Tech

The detrimental impact of pesticides on non-target organisms is one of the most urgent concerns in current agriculture. Double-stranded RNAs (dsRNAs) represent the most species-specific class of pesticides to date, potentially allowing control of a target pest without effecting other species. The unprecedented target-specificity of dsRNA is due to its nucleotide sequence-specific mode of action that results in post-transcriptional gene silencing, or RNA interference (RNAi), in the target species. The development and field use of dsRNAs, via both the insertion of transgenes into the plant genome and the application of dsRNA sprays, is a rapidly growing area of research. Simultaneously, there exists the growing prospect of harnessing RNAi within integrated pest management schemes.

Using the pollen beetle (Brassicogethes aeneus) and its host crop oilseed rape (Brassica napus) as a model crop?pest system, a team of researchers collectively from Estonian University of Life Sciences, Ghent University and Maastricht University examined how RNAi efficacy depends on duration of dietary exposure to dsRNA. To this end, the authors applied dsRNA (specifically designed to induce RNAi in the pollen beetle) to oilseed rape flowers, and analyzed RNAi-induced mortality between insects chronically fed dsRNA and insects fed dsRNA for 3 days. Most notably, their data suggest that, with chronic dietary exposure to dsRNA, reduced dsRNA concentrations can be applied in order to achieve a similar effect compared to short-term (e.g. 3 days) exposure to higher concentrations. This observation has important implications for optimizing dsRNA spray approaches to managing crop pests. Specifically, while crop pest management is likely to benefit from successive dsRNA spray treatments, this may still be of economic benefit in practice because lower concentrations (e.g. 5?10 times lower) may be suitable for an equally effective outcome.

This work is timely, as dsRNA spray approaches are increasingly under consideration due to not only reduced biotechnology requirements, but also less legal restrictions in certain countries (e.g. member states of the European Union), compared to the engineering and cultivation of RNAi cultivars. The study adds new insights to the current discussion surrounding the potential benefits of genetically engineered crops. Transgenic RNAi cultivars continuously produce the species-specific dsRNA within the plant's tissues, chronically exposing the target species to the pesticide as long as the pest continuously feeds on the crop. Thus, the authors highlight the need for research into the development and potential use of genetically engineered RNAi oilseed rape cultivars, given the enhanced RNAi efficacy resulting from chronic dsRNA feeding in the pollen beetle.

WASHINGTON--Deep in a Jamaican cave is a treasure trove of bat poop, deposited in sequential layers by generations of bats over 4,300 years.

Analogous to records of the past found in layers of lake mud and Antarctic ice, the guano pile is roughly the height of a tall man (2 meters), largely undisturbed, and holds information about changes in climate and how the bats' food sources shifted over the millennia, according to a new study.

"We study natural archives and reconstruct natural histories, mostly from lake sediments. This is the first time scientists have interpreted past bat diets, to our knowledge," said Jules Blais, a limnologist at the University of Ottawa and an author of the new study in the Journal of Geophysical Research: Biogeosciences, AGU's journal for research on the interactions among biological, geological and chemical processes across Earth's ecosystems.

Blais and his colleagues applied the same techniques used for lake sediments to a guano deposit found in Home Away from Home Cave, Jamaica, extracting a vertical "core" extending from the top of the pile to the oldest deposits at the bottom and taking it to the lab for biochemical analysis.

About 5,000 bats from five species currently use the cave as daytime shelter, according to the researchers.

"Like we see worldwide in lake sediments, the guano deposit was recording history in clear layers. It wasn't all mixed up," Blais said. "It's a huge, continuous deposit, with radiocarbon dates going back 4,300 years in the oldest bottom layers."

The new study looked at biochemical markers of diet called sterols, a family of sturdy chemicals made by plant and animal cells that are part of the food bats and other animals eat. Cholesterol, for example, is a well-known sterol made by animals. Plants make their own distinctive sterols. These sterol markers pass though the digestive system into excrement and can be preserved for thousands of years.

"As a piece of work showing what you can do with poo, this study breaks new ground," said Michael Bird, a researcher in environmental change in the tropics at James Cook University in Queensland, Australia, who was not involved in the new study. "They really extended the toolkit that can be used on guano deposits around the world."

Past climates, past diets

Like sediment and ice core records, the guano core extracted from the Jamaican cave recorded the chemical signatures of human activities like nuclear testing and leaded gasoline combustion, which, along with radiocarbon dating, helped the researchers to correlate the history seen in the guano with other events in Earth's climate history.

Bats pollinate plants, suppress insects and spread seeds while foraging for food. Shifts in bat diet or species representation in response to climate can have reverberating effects on ecosystems and agricultural systems.

"We inferred from our results that past climate has had an effect on the bats. Given the current changes in climate, we expect to see changes in how bats interact with the environment," said Lauren Gallant, a researcher at the University of Ottawa and an author of the new study. "That could have consequences for ecosystems."

The new study compared the relative amounts of plant and animal sterols in the guano core moving back in time though the layers of guano to learn about how bat species as a group shifted their exploitation of different food sources in the past.

The research team, which included bat biologists and a local caving expert, also followed living bats in Belize, tracking their food consumption and elimination to gain a baseline for the kinds of sterols that pass through to the poop when bats dine on different food groups.

Plant sterols spiked compared to animal sterols about 1,000 years ago during the Medieval Warm Period (900-1,300 CE), the new study found, a time when cores of lakebed sediments in Central America suggest the climate in the Americas was unusually dry. A similar spike occurred 3,000 years ago, at a time known as the Minoan Warm Period (1350 BCE).

"Drier conditions tend to be bad for insects," Blais said. "We surmised that fruit diets were favored during dry periods."

The study also found changes in the carbon composition of the guano that likely reflect the arrival of sugarcane in Jamaica in the fifteenth century.

"It's remarkable they can find biochemical markers that still contain information 4,000 years later," Bird said. "In the tropics, everything breaks down fast."

The approach demonstrated in the new study could be used to glean ecological information from guano deposits around the world, even those only a few hundred years old, Bird said.

"Quite often there are no lakes around, and the guano provides a good option for information about the past. It also contains biological information that lakes don't." Bird said. "There's a lot more work to do and a lot more caves out there."

A new algorithm can predict which genes cause cancer, even if their DNA sequence is not changed. A team of researchers in Berlin combined a wide variety of data, analyzed it with "Artificial Intelligence" and identified numerous cancer genes. This opens up new perspectives for targeted cancer therapy in personalized medicine and for the development of biomarkers.

In cancer, cells get out of control. They proliferate and push their way into tissues, destroying organs and thereby impairing essential vital functions. This unrestricted growth is usually induced by an accumulation of DNA changes in cancer genes - i.e. mutations in these genes that govern the development of the cell. But some cancers have only very few mutated genes, which means that other causes lead to the disease in these cases.

A team of researchers at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin and at the Institute of Computational Biology of Helmholtz Zentrum München developed a new algorithm using machine learning technology to identify 165 previously unknown cancer genes. The sequences of these genes are not necessarily altered - apparently, already a dysregulation of these genes can lead to cancer. All of the newly identified genes interact closely with well-known cancer genes and have been shown to be essential for the survival of tumor cells in cell culture experiments.

Additional targets for personalized medicine

The algorithm, dubbed "EMOGI" for Explainable Multi-Omics Graph Integration, can also explain the relationships in the cell's machinery that make a gene a cancer gene. As the team of researchers headed by Annalisa Marsico describe in the journal Nature Machine Intelligence, the software integrates tens of thousands of data sets generated from patient samples. These contain information about DNA methylations, the activity of individual genes and the interactions of proteins within cellular pathways in addition to sequence data with mutations. In these data, a deep-learning algorithm detects the patterns and molecular principles that lead to the development of cancer.

"Ideally, we obtain a complete picture of all cancer genes at some point, which can have a different impact on cancer progression for different patients", says Marsico, head of a research group at the MPIMG until recently and now at Helmholtz Zentrum München. „This is the foundation for personalized cancer therapy."

Unlike with conventional cancer treatments such as chemotherapy, personalized therapy approaches tailor medication precisely to the type of tumor. "The goal is to select the best therapy for each patient - that is, the most effective treatment with the fewest side effects. Additionally, we would be able to identify cancers already at early stages, based on their molecular characteristics."

"Only if we know the causes of the disease will we be able to counteract or correct them effectively," the researcher says. "That's why it's so important to identify as many mechanisms as possible that can induce cancers."

Better results by combination

"Until now, most research has focused on pathogenic changes in the genetic sequence, i.e., in the blueprint of the cell," says Roman Schulte-Sasse, a doctoral student on Marsico's team and first author of the publication. "At the same time, it has become apparent in recent years that epigenetic perturbations or dysregulated gene activity can lead to cancer as well."

This is why the researchers merged sequence data that reflect faults in the blueprint with information that represents events inside the cell. Initially, the scientists confirmed that mutations, or the multiplication of segments of the genome, are indeed the main drivers of cancer. Then, in a second step, they pinpointed gene candidates that are in a less direct context to the actual cancer-driving gene.

"For instance, we found genes whose sequence is mostly unchanged in cancer, and yet are indispensable to the tumor because they regulate energy supply," Schulte-Sasse says. These genes are out of control by other means, e.g. because of chemical changes on the DNA like methylations. These modifications leave the sequence information intact but govern a gene's activity. "Such genes are promising drug targets, but because they operate in the background, we can only find them by using complex algorithms."

In search of hints for further studies

The researcher's new program adds a considerable number of new entries to the list of suspected cancer genes, which has grown to between 700 and 1,000 in recent years. It was only through a combination of bioinformatics analysis and the newest Artificial Intelligence (AI) methods that the researchers were able to track down the hidden genes.

"The interactions of proteins and genes can be mapped as a mathematical network, known as a graph," Schulte-Sasse says. "You can think of it like trying to guess a railroad network; each station corresponds to a protein or gene, and each interaction among them is the train connection."

With the help of deep learning - the very algorithms that have helped artificial intelligence make a breakthrough in recent years - the researchers were able to discover even those train connections that had previously gone unnoticed. Schulte-Sasse had the computer analyze tens of thousands of different network maps from 16 different cancer types, each containing between 12,000 and 19,000 data points.

Suitable for other types of diseases as well

Hidden in the data are many more interesting details. "We see patterns that are dependent on the particular cancer and tissue" Marsico says. "We see this as evidence that tumors are triggered by different molecular mechanisms in different organs."

The EMOGI program is not limited to cancer, the researchers emphasize. In theory, it can be used to integrate diverse sets of biological data and find patterns there, explains Marsico. "It could be useful to apply our algorithm for similarly complex diseases for which multifaceted data are collected and where genes play an important role. An example might be complex metabolic diseases such as diabetes."

When winter storms threaten to make travel dangerous, people often turn to salt, spreading it liberally over highways, streets and sidewalks to melt snow and ice. Road salt is an important tool for safety, because many thousands of people die or are injured every year due to weather related accidents. But a new study led by Sujay Kaushal of the University of Maryland warns that introducing salt into the environment--whether it's for de-icing roads, fertilizing farmland or other purposes--releases toxic chemical cocktails that create a serious and growing global threat to our freshwater supply and human health.

Previous studies by Kaushal and his team showed that added salts in the environment can interact with soils and infrastructure to release a cocktail of metals, dissolved solids and radioactive particles. Kaushal and his team named these cascading effects of introduced salts Freshwater Salinization Syndrome, and it can poison drinking water and cause negative effects on human health, agriculture, infrastructure, wildlife and the stability of ecosystems.

Kaushal's new study is the first comprehensive analysis of the complicated and interconnected effects caused by Freshwater Salinization Syndrome and their impact on human health. This work suggests that the world's freshwater supplies could face serious threats at local, regional and global levels if a coordinated management and regulation approach is not applied to human sources of salt. The study, which calls on regulators to approach salts with the same level of concern as acid rain, loss of biodiversity and other high-profile environmental problems, was published April 12, 2021, in the journal Biogeochemistry.

"We used to think about adding salts as not much of a problem," said Kaushal, a professor in UMD's Department of Geology and Earth System Science Interdisciplinary Center. "We thought we put it on the roads in winter and it gets washed away, but we realized that it stuck around and accumulated. Now we're looking into both the acute exposure risks and the long-term health, environmental, and infrastructure risks of all these chemical cocktails that result from adding salts to the environment, and we're saying, 'This is becoming one of the most serious threats to our freshwater supply.' And it's happening in many places we look in the United States and around the world."

When Kaushal and his team compared data and reviewed studies from freshwater monitoring stations throughout the world, they found a general increase in chloride concentrations on a global scale. Chloride is the common element in many different types of salts like sodium chloride (table salt) and calcium chloride (commonly used for road salt). Drilling down into data from targeted regions, they also uncovered a 30-year trend of increasing salinity in places like the Passaic River in northern New Jersey and a 100-mile-plus stretch of the Potomac River that supplies drinking water to Washington, D.C.

The major human-related salt source in areas such the Northeastern U.S. is road salts, but other sources include sewage leaks and discharges, water softeners, agricultural fertilizers and fracking brines enriched with salts. In addition, indirect sources of salts in freshwater include weathering roads, bridges and buildings, which often contain limestone, concrete or gypsum, all of which release salt as they break down. Ammonium-based fertilizers can also lead to the release of salts in urban lawns and agricultural fields. In some coastal environments, sea-level rise can be another source of saltwater intrusion.

The study points to a growing body of research from around the world that shows how chemical cocktails released by all of these salt sources harm both natural and built environments. For example, changes in salt levels can allow invasive, more salt-tolerant species to take over a stream. Chemical cocktails released by salts can change the microbes in soil and water, and because microbes are responsible for decay and replenishment of nutrients in an ecosystem, that shift can lead to even more changes in the release of salts, nutrients and heavy metals into the environment.

In the built environment, salts can degrade roadways and infrastructure. They can also corrode water pipes causing the release of heavy metals into drinking water supplies as they did in Flint, Michigan.

"I am greatly surprised by the increasing scope and intensity of these problems as highlighted from our studies," said study co-author Gene E. Likens, founding president emeritus of the Cary Institute of Ecosystem Studies and a distinguished research professor at the University of Connecticut. "Increased salinization of surface waters is becoming a major environmental problem in many places in the world."

The variety of sources and complex interactions between salt and the environment are poorly understood, and every lake, stream and aquifer presents a different set of management challenges. The study suggests that management strategies must evaluate salt contributions from different sources on a watershed-ecosystem level and prioritize regulation accordingly, much the way nutrient loads in watersheds are currently managed.

Improvements in technology have helped reduce nutrient runoff, but safe and effective alternatives to road salts do not yet exist. Kaushal hopes that regulation, new technologies and a coordinated management approach can reduce the potential threats of Freshwater Salinization Syndrome on a broad scale.

"Ultimately, we need regulation at the higher levels, and we're still lacking adequate protection of local jurisdictions and water supplies," Kaushal said. "We have made dramatic improvements to acid rain and air quality, and we're trying to address climate change this way. What we need here is a much better understanding of the complicated effects of added salts and regulations based on that. This can allow us to avert a really difficult future for freshwater supplies."

Going forward, the study emphasizes the importance of increasing water monitoring efforts and using modern sensor technology to capture continuous data. High-frequency sensor data allows scientists and managers to detect peaks in salinity and water flow that may eventually help them to predict the chemical composition and accumulation of toxins due to Freshwater Salinization Syndrome.

In addition, Kaushal said field studies and experiments that trace the rapidly expanding effects of salt in the environment are needed to improve scientific understanding of the problem. He has been conducting such research in the streams running through and near UMD's College Park campus, an urban environment inside the Washington, D.C. Beltway.

Energy flows through a system of atoms or molecules by a series of processes such as transfers, emissions, or decay. You can visualize some of these details like passing a ball (the energy) to someone else (another particle), except the pass happens quicker than the blink of an eye, so fast that the details about the exchange are not well understood. Imagine the same exchange happening in a busy room, with others bumping into you and generally complicating and slowing the pass. Then, imagine how much faster the exchange would be if everyone stepped back and created a safe bubble for the pass to happen unhindered.

An international collaboration of scientists, including UConn Professor of Physics Nora Berrah and post-doctoral researcher and lead author Aaron LaForge, witnessed this bubble-mediated enhancement between two helium atoms using ultrafast lasers. Their results are now published in Physical Review X.

Measuring energy exchange between atoms requires almost inconceivably fast measurements, says LaForge.

"The reason why shorter time scales are needed is that when you look at microscopic systems, like atoms or molecules, their motion is extremely fast, roughly on the order of femtoseconds (10-15 s ), which is the time it takes them to move a few angstroms (10-10 m)," LaForge says.

Laforge explains these measurements are made with a so-called free-electron laser, where electrons are accelerated to nearly the speed of light, then using sets of magnets, the electrons are forced to undulate, which causes them to release short wavelength bursts of light. "With ultrafast laser pulses you can time-resolve a process to figure out how fast or slow something occurs," says LaForge.

The first step of the experiment was to initiate the process, says LaForge: "Physicists probe and perturb a system in order to measure its response by taking fast snapshots of the reaction. Thus, essentially, we aim to make a molecular movie of the dynamics. In this case, we first initiated the formation of two bubbles in a helium nanodroplet. Then, using a second pulse, we determined how fast they were able to interact."

With a second laser pulse the researchers measured how the bubbles interact: "After exciting the two atoms, two bubbles are formed around the atoms. Then the atoms could move and interact with one another without having to push against surrounding atoms or molecules," says LaForge.

Helium nanodroplets were used as a model system, since helium is one of the simplest atoms in the periodic table, which LaForge explains is an important consideration. Even though there are up to roughly a million helium atoms within a nanodroplet, the electronic structure is relatively simple, and the interactions are easier elucidate with fewer elements in the system to account for.

"If you go to more complex systems, things can get more complicated rather quickly. For instance, even liquid water is pretty complicated, since there can be interactions within the molecule itself or it can interact with its neighboring water molecules," LaForge says.

Along with bubble formation and the subsequent dynamics, the researchers observed energy transfer, or decay, between the excited atoms, which was over an order of magnitude faster than previously expected - as fast as 400 femtoseconds. At first, they were a bit perplexed about how to explain such a fast process. They approached theoretical physicist colleagues who could perform state-of-the-art simulations to better understand the problem.

"The results of our investigation were unclear but collaboration with theorists allowed us to nail down and explain the phenomenon," says LaForge.

He points out that an exciting aspect of the research is that we can push the envelope further in understanding the fundamentals of these ultrafast processes and pave the way for new research. The big innovation is being able to create a means to measure interactions down femtosecond or even attosecond (10-18 s) timescales. "It's really rewarding when you can perform a rather fundamental experiment that can also be applied to something more complex," says LaForge.

The process the researchers observed is called Interatomic Coulombic Decay (ICD), and is an important means for atoms or molecules to share and transfer energy. The bubbles enhanced the process, demonstrating how the environment can alter the speed at which a process occurs. Since ICD plays an important role in how living tissues react to radiation exposure - by creating low energy electrons which can go on to cause damage within tissues -- these findings are of biological importance, because it is likely that similar bubbles would form in other fluids, like water, and with other molecules like proteins.

"Understanding the timescale of energy transfer at the microscopic scale is essential to numerous scientific fields, such as physics, chemistry, and biology. The fairly recent development of intense, ultrafast laser technology allows for time-resolved investigations with unprecedented detail, opening up a wealth of new information and knowledge," says Berrah.

Creating a two-dimensional material, just a few atoms thick, is often an arduous process requiring sophisticated equipment. So scientists were surprised to see 2D puddles emerge inside a three-dimensional superconductor - a material that allows electrons to travel with 100% efficiency and zero resistance - with no prompting.

Within those puddles, superconducting electrons acted as if they were confined inside an incredibly thin, sheet-like plane, a situation that requires them to somehow cross over to another dimension, where different rules of quantum physics apply.

"This is a tantalizing example of emergent behavior, which is often difficult or impossible to replicate by trying to engineer it from scratch," said Hari Manoharan, a professor at Stanford University and investigator with the Stanford Institute for Materials and Energy Sciences (SIMES) at the Department of Energy's SLAC National Accelerator Laboratory, who led the research.

"It's as if when given the power to superconduct," he said, "the 3D electrons choose for themselves to live in a 2D world."

The research team calls this new phenomenon "inter-dimensional superconductivity," and in a report in the Proceedings of the National Academy of Sciences today, they suggest that this is how 3D superconductors reorganize themselves just before undergoing an abrupt shift into an insulating state, where electrons are confined to their home atoms and can't move around at all.

"What we found was a system where electrons behave in unexpected ways. That's the beauty of physics," said Carolina Parra, a postdoctoral researcher at SLAC and Stanford at the time of the study who carried out the experiments that led to the visualization of this intriguing result. "We were very lucky to find this behavior."

Electrons acting strangely

Although superconductivity was discovered more than a century ago, its usefulness was limited by the fact that materials became superconducting only at temperatures close to those of deep space.

So the announcement in 1986 that scientists had discovered a new and unexpected class of superconducting materials that operated at much higher - although still very cold - temperatures set off a tsunami of research that continues to this day, with the goal of figuring out how the new materials operate and developing versions that work at closer to room temperature for applications such as perfectly efficient power lines and maglev trains.

This study started with a high-temperature superconductor named BPBO for its four atomic ingredients - barium, lead, bismuth and oxygen. It was synthesized in the lab of Stanford Professor and SIMES investigator Ian Fisher by Paula Giraldo-Gallo, a PhD student at the time.

As researchers there put it through routine tests, including determining the transition temperature at which it flips between a superconducting and an insulating phase - like water changing to steam or ice - they realized that their data showed electrons behaving as if they were confined to ultrathin, 2D layers or stripes within the material. This was a puzzle, because BPBO is a 3D superconductor whose electrons are normally free to move in any direction they like.

Intrigued, Manoharan's team took a closer look with a scanning tunneling microscope, or STM - an instrument that can identify and even move individual atoms in the top few atomic layers of a material.

Interacting puddles

The stripes, they discovered, seemed to have no relationship with the way the material's atoms were organized or with tiny bumps and dips on its surface.

"Instead, the stripes were layers where electrons behave as if they are confined to 2D, puddle-like areas in the material," Parra said. "The distance between puddles is short enough that the electrons can 'see' and interact with each other in a way that allows them to move without resistance, which is the hallmark of superconductivity."

The 2D puddles emerged as the scientists carefully adjusted the temperature and other conditions toward the transition point where the superconductor would become an insulator.

Their observations closely match a theory of "emergent electronic granularity" in superconductors, developed by Nandini Trivedi of Ohio State University and colleagues.

"The predictions we had made went against the standard paradigm for superconductors," Trivedi said. "Usually, the stronger a superconductor is, the more the energy needed to break the bond between its superconducting electron pairs - a factor we call the energy gap. But my group had predicted that in this particular type of disordered superconductor, the opposite would be true: The system would form emergent puddles where superconductivity was strong but the pairs could be broken with much less energy than expected.

"It was quite thrilling to see those predictions being confirmed by the STM measurements from the Stanford group!"

Spreading the science

The results have practical implications for crafting 2D materials, Parra said.

"Most of the methods for making 2D materials are engineering approaches, like growing films a few atomic layers thick or creating a sharp interface between two materials and confining a 2D state there," she said. "This offers an additional way to get to these 2D superconducting states. It's cheaper, you don't need fancy equipment that requires very low temperatures and it doesn't take days and weeks. The only tricky part would be getting the composition of the material just right."

Parra now heads a lab at the Federico Santa Mari?a Technical University in Valparai?so, Chile, focusing on interdisciplinary studies of nanoscale biological materials. She recently won a grant to acquire and operate the first-ever low-temperature scanning tunneling microscope in South America, which she plans to use to continue this line of research.

"When I have this equipment in the lab," she said, "I will connect it with all the things I learned in Hari's lab and use it to teach a new generation of researchers that we're going to have working in nanoscience and nanotechnology in Chile."

Older adults with more harmful than healthy bacteria in their gums are more likely to have evidence for amyloid beta--a key biomarker for Alzheimer's disease--in their cerebrospinal fluid (CSF), according to new research from NYU College of Dentistry and Weill Cornell Medicine. However, this imbalance in oral bacteria was not associated with another Alzheimer's biomarker called tau.

The study, published in the journal Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, adds to the growing evidence of a connection between periodontal disease (gum disease) and Alzheimer's. Periodontal disease--which affects 70 percent of adults 65 and older, according to CDC estimates--is characterized by chronic and systemic inflammation, with pockets between the teeth and gums enlarging and harboring bacteria.

"To our knowledge, this is the first study showing an association between the imbalanced bacterial community found under the gumline and a CSF biomarker of Alzheimer's disease in cognitively normal older adults," said Angela Kamer, DDS, PhD, associate professor of periodontology and implant dentistry at NYU College of Dentistry and the study's lead author. "The mouth is home to both harmful bacteria that promote inflammation and healthy, protective bacteria. We found that having evidence for brain amyloid was associated with increased harmful and decreased beneficial bacteria."

Alzheimer's disease is characterized by two hallmark proteins in the brain: amyloid beta, which clumps together to form plaques and is believed to be the first protein deposited in the brain as Alzheimer's develops, and tau, which builds up in nerve cells and forms tangles.

"The mechanisms by which levels of brain amyloid accumulate and are associated with Alzheimer's pathology are complex and only partially understood. The present study adds support to the understanding that proinflammatory diseases disrupt the clearance of amyloid from the brain, as retention of amyloid in the brain can be estimated from CSF levels," said the study's senior author Mony J. de Leon, EdD, professor of neuroscience in radiology and director of the Brain Health Imaging Institute at Weill Cornell Medicine. "Amyloid changes are often observed decades before tau pathology or the symptoms of Alzheimer's disease are detected."

The researchers studied 48 healthy, cognitively normal adults ages 65 and older. Participants underwent oral examinations to collect bacterial samples from under the gumline, and lumbar puncture was used to obtain CSF in order to determine the levels of amyloid beta and tau. To estimate the brain's expression of Alzheimer's proteins, the researchers looked for lower levels of amyloid beta (which translate to higher brain amyloid levels) and higher levels of tau (which reflect higher brain tangle accumulations) in the CSF.

Analyzing the bacterial DNA of the samples taken from beneath the gumline under the guidance of NYU College of Dentistry microbiologist Deepak Saxena, PhD, the researchers quantified bacteria known to be harmful to oral health (e.g. Prevotella, Porphyromonas, Fretibacterium) and pro-oral health bacteria (e.g. Corynebacterium, Actinomyces, Capnocytophaga).

The results showed that individuals with an imbalance in bacteria, with a ratio favoring harmful to healthy bacteria, were more likely to have the Alzheimer's signature of reduced CSF amyloid levels. The researchers hypothesize that because high levels of healthy bacteria help maintain bacterial balance and decrease inflammation, they may be protective against Alzheimer's.

"Our results show the importance of the overall oral microbiome--not only of the role of 'bad' bacteria, but also 'good' bacteria--in modulating amyloid levels," said Kamer. "These findings suggest that multiple oral bacteria are involved in the expression of amyloid lesions."

The researchers did not find an association between gum bacteria and tau levels in this study, so it remains unknown whether tau lesions will develop later or if the subjects will develop the symptoms of Alzheimer's. The researchers plan to conduct a longitudinal study and a clinical trial to test if improving gum health--through "deep cleanings" to remove deposits of plaque and tartar from under the gumline--can modify brain amyloid and prevent Alzheimer's disease.

Respiratory disease increased markedly following one of Iceland's largest volcanic eruptions, a new study has found.

And the findings could have significant implications for actions taken to protect the health of the 800 million people globally living near active volcanoes. Indeed, only last month (March), lava burst through a crack in Iceland's Mount Fagradalsfjall in the first eruption of its type in more than 800 years.

The new research, led by the University of Leeds and the University of Iceland, examined the health impacts of pollution caused by the Holuhraun lava eruption in 2014-2015.

It shows that following exposure to emissions that changed chemically from gas to fine particles, incidents of respiratory disease in Iceland rose by almost a quarter, and the incidence of asthma medication dispensing by a fifth.

The findings, published today (10:00 GMT 12 April) in Nature Communications, highlight the need for decision-making authorities to prepare for health issues associated with returning emissions - known as mature plumes - in the days immediately following volcanic eruptions.

The report's co-lead author is Dr Evgenia Ilyinskaya, from the University of Leeds' School of Earth and Environment.

She said: "Volcanoes are a significant source of air pollution, but of course it's a source that cannot be controlled.

"Large volcanic eruptions can cause harmful air pollution both immediately, and also when the plume returns to the same area, which may happen without it triggering air pollution alerts.

"Our research shows that during prolonged eruptions such as Holuhraun, both young and mature plumes can be circulating at the same time, increasing the harmful health effects on those living in volcanic regions.

"This pollution return is not currently factored into responses to the threat to public health caused by volcanoes."

The Holuhraun eruption was one of the biggest of its kind in the last 200 years, releasing 11 million tonnes of sulphur dioxide that spread across Iceland and the Atlantic Ocean towards Europe.

During the six-months long eruption, residents of Iceland's capital, Reykjavík, were repeatedly exposed to the young and mature plumes, despite living 250km from the eruption site.

In their previous research, published in 2017, the scientists traced the evolution of the volcanic plume chemistry. They found that the plume had been swept by air currents towards the UK and mainland Europe before circling back to Icelandic cities and towns.

During this process, the plume composition matured as it lingered in the atmosphere - meaning that the volcanic sulphur dioxide had converted to particles.

These fine particles found in mature plumes are so small they can penetrate deep into the lungs, potentially causing serious health problems such as exacerbating asthma attacks.

In the returning plume, because the sulphur dioxide levels were reduced as the gas converted to particles, concentrations were therefore within European Commission air standards.

As a result, no health advisory message were in place in Iceland for the returning plume.

It is estimated that short and long-term exposure to these kind of fine particles, from both human-made and natural sources, cause over three million premature deaths globally per year and remains the single largest environmental health risk in Europe.

The new findings highlight the health risks of pollutants lingering in the atmosphere, and the implications for monitoring emissions from volcanic activity.

They point to the global need for health risk assessments and population safety management following volcanic eruptions.

Co-lead author Dr Hanne Krage Carlsen, from the University of Iceland and University of Gothenburg, said: "Iceland has some of the most complete health care records in the world. This was the first time a population of a considerable size and density could be assessed following major volcanic activity.

"This study provides the most robust evidence to date that exposure to a chemically-mature volcanic plume leads to increased use of a country's health care system.

"It also emphasizes that emissions from volcanoes are a region-wide issue, in this case potentially affecting the whole North Atlantic region.

"As the Holuhraun plume returned to Iceland, there was increased use of GPs and hospital emergency care units with regards to respiratory diseases. At the same time, there was a lack of public health advice.

"We recommend that future Government responses to volcanic air pollution globally considers both the implications to health caused by the initial eruptions, but also those of the returning plumes with additional threats to health."

Glioblastomas are the most common and most aggressive brain tumours. Their survival rate has barely increased over the last 50 years, indicating an urgent need to develop new therapeutic strategies. In a paper published this week in the journal Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research, the team led by Massimo Squatrito, Head of the Seve Ballesteros Foundation Brain Tumour Group at the Spanish National Cancer Research Centre (CNIO), proposes a novel therapeutic strategy based on the combination of temozolomide, the first-line treatment for these patients, and dianhydrogalactitol, a drug that is being tested in clinical trials and is already approved for the treatment of other tumours.

Currently, the main and virtually only treatment for glioblastomas is the combination of radiotherapy and the chemotherapy agent temozolomide, after surgical resection of the tumour mass. Like most chemotherapeutic agents used, temozolomide induces damage to the genetic material of tumour cells, causing them to break down and die. However, in almost half of the patients, such tumours become resistant to the drug and the tumour continues to grow even while undergoing treatment.

"Although the incidence of glioblastoma is not excessively high in adults, they are the most common brain tumours, and there are no effective treatments or markers of response to treatment or of the generation of resistance," says Squatrito.

DNA repair, the basis of resistance

Why do patients with glioblastoma stop responding to temozolomide? Squatrito and his team shed light on this central question last year in a paper published in the journal Nature Communications: some glioblastomas produce genomic rearrangements in the DNA repair gene MGMT, which increases its production and repairs the DNA damage induced by temozolomide so that the tumour manages to grow and evade treatment.

In the paper published now, the researchers studied temozolomide resistance in depth by using glioblastoma cell lines in which several key genes were silenced. The results show that this resistance not only depends on the MGMT gene but that it may also be mediated by failures in the MMR (DNA repair) pathway so that when any of its components are altered, tumour cells accumulate mutations that give them the ability to evade the effects of temozolomide.

Tumours are complex systems that use multiple tools to trick the body into supporting their growth and development. Combination therapies, targeting several components involved in the tumour process, are a revolution that brings hope to many patients. Advances in the understanding of the molecular biology of tumours allow the emergence of new therapies and targeted combinations thereof to fight the tumours and to avoid any type of resistance they may develop.

Combination therapy with dianhydrogalactitol

In the present study, the researchers focused on the drug dianhydrogalactitol, a chemotherapeutic agent that is able to cross the blood-brain barrier and reach the central nervous system, where it induces DNA damage in tumour cells. Dianhydrogalactitol is currently being tested in clinical trials for gliomas and other types of cancer such as ovarian cancer and is already approved in China for the treatment of acute myeloid leukaemia and lung cancer.

The results of this study show that temozolomide and dianhydrogalactitol act synergistically on tumour cells in vitro, resulting in slower growth of these cells compared to when they are treated with each drug individually. The researchers observed similar results in mice with brain tumours, which survived longer when treated simultaneously with temozolomide and dianhydrogalactitol.

Furthermore, the results suggest that, unlike temozolomide, the anticancer effects of dianhydrogalactitol are independent of the MGMT DNA repair gene and the MMR pathway. "Our data show that dianhydrogalactitol could be an effective treatment that circumvents the resistance mechanisms that arise during temozolomide treatment," explains Miguel Jiménez-Alcázar, first author of the paper.

"The results we obtained with this study are of great interest, as they could lead to a substantial improvement in the evolution of these patients," says Squatrito. "It now becomes a matter of urgency to take these finding to clinical practice to see if this combination of drugs increases survival; both drugs are clinically available, which could accelerate the timeline of this new approach," he concludes.

New York, NY (April 10, 2021) - A personalized cancer vaccine developed with the help of a Mount Sinai computational platform raised no safety concerns and showed potential benefit in patients with different cancers, including lung and bladder, that have a high risk of recurrence, according to results from an investigator-initiated phase I clinical trial presented during the virtual American Association for Cancer Research (AACR) Annual Meeting 2021, held April 10-15.

"While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments," said study author Thomas Marron, MD, PhD, Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine at Mount Sinai. "Cancer vaccines, which typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy."

To generate the personalized cancer vaccine, Dr. Marron and colleagues sequenced each patient's tumor and germline DNA and tumor RNA. They also identified the patient's tumor-specific target to help predict whether the patient's immune system would recognize the vaccine's targets.

The Mount Sinai computational pipeline, called OpenVax, allows the researchers to identify and prioritize immunogenic targets to synthesize and incorporate into the vaccine.

Following any standard cancer treatment such as surgery for solid tumors or bone marrow transplant for multiple myeloma, patients received 10 doses of the personalized vaccine over a six-month period. The vaccine was given with the immunostimulant, or adjuvant, poly-ICLC, which is "a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumor neoantigens," said study author Nina Bhardwaj, MD, PhD, Director of the Immunotherapy Program and the Ward-Coleman Chair in Cancer Research at The Tisch Cancer Institute at Mount Sinai.

"Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread," said Dr. Bhardwaj. "We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal--typically microscopic--residual disease. Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types."

Before the vaccine, the trial participants statistically had a high chance of disease recurrence. Thirteen patients received the Mount Sinai team's vaccine: 10 had solid tumor diagnoses and 3 had multiple myeloma.

After a mean follow-up of 880 days, four patients still had no evidence of cancer, four were receiving subsequent lines of therapy, four had died, and one chose not to continue the trial. The vaccine was well tolerated, with roughly one-third of patients developing minor injection-site reactions.

A phase 1 trial's primary goal is to determine the safety of an experimental treatment, which was achieved in this trial. Researchers also saw early potential benefits of the vaccine after blood tests of one of the patients showed an immune response from the vaccine, and two other patients had robust response to immunotherapy afterward, results that are normal after being exposed to a cancer vaccine.

HOUSTON - Researchers at The University of Texas MD Anderson Cancer Center have discovered that mutant KRAS and p53, the most frequently mutated genes in pancreatic cancer, interact through the CREB1 protein to promote metastasis and tumor growth. Blocking CREB1 in preclinical models reversed these effects and reduced metastases, suggesting an important new therapeutic target for the deadly cancer.

The findings were published today in Cancer Discovery and presented at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021 by Michael Kim, M.D., assistant professor of Surgical Oncology and Genetics.

"To our knowledge, this is the first study to show how these two major genetic drivers work together to promote tumor growth and metastasis," Kim said. "We learned that signaling downstream of mutant KRAS directly promotes mutant p53 activity. This discovery provides not only a new therapeutic target but unveils a vast transcriptional network that is activated downstream of these mutant proteins."

Mutations in KRAS and TP53, the two most frequently mutated genes in all human cancers, co-occur in roughly 70% of patients with pancreatic cancer. Mutant KRAS, found in 95% of pancreatic cancers, leads to an activated protein that aberrantly triggers many downstream signaling pathways. Mutant TP53 results in the loss of the proteins' tumor suppressor function, leaving the mutant protein capable of fueling additional oncogenic processes, such as metastasis.

Unfortunately, no current therapies are able to block the mutant forms of KRAS or p53 prevalent in pancreatic cancer, so there is a need to identify common, alternative therapeutic targets downstream of these proteins that could lead to more effective treatment regimens for pancreatic cancer, Kim explained.

To learn how mutant KRAS and p53 might be interacting, Kim's team of researchers collaborated with Gigi Lozano, Ph.D., chair of Genetics, to develop a novel mouse model of pancreatic cancer that expresses oncogenic KRAS and mutant p53 specifically in tumor cells, leaving the tumor microenvironment unaltered.

In this model, the team observed more than twice as many metastatic lesions than was seen when p53 was genetically removed, suggesting that the mutant proteins together cause a significant increase in metastatic potential. With further study, the researchers discovered mutant KRAS activates CREB1, a transcription factor that then directly interacts with mutant p53 to promote the aberrant expression of hundreds of genes.

This activation results in the increased expression of FOXA1, which in turns creates a new cascade of events leading to increased activity of the Wnt/β-catenin pathway, both of which promote cancer metastasis.

Using an available small-molecule drug to target CREB1 in this model resulted in decreased expression of FOXA1, β-catenin and associated target genes, along with a corresponding reduction in metastases. While early, these findings suggest that targeting CREB1 may be a viable strategy to block the metastatic effects of mutant KRAS and p53 in pancreatic cancer.

"The identification of this cooperative node suggests that there should be increased focus on CREB1 as a target that could be therapeutically exploited to improve patient outcomes," Kim said. "With the frequency of KRAS and TP53 mutations in human cancers, the implications of our findings may extend far beyond pancreatic cancer."

Going forward, the researchers hope to discover other important elements working downstream of mutant p53 that may affect the cancer cells or the surrounding tumor microenvironment. A greater understanding of this complex network may point to additional therapeutic targets or combination approaches to better treat pancreatic cancer.

Tokyo, Japan - Researchers from Tokyo Metropolitan University have shown that a quantity known as "thermoelectric conductivity" is an effective measure for the dimensionality of newly developed thermoelectric nanomaterials. Studying films of semiconducting single-walled carbon nanotubes and atomically thin sheets of molybdenum sulfide and graphene, they found clear distinctions in how this number varies with conductivity, in agreement with theoretical predictions in 1D and 2D materials. Such a metric promises better design strategies for thermoelectric materials.

Thermoelectric devices take differences in temperature between different materials and generate electrical energy. The simplest example is two strips of different metals welded together at both ends to form a loop; heating one of the junctions while keeping the other cool creates an electrical current. This is called the Seebeck effect. Its potential applications promise effective usage of the tremendous amount of power that is wasted as dissipated heat in everyday life, whether it be in power transmission, industrial exhaust, or even body heat. In 1993, it was theorized that atomically thin, one-dimensional materials would have the ideal mix of properties required to create efficient thermoelectric devices. The resulting search led to nanomaterials such as semiconducting single-walled carbon nanotubes (SWCNTs) being applied.

However, there was an ongoing issue that prevented new designs and systems from being accurately characterized. The key properties of thermoelectric devices are thermal conductivity, electrical conductivity, and the Seebeck coefficient, a measure of how much voltage is created at the interface between different materials for a given temperature difference. As material science advanced into the age of nanotechnology, these numbers weren't enough to express a key property of the new nanomaterials that were being created: the "dimensionality" of the material, or how 1D, 2D or 3D-like the material behaves. Without a reliable, unambiguous metric, it becomes difficult to discuss, let alone optimize new materials, particularly how the dimensionality of their structure leads to enhanced thermoelectric performance.

To tackle this dilemma, a team led by Professor Kazuhiro Yanagi of Tokyo Metropolitan University set out to explore a new parameter recently flagged by theoretical studies, the "thermoelectric conductivity." Unlike the Seebeck coefficient, the team's theoretical calculations confirmed that this value varied differently with increased conductivity for 1D, 2D and 3D systems. They also confirmed this experimentally, preparing thin films of single-walled carbon nanotubes as well as atomically thin sheets of molybdenum sulfide and graphene, archetypal materials in 1D and 2D respectively. Measurements conclusively showed that the thermoelectric conductivity of the 1D material decreased at higher values of conductivity, while the curve for 2D materials plateaued. They also note that this demonstrates how the dimensionality of the material is retained even when the material is prepared in macroscopic films, a great boost for efforts to leverage the specific dimensionality of certain structures to improve thermoelectric performance.

Combined with theoretical calculations, the team conclude that high thermoelectric conductivity, high conventional electrical conductivity, and low thermal conductivity are key goals for the engineering of new devices. They hope these measurable, tangible targets will bring much needed clarity and unity to the development of state-of-the-art thermoelectric devices.

Study: "Which U.S. Elementary Schoolchildren Are More Likely to Be Frequently Bullied?"
Authors: Paul Morgan (Pennsylvania State University), Adrienne D. Woods (Pennsylvania State University), Yangyang Wang (Pennsylvania State University), George Farkas (University of California, Irvine), Yoonkyung Oh (University of Texas Health Science Center), Marianne Hillemeier (Pennsylvania State University), Cynthia Mitchell (Pennsylvania State University)

This study was presented at the AERA 2021 Virtual Annual Meeting
Session: Friends, Enemies, and Bullies: Peer Relationships in Schools
Date/Time: Saturday, April 10, 10:40 a.m. - 12:10 p.m. ET

Main Findings:

Kindergarten children who frequently externalize problem behaviors (i.e., are aggressive or otherwise target their behavior at others) are at high risk of being frequently bullied later in 3rd-5th grades.

Children with higher academic achievement and who can better self-regulate their behaviors--two other factors that can be modified--are at slightly less risk of being frequently bullied in later grades, particularly girls.

Black children are at greater risk for reputational bullying, particularly boys. Children with disabilities are more likely to be bullied, including physically and socially.

Details:

The authors analyzed a nationally representative cohort of 11,780 U.S. kindergarten children to identify factors that predict frequent verbal, social, reputation, and/or physical victimization later in 3rd -- 5th grades. The data came from the U.S. Department of Education's Early Childhood Longitudinal Study: Kindergarten Cohort of 2010-2011, Children were followed from the fall of kindergarten until the spring of fifth grade in the 2015-16 academic year.

The study examined the role of behavioral functioning, academic achievement, parenting, and sociodemographic factors including family income, sex, race or ethnicity, and disability status.

The authors found that externalizing problem behaviors in kindergarten strongly and consistently increased children's risk for being frequently bullied by the upper elementary grades. Children entering kindergarten already engaging in externalizing problem behaviors may benefit from early school-based mental health services to address their maladaptive behaviors. Externalizing problem behaviors are modifiable through early intervention.

In contrast, results from the study suggest that increasing children's academic achievement and behavioral self-regulation would be expected to only slightly lower their risk for being frequently bulled, particularly for girls. These factors are also modifiable through early intervention. Greater academic achievement in kindergarten consistently, but weakly, predicted a lower risk for victimization but mostly among girls.

"Children who are frequently bullied are more likely to struggle emotionally, behaviorally, academically, and physically during school and so should be provided with additional mental health supports," said coauthor Paul Morgan, a professor of education and demography at Pennsylvania State University. "Yet which kindergarten children in the U.S. are already more likely to be frequently bullied during elementary school has been unclear. Our findings help to identify the key risk factors."

The authors found that internalizing problem behaviors also lowers children's risks for being bullied during elementary school. Being anxious or socially withdrawn may only begin to increase the risk for being bullied during adolescence.

While parenting behaviors are mostly unrelated to children's victimization, the results unexpectedly suggested that cognitively stimulating parenting may increase the risk of students being bullied, possibly due to the children being perceived as somehow different by their classmates.

The authors found that children from families with greater economic resources and those who are Hispanic are at lower risk of victimization, possibly due to experiencing greater social networks and family cohesion.

Boys are more likely to be physically bullied while young girls are more likely to be verbally socially, and reputationally bullied. Girls experienced more overall bullying than boys. The authors' results suggest that early screening and intervention efforts should differentiate the specific bullying risks experienced by boys and girls.

Boys who are Black or have disabilities are more likely to experience specific types of bullying than girls who are Black or have disabilities.

Overall, children with disabilities were more likely to be bullied including physically and socially.

The authors found that the greater risk for victimization among Black adolescents reported in prior research is specific to Black boys for reputational bullying during elementary grades. The study findings indicate that Black children's greater risk for reputational victimization is not explained by socio-demographic factors such as family income.

To request a copy of the working paper, or to talk to study authors, please contact AERA Communications: Tony Pals, Director of Communications, tpals@aera.net, cell: (202) 288-9333; Tong Wu, Communications Associate, twu@aera.net, cell: (202) 957-3802

An international research team led by Monash University has uncovered a new technique that could speed up recovery from bone replacements by altering the shape and nucleus of individual stem cells.

The research collaboration involving Monash University, the Melbourne Centre for Nanofabrication, CSIRO, the Max Planck Institute for Medical Research and the Swiss Federal Institute of Technology in Lausanne, developed micropillar arrays using UV nanoimprint lithography that essentially 'trick' the cells to become bone.

Nanoimprint lithography allows for the creation of microscale patterns with low cost, high throughput and high resolution.

When implanted into the body as part of a bone replacement procedure, such as a hip or knee, researchers found these pillars - which are 10 times smaller than the width of a human hair - changed the shape, nucleus and genetic material inside stem cells.

Not only was the research team able to define the topography of the pillar sizes and the effects it had on stem cells, but they discovered four times as much bone could be produced compared to current methods.

The findings were published in Advanced Science.

"What this means is, with further testing, we can speed up the process of locking bone replacements with surrounding tissue, in addition to reducing the risks of infection," Associate Professor Jessica Frith from Monash University's Department of Materials Science and Engineering said.

"We've also been able to determine what form these pillar structures take and what size they need to be in order to facilitate the changes to each stem cell, and select one that works best for the application."

Researchers are now advancing this study into animal model testing to see how they perform on medical implants.

Engineers, scientists and medical professionals have known for some time that cells can take complex mechanical cues from the microenvironment, which in turn influences their development.

However, Dr Victor Cadarso from Monash University's Department of Mechanical and Aerospace Engineering says their results point to a previously undefined mechanism where 'mechanotransductory signalling' can be harnessed using microtopographies for future clinical settings.

"Harnessing surface microtopography instead of biological factor supplementation to direct cell fate has far-reaching ramifications for smart cell cultureware in stem cell technologies and cell therapy, as well as for the design of smart implant materials with enhanced osteo-inductive capacity," Dr Cadarso said.

Professor Nicolas Voelcker from the Monash Institute of Pharmaceutical Sciences and Director of the Melbourne Centre for Nanofabrication said the study results confirm micropillars not only impacted the overall nuclear shape, but also changed the contents of the nucleus.

"The ability to control the degree of deformation of the nucleus by specifying the architecture of the underlying substrate may open new opportunities to regulate gene expression and subsequent cell fate," Professor Voelcker said.

Researchers at the Obesity Research Unit of the University of Helsinki have found that obesity clearly reduces mitochondrial gene expression in fat tissue, or adipose tissue. Mitochondria are important cellular powerplants which process all of our energy intake. If the pathways associated with breaking down nutrients are lazy, the changes can often have health-related consequences.

A total of 49 pairs of identical twins discordant for body weight participated in the study conducted at the University of Helsinki: their body composition and metabolism were studied in detail, and biopsies from adipose and muscle tissue were collected. Multiple techniques for analysing the genome-wide gene expression, the proteome and the metabolome were used in the study.

The study was recently published in the journal Cell Reports Medicine.

According to the findings, the pathways responsible for mitochondrial metabolism in adipose tissue were greatly reduced by obesity. Since mitochondria are key to cellular energy production, their reduced function can maintain obesity. For the first time, the study also compared the effects of obesity specifically on the mitochondria in muscle tissue in these identical twin pairs: muscle mitochondria too were found to be out of tune, but the change was less distinct than in adipose tissue.

The study provided strong evidence of a connection between the low performance of adipose tissue mitochondria and a proinflammatory state. Furthermore, the findings indicate that metabolic changes in adipose tissue are associated with increased accumulation of fat in the liver, prediabetic disorders of glucose and insulin metabolism as well as cholesterol.

"If mitochondria, the cellular powerplants, are compared to the engine of a car, you could say that the power output decreases as weight increases. A low-powered mitochondrial engine may also generate toxic exhaust fumes, which can cause a proinflammatory state in adipose tissue and, consequently, the onset of diseases associated with obesity," says Professor Kirsi Pietiläinen from the Obesity Research Unit, University of Helsinki.

"What was surprising was that the mitochondrial pathways in muscle had no association with these adverse health effects," Pietiläinen adds.

Obesity also affected amino acid metabolism

In the study, changes in mitochondrial function were also seen in amino acid metabolism. The metabolism of branched-chain amino acids, which are essential to humans, was weakened in the mitochondria of both adipose tissue and muscle tissue.

"This finding was of particular significance because the reduced breakdown of these amino acids and the resulting heightened concentration in blood have also been directly linked with prediabetic changes and the accumulation of liver fat in prior twin studies," says Pietiläinen.

Obesity, with its numerous associated diseases, is a common phenomenon that is continuously increasing in prevalence. While lifestyle influence the onset of obesity, genes also have a significant role.

"Identical twins have the same genes, and their weight is usually fairly similar. In fact, studying twins is the best way to investigate the interplay between genes and lifestyle. In spite of their identical genome, the genes and even mitochondria of twins can function on different activity levels. We utilised this characteristic in our study when looking into the effects of weight on tissue function," Pietiläinen says.