Tech

Translation of genes more complex than expected

video: MoonTag (blue) and SunTag (green) translation on different single mRNA molecules (red dots) in living cells.

Image: 
Sanne Boersma and Deepak Khuperkar © Hubrecht Institute

Researchers from the group of Marvin Tanenbaum at the Hubrecht Institute have shown that translation of the genetic information stored in our DNA is much more complex than previously thought. This discovery was made by developing a type of advanced microscopy that directly visualizes the translation of the genetic code in a living cell. Their study is published in the scientific journal Cell on June 6th.

From gene to protein

Each cell in our body contains the same DNA, yet different cells, like brain cells or muscle cells, have different functions. The differences in cell function depend on which parts of the genetic information (called genes) are active in each cell. The genetic information stored in these genes is translated by specialized translation factories called ribosomes. Ribosomes read the genetic code and assemble proteins based on the information stored in this genetic code analogous to a factory building a machine based on a blueprint. Proteins are the workhorses of our body and perform the functions encoded in our genes. For our cells and organs to function correctly, it is critical that the genetic information stored in our genes is translated accurately to proteins. If the genetic code is translated incorrectly, harmful proteins can be produced, which can lead to neurological diseases such as Huntington's disease.

The 'reading frame' of genes

The genetic code is translated in groups of 3 letters, each resembling a word, which is translated into a single part of the protein. If a ribosome starts translating the code at the wrong position, a shift in the 3-letter-code can occur. For example, the sentence below should read:

"the man saw his new red car"

However, if a ribosome starts translating this sentence one letter too late, the sentence would read:

"hem ans awh isn ewr edc ar"

In the case of the genetic code, this phenomenon is called 'out-of-frame' translation. Sanne Boersma, researcher at the Hubrecht Institute explains: "As illustrated by the example sentence, out-of-frame translation has a big effect on the protein and usually results in a protein that behaves differently and can damage the cell". Until now, it was unclear how the ribosome knows where to start translating the code, and how often the ribosome gets it wrong.

A new method: SunTag and MoonTag

The researchers developed a new method to visualize the decoding of our genetic information in living cells. They were able to label different protein products in different colors and visualize the production of each type of protein using advanced microscopy. Each protein was labeled using a specific label, or tag, called the SunTag and MoonTag, which they could see through the microscope (Figure). By combining the MoonTag and the SunTag, the researchers could now see for the first time how often out-of-frame translation takes place.

A big surprise

The researchers discovered that out-of-frame translation happens surprisingly frequently. In extreme cases, almost half of all the proteins that were built, used a different reading frame or code than the expected code. These surprising findings show that the genetic information stored in our DNA is far more complex than previously thought. Based on the new study, our DNA likely encodes thousands of previously unknown proteins with unknown functions. Sanne Boersma: "Because of our study, we can now ask very important questions: what do all these new proteins do? Do they have important functions in our body or are they waste side-products of translation that can damage our cells?"

Credit: 
Hubrecht Institute

New research helping to reveal more about megaviruses

image: Professor David Lamb, of Swansea University Medical School, who led the research.

Image: 
Swansea University

Swansea University has played a key role in transatlantic research to develop a greater understanding of megaviruses and their potential to cause life-threatening illnesses.

The findings, which have just been published in the prestigious Proceedings of the National Academy of Sciences of the United States of America (PNAS), examine the unexpected genes carried by these giant viruses found inside amoebae.

Professor David Lamb, (left) recipient of a highly prestigious Fulbright Scholarship, worked with his Swansea University Medical School colleagues Professor Steven Kelly, Dr Claire Price and Dr Andrew Warrilow on the paper On the occurrence of cytochrome P450 in viruses.

Professor Lamb explained that amoebae can be described as Trojan horses as they carry the megaviruses which can be as big as bacteria.

He said: "Some of these megaviruses have several thousand genes. We are cataloguing them and examining their properties.

"We know these viruses may be linked to some forms of pneumonia so gaining a better understanding of them will help us to develop ways of tackling those viruses."

The paper follows on from the time Professor Lamb spent in the US as one of Swansea University's first ever Fulbright Scholars.

His place on the prestigious programme saw him hosted by the Oceans and Human Health Department of the world-renowned Woods Hole Oceanographic Institute in Massachusetts where he spent a year developing his research into cytochrome P450 biodiversity.

The paper also saw the Swansea academics collaborate with Dr Jed Goldstone and Prof John Stegeman, from Woods Hole, Alec Follmer, Marie True and Professor Tom Poulos, from the University of California Irvine and Professor David Nelson at the University of Tennessee.

Professor Lamb added: "This is very interesting research and our findings herald a new era of understanding regarding the evolution of this important gene family, with implications for understanding the biology and the origin of the giant viruses themselves. "

Credit: 
Swansea University

Scientists propose a fresh look at the role of ferroptosis in the development of cancer

image: Possible modulation of tumor immunity by ferroptotic cancer cells.

Image: 
<em>Nature Reviews Cancer</em>

Professor of Ghent University (Belgium) and Lead Researcher at the Institute of Biology and Biomedicine of the Lobachevsky University (UNN) Dmitri Krysko together with scientists from Germany, Professor Marcus Conrad and Professor Jose Pedro Friedmann Angeli recently published an article in the journal Nature Reviews Cancer, one of the highest-rated journals that occupies the 2nd line in the oncology section among 223 journals in this category and has an impact factor of 42.78 according to WoS data.

Despite significant advances in medicine, cancer remains the second leading cause of death worldwide (WHO, 2018). One of the main approaches to the destruction of cancer cells, along with cancer immunotherapy, is to launch cell death through chemo- and radiotherapy. In their article, the researchers have proposed a new look at the role of ferroptosis (a type of cell death) in the development of cancer.

According to Dmitri Krysko, ferroptotic cancer cells can stimulate the immune system and lead to activation of anticancer immunity, thus contributing to the enhancement of the effectiveness of anticancer therapy. In this case, the so-called immunogenic cell death mechanism is launched. "On the other hand, according to published data, tumor cells dying by ferroptosis can cause suppression of an antitumor immune response, leading to the development and progression of a tumor in a human body. Thus, tumor cells that die by ferroptosis perform the dual function of a "double-edged sword," says Dmitri Krysko.

Cell death is an essential biological process that plays an active role both in human embryonic development and in the onset of various diseases. Every day, about 100 billion cells die in the human body. Cell death is controlled at the molecular, genetic and biochemical levels. Normally, dead cells are absorbed by cells of the human immune system without over-activating the immune system.

However, the development of many diseases is associated with an imbalance between the death of cells and their survival. Excessively massive or intensive one-time cell death in the body or high sensitivity of cells to death can cause inflammation and lead to the development of various neurodegenerative diseases. It is important to note that the development of resistance to cell death is directly related to the development of cancer and the subsequent ineffectiveness of anticancer therapy.

Modern antitumor therapy aims to trigger cell death in cancer cells, which, when dying, will activate the immune system. Over the past decades, scientists all over the world have been actively studying the molecular mechanisms of cell death and the interaction of cancer cells with the human immune system.

Ferroptosis is one of 12 types of regulated cell death, which was discovered only in 2012. Ferroptosis is different from other types of regulated cell death, such as apoptosis and necroptosis, and is triggered by the failure of the antioxidant defense mechanisms of cells, which leads to uncontrolled peroxidation of cell membrane lipids and to the death of cancer cells. Cancer cells that die by ferroptosis emit signals through which they interact with the cells of the body's immune system, which results in either the suppression of the immune response and the progression of the tumor or in the stimulation of an antitumor immune response. This indicates the immunogenic nature of cell death and leads to the involvement of the immune system in the fight against the tumor.

Professor Krysko continues, "In this paper, a fundamentally new concept of understanding the interaction between tumor cells dying by ferroptosis and the cells of the immune system is proposed and a new role of ferroptosis in the development and treatment of cancer is discussed."

Thus, the authors present some arguments that emphasize the ambiguous role of ferroptosis in the treatment of cancer. Further research directions are defined in this article that will help to answer the question: "Is ferroptosis an immunogenic or immunosuppressive form of cell death?"

Another important aspect is also demonstrated by the authors. It is related to the fact that during anticancer therapy tumor cells often acquire resistance to apoptosis, a type of cell death that is most often triggered by modern methods of chemotherapy and radiotherapy. This leads to a decrease in the effectiveness of treatment and the progression of cancer. In this case, it is important to use new methods of treatment aimed at launching alternative types of regulated cell death.

Thus, the launch of ferroptosis may help to overcome the resistance to cell death and increase the effectiveness of anti-tumor therapy. At this stage, it is too early to speak about the commercialization of these research results, since more fundamental research is required, including studies on mouse models. It is necessary to test and study in detail the feasibility of launching ferroptosis to enable the introduction of this method into clinical practice in the future.

"I would like to note that in 2018, UNN launched a unique project to study immunogenic cell death in gliomas, some of the most aggressive and metastatic brain tumors," says Professor Krysko.

Lobachevsky University researchers led by Professor Dmitri Krysko and Dr. Maria Vedunova, Director of the UNN Institute of Biology and Biomedicine, are studying the immunogenicity of cell death in gliomas in the framework of the Russian Science Foundation project No.18-15-00279 "Mechanisms of cell death in photodynamic therapy of neuro-oncological diseases".

Scientific experiments are conducted both in vitro and in vivo in mouse models. These studies are based on synergistic interaction and vast experience accumulated over many years by research teams on immunogenic cell death (led by Professor Dmitri Krysko) and on photodynamic therapy in neuro-oncology (led by Dr. Maria Vedunova).

Credit: 
Lobachevsky University

New computer attack mimics user's keystroke characteristics and evades detection, according to Ben-Gurion University cyber researchers

BEER-SHEVA, ISRAEL...June 6, 2019 - Ben-Gurion University of the Negev (BGU) cyber security researchers have developed a new attack called "Malboard." Malboard evades several detection products that are intended to continuously verify the user's identity based on personalized keystroke characteristics.

The new paper, Malboard: A Novel User Keystroke Impersonation Attack and Trusted Detection Framework Based on Side-Channel Analysis published in the Computer and Security journal, reveals a sophisticated attack in which a compromised USB keyboard automatically generates and sends malicious keystrokes that mimic the attacked user's behavioral characteristics.

Keystrokes generated maliciously do not typically match human typing and can easily be detected. Using artificial intelligence, however, the Malboard attack autonomously generates commands in the user's style, injects the keystrokes as malicious software into the keyboard and evades detection. The keyboards used in the research were products by Microsoft, Lenovo and Dell.

"In the study, 30 people performed three different keystroke tests against three existing detection mechanisms including KeyTrac, TypingDNA and DuckHunt. Our attack evaded detection in 83% to 100% of the cases," says Dr. Nir Nissim, head of the David and Janet Polak Family Malware Lab at Cyber@BGU, and a member of the BGU Department of Industrial Engineering and Management. "Malboard was effective in two scenarios: by a remote attacker using wireless communication to communicate, and by an inside attacker or employee who physically operates and uses Malboard."

New Detection Modules Proposed

Both the attack and detection mechanisms were developed as part of the master's thesis of Nitzan Farhi, a BGU student and member of the USBEAT project at BGU's Malware Lab.

"Our proposed detection modules are trusted and secured, based on information that can be measured from side-channel resources, in addition to data transmission," Farhi says. "These include (1) the keyboard's power consumption; (2) the keystrokes' sound; and (3) the user's behavior associated with his or her ability to respond to typographical errors."

Dr. Nissim adds, "Each of the proposed detection modules is capable of detecting the Malboard attack in 100% of the cases, with no misses and no false positives. Using them together as an ensemble detection framework will assure that an organization is immune to the Malboard attack as well as other keystroke attacks."

The researchers propose using this detection framework for every keyboard when it is initially purchased and daily at the outset, since sophisticated malicious keyboards can delay their malicious activity for a later time period. Many new attacks can detect the presence of security mechanisms and thus manage to evade or disable them.

The BGU researchers plan to expand work on other popular USB devices, including computer mouse user movements, clicks and duration of use. They also plan to enhance the typo insertion detection module and combine it with other existing keystroke dynamic mechanisms for user authentication since this behavior is difficult to replicate.

Credit: 
American Associates, Ben-Gurion University of the Negev

New research unlocks properties for quantum information storage and computing

TROY, N.Y. - Researchers at Rensselaer Polytechnic Institute have come up with a way to manipulate tungsten diselenide (WSe2) --a promising two-dimensional material--to further unlock its potential to enable faster, more efficient computing, and even quantum information processing and storage. Their findings were published today in Nature Communications.

Across the globe, researchers have been heavily focused on a class of two-dimensional, atomically thin semiconductor materials known as monolayer transition metal dichalcogenides. These atomically thin semiconductor materials--less than 1 nm thick--are attractive as the industry tries to make devices smaller and more power efficient.

"It's a completely new paradigm," said Sufei Shi, assistant professor of chemical and biological engineering at Rensselaer and corresponding author on the paper. "The advantages could be huge."

Shi and his research team, in partnership with staff from the Micro and Nano Fabrication Clean Room within the Center for Materials, Devices, and Integrated Systems at Rensselaer, have developed a method to isolate these thin layers of WSe2 from crystals so they can stack them on top of other atomically thin materials such as boron nitride and graphene.

When the WSe2 layer is sandwiched between two boron nitride flakes and interacts with light, Shi said, a unique process occurs. Unlike in a traditional semiconductor, electrons and holes strongly bond together and form a charge-neutral quasiparticle called an exciton.

"Exciton is probably one of the most important concepts in light-matter interaction. Understanding that is critical for solar energy harvesting, efficient light-emitting diode devices, and almost anything related to the optical properties of semiconductors," said Shi, who is also a member of the department of electrical, computer, and systems engineering at Rensselaer. "Now we have found that it actually can be used for quantum information storage and processing."

One of the exciting properties of the exciton in WSe2, he said, is a new quantum degree of freedom that's become known as "valley spin"--an expanded freedom of movement for particles that has been eyed for quantum computing. But, Shi explained, excitons typically don't have a long lifetime, which makes them unpractical.

In a previous publication in Nature Communications, Shi and his team discovered a special "dark" exciton that typically can't be seen but has a longer lifetime. Its challenge is that the "dark" exciton lacks the "valley-spin" quantum degree of freedom.

In this most recent research Shi and his team figured out how to brighten the "dark" exciton; that is, to make the "dark" exciton interact with another quasiparticle known as a phonon to create a completely new quasiparticle that has both properties researchers want.

"We found the sweet spot," Shi said. "We found a new quasiparticle that has a quantum degree of freedom and also a long lifetime, that's why it's so exciting. We have the quantum property of the 'bright' exciton, but also have the long lifetime of the 'dark' exciton."

The team's findings, Shi said, lay the foundation for future development toward the next generation of computing and storage devices.

At Rensselaer, Shi was joined on this publication by postdoctoral scholar Zhipeng Li and graduate students Tianmeng Wang and Zhen Lian, all from the department of chemical and biological engineering. This research was also done in close partnership with the National High Magnetic Field Lab and other research institutions.

Credit: 
Rensselaer Polytechnic Institute

The deep learning dive: how cells regulate division

image: Dr. Maria C. Cuitiño is a researcher at MUSC Hollings Cancer Center.

Image: 
MUSC Hollings Cancer Center

Combining tissue imaging and artificial intelligence, Hollings Cancer Center researchers at the Medical University of South Carolina probed deeper into how cell division cycles are regulated, in this study released online in the May 2019 issue of Cell Reports.

Addressing a long unanswered question of how cell division is controlled during development and normal maintenance in multicellular organisms, Maria Cuitino, Ph.D., and colleagues used animal models and applied deep learning tools to measure protein levels and expose cellular mechanisms that previously could only be estimated by cell culture systems. The findings begin to identify the possible early events associated with uncontrolled cell division, a key step in the early progression to cancer.

Past research revealed which molecules direct cells to divide or not divide, but this left many scientific gaps. Since bodies are made up of many different types of cells that come together to form complex organs, studying the whole body at once can be very complicated, but also can be very exciting and revealing, says Gustavo Leone, Ph.D., Hollings Cancer Center director and corresponding author on the study.

Previous studies that looked at individual cells in in vitro cell culture systems provided basic answers to the biology going on inside the cell but missed the interactions that occur when all of the cells are working together to form organs. Leone and his team's findings confirmed at least 80% of the previous knowledge derived from cell culture systems and addressed new important questions that needed to be answered.

"Not knowing when and where "on and off" switches for cell division are expressed is like having paint with no canvas. Now we have the canvas, and thus the cellular context, for how these proteins behave within cells in the body," Leone says.

The five-year project probed "when" and "where" a critical family of transcription factor proteins (E2F family) is expressed in mammalian cells. Mammals have at least nine different E2F transcription factors that have either activation (on) or repressive (off) functions. All units within cells must work properly to make a functioning organ. "Our DNA provides the code to make the multiple proteins, which are the functional units of our cells. Transcription is the first biological process that makes proteins from DNA, and transcription factors are the on and off switches for this process," Leone explains.

Cancer is one of the most common diseases that occurs when cells multiply in an uncontrolled manner. Understanding the on and off switches, the transcriptions factors, is essential to understand disease processes like cancer.

Instead of studying cell division regulation in cultured cells (or in vitro), the researchers used a whole-organism approach. Two major discoveries were made in this study. The most surprising discovery during this work was that the same E2F family of proteins are organized into two modules that work similarly in all cell types and organs in our bodies. "So it appears that a universal mechanism has evolved to control cell divisions, regardless of the diversity of cell types existing in our bodies," he says.

The second discovery was the development of tools that allow this level of precision in the analysis of proteins in complex tissues. Critical to the artificial tools developed in this study was Hollings Cancer Center researcher Thierry Pecot, Ph.D. "To be able to develop the tools that can detect the infrequent presence of transcription factors in every cell and quantify them is both clinically and biologically relevant," Pecot says.

The Leone lab harnessed the power of artificial intelligence to quantify transcription factors across numerous cells in mouse tissues. While deep learning-based tools have been used for medical imaging before, it was not advanced enough to recognize individual cells in microscopic images within tissues/organs. The technology used by the lab is similar to how self-driving cars recognize objects on the street and allowed the identification of individual cells.

Often the exact clinical relevance of a particular biological discovery is not clear for decades. Currently other papers and emerging data from this group show hints of the role of E2F in cancer. The Leone laboratory uncovered that three transcription factors (E2F3A, E2F8, E2F4) work together to control cell division, while two others combine to stop cell division. These findings provide the strong foundation for further studies to understand these complex mechanisms.

This National Institutes of Health-funded research was driven by an international team of researchers with broad training and expertise, with the lead authors originating from Argentina, France, and China, which allowed for a great breadth of thought processes and determination, Leone says. "Solid elegant research leads to more questions, and that is certainly true in this comprehensive in-depth study of mammal E2F transcription factors."

The study prompts important questions for future research, says Leone. Using advanced technology, "we uncovered when and where the on and off switch modules for cell division are expressed in intact organisms". However, we do not know why there are multiple on and off switches, and whether these switches have redundant roles."

Credit: 
Medical University of South Carolina

Just a phage? How bacteria's predators can shape the gut microbiome

The gut microbiome is a complex, interconnected ecosystem of species. And, like any ecosystem, some organisms are predators and some are prey. A new study led by investigators at Brigham and Women's Hospital and the Wyss Institute investigates the impact of bacteriophage, viruses that infect and kill bacteria. They find that phage can have a profound impact on the dynamics of the gut microbiome, not only affecting certain species directly but also having a cascading effect on others. Phage may also be impacting their human host by modulating metabolites, including chemical substances found in the brain. The team, which includes first author Bryan Hsu, PhD, and co-corresponding senior author Pamela Silver, PhD, at the Wyss Institute, and Lynn Bry, MD, PhD, at the Brigham and director of the Massachusetts Host-Microbiome Center, has published its results in Cell Host & Microbe.

"One of the major interests in my lab is understanding the changes in the dynamics of the gut microbiome. Bacteriophage are a huge component of the microbiome but haven't been studied much yet," said co-corresponding senior author Georg Gerber, MD, PhD, MPH, co-director of the Massachusetts Host-Microbiome Center and chief of the Division of Computational Pathology in the Department of Pathology at the Brigham. "Some people are exploring phage therapy, using phage to kill off microbes, but phage are also found naturally in the gut, co-existing with the rest of the ecosystem. We wanted to find out what they are doing in there."

To address this question, the team colonized the guts of mice with a defined set of human bacterial species and then added phages, tracking the growth of each microbe. Using high-throughput sequencing and computational analyses, the team found that the phage caused attritions of the species they preyed upon as expected, but with a rippling effect on the rest of the ecosystem including blooms of non-targeted species.

In addition to looking at the effects on microbes, the team also looked for effects on the metabolome -- chemical substances that can come from both the host and the bacteria present. They found that when they modulated the microbiome with phage, they could see targeted changes in the metabolome, including changes in neurotransmitter levels and bile acids.

"This finding fascinates me for followup and raises significant questions: Could we use phage to modulate these activities? Could this be an intervention for conditions, such as depression, where you'd want to change neurotransmitter levels?" said Gerber. "Even if they aren't used as a direct therapeutic, our study suggests that phage may be a good tool for understanding the potential effects of other therapeutics that alter the microbiome."

Gerber and colleagues are especially interested in looking at the intersection of phage and malnutrition in the developing world, given the profound effects on the metabolome and microbiome that malnutrition can have.

"We hope that our work will provide a framework to guide future investigations to elucidate the interplay between phage, the microbiota, and host health and disease," said Gerber.

Credit: 
Brigham and Women's Hospital

Berkeley Lab technology provides clarity amid Hawaiian water contamination concerns

image: At Gillin's Beach in the Mahaulepu watershed, signs were frequently posted warning beach goers not to swim. However, the team found no evidence of any contamination during an entire year year of monitoring.

Image: 
Eric Dubinsky/Berkeley Lab

One of the first things that comes to mind when you think of Hawaii are warm, tropical beaches with inviting, clear water. In fact, favorable beach water quality is the lifeblood for Hawaii's $18 billion annual tourist industry, the largest single contributor to the state's economy. So, it comes as no surprise that Hawaii water officials continuously monitor for sources of contamination that could threaten their main attraction.

For years, routine testing has shown that watersheds of the Mahaulepu Valley and Waikomo Stream in southeast Kauai frequently contain high counts of potentially pathogenic fecal indicator bacteria (FIB). Though past investigations have concluded that the FIB are not being introduced into the water via sewage leaks or illegal sewage dumping, the Hawaii Department of Health (DOH) remained concerned about the source. To better understand the cause of the high FIB counts, the DOH commissioned a study by Lawrence Berkeley National Laboratory (Berkeley Lab) microbial ecologists Gary Andersen and Eric Dubinsky.

The duo is frequently invited to lead microbial water assessment projects thanks to their expertise and unparalleled toolkit, which centers around a credit card-sized microbial detection technology called the PhyloChip. Invented by Andersen and others at Berkeley Lab in 2008, the PhyloChip has been used previously to monitor water in the San Francisco Bay Area, tropical waters around coral reefs, and throughout the city of Singapore.

After analyzing samples from 13 inland and coastal sites taken over the course of one year, the scientists concluded that there was no detectable human sewage in the Mahaulepu watershed, nor was there a significant presence of livestock or avian wildlife fecal matter. Two stream sites within the watershed did show isolated incidences of pig and cow fecal contamination, yet the popular beach area downstream from these sites was clean.

"The PhyloChip is able to rapidly profile the entire microbial community present in the water samples and use this information to detect bacteria that are unique to specific animal or human sources," said Dubinsky, who is also a project scientist in the University of California Berkeley's Department of Environmental Science, Policy & Management. "Unlike conventional fecal contamination tests, which use a handful or even just a single species to identify the potential for contamination, our approach uses a diverse set of hundreds of different bacteria that are characteristic of each fecal source. At the same time, it can detect nearly 60,000 species of bacteria and archaea, meaning that we can find dangerous microbes present in a water source even if we don't anticipate them."

In the neighboring Waikomo watershed - an area that includes Poipu beach, one of the island's most popular tourist destinations - Dubinsky and Andersen found only minimal evidence of human fecal contamination. The PhyloChip data suggested that one beach had been contaminated with human fecal matter by a nearby hotel's sewage well. Interestingly, this site had not been identified by past monitoring with traditional FIB tests.

Having allayed fears of widespread sewage system leaks, the scientists propose that the historically high FIB levels are a misleadingly alarming consequence of using old-school testing methods, none of which were designed for use in the tropics.

Dubinsky and Andersen believe that the presence of FIB in Kauai's water is likely due to enterococci and Clostridium perfringens - a genus and species, respectively, that typically grow inside animal digestive tracts - flourishing in the environment outside of their typical biological hosts. They note that this phenomenon is common in tropical regions, thanks to the heat and humidity, and the natural presence of these bacteria in water does not necessarily put people at greater risk of gastrointestinal illness. However, many standard fecal bacteria detection tests employed to monitor swimming holes and beaches use these organisms as markers of dangerous contamination.

"The PhyloChip is able to achieve an extremely high level of confidence in detecting specific sources of contamination through a unique process that examines over a million DNA sequences simultaneously," said Andersen, a senior scientist in the Biosciences Area.

In 2017, the PhyloChip caught the interest of the US Environmental Protection Agency (EPA). Ongoing studies between the Andersen lab and at the EPA are using the technology to evaluate agricultural fecal runoff in multiple watersheds through the U.S., including Nebraska, Kansas, Georgia, Louisiana, Washington, and Massachusetts. "Our goal is to replicate and review data produced through the PhyloChip method so that we can compare it to other source-tracking methods," said Steven Baker, the co-lead researcher on this project from EPA Region 7. "Increasing our confidence in identifying when specific sources of fecal contamination occur strengthens our ability to make the correct management decisions and helps us to prioritize where to place our mitigation efforts."

On top of its environmental monitoring applications, the PhyloChip could enable advances in understanding and improving human health. Second Genome, Inc. has licensed the technology to discover and develop therapeutics based on targets identified through the examination of the human microbiome.

Credit: 
DOE/Lawrence Berkeley National Laboratory

Intercultural communication crucial for engineering education

image: Researchers strongly recommend engineers learn about intercultural communication so they can be more effective in the diverse environment of the real world.

Image: 
irasutoya.com

In an increasingly connected world it helps to engage with other cultures without prejudice or assumption. This is true in engineering as it is in any other field, but UTokyo researchers reveal shortcomings in how intercultural communication is taught to potential engineers.

By its very nature, engineering is a diverse, global and multidisciplinary field. Whether it's microchip manufacturing, aircraft assembly, or infrastructure megaprojects, engineering requires strong international collaboration. It's easy to think the field as a whole must place intercultural communication high on the agenda. However, some researchers feel this is far from the case.

Assistant Professor Yu Maemura from the Department of Civil Engineering at the University of Tokyo and colleagues from universities in the U.K., Belgium and Australia analyzed a collection of written materials used in engineering education. The subject of these materials was intercultural communication and their analysis concludes education in this area is not just lacking but also behind the times.

"There's an assumption that intercultural communication is about language barriers, it's much more than that," says Maemura. "Culture is also discussed purely in terms of nationality, but this essentialist view is very limited."

Essentialism is the idea that culture is innate and people can be categorized by broad terms, such as nationality. Therefore, essentialists judge people by broad cultural characteristics.

"It's easy to imagine why people think this way, it's not only intuitive but it's also ingrained in us," continues Maemura. "Much could be gained if educators in engineering instead viewed culture as emergent rather than something as a given."

This view of culture is known as constructivism, which researchers believe better reflects reality.

"The constructivist view implies there may be more in common between two engineers from different countries than between an engineer and someone in a very different profession from the same country, depending on the topic and context of the communication," says Maemura. "With this in mind, good intercultural communication could actually improve collaborative efforts between otherwise disparate groups of engineers."

A key way to improve the educational situation, according to Maemura and his colleagues, would be to educate budding engineers about cultural differences within their own countries, and similarities between different countries. This could open their minds to the constructivist view of culture, helping them to engage better with their international collaborators.

"Even senior engineers such as managers go overseas and are not prepared to deal with all they encounter, manifesting in issues which can go unnoticed," Maemura concludes. "Communication is the biggest issue in collaborative environments. Perhaps projects could be completed more efficiently, cost effectively and to higher safety standards with better intercultural communication."

Credit: 
University of Tokyo

Toward a low-cost industrialization of lithium-ion capacitors

image: Consecutive prelithiation involving two additives (pyrene in yellow and Li3PO4 in red). The chemical analysis used in the electron microscopy image makes it possible to locate Li3PO4 (red areas).

Image: 
Joel Gaubicher, Institut des matériaux Jean Rouxel (CNRS/Université de Nantes)

Combining two additives instead of one to facilitate the incorporation of lithium within capacitors: that is the solution proposed by researchers from l'Institut des matériaux Jean Rouxel (CNRS/Université de Nantes), in collaboration with Münster Electrochemical Energy Technology (University of Münster, Germany), in order to promote the low-cost, simple, and efficient development of the lithium-ion capacitors used to store electrical energy. This research, published in Advanced Energy Materials on 5 June 2019, will enable the mass marketing of these components.

Electrochemical storage systems for electricity play a central role in the integration of renewable energy sources, and are about to take over the electro-mobility sector. There are two solutions for storing this energy: lithium-ion batteries, which have the advantage of large storage capacity, and capacitors, which have less capacity, but can charge and uncharge very rapidly a great number of times. Lithium-ion capacitors (LIC) combine the best of both worlds.

The materials that make up lithium-ion capacitors do not contain lithium ions (or electrons), unlike batteries. It is therefore necessary to proceed with a prelithiation stage in order to add them, so that the device can function. Two broad strategies are used today: either one of the capacitor's constituent materials is prelithiated before its integration, or an additive high in lithium ions will redistribute them among the capacitor's materials during the first charge. Yet these methods are costly and complex, and can diminish the device's capacity. What's more, the majority of prelithiation additives available deteriorate when in contact with the air and/or the solvents used to manufacture lithium-ion capacitors. In short, even though some of the solutions that have been proposed function today, there is no "miracle recipe" that is high-performance, sturdy, simple, and inexpensive.

Researchers from l'Institut des matériaux Jean Rouxel [1] (CNRS/Université de Nantes), in collaboration with Münster Electrochemical Energy Technology (University of Münster), met this challenge by using not just one but two additives coupled through consecutive chemical reactions. Their analysis shows that the primary barrier for earlier approaches was their use of a single additive, which had to not only provide lithium ions and electrons, but also meet all of the conditions of price, chemical stability, and performance. The use of two additives each with a specific role, with one providing lithium ions and the other electrons, offers much greater latitude, for they can be selected independently for their price, chemical properties, and performance. When a lithium-ion capacitor is charging, the first additive (pyrene, naturally present in certain types of coal) releases electrons and protons. The second additive, Li3PO4 (mass produced in the glass industry, for instance), captures these protons, and in turn releases lithium ions that are then available for prelithiation.

An additional advantage of this approach is that after prelithiation, the residue of one of the two additives used, pyrene, contributes to the storage of charges, thereby increasing the quantity of electrical energy stored in the device. The efficiency and versatility offered by this new approach opens the way for an inexpensive solution for prelithiation, resulting in lithium-ion capacitors that can store more energy. The breaking of this technological barrier should therefore enable a quicker commercialisation of these devices.

Credit: 
CNRS

Scientists edge closer to root causes of multiple sclerosis

image: Assistant professor in the UBC faculty of medicine's department of medical genetics.

Image: 
University of British Columbia

An international team of researchers led by the University of British Columbia has made a scientific advance they hope will lead to the development of preventative treatments for multiple sclerosis (MS).

In a study published today in PLOS Genetics, researchers found mutations in 12 genes believed to be largely responsible for the onset of MS in families with multiple members diagnosed with the disease.

"These genes are like a lighthouse illuminating where the root cause of MS is," said lead author Carles Vilariño-Güell, assistant professor in the UBC faculty of medicine's department of medical genetics and a Michael Smith Scholar.

MS is a disease that affects the central nervous system, in which cells from the immune system attack and damage the nerve cells' protective sheath. The disease often results in disability and can have a significant impact on quality of life.

For the study, researchers sequenced all known genes in three or more MS patients from 34 families and examined the genetic variants in family members both affected by and unaffected by MS. By looking at the genes of 132 patients, they identified 12 genetic mutations that can lead to an overactive autoimmune system that attacks myelin, the insulating layer around nerves in the brain and spinal cord.

Of people diagnosed with MS, only 13 per cent are believed to have a genetic form of the disease, but those presenting the mutations identified in this new study were estimated to have an up to 85 per cent chance of developing MS in their lifetime.

Vilariño-Güell aims to develop cellular and animal models with the identified mutations to mimic the biological processes responsible for the onset of MS in patients, with the goal of eventually developing preventative treatments for the disease.

"We have treatments that address the symptoms of MS, but not the causes. People with MS take drugs that reduce the attacks, but the disease still progresses," said Vilariño-Güell. "Now, with knowledge of these mutations, which suggest a common biological process that leads to increased inflammation in MS families, we can try to address the root causes."

The researchers hope the findings will one day lead to personalized treatments for MS patients and preventative strategies for those at greater risk of developing the disease.

Credit: 
University of British Columbia

Posture impacts how you perceive your food

TAMPA, Fla. (June 7, 2019)- Summertime is often filled with outdoor parties and food trucks, meaning you're spending more time standing up and eating. But if you want to actually enjoy your meal, researchers say you're better off finding a seat.

A new study published in the Journal of Consumer Research finds posture impacts taste perception, with food tasting better when you're sitting down. Lead author Dipayan Biswas, PhD, professor of marketing at the University of South Florida, is an expert in cross-modal effects and looked specifically at how the vestibular sense, which is responsible for balance, posture and spatial orientation, interacts with the gustatory sensory system, which impacts taste and flavor.

He found that holding a standing posture for even a few minutes prompts physical stress, muting taste buds. The force of gravity pushes blood to the lower parts of the body, causing the heart to work harder to pump blood back up to the top of the body, accelerating heart rate. This activates the hypothalamic-pituitary adrenal (HPA) axis and leads to increased concentrations of the stress hormone cortisol. This chain reaction reduces sensory sensitivity, which impacts food and beverage taste evaluation, food temperature perception and overall consumption volume.

When people experience discomfort, foods that normally taste good do not appear as pleasant to the palate. Biswas confirmed his hypothesis by having 350 participants rate the tastiness of a pita chip. Those who were standing gave it a less favorable rating than those who were sitting in a padded chair.

Researchers then provided participants classic bite-sized brownies baked at a local restaurant that were tested and widely considered pleasant tasting. Those who were sitting down rated them to be most delicious. However, when the baker altered the recipe and made the taste unpleasant by adding an extra ¼ cup of salt, the results were opposite. Participants standing up didn't notice the brownies tasting saltier to that extent, and actually rated them to have a relatively more favorable taste perception than those who sampled them while sitting down.

"This finding suggests that parents might be able to make unpleasant-tasting, healthy foods seem more palatable to reluctant children by having them eat standing up (vs. sitting down). In a similar vein, it might be beneficial to maintain a standing posture when consuming pharmaceutical products that have unpleasant tastes."

Biswas expanded the study by inducing additional stress. He required the participants to try fruit snacks while carrying a shopping bag, mimicking what happens when one tries samples at a grocery store or in a food court. Both sitting and standing participants reported the additional weight made the food item taste even worse. This highlights the underlying mechanism related to physical stress driving the effects of posture on taste evaluations.

In addition, the team tested posture's impact on temperature perception. Participants were provided cups of hot coffee. Those standing up reported it not being as intense as those who were sitting down. However, they drank less than those sitting, suggesting physical stress suppresses appetite. Eating while standing can also help with long-term weight loss goals. Specifically, eating while standing (vs. sitting) leads to lower amount of consumption. Moreover, a standing position leads to greater physical stress, which in turn makes the heart pump more blood.

Credit: 
University of South Florida

Fishing a line coupled with clockwork for daily rhythm

image: (A) KaiC forms a hexametric ring structure with 12 ATP molecules (represented by "T"). (B) 3D structure of two KaiC molecules in the ring harboring an ATP analog (PDB ID code: 4O0M). A part of the "tail" (colored by green and orange) is pulled back in the ring core before ATP breakdown. (C) Upon the degradation of ATP (T) into ADP (D), the KaiC tail leaps out from the ring core and captures KaiA. The KaiA binding to the KaiC tail facilitates ADP release and ATP incorporation, leading to the upregulation of autophosphorylation of KaiC as a process of the circadian clockwork.

Image: 
Koichi Kato

Organisms on this planet, including human beings, exhibit a biological rhythm that repeats about every 24 h to adapt to the daily environmental alteration caused by the rotation of the earth. This circadian rhythm is regulated by a set of biomolecules working as a biological clock. In cyanobacteria (or blue-green algae), the circadian rhythm is controlled by the assembly and disassembly of three clock proteins, namely, KaiA, KaiB, and KaiC. KaiC forms a hexameric-ring structure and plays a central role in the clock oscillator, which works by consuming ATP, the energy currency molecule of the cell. However, it remains unknown how the clock proteins work autonomously for generating the circadian oscillation.

The research groups at Graduate School of Pharmaceutical Sciences of Nagoya City University and Exploratory Research Center on Life and Living Systems (ExCELLS) and Institute for Molecular Science (IMS) of National Institutes of Natural Sciences investigated this mechanism by native mass spectrometry and nuclear magnetic resonance spectroscopy. They found that KaiC degrades ATP into ADP within its ring structure, which triggers the leaping out of the tail of KaiC from the ring. KaiA captures the exposed KaiC tail, facilitating ADP release from the ring, thereby setting the clock ahead.

This "fishing a line" mechanism explains the clockwork interplay of the KaiA and KaiC proteins. Elucidating this mechanism will provide deep insights into not only the circadian clock in cyanobacteria but also that in plants, animals, and humans under physiological and pathological conditions, including jet lag and sleep disorders.

Credit: 
National Institutes of Natural Sciences

Organic electronics: a new semiconductor in the carbon-nitride family

image: The illustration is alluding to the laser experiment in the background and shows the structure of TGCN.

Image: 
C. Merschjann/HZB

Some organic materials might be able to be utilised similarly to silicon semiconductors in optoelectronics. Whether in solar cells, light-emitting diodes, or in transistors - what is important is the band gap, i.e. the difference in energy level between electrons in the valence band (bound state) and the conduction band (mobile state). Charge carriers can be raised from the valence band into the conduction band by means of light or an electrical voltage. This is the principle behind how all electronic components operate. Band gaps of one to two electron volts are ideal.

A team headed by chemist Dr. Michael J. Bojdys at Humboldt University Berlin recently synthesised a new organic semiconductor material in the carbon-nitride family. Triazine-based graphitic carbon nitride (or TGCN) consists of only carbon and nitrogen atoms, and can be grown as a brown film on a quartz substrate.The combination of C and N atoms form hexagonal honeycombs similar to graphene, which consists of pure carbon.Just as with graphene, the crystalline structure of TGCN is two-dimensional.With graphene, however, the planar conductivity is excellent, while its perpendicular conductivity is very poor. In TGCN it is exactly the opposite: the perpendicular conductivity is about 65 times greater than the planar conductivity. With a band gap of 1.7 electron volts, TGCN is a good candidate for applications in optoelectronics.

HZB physicist Dr. Christoph Merschjann subsequently investigated the charge transport properties in TGCN samples using time-resolved absorption measurements in the femto- to nanosecond range at the JULiq laser laboratory, a JointLab between HZB and Freie Universität Berlin. These kinds of laser experiments make it possible to connect macroscopic electrical conductivity with theoretical models and simulations of microscopic charge transport. From this approach he was able to deduce how the charge carriers travel through the material. "They do not exit the hexagonal honeycombs of triazine horizontally, but instead move diagonally to the next hexagon of triazine in the neighbouring plane. They move along tubular channels through the crystal structure." This mechanism might explain why the electrical conductivity perpendicular to the planes is considerably higher than that along the planes. However, this is probably not sufficient to explain the actual measured factor of 65. "We do not yet fully understand the charge transport properties in this material and want to investigate them further", adds Merschjann. At ULLAS / HZB in Wannsee, the analysis lab used subsequent to JULiq, the setup is being prepared for new experiments to accomplish this.

"TGCN is therefore the best candidate so far for replacing common inorganic semiconductors like silicon and their crucial dopants, some of which are rare elements", says Bojdys. "The fabrication process we developed in my group at Humboldt-Universität, produces flat layers of semiconducting TGCN on an insulating quartz substrate. This facilitates upscaling and simple fabrication of electronic devices."

Credit: 
Helmholtz-Zentrum Berlin für Materialien und Energie

Fertilizer plants emit 100 times more methane than reported

ITHACA, N.Y. - Emissions of methane from the industrial sector have been vastly underestimated, researchers from Cornell University and Environmental Defense Fund have found.

Using a Google Street View car equipped with a high-precision methane sensor, the researchers discovered that methane emissions from ammonia fertilizer plants were 100 times higher than the fertilizer industry's self-reported estimate. They also were substantially higher than the Environmental Protection Agency (EPA) estimate for all industrial processes in the United States.

"We took one small industry that most people have never heard of and found that its methane emissions were three times higher than the EPA assumed was emitted by all industrial production in the United States," said John Albertson, co-author and professor of civil and environmental engineering. "It shows us that there's a huge gap between a priori estimates and real-world measurements."

The researchers' findings are reported in "Estimation of Methane Emissions From the U.S. Ammonia Fertilizer Industry Using a Mobile Sensing Approach," published in Elementa.

The use of natural gas has grown in recent years, bolstered by improved efficiency in shale gas extraction and the perception that natural gas is a less dirty fossil fuel.

"But natural gas is largely methane, which molecule-per-molecule has a stronger global warming potential than carbon dioxide," Albertson said. "The presence of substantial emissions or leaks anywhere along the supply chain could make natural gas a more significant contributor to climate change than previously thought."

To evaluate methane emissions from downstream industrial sources, the researchers focused on the fertilizer industry, which uses natural gas both as the fuel and one of the main ingredients for ammonia and urea products. Ammonia fertilizer is produced at only a couple dozen plants in the U.S.; factories are often located near public roadways, where emissions carried downwind can be detected - in this case by mobile sensors.

For this study, the Google Street View vehicle traveled public roads near six representative fertilizer plants in the country's midsection to quantify "fugitive methane emissions" - defined as inadvertent losses of methane to the atmosphere, likely due to incomplete chemical reactions during fertilizer production, incomplete fuel combustion or leaks.

The team discovered that, on average, 0.34 percent of the gas used in the plants is emitted to the atmosphere. Scaling this emission rate from the six plants to the entire industry suggests total annual methane emissions of 28 gigagrams - 100 times higher than the fertilizer industry's self-reported estimate of 0.2 gigagrams per year.

In addition, this figure far exceeds the EPA's estimate that all industrial processes in the United States produce only 8 gigagrams of methane emissions per year.

"Even though a small percentage is being leaked, the fact that methane is such a powerful greenhouse gas makes the small leaks very important," said Joseph Rudek, co-author and lead senior scientist at Environmental Defense Fund. "In a 20-year timeframe, methane's global warming potential is 84 times that of carbon dioxide."

Credit: 
Cornell University