Tech

A code for reprogramming immune sentinels

For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. The process is quick and effective, representing a pioneering contribution for applying direct reprogramming for inducing immunity. Importantly, the finding opens up the possibility of developing novel dendritic cell-based immunotherapies against cancer.

Our so-called dendritic cells function as the immune system's sentinels. Their task is to scan our tissues for foreign particles, such as bacteria, viruses or cancer cells, and to devour them. They subsequently break down the particles into smaller pieces, known as antigens, and present them on the surface to the immune system's killer cells (T-cells). In this way, the killer cells learn which infectious agents and cancer cells they are to search for and kill.

Due to these key features, dendritic cell-based strategies have been tested to treat cancer patients. However, cancer can affect the dendritic cells in such a way that they get lost or become dysfunctional. We therefore need to find new ways of generating dendritic cells for every patient. Now, for the first time, a research team in Lund has succeeded in obtaining dendritic cells by a process called direct reprogramming. They have identified three essential proteins (PU.1, IRF8 and BATF3) that are required and sufficient to change the identity of mouse cells to make them become dendritic cells instead. They have also confirmed that the same protein cocktail reprograms human skin-derived cells to dendritic cells. This study is now published and highlighted in the cover of the journal Science Immunology.

"From a tissue section taken from the skin, we can cultivate millions of cells and reprogram them to dendritic cells in a process that takes only nine days", says Filipe Pereira, the leader of the research team that conducted the study.

"Our study has shown that reprogrammed cells have the ability to effectively capture and present antigens to killer cells in the same way as 'natural' dendritic cells." The researchers can even direct the induced dendritic cells towards a particular target by presenting the right antigen to them in a test tube, before introducing the cells into the organism. This finding opens up future possibilities to develop new strategies for immunotherapy against solid tumours and blood cancers, beyond the treatments currently available.

"This represents an excellent opportunity to merge the fields of cellular reprogramming and cancer immunotherapy. Generating dendritic cells employing direct cell reprogramming is very attractive from a therapeutic perspective: our studies may be useful in the clinic for generation of patient-specific dendritic cells", according to Filipe Pereira.

Cancer immunotherapy employs the cellular components of a persons' immune system to fight cancer and it was awarded with the Nobel Prize in Physiology or Medicine this year. By using reprogrammed dendritic cells the probability of rejection by the organism is lower as these cells can be generated from the skin of each individual patient.

"Tumours often undergo a number of mutations, developing into a heterogeneous entity, which makes it more difficult for the immune system to identify them as a threat. In a more creative perspective, we now want to explore the process of dendritic cell reprogramming to develop a cancer gene therapy. We are aiming at injecting the three reprogramming proteins straight into the tumour forcing it to present their own tumour-specific antigens. This allows the activation of the killer cells against tumour cells and may lead to their elimination. We have named this concept TrojanDC in an analogy with Homero's Trojan horse. The great potential of this technology for cancer treatment lead us to start a new company together with Lund University for the development of this concept into a product that hopefully will reach cancer patients one day", says Filipe Pereira.

"Additionally, our studies open up the possibility of reprogramming other dendritic cell sub-types taking advantage of their distinct functional features. A better understanding of the mechanisms that determine the identity of immune sentinels and of how to use this knowledge to reprogram other cell types into dendritic cells could make these patient-specific cells useful in the clinic", concludes Filipe Pereira.

Credit: 
Lund University

Are amorphous solids elastic or plastic?

image: Left: Stability-reversibility map of hard sphere amorphous solids, represented in terms of volume and shear strains. Right: Typical stress-strain curves which show the reversible (green) and partially reversible (red) behaviors.

Image: 
JIN Yuliang

In a crystalline solid, the atoms form an ordered lattice. Crystalline solids respond elastically to small deformations: When the applied strain is removed, the macroscopic stress, as well as the microscopic configuration of the atomic lattice, goes back to the original state. On the other hand, a material behaves plastically if it does not return to its original state. In general, plasticity only occurs when the deformation is sufficiently large.

Unlike crystals, amorphous solids, such as glasses, granular matter, gels, foams, and emulsions, have disordered particle configurations. How do amorphous solids respond to a small deformation? Can standard elasticity describe amorphous solids?

To answer this question, Dr. JIN Yuliang from the Institute of Theoretical Physics (ITP) of the Chinese Academy of Sciences, together with his collaborators, systematically studied the mechanical properties of amorphous solids using a numerical model system.

Even though macroscopic properties such as stress and strain are reversible upon releasing a small deformation, microscopic configurations can be irreversible. The work needed to switch between before- and after-perturbation configurations is infinitesimal. This kind of amorphous solid is called marginally stable and results from a so-called Gardner transition, as predicted recently by mean-field theory.

The researchers further established a stability-reversibility map of hard-sphere amorphous solids, which unifies mechanical behaviors including elasticity, plasticity, yielding, and jamming.

According to the stability-reversibility map (Fig. 1), an amorphous solid has two typical behaviors, which depend on the extent of volume and shear strains. In the stable region, the amorphous solid is truly elastic and reversible, just like crystals. In the marginally stable region, on the other hand, elasticity is unavoidably mixed with plasticity, even for infinitesimal deformations. A marginally stable amorphous solid is only partially reversible.

The study shows that a more complete elastic theory is needed - one that can correctly incorporate amorphous solids. It also provides important insights into the design of next-generation mechanical materials such as metallic glasses.

Credit: 
Chinese Academy of Sciences Headquarters

High-temperature electronics? That's hot

image: A new organic plastic allows electronics to function in extreme temperatures without sacrificing performance.

Image: 
Purdue University/John Underwood

From iPhones on Earth to rovers on Mars, most electronics only function within a certain temperature range. By blending two organic materials together, researchers at Purdue University could create electronics that withstand extreme heat.

This new plastic material could reliably conduct electricity in up to 220 degrees Celsius (428 F), according to a paper published Thursday in the journal Science.

"Commercial electronics operate between minus 40 and 85 degrees Celsius. Beyond this range, they're going to malfunction," said Jianguo Mei, a professor of organic chemistry at Purdue University. "We created a material that can operate at high temperatures by blending two polymers together."

One of these is a semiconductor, which can conduct electricity, and the other is a conventional insulating polymer, which is what you might picture when you think of regular plastic. To make this technology work for electronics, the researchers couldn't just meld the two together - they had to tinker with ratios.

"One of the plastics transports the charge, and the other can withstand high temperatures," said Aristide Gumyusenge, lead author of the paper and graduate researcher at Purdue. "When you blend them together, you have to find the right ratio so that they merge nicely and one doesn't dominate the other."

The researchers discovered a few properties that are essential to make this work. The two materials need to be compatible to mixing and should each be present in roughly the same ratio. This results in an organized, interpenetrating network that allows the electrical charge to flow evenly throughout while holding its shape in extreme temperatures.

Most impressive about this new material isn't its ability to conduct electricity in extreme temperatures, but that its performance doesn't seem to change. Usually, the performance of electronics depends on temperature - think about how fast your laptop would work in your climate-controlled office versus the Arizona desert. The performance of these new polymer blend remains stable across a wide temperature range.

Extreme-temperature electronics might be useful for scientists in Antarctica or travelers wandering the Sahara, but they're also critical to the functioning of cars and planes everywhere. In a moving vehicle, the exhaust is so hot that sensors can't be too close and fuel consumption must be monitored remotely. If sensors could be directly attached to the exhaust, operators would get a more accurate reading. This is especially important for aircraft, which have hundreds of thousands of sensors.

"A lot of applications are limited by the fact that these plastics will break down at high temperatures, and this could be a way to change that," said Brett Savoie, a professor of chemical engineering at Purdue. "Solar cells, transistors and sensors all need to tolerate large temperature changes in many applications, so dealing with stability issues at high temperatures is really critical for polymer-based electronics."

The researchers will conduct further experiments to figure out what the true temperature limits are (high and low) for their new material. Making organic electronics work in the freezing cold is even more difficult than making them work in extreme heat, Mei said.

Credit: 
Purdue University

Targeted cognitive training benefits patients with severe schizophrenia

Schizophrenia is among the most difficult mental illnesses to treat, in part because it is characterized by a wide range of dysfunction, from hallucinations and mood disorders to cognitive impairment, especially verbal and working memory, which can be explained in part by abnormalities in early auditory information processing.

In recent years, targeted cognitive training (TCT) has emerged as a promising therapeutic intervention. TCT uses computerized training, such as sophisticated brain games, to target specific neural pathways, such as memory, learning and auditory-based senses, to beneficially alter the way they process information.

But while TCT has proven effective for mild to moderate forms of schizophrenia under carefully controlled conditions, it remains unclear whether the approach might benefit patients with chronic, refractory schizophrenia treated in non-academic settings, such as those cared for in locked residential rehabilitation centers.

In a study published in the December print issue of Schizophrenia Research, senior author Gregory A. Light, PhD, professor of psychiatry at UC San Diego School of Medicine and director of the Mental Illness, Research, Education and Clinical Center at Veterans Affaris San Diego Healthcare System, and colleagues investigated whether TCT improved auditory and verbal outcomes among the most difficult of schizophrenia patients.

"Chronic, treatment-refractory patients mandated to locked residential care facilities make up just a small subgroup of persons with schizophrenia, but they consume a disproportionately large share of mental health care resources," said Light. "Finding an effective therapy for them is critical."

Light's team studied 46 patients with schizophrenia psychosis recruited from a community-based residential treatment program, each following acute hospitalization. All were deemed "gravely disabled," unable to care for themselves, and under the guardianship of a private party or government agency. Participants were randomized to either standard treatment-as-usual (TAU) or TAU plus TCT, in which they used laptop computers to perform various learning and memory game exercises, often involving auditory cues.

The researchers found that among participants who completed the roughly three months of TAU-TCT treatment, verbal learning and auditory perception scores improved; and severity of auditory hallucinations lessened. Of note: The benefits were not negatively impacted by age, clinical symptoms, medication or illness duration. "Our results suggest that chronically ill, highly disabled patients can benefit from TCT," said Light. "That contradicts current assumptions."

Light cited some caveats. "We're somewhere between the Wild West and golden age of cognitive training for schizophrenia patients. There is much still to be learned and done," he said. Patients in this study represented some of the most difficult patients to treat, with therapy regimens that are highly complex. "We need to do a lot more research."

Light and others are doing so. In a recent paper published in Neuropsychopharmacology, for example, he and colleagues described the underlying mechanism involved in TCT to improve auditory function. And in past work, schizophrenia-and-auditory-cues.aspx Light and others have shown that deficiencies in the neural processing of simple auditory tones can evolve into a cascade of dysfunctional information processing in the brains of patients with schizophrenia.

Credit: 
University of California - San Diego

Climate players: Animals can swing a landscape's capacity to store carbon

Advances in remote sensing technologies are helping scientists to better measure how global landscapes -- from forests to savanna -- are able to store carbon, a critical insight as they evaluate the potential role of ecosystems in mitigating climate change.

One factor often ignored in these carbon cycle assessments, however, is the role of wild animals. Compared with the vast capacity for trees and plants to store carbon, the conventional wisdom goes, low-abundant animal populations simply can't have much effect on these global systems.

In a new paper published in Science, a team of researchers led by Yale's Oswald J. Schmitz makes the case that the very presence of wild animals can trigger direct or indirect feedback effects that alter a landscape's capacity to absorb, release, or transport carbon. In reviewing a growing body of research, they find that animals can increase or decrease rates of biogeochemical processes by 15 to 250 percent or more.

Indeed, they argue that failure to account for the role of animals can undermine the accuracy of any evaluation of ecosystem carbon budgets. They offer insights into how researchers might integrate animal ecology, ecosystem modeling, and remote sensing to more accurately predict and manage carbon cycling across landscapes.

"Some of us have been saying for a long time that it's not just animal abundance that matters but what these animals do that is important," said Schmitz, the Oastler Professor of Population and Community Ecology at the Yale School of Forestry & Environmental Studies, and lead author of the paper. "We're finally to the point that there's some pretty strong evidence to support these ideas."

The paper was co-authored by an interdisciplinary team from the University of California, Santa Cruz; Memorial University of Newfoundland; Northern Arizona University; Utah State University; the Universidade Estadual Paulista in Rio Claro, Brazil; and Stanford University.

Experimental and observational analyses have shown that changes in animal abundances can cause major shifts in capacity of ecosystems to store or exchange carbon. In some cases, these changes have even caused ecosystems to switch from carbon sources (when animals are not abundant) to carbon sinks (when they are).

In the Serengeti, for instance, the decimation of Wildebeest populations during the mid-20th century allowed ground vegetation to flourish, eventually promoting wildfires that consumed 80 percent of the ecosystem annually and led to a net release of carbon dioxide into the atmosphere; when disease management and anti-poaching efforts helped animal populations recover, a greater share of the carbon stored in vegetation was consumed by Wildebeest and released as dung, keeping it in the system and restoring the landscape as a CO2 sink.

In tropical forests, the conservation of large mammals maintains vital functional roles -- including seed dispersal by frugivores and support of plant production by herbivores -- that promote carbon storage; a 3.5-fold increase in the number of mammal species, one study finds, increases carbon retention by 230 to 400 percent.

But the presence of grazing herbivores in other places -- such as caribou and muskox in the Arctic or moose in boreal forests -- can cause a 15 to 70 percent decrease in CO2 uptake and storage.

Human impacts increasingly shape these relationships, whether it's through the reduction of wildlife populations through poaching, overfishing or lost habitat, or the reintroduction of species to landscapes.

Chris Wilmers, an associate professor of wildlife ecology and global change at the University of California, Santa Cruz, and co-author of the paper, says that humans have played a huge role in shaping animal communities, from the composition of species to the distances, directions, and speeds at which they move across landscapes.

"If we want to understand how our impacts on and/or management of animal populations scale up to influence ecosystem wide carbon cycling then we need tools that allow us to link the things animals do to their ultimate consequences on the carbon cycle," he said.

The authors review advances in spatial ecosystem ecology that can reveal the link between animal movements and patterns of carbon uptake and storage across landscapes. And they highlight developments in remote sensing that are enabling scientists to collect and analyze data needed to make these connections.

"We show the effects of animals are large and important, but also that remote sensing can greatly inform what we know about how animals alter ecosystems through time, whether appropriating biomass through herbivory or trampling or enhancing productivity through nutrient and seed dispersal," said Scott Goetz, a professor at Northern Arizona University who has conducted satellite remote sensing research for more than three decades, and another co-author.

"New remote sensing technology, like the GEDI Lidar instrument launched this week to the International Space Station, will help us do a much better job of capturing the influence of animals on plant biomass and productivity dynamics."

The impact of wild animals on the carbon cycle becomes increasingly relevant as researchers and policy-makers consider the use of natural ecological processes to recapture and store atmospheric carbon within ecosystems as a tool to tackle climate change.

Researchers rarely consider wildlife conservation as a strategy to increase an ecosystem's carbon storage capacity, said Schmitz. In fact, some believe managing wildlife habitat conflicts with the goal of creating carbon storage capacity.

"They think that animals either aren't important enough or that you can't take up carbon and conserve animals in the same landscape," he said. "Our message is that you can and should. It can be a win-win for both biodiversity conservation and carbon uptake."

Credit: 
Yale School of the Environment

New traffic rules in 'Graphene City'

video: Dr. Jun Zhu, professor of physics, explains the waveguides her team creates in 2D graphene with an eye to expanding electronics beyond silicon. An animation of color coded cars explains how electrons can be directed through the waveguides with precision.

Image: 
Materials Research Institute, Penn State

In the drive to find new ways to extend electronics beyond the use of silicon, physicists are experimenting with other properties of electrons, beyond charge. In work published today (Dec 7) in the journal Science, a team led by Penn State professor of physics Jun Zhu describes a way to manipulate electrons based on their energy in relation to momentum -- called "valley degree of freedom."

"Imagine you are in a world where electrons are colored -- red or blue," Zhu said, "and the roads that electrons travel on are also colored red or blue. Electrons are only allowed to travel on roads of the same color, so that a blue electron would have to turn into a red electron to travel on the red road."

Two years ago, Zhu's team showed that they could build color-coded, two-way roads in a material called bilayer graphene. Because of their color-coding, these roads are topological. In the current study, the researchers made a four-way intersection where the color-coding of the roads is switched on the other side. Therefore, you have a situation where a blue car traveling northbound comes to this intersection and discovers that on the other side of the intersection northbound roads are colored red. If the electron cannot change color, it is forbidden from traveling onward.

These roads are actually electron waveguides created by gates defined with extreme precision using state-of-the-art electron beam lithography. The colors are actually the valley index of the cars, and the color-coding of the roads is controlled by the topology of the waveguides, analogous to the left-driving and right-driving rules of different countries. Changing the color of the cars requires "inter-valley scattering," which is minimized in the experiment to enable the traffic control to work.

"What we have achieved here is a topological valley valve, which uses a new mechanism to control electron flow," Zhu said. "This is part of a fledging field of electronics called valleytronics. In our experiment, controlling the topology -- the valley-momentum locking of the electrons -- is what made it work."

In the study, the researchers asked where would the metaphorical blue car go if it could not travel onward?

"It will have to turn either left or right," said lead author Jing Li, Zhu's former doctoral student, now a director's postdoctoral fellow at Los Alamos National Lab.

"We have additional ways of controlling the turning traffic -- by moving the lane incrementally closer to a right or left turn, the percentage of electrons/cars turning right or left can be smoothly tuned to be 60 percent one way, 40 percent the other, or any other combination of percentages."

This controlled partition is called a "beam splitter," which is common for light but not easily accomplished with electrons. Zhu and Li said they are excited about this control they have achieved for their color-coded roadways, as it enables more advanced experiments down the road.

"The creation of the device requires many steps and fairly complicated e-beam lithography," Li said. "Thankfully, Penn State's state-of-the art nanofabrication facility as well as a team of professional support staff enabled us to do all this."

The next challenge for Zhu's team will be to try to build their devices to operate at room temperature rather than at the very cold temperatures they currently need. It is doable, Zhu believes, but challenging.

"The approach we took to make this device is scalable," Zhu said. "If large-area bilayer graphene and hexagonal boron nitride become available, we can potentially make a city of topological roads and shuttle electrons to places they need to go, all without resistance. That would be very cool."

Credit: 
Penn State

Eliminating the latent reservoir of HIV

A new study suggests that a genetic switch that causes latent HIV inside cells to begin to replicate can be manipulated to completely eradicate the virus from the human body. Cells harboring latent HIV are "invisible" to the natural defenses of the immune system.

The findings, which suggest a cure for HIV may be possible, are reported in the journal Proceedings of the National Academy of Sciences.

During infection, the DNA of HIV makes its way into the host cell's nucleus and integrates itself into the host genome. The Tat gene circuit is a key piece of HIV DNA that controls the HIV gene transcription and activation. When activated, it initiates a takeover of the cell's machinery to churn out new copies of the HIV virus, which eventually burst from the cell and infect neighboring cells. HIV-specific immune effector cells kill cells infected with HIV, but only when the cells are being used to produce more of the virus, meaning that the Tat gene circuit is switched on. In cells that are latently infected, the Tat gene circuit is off, and the cell goes about its normal business all the while harboring quiescent HIV.

"By targeting the Tat gene circuit with drugs or small molecules to activate it, we would be able to cause latently-infected cells to start producing more virus, and then they can be destroyed by the immune system," said Jie Liang, the Richard and Loan Hill Professor of Bioengineering in the University of Illinois at Chicago College of Engineering and a lead author of the paper. So far, there are no drugs successfully targeting this circuit.

People infected with the HIV virus can live relatively normal lives with exceedingly low or even undetectable viral loads thanks to powerful antiretroviral therapies that work to suppress viral replication. But even in people where the virus is undetectable, it doesn't mean it's completely absent. The HIV virus can hide in cells in an inactivated state, meaning it isn't actively replicating.

This is a dire situation and makes life-long antiretroviral therapy the only option for HIV infected patients.

"It is extremely difficult to flush latently-infected cells out of their latency," Liang said.

Techniques developed to reactivate latent HIV-infected cells so that they become susceptible to the body's natural immune response or to drug therapies have had mixed results -- mostly because the technique, known as "shock and kill," relies on a class of drugs called HDAC inhibitors that come with severe adverse effects.

"We need to better understand the mechanisms that regulate HIV latency so we can identify new opportunities for intervention and develop better drugs that can either lock viral particles in a latent state, or kill latent cells, or both," Liang said.

The Tat gene circuit has a random probability of being active or inactive, and the switch from inactive to active can happen spontaneously. "In HIV-infected cells, reactivation of the Tat gene circuit is still a very rare event," Liang said.

Liang and his colleagues developed advanced computational algorithms to study the Tat gene circuit under different conditions.

"Using different models and algorithms, we were able to accurately map a 'probability landscape' of the cellular reactions that can impact Tat gene circuit reactivation, and our results suggest new ways of targeting latent cells that may lead to the eradication of the HIV virus from a host," Liang said.

Liang and his colleagues identified ways to manipulate the Tat gene circuit so that the "shock and kill" technique would be more effective. They also looked at a "block and lock" strategy, where latent viral particles are locked into latency by permanently blocking activation of the Tat gene circuit.

"Our results suggest that by controlling HIV latency through manipulation of the Tat gene circuit, effective therapeutic strategies can be identified that would one day provide a cure for HIV," Liang said.

Credit: 
University of Illinois Chicago

Monitoring species: Are we looking long enough?

The conservation of animals relies heavily on estimates of their numbers. Without knowing how many individuals there are, it is impossible to know whether a population is thriving or dying out--and whether conservation efforts are getting the job done. But making those estimates is no mean feat, reports Easton R. White of the Center for Population Biology at the University of California, Davis, writing in BioScience. Unfortunately, he says, many monitoring periods of threatened species are short, a result of "short funding cycles and typical experimental time frames."

Perhaps more problematic, monitoring periods used by the International Union for Conservation of Nature and other organizations charged with evaluating population health are crudely determined: "For many populations, the IUCN criteria suggest that more years than necessary are required to assess a population as vulnerable. Conversely, for other populations, the IUCN criteria suggest sampling times that are less than the minimum time required for statistical power."

Statistical power, explains White, is the probability of detecting a trend if it actually exists, and using appropriately powered protocols will offer a truer representation of population health. With poorly powered monitoring, conservationists might not know, for instance, whether an effort to restore a threatened species was succeeding or leaving it in peril.

But what sampling period, precisely, is required for monitoring populations over time? White argues that according to his data, "72% of time series required at least 10 years of continuous monitoring in order to achieve a high level of statistical power."

Efforts to quantify necessary sampling periods are not unheard of, but this one, says White, constitutes the "first attempt to document the minimum sampling requirements for such a wide diversity and number of species." Indeed, White's analysis comprises 822 species in total and stands to upend traditional measurement protocols, which typically rely on "rules of thumb" rather than statistical power. "These results are evidence against overly simplified measures of minimum sampling time based on generation length or other life-history traits, such as those of the IUCN criteria." White argues that considering statistical power in sampling is essential to understanding population trends--but are conservation organizations ready to follow suit? Only time will tell.

Credit: 
American Institute of Biological Sciences

New insights in rust resistance in wheat

Researchers from Aarhus University have contributed to creating new knowledge about resistance to yellow rust, which is a serious fungal disease in wheat. The results can have global importance.

For more than 20 years, a large international group of researchers, including from Aarhus University, has worked purposefully to investigate the function and genetics of Yr15 resistance, a gene that protects wheat against yellow rust. Yellow rust is a widespread and serious fungal disease that causes many losses in wheat globally. The researchers' new knowledge is an important piece in the jigsaw regarding the development of new cultivars of wheat that are resistant to yellow rust. The results were recently published in Nature Communications.

Wheat is one of the world's most important crops. On the global scale 244 million hectares are grown, which is more area than any other crop. The yield is more than 750 million tons per year. Wheat is widely used for both food and feed so it is therefore important to protect it against fungal diseases.

Yellow rust threatens wheat

One of the diseases that can infect wheat is the fungal disease yellow rust. Approximately 88 percent of wheat production is susceptible to yellow rust and a conservative estimate says that the disease ruins at least five million tons of the global annual wheat harvest.

The pathogenic fungus evolves quickly to produce new, virulent strains, so there is a constant arms race between plant breeders to develop disease-resistant varieties of wheat and the rust fungus. With a better understanding of the mechanisms that the wheat plant uses for self-defence, plant breeders will be more well-equipped for the task. This is precisely the area in which the research group can contribute significant new results.

Defence mechanism investigated

The researchers zoomed in on the gene sequence of the Yr15 resistance gene in wheat. Yr15 is known for being one of the most effective resistance genes against yellow rust. The researchers found that Yr15 has a unique mode of action. Some of the members of the international group of researchers mapped the gene sequence of Yr15, while the researchers from Aarhus University investigated how the resistance gene prevents fungal growth inside the infected wheat plant.

- Yr15 is an old acquaintance and plant breeders already have it "in stock". The new and exciting finding is that we have discovered that Yr15 works differently than other resistance genes. It produces defence responses early in the infection process, and we have found only one single case where the fungus could bypass this defence, says Professor Mogens Støvring Hovmøller from the Department of Agroecology at Aarhus University and one of the researchers in the international group.

A whole artillery is needed

When you breed disease-resistant crops, it is necessary to have access to resistance genes that represent the whole array of modes of action. In this way, if the fungus overcomes one defence mechanism, other resistance genes may prevent the fungus from causing disease in the plant.

With the aid of advanced microscopy, the researchers at Aarhus University observed the actual defence responses associated with Yr15 resistance in wheat. The researchers at Aarhus University utilised their access to a wide array of fungal isolates hosted by the Global Rust Center at AU Flakkebjerg, where fungal isolates from all over the world are stored for the purpose of research in wheat rust.

Credit: 
Aarhus University

Microplastics found in all sea turtle species

Tests on more than 100 sea turtles - spanning three oceans and all seven species - have revealed microplastics in the guts of every single turtle.

Researchers from the University of Exeter and Plymouth Marine Laboratory, working with the Greenpeace Research Laboratories, looked for synthetic particles (less than 5mm in length) including microplastics in 102 sea turtles in the Atlantic, Pacific and Mediterranean.

Synthetic particles were found in all of the turtles, the most common being fibres, which can potentially come from sources including clothing, tyres, cigarette filters and maritime equipment such as ropes and fishing nets.

"The effect of these particles on turtles is unknown," said lead author Dr Emily Duncan, of the Centre for Ecology and Conservation on the University of Exeter's Penryn Campus in Cornwall.

"Their small size means they can pass through the gut without causing a blockage, as is frequently reported with larger plastic fragments.

"However, future work should focus on whether microplastics may be affecting aquatic organisms more subtly.

"For example, they may possibly carry contaminants, bacteria or viruses, or they may affect the turtle at a cellular or subcellular level. This requires further investigation."

In total, more than 800 synthetic particles were found in the 102 turtles studied.

But researchers only tested part of each animal's gut - so the total number of particles is estimated to be about 20 times higher.

Researchers do not currently understand how synthetic particles are ingested by turtles, but the likely sources are polluted seawater and sediments, and eating via prey or plants.

Professor Brendan Godley, senior author of the study, added: "It really is a great shame that many or even all of the world's sea turtles have now ingested microplastics.

"At the moment, this is not the main threat to this species group but it is a clear sign that we need to act to better govern global waste."

Necropsies were carried out on the turtles after they died either by stranding or bycatch (accidental catching in fishing).

The study sites were North Carolina, USA (Atlantic), Northern Cyprus (Mediterranean) and Queensland, Australia (Pacific).

The turtles with the most synthetic particles were in the Mediterranean - thought to have higher rates of contamination than the Atlantic or Pacific - but this study's sample sizes and methodology did not allow for detailed geographical comparisons.

Dr Penelope Lindeque, of Plymouth Marine Laboratory, said: "While this study has been successful, it does not feel like a success to have found microplastic in the gut of every single turtle we have investigated.

"From our work over the years we have found microplastic in nearly all the species of marine animals we have looked at; from tiny zooplankton at the base of the marine food web to fish larvae, dolphins and now turtles.

"This study provides more evidence that we all need to help reduce the amount of plastic waste released to our seas and maintain clean, healthy and productive oceans for future generations."

Louise Edge, plastics campaigner at Greenpeace, said: "This important research demonstrates the breadth of our plastics pollution problem.

"Our society's addiction to throwaway plastic is fuelling a global environmental crisis that must be tackled at source."

The paper, published in the journal Global Change Biology, is entitled: "Microplastic ingestion ubiquitous in marine turtles."

Credit: 
University of Exeter

Smokers who roll their own less inclined to quit

Smokers who roll their own cigarettes are less likely to try quitting smoking, according to a new study carried out by UCL.

The research, published today in BMJ Open and funded by Cancer Research UK, found that only 15.9% of the smokers who mainly rolled their own cigarettes were highly motivated to quit, compared to 20.3% of those who mainly smoked factory-made cigarettes.

The study found that the major reason for roll-your-own (RYO) smokers' disinclination to quit appeared to be the relatively cheap cost of RYO products compared with factory-made cigarettes. While average daily cigarette consumption by RYO users was broadly comparable to that of factory-made cigarette smokers, they only spent around half as much on smoking each week (£14.33 versus £26.79).

"Cost is consistently reported by smokers as one of the primary motives for quitting. With RYO cigarettes offering a lower cost alternative to factory-made cigarettes, RYO users may be more able to afford to continue to smoke and therefore less inclined to try to quit," explained the study's lead author, Dr Sarah Jackson (UCL Institute of Epidemiology & Health Care).

The research was conducted over a period of nine and a half years, from November 2008 to March 2018, using the Smoking Toolkit Study, an ongoing monthly study about smoking habits in England. Data was provided by over 38,000 English adults who were current smokers or who had quit in the past year.

Over half (56.3%) of the smokers surveyed said they exclusively smoked factory-made cigarettes and over a third (36.6%) said they exclusively smoked RYOs.

According to the Office for National Statistics (ONS) in 2017, 15.1% of the UK population are smokers - around 7.4m people - but even though the overall smoking prevalence in the UK is declining, use of RYO cigarettes is increasing. Between 1990 and 2017, RYO use in Britain increased from 2% to 28% in female and from 18% to 44% in male smokers.

"This shift from factory-made to RYO smoking was what prompted us to investigate the phenomenon in more detail. With a growing proportion of the smoking population using RYO, it is important to understand the extent to which RYO smoking influences smokers' desires to quit," said Dr Jackson.

"We found that RYO smokers were less motivated to stop smoking and less likely to make a quit attempt than smokers of factory-made cigarettes."

"This has important implications for tobacco control policy, given that a key strategy used by governments worldwide to reduce smoking is to raise taxes on tobacco in order to increase the cost of smoking."

Kruti Shrotri, Cancer Research UK's tobacco control expert, added: "RYO cigarettes are much cheaper, so it's not surprising that smokers using these cigarettes are less motivated to quit than those using factory-made ones. But it's important to know that there's no safe way to use tobacco. The Government needs to increase taxes on rolling tobacco to match the prices of factory-made cigarettes to help motivate smokers to quit, whatever type of tobacco they use.

"Smoking is the single biggest cause of cancer, preventable illness and avoidable death. We encourage smokers to talk to their local Stop Smoking Service, GP or pharmacist on how they can get support to quit."

Deborah Arnott, Chief Executive of ASH, said: "The evidence is clear, access to cheaper roll your own tobacco makes it less likely smokers will quit. And a major reason that factory-made cigarettes are more expensive is taxation. Tax is around 30p per cigarette for factory-made compared to less than half that for roll your own cigarettes. Significantly increasing roll your own taxes to remove this differential would be a win-win for the government, by discouraging smoking while at the same time increasing the total tax take."

Credit: 
University College London

Algae testbed experiment yields data useful for future projects

A unique experiment that explored how well algae grows in specific regions of the United States yielded data that could prove useful as the industry moves forward, according to research from the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) and Arizona State University (ASU).

Researchers established identical raceway-style ponds in five outdoor locations to cultivate and harvest three strains of algae during the four seasons. The project originated from a 2012 DOE award to ASU to lead the Algae Testbed Public-Private Partnership, a collaborative effort that includes NREL and focuses on providing year-over-year data on algal cultivation.

"This data is extremely valuable to anyone interested in growing algae outdoors in different regions of the United States," said Eric Knoshaug, a senior scientist in NREL's National Bioenergy Center and co-author of the newly published paper, "Unified Field Studies of the Algae Testbed Public-Private Partnership as the Benchmark for Algae Agronomics."

Published in Scientific Data, the paper's other co-authors are Ed Wolfrum and Lieve Laurens of NREL; Valerie Harmon of Harmon Consulting Inc.; and Thomas A. Dempster and John McGowen from the Arizona Center for Algae Technology and Innovation at ASU.

The testbed sites were in the Southwest desert, in Mesa, Arizona; the California coast, in San Luis Obispo; the inland Southeast, in Atlanta, Georgia; the Pacific tropics, in Kona, Hawaii; and the coastal Southeast, in Vero Beach, Florida. Ponds holding about 1,000 liters of water were installed near the end of 2013. Harvesting operations started in mid-2014 and continued through the middle of the next year. The data--everything from temperature and pH of the water to the amount of algae harvested and ambient weather conditions--were collected continuously.

Wolfrum and Knoshaug curated the resulting data. "Other researchers can take a look at this and use the data to quantify the effects of humidity, the effects of temperature, and the effects of light intensity because we kept all the variables we could constant," said Wolfrum, a principal researcher in NREL's Biosciences Center. "The only thing left is the geography and the environment." The paper goes into detail about how researchers collected the data and determined the quality of the information.

The 19-month experiment ended with Florida proving to be the best of the sites for algae production, with its humidity and year-round temperatures that don't dramatically swing between hot and cold. But not everyone interested in growing algae can do it in Florida, so the data enables others to make predictions on possible sites and to develop crop protection strategies.

Credit: 
DOE/National Renewable Energy Laboratory

How microbial interactions shape our lives

image: This is a super-resolution image of fly gut crypts colonized by the native Lactobacillus (red) and Acetobacter (green) bacteria. Fly cell nuclei appear blue.

Image: 
Benjamin Obadia

Baltimore, MD--The interactions that take place between the species of microbes living in the gastrointestinal system often have large and unpredicted effects on health, according to new work from a team led by Carnegie's Will Ludington. Their findings are published this week in the Proceedings of the National Academy of Sciences.

The gut microbiome is an ecosystem of hundreds to thousands of microbial species living within the human body. The sheer diversity within the human gut presents a challenge to cataloging and understanding the effect these communities have on our health.

Biologists are particularly interested in determining whether or not the microbiome as a whole is greater than the sum of its parts. In other words, to what extent do individual species influence our health and physiology, and to what degree are these impacts determined by interactions between the species present in our microbiomes?

Ludington and his team--including molecular biologists Alison Gould, Vivian Zhang, and Benjamin Obadia of University of California Berkeley; physicists Eric Jones and Jean Carlson of University of California Santa Barbara; and mathematicians Lisa Lamberti, Nikolaos Korasidis, and Niko Beerenwinkel of ETH Zurich and Alex Gavryushkin of University of Otago--used the naturally simple microbiome of fruit flies to comprehensively reveal the gut ecosystem. The team found that the interactions between species in the gut microbiome impact fly health and even longevity.

"The classic way we think about bacterial species is in a black-and-white context as agents of disease--either you have it, or you don't," Ludington said. "Our work shows that isn't the case for the microbiome. The effects of a particular species depend on the context of which other species are also present."

It has long been known from fruit fly studies that populations of gut bacteria can affect their host's development, fertility, and longevity. In 1927, Helen Steinfeld of UC Berkeley found that by simply removing the gut bacteria from her laboratory's fruit flies, she could extend their lifespans by 14 percent.

Ludington's team repeated the experiment and found a similar 23 percent lifespan extension when they removed their flies' particular microbiomes. But it was unclear to them how much of this influence was due to the individual species that were present and how much was due to their overall microbial ecology.

Ludington and his team built off Steinfeld's work to dissect the fruit fly gut microbiome and better understand how these microorganisms shape the lives of their insect hosts.

They developed a system for mapping all the possible interactions between the five species of bacteria found in the fly gut in order to see how they affected an insect's development, production of offspring, and lifespan, which combine to determine its fitness. The analysis of the interactions required developing new mathematical approaches, which are based on the geometry of a five-dimensional cube, where each species is a new dimension.

The team found that the interactions that take place between the microbial populations are as important to the fly's physiology as which individual species are present. In terms of the 23 percent change in lifespan, individual species can account for only one quarter of the effect, while interactions account for the rest. These interactions are highly influential to some, but not all, of the factors that determine a fly's likelihood of passing its genetic material on to a new generation.

"As we examined the total of what we call a fly's fitness--it's chances of surviving and creating offspring--we found that there was a tradeoff between having a short lifespan with lots of offspring, versus having a long lifespan with few offspring," Ludington explained. "This tradeoff was mediated by microbiome interactions. That means that if we want to understand how the microbiome impacts our health, we need to develop a predictive understanding of how combinations of bacteria affect the host, not just the individual species."

Additionally, the measurement and analysis tools developed for this research project demonstrate that the fruit fly is a good model for understanding more complex microbiome interactions in humans and other animals, which will be important for future work.

Credit: 
Carnegie Institution for Science

Toxic chemicals calling: Cell phones a source of flame retardants?

TORONTO, ON (Canada) - Cell phones - much has been written about their detrimental effects on attention spans, stress levels and dinner table conversations. People are in constant contact with their cell phones at all hours of the day. New research from the University of Toronto (U of T) suggests they could also be a source of toxic chemicals, or at least an indicator of the chemicals to which people are exposed.

In a study published today in Environment International, scientists from U of T found that levels of several toxic chemicals on the cell phones of Canadian women aged 18-44 were related to levels of those chemicals in their bodies and on their hands. It is the first study to identify handheld electronic devices as a potential source of exposure to organophosphate esters, chemicals often used either as flame retardants or plasticizers that make materials such as polyvinyl chloride more flexible and durable.

"We are concerned with these chemicals as they have been linked to neurotoxicity, decreased fertility and thyroid problems," says Miriam Diamond, a professor in the Department of Earth Sciences in the Faculty of Arts & Science at U of T and lead author of the study. "What we don't know for certain though is whether electronic devices are the source of the chemicals or an indicator of total exposure from other sources, or both."

The researchers found correlations between levels of organophosphate esters on electronic devices and levels on hands and in urine. Further, they found that levels of the flame retardants and plasticizers were higher on handheld devices such as cell phones and tablets, than non-handheld electronics such as televisions and desktop computers.

As such, handheld devices like cell phones may be sources of some of these compounds, but also may serve as time-integrated samplers, providing an indication of chemical exposure across the different environments where people spend time each day - for example, their homes, cars and workplaces.

These new findings come amidst calls for increased focus on the environmental and human health impacts of electronics. Existing electronics industry standards cover thermal, electrical, optical and even acoustic product safety, but do not specify how materials should be screened for possible toxicological impacts.

"Earlier this year the U.S. Consumer Product Safety Commission granted a petition to ban the use of certain harmful flame retardant chemicals in electronics and other products," says Diamond. "The organophosphate esters identified in this new study are often used as replacements for the banned chemicals, and increasing evidence indicates that these replacement chemicals are harmful as well."

Diamond says that given the ubiquity of these devices that are in so many people's hands all the time, from kids to adults, "periodically wiping down your cell phone should lower the levels of these toxic chemicals on the device and hence on your hands. She also adds that "we need to be aware of - and try to reduce - how much we use our handheld devices, especially by kids."

Credit: 
University of Toronto

The distance of microbial competitions shapes their community structures

Inside the microbial communities that populate our world, microbes are fighting for their lives.

These tiny organisms are in the soil, in the oceans, and in the human body. Microbes play several important roles - they can decompose waste, make oxygen and promote human health.

Within communities, microbes constantly compete with each other for space, nutrients and other resources. Their competitions can occur across multiple spatial scales, whether the microbes are close together or far apart.

When microbes are close together, they assemble a molecular device to inject toxins into their neighbors, suppressing their growth. When far apart, microbes release a small toxic molecule that travels through the community into other cells, causing their death.

Ting Lu, an associate professor of bioengineering at the University of Illinois and a member of the Carl R. Woese Institute for Genomic Biology, wanted to know if the varying distances of interactions affect the organization of microbial communities. Addressing this question can help researchers understand how these communities assemble.

Lu and his lab members --Venhar Celik Ozgen, Wentao Kong, Andrew Blanchard, and Feng Liu -- developed mathematical models and a set of synthetic microbial communities to study the role of varying distances during microbial battles. They created ecosystems that involved one-directional competition, where one microbe kills another, and ecosystems with bidirectional competition, where two types of microbes kill each other.

Their results, published in Science Advances, reveal an important reciprocal relationship between space and time.

In the community where one type of microbe kills another, the researchers found that long-range competition was more effective, as it took less time for the microbe to kill its competitor at a long range than at a short range.

Next, they studied the community where two types of microbes kill each other. Lu said their findings can best be understood by picturing two armies meeting in a battlefield, where one army has swords (contact-dependent molecular killing devices) and the other has arrows (diffusible toxic molecules that attack other microbes).

"When those two armies have a close fight, the sword is more potent because it can kill the enemy right away," Lu said. "However, if those parties are separated by a river, for instance -- although the sword is more lethal, it's out of their range."

At a close range, the contact-dependent devices were more effective. At long distances, diffusible molecules were more effective. That's why, in such two-way competitions, the density of the microbial population matters. If the population is dense, microbes are forced to compete at a close range, and those who use contact-dependent devices win. If the microbes are more spaced out, they compete at a long range, and those using diffusible molecules win.

The authors said that, to their knowledge, this is the first experiment to dissect the role of spatial interaction scale in the organization of microbial ecosystems. Lu said their results deepen their knowledge of how microbial communities assemble and function.

Their findings will also help with creating artificial microbial ecosystems, which can be used to treat diseases or increase plant growth.

"By learning the underlying organization . . . (it will) also help us design better ecosystems which can deliver functions more effectively and in more potent ways," Lu said.

Lu said the variation of interaction distances also frequently occurs in animal and plant cells, so their findings can provide insight into the organization of multicellular organisms as well.

"Although we focus on studying the spatial organization of microbe populations, we believe the knowledge that we learn for bacteria could be generalized and translated to other living systems," Lu said.

Credit: 
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign