Culture

Researchers have identified a genetic mutation that caused an 11-year-old girl to suffer a fatal reaction to infection with the Hepatitis A virus (HAV). The study, which will be published June 18 in the Journal of Experimental Medicine, reveals that mutations in the IL18BP gene causes the body’s immune system to attack and kill healthy liver cells, and suggests that targeting this pathway could prevent the deaths of patients suffering rapid liver failure in response to viral infection.

HAV infects the liver and usually causes a relatively mild illness that clears up in a matter of weeks or months. But as many as 1 in 200 HAV patients suffer a much more severe response known as fulminant viral hepatitis (FVH) that is characterized by a rapid loss of liver tissue and catastrophic liver failure, resulting in the release of toxins that damage the brain. The condition is usually fatal unless the patient receives a liver transplant.

Other hepatitis viruses can also cause FVH, but the reason why some patients suffer such a severe response to infection is unclear. It typically occurs in children and young adults who are otherwise healthy and have no prior history of liver disease or immunodeficiencies.

A team of researchers led by Professor Jean-Laurent Casanova at The Rockefeller University in New York identified an 11-year-old girl in France who died of FVH after becoming infected with HAV. The researchers sequenced the girl’s DNA and discovered that she carried identical mutations in both copies of the IL18BP gene, which encodes a protein called interleukin-18 binding protein (IL-18BP).

IL-18BP can bind and neutralize interleukin-18 (IL-18), a powerful ‘cytokine’ molecule that the body produces in response to infection in order to activate certain types of immune cells and promote inflammation. Casanova and colleagues determined that the mutation identified in the patient’s IL18BP gene prevented the IL-18BP protein from neutralizing IL-18.

To understand how this might affect the body’s response to HAV infection, the researchers incubated human liver cells with Natural Killer (NK) cells, a type of immune cell that targets virally infected cells. Casanova and colleagues discovered that, in the absence of IL-18BP, IL-18 enhanced NK cells’ ability to target and kill liver cells, whether they were infected with HAV or not. Addition of IL-18BP blocked this IL-18–induced toxicity, suggesting that IL-18BP usually prevents an excessive reaction to HAV infection but that patients carrying mutations in this gene are susceptible to FVH.

“Our findings provide a proof of principle that FVH can be caused by inborn errors in single genes,” Casanova says. “Human IL-18BP injections have been approved for clinical use for indications unrelated to liver conditions and has been proposed as a treatment for preventing acetaminophen-induced liver damage. Neutralizing IL-18 with IL-18BP might be beneficial to patients with FVH caused by HAV and possibly other viruses as well.”

WASHINGTON -- Materials science researchers with the U.S. Naval Research Laboratory have found a remnant of ancient dust from the early stages of the solar system inside a primitive meteorite, named La Paz Icefield 02342 after the location of its discovery in Antarctica.

NRL scientists Rhonda Stroud and Bradley De Gregorio contributed to a paper describing the find, which published in Nature Astronomy, April 15.

To examine these tiny grains within the larger particle, the researchers relied on a unique capability of NRL's Nanoscience Institute, which has a state-of-the-art aberration-corrected scanning transmission electron microscope that can shape its emitted electron beam to optimize image quality and resolution.

The microscope is one of only a few of its kind in the world. Along with other state-of-the art measurement and nanofabrication equipment located in the Institute, it enables NRL scientists and engineers to discover and develop new nanotechnology for the Navy and the Marine Corps.

"Having this capability at the lab is ideal," De Gregorio said. "It helps us stay on the cutting edge of science, and contributes to amazing studies like this one."

De Gregorio, a researcher with NRL's Materials Science and Technology Division, called the confluence of cosmic events that led to the finding "amazing," and "an incredible journey" for an ancient dust particle.

"This particle formed at the beginning of our solar system," he said. "[It] had to travel from the outer comet-forming regions, become embedded in asteroids forming in the interior of our system. [Then an asteroid had to] break apart in just the right way to form a meteoroid with the dust particle in it. Then the meteorite had to land on Antarctica in just the right spot to be collected by a field scientist."

The researchers validated the dust's cometary heritage from its pre-solar grains, tiny particles of primarily carbon, which have a specific isotopic chemical signature not found in material originating within our solar system, and from the presence of glassy grains containing nanoscale iron metal and sulfides, which are commonly found in other studies of comet dust.

The meteorite was collected in Antarctica during the 2002 field season of NASA's Antarctic Search for Meteorites (ANSMET) program. This work was funded by NASA's Science Mission Directorate, through grants NNX10AI63G and NNH16AC42I, and by Spanish Ministry of Science grants AYA 2011-26522 and AYA 2015-67175-P.

Bad news, Jurassic Park fans--the odds of scientists cloning a dinosaur from ancient DNA are pretty much zero. That's because DNA breaks down over time and isn't stable enough to stay intact for millions of years. And while proteins, the molecules in all living things that give our bodies structure and help them operate, are more stable, even they might not be able to survive over tens or hundreds of millions of years. In a new paper published in eLife, scientists went looking for preserved collagen, the protein in bone and skin, in dinosaur fossils. They didn't find the protein, but they did find huge colonies of modern bacteria living inside the dinosaur bones.

"This is breaking new ground--this is the first time we've discovered this unique microbial community in these fossil bones while they're buried underground," says lead author Evan Saitta, a postdoctoral researcher at the Field Museum. "And I would say that it's another nail in the coffin in the idea of dinosaur proteins getting preserved intact."

Saitta began researching organic molecules in fossils as part of his doctoral thesis at the University of Bristol. "My PhD work focused on how soft tissues fossilize and how these materials break down. Some molecules can survive in the fossil record, but I suspect proteins can't; they're unstable on those timescales in the conditions of fossilization," explains Saitta.

However, some paleontologists have reported finding dinosaur bones that contain exceptionally preserved traces of the protein collagen, along with soft tissues like blood and bone cells. "There's been an uptick in interest in these supposed dinosaur proteins," says Saitta. So, he set out to try to independently verify the presence of collagen in dinosaur fossils.

Saitta took pains to collect dinosaur fossils under as sterile conditions as possible so that new proteins or bacteria wouldn't be introduced to the fossils and skew the results. He took a pickaxe, saw, blowtorch, ethanol, and bleach, out to Dinosaur Provincial Park in Alberta, Canada.

"There's a single layer where there's practically more bone than rock, it's ridiculous how concentrated the bones are," says Saitta. A site with lots of bone was key, because a slow, meandering dig would open up the fossils to more chances to be contaminated by the surface world. "To collect these bones in a very controlled, sterile way, you need a dig site with a ton of bone because you have to find the bone quickly, expose just enough of one end to know what it is, then aseptically collect the unexposed bit of the bone and surrounding rock all in one." Saitta collected 75-million-year-old fossils from Centrosaurus--a smaller cousin of Triceratops--and then took the bones back to various laboratories to examine their organic composition.

Saitta and his colleagues compared the biochemical makeup of the Centrosaurus fossils with modern chicken bones, sediment from the fossil site in Alberta, and thousands-of-years-old shark teeth that washed up on the shore of Saitta's hometown of Ponte Vedra Beach, Florida. "We visited multiple labs, and the different techniques gave us consistent and easily interpretable results, suggesting that the aseptic collection was sufficient," says Saitta. They found that the Centrosaurus fossils didn't seem to contain the collagen proteins present in fresh bones or the much younger shark teeth. But they did find something else: "We see lots of evidence of recent microbes," explains Saitta. "There's clearly something organic in these bones." And since the labwork indicates that Saitta's anti-contamination measures worked, these organic materials must have gotten there naturally.

"We found non-radiocarbon dead organic carbon, recent amino acids, and DNA in the bone--that's indicative that the bone is hosting a modern microbial community and providing refuge," Saitta says. He thinks, as others have previously suggested, that the modern microbes and their secretions, called biofilm, are likely what other researchers have seen in fossils and reported as dinosaur soft tissues. "I suspect that if we began to do this kind of analysis with other specimens, it would begin to explain some of the so-called dinosaur soft tissue discoveries," he says.

Surprisingly, the modern microbes present in the dinosaur bones aren't quite the same run-of-the-mill bacteria living in the surrounding rock. "It's a very unusual community," says Saitta. "Thirty percent of the sequences are related to Euzebya, which is only reported from places like Etruscan tombs and the skin of sea cucumbers, as far as I know."

Saitta and his colleagues aren't sure why these particular microbes are living in the dinosaur bones, but he's not shocked that bacteria are drawn to the fossils. "Fossil bones contain phosphorus and iron, and microbes need those as nutrients. And the bones are porous--they wick up moisture. If you were a bacterium living in the ground, you'd probably want to live in a dinosaur bone," he says. "These bacteria are clearly having a jolly good time in these bones."

The discovery could help further the emerging field of molecular paleontology, says Saitta. "It's one of the new frontiers of modern paleontology. We are beginning to undertake a very different kind of fossil hunting. We're not just looking for bones and teeth, hoping to find new species, we're doing molecular fossil hunting--it opens up an entirely new line of evidence by which to study life in the past. Molecular fossils can tell us things we never thought we'd be able to investigate. Distinguishing what is modern from what is ancient is important."

The Academy of Management Journal has just published a paper titled Collective emotions in institutional creation work, which has been produced at Aalto University School of Business in collaboration with the University of Birmingham. The paper addresses the often overlooked issue of how communities rebuild long after the NGOs have moved onto the next disaster.

Steffen Farny, Ewald Kibler and Simon Down have prepared the paper based on research that looks at how communities can better cope and move on from the trauma of natural disasters, and build passion and hope for the future. Farny says ´Aside from the physical damage, the aftermath of a natural disaster can also create a cultural trauma, so we wanted to look beyond the first phase of disaster response, and focus on the longer-term repercussions and approaches to rebuilding`. They turned their attention to the aftermath of the Haitian earthquake of 2010, which killed and displaced hundreds of thousands of people, and collapsed the government in the process.

The immediate disaster relief effort, provided by international NGOs was adequate according to a UN report as it saved lives and re-established basic routines and supplies, but what the NGOs couldn't and didn't do was rebuild trust and hope for the future. Nor could they do much about the need for new schools and factories.

Research in Haiti and other disaster-hit regions has shown that local communities struggle to escape cycles of aid dependency, and local and national authorities struggle to change this situation.

Another often overlooked problem of international disaster recovery efforts is that the aid effort itself can create additional issues, not least of which is a trust barrier. New toilet facilities might be built through the efforts of NGOs, but they remain unused for lack of water supply, servicing or proper waste-water treatment. Aid workers can also create problems, as has been seen in the much-publicised scandal involving those in Oxfam exploiting local sex workers.

Farny and his colleagues were able to get invaluable access to the stricken community of Limonade through linking-up with two local social entrepreneurs Steve and Gabi, who had returned to Haiti in the mid-2000s after public sector careers in the US. Down happily points out, ´Through focussing on just one community for the study, and working with Steve and Gabi and their Sonji Ayiti (Remember Haiti) social enterprise (https://www.sonje-ayiti.org), we had a rich case to work from`.

With minimal resources, Steve and Gabi mobilised villagers to build a new school (called the 'School of Hope') out of an old UN tent. They built new toilet centres, reducing the threat of Cholera, assisted with creating new farmers' cooperatives and most recently, a new campus of the University of Haiti. These efforts helped to develop a trust that progress would be sustained and would go beyond the first phase of disaster response.

The paper also details the emergence of symbolic recovery in the second phase of disaster response and indications of a prosperous future, but through dedicated action by those such as Steve and Gabi, local people can develop hope and passion for rebuilding their community and infrastructure that will stand stronger than before.

Kibler concludes, ´We hope that our work informs current post-disaster management practice and policy as well as gives a framework for further study of positive collective emotions in community development.'

Princeton University researchers have developed a new, scalable cell culture system that allows for detailed investigation of how host cells respond to infection with hepatitis B (HBV) and delta virus (HDV). The paper describing their findings was published online on June 18, 2019 in the journal Hepatology.

HBV causes an acute illness that is usually rapidly cleared by adults with intact immune systems, but young children and people with HIV are at particular risk of chronic HBV infection, which can lead to cirrhosis or cancer of the liver. Infection with HBV also renders a person vulnerable to infection with HDV, which can cause acute liver failure and/or accelerate the progression to cirrhosis or cancer. Fortunately, an effective vaccine exists for HBV, and because HDV requires HBV in order to reproduce, both can be considered preventable diseases. However, the expense and limited availability of the vaccine leaves millions at risk for infection worldwide.

A better understanding of how the viruses affect the cells they infect would assist in the development of drugs to combat or even cure infection, but HBV and HDV only infect liver cells (hepatocytes) from humans and chimpanzees. Such cells are difficult to obtain, and when grown outside the body in cell culture, they undergo a process called de-differentiation: over the course of just a few days, they lose their specialized characteristics and functionality. When this happens, they also lose the ability to be infected with HBV and HDV, creating a significant obstacle to studying chronic viral infection.

"Attempts have been made since the mid-1980s to establish robust - and, importantly, persistent - infection in primary human hepatocytes (PHHs) with limited success," said Alexander Ploss, an associate professor in the Department of Molecular Biology at Princeton and leader of the study.

Studies with other tissues have shown that specialized cell types sometimes require the support of other types of cells in order to maintain their differentiated status. Hepatocytes make up the majority of cells in the liver, but the tissue also contains many other cell types, which are collectively referred to as "non-parenchymal cells." Recently, graduate student Benjamin Winer, together with colleagues in Ploss' lab and at the Hurel Corporation, demonstrated that freshly isolated human hepatocytes can be grown together with non-parenchymal cells on a supporting surface made of collagen. In this cell culture system, which the researchers call a self-assembling co-culture of primary human hepatocytes (SACC-PHH), the hepatocytes retain their differentiated state and can support chronic HBV infection for up to 40 days.

"This system has created unprecedented opportunities to study host responses to hepatitis virus, especially in the context of persistent infection," Ploss said.

In the new study, Winer and colleagues investigated how hepatocytes respond to infection with HBV and HDV. First, they tested whether SACC-PHH can support infection with both viruses. HBV hijacks the cell's protein-making machinery to make viral proteins, and HDV co-opts HBV proteins to assemble itself. Therefore, HDV can only reproduce when it infects cells at the same time as HBV (co-infection) or in cells already chronically infected with HBV (super-infection). The researchers found that both of these scenarios can occur in SACC-PHH, even when the culture system has been scaled down to tiny 384 microwell culture plates -- a development that makes the system well suited for high-throughput screening of candidate drugs. Accordingly, the team showed that prophylactic treatment with two candidate antivirals, entecavir and Myrcludex B, could reduce levels of both hepatitis viruses in SACC-PHH.

Viral infection provokes many changes in the host cell, ranging from metabolic adaptations to the activation of innate immune defenses that can recognize and destroy a virus inside the cell. To explore what changes hepatocytes experience in response to HBV/HDV infection, the authors looked at which genes were being expressed using a technique called RNA-Seq analysis. The data showed that cells infected with HBV exhibit elevated expression of genes involved in oxidative phosphorylation and interaction with the extracellular environment. By contrast, cells additionally infected with HDV had similar gene expression patterns as uninfected cells.

Interestingly, even though the hepatocytes' innate immune signaling pathways were intact and could be stimulated by addition of chemicals such as poly(I:C), HBV infection did not activate these defenses. On the other hand, treatment with poly(I:C) helped suppress HBV growth, suggesting the virus flies under the radar of cells' defenses to establish persistent infection.

How innate immune defenses affect HBV/HDV co-infection appears more nuanced. Stimulation of innate immune pathways with poly(I:C) had little effect on HDV. HBV/HDV co-infection also failed to activate defense pathways in the hepatocytes of most human donors studied, but one donor showed innate immune activation upon co-infection, indicating a person's genetic makeup may influence their ability to combat the infection.

"We believe that our optimized, high-throughput SACC-PHH platform is a unique resource for investigating hepatotropic pathogens, and that our data will help advance understanding persistent infections by HBV and HDV," Ploss said.

More than 30 microbiologists from 9 countries have issued a warning to humanity - they are calling for the world to stop ignoring an 'unseen majority' in Earth's biodiversity and ecosystem when addressing climate change.

'Scientist's warning to humanity: microorganisms and climate change' was published today in the journal Nature Reviews Microbiology. Professor Rick Cavicchioli, microbiologist at the School of Biotechnology and Biomolecular Sciences at UNSW Sydney, has led the global effort.

With their statement, the researchers are hoping to raise awareness both for how microbes can influence climate change and how they will be impacted by it - calling for including microbes in climate change research, increasing the use of research involving innovative technologies, and improving education in classrooms.

"Micro-organisms, which include bacteria and viruses, are the lifeforms that you don't see on the conservation websites," says Professor Cavicchioli.

"They support the existence of all higher lifeforms and are critically important in regulating climate change.

"However, they are rarely the focus of climate change studies and not considered in policy development."

Professor Cavicchioli calls microbes the 'unseen majority' of lifeforms on earth, playing critical functions in animal and human health, agriculture, the global food web and industry.

For example, the Census of Marine Life estimates that 90% of the ocean's total biomass is microbial. In our oceans, marine lifeforms called phytoplankton take light energy from the sun and remove carbon dioxide from the atmosphere as much as plants. The tiny phytoplankton form the beginning of the ocean food web, feeding krill populations that then feed fish, sea birds and large mammals such as whales.

Sea ice algae thrive in sea ice 'houses'. If global warming trends continue, the melting sea ice has a downstream effect on the sea ice algae, which means a diminished ocean food web.

"Climate change is literally starving ocean life," says Professor Cavicchioli.

Beyond the ocean, microbes are also critical to terrestrial environments, agriculture and disease.

"In terrestrial environments, microbes release a range of important greenhouse gases to the atmosphere (carbon dioxide, methane and nitrous oxide), and climate change is causing these emissions to increase," Professor Cavicchioli says.

"Farming ruminant animals releases vast quantities of methane from the microbes living in their rumen - so decisions about global farming practices need to consider these consequences.

"And lastly, climate change worsens the impact of pathogenic microbes on animals (including humans) and plants - that's because climate change is stressing native life, making it easier for pathogens to cause disease.

"Climate change also expands the number and geographic range of vectors (such as mosquitos) that carry pathogens. The end result is the increased spread of disease, and serious threats to global food supplies."

Greater commitment to microbe-based research needed

In their statement, the scientists call on researchers, institutions and governments to commit to greater microbial recognition to mitigate climate change.

"The statement emphasises the need to investigate microbial responses to climate change and to include microbe-based research during the development of policy and management decisions," says Professor Cavicchioli.

Additionally, climate change research that links biological processes to global geophysical and climate processes should have a much bigger focus on microbial processes.

"This goes to the heart of climate change, so if micro-organisms aren't considered effectively it means models cannot be generated properly and predictions could be inaccurate," says Professor Cavicchioli.

"Decisions that are made now impact on humans and other forms of life, so if you don't take into account the microbial world, you're missing a very big component of the equation."

Professor Cavicchioli says that microbiologists are also working on developing resources that will be made available for teachers to educate students on the importance of microbes.

"If that literacy is there, that means people will have a much better capacity to engage with things to do with microbiology and understand the ramifications and importance of microbes."

In malignant tumours, the cells usually proliferate quickly and uncontrollably. A research team from the Biocenter of Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, has discovered that two important regulators of cell division can interact in this process. If this is the case, affected patients have particularly poor chances of survival. A special form of lung cancer was investigated.

The JMU team led by Professor Stefan Gaubatz and Dr. Grit Pattschull from the Chair of Biochemistry and Molecular Biology II analysed the activities of the protein YAP and the protein complex MMB (Myb-MuvB). According to the researchers, the former protein is only able to initiate cell division when it interacts with a subunit of the MMB complex. The molecular details of these processes are currently described in the journal Cell Reports.

"Our results show for the first time that there is a connection between these two cancer-relevant signalling pathways," said Professor Gaubatz. If this connection can be broken, this could possibly be applied for cancer therapy.

Next, the JMU research team will investigate the exact details of the interaction between YAP and the MMB protein complex. In particular, the researchers hope to identify further proteins that are involved in the interaction of the two signalling pathways. The long-term goal is to suppress tumour growth by blocking the interaction.

A collaborative team of scientists from the US and Australia has named a new plant species from the remote Outback. Bucknell University biology postdoctoral fellow Angela McDonnell and professor Chris Martine led the description of the plant that had confounded field biologists for decades because of the unusual fluidity of its flower form. The discovery, published in the open access journal PhytoKeys, offers a powerful example of the diversity of sexual forms found among plants.

The new species of bush tomato discovered in remote Australia provides a compelling example of the fact that sexuality among Earth's living creatures is far more diverse - and interesting - than many people likely realize.

Bucknell University postdoctoral fellow Angela McDonnell and biology professor Chris Martine led the study following an expedition last year to relocate populations of the new plant, which were first noted by Australian botanists during the 1970s.

Herbarium specimens from those few earlier collections are peppered with notes regarding the challenge of identifying the sexual condition of this plant, which appeared at various times to be female, male, or bisexual.

According to Martine, about 85% of the planet's quarter-million flowering plant species have flowers that are bisexual - with both male and female organs present in every blossom.

"So that's already quite different than what some people might expect; but the remaining 15% or so come in all sorts of forms that push the envelope further, including unisexual flowers and (like we see in a plant like Cannabis) whole plants that are either male or female."

"For the most part, a given plant species will stick to one primary and predictable type of sexual expression," said Martine "but what makes Solanum plastisexum stand out is that it is one of a just a few plants that kind of do it all. It really seems like you never know what you'll get when you come across it."

When DNA studies in Martine's lab offered proof that these plants were not only all the same thing, but a species not yet described, he, McDonnell, Jason Cantley (San Francisco State University), and Peter Jobson (Northern Territory Herbarium in Alice Springs) set out to hunt for populations along the unpaved Buchanan Highway in the remote northwestern region of the Northern Territory.

The botanists were able to collect numerous new specimens and have now published the new species description in the open-access journal PhytoKeys, choosing the name Solanum plastisexum as a nod to the notable variation exhibited by this plant in its sexual condition.

"This name, for us, is not just a reflection of the diversity of sexual forms seen in this species," wrote the authors in the article. "It is also a recognition that this plant is a model for the sort of sexual fluidity that is present across the Plant Kingdom - where just about any sort of reproductive form one can imagine (within the constraints of plant development) is present."

Also known as the Dungowan bush tomato, Solanum plastisexum is a distant cousin of the cultivated eggplant and is a close relative of two other Australian species recently discovered by Martine and colleagues that were also published in PhytoKeys: Solanum watneyi, named for Mark Watney, the space botanist of the book/film The Martian; and Solanum jobsonii, a species named last year for S. plastisexum co-author Jobson.

The scientists hope that the naming of this latest new species turns a spotlight on the fact that nature is full of examples for the myriad ways in which living things behave sexually.

"In a way, S. plastisexum is not just a model for the diversity of sexual/reproductive form seen among plants - it is also evidence that attempts to recognize a "normative" sexual condition among the planet's living creatures is problematic."

"When considering the scope of life on Earth," the authors conclude, "The notion of a constant sexual binary consisting of two distinct and disconnected forms is, fundamentally, a fallacy."

Government policy and infrastructure have a substantial impact on hospitalization of older adults, according to a University of Waterloo study.

The study examined the experiences of 254,664 patients in home-care programs and 162,045 residents in long-term care in Alberta, British Columbia and Ontario.

It found that home-care patients in Alberta and British Columbia are more likely to be sent to hospital than those in Ontario, regardless of the severity of a person's medical condition. The study also found that long-term care residents in Alberta and B.C. were half as likely to be sent to hospital compared with those in Ontario.

"We were surprised by the magnitude of the influence of health care policies, infrastructure and professional practices," said George Heckman, a public health professor at the University of Waterloo and Schlegel Research Chair in Geriatrics. "It's important to understand the factors that send vulnerable populations to hospital because hospitals are generally where health complications arise."

"Often, patients are too sick to be rapidly discharged from hospital, and as their numbers continue to rise, it can lead to hallway medicine," added Heckman. "Since many governments have identified hallway medicine as a challenge they'd like to address, learning how to change health care so that it is focused on patients' needs instead of system needs and design quirks will be key."

The researchers used several comprehensive data sets, including data from the Canadian Institute for Health Information and several interRAI assessment systems, to track emergency department visits, hospitalizations and death.

Heckman said the next step is to examine the healthcare policies in the three provinces to determine why these regional differences exist. Alberta, for instance, has increased the focus on assisted living in recent years, which could explain why there were fewer transfers to hospital from long-term care.

As Charles Darwin wrote in at the end of his seminal 1859 book On the Origin of the Species, "whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved." Scientists have since long believed that the diversity and range of forms of life on Earth, provide evidence that biological evolution spontaneously innovates in an open-ended way, constantly inventing new things. However, attempts to construct artificial simulations of evolutionary systems tend to run into limits in the complexity and novelty which they can produce. This is sometimes referred to as "the problem of open-endedness." Because of this difficulty, to date scientists can't easily make artificial systems capable of exhibiting the richness and diversity of biological systems.

In a new study published in the journal Artificial Life, a research team led by Nicholas Guttenberg and Nathaniel Virgo of the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology, Japan, and Alexandra Penn of The Centre for Evaluation of Complexity Across the Nexus (CECAN), University of Surrey UK (CRESS), examine the connection between biological evolutionary open-endedness and recent studies in machine learning, hoping that by connecting ideas from artificial life and machine learning, it will become possible to combine neural networks with the motivations and ideas of artificial life to create new forms of open-endedness.

One source of open-endedness in evolving biological systems is an "arms race" for survival. For example, faster foxes may evolve to catch faster rabbits, which in turn may evolve to become even faster to get away from the faster foxes. This idea is mirrored in recent developments involving placing networks in competition with each other to produce things such as realistic images using generative adversarial networks (GANs), and to discover strategies in games such as Go, which can now easily beat top human players. In evolution, factors such as mutation can limit the extent of an arms race. However, as neural networks have been scaled up, no such limitation seems to exist and the network can continue to improve as additional data is fed to their algorithms.

Guttenberg had been studying evolutionary open-endedness since graduate school, but it was only in the last few years that his focus shifted to artificial intelligence and neural networks. Around that time, methods such as GANs were invented, which struck him as very similar to the open-ended co-evolutionary systems he had previously worked on. Suddenly, he saw an opportunity to tear down a barrier between the communities to help make progress on something which had for him been a persistently important and interesting problem.

The researchers showed that while they can use scaling analyses to demonstrate open-endedness in evolutionary and cognitive contexts, there is a difference between making something which, for example, becomes infinitely good at making cat pictures and something which, having tired of making cat pictures, decides to go on to making music instead. In artificial evolutionary systems, these sorts of major qualitative leaps have to be anticipated by the programmer - they'd need to make an artificial world in which music is possible for the "organisms" to decide to be musicians. In systems such as neural networks, concepts such as abstraction are more easily captured, and so one can start to imagine ways in which populations of interacting agents could create new problems to be solved among themselves.

This work raises some deep and interesting questions. For example, if the drive for qualitatively different novelty in a computational system arises internally from abstraction, what determines the "meaning" of the novelty artificial systems generate? Machine learning has been shown to sometimes lead to the creation of artificial languages by interacting computational agents, but these languages are still grounded in the task the agents are cooperating to solve. If the agents really do rely on the interactions within the system to drive open-endedness far from whatever was provided as starting material, would it even be possible to recognize or interpret the things that come out, or would one have to be an organism living in such a system in order to understand its richness?

Ultimately, this study suggests it may be possible to make artificial systems that autonomously and continuously invent or discover new things, which would constitute a significant advance in artificial intelligence, and may help in understanding the evolution and origin of life.

Geneticists exploring the dark heart of the human genome have discovered big chunks of Neanderthal and other ancient DNA. The results open new ways to study both how chromosomes behave during cell division and how they have changed during human evolution.

Centromeres sit in the middle of chromosomes, the pinched-in "waist" in the image of a chromosome from a biology textbook. The centromere anchors the fibers that pull chromosomes apart when cells divide, which means they are really important for understanding what happens when cell division goes wrong, leading to cancer or genetic defects.

But the DNA of centromeres contains lots of repeating sequences, and scientists have been unable to properly map this region.

"It's the heart of darkness of the genome, we warn students not to go there," said Charles Langley, professor of evolution and ecology at UC Davis. Langley is senior author on a paper describing the work published in the journal eLife.

Langley and colleagues Sasha Langley and Gary Karpen at the Lawrence Berkeley Laboratory and Karen Miga at UC Santa Cruz reasoned that there could be haplotypes -- groups of genes that are inherited together in human evolution -- that stretch over vast portions of our genomes, and even across the centromere.

That's because the centromere does not participate in the "crossover" process that occurs when cells divide to form sperm or eggs. During crossover, paired chromosomes line up next to each other and their limbs cross, sometimes cutting and splicing DNA between them so that genes can be shuffled. But crossovers drop to zero near centromeres. Without that shuffling in every generation, centromeres might preserve very ancient stretches of DNA intact.

The researchers looked for inherited single nucleotide polymorphisms -- inherited changes in a single letter of DNA -- that would allow them to map haplotypes in the centromere.

They first showed that they could identify centromeric haplotypes, or "cenhaps," in Drosophila fruit flies.

That finding has two implications, Langley said. Firstly, if researchers can distinguish chromosomes from each other by their centromeres, they can start to carry out functional tests to see if these differences have an impact on which piece of DNA is inherited. For example, during egg formation, four chromatids are formed from two chromosomes, but only one makes it into the egg. So scientists want to know: Are certain centromere haplotypes transmitted more often? And are some haplotypes more likely to be involved in errors?

Secondly, researchers can use centromeres to look at ancestry and evolutionary descent.

Turning to human DNA, the researchers looked at centromere sequences from the 1000 Genomes Project, a public catalog of human variation. They discovered haplotypes spanning the centromeres in all the human chromosomes.

Haplotypes from half a million years ago

In the X chromosome in these genome sequences, they found several major centromeric haplotypes representing lineages stretching back a half a million years. In the genome as a whole, most of the diversity is seen among African genomes consistent with the more recent spread of humans out of the African continent. One of the oldest centromere haplotype lineages was not carried by those early emigrants.

In chromosome 11, they found highly diverged haplotypes of Neanderthal DNA in non-African genomes. These haplotypes diverged between 700,000 to a million years ago, around the time the ancestors of Neanderthals split from other human ancestors. The centromere of chromosome 12 also contains an even more ancient, archaic haplotype that appears to be derived from an unknown relative.

This Neanderthal DNA on chromosome 11 could be influencing differences in our sense of smell to this day. The cells that respond to taste and smell carry odorant receptors triggered by specific chemical signatures. Humans have about 400 different genes for odorant receptors. Thirty-four of these genes reside within the chromosome 11 centromere haplotype. The Neanderthal centromeric haplotypes and a second ancient haplotype account for about half of the variation in these odorant receptor proteins.

It's known from work by others that genetic variation in odorant receptors can influence sense of taste and smell, but the functional effects of the variation found in this study are yet to be discovered and their impact on taste and smell analyzed.

Scientists in the FinnBrain research project of the University of Turku, Finland, discovered that the gut microbes of a 2.5-month-old infant are associated with the temperament traits manifested at six months of age. Temperament describes individual differences in expressing and regulating emotions in infants, and the study provides new information on the association between behaviour and microbes. A corresponding study has never been conducted on infants so young or in the same scale.

Rodent studies have revealed that the composition of gut microbiota and its remodelling is connected to behaviour. In humans, gut microbes can be associated with different diseases, such as Parkinson's disease, depression and autism spectrum disorders, but little research has been conducted on infants.

Doctoral Candidate, Doctor Anna Aatsinki from the FinnBrain research project at the University of Turku, Finland, discovered in her study on 303 infants that different temperament traits are connected with individual microbe genera, microbial diversity and different microbe clusters.

"It was interesting that, for example, the Bifidobacterium genus including several lactic acid bacteria was associated with higher positive emotions in infants. Positive emotionality is the tendency to experience and express happiness and delight, and it can also be a sign of an extrovert personality later in life," says Aatsinki.

Temperament Can Predict Later Development

One of the findings was that greater diversity in gut bacteria is connected to lesser negative emotionality and fear reactivity. The study also considered other factors that significantly affect the diversity of the microbiota, such as the delivery method and breastfeeding.

The findings are interesting as strong fear reaction and negative emotionality can be connected to depression risk later in life. However, the association with later diseases is not straightforward and they are also dependent on the environment.

"Although we discovered connections between diversity and temperament traits, it is not certain whether early microbial diversity affects disease risk later in life. It is also unclear what are the exact mechanisms behind the association," adds Aatsinki.

"This is why we need follow-up studies as well as a closer examination of metabolites produced by the microbes."

A new study in the Faculty of Public Health's Journal of Public Health finds that tobacco and alcohol usage are extremely common in British reality television shows.

The researchers measured depictions of alcohol and tobacco products on Celebrity Big Brother, Made in Chelsea, The Only Way is Essex, Geordie Shore, and Love Island, all airing on UK channels for a total of 112 episodes between January and August 2018. The researchers measured the number of one-minute intervals containing tobacco and/or alcohol imagery, including actual use, implied use, tobacco or alcohol related materials, and product-specific branding, and estimated viewer exposure to the imagery on screen.

Researchers here combined audience viewing figures with mid-year population estimates for 2017 to estimate overall and individual impressions--separate incidents seen--by age group for each of the coded episodes.

Alcohol content appeared in all 112 episodes and in 2212 one-minute intervals, or 42% of all intervals studied. 18% of intervals included actual alcohol consumption, while 34% featured inferred consumption, predominantly characters holding alcoholic beverages. The greatest number of intervals including any alcohol content occurred in Love Island. Alcohol branding occurred in 1% of intervals and was most prevalent in Geordie Shore (51 intervals, 69% of episodes). Forty brands were identified, the most common being Smirnoff vodka (23 intervals, all but one of which occurred in Geordie Shore).

Tobacco content appeared in 20 episodes, in 110 or 2% of all intervals studied. Almost all (98%) of this content occurred in a single reality TV series, Celebrity Big Brother. This included actual tobacco use, inferred tobacco use, and tobacco paraphernalia. Tobacco branding was not present.

When all the data were combined with audience viewing figures and population estimates, the researchers estimate that the 112 episodes delivered 4.9 billion overall alcohol impressions to the UK population, including 580 million to children under the age of 16, as well as 214 million overall tobacco impressions, including 47 million to children under 16.

"Recent data shows that 44% of 11-15 year-olds in England have had an alcoholic drink, and 19% have tried smoking. Starting to smoke or drink alcohol at a young age is a strong predictor of dependence and continued use in later life," said the study's lead author, Alexander Barker. "Given that seeing alcohol or tobacco imagery in the media promotes use among young people, this study therefore identifies reality television shows as a major potential driver of alcohol and tobacco consumption in young people in the UK. Tighter scheduling rules, such as restricting the amount of content and branding shown in these programmes, could prevent children and adolescents from being exposed to the tobacco and alcohol content."

Terminally ill patients who request that physicians make decisions on their behalf are more likely to receive aggressive treatments in the weeks before they die, according to a Rutgers study.

The study, published in the Journal of Pain and Symptom Management, is the first to examine if personal beliefs and attitudes of both patients and physicians affect end-of-life treatments that can be painful and risky.

The findings call attention to the fact that patients are accepting aggressive treatments and highlight the need for better education about end-of-life care.

"Some physicians are very comfortable taking over the decision-making for their terminally ill patients. An important and surprising finding is that when physicians do take charge of treatment decisions, patients are more likely to receive aggressive interventions at the end of life," said lead author Paul Duberstein, chair of the Department of Health Behavior, Society and Policy at Rutgers School of Public Health. "As a result, patients end up in intensive care units or emergency rooms in the days before death, even though most people would rather die peacefully at home.

The researchers examined chemotherapy use and hospitalizations or emergency department visits in the last 30 days of life of 265 patients who had been cared for by 38 oncologists. They found that patients of physicians who were comfortable offering aggressive medical interventions were more likely to receive chemotherapy and endure difficult hospitalizations in the days and weeks before dying. Patients who had unfavorable attitudes toward palliative care and those who wanted to try medically unproven cancer treatments were also more likely to receive aggressive interventions.

"Many studies have examined doctor's attitudes, but few have examined if doctors' attitudes affect end-of-life care," Duberstein said. "We found that doctors' attitudes can have detrimental impacts and prevent those who are close to death from receiving the emotional support needed at that time."

The findings show the importance of providing patients with access to information about how doctors handle high-stakes treatment decision-making. "That information is not publicly available, but it needs to be," he said.

The findings also have clinical and ethical implications regarding the care of patients with advanced diseases.

"We need to do a much better job teaching doctors about the psychology of death and dying, improving the way we educate the public about the benefits of palliative care and providing care for patients and families with advanced disease," Duberstein said.

DNA, the hereditary material, may have appeared on Earth earlier than has been assumed hitherto. Ludwig-Maximilians-Universitaet (LMU) in Munich chemists led by Oliver Trapp show that a simple reaction pathway could have given rise to DNA subunits on the early Earth.

How were the building-blocks of life first formed on the early Earth? As yet, only partially satisfactory answers to this question are available. However, one thing is clear: The process of biological evolution that has given rise to the diversity of life on our planet must have been preceded by a phase of chemical evolution. During this 'prebiotic' stage, the first polymeric molecules capable of storing information and reproducing themselves were randomly assembled from organic precursors that were available on the early Earth. The most efficient replicators subsequently evolved into the macromolecular informational nucleic acids - DNA and RNA - that became the basis for all forms of life on our planet.

For billions of years, DNA has been the primary carrier of hereditary information in biological organisms. DNA strands are made up of four types of chemical subunits, and the genetic information it contains is encoded in the linear sequence of these 'nucleosides'. Moreover, the four subunits comprise two complementary pairs. Interactions between two strands with complementary sequences are responsible for the formation of the famous double helix, and play a crucial role in DNA replication. RNA also has vital functions in the replication of DNA and in the translation of nucleotide sequences into proteins.

Which of these two types of nucleic acid came first? The unanimous answer to that question up to now was RNA. Plausible models that explain how RNA molecules could have been synthesized from precursor compounds in prebiotic settings were first proposed decades ago, and have since received substantial experimental support. Moreover, its conformational versatility allows RNA both to store information and to act as a catalyst. These insights have led to the idea of an 'RNA world' that preceded the emergence of DNA, which is now well established among specialists. How then were the first DNA subunits synthesized? The generally accepted view is that this process was catalyzed by an enzyme - a comparatively complex biomolecule whose emergence would have required millions of years of evolution.

But now a team of chemists led by LMU's Professor Oliver Trapp has proposed a much more direct mechanism for the synthesis of DNA subunits from organic compounds that would have been present in a prebiotic environment. "The reaction pathway is relatively simple," says Trapp, which suggests it could well have been realized in a prebiotic setting. For example, it does not require variations in reaction parameters, such as temperature. In Trapp's experiments, the necessary ingredients are water, a mildly alkaline pH and temperatures of between 40 and 70°C. Under such conditions, adequately high reaction rates and product yields are achieved, with high selectivity and correct stereochemistry.

Each of the nucleoside subunits found in DNA is made up of a nitrogen-containing base and a sugar called deoxyribose. Up to now, it was thought that deoxynucleosides could only be synthesized under prebiotic conditions by directly coupling these two - preformed - components together. But no plausible non-enzymatic mechanism for such a step had ever been proposed. The essential feature of the new pathway, as Trapp explains, is that the sugar is not linked to the base in a single step. Instead, it is built up on the preformed base by a short sequence of reaction steps involving simple organic molecules such as acetaldehyde and glyceraldehyde. In addition, the LMU researchers have identified a second family of possible precursors of DNA in which the deoxyribose moiety is replaced by a different sugar.

According to the authors of the study, these results suggest that the earliest DNA molecules could have appeared in parallel with RNA - some 4 billion years ago. This would mean that DNA molecules emerged around 400 million years earlier than previously thought.