Earth

Oncotarget published "Landscape of somatic mutations in breast cancer: new opportunities for targeted therapies in Saudi Arabian patients" which reported that the association between genetic polymorphisms in tumor suppressor genes and the risk of BCa has been studied in many ethnic populations with conflicting conclusions while Arab females and Saudi Arabian studies are still lacking.

The authors screened a cohort of Saudi BCa patients by NGS using a bespoke gene panel to clarify the genetic landscape of this population, correlating and assessing genetic findings with clinical outcomes.

They identified a total of 263 mutations spanning 51 genes, including several frequently mutated.

Among the genes analyzed, the highest mutation rates were found in PIK3CA, BRCA2, BRCA1, TP53, MSH2, PMS2, BARD1, MLH1, CDH1, RAD50, MSH6, NF1, in addition to others.

They identified multiple common recurrent variants and previously reported mutations.

They also reveal the landscape of the mutations associated with BCa in Saudi women, highlighting the importance of routine genetic sequencing in implementation of precision therapies in KSA.

Dr. Malak Abedalthagafi from The King Fahad Medical City and King Abdulaziz City for Science and Technology said, "Worldwide, breast cancer is the most common cancer in women."

"Worldwide, breast cancer is the most common cancer in women."

A positive ER and/or PR, either positive HER2 or negative HER2, and high levels of Ki67 suggest a luminal B BCa subtype, which makes up less than 20% of all BCa cases and has lower survival rates than luminal A.

The absence of ER and PR expression accompanied by high expression of HER2 and proliferation gene clusters and low expression of luminal and basal clusters, as detected by IHC, suggests a HER2-enriched BCa subtype, which accounts for 10% to 15% of all cases and has a poorer prognosis than luminal cancers.

Three significant pathways govern mammary gland and BCa stem cell development:

Estrogen receptor signaling;

HER2 signaling; and

Canonical Wnt signaling.

In ER signaling, estrogen binds membrane estrogen receptors and triggers a cascade of events that ultimately promote the binding of nuclear estrogen receptors with estrogen response elements.

Other pathways involved in BCa development include cyclin-dependent kinase signaling, notch signaling, sonic hedgehog signaling, breast tumor kinase signaling, and PI3K/AKT/mTOR signaling.

WES also facilitated both the identification of the FANCM gene as a susceptible gene for triple-negative BCa and the association of XCR1, DLL1, TH, ACCS, SPPL3, CCNF and SRL with BCa.

In this study, they screened a cohort of Saudi BCa patients using a cancer-specific gene panel to ascertain the mutation spectrum and explore the possible clinical implications of the identified somatic variants in BCa development.

The Abedalthagafi Research Team concluded in their Oncotarget Research Output that the authors identified somatic mutation variants in Saudi BCa patients; BRCA1, BRCA2, TP53, and PIK3CA were found to be among the most common.

In total, they identified 39 novel mutations that were not reported before and were predicted to be pathogenic.

Their study has pertinent limitations.

Further, their limited sample size, particularly for limited somatic genomics aberrations analyzes, may limit generalizability.

More regional studies are still needed.

A new study published in the journal Diversity and Distributions predicts massive range declines of Africa's great apes - gorillas, chimpanzees and bonobos - due to the impacts of climate change, land-use changes and human population growth.

For their analysis, the authors compiled information on African ape occurrence held in the IUCN SSC A.P.E.S. database, a repository that includes a remarkable amount of information on population status, threats and conservation for several hundred sites, collected over 20 years.

The first-of-its-kind study quantifies the joint effects of climate, land-use, and human population changes across African ape ranges for the year 2050 under best- and worst-case scenarios. "Best case" implies slowly declining carbon emissions and that appropriate mitigation measures will be put in place. "Worst case" assumes that emissions continue to increase unchecked - business as usual.

Under the best-case scenario, the authors predict that great apes will lose 85 percent of their range, of which 50 percent will be outside national parks and other areas protected by legislation. Under the worst-case scenario, they predict a 94 percent loss, of which 61 percent will be in areas that are not protected.

This paper examines whether great apes can or cannot disperse away from where they are currently found, and the best- and worst-case scenarios in each case. For example, mountains are currently less suitable than lowland areas for some great ape species. However, climate change will render some lowlands less suitable - warmer, drier, perhaps less food available - but the nearby mountains will take on the characteristics that those lowlands currently have. If great apes are able to physically move from the lowlands to the mountains, they may be able to survive, and even increase their range (depending on the species, and whether it is the best- or worst-case scenario). However, they may not be able to travel (disperse) away from the lowlands in the time remaining between today and 2050.

Joana Carvalho, postdoctoral researcher in the Faculty of Science, Liverpool John Moores University, lead author of the study says: "By integrating future climate and land-use changes as well as human population scenarios, this study provides strong evidence for synergistic interactions among key global drivers constraining African ape distribution."

Carvalho adds: "Importantly, massive range loss is widely expected outside protected areas, which reflects the insufficiency of the current network of protected areas in Africa to preserve suitable habitats for great apes and effectively connect great ape populations."

Fiona Maisels of the Wildlife Conservation Society (WCS), and a co-author of the study, said: "As climate change forces the different types of vegetation to essentially shift uphill, it means that all animals - not only great apes - that depend on particular habitat types will be forced to move uphill along with the vegetation, or become locally extinct. And when the hills are low, many species, great and small, will not be able go higher than the land allows, and huge numbers of animals and plants will simply vanish."

The authors argue that effective conservation strategies require careful planning for each species that focuses on both existing and proposed protected areas - the creation and management of which can be informed by these habitat suitability models. Additionally, efforts to maintain connectivity between the habitats predicted to be suitable in the future will be crucial for the survival of African apes. Conservation planners urgently need to integrate land-use planning and climate change mitigation and adaptation measures into government policy of great ape range countries.

The study highlights the need for urgent action to combat both biodiversity loss and climate change if great apes are to continue into the future. Governments must protect and conserve the habitats of great apes--where they are now, and where they will need to move. Governments attending the upcoming Convention on Biological Diversity CoP 15 in September and the UN Climate Change Conference in November should adopt meaningful commitments to protect and conserve great apes and their habitats and combat climate change.

The results of the study corroborate other recent studies showing that African ape populations and their habitats are declining dramatically. All African great apes are classified either as Endangered (mountain gorillas, bonobos, Nigeria-Cameroon chimpanzees, eastern chimpanzees, and central chimpanzees) or Critically Endangered (Cross River gorillas, Grauer's gorillas, western lowland gorillas, and western chimpanzees) on the IUCN Red List of Threatened Species, and all are regarded as flagship species for conservation.

Hjalmar Kuehl, from iDiv in Leipzig, Germany, and senior author of the study said: "There must be global responsibility for stopping the decline of great apes. Global consumption of natural resources extracted from ape range countries is a major driver of great ape decline. All nations benefitting from these resources have a responsibility to ensure a better future for great apes, their habitats and the people living therein by developing more sustainable economies."

Oncotarget published "Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma" which reported that although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy.

Using quantitative multiplex immunohistochemistry, the authors analyzed skin squamous-cell carcinoma (sSCC) sections from 36 patients.

CD8 T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8 T cell density in tumor areas.

An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density.

Since both metastasis and perineural infiltration are known to affect tumor progression and patients' prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. This Oncotarget data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma.

Dr. Karin Schaeuble from The University Hospital Lausanne said, "Over the last few years, oncology research is increasingly focused on the understanding of mutual interactions between cancer, stromal and immune cells in the tumor microenvironment."

"Over the last few years, oncology research is increasingly focused on the understanding of mutual interactions between cancer, stromal and immune cells in the tumor microenvironment."

Specific growth factors like vascular endothelial growth factor -C and -D secreted by tumor cells and/or immune cells stimulate lymphangiogenesis in the vicinity of the tumor.

Lymphatic vessels offer a route for cancer cells to disseminate, enhanced by secretion of different chemokines such as CCL21 that actively supports tumor cell invasion into lymphatic vessels and promotes lymph node metastases.

Investigations into the immune cell composition showed the presence of various immune cells in sSCC.

On the other hand, the presence of lymphatic vessels in the tumour immune microenvironment (TME) has also been shown to support adaptive anti-tumoral immune responses by carrying immune cells and antigens to the draining LNs.

For further investigation of possible associations of lymphatic vessels with stroma and T cells, they performed a comprehensive analysis of the abundance and localization of lymphatic vessels in 36 patients with sSCC.

The Schaeuble Research Team concluded in their Oncotarget Research Output that an entirely new observation is that perineural infiltrated sSCC in absence of metastases are characterized by low LVD compared to tumors without PNI.

Since both are known to affect tumor progression and patients' prognosis, it may be particularly important to identify the underlying mechanisms triggering either lymphangiogenesis or PNI, thus opening future options for therapeutic targeting.

AMES, Iowa - Scientists have invested great time and effort into making connections between a plant's genotype, or its genetic makeup, and its phenotype, or the plant's observable traits. Understanding a plant's genome helps plant biologists predict how that plant will perform in the real world, which can be useful for breeding crop varieties that will produce high yields or resist stress.

But environmental conditions play a role as well. Plants with the same genotype will perform differently when grown in different environments. A new study led by an Iowa State University scientist uses advanced data analytics to help scientists understand how the environment interacts with genomics in corn, wheat and oats. The results could lead to more accurate and faster models that will allow plant breeders to develop crop varieties with desirable traits.

The study was published recently in the peer-reviewed academic journal Molecular Plant.

Jianming Yu, a professor of agronomy and the Pioneer Distinguished Chair in Maize Breeding, said the study sheds light on phenotypic plasticity, or the ability of crops to adapt to environmental changes. This could help plant breeders get a better understanding of how "shapable" plant species are, or how much potential they have to perform well in different environments.

"We knew that genetic performance is context dependent. It's not static; It's dependent on environmental conditions," said Xianran Li, an adjunct associate professor and the first author of the study. "Two alleles of a gene perform differently in one environment but the same in another. What is challenging is to understand the interplay between genes and the environment under the natural field conditions. The obvious obstacle is that natural environments are much more complex than controlled laboratory conditions. How can we detect the major signals plants perceive?"

The study made use of previously gathered data on the three crop species from across the globe. A group of 17 scientists from four institutions contributed to the current study, but a much larger group of scientists carried out the initial experiments that generated the data. The dataset included 282 inbred lines of corn evaluated in the United States and Puerto Rico; 288 inbred lines of wheat evaluated in Africa, India and Middle Eastern countries; and 433 inbred populations of oats evaluated in the United States and Canada. The data included environmental conditions such as temperature and availability of sunlight. The phenotypic data analyzed in the study included yields, plant height and flowering time, or the window of time during which the plant reaches the reproductive stage.

Advanced data analytics allowed the researchers to develop an environmental index, extracting the major differentiating pattern among the studied natural field conditions. With this explicit environmental dimension defined, how individual genes respond to external signals and collectively lead to the varied final performance of an organism can be systematically evaluated.

"It is like the undiscernible pulses of a plant's perception of the outside conditions now become visible on a monitor screen," said Tingting Guo, a research scientist in agronomy and co-first author of the study.

The study "presents an integrated framework that not only reveals the genetic effect dynamics along an identified environmental index but also enables accurate performance predictions and forecasting," the authors wrote in the paper.

"We are pleased to be able to design such a framework to cover two major research areas, genome-wide association studies and genomic selection (GWAS and GS)," Yu said.

The study found the integrated framework predicted flowering time and plant height accurately, while predictions for yields were more difficult. Li said that's most likely due to how many different environmental parameters, beyond just temperature and sunlight, affect yield at different growth stages. The research team will continue refining its methods to account for more environmental factors in an effort to better predict yields.

Yu and his collaborators first developed their initial data analytics in sorghum but have since expanded their research to include other major global crops. This could help plant scientists design a better plan for finding varieties to test. Yu said applying advanced data analytics to all the available genomic, phenotypic and environmental data can help breeders zero in on varieties they're interested in much faster and more efficiently.

"We believe we have the requisite amount of data to make better predictions about plant performance," Yu said. "Now, we're trying to gain knowledge and wisdom from the data to guide the real-world decision-making process."

CAMBRIDGE, MA -- About 60 percent of drugs on the market have hydrophobic molecules as their active ingredients. These drugs, which are not soluble in water, can be difficult to formulate into tablets because they need to be broken down into very small crystals in order to be absorbed by the human body.

A team of MIT chemical engineers has now devised a simpler process for incorporating hydrophobic drugs into tablets or other drug formulations such as capsules and thin films. Their technique, which involves creating an emulsion of the drug and then crystallizing it, allows for a more powerful dose to be loaded per tablet.

"This is very important because if we can achieve high drug loading, it means that we can make smaller dosages that still achieve the same therapeutic effect. This can greatly improve patient compliance because they just need to take a very small drug and it's still very effective," says Liang-Hsun Chen, an MIT graduate student and the lead author of the new study.

Patrick Doyle, the Robert T. Haslam Professor of Chemical Engineering, is the senior author of the paper, which appears today in Advanced Materials.

Nanoemulsions

Most medicines consist of an active ingredient that is combined with other compounds called excipients, which help to stabilize the drug and control how it is released in the body. The resulting tablets, capsules, or films are called formulations.

Currently, to create formulations of hydrophobic drugs, pharmaceutical companies use a process that requires milling the compound down to nanocrystals, which are easier for human cells to absorb. These crystals are then blended with excipients. One excipient that is often mixed with hydrophobic drugs is methylcellulose, a compound derived from cellulose. Methylcellulose dissolves easily in water, which helps drugs to be released faster in the body.

This method is widely used, but has many inefficiencies, according to the MIT team. "The milling step is very time consuming and energy intensive, and the abrasive process can cause changes in active ingredient properties, which can undermine the therapeutic effects," Chen says.

He and Doyle set out to come up with a more efficient way to combine hydrophobic drugs with methylcellulose, by forming an emulsion. Emulsions are mixtures of oil droplets suspended in water, such as the mixture formed when an oil and vinegar salad dressing is shaken up.

When these droplets are on the scale of nanometers in diameter, this kind of mixture is called a nanoemulsion. To create their nanoemulsion, the researchers took a hydrophobic drug called fenofibrate, which is used to help lower cholesterol, and dissolved it in an oil called anisole. Then they combined this oil phase with methylcellulose dissolved in water, using ultrasonication (sound waves) to create nanoscale oil droplets. Methylcellulose helps to keep the water and oil droplets from separating again because it is amphiphilic, meaning that it can bind to both the oil droplets and the water.

Once the emulsion is formed, the researchers can transform it into a gel by dripping the liquid into a heated water bath. As each drop hits the water, it solidifies within milliseconds. The researchers can control the size of the particles by changing the size of tip that is used to drip the liquid into the water bath.

"The particle formation is nearly instantaneous, so everything that was in your liquid drop gets converted to a solid particle without any loss," Doyle says. "After drying, we have nanocrystals of fenofibrate uniformly distributed in the methylcellulose matrix."

Smaller pills, more drug

Once the nanocrystal-loaded particles are formed, they can be crushed into powder and then compressed into tablets, using standard drug manufacturing techniques. Alternatively, the researchers can pour their gel into molds instead of dripping it into water, allowing them to create drug tablets in any shape.

Using their nanoemulsion technique, the researchers were able to achieve drug loading of about 60 percent. In contrast, the currently available formulations of fenofibrate have a drug concentration of about 25 percent. The technique could be easily adapted to load even higher concentrations by increasing the ratio of oil to water in the emulsion, the researchers say.

"This can enable us to make more effective and smaller drugs that are easier to swallow, and that can be very beneficial for many people who have difficulty swallowing drugs," Chen says.

This method can also be used to make thin films -- a type of drug formulation that has become more widely used in recent years, and is especially beneficial for children and older people. Once a nanoemulsion is made, the researchers can dry it into a thin film that has drug nanocrystals embedded in it.

It is estimated that about 90 percent of the drugs now in development are hydrophobic, so this approach could potentially be used to develop formulations for those drugs, as well as hydrophobic drugs that are already in use, the researchers say. Many widely used drugs, including ibuprofen and other anti-inflammatory drugs such as ketoprofen and naproxen, are hydrophobic.

"The flexibility of the system is that we can choose different oils to load different drugs, and then make it into a nanoemulsion using our system. We don't need to do a lot of trial-and-error optimization because the emulsification process is the same," Chen says.

Many mainstream depictions of immigration at the southern border of the United States paint a dark picture, eliciting imagery of violent gang members and child trafficking. But how many undocumented immigrants are really involved in this kind of activity? Many people may be surprised to learn the answer is far fewer than they think.

A new study from the Peace and Conflict Neuroscience Lab (PCNL) at the Annenberg School for Communication found that Americans dramatically overestimate the number of migrants affiliated with gangs and children being trafficked, and that this overestimation contributes to dehumanization of migrants, lack of empathy for their suffering, and individuals' views on immigration policy. In addition, the researchers developed and tested interventions to address this misinformation and increase empathy for undocumented immigrants.

"We noticed that false narratives about undocumented immigrants as criminals or as having criminal intentions are commonly circulated in the public," says Samantha Moore-Berg, a PCNL postdoctoral fellow and lead author of the study. "We were curious about the impact of these narratives on attitudes toward immigrants and immigration policy support, and whether by correcting these narratives, we are able to foster more positive attitudes toward immigrants."

The study aimed to compile data on Americans' (mis)perceptions of immigrants' motivations for crossing the southern border, determine whether those (mis)perceptions affected Americans' policy positions, and develop successful interventions for addressing (mis)perceptions and increasing empathy.

Study participants, on average, estimated that 15% of migrants at the southern border are affiliated with gangs and 25 to 35% of children at the southern border are being used as props by adults who are not their parents for immigration purposes. In reality, the Department of Homeland Security suspects approximately 1% of immigrants have gang connections and fewer than 0.1% of children are being trafficked.

The researchers found that participants' erroneous beliefs about immigrants affected their views on immigration policy and caused them to view immigrants with less empathy and to dehumanize them more. However, after a successful intervention, which included viewing the correct statistics on immigrant behavior and watching an emotional video of an immigrant parent and child being reunited after the U.S. separated them at the border, participants' levels of empathy for immigrants increased, their dehumanization of immigrants decreased, and their support of less punitive immigration policy increased.

"By both correcting these false narratives about immigrants and unlocking empathy toward them, we were able to foster more positive attitudes toward immigrants and encourage greater support for more humane immigration policies" Moore-Berg says. "This gives us hope that by shifting narratives about immigrants to be both more accurate and empathetic, we can ultimately foster greater acceptance of immigrants."

"Empathy, Dehumanization, and Misperceptions: A Media Intervention Humanizes Migrants and Increases Empathy for Their Plight, but Only If Misinformation about Migrants Is Also Corrected," was published today in Social Psychological and Personality Science. In addition to Moore-Berg, authors include Boaz Hameiri (Tel Aviv University) and the late Emile Bruneau.

Once viewed merely as a producer of the cerebrospinal fluid (CSF) bathing the brain and spinal cord, the choroid plexus is now known to be a key player in brain development and immunity. These fronds of brain tissue, located in the CSF-filled brain cavities known as ventricles, secrete instructive cues into the CSF to regulate brain development. They also function as an important barrier between the brain and the rest of the body.

Maria Lehtinen, PhD, of Boston Children's Hospital has done much of the pioneering work in understanding this once-obscure tissue. In new work published in Cell, Lehtinen, Neil Dani, PhD, and other colleagues at Boston Children's and the Broad Institute created a cellular and spatial "atlas" of the choroid plexus during different life stages (early development, adulthood, old age).

The map provides a benchmark to accelerate future studies investigating the lifelong regulation of this diminutive but influential brain structure.

"To fully understand the choroid plexus and its functions, we needed to identify its constituent cell types and their molecular composition," says Dani, who was co-first author on the paper with Rebecca Herbst, a PhD student at the Broad Institute. "Such insights had been missing in the community."

Extracting choroid plexus tissue

Isolating choroid plexus tissue from embryonic, adult, and aged mice was a job in itself. It required special micro-dissection approaches since these tissues lie deep within the brain's ventricles.

"Figuring out how to dissect out intact third-ventricle choroid plexus was particularly challenging," says Dani.

With tissue from each of the animals' three ventricles in hand, the researchers performed RNA sequencing of more than 98,000 cells and cell nuclei to compare their gene expression profiles (what genes were turned on or off). This enabled them to catalog different cell types and subtypes in choroid plexus from each ventricle, across different ages -- the first time this has ever been done.

"We had previously done bulk RNA sequencing of choroid plexus tissue, but that was like putting everything in a blender," says Lehtinen, who was co-senior author on the paper with Naomi Habib, PhD and Aviv Regev, PhD at the Broad Institute. "We didn't know which cells were secreting what. Sequencing cell by cell gives us a blueprint of what cells are where over the course of the lifespan. Knowing the different types of cells, we can explore their roles and functions, how they are talking to each other, and how the tissue is built."

A choroid plexus inventory

The investigations revealed a complex "architecture" of choroid plexus tissue specific to each ventricle. Gene expression varied especially among epithelial and fibroblast cells in the developing brain.

"We think the differences might have to do with helping guide the development of nearby brain regions," says Lehtinen. "There are different 'cocktails' of factors secreted into different ventricles, in different patterns."

In addition to the core cell types, the researchers found several neuronal subtypes. "Typically, the choroid plexus is not thought to have too many neurons," says Lehtinen. "What they're doing in the choroid plexus is still up for discussion and experimentation."

The sequencing data also revealed differences in the cells' secretions and molecular makeup.

"We were intrigued by the expression of insulin in the epithelial cells of the developing third ventricle choroid plexus," says Dani. "Whether this is a viable and functional central source of insulin in the brain needs further investigation. We also found that some epithelial and mesenchymal cells expressed ACE2 receptors, which the SARS-CoV-2 virus uses to enter cells. This underscores the need to understand how the choroid plexus functions not just in health but in disease."

Defending the brain

The team found a great deal of immune activity in the choroid plexus, with several kinds of immune cells residing there, most commonly macrophages. Immune signaling activity varied with age, with more inflammatory signals picked up in samples from aged brains.

"We can now start to analyze how different populations of immune cells are activated and how they respond to injury," says Lehtinen. "This gives us a baseline and a set of molecular markers to start looking at."

Other findings revealed the arrangement of arteries, veins, and capillaries in the choroid plexus, and their organization in relation to adjacent brain regions.

"Some of these vessels expressed blood-brain barrier proteins, which was not described before" notes Dani. "Once we mapped them, we found them to be continuous with arteries from adjacent brain regions."

A therapeutic 'window'?

With this resource in hand, the scientific community now has much to explore. Lehtinen and Dani believe that once the choroid plexus is better understood, it could provide a target for neurologic drugs.

"Gene therapy directed toward the CSF and choroid plexus could be an exciting therapeutic approach," says Lehtinen. "It's not going to fix everything, but it could have a sizeable impact."

In other work, Lehtinen and colleagues recently showed that before birth, the choroid plexus can be a conduit for inflammation caused by maternal infection, paving the way for studies of neurodevelopmental conditions such as autism. Another study found that a protein in the choroid plexus helps reduce excess fluid levels in the brain, potentially providing a target for treating hydrocephalus.

The world is one step closer to ultimately secure conference calls, thanks to a collaboration between Quantum Communications Hub researchers and their German colleagues, enabling a quantum-secure conversation to take place between four parties simultaneously.

The demonstration, led by Hub researchers based at Heriot-Watt University and published in Science Advances, is a timely advance, given the global reliance on remote collaborative working, including conference calls, since the start of the C19 pandemic.

There have been reports of significant escalation of cyber-attacks on popular teleconferencing platforms in the last year. This advance in quantum secured communications could lead to conference calls with inherent unhackable security measures, underpinned by the principles of quantum physics.

Senior author, Professor Alessandro Fedrizzi, who led the team at Heriot-Watt, said: "We've long known that quantum entanglement, which Albert Einstein called 'spooky action at a distance' can be used for distributing secure keys. Our work is the first example where this was achieved via 'spooky action' between multiple users at the same time -- something that a future quantum internet will be able to exploit."

Secure communications rely upon the sharing of cryptographic keys. The keys used in most systems are relatively short and can therefore be compromised by hackers, and the key distribution procedure is under increasing threat from quickly advancing quantum computers. These growing threats to data security require new, secure methods of key distribution.

A mature quantum technology called Quantum Key Distribution (QKD), deployed in this demonstration in a network scenario for the first time, harnesses the properties of quantum physics to facilitate guaranteed secure distribution of cryptographic keys.

QKD has been used to secure communications for over three decades, facilitating communications of over 400km over terrestrial optical fibre and recently even through space, however, crucially, these communications have only ever occurred exclusively between two parties, limiting the practicality of the technology used to facilitate secure conversations between multiple users.

The system demonstrated by the team here utilises a key property of quantum physics, entanglement, which is the property of quantum physics that gives correlations - stronger than any with which we are familiar in everyday life - between two or more quantum systems, even when these are separated by large distances.

By harnessing multi-party entanglement, the team were able to share keys simultaneously between the four parties, through a process known as 'Quantum Conference Key Agreement', overcoming the limitations of traditional QKD systems to share keys between just two users, and enabling the first quantum conference call to occur with an image of a Cheshire cat shared between the four parties, separated by up to 50 km of optical fibre.

Entanglement-based quantum networks are just one part of a large programme of work that the Quantum Communications Hub, which is funded by EPSRC as part of the UK National Quantum Technologies Programme, is undertaking to deliver future quantum secured networks.

The technology demonstrated here has potential to drastically reduce the resource costs for conference calls in quantum networks when compared to standard two-party QKD methods. It is one of the first examples of the expected benefits of a future quantum internet, which is expected to supply entanglement to a system of globally distributed nodes.

Researchers at the University of Adelaide have used more than two decades of satellite-derived environmental data to form hypotheses about the possible foraging habitats of pre-contact Aboriginal peoples living in Australia's Western Desert.

As one of the most arid and geographically remote regions of Australia, the Western Desert has always presented severe challenges for human survival. Yet despite the harsh conditions, Aboriginal peoples have maintained an enduring presence, continuously adapting to environmental variations through complex socioeconomic strategies.

In the study published in Scientific Reports, the researchers used Earth Observation data to model the most suitable habitats for traditional foraging activities, identifying where surface water was most abundant and vegetation was greenest to infer which areas of the landscape past Aboriginal peoples were likely to have utilised. The study also drew on previous research into traditional subsistence and settlement practices, enabling researchers to estimate daily foraging range in proximity to water.

Lead author of the study, Postdoctoral Researcher Dr Wallace Boone Law, says the fine scale of the satellite model developed enabled the team to depict the highly variable nature of environmental and hence potential foraging habitats in the Western Desert.

"Where earlier studies depicted the Western Desert as a relatively uniform environment, our study shows the region to be highly dynamic and variable, both in its environmental conditions and foraging potential," Dr Law said.

"For example, desert dunefields were once thought to have been a periodic barrier to occupation, but our work shows this is not true for all sandridge deserts. Some dunefield areas offer good foraging habitats, particularly amongst interdunal swale areas.

"However, we also found that there are large, impoverished regions of the Western Desert that would have been extremely challenging for survival, based on terrain ruggedness and access to food and water resources.

"We believe it is likely that some of these poorly-suited foraging areas would have been difficult for survival for the past 21,000 years, and because Aboriginal peoples were highly knowledgeable about the distribution of resources across the Western Desert, we hypothesise those locations would have been rarely used in the past. And further, we predict that the archaeological record of these difficult habitats will point to ephemeral episodes of occupation.

"We suggest that some low-ranked areas of habitat suitability were resource-poor and not economically attractive to foraging activities, even in the best environmental circumstances," said Dr Law.

The researchers hope that archaeologists can use the study to explore many large areas of the Western Desert that have yet to be thoroughly investigated.

"Our findings highlight how future models of forager land use can be integrated with Earth Observation data to better comprehend the environmental complexity and fine scale of resource variability in these vast, remote and diverse places," said Dr Law.

"We hope our research into the changing environment in pre-contact Australia will assist with fostering a new era of research in partnership with Indigenous communities to provide further understanding of the industrious, versatile and resilient Aboriginal peoples of the Western Desert."

In the Kumano Sea, off the southeast coast of Japan, an evolutionary mystery lay in wait. Researchers collected samples from the muddy sea floor, including hermit crabs, mollusks and discarded shells. Here, in and on these shells, they found scale worms living mostly in pairs with a striking difference compared to the almost 900 already known species of scale worms: one was a quarter the size of its mate.

The discovery was published on March 29 as the cover of the Journal of Zoological Systematics and Evolutionary Research.

"The species is characterized by males being dwarf, with their minute bodies always riding on the dorsal side of females," said paper author Naoto Jimi, postdoctoral researcher at the National Institute of Polar Research, Research Organization of Information and Systems. "It is the first case of extreme sexual size dimorphism in scale worms."

Scale worms are found in every ocean, from low tidal areas to deep seas. They are characterized by the scale-like structures on their backs, and nearly half of them are symbiotic, depending on a host organism to survive. Named after Issun Boushi, a Japanese fairy tale character only three centimeters tall, the recently discovered scale worm is the first demonstrating male dwarfism.

"Extreme sexual size dimorphism is one of the most striking phenomena in evolutionary biology," Jimi said. "While the origin has been well discussed and some causes have been suggested, the evolutionary history remains unclear."

The researchers conducted extensive observations, as well as morphological and genetic analyses. They found that the scale worms always lived in shells, occupied or not, and males were never found without a female counterpart, but single females were occasionally found. In more than 200 sea collections, they never found this scale worm species living without a shell. However, their ancestral analysis revealed that the species likely descended from free-living organism.

"Our data strongly suggest that, based on the ecological and behavioral features, the development of male dwarfism in E. issunboushi is more likely to be related with their symbiotic lifestyle inside gastropod shells occupied by a hermit crab," Jimi said, noting that other symbiotic species live in the same habitat but have not evolved male dwarfism. "The unique environmental and ecological traits may have led to the development of the dwarf male, but this needs to be tested based on additional cases in the future."

(Geneva, 5 June 2021) Procedures to prevent the direct transmission of hepatitis B virus (HBV) from mother to child, particularly during and after pregnancy, have significant fragmentation and gaps, a new survey presented at the 6th World Congress of Paediatric Gastroenterology, Hepatology and Nutrition has shown.

The results, based on 76 delivery hospitals from ten major European countries*, identified significant variances in maternal HBV screening frequency during pregnancy: 53% in the first trimester, 1% in the second trimester and 46% in the third trimester. Alarmingly, only 38% of those women who tested positive with high HBV-DNA levels were treated during the final 12 weeks of pregnancy despite the vast majority of centres (88%) having written protocols for preventing mother-to-child transmission of HBV infection.

The prevention of direct transmission of HBV infection from mother to child is seen as a crucial step towards reducing its incidence as part of the World Health Organization (WHO) global health sector strategy for eliminating viral hepatitis as a major public health threat by 2030. If current trends continue, 19 million hepatitis-related deaths are anticipated from 2015 to 2030.2 By identifying the barriers and challenges, this research represents a key step in preventing this outcome and towards full adherence to international guidelines across European countries.

The new survey also discovered that post-vaccination testing of infants from HBV positive mothers is provided in less than half of centres, even though 10-20% of vaccinated infants still acquire HBV when their mothers had high levels of the virus. This means that infected children, despite being immunised, may not be diagnosed. This is particularly significant in cases where the determination of HBV status occurs in the third trimester, which may be too late to start antiviral therapy in women with high HBV-DNA levels. To compound this concerning revelation further, inconsistency has been reported across all centres on the timing of the HBV vaccine schedule.

Lead author on the research, Michele Pinon from the University of Turin, commented: 'This survey provides a strong indication that significant variance and gaps exist in hospital policies and procedures to prevent direct mother-to-child transmission of HBV across Europe. There is a clear need to implement a multidisciplinary clinical pathway involving obstetricians, neonatologists, and hepatologists, with a stronger connection between the phases before, during and after birth.'

The web-based survey, supported by Penta Foundation and distributed by INCIPIT (Italian Network for Paediatric Clinical Trials), was focused on the prevention strategies adopted before, at, and after birth. A single response was provided in response to the survey by the most experienced physician(s) from each of the 76 participating hospitals.

Speaking on the survey, Chair of the ESPGHAN Hepatology Committee, Giuseppe Indolfi, who was also involved in the research, stated, 'The disjointed and inconsistent nature of practices for prevention of HBV vertical transmission across Europe revealed by this survey is a considerable cause for concern. Procedures must be rectified as soon as possible as we build towards achieving the WHO goal to eradicate the threat of viral hepatitis by 2030.'

Philadelphia, June 4, 2021--ADHD medications may lower suicide risk in children with hyperactivity, oppositional defiance and other behavioral disorders, according to new research from the Lifespan Brain Institute (LiBI) of Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania. The findings, published today in JAMA Network Open, address a significant knowledge gap in childhood suicide risk and could inform suicide prevention strategies at a time when suicide among children is on the rise.

"This study is an important step in the much-needed effort of childhood suicide prevention, as it leverages data collected from approximately 12,000 U.S. children to identify an actionable target to reduce childhood suicides," said senior author Ran Barzilay, MD, PhD, an assistant professor at LiBI. "Early diagnosis and treatment of behavioral symptoms with ADHD medication, particularly among children with severe externalizing symptoms, may serve not only to improve learning and behavior problems, but also to decrease suicidality risk."

Suicide rates among children have been steadily rising. According to the CDC, suicide was the second leading cause of death among individuals between the ages of 10 and 24 in 2018. Yet the rates are still relatively low in preadolescent children, making it difficult to identify factors that may lead to or prevent suicidal tendencies in this age range. Additionally, there are ethical limitations in enrolling potentially suicidal youth in placebo-controlled randomized clinical trials.

"In an ideal world, we want to test a medication effect on suicidality with a randomized prospective trial," Barzilay said. "But given the challenges of conducting such studies, we are obligated as a society and as scientists to generate clinical insights using data collected in large-scale observational studies of children."

The LiBI researchers, in concert with Gal Shoval, MD of Tel Aviv University, circumvented this barrier by leveraging data from the Adolescent Brain Cognitive Development (ABCD) Study. As the largest long-term study of brain development and health in the country, the ABCD Study sample includes a cohort of 11,878 children between the ages of 9 and 10 who were recruited through school systems. The cohort spans 21 sites across the United States, encompassing more than 20% of the U.S. population in this age group, and includes comprehensive data on child development, including data on mental, social, and emotional health. The magnitude and breadth of data collected in the ABCD study allowed the research team to control for multiple confounders and to dissect specifically the association of ADHD medications with suicidal tendencies.

Performing a secondary analysis of the ABCD Study data, the LiBI researchers found that of the 11,878 children in the study, 8.5% were treated with ADHD medication, such as methylphenidate, Adderall or clonidine, and 8.8% reported past or current suicidality. The researchers found that children expressing suicidal tendencies had more externalizing symptoms and were more likely to receive ADHD medication than non-suicidal children. However, among children who demonstrated significant externalizing behaviors, those taking ADHD medications had lesser odds for suicidality, suggesting a moderating role for ADHD medications in these children.

To study whether this effect endured, the researchers analyzed data from participants' one-year follow-up assessments. They found that children with high externalizing symptoms who were treated with ADHD medications at baseline were less likely to be suicidal one year later. Children who were not receiving ADHD medications at baseline but had high externalizing symptoms were more likely to be suicidal at the one-year follow up.

"Given the connection between childhood suicidality and poor adult mental health, these findings emphasize the importance of better and more thorough screening of school-aged children for externalizing behavioral symptoms," Barzilay said. "These symptoms are treatable, and addressing them early has the strong potential to prevent and mitigate serious mental health issues later in life."

DALLAS - June 4, 2021 - Increasing a protein concentrated in brown fat appears to lower blood sugar, promote insulin sensitivity, and protect against fatty liver disease by remodeling white fat to a healthier state, a new study led by UT Southwestern scientists suggests. The finding, published online in Nature Communications, could eventually lead to new solutions for patients with diabetes and related conditions.

"By taking advantage of this natural system, we may be able to help make fat depots more metabolically healthy and potentially prevent or treat obesity-associated diabetes," says study leader Perry E. Bickel, M.D., associate professor of internal medicine at UTSW.

Tens of millions of Americans have Type 2 diabetes, a disease characterized by elevated blood sugar and resistance to insulin, the hormone that allows cells to use blood sugar for energy. This disease has been linked to obesity, with excess white adipose tissue (WAT) - fat tissue that holds the majority of the body's stored energy - associated with elevated blood sugar and insulin resistance in susceptible people. Humans and other mammals also have a second type of fat, known as brown adipose tissue (BAT), which is able to burn fat as a way to increase body heat in cold temperatures. BAT has been investigated as a potential target for weight loss, says Bickel, but may also have a role in improving blood sugar independent of weight loss.

In the study, Bickel and his colleagues, including co-leader Violeta I. Gallardo-Montejano, M.D., an instructor at UTSW, found that brown fat could play an important protective role against diabetes. The researchers made this discovery while studying perilipin 5 (PLIN5), a protein that coats lipid droplets inside cells, particularly in BAT.

When the team genetically engineered mice that made extra PLIN5 in BAT, the animals maintained significantly lower blood sugar concentrations and higher insulin sensitivity during glucose tolerance tests, compared with mice with normal PLIN5 levels. They also had less fatty livers, a condition associated with Type 2 diabetes.

Searching for the mechanism behind these positive changes, the scientists found that the BAT's mitochondria in the genetically engineered mice had adapted to burn even more fat, similar to what's seen in animals placed in cold temperatures. However, the adaptation wasn't enough to explain the blood sugar-lowering effect. Looking closer, the researchers found that the white adipocytes of animals that had extra PLIN5 in their brown adipocytes were smaller and had reductions in some markers of inflammation - changes that are associated with improved sensitivity to insulin and metabolism of sugar.

Bickel notes that BAT appears to communicate with WAT in some unknown way, potentially sending a molecular factor through the bloodstream when PLIN5 levels increase inside brown adipocytes.

"The next question we want to address," says Bickel, "is what that factor is and whether we can harness it for therapeutic benefit."

Overview:

Certain cyanobacteria can change the absorbing light colors for photosynthesis using a green- and red-light sensing photosensor protein. A Japanese research group elucidated the molecular structure of RcaE, a representative member of the photosensors. They revealed the unique conformation of the bilin chromophore and the unique protein structure that potentially functions as a proton transfer route to bilin. They also demonstrated that RcaE undergoes protonation and deprotonation of the bilin chromophore during the green and red photoconversion. These results provide insights into how cyanobacteria evolved photosensors with diverse spectral sensitivities and contribute to the development of new photoswitches of gene expression.

Details:

Certain cyanobacteria can utilize both green and red lights for photosynthesis by using their light-harvesting antenna supercomplex called phycobilisome. They can control the absorptive maxima of phycobilisome, which results in remarkable changes in cell color. This phenomenon is regulated by RcaE that belongs to cyanobacteriochrome family of photosensors. RcaE harbors a bilin chromophore and photoconverts green- and red-absorbing states to sense ambient light colors. Although the green and red photoconversion is involved in bilin photoisomerization and subsequent change in bilin protonation state, the structural basis of this photoconversion remains unknown.

The research group comprised Takayuki Nagae (Nagoya University), Masaki Mishima (Tokyo University of Pharmacy and Life Science), Yuu Hirose (Toyohashi University of Technology), Masashi Unno (Saga University), Kei Wada (Miyazaki University), and Yutaka Itoh (Tokyo City University). They determined the high-resolution structure of RcaE in its red-absorbing state via X-ray crystallography. The bilin chromophore showed a conformation with co-planar A-C rings, wherein the nitrogen atoms were facing inward; the nitrogen of the tilted D-ring was facing outward (classified as C15-E,syn structure). Additionally, they identified a porous cavity containing water molecules in the bilin-binding pocket of RcaE. The clustered water molecules were connected with the nitrogen atoms of bilin A-C rings by a hydrogen bond network through the conserved acidic residue, Glu217.

The research group demonstrated by molecular dynamic simulations that the water molecules in the cavity were exchanged with the solvent water. They also demonstrated by 15N NMR spectroscopy that four pyrrole nitrogen atoms of bilin are fully protonated in the red-absorbing state, whereas one nitrogen atom is deprotonated in the green-absorbing state. They assume that the unique porous cavity functioned as a proton exit or inlet pathway during the green and red photoconversion. Considering previous study reports on Raman spectroscopy of RcaE, they proposed that bilin deprotonation occurred in the B-ring nitrogen with the C15-Z,anti structure. They are currently working on the crystallization of the green-absorbing state of RcaE to confirm this model.

Elucidating the structure and spectral tuning mechanisms of RcaE provides insights into how cyanobacteria have evolved diverse cyanobacterial subfamilies to acclimate to different light environments. Green and red light-sensing cyanobacteriochromes have been utilized in synthetic biology as sophisticated photoswitches that control gene expression. Amino acid residue modification based on RcaE structure will contribute to the development of new photoswitches with desirable photosensitivities.

Since the era of meteorological satellites began in the 1950s, continuous remote sensing instrument improvements have elevated Earth science and have significantly increased available atmospheric observations. Likewise, scientists have made considerable advancements in understanding Earth's atmosphere, climate, and environment. Furthering growth of atmospheric science within the last 20 years, satellite-based infrared (IR) sounders onboard low Earth orbiting (LEO) satellites have provided high spectral (or hyperspectral) IR radiances. These sounders can determine small differences in reflected IR wavelengths, which help identify different targets of the atmosphere. These data have significantly improved global numerical weather prediction (NWP) modelling and forecasting.

Despite global coverage, each LEO sounder provides observations only twice per day for a given location. However, the hyperspectral IR sounders from geostationary Earth orbiting (GEO) satellites can provide higher resolution 4-D temperature (including time), moisture, and dynamic motion information needed to initialize, or start a model simulation. To accurately reflect atmospheric changes throughout an entire 24-hour period, LEO satellites can provide more frequent data updates for NWP models to use.

Scientists are developing data assimilation methods for NWP models that will increase the quality of initialization data from satellites. The Observing System Simulation Experiment (OSSE) is designed to use data assimilation to investigate the potential impact of future atmospheric observing systems. Traditional OSSE processes require significant effort to compute, simulate, and calibrate information, then assimilate the data to produce a forecast. Therefore, model meteorologists are working to make this process more efficient.

"We studied the added-value from a GEO-hyperspectral IR sounder using the hybrid OSSE method." said Prof. Jun Li, a distinguished scientist with the University of Wisconsin-Madison Cooperative Institute for Meteorological Satellite Studies.

Compared to the traditional OSSE, in a hybrid OSSE, most of the data are real observations, except for observations from new sensors, which are simulated frequently through small grid, high resolution global atmospheric analysis or reanalysis. A detailed proposal of hybrid OSSE applications is included in a new paper published in Advances in Atmospheric Sciences, which is also part of a special issue on Fengyun Meteorological Satellites: Data, Application and Assessment

Before they assessed the impact of the new method, Prof. Li and his team had to validate simulated radiances from the new GEO hyperspectral IR sensor to verify that simulating new sensor data would work in the hybrid OSSE system. They used two local severe storms cases from 2018 and 2019 in the Great Plains and Midwestern United States to evaluate the value-added impacts from the GEO hyperspectral IR data.

"We are glad to find improved atmospheric temperature, moisture, and precipitation forecasts, along with some improvements in the wind forecasts." commented Prof. Li regarding the research results.

Overall, the team's impact study presents added value, resulting in a 5% Root Mean Square Error (RMSE) reduction when GEO hyperspectral IR data are used in lieu of LEO data. This indicates potential applications of a GEO hyperspectral IR sounder that may improve local severe storm forecasts.