Culture

To produce your thoughts and actions, your brain processes information in a hierarchy of regions along its surface, or cortex, ranging from "lower" areas that do basic parsing of incoming sensations to "higher" executive regions that formulate your plans for employing that newfound knowledge. In a new study, MIT neuroscientists seeking to explain how this organization emerges report two broad trends: In each of three distinct regions, information encoding or its inhibition was associated with a similar tug of war between specific brain wave frequency bands, and the higher a region's status in the hierarchy, the higher the peak frequency of its waves in each of those bands.

By making and analyzing measurements of thousands of neurons and surrounding electric fields in three cortical regions in animals, the team's new study in the Journal of Cognitive Neuroscience provides a unifying view of how brain waves, which are oscillating patterns of the activity of brain cells, may control the flow of information throughout the cortex.

"When you look at prior studies you see examples of what we found in many regions, but they are all found in different ways in different experiments," said Earl Miller, Picower Professor of Neuroscience in The Picower Institute for Learning and Memory and senior author of the study. "We wanted to obtain an overarching picture so that's what we did. We addressed the question of what does this look like all over the cortex."

Added co-first author Mikael Lundqvist of Stockholm University and MIT: "Many, many studies have looked at how synchronized the phases of a particular frequency are between cortical regions. It has become a field by itself, because synchrony will impact the communication between regions. But arguably even more important would be if regions communicate at different frequencies altogether. Here we find such a systematic shift in preferred frequencies across regions. It may have been suspected by piecing together earlier studies, but as far as I know hasn't been shown directly before. It is a simple but potentially very fundamental observation."

The paper's other first author is Picower Institute postdoc Andre Bastos.

To make their observations the team gave animals the task of correctly distinguishing an image they had just seen - a simple feat of visual working memory. As the animals played the game, the scientists measured the individual spiking activity of hundreds of neurons in each animal in three regions at the bottom, middle and top of the task's cortical hierarchy - the visual cortex, the parietal cortex and the prefrontal cortex. They simultaneously tracked the waves produced by this activity.

In each region they found that when an image was either being encoded (when it was first presented) or recalled (when working memory was tested), the power of theta and gamma frequency bands of brain waves would increase in bursts and power in alpha and beta bands would decrease. When the information had to be held in mind, for instance in the period between first sight and the test, theta and gamma power went down and alpha and beta power went up in bursts. This functional "push/pull" sequence between these frequency bands has been shown in several individual regions, including the motor cortex, Miller said, but not often simultaneously across multiple regions in the course of the same task.

The researchers also observed that the bursts of theta and gamma power were closely associated with neural spikes that encoded information about the images. Alpha and beta power bursts, meanwhile, were anti-correlated with that same spiking activity.

While this rule applied across all three regions, a key difference was that each region employed a distinct peak within each frequency band. While the visual cortex beta band, for instance, peaked at 11 Hz, parietal beta peaked at 15 Hz and prefrontal beta peaked at 19 Hz. Meanwhile visual cortex gamma occurred at 65 Hz, parietal gamma topped at 72 Hz and prefrontal gamma at 80 Hz.

"As you move from the back of the brain to the front, all the frequencies get a little higher," Miller said.

While both main trends in the study - the inverse relationships between frequency bands and the systematic rise in peak frequencies within each band - were both consistently observed and statistically significant, they only show associations with function, not causality. But the researchers said they are consistent with a model in which alpha and beta alternately inhibit, or release, gamma to control the encoding of information - a form of top-down control of sensory activity.

Meanwhile, they hypothesize that the systematic increase in peak frequencies up the hierarchy could serve multiple functions. For instance, if waves in each frequency band carry information, then it higher regions would sample at a faster frequency to provide more fine-grained sampling of the raw input coming from lower regions. Moreover, faster frequencies are more effective at entraining those same frequencies in other regions, giving higher regions an effective way of controlling activity in lower ones.

"The increased frequency in the oscillatory rhythms may help sculpt information flow in the cortex," the authors wrote.

Photonic systems consisting of multiple plasmonic/dielectric resonators coupled in different ways attracted immense research interests. Compared to simple photonic systems containing only one resonator, Such coupled systems exhibit more fascinating near-field (NF) properties (e.g., local field enhancement) and far-field (FF) responses manifested by unusual line-shapes dictated ultimately by how the involved resonators are coupled together, making them particularly useful in real applications.

Despite of great advances on experimental side, theoretical understandings on such systems are far from satisfactory. Available theoretical tools either cannot reveal the underlying physics (say, brute-force computations) or are empirical in nature (say, the coupled-mode-theory (CMT)) involving parameters retrieved from simulations, , which also hinders the fast designs of appropriate systems with desired NF and FF properties.

In a newly published paper in Light: Science & Application, Prof. Lei Zhou's group from Physics Department of Fudan University in China, derived a formal theoretical framework from first principles (i.e., Maxwell's equations), with all involved parameters directly computable via wave-function integrations without fitting procedures, to predict the fascinating properties of coupled photonic systems before having numerically simulated them (as always needed in previous parametrized models). To illustrate the powerfullness of their theory, they illustrate how to employ it to freely "design" the line-shape of a coupled system through modulating the couplings between resonators. In particular, they successfully construct a completely "dark" mode with vanishing radiative loss (i.e. a bound state in continuum), which have many applications in photonics. All theoretical predictions are verified by our experiments at near-infrared frequencies with excellent accuracies.

The established theoretical framework opens an alternative avenue to design the couplings, which have offered such complex photonic systems more opportunities to control NF and FF light environments as desired, making them particularly useful in applications such as nano-lasers, fluorescence enhancements and information transport. These scientists summarize their theory derived from first principles:

"...resemble the two equations in coupled mode theory, but our theory is different and processes the following merits. In the empirical CMT, the key parameters defined are usually obtained by fitting with numerical simulations, while the remaining ones can be derived by energy-conservation and time-reversal arguments. In contrast, here in our theory all parameters can be unambiguously evaluated, and therefore one can use it to predict the line-shapes of coupled systems before performing numerical simulations on them. Moreover, the empirical CMT cannot explicitly consider the NF couplings between resonators, while in our approach NF couplings can be unambiguously determined and explicitly included in determining the line-shape."

"Once the leaky eigen modes of every single scatter are obtained, we can predict the line-shapes of the coupled systems without necessarily performing simulations on them." They added.

"The significances of our work are clear: 1) On practical side, researchers (especially experimentalists) now have a powerful tool to "design" the coupled systems meeting their desires before performing simulations on a series of "trial" systems to search the best one; 2) On theoretical side, our theory provides a solid mathematics/physics basis for the empirical CMT widely used in the community, and more importantly, uncovers the clear physical meanings of those empirical parameters defined in the CMT; 3) The theory can be easily extended to study other wave systems (e.g., phononic systems). We believe that the general significance of this research and the new opportunities created by it should trigger intensive interests to a wide range of scientists." the scientists forecast.

Lithuanian researchers from Kaunas University of Technology and Vilnius University synthesised and tested a bio-based resin for optical 3D printing (O3DP). The bio-based resin made from renewable raw materials proved to be universal for both table-top 3D printers and state-of-the-art ultrafast laser, suitable for O3DP in the scales from nano- to macro- dimensions. This, according to the researchers, is a unique property for a single photo-resin.

Optical 3D printing (O3DP) is a rapid prototyping tool and an additive manufacturing technique being developed as a choice for efficient and low waste production, yet currently associated with petroleum-derived resins. During O3DP, the photo-curable resin is solidified by treating it with light; such technology makes 3D printing very flexible and precise - the elements can reach sub-micrometres, and also can reach macro- dimensions. The main shortcoming of O3DP is connected to the limitations of the printing materials: their origin, physical and chemical properties, which make the resins not suitable for all setups.

"A universal bio-based resin developed by KTU researchers can be used for a multi-scale 3D printing. Up to now, no single resin was developed which would allow manufacturing of ultra-fine nano-/micro-features and macro-objects out of the same composition", says Dr Mangirdas Malinauskas, Laser NanoPhotonics Research Group Leader at Laser Research Centre of Vilnius University (VU).

During the experiment conducted by VU researchers, a multi-scale (up to 5 orders) optical 3D printing of bio-based compound was performed using both state-of-the-art laser nanolithography setup and a common table-top 3D printer. Additionally, chess-like figures were made in an industrial line commercially delivering small batch production services (3D Creative). The bio-based photo-resin proved suitable for all applications without any further modifications. According to Dr Malinauskas, this is a unique property for any single photo-resin (regardless of its origin).

The novel bio-based photo-resin was developed at Kaunas University of Technology (KTU). The research group working at the KTU Department of Polymer Chemistry and Technology and headed by Dr Jolita Ostrauskaite designed formulations of photo-curable resins for optical 3D printing, as well as synthesised, characterised and investigated the rheological, mechanical, thermal properties of polymer materials obtained from these resins.

"Currently, only thermoplastic bio-based polymers used in thermal 3D printing technology are commercially available. KTU scientists have developed a bio-based photo-curable resin which can be used for optical 3D printing. Bio-based photo-curable resins for such technologies are not currently available on the market", says Dr Ostrauskaite.

According to her, the biggest advantage of the novel bio-based photo-curable resin is the ability to obtain their components from renewable raw materials, moreover, these components can be purchased in commercially large quantities.

Although the novel bio-based photo-resin is not commercialised yet, the researchers claim that it could be used immediately on demand in industrial lines as it was shown to be compatible with commercially available setups of JSC 3D Creative. As the developed material is still very new, further investigation is needed for its safe and economical use in industry.

This eco-innovation is advanced further within the InterReg project EcoLabNet, a Baltic region-based network consisting of RDI and SME's.

(Vienna, 08 September 2020) Polycythaemia vera is a chronic malignant disease of the haematopoietic system and is treated with interferon-alpha-based drugs, in most cases with long-lasting success. However, in some cases this therapy is unsuccessful for reasons that are not yet understood. A research group led by Robert Kralovics from MedUni Vienna's Department of Laboratory Medicine and from CeMM has now conducted genetic association studies, which show that patients with certain DNA variants commonly found in the population do not respond sufficiently to the treatment. Hence, personalised determination of genetic factors may lead to improved forms of treatment. The study has been published in the leading journal "Blood".

Polycythaemia vera (PV) is one of a group of diseases called myeloproliferative neoplasms (MPN), which are rare chronic malignant blood diseases. A feature of MPN is the over-production of various blood cells. Sustained therapeutic success can be achieved by the administration of drugs based on interferon alpha (IFNa), which can eliminate the mutated cell clone and are able to permanently restrict malignant cell growth. However, the treatment is not equally successful in all patients.

Up until now, there was no explanation as to why patients respond differently to the treatment, although we know from other diseases that genetic factors can play a crucial role. The research group led by molecular biologist Robert Kralovics from MedUni Vienna's Department of Laboratory Medicine and from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences has now investigated a possible effect of hereditary DNA variants in PV patients given the novel drug ropeginterferon alfa-2b in the context of clinical trials. Genome-wide association studies (GWAS) were conducted first of all but these did not indicate any marked influence of genetic markers on therapeutic success. This suggests that all PV-patients are suitable for treatment with IFNa, regardless of their genetic makeup.

A feature of GWAS is that they only identify strong genetic associations but struggle to highlight weaker causal correlations. Therefore, the research team carried out targeted association analyses in the chromosomal region of the IFNL4 gene, which had previously been described in association with IFNa-based treatment of a completely different disease (hepatitis C). These analyses showed a strong effect due to a specific combination of two hereditary DNA variants in the IFNL4 gene (IFNL4 diplotype), which is widespread in the population. Patients with a specific IFNL4 diplotype status show significant resistance of the mutated malignant cell clone during the course of treatment. This affects around one third of patients.

The study suggested that genetic determination of IFNL4 diplotype status could enable customised, more effective treatment, since a significant reduction of the malignant cell clone is crucial to the therapeutic success. The IFNL4 diplotype status has the potential to serve as a pharmacogenetic marker for the development of personalised forms of treatment for PV and other myeloproliferative neoplasms.

Over the long-term, what one partner in a two-person relationship wishes to avoid, so too does the other partner - and what one wants to achieve, so does the other. These effects can be observed regardless of gender, age and length of the relationship, as researchers from the University of Basel report in a study of more than 450 couples.

The research team from the University of Basel's Faculty of Psychology wanted to examine the short- and long-term interdependence of approach goals and avoidance goals within couples. The participants reported whether they had tried to avoid conflicts or share meaningful experiences with their partner that day. This was followed by an analysis of how the information affected the goals of the partner.

The goals of each person were recorded daily over the course of two 14-day measurement periods at an interval of 10 to 12 months; 456 male-female couples took part. The average age of the participants was just under 34 years old, and the average relationship length was almost 10 years. The study appeared in the latest issue of The Journal of Gerontology.

Delayed effects

The study showed that when one person within a couple avoids distress and conflicts, for example, the other tries to do the same. And conversely, when one person seeks personal growth and meaningful experiences, the other wants to achieve them too. The team of psychologists, led by first author Professor Jana Nikitin, found significant delayed effects between the partners. These appeared regardless of gender, age or relationship length.

It was notable that the daily goals of one partner - which can change - mainly coincided with the medium- and longer-term goal trends of the other partner. It therefore takes several days to months for the long-term relationship goals of one partner to have an impact on the goals of the other. "This could be an adaptive mechanism to maintain the stability of the relationship," says Nikitin, "by not being influenced by every momentary shift made by the partner."

Scientists review macrophage activation syndrome -- a feature of the cytokine storm that kills patients with severe cases of COVID-19, as well as possible treatments.

A significant percentage of COVID-19 cases are severe enough to warrant admission to hospital for monitoring and treatment. A substantial number of these patients die from the disease after appearing to respond well to treatment. The major cause of these deaths is a phenomenon called the cytokine storm, which occurs when hyperactivation of immune cells leads to a large amount of cytokines (cell signalling molecules), which in turn trigger systemic hyperinflammation. If untreated, this leads to multiple organ failure and, finally, death. If the cytokine storm could be weakened or prevented, the number of mortalities due to this phenomenon would drastically decrease, reducing the overall mortality to COVID-19.

Ryo Otsuka and Ken-ichiro Seino from the Institute for Genetic Medicine (IGM) at Hokkaido University reviewed the existing research on macrophage activation syndrome (MAS). Their work, published in the journal Inflammation and Regeneration, addresses the role that MAS plays in COVID-19, and highlights how existing therapies for MAS have shown initial success in ameliorating severe COVID-19 cases.

The cytokine storm occurs in other diseases and disorders such as influenza, pneumonia and sepsis, and has been studied in some detail. Along with MAS, an associated syndrome is the Acute Respiratory Distress Syndrome (ARDS), which is characterized by rapid onset of widespread inflammation in the lungs - a common feature of severe COVID-19 cases. Thus, the scientists reviewed the links between MAS and ARDS and the role MAS played in COVID-19.

Their review explained that MAS in COVID-19 was accompanied by ARDS, and that far more cytokines were involved than in previously documented cases of MAS. This difference is caused by the SARS-CoV-2 virus. When the virus enters the cells, it triggers an inflammatory response as the cells fight against it. The virus also triggers the inflammatory response by causing pyroptosis (a type of cell death caused when it infects cells), which activates macrophages. Additionally, the virus enters macrophages, activating them. The activated macrophages recruit T cells, which activate more macrophages, triggering a positive feedback loop. This causes MAS, which in turn leads to ARDS - which, untreated, is fatal.

According to this review, MAS is directly triggered by cytokines such as interleukin-6 (IL-6) and Tumor Necrosis Factor α (TNFα), and indirectly by IL-1. The scientists discussed previous case studies that had used therapies targeting these molecules to suppress MAS.

The review covered therapies targeting the molecules that cause MAS which show promise in reducing the severity of COVID-19. Preliminary trials have been carried out on tocilizumab (an IL-6 blocker) for severe cases in China, and on anakinra (an anti-IL-1 medication) for non-severe cases in Italy, and the results are generally positive. Additionally, in a trial conducted on 19 patients in the USA, treatment with acalabrutinib, a drug that targets the production of IL-1, also had favourable outcomes in severe COVID-19 cases. There are currently many clinical trials underway, testing many drugs that act on different aspects and stages of infection by SARS-CoV-2. "The clinical trials that show promise must be replicated on a much larger scale before their effectiveness can be validated," says Ryo Otsuka. "In the process, we may discover clues to a novel treatment."

Assistant Professor Otsuka and Professor Seino, from the Division of Immunobiology at IGM, study tumor and transplant immunology, including the roles of interleukins and macrophages.

For the brain to work efficiently, it is important that a nerve impulse arrives at its destination as quickly and as precisely as possible. It has been long been known that the nerve fibres - also known as axons - pass on these impulses. In the course of evolution, an insulating sheath - myelin - developed around the axons which increases the speed of conduction. This insulating sheath is formed by the second type of cell in the nervous system - the glial cells, which are one of the main components of the brain. If, as a result of disease, myelin is depleted, this leads to neurological disorders such as Multiple Sclerosis or Morbus Charcot-Marie-Tooth.

Researchers at the University of Münster have discovered that glial cells not only control the speed of nerve conduction, but also influence the precision of signal transduction. In the absence of these insulating sheaths, short-circuit-like processes occur, which influence the accuracy of the stimulus transmission. The research results have been published in the journal Nature Communications.

Background and methodology

Glial cells are not only indispensable for providing energy - they also have a broad range of other tasks in the brain. They are responsible for transport of metabolite and xenobiotics, regulating fluid exchanges, and maintaining ion homeostasis. In order to better understand the importance of glial cells for neuronal signaling, a team of researchers headed by Prof. Christian Klämbt at the Institute of Neuro- and Behavioural Biology at the University of Münster studied changes in behaviour after the induced activation of individual neurones in fruit flies (Drosophila melanogaster). "For this purpose," says Christian Klämbt, "we either removed individual glial cells from the nervous system or specifically disturbed their development concomitant to a light-induced, optogenetic, neuronal activation."

As a result of these activities, the researchers were first able to ascertain that glial cells control the radial growth of the axons. Smaller axons have, as expected, a slower conduction speed - which was determined by electrophysiological measurements in a collaboration with colleagues at the University of Bonn. Astonishingly, it became apparent that a slower conduction speed does not lead to any change in movement behaviour. The more important contribution made here by glial cells is the formation of membrane processes between individual axons - which prevents electrical coupling (i.e. short circuits) and thus makes a decisive contribution to the precision of neuronal signaling. The researchers undertook a detailed analysis of larval locomotion by means of a special custom made device. The development of the so-called FIM (Frustrated total internal reflection-based Imaging Method), together with self-developed software, allows a high-resolution depiction and analysis of movements made by even minute organisms. This led to a spin-off being set up - the "qubeto" company - which now continues the development of this technology and makes it available to the scientific community.

The function of glial cells as active modulators of the speed and, in particular, the precision of stimulus conduction, has not previously been described. "What our research makes clear is the role played by glial cells as active components in the nervous system," says Christian Klämbt, summing up the research results. "With these new findings we are creating a basis for a better understanding of some of the symptoms of diseases of the nervous system."

In photosynthesis, solar energy is converted into chemical energy, which is then used in nature to produce organic molecules from carbon dioxide. In plants, algae and cyanobacteria, the key photosynthesis reactions take place in two complex structures known as photosystems. These are located in a special membrane system, the thylakoids. However, many details of their molecular structure and the way the proteins are incorporated into the membranes have yet to be explored. A team led by Professor Conrad Mullineaux from the Institute of Biology and Chemistry at Queen Mary University London, UK, Professor Annegret Wilde and Professor Wolfgang Hess from the Institute of Biology III at the University of Freiburg and Professor Satoru Watanabe from the Institute of Biosciences at the Agricultural University of Tokyo, Japan, has published a study in the current issue of Nature Plants: The mRNAs are transported to the thylakoid membranes and the respective proteins are produced there on the spot.

The researchers used molecular genetic, bioinformatics and high-resolution microscopic approaches at the single cell level for their investigations. The results confirm that mRNA molecules encode much more than just the sequence of the protein. They also carry signals that appear to control the position and coordination of the photosystem structure. The team was able to identify two proteins likely to be involved in this process by interacting with these mRNAs. The researchers say this opens the way to a detailed understanding of the molecular mechanisms involved and provides new approaches to make these processes useful for photobiotechnology.

Researchers at the Department of Energy's Oak Ridge National Laboratory used quantum optics to advance state-of-the-art microscopy and illuminate a path to detecting material properties with greater sensitivity than is possible with traditional tools.

"We showed how to use squeezed light - a workhorse of quantum information science - as a practical resource for microscopy," said Ben Lawrie of ORNL's Materials Science and Technology Division, who led the research with Raphael Pooser of ORNL's Computational Sciences and Engineering Division. "We measured the displacement of an atomic force microscope microcantilever with sensitivity better than the standard quantum limit."

Unlike today's classical microscopes, Pooser and Lawrie's quantum microscope requires quantum theory to describe its sensitivity. The nonlinear amplifiers in ORNL's microscope generate a special quantum light source known as squeezed light.

"Imagine a blurry picture," Pooser said. "It's noisy and some fine details are hidden. Classical, noisy light prevents you from seeing those details. A 'squeezed' version is less blurry and reveals fine details that we couldn't see before because of the noise." He added, "We can use a squeezed light source instead of a laser to reduce the noise in our sensor readout."

The microcantilever of an atomic force microscope is a miniature diving board that methodically scans a sample and bends when it senses physical changes. With student interns Nick Savino, Emma Batson, Jeff Garcia and Jacob Beckey, Lawrie and Pooser showed that the quantum microscope they invented could measure the displacement of a microcantilever with 50% better sensitivity than is classically possible. For one-second long measurements, the quantum-enhanced sensitivity was 1.7 femtometers - about twice the diameter of a carbon nucleus.

"Squeezed light sources have been used to provide quantum-enhanced sensitivity for the detection of gravitational waves generated by black hole mergers," Pooser said. "Our work is helping to translate these quantum sensors from the cosmological scale to the nanoscale."

Their approach to quantum microscopy relies on control of waves of light. When waves combine, they can interfere constructively, meaning the amplitudes of peaks add to make the resulting wave bigger. Or they can interfere destructively, meaning trough amplitudes subtract from peak amplitudes to make the resulting wave smaller. This effect can be seen in waves in a pond or in an electromagnetic wave of light like a laser.

"Interferometers split and then mix two light beams to measure small changes in phase that affect the interference of the two beams when they are recombined," Lawrie said. "We employed nonlinear interferometers, which use nonlinear optical amplifiers to do the splitting and mixing to achieve classically inaccessible sensitivity."

The interdisciplinary study, which is published in Physical Review Letters, is the first practical application of nonlinear interferometry.

A well-known aspect of quantum mechanics, the Heisenberg uncertainty principle, makes it impossible to define both the position and momentum of a particle with absolute certainty. A similar uncertainty relationship exists for the amplitude and phase of light.

That fact creates a problem for sensors that rely on classical light sources like lasers: The highest sensitivity they can achieve minimizes the Heisenberg uncertainty relationship with equal uncertainty in each variable. Squeezed light sources reduce the uncertainty in one variable while increasing the uncertainty in the other variable, thus "squeezing" the uncertainty distribution. For that reason, the scientific community has used squeezing to study phenomena both great and small.

The sensitivity in such quantum sensors is typically limited by optical losses. "Squeezed states are fragile quantum states," Pooser said. "In this experiment, we were able to circumvent the problem by exploiting properties of entanglement." Entanglement means independent objects behaving as one. Einstein called it "spooky action at a distance." In this case, the intensities of the light beams are correlated with each other at the quantum level.

"Because of entanglement, if we measure the power of one beam of light, it would allow us to predict the power of the other one without measuring it," he continued. "Because of entanglement, these measurements are less noisy, and that provides us with a higher signal to noise ratio."

ORNL's approach to quantum microscopy is broadly relevant to any optimized sensor that conventionally uses lasers for signal readout. "For instance, conventional interferometers could be replaced by nonlinear interferometry to achieve quantum-enhanced sensitivity for biochemical sensing, dark matter detection or the characterization of magnetic properties of materials," Lawrie said.

For more than a decade, scientists have accepted that cholesterol - a key component of cell membranes - did not uniformly affect membranes of different types. But a new study led by Assistant Professor Rana Ashkar of the Virginia Tech Department of Physics finds that cholesterol actually does adhere to biophysical principles.

The findings, published recently in the Proceedings of the National Academy of Sciences, have far-reaching implications in the general understanding of disease, the design of drug delivery methods, and many other biological applications that require specific assumptions about the role of cholesterol in cell membranes.   

"Cholesterol is known to promote tighter molecular packing in cell membranes, but reports about how it stiffens membranes have been so conflicting," said Ashkar, who is a faculty member in the Virginia Tech College of Science. "In this work, we show that, at the nanoscale level, cholesterol indeed causes membrane stiffening, as predicted by physical laws. These findings affect our understanding of the biological function of cholesterol and its role in health and disease."

According to the study, cell membranes are thin layers of fatty molecules that define cell boundaries and regulate various biological functions, including how viruses spread and how cells divide. To enable such functions, membranes should be able to bend and permit shape changes. This bending propensity is determined by how packed the molecular building blocks are; tighter packing results in stiffer membranes that cannot bend so easily, Ashkar added.

Cholesterol's impact on cell membranes at the molecular level

Cholesterol is found in high quantities in bacon, egg, cheese, and many other comfort foods. While too much cholesterol can harm the body, regulated amounts of cholesterol in cell membranes are absolutely necessary for the normal function of cells. Anomalies in cholesterol amounts are often associated with various disease conditions.

Besides cholesterol, our cell membranes are primarily formed of lipids, which are small, fatty molecules that self-assemble into bilayer structures when present in water - and nearly 60 percent of the human body is made of water. Together, lipids and cholesterol form the barriers that define our cells and regulate the cellular exchange of nutrients.

At the molecular level, cholesterol possesses a slick and rigid structure. When it interacts with our cell membranes, it jams itself right in between lipids, which results in a more densely packed membrane. According to structure-property relations, this would naturally result in a stiffer membrane.

Yet, for the past 10 or so years, physicists and biologists have assumed that cholesterol had nearly no effect on the stiffness of membranes formed of cis-unsaturated lipids, a common type of lipid found in our cells, despite its well-documented effect on lipid packing.

"It defied our understanding of what cholesterol does to cell membranes," Ashkar said. "It also contradicts standard structure-property relationships in self-assembled materials."

These perceptions are important because in ideal circumstances, cell membranes should maintain a semi-rigid structure: rigid enough to keep its form, but flexible enough to allow for the dynamic movement of signaling proteins and functional domains. Misconceptions about how cholesterol stiffens cell membranes impact our understanding of membrane function.

The data initially made little sense, but as she probed deeper, Ashkar found a clear case of how soft materials can "apparently" exhibit different properties, depending on the parameters of the observation method. She found that over short length and time scales over which important signaling events occur -- we're talking nanometers and nanoseconds -- the added cholesterol induces membrane stiffening that one would expect.

Proving her point

To contradict an established doctrine in science requires more than just one set of data points. "We found these results a while back, but they were met with skepticism because they're so against the existing notions," Ashkar said.

Ashkar's first tests used neutron spin-echo spectroscopy, a unique probe that enables the study of materials on the nanoscale. These experiments were performed at the two major neutron scattering facilities in the United States, the NIST Center for Neutron Research and the Spallation Neutron Source at Oak Ridge National Laboratory.

Ashkar bolstered her evidence with computer modeling simulations, in collaboration with George Khelashvilli, an assistant professor at the Weill Cornell Medicine Department of Physiology & Biophysics, and further validated the experimental findings with recent nuclear magnetic resonance measurements, in collaboration with Michael Brown, a professor of chemistry and biochemistry at the University of Arizona. The data consistency in all three methods provided thorough evidence for Ashkar's hypothesis and confirmed standard structure-property relations in lipid membranes.

"These results call for a reassessment of existing constructs of how cholesterol affects lipid membranes," Ashkar said. "If we don't have the right assumptions, we cannot make the right predictions, and we will not have the right design for the treatment of viruses, diseases, or other biological anomalies."

Panthasaurus maleriensis lived about 225 million years ago in what is now India. It is an ancestor of today's amphibians and has been considered the most puzzling representative of the Metoposauridae. Paleontologists from the universities of Bonn (Germany) and Opole (Poland) examined the fossil's bone tissue and compared it with other representatives of the family also dating from the Triassic. They discovered phases of slower and faster growth in the bone, which apparently depended on the climate. The results have now been published in the journal PeerJ.

Temnospondyli belong to the ancestors of today's amphibians. This group of animals became extinct about 120 million years ago in the Early Cretaceous. The Temnospondyli also include the Metoposauridae, a fossil group that lived exclusively in the Late Triassic about 225 million years ago. Remains of these ancestors are present on almost every continent. In Europe, they are found mainly in Poland, Portugal and also in southern Germany.

Panthasaurus maleriensis, the most puzzling representative of the Metoposauridae to date, lived in what is now India, near the town of Boyapally. "Until now, there were hardly any investigation opportunities because the fossils were very difficult to access," explains Elzbieta Teschner from the University of Opole, who is working on her doctorate in paleontology in the research group of Prof. Dr. Martin Sander at the University of Bonn. Researchers from the Universities of Bonn and Opole, together with colleagues from the Indian Statistical Institute in Kolkata (India), have now examined the tissue of fossil bones of a metoposaur from the Southern Hemisphere for the first time. The amphibian, which resembled a crocodile, could grow up to three meters in length.

Valuable insight into the bone interior

"The investigated taxon is called Panthasaurus maleriensis and was found in the Maleri Formation in Central India," notes Teschner with regard to the name. So far, the fossil has only been examined morphologically on the basis of its external shape. "Histology as the study of tissues, on the other hand, provides us with a valuable insight into the bone interior," says Dr. Dorota Konietzko-Meier from the Institute for Geosciences at the University of Bonn. The histological findings can be used to draw conclusions about age, habitat and even climate during the animal's lifetime.

The histological examinations revealed that the young animals had very rapid bone growth and that this growth decreased with age. The Indian site where the bones were found provides evidence of both young and adult animals, in contrast to Krasiejów (south-western Poland), where only young animals were found. Geological and geochemical data show that the Late Triassic consisted of alternating dry and rainy periods, as in the present monsoon climate of India. "This sequence is also reflected in the material examined," says Teschner. "There are phases of rapid growth, known as zones, and a slowdown, known as annulus." Normally, one can still observe stagnation lines in the bones, which develop during unfavorable phases of life, for example during very hot or very cold seasons.

In Panthasaurus maleriensis, however, growth never comes to a complete cessation. In comparison: the Polish Metoposaurus krasiejowensis shows the same alternation of zones and annuli in one life cycle and no stagnation lines, whereas the Moroccan representative of the metoposaurs Dutuitosaurus ouazzoui shows stagnation lines - that is, a complete stop in growth - in each life cycle.

The different growth phases in the bones allow for a comparison of climatic conditions. This means that the climate in the Late Triassic would have been milder in Central India than in Morocco, but not as mild as in the area that today belongs to Poland. Sander: "Fossil bones therefore offer a window into the prehistoric past."

From wildfires in California to hurricanes battering the Gulf, the United States has been assailed by natural disasters from coast to coast. But how can the United States address, mitigate, and adapt to the widespread destruction from wildfires and floods as they intensify from unchecked climate change?

According to a new survey by researchers at Stanford University, Resources for the Future, and ReconMR, Americans overwhelmingly want leaders at the federal and state levels to enact policies to adapt to wildfires and floods.

The second in a six-part series, the natural disasters installment of Climate Insights 2020: Surveying American Public Opinion on Climate Change and the Environment explores how Americans see climate change in relation to wildfire and inland flood adaptation policies.The report gives policymakers and the public an idea of where Americans stand on prospective policies, the role of governments, and who should pay for prevention and adaptation.

“We’ve found that Americans favor action,” report author and Stanford University professor Jon Krosnick said. “Liberals and conservatives, wealthy and not, people want public policy that will protect future generations and the most vulnerable. This is a strong signal to lawmakers that the public is supportive of new policies.”

Topline Findings

The majority of Americans favor a mix of state and federal government efforts to protect people from future wildfire and flood damage. However, most Americans prefer that people in fire- and flood-prone areas shoulder the costs of prevention and adaptation policies.
Americans who believe in the existence of climate change and people who are told that there is a link between climate change and natural disasters are more likely to support adaptation policies.
People who think climate change threatens future generations are far more likely to support adaptation policies than those who do not. Belief in this threat is the strongest predictor of policy support studied in this survey.
Black and Hispanic Americans are more supportive of government efforts than white, non-Hispanic Americans. This may be explained by the fact that people in historically marginalized communities disproportionately live in areas that are and will be most affected by climate change.
Contrary to the luxury goods hypothesis, lower-income people (with incomes less than $35,000) were more likely to support government adaptation policies than people with incomes of $35,000 and more.

“While issues of climate change and the environment often feel divided—and even divisive—in the United States, it’s interesting to see that the majority of Americans support adaptation policies to help us remain resilient in the face of fire and flood,” RFF Senior Fellow Margaret Walls said. “What’s more, the relationship between support for these adaptation policies and belief in climate change drives home the fact that education and trust in science is the bedrock upon which public policy must be built.”

To learn more about these findings, read the natural disasters installment of Climate Insights 2020 by Jon Krosnick, social psychologist at Stanford University and RFF university fellow, and Bo MacInnis, lecturer at Stanford University and PhD economist. You can also try out our data tool, which allows users to explore the data in greater depth.

Future installments in the survey series will focus on green stimulus, political dynamics, electric vehicles, and an overall synthesis. The first installment of this report, which focused on overall trends, was published on August 24, 2020.

Besides providing healthcare to millions, Medicaid helps recipients make healthier food choices according to UConn research published in the journal Health Economics. UConn Professor of Agricultural and Resource Economics, Rigoberto Lopez, Rebecca Boehm now an economist with the Union of Concerned Scientists, and Xi He now a post-doctoral researcher at the Iowa State were interested in investigating the impact of Medicaid on food choices.

Medicaid is beneficial to recipients in a multitude of ways, by reducing emergency room visits, increasing access to preventive healthcare, while reducing out-of-pocket medical costs and debt, for instance. The program is highly politicized and is met with criticism and assumptions that it is too costly, yet research has shown the program actually saves states money.

He, Lopez, and Boehm were interested in looking at other potential benefits of the program and also hoped to bridge some gaps in the literature says He,

"There are many studies about the impact of Medicaid on mental health or on health spending but few studies have looked at how Medicaid affects food choices."

He explains that by virtue of spending less on healthcare, new Medicaid recipients would have more room in their budget for food and therefore may spend more money on the same unhealthy foods and beverages they have always purchased. On the other hand, with more access to healthcare and health education through contact with providers, the researchers surmised that purchasing patterns could improve, says He.

To see if this was the case, the researchers looked at purchases of beverages such as carbonated soft drinks, juice, milk and other non-alcoholic beverages before and after the expansion of Medicaid and compared purchases in states that did and did not expand the program under the Affordable Care Act. In a way, the states that did not expand Medicaid were the control group for their study. They also compared purchase preferences for sugar content of these beverages.

"We found that households in expansion states significantly increased their purchase of diet soda and bottled water, but there was no change in purchase of regular soda. But overall, these results indicate that Medicaid expansion, in states that did expand, shifted people's purchases to products with less sugar," says He.

Access to healthcare has wide-ranging positive effects on the lives and habits of recipients. The added benefit of knowledge resulting from access to healthcare is not a policy mechanism that is usually discussed says Boehm,

"With so many people working to help people eat healthier and to reduce obesity in the US, I don't hear a lot of talk about how the provision of healthcare through this income effect we proposed in this study can help people eat and drink healthier."

Lopez says programs like Medicaid are often unfairly attacked and those attacks are done so without the numbers and data, therefore it is vital that research like this reaches decision makers.

"Besides the obvious benefit of subsidized healthcare, there is an additional spillover of the program in promoting a healthy diet by reducing one of the three evils of the American diet - sugar -- which is bad in all respects from calories to cancer to obesity. The program contributes not just to cover the treatment of patients but also in a more preventive way," says Lopez.

The researchers add that now with the pandemic, prevention and access to healthcare is more vital than ever. This is especially true for those with pre-existing conditions and conditions that put people at an increased risk for corona virus, such as obesity.

Continued research on the implications of programs such as Medicaid are needed, says Lopez, who says policy decisions need to be made based on research, not politics.

"It's important to see if we spend this money on Medicaid, we're getting some of it back even if it's indirect," says Boehm. "Policy makers need to have this information. Not all states expanded Medicaid under the ACA, so if we have these results saying we see diet quality benefits that may help push other states to join the expansion.

September 8, 2020 - High-intensity focused ultrasound (HIFU) - a technology used to treat localized prostate cancer - has shown adequate control of prostate cancer while avoiding major side effects of surgery or radiation therapy, according to a new study in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Approved by the US Food and Drug Administration (FDA) in 2015 for prostate tissue ablation, the HIFU technology has gained popularity and is becoming widely available in the United States. This new study - reflecting the authors' experience as "first adopters" - is the "initial and largest" series of HIFU focal therapy as primary treatment for localized prostate cancer in the United States.

With this non-invasive high-intensity focal ultrasound strategy, nearly 90 percent of men with localized prostate cancer were able to avoid or delay radical treatment (surgery or radiation), suggests the study by Andre Luis Abreu, MD, of University of Southern California, Los Angeles, and colleagues. They write, "Focal HIFU ablation is safe and provides excellent potency and continence preservation with adequate short-term cancer control."

Promising Results with HIFU in 100 Men with Localized Prostate Cancer

With several options available, men with localized prostate cancer can feel overwhelmed when making a decision about their treatment. While radical prostatectomy and radiation therapy can effectively treat the cancer, they have high rates of side effects, including impotence (partial or no erections) and incontinence (involuntary urine leak). For very carefully selected patients with low-risk and non-aggressive (indolent) prostate cancer, active surveillance may be utilized to monitor any growth of the disease.

For those seeking alternatives, HIFU is an option which enables the surgeon to precisely target the area of the prostate where the cancer is located. Using high-intensity focused ultrasound energy to rapidly heat and destroy the targeted area of the prostate, HIFU is a non-surgical and non-radiation, one-stop and outpatient treatment.

This approach, called partial gland ablation aims "to avoid or delay radical treatment and its inherent quality of life deterioration," Dr. Abreu and coauthors write. They reviewed their experience with HIFU in 100 men (average age 65 years) with localized prostate cancer.

Outcomes were assessed a median of 20 months after hemi-gland HIFU ablation of the prostate. The primary outcome of interest was "treatment failure," including recurrent prostate cancer, the need for radical treatment, namely radiation therapy or surgery (radical prostatectomy) to remove the entire prostate, or occurrence of prostate cancer metastases or death.

At follow-up, nearly three-fourths of the men (73 percent) were free of treatment failure. With 76 percent of patients having no evidence of "clinically significant" prostate cancer, the results suggested that HIFU provides "adequate control" of the cancer within the prostate.

Researchers also noted the use of HIFU avoided complications and side effects - including sexual (impotence) and urinary (incontinence) - associated with radical prostatectomy or radiation therapy. Although minor complications occurred after HIFU in 13 percent of the patients, there were no serious complications, no fistulas, no blood transfusion or deaths. For those who responded to validated questionnaires, sexual function (erections) was preserved and urinary symptoms improved. All patients were continent after treatment.

"We believe these data represent the actual clinical practice in the United States," Dr. Abreu and colleagues conclude. "This study provides the initial US HIFU data to prostate cancer stakeholders, including clinicians, patients, and the FDA."

Robust and widespread antibody testing has emerged as a key strategy in the fight against SARS-CoV-2, the virus responsible for the COVID-19 pandemic. However current testing methods are too inaccurate or too expensive to be feasible on a global scale. But now, scientists at the Okinawa Institute of Science and Technology Graduate University (OIST) have developed a rapid, reliable and low-cost antibody test.

The device, described in a proof-of-concept study published this week in Biosensors and Bioelectronics, uses portable lab-on-a-chip technology to accurately measure the concentration of antibodies present in diluted blood plasma.

Antibodies are proteins produced by the immune system to neutralize the virus. Research has found that COVID-19 antibodies are present in the later stages of infection and can linger in the blood after the infection has cleared, allowing previously infected individuals to be identified. Antibody tests are thus an important means of determining the full spread of the coronavirus - information that is crucial to guide public health policies.

And yet many nations have so far failed to employ large-scale antibody testing.

"Many existing platforms for antibody tests are accurate and reliable, but they are costly and need to be carried out in a lab by trained operators. This means that it can take hours, or even days, to obtain results," said Dr. Riccardo Funari, first author and postdoctoral researcher in the Micro/Bio/Nanofluidics Unit at OIST. "Other tests are easier to use, portable and rapid, but are not sufficiently accurate, which hampers testing efforts."

The researchers avoided this trade-off between accuracy and accessibility by developing an alternative antibody testing platform that combines a powerful light-sensing technology with a microfluidic chip. The chip provides results within 30 minutes and is highly sensitive, detecting even the lowest clinically-relevant antibody concentration. Each chip is cheap to manufacture and negates the need for a lab or trained operators, increasing the feasibility of nation-wide testing.

And there's another distinctive advantage of this newly developed platform. "The test doesn't just detect whether the antibodies are present or absent - it also provides information about the quantity of antibodies produced by the immune system. In other words, it's quantitative," said Professor Amy Shen, who leads the Micro/Bio/Nanofluidics Unit. "This greatly expands its potential applications, from treating COVID-19 to use in developing vaccines."

Illuminating the antibodies

The antibody testing platform consists of a microfluidic chip which is integrated with a fiber optic light probe. The chip itself is made from a gold-covered glass slide with an embedded microfluidic channel. Using an electric voltage, the team fabricated tens of thousands of tiny spiky gold structures, each one smaller than the wavelength of light, on a glass slide.

The researchers then modified these gold nanospikes by attaching a fragment of the SARS-CoV-2 spike protein. This protein is crucial for helping the coronavirus infect cells and causes a strong reaction from an infected person's immune system.

In this proof-of concept study, the scientists demonstrated the principle behind how the test detects antibodies by using artificial human plasma sample spiked with COVID-19 antibodies that are specific to the spike protein.

Using a syringe pump, the sample is drawn through the chip. As the plasma flows past the protein-coated gold nanospikes, the antibodies bind to the spike protein fragments. This binding event is then detected by the fiber optic light probe.

"The detection principle is simple but powerful," said Dr. Funari. He explained that is it based on the unique behavior of electrons on the surface of the gold nanospikes, which oscillate together when hit by light. These resonating electrons are highly sensitive to changes in the surrounding environment, such as the binding of antibodies, which causes a shift in the wavelength of light absorbed by the nanospikes.

"The more antibodies that bind, the larger the shift in the wavelength of the absorbed light," added Dr. Funari. "The fiber optic probe is connected to a light detector which measures this shift. Using that information, we can determine the concentration of antibodies within the plasma sample."

A bright future

The large-scale roll-out of a quantitative test could greatly impact how COVID-19 is treated.

For example, quantitative tests could help doctors track how effectively a patient's immune system is fighting the virus. It could also be used to help identify suitable donors for a promising experimental treatment, called plasma transfusion therapy, where a recovered patient's antibody-rich blood is donated to currently infected patients to help them fight the virus.

Being able to measure the level of immune response can also aid vaccine development, allowing researchers to determine how effectively a trial vaccine triggers the immune system.

However, the researchers emphasized that the device is still undergoing active development. The unit aims to reduce the chip size to cut manufacturing costs and is also working on improving the reliability of the test.

"We have shown that the device works to detect different concentrations of the spike protein antibody in artificial human plasma samples. We now want to expand the test so that the chip can detect multiple different antibodies at the same time," said Dr. Funari. "Once the device is optimized, we plan to collaborate with local hospitals and medical institutions to perform tests on real patient samples."