Brain

Scientists find out how nutrition affects the recovery of patients after cardiac surgery

image: Cardiac surgeons of the Saint-Petersburg State University (SPSU) N.I.Pirogov Clinic of High Medical Technologies

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SPbU

Nutrients are the structural components of food that the body needs to function properly. They are divided into macronutrients (proteins, fats, carbohydrates) and micronutrients (vitamins, provitamins, various minerals, and so on). Their shortage is called nutritional deficiency.

'Modern medicine pays little attention to nutritional deficiencies in cardiac surgery patients. At the same time, in oncology, paediatrics, gastroenterology, nutrition is treated more closely. To remedy this situation, in 2011 we began a study that included the task of identifying the
prevalence of nutritional deficiency among those who underwent cardiac surgery,' says Sergey Efremov, the main author of the article, an anaesthesiologist-resuscitator, Head of the Research Department at the Pirogov Clinic of High Medical Technologies, St Petersburg University.

In medicine, there is a special term - cardiac cachexia. It is the extreme emaciation of the body in patients with severe cardiac failure. The reasons can be many: from low cardiac output to drugs that suppress appetite. Symptoms of cardiac cachexia include weakness and rapid weight loss. As a result, nutrients are not supplied to the body in the right quantities.

'The problem is also complicated by the fact that most often patients with such a diagnosis do not appear to be starving. Oedema may even make them seem overweight. That is why it was of paramount importance for us to find a reliable tool for identifying this condition,' says Sergey Efremov.

For eight years, the researchers have been monitoring more than 1,000 subjects who underwent cardiac surgery. Upon admission to the clinic, using a questionnaire survey on various scales, they found out patients' nutritional status: a set of indicators characterising the quantitative ratio
of muscle and fat mass. They also collected other preoperative and postoperative data on study participants. Then after one, three and eight years, they were telephoned and asked about their health.

'As a result of the study, we have found that the patient's nutritional status has an important prognostic value, since it enables us to identify the postoperative complication rate. As expected, the higher the degree of nutritional deficiency, the higher the probability of a negative scenario.
Additionally, we have managed to identify a small group of cardiac surgery patients who are more susceptible to this condition. These are the patients with valvular heart disease,' says Sergey Efremov.

According to Sergey Efremov, there are several scales for assessing nutritional status in the world. However, none of them has been developed specifically for patients with cardiovascular pathology. By comparing them, the researchers have selected a screening tool that has the greatest sensitivity and specificity for solving the problem. It is the MUST scale (Malnutrition Universal Screening Tool), which can be introduced into the everyday work of clinics. Any medical worker in the emergency department is able to assess the patient's condition with its help. To do this, it is necessary to just ask a few simple questions. If the scale reveals malnutrition, a doctor will join the case to find out detailed information about the patient's nutritional status.

'The Pirogov Clinic has recently become a part of St Petersburg University. And for us, its employees, it is very important to integrate with other departments of the University within the framework of project activities. That is why I am very pleased that students from the Faculty of Medicine at St Petersburg University took part in this research. They were actively engaged in collecting, systematising and analysing data. Largely thanks to their contribution, it became possible to complete this study,' notes Sergey Efremov.

The scientists see continuation of work in the search for solutions to improve the condition of patients with nutritional deficiencies. In particular, they plan to investigate the efficiency of various clinical nutritional formulas in cardiac surgery.

Credit: 
St. Petersburg State University

Experiment takes 'snapshots' of light, stops light, uses light to change properties of matter

PITTSBURGH--Light travels at a speed of about 300,000,000 meters per second as light particles, photons, or equivalently as electromagnetic field waves. Experiments led by Hrvoje Petek, an R.K. Mellon professor in the Department of Physics and Astronomy examined ideas surrounding the origins of light, taking snapshots of light, stopping light and using it to change properties of matter.

Petek worked with students and collaborators Prof. Chen-Bin (Robin) Huang of the National Tsing Hua University in Taiwan, and Atsushi Kubo of the Tsukuba University of Japan on the experiments. Their findings were reported in the paper, "Plasmonic topological quasiparticle on the nanometre and femtosecond scales," which was published in the Dec. 24 issue of Nature magazine.

Petek credited graduate student Yanan Dai for his foresight and work in the process.

"The denouement of the research, however, is that Yanan, who performed the experiments and provided the theoretical modeling, demonstrated that he was educated far beyond his Professor's level and could interpret incisively the nanofemto topological properties and interactions of optical fields," he said.

The team performed an ultrafast microscopy experiment, where they trapped green light pulses of 20 fs (2x10-14 s) duration as composite light-electron density fluctuation waves, known as surface plasmon polaritons, and imaged their propagation on a silver surface at the speed of light. But they did this with a twist so that the light waves came together from two sides to form a light vortex where light waves appear to circulate about a stationary common core as a whirlwind of waves. They could generate a movie of how light waves churn on their nanometer (10-9 m) wavelength scale by imaging electrons that two light photons coming together cause to emit from the surface.

Gathering all such electrons with an electron microscope forms images where the light had passed, thus enabling the researchers to take its snapshot. Of course, if nothing is faster than light, one cannot take its snapshot, but by sending in two light pulses with their time separation advanced in 10-16 s steps, they could image how light waves come together causing their joint amplitude to rise and fall at fixed points in space forming a light vortex on the nano (10-9 m)-femto (10-15 s) scale.

Such light vortices form when you shine your red or green laser pointer onto a rough surface and see a speckle reflection, but they also have a cosmological significance. The light vortex fields can potentially cause transitions in the quantum mechanical phase order in solid state materials, such that the transformed material structure and its mirror image cannot be superimposed. In other words, the sense of the vortex rotation generates two materials that are topologically distinct.

Petek said such topological phase transitions are at the vanguard of physics research because they are thought to be responsible for some aspects of the structure of the Universe.

"Even the forces of nature including light, are thought to have emerged as symmetry breaking transitions of a primordial field. Thus, the ability to record the optical fields and plasmonic vortices in the experiment opens the way to perform ultrafast microscopy studies of related light-initiated phase transitions in condensed matter materials at the laboratory scale," he said.

Credit: 
University of Pittsburgh

Trophoblast motility in a gelatin hydrogel

image: Journal brings together scientific and medical experts in the fields of biomedical engineering, material science, molecular and cellular biology, and genetic engineering.

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Mary Ann Liebert, Inc., publishers

New Rochelle, NY, December 18, 2020--Trophoblast cells, which surround the developing blastocyst in early pregnancy, play an important role in implantation in the uterine wall. A new multidimensional model of trophoblast motility that utilizes a functionalized hydrogel is described in the peer-reviewed journal Tissue Engineering, Part A. Click here to read the full-text article free on the Tissue Engineering website through January 18, 2020.

This valuable new tool, based on a methacrylamide-functionalized gelatin hydrogel, can be used for three-dimensional trophoblast spheroid motility assays. It can resolve quantifiable differences in outgrowth area and viability in the presence of a known invasion promoter and a known invasion inhibitor.

"Implantation involves a highly coordinated molecular dialogue between endometrial cells and trophoblast cells," state Brendan Harley and coauthors, University of Illinois at Urbana-Champaign. "Developing a deeper understanding of the biological mechanisms surrounding implantation may provide critical insights into pregnancy and pregnancy disorders."

"Dr. Harley and his colleagues at Illinois have provided a fundamental work to the growing field of pregnancy models, with a particular focus on the role of trophoblast migration. Here, the research team nicely showed that key factors - EGF and TGF-beta1 - play a critical role in modulating trophoblast motility, and thus provide a pathway for better understanding these events during normal and complex pregnancies," says Tissue Engineering Co-Editor-in-Chief John P. Fisher, PhD, Fischell Family Distinguished Professor & Department Chair, and Director of the NIH Center for Engineering Complex Tissues at the University of Maryland.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Discovery of chemical clue may lead to solving cacao's black pod rot mystery

image: The researchers have created a streamlined sample-collection protocol that only requires a single leaf disc. The leaf discs are preserved in a solvent that prevents degradation of clovamide, allowing large-scale sampling in greenhouses and fields without the need for refrigeration.

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Ben Knollenberg/Penn State

The finding of relatively high levels of the antimicrobial compound clovamide in the leaves of a disease-resistant strain of cacao has significant implications for breeding trees that can tolerate black pod rot, according to Penn State researchers who conducted a novel study.

The discovery is significant because this fungal disease is a serious problem in all areas of the world where cacao is grown, noted researcher Mark Guiltinan, J. Franklin Styer Professor of Horticultural Botany and professor of plant molecular biology, College of Agricultural Sciences. Black pod rot, caused by the fungus Phytophthora, causes pod losses of up to 30% and kills as many as 10% of the trees annually.

"This is the first time that clovamide has been implicated in cacao resistance to pathogens, and the innovative method we used to measure the compound in the leaves could have a major impact in the quest to develop highly productive, disease-resistant varieties of cacao," Guiltinan said. "But these results may have consequences for advancing disease resistance in other plant species, as well."

In the study, leaves of a cacao variety known as "Scavina 6," which is tolerant of the fungus that causes black pod rot, were found to accumulate dramatically higher levels of clovamide and several other metabolites known to be involved in responses to stress -- compared to a susceptible cacao strain, "Imperial College Selection 1." Clovamide was the most abundant compound in Scavina 6 leaf extracts, with concentrations up to 58-fold higher than in Imperial College Selection 1.

Researchers discovered this dramatic difference in clovamide accumulation by comparing the abundance of hundreds of specialized metabolites in the two cacao strains using liquid chromatography and tandem mass spectrometry at Penn State's Metabolomics Facility, part of the Huck Institutes of the Life Sciences.

"These results pointed to clovamide as a potential contributor to disease resistance, and laboratory tests supported this hunch," Guiltinan said.

Laboratory assays demonstrated that the compound inhibits the growth of three pathogens of cacao in the Phytophthora genus. Also, in another experiment, clovamide inhibited the activity of the enzymes proteinase and pectinase, which are known to break down plant cell walls. Based on this evidence, it is likely that clovamide prevents pathogens' ability to break down cell walls while killing and digesting plant tissue, the researchers said.

The study's findings, published today (Dec. ??) in Frontiers in Plant Science, promise to enhance plant-breeding efforts to develop highly productive varieties of cacao that can withstand the onset of black pod rot, lead researcher Ben Knollenberg suggested. A postdoctoral scholar in plant science at Penn State, he said the method researchers used to measure clovamide levels in leaves could greatly streamline and condense the breeding process.

"The Scavina 6 strain has been utilized as a parent in cacao-breeding programs for decades, but it hasn't been clear why it's resistant to black pod rot, which makes breeding for resistance difficult," he said. "Breeders cross Scavina 6 with higher-yielding varieties, for example, and they get a bunch of seeds or offspring, which may or may not have inherited the disease resistance. Evaluating the disease resistance of this new generation of trees requires years of growth and measurements in field trials, which requires land, labor and money."

If breeders can screen for leaf clovamide content when the trees are just seedlings in the greenhouse, they can eliminate trees that lack the trait before transplanting the seedlings to the field, Knollenberg pointed out. This will increase the chances of obtaining disease-resistant varieties and will reduce the resources required for cacao breeding.

"This is essentially 'marker-assisted selection,' which typically employs markers based on DNA sequences, but in this case, it involves a chemical trait or a 'metabolic marker,'" he said.

The researchers hope that using clovamide as a resistance marker becomes a useful tool in cacao breeding programs, which would be especially welcome because much of the cacao tree crossing is done in countries that don't have well-funded breeding programs.

"We think this will accelerate breeding and make it more efficient so that breeders can develop resistant varieties more quickly," Knollenberg said. "For example, instead of growing 1,000 trees to evaluate resistance, with the ability to measure the relative abundance of clovamide in the leaf tissues, they could grow just the 100 highest-clovamide trees instead."

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Penn State

New mechanisms to control dental procedure spray emissions

Alexandria, Va., USA -- Since the onset of COVID-19 the potential risk of dental procedure spray emissions for SARS-CoV-2 transmission has challenged care providers and policy makers alike. The study, "Mechanisms of atomization from rotary dental instruments and its mitigation," published in the Journal of Dental Research (JDR), found that there are multiple mechanisms for atomization of fluids from rotatory instruments and that parameters can be controlled to modify key spray characteristics during the current crisis.

Using high speed imaging and laser light-sheet illumination, procedural sprays were studied with variables including rotation speed, burr to tooth contact and coolant pre-misting. Elimination of pre-misting (mixing of coolant water and air prior to burr contact) and use of relatively low rotation speeds resulted in significant reduction in small droplets. Cutting efficiency was reduced, but sufficient coolant effectiveness appeared to be maintained.

"This research demonstrates that spray from dental instruments can be controlled without losing the ability to carry out dental treatment," said JDR Editor-in-Chief Nicholas Jakubovics. "Being able to modify the spray creates a safer experience for patients and oral health care providers during this current pandemic."

Credit: 
International Association for Dental, Oral, and Craniofacial Research

Record-setting thermoelectric figure of merit achieved for metal oxides

image: The barium-cobalt oxide film (top right, approximately 1 cm2) being exposed to an open flame to generate voltage. (Photo: Hiromichi Ohta)

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Hiromichi Ohta

Scientists at Hokkaido University have developed a layered cobalt oxide with a record-setting thermoelectric figure of merit, which can be used to enhance thermoelectric power generation.

Waste heat is a highly promising source of renewable energy; however, the efficiency of using heat to generate energy has historically been much lower than hydroelectric, wind or solar power. While there are a number of materials that can be used for the generation of energy from waste heat, they all suffer from various issues ranging from low stability to low efficiency. Nevertheless, the fact that a large number of industries generate copious amounts of waste heat have driven research into this field.

A team of scientists led by Professor Hiromichi Ohta at the Research Institute for Electronic Science (RIES), Hokkaido University, has recently developed a layered cobalt oxide with a record-setting thermoelectric figure of merit for metal oxides at room temperature. Their findings were published in the journal Journal of Materials Chemistry A.

Thermoelectric conversion is driven by the Seebeck effect: when there is a temperature difference across a conducting material, an electric current is generated. Historically, the efficiency of heat-to-electricity conversion of metal oxides was very low; however, metal oxide-based thermoelectric devices are highly desired due to their environmental compatibility. The thermoelectric conversion efficiency of a device depends on a key factor called the thermoelectric figure of merit (ZT).

Hiromichi Ohta's group has developed a layered cobalt oxide that exhibits a high ZT and is stable across a range of operating temperatures. Well-known sodium-cobalt oxide, where sodium and cobalt oxide layers alternate, shows a very low ZT of around 0.03, but the material developed by Ohta's group achieved a ZT of 0.11. The group replaced the sodium by other alkali or alkaline earth metals: calcium, strontium, and barium.

The layered barium-cobalt oxide material exhibited a record-setting ZT of 0.11 at room temperature. The increase in ZT is directly caused by the decreased thermal conductivity of barium. As the scientists hypothesized, the greater the atomic mass, the lower the thermal conductivity, resulting in higher ZT. This is due to the fact that heavier atoms suppress the vibrations in the cobalt oxide layers caused by heating. Further research is required to optimize the material's composition for higher efficacy and stability, as well as determining the most useful practical applications.

Hiromichi Ohta is the head of the Laboratory of Functional Thin Film Materials at the RIES, Hokkaido University. His areas of research include Thermoelectrics, Thermopower modulation, Optoelectronics and Iontronics.

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Hokkaido University

Diversity, severity of autism symptoms linked to mutation locations

NEW YORK, NY (Dec. 22, 2020)--One of the most recognizable characteristics of autism is an amazing diversity of associated behavioral symptoms. Clinicians view autism as a broad spectrum of related disorders, and the origin of the disease's heterogeneity has puzzled scientists, doctors, and affected families for decades.

In a recent study, researchers at Columbia University Vagelos College of Physicians and Surgeons have made an important step towards understanding the biological mechanisms underlying the cognitive and behavioral diversity of autism cases triggered by de novo truncating mutations. These mutations occur in parents' germline cells and usually strongly disrupt the functions of target genes. De novo truncating mutations are responsible for close to 5% of autism cases and up to 20% of cases seen clinically.

Autism spectrum disorders that are triggered by a single disrupted gene represent a relatively simple genetic type of the disease. The perplexing observation that scientists were grappling with for many years is that even when truncating mutations occur in the same gene, they often lead to a wide range of symptoms and behavioral patterns in different children.

The new study found that the severity of autism symptoms often depends on which specific functional unit within a gene is the target of a mutation.

"It turns out that we weren't looking closely enough at how and where an autism gene is mutated," says study leader Dennis Vitkup, PhD, associate professor of systems biology and of biomedical informatics at Columbia University Vagelos College of Physicians.

Human genes, similar to genes of other eukaryotic species, are composed of separate coding units, called exons, which are frequently joined together in different combinations across tissues and developmental stages. "Upon closer examination, we found that different children with truncating mutations in the same exon have strikingly similar behavioral symptoms and disabilities," Vitkup says.

The study was published online in the journal Molecular Psychiatry.

Same Exon, Similar Symptoms

In the study, Vitkup and colleagues Andrew H. Chiang, Jonathan Chang, and Jiayao Wang analyzed genetic and clinical data from over 2,500 people with autism, focusing on cases resulting from truncating mutations.

When the researchers compared random pairs of children with autism, they found that their nonverbal, verbal, and overall IQ scores differed on average by more than 30 points. Children with truncating mutations in the same gene showed similar differences.

However, when the researchers compared autistic children affected by mutations in the same exon of the same gene, their IQs differed by less than ten points, which is comparable to the IQ measurement errors. The researchers observed very similar patterns for multiple other scores characterizing children's communication, social, and motors skills.

"This tells us that, with autism-associated truncating mutations, it's the exon, and not the whole gene, that often represents a functional unit of impact," Vitkup says.

More Severe Symptoms Associated with Frequently Used Exons

The researchers demonstrated that the behavioral and cognitive severity of autism is proportional to the likelihood with which targeted exons are used in gene transcripts, with more severe effects associated with mutations in more frequently used exons. When mutations occur in the same exon, the resulting expression-level changes are especially similar, leading to similar clinical consequences.

Surprisingly, the study also showed that the gene expression changes caused by truncating mutations can be quite mild. "Our analysis demonstrates that autism cases can be triggered by relatively small changes in overall gene dosage, often as small as 15%," says the study's first author Andrew Chiang, a graduate student in the Department of Biomedical Informatics.

Implications for Precision Medicine

The study may have significant implications for precision medicine. Diagnostic and prognostic tests may now pay special attention to specific exons affected by truncating mutations.

The study also suggests a therapeutic approach for alleviating the consequences of truncating mutations in autism. "It would be very hard to develop drugs for thousands of different mutations in many hundreds of target autism genes," Vitkup says, "but our study demonstrates that behavioral abnormalities often originate from relatively small decreases in the target gene's dosage. These genetic insults may be, at least partially, compensated by increasing the expression of an unaffected gene copy using new molecular tools such as CRISPR."

Credit: 
Columbia University Irving Medical Center

Slow start of plate tectonics despite a hot early Earth

Writing in PNAS, scientists from Cologne university present important new constraints showing that plate tectonics started relatively slow, although the early Earth's interior was much hotter than today.

In an international collaboration earth scientists at the University of Cologne discovered that during Earth's early history mantle convection on, i.e. the internal mixing of our planet, was surprisingly slow and spatially restricted. This finding is unexpected because our planet was much hotter during the first hundreds of million years after its formation. Therefore, it has been assumed that mantle convection on Earth was much faster in its infancy. According to their study „Convective isolation of Hadean mantle reservoirs through Archean time", however, the earth did not experience full speed mantle convection until 3 billion years ago, when modern plate tectonics is believed to have fully operated.

For their study, the geologists investigated up to 3.5 billion years old igneous rocks from NW Australia that cover 800 million years of Earths early history. The analysis of these rock successions revealed that the oldest samples exhibit small anomalies in the isotope abundances of the element tungsten (W) that progressively diminish with time. The origin of these anomalies, namely the relative abundance of 182W, relates to ancient heterogeneities in the terrestrial mantle that must have formed immediately after formation of the Earth more than 4.5 billion years ago. The preservation of these 182W anomalies in the igneous rocks from NW Australia demonstrate that pristine mantle reservoirs from the beginning of our planet were conserved over timescales exceeding more than one billion years. This finding is very surprising, because higher mantle temperatures in the early Earth suggest that mantle convection was more extensive and much faster than today. Interestingly, the observed 182W anomalies start to diminish at around 3 billion years ago, within a geological era that is assumed to mark the beginning of modern plate tectonics. The onset of modern plate tectonics, involving subduction processes and mountain uplift, has been shown to be a key event triggering the emergence of large continental masses and an oxygen-rich atmosphere, all of which set the stage for the origin of more complex life.

Credit: 
University of Cologne

How a large protein complex assembles in a cell

image: The nuclear pore complexes (orange structures), some of which are in the process of assembly, are among the largest protein complexes in a cell.

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Visualization: Olga V Posukh, Institute of Molecular and Cellular Biology, Novosibirsk

Cells produce a great number of different protein complexes, each of which is made up of many individual proteins. These protein complexes, like ribosomes for example, are what regulate almost all of a cell's life-sustaining biological functions.

Biologists have succeeded in determining the structure of many of these complexes, but there is less research so far on how the individual proteins assemble and then change over time. Conventional approaches have thus far proved insufficient for studying the exact course that these reactions in cells take, especially where large complexes are concerned.

A group of ETH researchers led by Karsten Weis and research associate Evgeny Onischenko at ETH Zurich's Institute of Biochemistry are now presenting a new approach. Their method makes it possible to track the dynamics of protein complex assemblies, even for very large ones, with high temporal resolution. The study has just been published in the journal Cell.

Inspired by metabolic analysis

The ETH researchers call their new approach KARMA, which stands for kinetic analysis of incorporation rates in macromolecular assemblies and is based on methods for investigating metabolic processes. Scientists researching metabolism have long used radioactive carbon in their work, e.g., to label glucose molecules, which cells then take up and metabolise. The radioactive labelling enables researchers to track where and at what point in time the glucose molecules or their metabolites appear.

"This type of research inspired us to apply a similar principle in exploring the reactions that take place in the assembly of protein complexes," Weis explains. In their approach, the ETH researchers work with labelled amino acids, the fundamental building blocks of proteins, which contain heavier carbon and nitrogen isotopes. In a culture of yeast cells, the team replaces the lightweight amino acids with their heavier counterparts. The yeast uses these heavy amino acids in protein synthesis, which shifts the molecular weight of all newly produced proteins.

A time scale for the assembly of a complex

To isolate protein complexes, the researchers remove yeast cells from the cultures at regular intervals and employ mass spectrometry to measure the tiny weight difference between molecules with heavier amino acids and those without. This indicates the age of a protein in a complex. Basically, the older the protein, the earlier it was incorporated into the complex. Based on these age differences, the researchers apply kinetic state models to ultimately reconstruct the precise assembly sequence of a given protein complex.

As a case study to validate their method, Weis and his team chose the nuclear pore complex in yeast cells. This structure has some 500 to 1,000 elements composed of about 30 different proteins each in multiple copies, thus making it one of the largest known protein complexes.

Using KARMA, the ETH biochemists were able to obtain a detailed map of which modules are integrated into the structure and when. One of their findings was a hierarchical principle: individual proteins form subunits within a very short time, which then assemble from the centre out to the periphery in a specific sequence.

Durable scaffold

"We've demonstrated for the first time that some proteins are used very quickly in the assembly of the pore complex, while others are incorporated only after about an hour. That's an incredibly long time," Weis says. A yeast cell divides every 90 minutes, which means it would take almost a whole generation to complete assembly of this vital pore complex. Precisely why the assembly of new pores takes so long in relation to the yeast reproduction cycle is not known.

The ETH researchers also show that once assembly of the pore is complete, parts of the complex are highly stable and durable - in the inner scaffold, for example, hardly any components are replaced during its lifetime. By contrast, proteins at the periphery of the nuclear pore complex are frequently replaced.

Defective nuclear pores facilitate disease

Nuclear pores are some of the most important protein complexes in cells, as they are responsible for the exchange of substances and molecules between the cell nucleus and cytoplasm. For example, they transport messenger RNA from the nucleus to the cellular machinery outside the nucleus, which needs these molecules as blueprints for new proteins.

Moreover, nuclear pores play direct and indirect roles in human disease. Accordingly, changes in the nuclear pore and its proteins can impact the development of conditions like leukaemia, diabetes or neurodegenerative diseases such as Alzheimer's. "Generally speaking, though, the reasons why pore defects cause these disease patterns are not well understood," Weis says, explaining that KARMA might help to gain deeper insight into such issues in the future.

Versatile platform

"Although we applied KARMA to only one protein complex in this study, we're excited about its future applications. Our method will now enable us to decipher the sequence of a whole host of biological processes," Weis says. Their technique can be used, for example, to study molecular events that occur during the infection cycle of viruses such as COVID-19 and potentially help to find new drug candidates that break that cycle.

The new method can also be applied to other biological molecules besides proteins, such as RNA or lipids.

Credit: 
ETH Zurich

Study shows significant sex, age differences for nonfatal opioid overdoses in youth

Boston - Results of a national study show significant sex and age-based differences among youth and young adults who experience a nonfatal opioid overdose. Female youth between the ages of 11 and 16 have a higher incidence of nonfatal opioid overdose compared to male youth of the same age. That reverses at age 17, however, as males between 17 and 24 have a higher incidence of nonfatal opioid overdose compared to their female peers. Led by researchers from the Grayken Center for Addiction at Boston Medical Center and published in JAMA Network Open, the study reveals specific sex-based risk factors that could be used to develop more effective strategies to screen for and prevent opioid overdoses in adolescents and young adults.

A study published in 2018 shows alarming trends related to opioid overdoses among adolescents between the ages of 15 and 19. There was a 404 percent increase in opioid overdoses from 1999 to 2016, and the mortality for opioid overdoses increased 268 percent during that time period. Yet, many youth and young adults diagnosed with a substance use disorder, or opioid use disorder, do not receive medication to treat their condition.

"We know that adolescents and young adults are impacted by the opioid overdose epidemic, but there are not enough data about how or if their risks may be different from adults," said Sarah Bagley, MD, MSc director of Boston Medical Center's adolescent and young adult addiction treatment program and the study's corresponding author. "In order to help curb this increase, we need to better understand the issues facing our patients so that we can develop tailored approaches to address any underlying conditions that may contribute to the risks for overdose."

This retrospective cohort study examined characteristics of nonfatal opioid overdoses experienced by both males and females, and then compared the incidence of nonfatal opioid overdoses in male and female adolescents and young adults. The study's data was obtained from IBM Marketscan Commercial and included a cohort of 20,312 youth between the ages of 11 and 24 who experienced a nonfatal overdose between January 1, 2006 and December 31, 2017. The median age of individuals included in the cohort was 20, and approximately 42 percent were female, and all were commercially insured.

The research data showed that females had a higher prevalence of anxiety and depression, and a history of self-harm and suicide attempts. Male youth had a higher prevalence of other substance use disorders, including alcohol and cannabis. Between the ages of 11 and 16, females had significantly higher incidence of nonfatal overdoses, but at the age of 17, that changes as males then have higher incidence of nonfatal opioid overdoses.

"The study results provide significant insight into the co-occurring issues impacting our adolescent and young adult patients," added Bagley, who is also an assistant professor of medicine and pediatrics at Boston University School of Medicine. "We hope that this data will serve as a basis for developing targeted interventions to prevent nonfatal opioid overdoses, as well as strategies for more effective access and engagement in treatment for this population."

Credit: 
Boston Medical Center

Chemists synthesize 'flat' silicon compounds

image: 3D representation of one of the new molecules. Silicate ions in tetrahedral arrangement can be seen in the spherical soap bubbles for comparison.

Image: 
© Jens Rump / University of Bonn

Chemists at the University of Bonn (Germany) have synthesized extremely unusual compounds. Their central building block is a silicon atom. Different from usual, however, is the arrangement of the four bonding partners of the atom, which are not in the form of a tetrahedron around it, but flat like a trapezoid. This arrangement is usually energetically extremely unfavorable, yet the molecules are very stable. Their properties are completely unknown so far; researchers now want to explore them. The results will be published in the Journal of the American Chemical Society, but are already available online.

Like its relative carbon, silicon generally forms four bonds with other atoms. When it does, the result is usually a tetrahedron. The silicon atom is located in the center, its bonding partners (the so-called ligands) at the tetrahedral corners. This arrangement is most favorable energetically. It therefore arises quasi automatically, just as a soap bubble is usually spherical.

Researchers led by Prof. Dr. Alexander C. Filippou of the Institute for Inorganic Chemistry at the University of Bonn have now constructed silicon-containing molecules that are as unusual as a cube-shaped soap bubble. In these, the four ligands do not form a tetrahedron, but a distorted square, a trapezoid. They lie in one plane together with the silicon. "Despite this, the compounds are so stable that they can be filled into bottles and stored for weeks without any problems," explains Dr. Priyabrata Ghana, a former doctoral student who has since moved to RWTH Aachen University.

Molecular exotics are unusually stable

The researchers themselves were surprised by this unusual stability. They discovered the reason by modeling the molecules on the computer. The ligands also form bonds with each other. In the process, they form a solid framework. This appears to be so strong that it completely prevents the trapezoidal arrangement from "snapping" into a tetrahedron. "Our computer calculations indicate that there is no structure for the molecules that would be more energetically favorable than the planar trapezoidal shape," emphasizes Jens Rump, a doctoral student at the Institute for Inorganic Chemistry.

The researchers grew crystals of the substances and then blasted them with X-rays. The X-ray light is scattered by the atoms and changes its direction. These deviations can therefore be used to calculate the spatial structure of the molecules in the crystal. Together with spectroscopic measurements, this method confirmed that ligands and silicon are indeed in the same plane in the new molecules.

Although the synthesis of the exotic compounds must be carried out under inert gas, it is otherwise comparatively simple. Producing the starting materials, on the other hand, is complex; one of them was first synthesized only just over ten years ago and has already been the source for the synthesis of several novel classes of silicon compounds.

The influence of the unusual structure on the properties of silicon, an important element for the electronics industry, is completely unclear at the moment. At any rate, for a long time it was considered completely impossible to produce such compounds.

Credit: 
University of Bonn

New energy conversion layer for biosolar cells

image: A bioelectrode with the protein complex Photosystem I under irradiation with red light for measurement of the photocurrent response.

Image: 
Felipe Conzuelo

A research team from the Ruhr-Universität Bochum (RUB), together with colleagues from Lisbon, has produced a semi-artificial electrode that could convert light energy into other forms of energy in biosolar cells. The technique is based on the photosynthesis protein Photosystem I from cyanobacteria. The group showed that they could couple their system with an enzyme that used the converted light energy to produce hydrogen. The results were published online in advance in October 2020 in the journal Angewandte Chemie.

For the work, the RUB group consisting of Panpan Wang, Dr. Fangyuan Zhao, Dr. Julian Szczesny, Dr. Adrian Ruff, Dr. Felipe Conzuelo and Professor Wolfgang Schuhmann from the Center for Electrochemistry cooperated with the team consisting of Anna Frank, Professor Marc Nowaczyk and Professor Matthias Rögner from the Chair of Biochemistry of Plants as well as colleagues from the Universidade Nova de Lisboa.

Short-circuit danger

Photosystem I is part of the photosynthesis machinery in cyanobacteria and plants. With the help of light energy, it can separate charges and thus generate high-energy electrons that can be transferred to other molecules, for example to protons for the production of hydrogen.

In earlier work, the Bochum scientists had already used the light-collecting protein complex photosystem I to design electrodes for biosolar cells. For this purpose, they covered an electrode with a photosystem I monolayer. In such monolayers, the photosystems are not stacked on top of each other, but lie side by side in the same plane. Photosystem I, however, usually occurs as a trimer, i.e. three photosystems are always linked together. Since the trimers cannot be packed close together, holes appear in the monolayer, which can lead to short circuits. This impairs the performance of the system. It was precisely this problem that the scientists solved in the present work.

Holes in the photosystem layer plugged

In the cyanobacterium Thermosynechococcus elongatus, photosystem I exists mainly as a trimer. Using a new extraction technique, the researchers were able to isolate additionally monomers from the organism, creating a photosystem I monolayer on the electrode in which the monomers filled the holes between the trimers. In this way, they reduced the short-circuit effects. The system achieved current densities twice as high as a system consisting only of trimers.

To show what the technique could be in principle used for, the scientists coupled it to a hydrogenase enzyme that produced hydrogen using electrons provided by the photosystem. "Future work will be directed toward even more efficient coupling between the photosystem monolayer and the integrated biocatalysts to realize practical biosystems for solar energy conversion," the authors preview in their publication.

Credit: 
Ruhr-University Bochum

Big step with small whirls

image: The skyrmions are created in an ultra-high vacuum deposition chamber: Using sputter deposition technology, a team of Empa researchers has succeeded in producing distinguishable skyrmions within finely tuned, ultra-thin metal layers at room temperature.

Image: 
Empa

Many of us may still be familiar with the simple physical principles of magnetism from school. However, this general knowledge about north and south poles quickly becomes very complex when looking at what happens down to the atomic level. The magnetic interactions between atoms at such minute scales can create unique states, such as skyrmions.

Skyrmions have very special properties and can exist in certain material systems, such as a "stack" of different sub-nanometer-thick metal layers. Modern computer technology based on skyrmions - which are only a few nanometers in size - promises to enable an extremely compact and ultrafast way of storing and processing data. As an example, one concept for data storage with skyrmions could be that the bits "1" and "0" are represented by the presence and absence of a given skyrmion. This concept could thus be used in "racetrack" memories (see info box). However, it is a prerequisite that the distance between the skyrmion for the value "1" and the skyrmion gap for the value "0" remains constant when moving during the data transport, otherwise large errors could occur.

As a better alternative, skyrmions having different sizes can be used for the representation of "0" and "1". These could then be transported like pearls on a string without the distances between the pearls playing a big role. The existence of two different types of skyrmions (skyrmion and skyrmion bobber) has so far only been predicted theoretically and has only be shown experimentally in a specially-grown monocrystalline material. In these experiments, however, the skyrmions exist only at extremely low temperatures. These limitations make this material unsuitable for practical applications.

Experience with ferromagnetic multilayer systems and magnetic force microscopy

The research group led by Hans Josef Hug at Empa has now succeeded in solving this problem: "We have produced a multilayer system consisting of various sub-nanometer-thick ferromagnetic, noble metal and rare-earth metal layers, in which two different skyrmion states can coexist at room temperature," says Hug. His team had been studying skyrmion properties in ultra-thin ferromagnetic multilayer systems using the magnetic force microscope that they developed at Empa. For their latest experiments, they fabricated material layers made from the following metals: iridium (Ir), iron (Fe), cobalt (Co), platinum (Pt) and the rare-earth metals terbium (Tb) and gadolinium (Gd).

Between the two ferromagnetic multilayers that generate skyrmions - in which the combination of Ir/Fe/Co/Pt layers is overlaid five times - the researchers inserted a ferrimagnetic multilayer consisting of a TbGd alloy layer and a Co layer. The special feature of this layer is that it cannot generate skyrmions on its own. The outer two layers, on the other hand, generate skyrmions in large numbers.

The researchers adjusted the mixing ratio of the two metals Tb and Gd and the thicknesses of the TbGd and Co layers in the central layer in such a way that its magnetic properties can be influenced by the outer layers: the ferromagnetic layers "force" skyrmions into the central ferrimagnetic layer. This results in a multilayer system where two different types of skyrmions exist.

Experimental and theoretical evidence

The two types of skyrmions can easily be distinguished from each other with the magnetic force microscope due to their different sizes and intensities. The larger skyrmion, which also creates a stronger magnetic field, penetrates the entire multilayer system, i.e. also the middle ferrimagnetic multilayer. The smaller, weaker skyrmion, on the other hand only exists in the two outer multilayers. This is the great significance of the latest results with regard to a possible use of skyrmions in data processing: if binary data - 0 and 1 - are to be stored and read, they must be clearly distinguishable, which would be possible here by means of the two different types of skyrmions.

Using the magnetic force microscope, individual parts of these multilayers were compared with each other. This allowed Hug's team to determine in which layers the different skyrmions occur. Furthermore, micromagnetic computer simulations confirmed the experimental results. These simulations were carried out in collaboration with theoreticians from the universities of Vienna and Messina.

Empa researcher Andrada-Oana Mandru, the first author of the study, is hopeful that a major challenge towards practical applications has been overcome: "The multilayers we have developed using sputtering technology can in principle also be produced on an industrial scale", she said. In addition, similar systems could possibly be used in the future to build three-dimensional data storage devices with even greater storage density. The team recently published their work in the renowned journal Nature Communications.

Racetrack Memory

The concept of such a memory was designed in 2004 at IBM. It consists of writing information in one place by means of magnetic domains - i.e. magnetically aligned areas - and then moving them quickly within the device by means of currents. One bit corresponds to such a magnetic domain. This task could be performed by a skyrmion, for example. The carrier material of these magnetic information units are nanowires, which are more than a thousand times thinner than a human hair and thus promise an extremely compact form of data storage. The transport of data along the wires also works extremely fast, about 100,000 times faster than in a conventional flash memory and with a much lower energy consumption.

Credit: 
Swiss Federal Laboratories for Materials Science and Technology (EMPA)

Melody of an Alpine summit falling apart

image: Across the summit of the 2592-metre-high Hochvogel in the Allgäu region of Germany, a dangerous crack is gaping and growing. The southern side of the mountain threatens to slide into the Austrian Hornbach Valley, releasing up to 260,000 cubic meters of limestone debris - corresponding to ~260 single-family houses.

Image: 
TU München

The entire summit of the 2592 metres high Hochvogel is sliced by a five metres wide and thirty metres long fracture. It continues to open up by up to half a centimetre per month. Throughout the years, the southern side of the mountain has already subsided by several meters; and at some point it will fail, releasing up to 260,000 cubic meters of limestone debris down into the Hornbach Valley in Austria. Such a volume would roughly correspond to 260 family houses. When this will happen is hard to predict by conventional methods. Researchers of the Helmholtz Centre Potsdam - German Research Centre for Geosciences and the Technical University of Munich have approached this question by seismic sensors. The devices record the subtle vibration of the peak: similar to a violin string which is pulled more or less does the pitch of the summit change as it becomes stressed, an effect that allows unique insight to the preparation phase of an upcoming rock slide. Thus, also a timely warning should become possible - even if human dwellings are not threatened directly at this site. The study has recently been published in the journal Earth Surface Processes and Landforms.

Rock slope failures shape the landscape

Large rock slope failures happen again and again. They play a central role in the long-term evolution of landscapes. And they are of fundamental interest in land use planning and hazard aspects. However, because they occur suddenly and then proceed at high speed, such mass movements are difficult to study. In general, it is clear that mechanical load or temperature fluctuations build up stress inside the rock, which is then released in processes of disintegration: cracks evolve on different spatial scales. At some point, the structure has become unstable enough to ultimately break apart. While the failure phase has already been well studied, there are still considerable knowledge gaps regarding their longer-term precursors. One reason is that the installation of permanent measurement equipment in high mountains is difficult and costly. The other reason is that long-term monitoring has so far often been carried out using remote sensing data or sensors that collect only point data. None of these approaches has been able to record the processes inside a rock volume at sufficient temporal and spatial detail, continuously and in a larger spatial context.

To understand when and why the instable rock mass at the Hochvogel becomes mobile, in 2018 researchers around Michael Dietze of the GFZ had deployed a network of six seismometers at the summit, each at a distance of thirty to forty meters from each other. For several months, the sensors have recorded the frequency with which the mountain swings back and forth. The vibrations are caused by wind and numerous small excitations of the Earth's surface, and the summit's frequency is determined by factors such as temperature, rock stress and material weakening.

New monitoring method with seismometers

During the summer of 2018, the researchers were able to measure a recurring sawtooth-like frequency pattern: Over a period of five to seven days, it rose repeatedly from 26 to 29 Hertz, only to drop back to its original value within less than two days. The increase in frequency is caused by stress increase within the rock mass. As the frequency drops, the sensors also recorded an increased rate of crack signals, as they are known to happen when rock is being torn apart. This cyclic increase and decrease of stress by jerky movement is also called stick slip motion. It is a typical precursor of large mass movements. The decisive factor here is that the closer this event comes, the shorter the observed cycles become, making them an important hazard indicator.

"With the help of the seismic approach, we can now for the first time sense, record and process this cyclical phenomenon continuously and almost at real time", says Michael Dietze, post-doctoral researcher in the Geomorphology Section at GFZ. He collaborates with colleagues from the Technical University of Munich in the AlpSenseBench project, which focuses on instrumentation of further Alpine peaks to study progressive rock instability evolution.

Dietze estimates that the new seismic approach is still a fair bit from becoming a routine application: "We have currently shown the proof of concept, so to speak, and now the results have to be repeated elsewhere". From a technical point of view, that shouldn't be too difficult, Dietze believes. And with the increased activity on the many more peaks in the Alps, there are also plenty of areas of application.

Outlook: Role of water and ice in the fissures

In the course of their measurements, which - with interruptions due to lightning strikes - extended from July to October, the researchers made another interesting discovery: While the sawtooth-like build-up and release of stress was clearly visible in the first few months after snow melt, it disappeared in late summer of the drought year 2018. Apparently, the summit ran short in an essential lubricant during the summer: water. By then, only a diurnal up and down of the summit's vibration frequency played a role: during the cold night hours the rock contracts, fissures become larger and the connection to the solid rock becomes less rigour, resulting in a decreasing vibration frequency. In turn, the heat of the sun lets the rock mass expand, closing small fissures and thus causing a rise of the vibration frequency.

Over a period of two more years, the researchers will now investigate how these dirurnal and longer period cycles interact and how the chilly winters will affect the deep, water filled crevices that cut the Hochvogel. This includes investigating the consequences of rock mass activity at the summit for the south facing hillslope by a larger seismic network that stretches down towards the Hornbachtal. Settlements in that valley will not be threatened by mass wasting along the slopes, but the access of the peak from this area has already been closed years ago due to an imminent rockfall risk.

Credit: 
GFZ GeoForschungsZentrum Potsdam, Helmholtz Centre

Surveillance of antimicrobial resistance could be more challenging outside of the EU

In a new report from the Microbiology Society, experts from around the UK explain the desperate need for long-term and ambitious funding for surveillance and research into antimicrobial resistance (AMR).

The next pandemic is likely to be associated with antimicrobial resistance, they say, and improved surveillance systems to monitor the evolution of AMR over time will be critical to avoid a surge in drug-resistant infections.

"In Ireland, the task of setting up an efficient AMR surveillance system is likely to be directed by the EU. The UK, however, will need to develop its own strategy, which may prove more challenging out of the EU and will require the appropriate funding and direction" the report says.
"Monitoring and identifying AMR is essential in order to identify outbreaks, trace transmission chains, and identify how AMR is evolving and what factors contribute to its evolution, and for local, national and international surveillance efforts. Further being able to detect the rise of AMR and its spread will help safeguard our economies from future pandemics."

The report further explains the urgent need for improved communication and education about AMR, which is described as a "slow-motion pandemic." Current momentum around infectious disease research should be used to raise awareness and understanding of AMR. With this opportunity comes a threat, however. According to the report, there is a risk of AMR messaging being diluted by the current information around the Covid-19 pandemic.

The report highlights the threat AMR poses to society and contains six key recommendations from the microbiology community. These recommendations focus on research, surveillance and collaboration, and how new interventions can be developed to tackle the threat of AMR.

Tackling the issue of AMR aligns with many of the SDGs; specifically, those related to poverty (SDG 1), human health (SDG 3), food security and agriculture (SDG 2), clean sanitation (SDG 6) and economic growth (SDG 8). Microbiology is at the forefront of developing novel antimicrobial compounds, vaccine research, providing sustainable solutions for treating livestock and crop diseases, unravelling disease transmission patterns across ecosystems and informing which antimicrobials should be prescribed when. Therefore, the microbiology community is pivotal for AMR research and can have a major influence in this area, which can contribute to delivering the SDGs.

The current landscape of AMR research in the UK and Ireland is highly active and expansive. However, the challenge is significant, and some aspects of the research must be augmented in order to provide new solutions to infections caused by antimicrobial-resistant organisms. Whilst basic research is fundamental to understanding the how and why, the field also needs to be more applied, aiming to translate findings into new interventions through enhanced interactions with other disciplines and industrial partners.

Credit: 
Microbiology Society