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RICHLAND, Wash. -- The rogue cellular engine that drives a majority of ovarian cancers remains frustratingly difficult to disable. A new study comparing cancerous tissue with normal fallopian tube samples advances important insights about this machinery and confirms biological hallmarks of survival.

High-grade serous carcinoma is the most common type of ovarian cancer, and it has the lowest survival rate. To better understand the disease and its progression, researchers at the U.S. Department of Energy's Pacific Northwest National Laboratory and their collaborators examined the proteome--thousands of proteins--in tissue samples taken from 83 patients around the world. Their results, published in the journal Cell Reports Medicine in April, could help identify more targeted treatments.

Hunting for Ovarian Cancer's 'Off' Switches

Successful treatment of any cancer involves stopping its abnormal cells from replicating and spreading. In the case of ovarian cancer--the fifth leading cause of cancer deaths in women--scientists are hunting for the right "off" switches to target.

"Cells are very complex pieces of machinery. There are many ways you can break the machinery and then end up with cancer," said Karin Rodland, a PNNL scientist and the study's corresponding author. "If you don't know what's broken, you can't fix it."

A relatively new profiling technique called proteogenomics provides clues. Developed over the last two decades, proteogenomics looks not only at the genetics of cells but how they communicate and function via thousands of proteins. While earlier research methods focused on how genetic mutations are expressed via ribonucleic acid, or RNA, proteomic analysis reveals even more detail about what happens among cancerous cells.

Now, scientists are working to understand this universe of proteins as part of the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium. As part of that effort, a landmark proteogenomic analysis of archived tumor samples in 2016 pinpointed specific cellular processes associated with ovarian high-grade serous carcinoma.

The new study confirms those findings and offers an even sharper picture by comparing cancerous tissue to normal fallopian tube samples, supporting the notion that ovarian cancer begins not on the surface of the ovary, as previously thought, but at the end of the fallopian tube.

The study also offered more robust data because the tissue samples were collected using strict surgical protocols that eliminated the body's stress response to surgery as a potential complicating factor.

"To our knowledge, this is the first really deep protein-level comparison of fallopian tube tissue and ovarian cancer tissue," Rodland said. "Being able to replicate the 2016 finding in a second cohort of women who were racially and ethnically diverse proves the strength of the initial observation."

Added Tao Liu, a PNNL scientist and the study's co-corresponding author: "This carefully procured cohort of tissue specimens, and the comprehensive, simultaneous analysis of both proteins and phosphorylated proteins, allows us to accurately recapitulate the cellular activities such as stress response and replication in the cancer and relevant normal tissues."

The Broken Machinery Behind Ovarian Cancer

The researchers linked two processes specifically to high-grade serous carcinoma, which is sometimes called "the disease of broken chromosomes." The first involves the stress response that results from the runaway production of tumor cells. This effect, known as proliferation-induced replication stress, creates instability in the tumor's genome.

The second process is homologous repair deficiency, an inability to repair damaged cells. The two processes combined are what create ovarian cancer's stubborn, uncontrolled growth patterns.

"It's not just that the tumor cells are stuck in the 'on' position for growth," Rodland said. "In ovarian cancer, there is also a background of deficient DNA repair. So whenever the cell replicates, you introduce mutations and broken chromosomes."

The study, which was supported by CPTAC and the National Institutes of Health, also confirmed previous findings that linked an abundance of certain proteins with higher survival rates.

Identifying proteins associated both with the processes that drive ovarian cancer and with increased survival chances opens up possible treatment strategies that target specific proliferation pathways, including the use of medicines currently on the market.

"Doctors could use this data to stratify treatment options," Rodland said. "We also can study the women who have shorter survival times and then perhaps come up with an alternative therapy that would work better for these women than the standard therapy."

Assistant professor of electrical and computer engineering Rose Faghih is not afraid of fear. If continuously monitored, she sees it as a tool to improve mental health treatment. So, she and doctoral student Dilranjan Wickramasuriya in the University of Houston Computational Medicine Lab (CML), who have previously tracked the fear response through sweat, or skin conductance, have now illustrated that the sympathetic nervous system's activation level can be tracked continuously.

"We developed a mixed filter algorithm to continuously track a person's level of sympathetic nervous system activation using skin conductance and heart rate measurements," reports Faghih in the journal PLOS One. "This level of sympathetic activation is closely tied to what is known as emotional arousal or sympathetic arousal."

The sympathetic nervous system controls what is commonly known as the "fight or flight" response, activated when the body is confronted by fear. Sympathetic nerves are a primary part of the response, and their arousal propels a person to action. When the sympathetic nervous system is activated, the heart starts pumping blood faster to send more oxygen to muscles. Then, tiny bursts of sweat released by the body cause a cooling effect.

"Using measurements of the variations in the conductivity of the skin and the rate at which the heart beats, and by developing mathematical models that govern these relationships, CML researchers have illustrated that the sympathetic nervous system's activation level can be tracked continuously," reports Faghih.

The ability to track arousal from skin conductance and heart rate together is an important precursor to the development of wearable monitors that could aid in patient care. The algorithm could be embedded in a wearable electronic device to monitor a patient diagnosed with a fear or anxiety disorder.

"Anxiety and trauma-related disorders are often accompanied by a heightened sympathetic tone and these methods could find clinical applications in remote monitoring for therapeutic purposes," she said.

Nearly all the countries of the world ratified the Paris Agreement in 2016. The accord aims to limit the increase of the world's temperature to less than 2 degrees Celsius above pre-industrial temperatures. To do this, global greenhouse gas emissions would have to decrease roughly 25% below 2010 levels by 2030 and reach almost zero by 2070. As one of the largest emitters of greenhouse gases, the United States--which intends to withdraw from the Paris Agreement--will play a central role in whether these targets are met.

In this context, a new study looked at U.S. tax policy as it relates to carbon dioxide (CO2), from 2015 through 2030. The study found only limited short-term opportunities for decarbonization (reducing greenhouse gas emissions) outside the electricity sector. The result is substantial CO2 tax revenue. The findings shed light on future tax policy decisions.

The study, conducted by researchers at Carnegie Mellon University (CMU), appears in Environmental Research Communications.

"Our findings point to clear opportunities to replace revenue from distortionary taxes (like the income tax) with revenue from carbon taxes, which enhance the efficiency of the U.S. economy." says Nicholas Muller, Associate Professor of Economics, Engineering, and Public Policy at CMU's Tepper School of Business, who coauthored the study.

The researchers used an energy-optimization model to simulate energy use by sector, fuel type and technology, system costs, and pollution emissions under two carbon tax policies. Their analysis included CO2 emissions as well as emissions of local air pollutants such as sulfur dioxide, nitrogen oxides, and particulate matter.

The study found that opportunities for significant reductions of CO2 in the short-term were limited to the electric-generation sector. As such, the other sectors subject to carbon taxation continued emitting. This will produce substantial carbon tax revenue. In total, revenues amounted to between 8% and 34% of all federal income tax revenue. Because carbon taxes provide strong incentives for innovation in low-carbon technologies, the authors project that enduring carbon taxes will enhance abatement in other sectors which will reduce future revenue.

Deep uncertainties in the climate system and the future effects of climate change on human civilization mean that the correct carbon tax rate is not known. Acknowledging this uncertainty, the authors explored the consequences of erroneous CO2 taxes. They found that it would be four times more costly to the economy to under tax CO2 than to over tax it, which they argue makes the case for invoking the precautionary principle (erring on the side of more aggressive CO2 policy rather than lax policy) on the grounds of efficiency.

"The reductions in CO2 emissions that we project would put the United States on track to meet the nationally determined contributions established under the Paris Agreement," says Michael Buchdahl Roth, doctoral student in the Department of Engineering and Public Policy at CMU. "But our results also suggest a need for cost-effective low carbon technology innovation that would allow decarbonization beyond the electricity generation sector. It's possible that the dynamic incentives that result from imposing environmental taxation could spur such technological developments."

WASHINGTON, May 19, 2020 -- Heart disease is the leading cause of death in the United States and other industrialized nations, and many patients face limited treatment options. Fortunately, stem cell biology has enabled researchers to produce large numbers of cardiomyocytes, the cells that make up the heart or cardiac muscle and have the potential to be used in advanced drug screens and cell-based therapies.

One of the pitfalls of these stem cell-generated cardiomyocytes is that they do not represent adult human cardiomyocytes but remain immature without further intervention. Additionally, current image analysis techniques do not allow researchers to analyze heterogeneous, multidirectional, striated myofibrils typical of immature cells to determine when new interventions are coaxing the cells to organize.

In the Journal of Applied Physics, from AIP Publishing, researchers showcase an algorithm that combines gradient methods with fast Fourier transforms, the scanning gradient Fourier transform or SGFT technique, to quantify myofibril structures in heart cells with considerable accuracy. Myofibrils are the elongated contractile unit of a muscle cell.

"If you look at adult human cardiac tissue, everything is not in perfect alignment. Everything is not stacked nicely and neatly like a bookshelf," said Wendy Crone, an author of the paper. "The structures are more complicated. We wanted to be able to quantify the organization."

This level of analysis, combined with new emerging studies of the effects of cell mutation, has the potential to produce new insights regarding the mechanisms underlying the generation of myofibrils and various cardiomyopathies, which make it harder for the heart muscle to pump blood to the rest of the body.

"There is myofibril disarray in certain diseases of the heart," said Crone. "With our technique, we can quantify the disarray, which provides a better understanding of the severity of disease in heart cells."

The heterogeneous, striated patterning that this new method can detect and quantify occurs in countless other instances in biology and elsewhere. For instance, the SGFT technique clearly detects the distribution of collagen organization and orientation in breast tissue biopsies, which is significant since breast tissue with cancer has more organized collagen structures. As prior studies have shown, the morphology of collagen fibers in breast cancer tissue is a strong prognostic indicator of the malignancy of the tumor.

The SGFT technique could also potentially be used to quantify striated patterns in early stage neurons derived from stems cells.

"Our code can quantify the organization of neural rosettes, too," said Crone.

The COVID-19 global lockdown has had an "extreme" effect on daily carbon emissions, but it is unlikely to last - according to a new analysis by an international team of scientists.

The study published in the journal Nature Climate Change shows that daily emissions decreased by 17% - or 17 million tonnes of carbon dioxide - globally during the peak of the confinement measures in early April compared to mean daily levels in 2019, dropping to levels last observed in 2006.

Emissions from surface transport, such as car journeys, account for almost half (43%) of the decrease in global emissions during peak confinement on April 7. Emissions from industry and from power together account for a further 43% of the decrease in daily global emissions.

Aviation is the economic sector most impacted by the lockdown, but it only accounts for 3% of global emissions, or 10% of the decrease in emissions during the pandemic.

The increase in the use of residential buildings from people working at home only marginally offset the drop in emissions from other sectors.

In individual countries, emissions decreased by 26% on average at the peak of their confinement.

The analysis also shows that social responses alone, without increases in wellbeing and/or supporting infrastructure, will not drive the deep and sustained reductions needed to reach net zero emissions.

Prof Corinne Le Quéré of the University of East Anglia, in the UK, led the analysis. She said: "Population confinement has led to drastic changes in energy use and CO2 emissions. These extreme decreases are likely to be temporary though, as they do not reflect structural changes in the economic, transport, or energy systems.

"The extent to which world leaders consider climate change when planning their economic responses post COVID-19 will influence the global CO2 emissions paths for decades to come.

"Opportunities exist to make real, durable, changes and be more resilient to future crises, by implementing economic stimulus packages that also help meet climate targets, especially for mobility, which accounts for half the decrease in emissions during confinement.

"For example in cities and suburbs, supporting walking and cycling, and the uptake of electric bikes, is far cheaper and better for wellbeing and air quality than building roads, and it preserves social distancing."

The team analysed government policies on confinement for 69 countries responsible for 97% of global CO2 emissions. At the peak of the confinement, regions responsible for 89% of global CO2 emissions were under some level of restriction. Data on activities indicative of how much each economic sector was affected by the pandemic was then used to estimate the change in fossil CO2 emissions for each day and country from January to April 2020.

The estimated total change in emissions from the pandemic amounts to 1048 million tonnes of carbon dioxide (MtCO2) until the end of April. Of this, the changes are largest in China where the confinement started, with a decrease of 242 MtCO2, then in the US (207 MtCO2), Europe (123 MtCO2), and India (98 MtCO2). The total change in the UK for January-April 2020 is an estimated 18 MtCO2.

The impact of confinement on 2020 annual emissions is projected to be around 4% to 7% compared to 2019, depending on the duration of the lockdown and the extent of the recovery. If pre-pandemic conditions of mobility and economic activity return by mid-June, the decline would be around 4%. If some restrictions remain worldwide until the end of the year, it would be around 7%.

This annual drop is comparable to the amount of annual emission reductions needed year-on-year across decades to achieve the climate objectives of UN Paris Agreement.

Prof Rob Jackson of Stanford University and Chair of the Global Carbon Project who co-authored the analysis, added: "The drop in emissions is substantial but illustrates the challenge of reaching our Paris climate commitments. We need systemic change through green energy and electric cars, not temporary reductions from enforced behavior."

The authors warn that the rush for economic stimulus packages must not make future emissions higher by delaying New Green Deals or weakening emissions standards.

Tokyo, Japan -- A prosthesis is an artificial device that replaces an injured or missing part of the body. You can easily imagine a stereotypical pirate with a wooden leg or Luke Skywalker's famous robotic hand. Less dramatically, think of old-school prosthetics like glasses and contact lenses that replace the natural lenses in our eyes. Now try to imagine a prosthesis that replaces part of a damaged brain. What could artificial brain matter be like? How would it even work?

Creating neuroprosthetic technology is the goal of an international team led by by the Ikerbasque Researcher Paolo Bonifazi from Biocruces Health Research Institute (Bilbao, Spain), and Timothée Levi from Institute of Industrial Science, The University of Tokyo and from IMS lab, University of Bordeaux. Although several types of artificial neurons have been developed, none have been truly practical for neuroprostheses. One of the biggest problems is that neurons in the brain communicate very precisely, but electrical output from the typical electrical neural network is unable to target specific neurons. To overcome this problem, the team converted the electrical signals to light. As Levi explains, "advances in optogenetic technology allowed us to precisely target neurons in a very small area of our biological neuronal network."

Optogenetics is a technology that takes advantage of several light-sensitive proteins found in algae and other animals. Inserting these proteins into neurons is a kind of hack; once they are there, shining light onto a neuron will make it active or inactive, depending on the type of protein. In this case, the researchers used proteins that were activated specifically by blue light. In their experiment, they first converted the electrical output of the spiking neuronal network into the checkered pattern of blue and black squares. Then, they shined this pattern down onto a 0.8 by 0.8 mm square of the biological neuronal network growing in the dish. Within this square, only neurons hit by the light coming from the blue squares were directly activated.

Spontaneous activity in cultured neurons produces synchronous activity that follows a certain kind of rhythm. This rhythm is defined by the way the neurons are connected together, the types of neurons, and their ability to adapt and change.

"The key to our success," says Levi, "was understanding that the rhythms of the artificial neurons had to match those of the real neurons. Once we were able to do this, the biological network was able to respond to the "melodies" sent by the artificial one. Preliminary results obtained during the European Brainbow project, help us to design these biomimetic artificial neurons."

They tuned the artificial neuronal network to use several different rhythms until they found the best match. Groups of neurons were assigned to specific pixels in the image grid and the rhythmic activity was then able to change the visual pattern that was shined onto the cultured neurons. The light patterns were shown onto a very small area of the cultured neurons, and the researchers were able to verify local reactions as well as changes in the global rhythms of the biological network.

"Incorporating optogenetics into the system is an advance towards practicality", says Levi. "It will allow future biomimetic devices to communicate with specific types of neurons or within specific neuronal circuits." The team is optimistic that future prosthetic devices using their system will be able to replace damaged brain circuits and restore communication between brain regions. "At University of Tokyo, in collaboration with Pr Kohno and Dr Ikeuchi, we are focusing on the design of bio-hybrid neuromorphic systems to create new generation of neuroprosthesis", says Levi.

Osaka, Japan - Researchers at The Institute of Scientific and Industrial Research at Osaka University introduced a new liquid-phase fabrication method for producing nanocellulose films with multiple axes of alignment. Using 3D-printing methods for increased control, this work may lead to cheaper and more environmentally friendly optical and thermal devices.

Ever since appearing on the original Star Trek TV show in the 1960s, the game of "three-dimensional chess" has been used as a metaphor for sophisticated thinking. Now, researchers at Osaka University can say that they have added their own version, with potential applications in advanced optics and inexpensive smartphone displays.

Many existing optical devices, including liquid-crystal displays (LCDs) found in older flat-screen televisions, rely on long needle-shaped molecules aligned in the same direction. However, getting fibers to line up in multiple directions on the same device is much more difficult. Having a method that can reliably and cheaply produce optical fibers would accelerate the manufacture of low-cost displays or even "paper electronics"—computers that could be printed from biodegradable materials on demand.

Cellulose, the primary component of cotton and wood, is an abundant renewable resource made of long molecules. Nanocelluloses are nanofibers made of uniaxially aligned cellulose molecular chains that have different optical and heat conduction properties along one direction compared to the another.

In newly published research from the Institute of Scientific and Industrial Research at Osaka University, nanocellulose was harvested from sea pineapples, a kind of sea squirt. They then used liquid-phase 3D-pattering, which combined the wet spinning of nanofibers with the precision of 3D-printing. A custom-made triaxial robot dispensed a nanocellulose aqueous suspension into an acetone coagulation bath.

"We developed this liquid-phase three-dimensional patterning technique to allow for nanocellulose alignment along any preferred axis," says first author Kojiro Uetani. The direction of the patterns could be programmed so that it formed an alternating checkerboard pattern of vertically- and horizontally-aligned fibers.

To demonstrate the method, a film was sandwiched between two orthogonal polarizing films. Under the proper viewing conditions, a birefringent checkerboard pattern appeared. They also measured the thermal transfer and optical retardation properties.

"Our findings could aid in the development of next-generation optical materials and paper electronics," says senior author Masaya Nogi. "This could be the start of bottom-up techniques for building sophisticated and energy-efficient optical and thermal materials."

Acoustofluidics is the fusion of acoustics and fluid mechanics which provides a contact-free, rapid and effective manipulation of fluids and suspended particles. The applied acoustic wave can produce a non-zero time-averaged pressure field to exert an acoustic radiation force on particles suspended in a microfluidic channel. However, for particles below a critical size the viscous drag force dominates over the acoustic radiation forces due to the strong acoustic streaming resulting from the acoustic energy dissipation in the fluid. Thus, particle size acts as a key limiting factor in the use of acoustic fields for manipulation and sorting applications that would otherwise be useful in fields including sensing (plasmonic nanoparticles), biology (small bioparticle enrichment) and optics (micro-lenses).

Although acoustic nanoparticle manipulation has been demonstrated, terahertz (THz) or gigahertz (GHz) frequencies are usually required to create nanoscale wavelengths, in which the fabrication of very small feature sizes of SAW transducers is challenging. In addition, single nanoparticle positioning into discrete traps has not been demonstrated in nanoacoustic fields. Hence, there is a pressing need to develop a fast, precise and scalable method for individual nano- and submicron scale manipulation in acoustic fields using megahertz (MHz) frequencies.

An interdisciplinary research team led by Associate Professor Ye Ai from Singapore University of Technology and Design (SUTD) and Dr. David Collins from University of Melbourne, in collaboration with Professor Jongyoon Han from MIT and Associate Professor Hong Yee Low from SUTD, developed a novel acoustofluidic technology for massively multiplexed submicron particle trapping within nanocavities at the single-particle level.

The acoustofluidic device uses surface acoustic waves (SAWs) as the actuation source and contains an elastic nanocavity layer located at the interface of the microfluidic channel and the acoustic transducer. The generated SAW gives rise to acoustically-driven deformations in the nanocavities and produces a time averaged acoustic field that generates a nanoscale acoustic force gradients along the channel.

By taking advantage of this unique nanoscale acoustic force field to overcome the Brownian motion and acoustic streaming, the team was able to manipulate millions of individual nano- and submicron scale particles towards the nanocavities. Nanocavity layer implementation on the SAW actuator provides discrete trapping positions where individual nanoparticles can be confined by exposure to SAW and released with the cessation of SAW excitation. This is a fast-processing and contact-free trapping system with the potential for widespread application in sorting, patterning and size-selective capture of sub-micron and nanoscale objects.

This work has been published in Small, a top-tier, multidisciplinary journal, covering a broad spectrum of topics in nano- and microscale experimental and theoretical studies, and has been featured on the inside cover of the issue. SUTD graduate students and postdoctoral fellows, including Mahnoush Tayebi, Richard O'Rorke and Him Cheng Wong participated in this research project.

Understanding and predicting how molecules recognize each other are the key issues in the field of supramolecular chemistry and biology, etc., where the non-covalent bindings play an essential role. Among many types of non-covalent interactions, ion-π interactions, including both cation-π and anion-π interactions, are practically important in regulating many important vital processes, such as gene expression, nicotine addiction and ion channel, etc., through recognizing specific ions by the receptors. A deep insight into how the inherent binding nature determines the trends of a set of ion-π systems is critical for rational designs of drugs and advanced functional materials.

The most popular viewpoint of theory and experiment so far is that the binding interactions of ion-π systems, both cation-π and anion-π, are governed by the electrostatic interactions and the ion-induced polarizations together. Thus, the necessity of two kinds of descriptors for searching for the desired ion-π complexes has been well recognized in this field. And the widely applied descriptors are the quadrupole moment (Qzz), electrostatic potential (ESP) and the polarizability (azz) of the π systems. These models treat ions as point charges, which lead to the lack of information from the ions, and can be especially problematic for the multi-shaped ions. However, for molecular communication based on ion-π interactions, usually it is ions that carry the information read by the receptors containing one or several arene rings. Consequently, the key role of information-carrying ions cannot be recognized when these widely used models are employed.

Recently, Zhangyun Liu, Zheng Chen, Jinyang Xi and Xin Xu from Fudan University proposed a new descriptor named the orbital electrostatic energy (OEE), which describes the electrostatic properties of both ions and the arene π systems in detail via electron density distributions on orbitals (Figure a). Note that, if the ion is simplified as a point charge, the OEE model is reduced naturally to the widely used ESP model. Qzz can be related to ESP by a multipole expansion, which represents a further simplification, where the information to differentiate different binding sites of the arene π system is dropped off.

A complete description of the ion-π interactions would have to invoke high-level calculations, such as an expensive coupled-cluster (CC) based method. The authors have used XYG3, which is an accurate yet efficient density functional theory method, to set up a data set of ion-π interactions made of not only simple (e.g., Na+, and Cl-) ion-π systems but also multiply-shaped (e.g., NH4+, C(NH2)3+, N3-, NO3-, BF4-, and SCN-) ion-π systems. Of course, it can be anticipated that the point charge based models should be reasonable for simple ions, which becomes erroneous for multiply-shaped ions.

To explore the binding nature, one can, in principle, carry out a detailed energy decomposition analysis (EDA) on a given system. However, a typical EDA calculation requires several constrained (variational) calculations, which can be expensive and may even fail to converge. On the other hand, people are usually more interested in finding the trend for a set of ion-π complexes, digging out some useful concepts which can help the future rational design. In this context, it is more direct and convenient to correlate the total binding energies (BEs) with certain descriptors, e.g. ESP, Qzz, and azz, as commonly done in the literature. However, it is vital that these descriptors can capture the fundamental physics of the interactions under study. The model should be as simple as possible but not simpler.

In this work, different descriptors have been explored with qualitative or quantitative differences in probing the physical nature of the ion-π interactions, in order to understand how the physical nature (i.e., the electrostatic effect and/or the polarization effect) controls the BE trend for a set of ion-π complexes. The authors found that the more accurate the descriptor is in describing the electrostatic effect, the stronger the correlation is between the descriptor and the BEs of the related ion-π complexes. The OEE is the only descriptor which strongly correlates to the BEs of both simple ion-π and multiply-shaped ion-π complexes (Figure b-c). On the other hand, unless the electrostatic effect is accurately characterized, the polarization effect can hardly refine the predictions in trends of ion-π interactions. In combination with the OEE, including polarization contributions can lead to highly accurate predictions of the cation-π binding strengths, although the same does not hold true for the anion-π complexes. These results demonstrated that it is the electrostatic contribution that controls the trend of the BEs for a set of related ion-π complexes, while the polarization effect is only important in the cation-π complexes rather than in the anion-π complexes in this regard. Based on this understanding, the authors designed a protocol where the OEEs are calculated at a low-level method, which are then used as a descriptor for the prediction of the total BEs at a high-level method.

Many EDA methods are able to yield the OEE value, while the present authors suggested to use OEE as a descriptor as opposed to ESP and Qzz, and found that OEE is solely responsible for the total BE trend, acting as a useful guide for the screening or design of a specific ion-π system. As electrostatic interactions are ubiquitous, it is anticipated that the OEE descriptor can be a useful tool in many areas such as supramolecular chemistry and biological chemistry.

In Germany about 18 million people suffer from non-alcoholic fatty liver. The causes of this disease are manifold and include environmental as well as genetic factors. DZD researchers have now discovered new genes that play a role in the development of fatty liver. In humans and mice, respectively, the genes IRGM, Ifgga2 and Ifgga4 are responsible for the production of regulatory proteins of the family of immunity-related GTPases which counteract fat accumulation in the liver. However, a genetic variation leads to the formation of fewer of these proteins. The results have now been published in the Journal of Hepatology.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in Europe and the United States. In Europe about 20-30 percent of the population are affected. NAFLD is often associated with other diseases such as obesity, type 2 diabetes, high blood pressure (arterial hypertension) and a fat metabolism disorder (dyslipidemia). In addition to an unhealthy lifestyle with a high-fat, high-sugar diet and lack of exercise, a genetic predisposition is also responsible for the development of this liver disease. However, for this complex disease not only one gene butrather the interactions of different genes and epigenetic * factors are responsible. Researchers have now discovered a new family of genes that play an important role in preventing fatty liver development. In humans and mice, these genes produce regulatory proteins from the family of immunity-related GTPases that counteract fat accumulation in the liver. However, if there is a genetic modification, fewer proteins are formed. Studies show that the liver of patients with NAFLD and mice with fatty liver have significantly lower amounts of these proteins. The study, which has now been published in the Journal of Hepatology, was carried out by a team of researchers of the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), the German Diabetes Center (DDZ) and Helmholtz Zentrum München - all partners of the German Center for Diabetes Research (DZD).

New genes identified

Using molecular markers and statistical methods - quantitative trait locus (QTL) analysis - genes that cause complex human diseases can be identified in mouse strains. For example, the research team discovered a region on mouse chromosome 18 that was associated with altered amounts of fat in the liver. If the genes Ifgga2 and Ifgga4 are expressed, proteins of the family of immunity-related GTPases are formed - in the mouse the proteins IFGGA2 and IFGGA4 and in humans the protein IRGM. These proteins increase a certain form of fat degradation and thus counteract the development of fatty liver.

The reason for a lower expression in mice with a fatty liver is a small genetic variation. "Due to the loss of only a single base in a gene sequence, which increases the expression of a certain gene, the two related proteins IFGGA2 and IFGGA4 are hardly produced in liver cells of mice that are susceptible to fatty liver," said Professor Annette Schürmann, head of the Department of Experimental Diabetology at the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) and spokesperson for the German Center for Diabetes Research (DZD). Patients with NAFLD also have significantly lower amounts of the corresponding protein (IRGM). As a result, the fat content in the liver can increase three to four-fold.

Proteins increase specific degradation of fat in the liver (lipophagy)

Functional studies have shown that an overproduction of immunity-related GTPases in liver cells or in the liver of mice, significantly reduced their fat content. "The reason for this is the induction of a particular form of autophagy that is specific for the degradation of fats and is therefore called lipophagy," explained Dr. Wenke Jonas, who co-directed the study together with Professor Schürmann. Autophagy is a type of cellular disposal and recycling process through which the cell's own components are degraded. The researchers have observed that after the uptake of fatty acids in liver cells, the immunity-related GTPases migrate to the lipid droplets. There they bind to an enzyme involved in fat degradation (adipocyte triglyceride lipase, ATGL) and ensure that a central protein of autophagy (LC3B) binds to the fat droplet. Due to the autophagy of lipid droplets, the amount of fat is reduced and thus the development of fatty liver is prevented.

The researchers were also able to show that the immunity-related GTPases affect the amount of fat in the liver in the following two studies: If they inhibited the synthesis of the proteins, mice stored more fat in the liver cells. If, on the other hand, the production of the proteins in liver cells was increased, the cells stored considerably less fat.

"Our work has identified further important genes that cause fatty liver disease. The study results also deepen our understanding of which cellular processes have to be stimulated to counteract fatty liver development," said Schürmann. "Our next goal is to clarify which measures - such as diets or certain drugs - can increase the amount of immunity-related GTPases in order to reduce fat storage in the liver."

* Epigenetics investigates those properties of genes that are not revealed by the DNA sequence itself, but by their expression. Epigenetic information is mediated by methyl groups or other biomolecules which, like chemical locks, deny or release access to certain DNA sequences and thus control their activation. Which epigenetic code is established in a person and whether it changes in the course of life is determined not only by the body's own signal substances but also by eating habits and other aspects of lifestyle.

The known Madagascar copal is a more recent resin from what was thought -it has about a few hundred years- and trapped pieces in this material are not as palaeontological important as thought traditionally. This is one of the conclusions of the new article in the journal PLOS ONE, whose first author is Xavier Delclòs, professor at the Faculty of Earth Sciences and member of the Biodiversity Research Institute (IRBio) of the University of Barcelona.

The study states that the well-known Madagascar copal is not a semi-fossilized resin but a material made during the Antropocene, historical period in which human impact was extreme globally. The findings would require going over the described taxon during the last hundred and fifty years to avoid taxonomic mistakes and unprecise paleoenvironmental reconstructions, the study notes.

Other participants in this study, the first to describe the oldest age and geographical origin of the Madagascar copal, are Enrique Peñalver, from the Spanish Geological and Mining Institute (IGME), Voajanahary Ranaivosoa, from the University of Antananarivo (Madagascar) and Mónica M. Solórzano Kraemer, from the Senckenberg Research Institute (Frankfurt, Germany).

From Tanzania coasts to Indian markets

Known for hundreds of years, the Madagascar copal crossed the trade routes from Tanzania to China through the Indian Ocean and the Indian markets. Sold as incense at first, it became pricey due to its high value to make varnish. More recently, it was used as disinfectant -burnt in Madagascar houses- and it was sold to scientists and tourists for its high content of arthropods inside.

This ancient resin which was not completely fossilized comes from Hymenaea verrucosa trees, a fabacean that grows in the eastern coast of Madagascar, one of the most threatened and fragile ecosystems in the world.

Wrong dating for an ancient resin

According to the study, the scientific community studied the biological remains inside the copal, named bioinclusions, and dated these findings from a few tens to millions of years. However, the origin of the studied material was never found -it is not cited in any study-, and the exact age of the studied pieces was never proved.

"The correct dating of the copal, as an important factor for a planetological study, can influence all the following paleo-biological studies, such as those related to phylogeny, paleobiogeography, and paleoclimatology", notes Professor Xavier Delclòs, from the Department of Earth and Ocean Dynamics of the UB.

According to the study, some found species in the Madagascar copal -thought to be extinct- could be now in forest habitats that were not considered to be their natural habitats. This can explain the occasional presence of arthropod species inside this old resin and which are currently living in the area.

The study notes that any new described taxon after the Madagascar copal should be attached the dating of Carbon-14 for the studied sample (at least, the sample including the main piece or holotype). Also, museums with Malagasy copal specimen pieces should review the dating with the Carbon-14 system.

An Anthropocene resin to protect Malagasy biodiversity

The loss of biodiversity during the Anthropocene is a threat in different areas of the planet, especially in warm areas of biodiversity such as the island of Madagascar. This study shows the scientific value of the Madagascar copal as a source of biological and paleobiological information to study the loss of biodiversity during the Anthropocene in Malagasy areas which are important areas of threatened biodiversity.

"The Madagascar copal is a file of great scientific interest. It represents a part of the Malagasy biodiversity and ecosystem during historical periods and can contain extinct species due to the high rate of deforestation in the Red Island over the last three hundred years", note the authors. "If this intense deforestation continues at the current rate, it is likely for the preserved species in the resin of Hymenaea trees -together with historical entomological collections- to become the only knowledge reservoirs to do research on a part of the entomofauna of fragile tropical forests of Madagascar lowlands", conclude researchers.

Kyoto, Japan -- Fais attention! Serpent!

You may not speak French, but if someone behind you in a forest shouted this, you'd likely understand and become instantly alert.

And according to a new report from Kyoto University's Hakubi Center for Advanced Research, the same thing happens in birds.

Previous reports have shown that animals with shared predators can eavesdrop on and respond to each other's calls, indicating that they can partly understand other species. Toshitaka Suzuki, publishing in Current Biology, noticed a similar phenomenon among two different bird species while conducting field studies.

"Many birds have specific alarm calls, warning others about a predator," explains Suzuki. "I was studying how a specific call of a small bird named the Japanese tit, Parus minor, evokes a visual image of the predator in their minds, in particular, a snake."

But he then observed that another bird, the coal tit or Periparus ater, also often approached the experimental area during these alarm calls.

"I wondered if these other birds also mentally retrieve 'snake' images from these calls. While they are in the same taxonomic group their calls are otherwise vastly different."

To demonstrate this, Suzuki set up an experiment under controlled conditions to investigate if the coal tits can anticipate and react appropriately even when they have not yet seen the predator in question. Snake-specific warning calls of the Japanese tit were played, and a stick was moved to mimic a snake gliding across the ground or up a tree.

"A variety of bird calls were played, but it was only the snake-specific ones which caused the coal tits to approach and inspect the stick," states Suzuki. "Additionally, when the stick was moved unlike a snake, such as in a rocking motion, none of the birds approached even when the warning calls were played."

These results show that the birds likely visualize a snake and react appropriately when they hear the snake-specific call from the other species, supported by visual confirmation. This work therefore represents the first evidence of visual search activity evoked via eavesdropping on another animal's alarm calls.

Suzuki intends to pursue this study to further explore how birds associate another species' calls with predators, hoping eventually to provide the basis for a new model for speech acquisition that may even be applicable to humans.

"Nature unveiling herself before science" is a sculpture by Louis-Ernest Barrias on display at the Musée d'Orsay in Paris. A research collaboration of the University of Vienna and the Sorbonne in Paris now took this credo to heart. "In order to create efficient functional materials, nature offers the best recipes by providing evolutionarily successful concepts," says Dennis Kurzbach from the Institute of Biological Chemistry. Kurzbach and his colleagues applied a jointly developed technology, based on NMR spectroscopy, to reveal the secrets of biomineralisation.

Closing gaps of precision

NMR (nuclear magnetic resonance) is an important method to determine the structures of molecules in solution, albeit limited resolution. In order to facilitate real-time monitoring of rapid chemical processes, Dennis Kurzbach and his team developed a new prototype that, based on hyperpolarisation (more specifically Dissolution Dynamic Nuclear Polarisation, D-DNP), provides the scientists with up to 10,000-fold amplified signals in NMR experiments.

With this D-DNP prototype, the scientists can monitor processes taking place on the milliseconds timescale, while at the same time single atoms can be resolved. The prototype encompasses an already patented system to mix various interaction partners within milliseconds and to initiate real-time detection.

Precipitation of ionic solids from solution

Dennis Kurzbach, an expert in methods development, started the proof-of-concept with his Parisian colleague Thierry Azaïs, who was interested in a better understanding of the initial steps of biomineralisation. Using D-DNP monitoring, the scientists probed fast interaction kinetics such as those underlying the formation of pre-nucleation species that develop within milliseconds when calcium and phosphate ions meet in solution and that precede non-classical solid-liquid phase separation. "For the first time, we were able to analytically characterise these pre-nucleation species at high resolution," Kurzbach explains, who has established the cutting-edge technology in the NMR Core Facility of the Faculty of Chemistry within the framework of his ERC Starting Grant.

With their new insights and technology, the researchers are also contributing material to a long-lasting dispute about the theory behind the biomineralisation of calcium phosphate. "Some researchers doubt that the pre-nucleation species can be integrated into the classical theoretical framework developed over decades," says Dennis Kurzbach.

The researcher's study also provides a kick-off for a recently granted project funded by the Austrian Science Fund FWF, in which Kurzbach intends to use his technology to advance the characterisation of biominerals as well as of the initial chemical processes before nucleation. For example, he aims at clarifying whether the size of the newly discovered species is controllable and if so, whether it is possible to engineer future hardness or brittleness of the macroscopic material.

"Moreover, it will be interesting to see whether we can help to solve the current theoretical shortcomings," Kurzbach says, who graduated not only in chemistry, but also in philosophy. "For me, our research goals are also strongly reflected by Aristoteles' ideas: All human beings strive by nature after knowledge." The D-DNP technology now makes it possible to deepen our knowledge of the nature of the materials, which provides important properties to people and society.

Higher frequencies mean faster data transfer and more powerful processors - the formula that has been driving the IT industry for years. Technically, however, it is anything but easy to keep increasing clock rates and radio frequencies. New materials could solve the problem. Experiments at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) have now produced a promising result: An international team of researchers was able to get a novel material to increase the frequency of a terahertz radiation flash by a factor of seven: a first step for potential IT applications, as the group reports in the journal Nature Communications (DOI: 10.1038/s41467-020-16133-8).

When smartphones receive data and computer chips perform calculations, such processes always involve alternating electric fields that send electrons on clearly defined paths. Higher field frequencies mean that electrons can do their job faster, enabling higher data transfer rates and greater processor speeds. The current ceiling is the terahertz range, which is why researchers all over the world are keen to understand how terahertz fields interact with novel materials. "Our TELBE terahertz facility at HZDR is an outstanding source for studying these interactions in detail and identifying promising materials," says Jan-Christoph Deinert from HZDR's Institute of Radiation Physics. "A possible candidate is cadmium arsenide, for example."

The physicist has studied this compound alongside researchers from Dresden, Cologne, and Shanghai. Cadmium arsenide (Cd3As2) belongs to the group of so-called three-dimensional Dirac materials, in which electrons can interact very quickly and efficiently, both with each other and with rapidly oscillating alternating electric fields. "We were particularly interested in whether the cadmium arsenide also emits terahertz radiation at new, higher frequencies," explains TELBE beamline scientist Sergey Kovalev. "We have already observed this very successfully in graphene, a two-dimensional Dirac material." The researchers suspected that cadmium arsenide's three-dimensional electronic structure would help attain high efficiency in this conversion.

In order to test this, the experts used a special process to produce ultra-thin high-purity platelets from cadmium arsenide, which they then subjected to terahertz pulses from the TELBE facility. Detectors behind the back of the platelet recorded how the cadmium arsenide reacted to the radiation pulses. The result: "We were able to show that cadmium arsenide acts as a highly effective frequency multiplier and does not lose its efficiency, not even under the very strong terahertz pulses that can be generated at TELBE," reports former HZDR researcher Zhe Wang, who now works at the University of Cologne. The experiment was the first ever to demonstrate the phenomenon of terahertz frequency multiplication up to the seventh harmonic in this still young class of materials.

Electrons dance to their own beat

In addition to the experimental evidence, the team together with researchers form the Max Planck Institute for the Physics of Complex Systems also provided a detailed theoretical description of what occurred: The terahertz pulses that hit the cadmium arsenide generate a strong electric field. "This field accelerates the free electrons in the material," Deinert describes. "Imagine a huge number of tiny steel pellets rolling around on a plate that is being tipped from side to side very fast."

The electrons in the cadmium arsenide respond to this acceleration by emitting electromagnetic radiation. The crucial thing is that they do not exactly follow the rhythm of the terahertz field, but oscillate on rather more complicated paths, which is a consequence of the material's unusual electronic structure. As a result, the electrons emit new terahertz pulses at odd integer multiples of the original frequency - a non-linear effect similar to a piano: When you hit the A key on the keyboard, the instrument not only sounds the key you played, but also a rich spectrum of overtones, the harmonics.

For a post 5G-world

The phenomenon holds promise for numerous future applications, for example in wireless communication, which trends towards ever higher radio frequencies that can transmit far more data than today's conventional channels. The industry is currently rolling out the 5G standard. Components made of Dirac materials could one day use even higher frequencies - and thus enable even greater bandwidth than 5G. The new class of materials also seems to be of interest for future computers as Dirac-based components could, in theory, facilitate higher clock rates than today's silicon-based technologies.

But first, the basic science behind it requires further study. "Our research result was only the first step," stresses Zhe Wang. "Before we can envision concrete applications, we need to increase the efficiency of the new materials." To this end, the experts want to find out how well they can control frequency multiplication by applying an electric current. And they want to dope their samples, i.e. enrich them with foreign atoms, in the hope of optimizing nonlinear frequency conversion.

In an effort to create first-of-kind microelectronic devices that connect with biological systems, University of Maryland (UMD) researchers are utilizing CRISPR technology in a novel way to electronically turn "on" and "off" several genes simultaneously. Their technique, published in Nature Communications, has the potential to further bridge the gap between the electronic and biological worlds, paving the way for new wearable and "smart" devices.

"Faced with the COVID-19 pandemic, we now have an even deeper understanding of how 'smart' devices could benefit the general population," said William E. Bentley, professor in UMD's Fischell Department of Bioengineering and Institute for Bioscience and Biotechnology Research (IBBR), and director of the Robert E. Fischell Institute for Biomedical Devices. "Imagine what the world would be like if we could wear a device and access an app on our smartphone capable of detecting whether the wearer has the active virus, generated immunity, or has not been infected. We don't have this yet, but it is increasingly clear that a suite of technologies enabling rapid transfer of information between biology and electronics is needed to make this a reality. "

With such a device, this information could be used, for example, to dynamically and autonomously conduct effective contact tracing, Bentley said.

In the past 60 years, microelectronics have greatly evolved from the first implantable pacemaker to personal wearables that harness the power of interrelated computing devices - better known as the Internet of things, or IoT. The next great wave of microelectronics could include devices that tap into and control molecules - such as glucose, hormones, or DNA - to better human health. But, a major roadblock remains.

Despite how advanced current smart devices might be, today's microelectronic devices process information using materials such as silicon, gold, or chemicals, and an energy source that provides electrons. But, free electrons do not exist in biological systems. As such, there remains a technology gap between microelectronics and the biological world.

Over two years ago, Bentley, his IBBR and Fischell Institute colleague, Gregory F,. Payne, and their teams published research on a loophole they discovered.

In biological systems, there already exists a small class of molecules capable of shuttling electrons. These molecules, known as "redox" molecules, can transport electrons to any location. To do this, redox molecules must first undergo a series of chemical reactions - oxidation or reduction reactions - to transport electrons to the intended target.

By engineering cells with synthetic biology components, Bentley's research team created a sophisticated synthetic "switching" system in bacterial cells that recognizes electrons instead of more traditional molecular signals and incorporates the biologically programmable genetic circuitry of CRISPR. Best known for gene editing, CRISPR control functions were modified to work with SoxR, a regulatory protein that is responsive to redox molecules and is found in E.coli. Instead of editing genes, the team is using CRISPR to focus a cell's metabolic machinery to carry out desired functions.

The group's process involves what is known as downregulation and upregulation, whereby, a cell either decreases (downregulation) or increases (upregulation) the quantity of a particular component - such as a protein - in response to an external stimulus. The team successfully demonstrated that, using CRISPR, they could electrically program the upregulation and downregulation of specific genes in E.coli as well as in Salmonella. In this way, the team proved that information programmed electrically can be transmitted to and within many strains of bacteria using the same medium of redox as a communication channel.

Even more, the group created and applied CRISPR technology to take advantage of the signal processing capabilities in electronics and telecommunications. They immobilized cells in a gel and used electronic signals to create a well-defined chemical gradient of the CRISPR-controlling extracellular signal. They showed that cells exposed to the most highly oxidized pyocyanin - a metabolite capable of participating in a redox reaction - showcased the highest level of CRISPR activity, while the cells exposed to minimally oxidized pyocyanin demonstrated the lowest level of CRISPR activity. In so doing, the team effectively supported their hypothesis that electrical signals could be used to spatially control CRISPR.

While CRISPR is universally considered an agile tool for biology, this work represents the first demonstration of how CRISPR can be used in bioelectronics to electronically target and control select genes, simultaneously.

"Our next steps involve ramping up our bioelectronics work so that the next generation communication devices can indeed incorporate biological information that is obtained locally," Bentley said.