Future of environmental stress response control system

The full picture of how these mechanisms control environmental stress response in cells has not yet been elucidated. However, this discovery will open a new research direction that may reveal the detailed mechanisms of how these various cellular sensors respond and how they work together in the future.

In addition, the newly discovered regulatory mechanism of this MAP kinase pathway will be useful in human diseases, because many are caused by excessive or deficient activities of MAP kinase pathways. Based on these findings, we can anticipate development of treatments and therapeutics for human diseases such as cancer and autoimmune diseases in the future.

Walter and Eliza Hall Institute researchers have narrowed the focus on which survival proteins are important for the survival of B cell lymphomas, eliminating the protein BCL-W from the 'suspect list'.

Using gene editing technology, the research team showed that human B cell lymphoma cell lines can survive without BCL-W - dismissing this protein as a potential therapeutic target for these particular B cell lymphomas. The discovery upends earlier speculation that BCL-W could be an important survival factor for B cell lymphomas, and will focus future research efforts on more important targets.

The research, led by Dr Gemma Kelly and Dr Sarah Diepstraten, was published in the journal Blood Advances.

At a glance

BCL-W is a protein that prevents apoptotic cell death. Earlier research had suggested that BCL-W may be important for the survival of B cell lymphomas, making it an attractive therapeutic target.

Our researchers showed that BCL-W was not required for the survival of human B cell lymphoma cell lines.

This discovery suggests that medicines targeting BCL-W would not be effective treatments for the majority of B cell lymphomas.

Lymphoma survival factors

BCL-W is a member of the BCL-2 protein family, and promotes cancer cell survival by inhibiting apoptotic cell death. Other pro-survival members of the BCL-2 family, including the proteins BCL-2 and MCL-1, have shown promise as targets for anti-cancer drugs, particularly for certain leukaemias and lymphomas.

Dr Kelly said that recent research from other groups showed that many B cell lymphomas had increased levels of BCL-W, suggesting that this protein may promote cancer cell survival.

"This led to speculation that drugs targeting BCL-W could be useful for treating B cell lymphomas," she said.

Eliminating a suspect

To investigate whether inhibiting BCL-W could be effective in treating B cell lymphomas, the team reduced the amount of BCL-W protein within B cell lymphoma cell lines.

Dr Diepstraten said that in the B cell lymphoma cell lines tested, losing BCL-W did not impact cell survival. "We showed BCL-W was not required by these lymphoma cells, suggesting that drugs targeting BCL-W would not be effective treatments for all B cell lymphomas," Dr Diepstraten said.

"We also investigated the possibility that high levels of BCL-W in lymphomas might cooperate with other related survival proteins, such as BCL-2 or MCL-1, to promote survival," she said. "However, this was not the case: loss of BCL-W did not sensitise lymphoma cells to drugs that inhibit BCL-2 or MCL-1."

Shifting focus

Dr Kelly said the results showed that, at least for certain B cell lymphomas, targeting BCL-W should not be a priority for future research and drug development. "It is likely that other pro-survival proteins are much more important in these diseases," she said.

"BCL-W is considered to be a particularly appealing therapeutic target because it is not required for the function of most normal (non-cancerous) cells in the body, so we would not expect drugs targeting BCL-W to have significant side-effects.

"While BCL-W may not be a critical survival factor for B cell lymphomas, it is possible that BCL-W may contribute to the survival or drug resistance of other types of cancer - meaning that BCL-W inhibitors could be relevant in these cases," Dr Kelly said.

The work extends the Walter and Eliza Hall Institute's long-term interest in the proteins controlling apoptosis, and how they contribute to diseases including cancer. BCL-W was in fact discovered at the Institute - the 'W' stands for Walter and Eliza Hall Institute.

New research from the University of Notre Dame is shedding light on the unexpected effects climate change could have on regional instability and violent conflict.

Previous studies have linked drought to instances of intense conflict. As climate change is expected to bring hotter, dryer conditions to certain regions around the world, with it has come the expectation that conflict, too, will rise.

But this notion is more nuanced, according to the Notre Dame study, published in the Proceedings of the National Academy of Sciences.

"There is a strong scientific consensus that climate change will lead to more droughts in many regions of the world, and so often the prediction is made that through this mechanism, climate change leads to more conflict," said Michèle Müller-Itten, assistant professor in the Department of Economics at Notre Dame, and lead author of the study. "We show that the relationship isn't quite as straightforward, and in order to make valid predictions for a specific time and place, we need to know not just how the average growing conditions will change, but we also need to understand the variability of income."

For the study, Müller-Itten and her team considered a stylized theoretical model of how rainfall variability would impact two groups of farmers and how they might weigh the opportunity cost of lower yields versus the potential loot of conflict. The interdisciplinary team connected rainfall, crop and conflict models to analyze the implications of a realistic change in water availability. For example, climate change will lead to more frequent crop failure, which lowers the returns from farming, and hence the opportunity cost. At the same time, climate change also lowers the long-term profitability of farmland, which makes attacking less attractive. It is not clear which effect dominates.

"Many people think that climate change impacts automatically mean harsher conditions and thus more fighting," said Diogo Bolster, another co-author of the study, professor and Frank M. Freimann Collegiate Chair in Hydrology, and associate director of Notre Dame's Environmental Change Initiative. "However, if climate change also means fewer overall resources, and those resources are the incentive for fighting, the conflict may not be worth the cost."

The study provides a new perspective on how climate is a contributing factor to conflict and highlights how expectations and adaptation can change predicted outcomes.

"There are other mechanisms that could explain the past correlation between water availability and conflict. For global leaders, it is not enough to simply know that water and conflict happen to be related," said Müller-Itten. "For effective policy design, they need to understand the linkage. Our predictions offer a way to disentangle the possible explanations."

The number of political candidate television advertisements that refer to guns increased significantly across four election cycles in U.S. media markets, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

The study, to be published in the February issue of Health Affairs, analyzed more than 14 million televised campaign advertisements that aired for candidates running for president, U.S. Congress, governor, and state legislatures in 210 U.S. media markets over four election cycles in 2012, 2014, 2016, and 2018. The researchers found that the number of political ads aired that referenced guns increased by 369,600, an eightfold increase from one percent of candidate-related television political ads aired in 2012 to 8 percent in 2018.

Among the televised political ads aired that referenced guns, the share with gun regulation-oriented messages that were focused on reducing gun violence increased almost threefold over time-from 10 percent of all gun-related political ads aired in the 2012 election, to 37 percent in the 2018 election. Alternatively, pro-gun rights advertisements decreased from 86 percent of all gun-related political ads aired in the 2012 election, to less than half--46 percent--in the 2018 election.

"In the past, if guns were mentioned in political ads about candidates, it was in a pro-gun rights context," says lead author Colleen L. Barry, PhD, MPP, Fred and Julie Soper Professor and Chair of the Department of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health. "Our study indicates that a real shift has occurred in political discourse over the role of guns in our society. The upswing we are seeing in gun regulation messaging in political ads aimed at reducing gun violence is striking."

With gun-related deaths and mass shooting events on the rise in the U.S., gun policy has emerged as an important part of candidates' campaign policy platforms in the 2020 election cycle. Television advertisements remain an important tool for candidates to share their views on policy issues, including guns. In the 2016 election cycle, candidates spent over $6 billion dollars total on media, and the total cost in the 2020 election cycle is projected to reach $10 billion with nearly half spent on electronic media (broadcast and cable television and radio).

For the study, the researchers analyzed broadcast television ads collected by Kantar/CMAG, a campaign media analysis firm, and available through the Wesleyan Media Project. The Wesleyan Media Project is a research center based at Wesleyan University that tracks and analyzes advertising by candidates during elections. Researchers from the Wesleyan Media Project collaborated with the Bloomberg School research team on the study.

The study sample included 28,946 unique political ads that aired in 210 U.S. media markets 14 million times from the beginning of January the year before an election (2011, 2013, 2015, and 2017) through Election Day of the election year (2012, 2014, 2016, 2018). Ads were included if they mentioned a specific candidate for political office. Researchers excluded issue ads that did not mention a specific candidate for office and excluded airings on national network and national cable television.

The research team coded each unique ad based on audio and visual content. Researchers first identified ads referencing guns and then coded them for whether the gun reference in the ad was: pro-gun rights, pro-gun regulation, both, or neither. Researchers also coded for whether ads mentioned the National Rifle Association, and included a reference to support for or opposition to specific gun policies. The research team also examined where ads aired across the 210 U.S. media markets to identify geographic shifts overtime in gun-related references.

Over the four election cycles, five percent, or 721,238 of the 14.17 million campaign ads that aired on television, had gun-related references. Overall, 51 percent were gun rights references and 29 percent were gun regulation messages. For 20 percent of political aired ads, the reference to guns was more neutral in tone and did not include an overt gun rights or gun-regulation message.

Thirty-five percent of the political ads aired that referenced guns mentioned the NRA, and that share remained relatively stable over each of the four election cycles. However, researchers noted a shift over time from nearly all mentions of the NRA in political ads aired being pro-NRA in the 2012 election to an even split in the 2018 election between pro-NRA and anti-NRA references.

The researchers found that very few of the televised political ads that mentioned guns referenced specific policies. By far, the most commonly referenced policy was support of the Second Amendment. Twenty-one percent of gun-related ads mentioned support for the Second Amendment and this share was stable over each of the four election cycles. Only eight percent of political ads aired that mentioned guns included a reference to support for universal background checks. Eight percent also referenced a ban on assault weapons. Even fewer political ads, only five percent, mentioned support for restricting guns from dangerous people.

"We were surprised to see so few ads focused on keeping guns out of the hands of dangerous people," says Barry. "Extreme risk protection order laws temporarily removing guns from individuals at risk of gun violence have now been enacted by state legislatures around the country in the past couple of years. However, this approach to reducing gun violence has not yet become a major theme in political candidate advertising."

The study also found enormous geographic variation in the volume of candidate-related ads aired featuring gun rights versus gun regulation messages. Researchers identified five media markets with more than 10,000 gun rights ads aired in West Virginia and Montana. Media markets with 10,000 or more gun regulation ads aired were in Chicago, Philadelphia, Washington, D.C., and Miami.

Various locations in Alabama, Tennessee, South Dakota, and Georgia had the biggest increases in gun rights political ads aired over time. Shifts also occurred geographically in gun regulation messages. During the 2012 election cycle, no media markets had more than 1,000 pro-regulation airings. However, over the next three election cycles, media markets in New England, the Mid-Atlantic, and the West experienced substantial increases in candidate-related ads aired featuring gun regulation messages. These pro-regulation messages spread over time to new geographic regions including Colorado, New Mexico, Missouri, Minnesota, and other parts of Florida beyond Miami.

"We see substantial geographic differences in whether and how guns are mentioned in candidate-related political ads," says Barry. "Depending on where you live, you are likely to hear very different messages from candidates for political office about the role of guns in our society."

An international team of researchers has discovered the hydrogen atoms in a metal hydride material are much more tightly spaced than had been predicted for decades--a feature that could possibly facilitate superconductivity at or near room temperature and pressure.

Such a superconducting material, carrying electricity without any energy loss due to resistance, would revolutionize energy efficiency in a broad range of consumer and industrial applications.

The scientists conducted neutron scattering experiments at the Department of Energy's Oak Ridge National Laboratory on samples of zirconium vanadium hydride at atmospheric pressure and at temperatures from -450 degrees Fahrenheit (5 K) to as high as -10 degrees Fahrenheit (250 K)--much higher than the temperatures where superconductivity is expected to occur in these conditions.

Their findings, published in the Proceedings of the National Academy of Sciences, detail the first observations of such small hydrogen-hydrogen atomic distances in the metal hydride, as small as 1.6 angstroms, compared to the 2.1 angstrom distances predicted for these metals.

This interatomic arrangement is remarkably promising since the hydrogen contained in metals affects their electronic properties. Other materials with similar hydrogen arrangements have been found to start superconducting, but only at very high pressures.

The research team included scientists from the Empa research institute (Swiss Federal Laboratories for Materials Science and Technology), the University of Zurich, Polish Academy of Sciences, the University of Illinois at Chicago, and ORNL.

"Some of the most promising 'high-temperature' superconductors, such as lanthanum decahydride, can start superconducting at about 8.0 degrees Fahrenheit, but unfortunately also require enormous pressures as high as 22 million pounds per square inch, or nearly 1,400 times the pressure exerted by water at the deepest part of Earth's deepest ocean," said Russell J. Hemley, Professor and Distinguished Chair in the Natural Sciences at the University of Illinois at Chicago. "For decades, the 'holy grail' for scientists has been to find or make a material that superconducts at room temperature and atmospheric pressure, which would allow engineers to design it into conventional electrical systems and devices. We're hopeful that an inexpensive, stable metal like zirconium vanadium hydride can be tailored to provide just such a superconducting material."

Researchers had probed the hydrogen interactions in the well-studied metal hydride with high-resolution, inelastic neutron vibrational spectroscopy on the VISION beamline at ORNL's Spallation Neutron Source. However, the resulting spectral signal, including a prominent peak at around 50 millielectronvolts, did not agree with what the models predicted.

The breakthrough in understanding occurred after the team began working with the Oak Ridge Leadership Computing Facility to develop a strategy for evaluating the data. The OLCF at the time was home to Titan, one of the world's fastest supercomputers, a Cray XK7 system that operated at speeds up to 27 petaflops (27 quadrillion floating point operations per second).

"ORNL is the only place in the world that boasts both a world-leading neutron source and one of the world's fastest supercomputers," said Timmy Ramirez-Cuesta, team lead for ORNL's chemical spectroscopy team. "Combining the capabilities of these facilities allowed us to compile the neutron spectroscopy data and devise a way to calculate the origin of the anomalous signal we encountered. It took an ensemble of 3,200 individual simulations, a massive task that occupied around 17% of Titan's immense processing capacity for nearly a week--something a conventional computer would have required ten to twenty years to do."

These computer simulations, along with additional experiments ruling out alternative explanations, proved conclusively that the unexpected spectral intensity occurs only when distances between hydrogen atoms are closer than 2.0 angstroms, which had never been observed in a metal hydride at ambient pressure and temperature. The team's findings represent the first known exception to the Switendick criterion in a bimetallic alloy, a rule that holds for stable hydrides at ambient temperature and pressure the hydrogen-hydrogen distance is never less than 2.1 angstroms.

"An important question is whether or not the observed effect is limited specifically to zirconium vanadium hydride," said Andreas Borgschulte, group leader for hydrogen spectroscopy at Empa. "Our calculations for the material--when excluding the Switendick limit--were able to reproduce the peak, supporting the notion that in vanadium hydride, hydrogen-hydrogen pairs with distances below 2.1 angstroms do occur."

In future experiments, the researchers plan to add more hydrogen to zirconium vanadium hydride at various pressures to evaluate the material's potential for electrical conductivity. ORNL's Summit supercomputer--which at 200 petaflops is over 7 times faster than Titan and since June 2018 has been No. 1 on the TOP500 List, a semiannual ranking of the world's fastest computing systems--could provide the additional computing power that will be required to analyze these new experiments.

HAMILTON, Feb. 3, 2020 - A collaboration between McMaster and Harvard researchers has generated a new platform in which light beams communicate with one another through solid matter, establishing the foundation to explore a new form of computing.

Their work is described in a paper published today in the Proceedings of the National Academy of Sciences.

Kalaichelvi Saravanamuttu, an associate professor of Chemistry and Chemical Biology at McMaster, explains that the technology brings together a form of hyrdrogel developed by the Harvard team with light manipulation and measurement techniques performed in her lab, which specializes in the chemistry of materials that respond to light.

The translucent material, which resembles raspberry Jell-O in appearance, incorporates light-responsive molecules whose structure changes in the presence of light, giving the gel special properties both to contain light beams and to transmit information between them.

Typically, beams of light broaden as they travel, but the gel is able to contain filaments of laser light along their pathway through the material, as though the light were being channeled through a pipe.

When multiple laser beams, each about half the diameter of a human hair, are shone through the same material, the researchers have established that they affect one another's intensity, even without their optical fields overlapping at all - a fact that proves the gel is "intelligent."

The interaction between those filaments of light can be stopped, started, managed and read, producing a predictable, high-speed output: a form of information that could be developed into a circuit-free form of computing, Saravanamuttu explains.

"Though they are separated, the beams still see each other and change as a result," she says. "We can imagine, in the long term, designing computing operations using this intelligent responsiveness."

While the broader concept of computing with light is a separate and developing field unto itself, this new technology introduces a promising platform, says Derek Morim, a graduate student in Saravanamuttu's lab who is co-first author on the paper.

"Not only can we design photoresponsive materials that reversibly switch their optical, chemical and physical properties in the presence of light, but we can use those changes to create channels of light, or self-trapped beams, that can guide and manipulate light," he says. "Further study may allow us to design even more complex materials to manipulate both light and material in specific ways."

Amos Meeks, a graduate student at Harvard's John A. Paulson School of Engineering and Applied Sciences, said the technology helps to advance the idea of all-optical computing, or computations done solely with beams of light.

"Most computation right now uses hard materials such as metal wires, semiconductors and photodiodes, to couple electronics to light," said Meeks, who is also co-first author of the research. "The idea behind all optical computing is to remove those rigid components and control light with light. Imagine, for example, an entirely soft, circuitry-free robot driven by light from the sun."

A new Scientific Reports paper puts an evolutionary twist on a classic question. Instead of asking why we get cancer, Leonardo Oña of Osnabrück University and Michael Lachmann of the Santa Fe Institute use signaling theory to explore how our bodies have evolved to keep us from getting more cancer.

It isn't obvious why, when any cancer arises, it doesn't very quickly learn to take advantage of the body's own signaling mechanisms for quick growth. After all, unlike an infection, cancers can easily use the body's own chemical language. "Any signal that the body uses, an infection has to evolve to make," says Lachmann. "If a thief wants to unlock your house, they have to figure out how to pick the lock on the door. But cancer cells have the keys to your house. How do you protect against that? How do you protect against an intruder who knows everything you know, and has all the tools and keys you have?" Their answer: You make the keys very costly to use.

Oña and Lachmann's evolutionary model reveals two factors in our cellular architecture that thwart cancer: the expense of manufacturing growth factors ("keys") and the range of benefits delivered to cells nearby. Individual cancer cells are kept in check when there's a high energetic cost for creating growth factors that signal cell growth. To understand the evolutionary dynamics in the model, the authors emphasize the importance of thinking about the competition between a mutant cancerous cell and surrounding cells. When a mutant cell arises and puts out a signal for growth, that signal also provides resources to adjacent, non-mutated cells. Thus, when the benefits are distributed to a radius around the signaling cell, the mutant cells have a hard time out-competing their neighbors and can't get established. The cancer loses the ability to give the signal.

The work represents a novel application of evolutionary biology toward a big-picture understanding of cancer. Oña and Lachmann draw from the late biologist Amos Zahavi's handicap principle, which explains how evolutionary systems are stabilized against "cheaters" when dishonest signals are costlier to produce than the benefit they provide. The male peacock's elaborate tail is the classic example of a costly signal - an unhealthy bird would not have the energetic resources to grow an elaborate tail, and thus could not "fake" a signal of their evolutionary fitness. By the handicap principle, a cancer cell would be analogous to the unhealthy peacock that can't afford to signal for attention.

So how do some cancer cells overcome these evolutionary constraints? The authors point out that their model only addresses the scenario of an individual cancer trying to invade a healthy population. Once a cancer has overcome the odds of extinction and reached a certain critical size, other dynamics prevail.

"Many mechanisms seem to have evolved to prevent cancer -- from immune system control, cell death, limits on cell proliferation, to tissue architecture," the authors write. "Our model only studies the reduced chance for invasion."

"Cancer is incredibly complex," Lachmann says, "and our model is relatively simple. Still, we believe it's an important step toward understanding cancer and cancer prevention in evolutionary terms."

NASA's Terra satellite saw yet another fire, known as the Orroral Valley Fire, break out in the Canberra region of Australia, specifically in and around the ?Namadgi National Park. In one week, these fires have consumed 62,988 hectares (155,646 acres) according to the Australian Capital Territory Emergency Services Agency as of Feb. 04, 2020 (2:30 am local Australian time). The Department of Defence in Australia has reported that a firefighting helicopter's landing lights created the heat needed to spark the new fire. Since the area is tinder-dry, any bit of heat can provide the ignition for a new blaze. Below is a sliding image showing the true- and false-color images of the fire on Feb. 03, 2020 taken by the Terra satellite using the MODIS (Moderate Resolution Imaging Spectroradiometer) instrument. The dark red-brown color represents areas where the fires have burned the land.

NASA/NOAA's Suomi NPP satellite also captured an image of the fires using their Day/Night band on the VIIRS ?(Visible Infrared Imaging Radiometer Suite) instrument. At night the fires can clearly be seen in this image from February 02, 2020. The fire line of the new blaze is extremely close to the city of Canberra, the capital of Australia. This area is under a State of Emergency until at least Sunday. Fire crews have, to date, been able to save all structures in the Australian Capital Territory.

NASA's satellite instruments are often the first to detect wildfires burning in remote regions, and the locations of new fires are sent directly to land managers worldwide within hours of the satellite overpass. Together, NASA instruments detect actively burning fires, track the transport of smoke from fires, provide information for fire management, and map the extent of changes to ecosystems, based on the extent and severity of burn scars. NASA has a fleet of Earth-observing instruments, many of which contribute to our understanding of fire in the Earth system. Satellites in orbit around the poles provide observations of the entire planet several times per day, whereas satellites in a geostationary orbit provide coarse-resolution imagery of fires, smoke and clouds every five to 15 minutes. For more information visit: https://www.nasa.gov/mission_pages/fires/main/missions/index.html